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Lijuan Shi,1 Jieyu Xiao,1 Juanjuan Guo,1 Saijun Zeng,2 Suhong Wang,3 Jingbo Gong4 1School of Education, Hunan University of Science and Technology, Xiangtan, Hunan, People’s Republic of China; 2Yiyang Special Education School, Yiyang, Hunan, People’s Republic of China; 3Department of Clinical Psychology, The Third Affiliated Hospital, Soochow University, Changzhou, People’s Republic of China; 4Shanghai Changning Mental Health Centre, Affiliated Mental Health Center of East China Normal University, Shanghai, People’s Republic of ChinaCorrespondence: Jingbo Gong, Shanghai Changning Mental Health Center, Affiliated Mental Health Center of East China Normal University, Shanghai, 200335, People’s Republic of China, Email yefenhua@126.com Suhong Wang, Department of Clinical Psychology, the Third Affiliated Hospital, Soochow University, Changzhou, People’s Republic of China, Email yarmine@gmail.comBackground: Non-suicidal self-injury (NSSI) is a serious mental health problem among adolescents and young adults. Childhood trauma is a distal factor for NSSI and can also lead to cognitive abnormalities and maladaptive emotion regulation during the growth and development of individuals. However, it is unclear how childhood trauma and cognitive-emotional factors interact with NSSI.Objective: This study investigated the roles of childhood trauma and cognitive-emotional factors in NSSI among Chinese college students using network analysis.Methods: A total of 999 students from a university in central China were included in this study. Network analysis was used to examine the interrelationships between the frequency of NSSI thoughts and behaviors, childhood trauma subtypes (measured using the Childhood Trauma Questionnaire-Short Form), and cognitive-emotional factors such as early maladaptive schemas (EMSs) (measured using the Young Schema Questionnaire-Short Form), core self-evaluation (measured using the Core Self-Evaluations Scale), and emotion regulation (ER) strategies (measured using the Emotion Regulation Questionnaire). Structural equation modeling was used to further explore the role of the nodes most closely related to NSSI in the network analysis.Results: Emotional abuse and disconnection/rejection EMS are found to be directly related to NSSI thoughts (edge weight = 0.16 and 0.08, respectively). Disconnection/rejection EMS partially mediated (28.64%) the relationship between emotional abuse and NSSI thoughts, with a higher level of expression suppression corresponding to a greater positive relationship between emotional abuse and the disconnection/rejection EMS (p < 0.01).Conclusion: Our findings were in line with the cognitive-emotional model of NSSI, highlighting the importance of NSSI prevention in identifying risk groups who experienced emotional abuse in childhood and tended to use expressive suppression as an ER strategy.Keywords: childhood trauma, early maladaptive schema, emotion regulation strategy, non-suicidal self-injury, network analysis

Xiaoyue Feng,1,&ast; Jianli Shang,1,&ast; Zhengping Gu,1 Junhua Gong,1 Yong Chen,1,2 Youting Liu1,2 1R&D Department, Beijing UPROVEN Medical Technology Co., Ltd., Beijing, Daxing, People’s Republic of China; 2Beijing UPROVEN Institute of Dermatology, Beijing, Daxing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Youting Liu, R&D Department, Beijing UPROVEN Medical Technology Co., Ltd., Yard 5, Tianhua Avenue, Beijing, Daxing, 102699, People’s Republic of China, Tel +86 18510256963, Email YtLiu.adpt@outlook.comAbstract: AZA is a non-phenolic, saturated dicarboxylic acid with nine carbon atoms, naturally produced by the yeast Malassezia. It has diverse physiological activities, including antibacterial, anti-keratinizing, antimelanogenic, antioxidant and anti-inflammatory effects. AZA is widely used in dermatology and is FDA-approved for treating papulopustular rosacea. It also shows significant efficacy in acne vulgaris and melasma. This review summarizes the mechanisms of action and clinical applications of AZA, aiming to provide theoretical support for its clinical and cosmetic use and to facilitate further research.Keywords: azelaic acid, mechanism, rosacea, acne, melasma, safety

Zhiliang Li,1,2,&ast; Jiali Yang,1,3,&ast; Yang Sun,1 Shuo Han,1 Jietao Gong,1 Yi Zhang,1,3 Zhiyuan Feng,1 Hong Yao,4 Peiying Shi1,5 1College of Bee Science and Biomedicine, Fujian Agriculture and Forestry University, Fuzhou, 350002, People’s Republic of China; 2College of Food Science, Fujian Agriculture and Forestry University, Fuzhou, 350002, People’s Republic of China; 3College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou, 350002, People’s Republic of China; 4Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, 350122, People’s Republic of China; 5State and Local Joint Engineering Laboratory of Natural Biotoxins, Fujian Agriculture and Forestry University, Fuzhou, 350002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Yao, Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, 350122, People’s Republic of China, Email hongyao@mail.fjmu.edu.cn Peiying Shi, College of Bee Science and Biomedicine, Fujian Agriculture and Forestry University, Fuzhou, 350002, People’s Republic of China, Email peiyshi@126.comPurpose: Bee pollen possesses favorable anticancer activities. As a medicinal plant source, Schisandra chinensis bee pollen (SCBP) possesses potential pharmacological properties, such as reducing cisplatin-induced liver injury, but its anti–liver cancer effect is still rarely reported. This paper aims to investigate the effect and mechanism of SCBP extract (SCBPE) on hepatocellular carcinoma HepG2 cells.Methods: The effect of SCBPE on cell proliferation and migration of HepG2 cells was evaluated based on MTT assay, morphology observation, or scratching assay. Furthermore, tandem mass tag-based quantitative proteomics was used to study the effect mechanisms. The mRNA expression levels of identified proteins were verified by RT-qPCR.Results: Tandem mass tag-based quantitative proteomics showed that 61 differentially expressed proteins were obtained in the SCBPE group compared with the negative-control group: 18 significantly downregulated and 43 significantly upregulated proteins. Bioinformatic analysis showed the significantly enriched KEGG pathways were predominantly ferroptosis-, Wnt-, and hepatocellular carcinoma-signaling ones. Protein–protein interaction network analysis and RT-qPCR validation revealed SCBPE also downregulated the focal adhesion–signaling pathway, which is abrogated by PF-562271, a well-known inhibitor of FAK.Conclusion: This study confirmed SCBPE suppressed the cell proliferation and migration of hepatocellular carcinoma HepG2 cells, mainly through modulation of ferroptosis-, Wnt-, hepatocellular carcinoma-, and focal adhesion–signaling pathways, providing scientific data supporting adjuvant treatment of hepatocellular carcinoma using SCBP. Keywords: Schisandra chinensis bee pollen extract, HepG2 cells, proteomics, ferroptosis, Wnt-signaling pathway, focal adhesion–signaling pathway

Lihua Zhou,1,&ast; Kun Zhang,2,3,&ast; Juanjuan Guo,4 Jianbo Liu,5 Suhong Wang,6 Jingbo Gong7 1College of Education Science, Hengyang Normal University, Hengyang, People’s Republic of China; 2Suzhou Guangji Hospital, Suzhou, People’s Republic of China; 3Affiliated Guangji Hospital of Soochow University, Suzhou, People’s Republic of China; 4School of Education, Hunan University of Science and Technology, Xiangtan, Hunan, People’s Republic of China; 5Department of Child Psychiatry of Shenzhen Kangning Hospital, Shenzhen Mental Health Center, School of Mental Health, Shenzhen University, Shenzhen, People’s Republic of China; 6Department of Clinical Psychology, The Third Affiliated Hospital, Soochow University, Changzhou, People’s Republic of China; 7Shanghai Changning Mental Health Centre, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingbo Gong, Shanghai Changning Mental Health Center, Shanghai, 200335, People’s Republic of China, Email yefenhua@126.com Suhong Wang, Department of Clinical Psychology, The Third Affiliated Hospital, Soochow University, Changzhou, People’s Republic of China, Email yarmine@gmail.comBackground: The present study aimed to investigate the potential role of perceived stress, impulsivity trait, executive dysfunction in non-suicidal self-injury (NSSI) thoughts among college students, as well as the gender differences.Methods: A sample of 890 university students completed self-report measures of NSSI thoughts in the past month, the level of perceived stress, impulsivity traits, and executive dysfunction.Results: Compared to those with low level of perceived stress, participants with high level of perceived stress reported significant higher levels of impulsivity trait and executive dysfunction, and higher frequency of NSSI thoughts, and there were no gender differences. Male participants with NSSI thoughts, compared to males without NSSI thoughts, reported significant higher levels of perceived stress and executive dysfunction. Female participants with NSSI thoughts, compared to females without NSSI thoughts, reported significant higher levels of perceived stress, impulsivity trait, and executive dysfunction. Hierarchical regression analysis revealed only executive dysfunction was associated with NSSI thoughts in males, while only perceived stress was associated with NSSI thoughts in females.Conclusion: This study revealed different influence factors for NSSI thoughts in male and female college students. NSSI thoughts in males were more likely associated with executive dysfunction while in females were due to recently perceived stress.Keywords: perceived stress, impulsivity, executive dysfunction, non-suicidal self-injury, gender difference

Jianmin Gong,1,2,&ast; Bo Shi,1,3,&ast; Ping Yang,1 Adeel Khan,4 Tao Xiong,2 Zhiyang Li1 1Department of Clinical Laboratory, Nanjing Drum Tower Hospital, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, 210000, People’s Republic of China; 2College of Life Science, Yangtze University, Jingzhou, 434025, People’s Republic of China; 3Department of Clinical Laboratory, Nanjing Jiangning Hospital of Chinese Medicine (CM), Nanjing, 211100, People’s Republic of China; 4Department of Biotechnology, University of Science and Technology Bannu, Bannu, 28100, Islamic Republic of Pakistan&ast;These authors contributed equally to this workCorrespondence: Tao Xiong, College of Life Science, Yangtze University, Jingzhou, 434025, People’s Republic of China, Tel +8613872387410, Email xiongtao@yangtzeu.edu.cn Zhiyang Li, Department of Clinical Laboratory, Nanjing Drum Tower Hospital, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, 210008, People’s Republic of China, Tel +8618951703765, Email lizhiyang@nju.edu.cnBackground: Hypertrophic cardiomyopathy (HCM) is a dominantly inherited disease associated with sudden immune cell associations that remain unclear. The aim of this study was to comprehensively screen candidate markers associated with HCM and immune cells and explore potential pathogenic pathways.Methods: First, download the GSE32453 dataset to identify differentially expressed genes (DEGs) and perform Gene Ontology and pathway enrichment analysis using DAVID and GSEA. Next, construct protein-protein interaction (PPI) networks using String and Cytoscape to identify hub genes. Afterward, use CIBERSORT to determine the proportion of immune cells attributed to key genes in HCM and conduct ROC analysis based on the external dataset GSE36961 to evaluate their diagnostic value. Finally, validate the expression of key genes in the hypertrophic cardiomyocyte model through qRT-PCR using data from the HPA database.Results: Comprehensive analysis revealed that there were 254 upregulated genes and 181 downregulated genes in HCM. The enrichment study underscored pathways of inflammatory signaling, including MAPK and PI3K-Akt pathways. Pathways abundant in genes associated with HCM encompassed myocardial contraction and NADH dehydrogenase activity. Additionally, the analysis of immune infiltration revealed a notable increase in macrophages, NK cells, and monocytes in the HCM group, showing statistically significant variances in CD4 memory resting T cell infiltration when compared to the healthy control group. Within the validation dataset GSE36961, the Area Under the Curve (AUC) scores for eight crucial genes (FOS, CD86, CD68, BDNF, PIK3R1, PLEK, RAC2, CCL2) each exceeded 0.8. The HPA database revealed the positioning traits and paths of these eight crucial genes in smooth muscle cells, myocardial cells, and fibroblasts. The outcomes of the qRT-PCR were aligned with the sequencing findings.Conclusion: Bioinformatics analysis unveiled pivotal genes, pathways, and immune involvement, illuminating the molecular underpinnings of HCM. These findings suggest promising therapeutic targets for clinical applications.Keywords: hypertrophic cardiomyopathy, bioinformatic, immune cells infiltration, biomarker

Rongyao Liang,1,&ast; Pei Li,1,2,&ast; Na Yang,1 Xiaoyi Xiao,1 Jing Gong,1 Xingyuan Zhang,1 Yunuan Bai,1 Yanlong Chen,1 Zhiyong Xie,3 Qiongfeng Liao1 1School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, People’s Republic of China; 2Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, People’s Republic of China; 3School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiongfeng Liao, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, People’s Republic of China, Tel +86 2039358081, Email zyfxliao@gzucm.edu.cn Zhiyong Xie, School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou, 510006, People’s Republic of China, Tel +86 075523260207, Email xiezhy@mail.sysu.edu.cnPurpose: Given the potent immunostimulatory effects of bacterial outer membrane vesicles (OMVs) and the significant anti-colon tumor properties of Parabacteroides distasonis (Pd), this study aimed to elucidate the role and potential mechanisms of Pd-derived OMVs (Pd-OMVs) against colon cancer.Methods: This study isolated and purified Pd-OMVs from Pd cultures and assessed their characteristics. The effects of Pd-OMVs on CT26 cell uptake, proliferation, and invasion were investigated in vitro. In vivo, a CT26 colon tumor model was used to investigate the anti-colon tumor effects and underlying mechanisms of Pd-OMVs. Finally, we evaluated the biosafety of Pd-OMVs.Results: Purified Pd-OMVs had a uniform cup-shaped structure with an average size of 165.5 nm and a zeta potential of approximately − 9.56 mV, and their proteins were associated with pathways related to immunity and apoptosis. In vitro experiments demonstrated that CT26 cells internalized the Pd-OMVs, resulting in a significant decrease in their proliferation and invasion abilities. Further in vivo studies confirmed the accumulation of Pd-OMVs in tumor tissues, which significantly inhibited the growth of colon tumors. Mechanistically, Pd-OMVs increased the expression of CXCL10, promoting infiltration of CD8+ T cells into tumor tissues and expression of pro-inflammatory factors TNF-α, IL-1β, and IL-6. Notably, Pd-OMVs demonstrated a high level of biosafety.Conclusion: This paper elucidates that Pd-OMVs can exert significant anti-colon tumor effects by upregulating the expression of the chemokine CXCL10, thereby increasing the infiltration of CD8+ T cells into tumors and enhancing antitumor immune responses. This suggests that Pd-OMVs may be developed as a novel nanoscale potent immunostimulant with great potential for application in tumor immunotherapy. As well as developed as a novel nano-delivery carrier for combination with other antitumor drugs. Keywords: Parabacteroides distasonis, outer membrane vesicles, colon tumor, CXCL10, CD8+ T cells

Yiqun Liao,1 Junjie Gong,1 Xiaoliang Yuan,2 Xiaoling Wang,1 Yuanhong Huang,3 Xiaohong Chen1 1Department of Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, People’s Republic of China; 2Department of Respiratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, People’s Republic of China; 3Department of Laboratory Medicine, Ganzhou Municipal Hospital, Ganzhou, People’s Republic of ChinaCorrespondence: Yuanhong Huang, Department of Laboratory Medicine, Ganzhou Municipal Hospital, NO. 49 Dagong Road, Zhanggong District, Ganzhou, Jiangxi Province, 341000, People’s Republic of China, Email 11987825@qq.com Xiaohong Chen, Department of Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, NO. 23 Qingnian Road, Zhanggong District, Ganzhou, Jiangxi Province, 341000, People’s Republic of China, Email ccxxhh1997@163.comAbstract: Hypervirulent Klebsiella pneumoniae (hvKP) has emerged as a novel variant of K. pneumoniae, exhibiting distinct phenotypic and genotypic characteristics that confer increased virulence and pathogenicity. It is not only responsible for nosocomial infections but also community-acquired infections, including liver abscesses, endophthalmitis, and meningitis, leading to significant morbidity and mortality. HvKP has been reported all over the world, but it is mainly prevalent in Asia Pacific, especially China. Moreover, hvKP can acquire carbapenemase genes resulting in the emergence of carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP), which possesses both high virulence and drug resistance capabilities. Consequently, CR-hvKP poses substantial challenges to infection control and presents serious threats to global public health. In this paper, we provide a comprehensive summary of the epidemiological characteristics, virulence factors, and mechanisms underlying carbapenem resistance in hvKP strains with the aim of offering valuable insights for practical prevention strategies as well as future research.Keywords: hypervirulent Klebsiella pneumoniae, virulence factors, plasmid, drug resistance

Fan Liu,1,&ast; Huan Yu,1,&ast; Qing Xu,2,&ast; Jianwei Gong,1 Ming Huo,3,4 Fei Huang1,3 1School of Health and Life Sciences, Binzhou Medical University, Yantai, People’s Republic of China; 2Yaitai Hospital, Binzhou Medical University, Yantai, People’s Republic of China; 3School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao, People’s Republic of China; 4Beijing Chaoyang Sanhuan Cancer Hospital, Beijing, 100122, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ming Huo, School of Health and Life Sciences, University of Health and Rehabilitation Sciences, 17 Shandong Road, Qingdao, 266071, People’s Republic of China, Email huoming8@gmail.com Fei Huang, School of Health and Life Sciences, Binzhou Medical University, 346 Guanhai Road, Laishan, Shandong Province, 264003, People’s Republic of China, Email hfei22518@163.comPurpose: Falls are a significant factor affecting the health of older adults and are closely related to cognitive function. Adopting an effective method to evaluate the risk of falls in older adults is essential for improving their healthcare. This study combined cognitive and motor functions to determine a reliable probe reaction time during water-carrying walking.Patients and Methods: We divided 100 community-dwelling older adults (aged 65 years and over) into two groups according to their fall history: the fall group and no-fall group. All subjects were tested on fall tasks using the timed up-and-go (TUG) test, 10-m walk timing test, trail marking test part-A (TMT-A), and water-carrying walking probe reaction time (P-RT).Results: The fall group showed slower walking speeds and longer TUG, TMT-A, and P-RT times than the no-fall group. In the logistic regression analysis with falls as the dependent variable, water-carrying walking P-RT was identified as a useful factor, and the cut-off value of the water-carrying walking P-RT was 454 ms, which was evaluated using the receiver operating characteristic curve.Conclusion: The P-RT of the water-carrying walking test was found to be credible and useful for evaluating the fall risk in older adults. Therefore, it is recommended that the P-RT-based dual-task be used as a predictive indicator of future falls in the older population.Keywords: falls, probe reaction time, older adults, dual task

Xiaoli Xiang,1,2 Zhicheng Zhang,1 Ying Liu,1 Wenxuan Xu,1 Ju Gong,3 Sheng Yu,4 Lan Zhang,5 Tingwang Jiang1 1Department of Key Laboratory, Affiliated Changshu Hospital of Nantong University, Changshu, People’s Republic of China; 2Department of Ophthalmology, Affiliated Changshu Hospital of Nantong University, Changshu, People’s Republic of China; 3Department of Emergency Medicine, Affiliated Changshu Hospital of Nantong University, Changshu, People’s Republic of China; 4Department of Critical Care Medicine, Affiliated Changshu Hospital of Nantong University, Changshu, People’s Republic of China; 5Information Center, Affiliated Changshu Hospital of Nantong University, Changshu, People’s Republic of ChinaCorrespondence: Tingwang Jiang, Department of Key Laboratory, Affiliated Changshu Hospital of Nantong University, No. 68 Haiyu Nan Road, Changshu, Jiangsu Province, People’s Republic of China, Tel +86 15995921425, Fax +86 512-52277250, Email jtwgyp@163.comPurpose: To evaluate the potential relationships between serum interleukin (IL)-2, IL-4, IL-6, IL-10, IL-17, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α levels and occurrence of respiratory failure in patients with early-stage COVID-19 disease.Patients and Methods: We analyzed clinical characteristics, laboratory parameters, and immunoinflammatory markers in 302 patients diagnosed with SARS-CoV-2 infection who required hospitalization at Changshu Hospital of Nantong University. IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ, and TNF-α levels in the peripheral blood of patients hospitalized five days after disease onset were measured using multiplex bead-based flow fluorescent immunoassay (MBFFI).Results: Patients with respiratory failure had higher serum IL-4 [0 (0, 0.54) pg/mL], IL-6 [40.76 (12.33, 90.28) pg/mL], IL-10 [6.65 (4.12, 11.34) pg/mL], and IL-17 [9.48 (4.31, 12.13) pg/mL] levels than patients without respiratory failure (P=0.042, P< 0.0001, P=0.012, and P=0.036, respectively). Serum IL-2, IFN-γ, and TNF-α levels were not significantly different between the two groups. The occurrence of respiratory failure was positively correlated with sex (R=0.122, P=0.034), lactic acid (R=0.193, P=0.007), white blood cell count (R=0.121, P=0.038), erythrocyte distribution width (R=0.131, P=0.024), thyrocalcitonin (R=0.280, P< 0.0001), and D-dimer levels (R=0.214, P< 0.0001) but negatively correlated with oxygen partial pressure (R=− 0.208, P=0.004), oxygen saturation (R=− 0.220, P=0.002), lymphocyte count (R=− 0.129, P=0.026), and calcium (R=− 0.152, P=0.042). Among the immunoinflammatory biomarkers, the occurrence of respiratory failure was positively correlated with IL-4 (R=− 0.117, P=0.042), IL-6 (R=0.206, P< 0.0001), IL-10 (R=0.145, P=0.012), and IL-17 (R=0.121, P=0.036) levels.Conclusion: Serum levels of pro-inflammatory cytokines IL-6 and IL-17 and anti-inflammatory cytokines IL-4 and IL-10 were significantly elevated in patients with respiratory failure and weakly positively correlated with the occurrence of respiratory failure. Further studies are required to explore these key immune mechanisms to help clinicians better manage acute complications, long-term sequelae, and possible future COVID-19 variants and be flexible in managing future epidemics and similar public health threats.Keywords: COVID-19, respiratory failure, hypoxemia, biomarkers, cytokines, disease progression

Jiaojiao Gong,1,2 Renjie Yu,1 Xiaoxia Hu,1 Huating Luo,1 Qingzhu Gao,3 Yadi Li,1 Guili Tan,1 Haiying Luo,1 Bo Qin1 1Department of Infectious Diseases, Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Nephrology, Bishan Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Bo Qin, Department of Infectious Diseases, Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Email cqmuqb@163.comPurpose: The accurate prediction of non-cirrhotic hepatocellular carcinoma (NCHCC) risk facilitates improved surveillance strategy and decreases cancer-related mortality. This study aimed to explore the correlation between immunogenic cell death (ICD) and NCHCC prognosis using The Cancer Genome Atlas (TCGA) datasets, and the potential prognostic value of ICD-related genes in NCHCC.Methods: Clinical and transcriptomic data of patients with NCHCC patients were retrieved from TCGA database. Weighted gene co-expression network analysis was performed to obtain the NCHCC phenotype-related module genes. Consensus clustering analysis was performed to classify the patients into two clusters based on intersection genes among differentially expressed genes (DEGs) between cancer and adjacent tissues, NCHCC phenotype-related genes, and ICD-related genes. NCHCC-derived tissue microarray was used to evaluate the correlation of the expression levels of key genes with NCHCC prognosis using immunohistochemical staining.Results: Cox regression analyses were performed to construct a prognostic risk score model comprising three genes (TMC7, GRAMD1C, and GNPDA1) based on DEGs between two clusters. The model stratified patients with NCHCC into two risk groups. The overall survival (OS) of the high-risk group was significantly lower than that of the low-risk group. Univariable and multivariable Cox regression analyses revealed that these signature genes are independent predictors of OS. Functional analysis revealed differential immune status between the two risk groups. Next, a nomogram was constructed, which demonstrated the potent distinguishing ability of the developed model based on receiver operating characteristic curves. In vitro functional validation revealed that the migration and invasion abilities of HepG2 and Huh7 cells were upregulated upon GRAMD1C knockdown but downregulated upon TMC7 knockdown.Conclusion: This study developed a prognostic model comprising three genes, which can aid in predicting the survival of patients with NCHCC and guide the selection of drugs and molecular markers for NCHCC.Keywords: immunogenic cell death-related genes, non-cirrhotic hepatocellular carcinoma, risk stratification, nomogram

Lingzhou Zhao,&ast; Jiali Gong,&ast; Qinli Qi,&ast; Changcun Liu, Hongxing Su, Yan Xing, Jinhua Zhao Department of Nuclear Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinhua Zhao; Yan Xing, Department of Nuclear Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100, Haining Road, Shanghai, 200080, People’s Republic of China, Tel/Fax +86 21 3779 8352, Email zhaojinhua1963@126.com; xy.1@163.comPurpose: The unique structure of nanobodies is advantageous for the development of radiopharmaceuticals for nuclear medicine. Nanobodies targeted to human epidermal growth factor receptor 2 (HER2) can be used as tools for the imaging and therapy of HER2-overexpressing tumors. In this study, we aimed to describe the generation of a 131I-labeled anti-HER2 nanobody as a targeted radionuclide therapy (TRNT) agent for HER2-positive breast cancer.Methods: The anti-HER2 nanobody NM-02 was labeled with 131I using the iodogen method, and its radiochemical purity and stability in vitro were assessed. The pharmacokinetic profile of 131I-NM-02 was investigated in normal mice. Tumor accumulation, biodistribution, and therapeutic potential of 131I-NM-02 were evaluated in HER2-positive SKBR3 xenografts; HER2-negative MB-MDA-231 xenografts were used as the control group.Results: 131I-NM-02 could be readily prepared with satisfactory radiochemical purity and stability in vitro. Apparent tumor uptake was observed in HER2-positive tumor-bearing mice with rapid blood clearance and favorable biodistribution. 131I-NM-02 could significantly inhibit tumor growth and extend the life of these mice with good organ compatibility. Negligible tumor accumulation and inhibitory effects of 131I-NM-02 were observed in the negative control group.Conclusion: 131I-NM-02 has the potential to be explored as a novel tool for TRNT of HER2-positive breast cancer.Keywords: human epidermal growth factor receptor 2, nanobody, 131I, targeted radionuclide therapy

Yiqun Liao,1 Junjie Gong,1 Xiaoliang Yuan,2 Hongfei Lu,1 Lixia Jiang1 1Department of Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, People’s Republic of China; 2Department of Respiratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzho, People’s Republic of ChinaCorrespondence: Yiqun Liao, Department of Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, 23 Qingnian Road, Zhanggong District, Ganzhou, 341000, Jiangxi Province, People’s Republic of China, Tel +86-15979704263, Email joanna_qun@163.comBackground: The global prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) has become a serious challenge for nosocomial infection and attracted worldwide attention. This study explored the drug resistance genes and molecular characteristics for CRKP, providing a reference for nosocomial prevention and control.Methods: A total of 42 CRKP isolates were collected from the First Affiliated Hospital of Gannan Medical University (Ganzhou, China) from January 2018 to February 2021. The drug resistance of CRKP was tested by the VitekII Compact system. Drug resistance gene expression was detected by poly-merase chain reaction (PCR), and molecular typing was performed by pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST).Results: All the 42 CRKP isolates were multi-drug resistant. Among them, 35 isolates (83.3%) produced blaKPC-2 and 12 isolates (28.6%) produced blaNDM-1. The detection rate of blaIMP-4 and blaOXA-48 was 2.4% (1/42), respectively. Twelve isolates (28.6%) carried both blaKPC-2 and blaNDM-1, one isolate (2.4%) carried both blaKPC-2 and blaIMP-4, and one isolate (2.4%) carried blaKPC-2, blaNDM-1 and blaOXA-48. A variety of other extended-spectrum beta-lactamases (ESBLs) were also detected. All 42 isolates carried blaSHV and blaCTX-M-1, 27 isolates (64.3%) carried blaTEM and 12 isolates (28.6%) carried blaCTX-M-9. The MLST data classified the 42 CRKP isolates into 11 sequence types, mainly ST11, accounting for 61.9% (26/42), of which 92.3% of isolates (24/26) carrying blaKPC-2. The PFGE results demonstrated that the 42 CRKP isolates could be divided into 20 clusters A-T, with cluster A (26.2%, 11/42) and cluster H (21.4%, 9/42) dominating, which were all ST11.Conclusion: The CRKP isolates were severely multi-drug resistant, and the main resistant gene was blaKPC-2 production, carrying multiple ESBLs genes simultaneously. The MLST and PFGE revealed that the ST11-blaKPC-2 Klebsiella pneumoniae was the main clonotype. Our findings may offer help to antibiotics selection and nosocomial infection prevention and control.Keywords: carbapenem-resistant Klebsiella pneumoniae, drug resistance genes, homology, molecular epidemiological characteristics

Jian Gong,1,2,&ast; Weiwei Wu,3,&ast; Liguo Qiu,1,2 Xi Wang,1,2 Jianwei Bao,1,2 Jinjing Wang,4 Lifang Cheng,1,2 Zhiyuan Fu,1,5 Fengming Hu1,2 1Department of Integrated Traditional Chinese and Western Medicine of Dermatology, Dermatology Hospital of Jiangxi Province, Nanchang, Jiangxi, People’s Republic of China; 2Jiangxi Provincial Clinical Research Center for Skin Diseases, Nanchang, Jiangxi, People’s Republic of China; 3Department of Plastic and Dermatological Surgery, The Fifth People’s Hospital of Hainan Province, Haikou, Hainan, People’s Republic of China; 4Clinical School of Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, People’s Republic of China; 5Department of Pharmacy, Dermatology Hospital of Jiangxi Province, Nanchang, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiyuan Fu, Department of Pharmacy, Dermatology Hospital of Jiangxi Province, Nanchang, Jiangxi, People’s Republic of China, Tel +86 13970827820, Fax +86-0791-85207512, Email 1074586168@qq.com Fengming Hu, Department of Integrated Traditional Chinese and Western Medicine of Dermatology, Dermatology Hospital of Jiangxi Province, Nanchang, Jiangxi, People’s Republic of China, Tel +86 13970935828, Fax +86-0791-85207512, Email 18970802429@163.comAbstract: Psoriasis is an immune-mediated chronic inflammatory dermatosis influenced by hereditary and environmental factors. Human immunodeficiency virus (HIV) infection affects the immune system and exacerbates psoriatic lesions. We report the case of a 33-year-old male patient diagnosed with psoriasis vulgaris, psoriatic arthritis and HIV infection. Acitretin capsules, etanercept and high-active antiretroviral therapy (HAART) were effective. Two months after etanercept was discontinued, his condition worsened. After switching to secukinumab combined with HAART, the symptoms of psoriatic arthritis resolved rapidly after four weeks, with a Disease Activity Index for Psoriatic Arthritis score of 0. The time to achieve psoriasis area and severity index 40, 75, 90, and 100 were 2, 4, 8, and 29 weeks. The treatment was maintained for 1 year with no adverse reactions. Regarding the stable CD4+ T lymphocyte count and the viral load, administering anti-IL-17 monoclonal antibodies is an effective treatment option for psoriasis patients.Keywords: psoriasis, HIV, etanercept, secukinumab, biologics

Fan Liu,1,&ast; Huan Yu,1,&ast; Qing Xu,2,&ast; Jianwei Gong,1 Ming Huo,3 Fei Huang1,3 1School of Health and Life Sciences, Binzhou Medical University, Yantai, People’s Republic of China; 2Yaitai Hospital, Binzhou Medical University, Yantai, People’s Republic of China; 3School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ming Huo, School of Health and Life Sciences, University of Health and Rehabilitation Sciences, 17 Shandong Road, Qingdao, 266071, People’s Republic of China, Email huoming8@gmail.com Fei Huang, University of Health and Rehabilitation Sciences, Binzhou Medical University, 346 Guanhai Road, Laishan, Shandong Province, 264003, People’s Republic of China, Email hfei22518@163.com

Mingfang Li,1 Jiaojiao Shi,1 Ming Chu,1 Youmei Shen,1 Shimeng Zhang,1 Xingxing Sun,1 Hengli Zhang,1 Qing Yan,1 Jinlong Gong,2 Gregory YH Lip,3,4 Minglong Chen1,5 1Division of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Division of Cardiology, Jiangdu People’s Hospital, Yangzhou, People’s Republic of China; 3Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, UK; 4Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; 5Division of Cardiology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of ChinaCorrespondence: Minglong Chen, Division of Cardiology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People’s Republic of China, Tel +86-25-68303115, Fax +86-25-6813-6479, Email chenminglong@njmu.edu.cnAbstract: China has a large population of elderly in rural areas. Village doctors are acting as health-care gatekeepers for the rural elderly in China and are encouraged to provide more long-term care for patients with chronic diseases such as atrial fibrillation (AF). The data of AF registries from the rural elderly are limited. The present registry aims to provide contemporary data on the current AF-related health status of the rural elderly and the gaps in management of AF by village doctors. This study has two phases. The first phase is a cross-sectional study of AF screening in two rural towns of eastern China. All the residents aged ≥ 65 years are eligible and will be invited to attend a government-led health examination or an in-house AF screening program. The AF detection rate, the awareness of AF and the usage of oral anticoagulants and smartphones by AF patients, and the ability to diagnose and manage AF by village doctors will be assessed. Participants with AF detected in the first phase are eligible for the second phase. A variety of modes of intensified education will be provided to all AF patients and their family members to enrich their AF-related knowledge. Their village doctors will be offered a lecture-based training program focusing on Atrial fibrillation Better Care (ABC) pathway. Follow-up will be conducted for 1 year. The primary endpoint is the composite of all stroke and all-cause mortality. The first phase of AF screening was conducted between April 2019 and June 2019, and 18,712 participants with the mean age of 73.1± 5.8 years were enrolled. The second phase that includes 810 patients with AF, started on 1 May 2019. This study will provide a perspective of primary care system and would indirectly reflect the current status of chronic disease care in rural China.Keywords: atrial fibrillation, elderly, village doctors, rural China

Runan Zuo,1 Yan Zhang,1 Xiaorong Chen,1 Shiheng Hu,1 Xinhao Song,1 Xiuge Gao,1 Jiahao Gong,1 Hui Ji,1 Fengzhu Yang,1 Lin Peng,1 Kun Fang,2 Yingjun Lv,1 Junren Zhang,1 Shanxiang Jiang,1 Dawei Guo1 1Engineering Center of Innovative Veterinary Drugs, Center for Veterinary Drug Research and Evaluation, MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, People’s Republic of China; 2The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, People’s Republic of ChinaCorrespondence: Dawei Guo; Shanxiang Jiang, Engineering Center of Innovative Veterinary Drugs, Center for Veterinary Drug Research and Evaluation, MOE Joint International Research Laboratory of Animal, Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, 210095, People’s Republic of China, Tel +86 25-84396215, Fax +86-25-84398669, Email gdawei0123@njau.edu.cn; nauvy@sina.comBackground: Halofuginone (HF)-loaded TPGS polymeric micelles (HTPM) were successfully fabricated using the thin-film hydration technique. HTPM via intravenous injection have been demonstrated to exert an excellent anticancer effect against triple-negative breast cancer (TNBC) cells and subcutaneous xenografts. In the present study, we further explored the potential treatment effect and mechanism of orally administered HTPM alone and in combination with surgical therapy on TNBC in subcutaneous and orthotopic mouse models.Methods: Herein, the stability and in vitro release behavior of HTPM were first evaluated in the simulated gastrointestinal fluids. Caco-2 cell monolayers were then used to investigate the absorption and transport patterns of HF with/without encapsulation in TPGS polymeric micelles. Subsequently, the therapeutic effect of orally administered HTPM was checked on subcutaneous xenografts of TNBC in nude mice. Ultimately, orally administered HTPM, combined with surgical therapy, were utilized to treat orthotopic TNBC in nude mice.Results: Our data confirmed that HTPM exhibited good stability and sustained release in the simulated gastrointestinal fluids. HF was authenticated to be a substrate of P-glycoprotein (P-gp), and its permeability across Caco-2 cell monolayers was markedly enhanced via heightening intracellular absorption and inhibiting P-gp efflux due to encapsulation in TPGS polymeric micelles. Compared with HF alone, HTPM showed stronger tumor-suppressing effects in subcutaneous xenografts of MDA-MB-231 cells when orally administered. Moreover, compared with HTPM or surgical therapy alone, peroral HTPM combined with partial surgical excision synergistically retarded the growth of orthotopic TNBC. Fundamentally, HTPM orally administered at the therapeutic dose did not cause any pathological injury, while HF alone led to weight loss and jejunal bleeding in the investigated mice.Conclusion: Taken together, HTPM could be applied as a potential anticancer agent for TNBC by oral administration.Graphical Abstract: Keywords: triple-negative breast cancer, Halofuginone hydrobromide, TPGS polymeric micelles, subcutaneous xenografts, orthotopic xenografts, oral administration

Yuanyuan Geng,1,&ast; Weiwei Wu,2,3,&ast; Rouyu Li,4– 6 Juan Xu,1 Ruixue Gu,1 Jiejie Lu,2 Wenai Zheng,7 Fei Zhao,1 Jianzhong Zhang,1 Jie Gong1 1National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China; 2Department of Dermatology, The Fifth People’s Hospital of Hainan Province, Haikou, People’s Republic of China; 3National Clinical Research Center for Skin and Immune Disease, Beijing, People’s Republic of China; 4Department of Dermatology, Peking University First Hospital, Beijing, People’s Republic of China; 5Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, People’s Republic of China; 6Research Center for Medical Mycology, Peking University, Beijing, People’s Republic of China; 7Department of Laboratory Medicine, The Fifth People’s Hospital of Hainan Province, Haikou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Gong Tel +86 10 5890 0368Email gongjie@icdc.cnBackground: Founder events have been observed among numerous plants and animal species living on oceanic islands due to the geographic separation of these islands and the small amount of original life they harbor. However, there has been little research on the ecological characteristics of pathogenic microorganisms on islands. Trichophyton rubrum ranks the most common isolated dermatophyte causing dermatophytosis in clinic and has become an epidemic strain worldwide in recent decades.Objective: To study the phylogenetic characteristics and the distribution pattern of genetic polymorphism of T. rubrum in China, which further provide theoretical basis for the prevention and control of T. rubrum.Methods: In the present study, we sequenced and analyzed the genetic characteristics of 204 T. rubrum isolates from Hainan Island and other sites in China. Phylogenetic analysis and genetic polymorphisms were studied based on a total of 41,409 high-quality whole-genome SNPs.Results: The majority of the isolates from Hainan Island clustered together. Mixed T. rubrum population differentiation was observed among the strains of different geographical origins. In addition, the genetic diversity (π) of the Hainan isolates was low and showed no significant difference from that of isolates from other sites.Conclusion: This study is the first to discuss general ecological and evolutionary principles related to pathogenic fungi. Our findings reveal a founder effect during the origination of T. rubrum on Hainan Island and provide guidance regarding prevention and treatment strategies.Keywords: founder effects, Trichophyton rubrum, genetic diversity, population differentiation

Junfeng Gong,&ast; Liwen Luo,&ast; Huan Liu, Changqing Li, Yu Tang, Yue Zhou Department of Orthopedics, The Second Affiliated Xinqiao Hospital of Army Military Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yue Zhou; Yu TangDepartment of Orthopedics, The Second Affiliated Xinqiao Hospital of Army Military Medical University, Xinqiao Street, Shapingba District, Chongqing, People’s Republic of ChinaTel +86 13908390792; +86 18623422628Fax +86 23-68755012Email happyzhou@vip.163.com; tangyu628@qq.comPurpose: We aimed to explore the role of enhanced recovery after surgery (ERAS) in patients who underwent percutaneous endoscopic lumbar interbody fusion (PELIF).Patients and Methods: We performed a retrospective, observational, cohort study on 91 patients who underwent PELIF for degenerative disc disease. The primary outcomes were postoperative opioid consumption, hospital length of stay (LOS), and hospital cost.Results: Forty-six patients comprised the ERAS group, and 45 patients comprised the pre-ERAS group (control group). The groups had comparable demographic characteristics. Good compliance with the ERAS pathway was observed in the ERAS group. Patients in the ERAS group used significantly fewer morphine equivalents compared with the pre-ERAS group (25.0 vs 33.3, respectively; p = 0.017). Hospital LOS did not decrease significantly in the ERAS group compared with the pre-ERAS group (3.1days vs 3.4 days, respectively; p = 0.096). Likewise, there was no significant difference in hospital cost between the pre-ERAS group and the ERAS group ($10,598.60 vs $10,384.50, respectively; p = 0.468).Conclusion: In the present study, the benefit of ERAS in the context of PELIF was limited. Although a multidisciplinary ERAS protocol can improve analgesia and decrease opioid consumption, no significant reduction in hospital LOS and cost was observed.Keywords: enhanced recovery after surgery, hospital length of stay, opioid use, hospital costs, percutaneous endoscopic spine surgery

Jennifer Gong,1 Simone Cheung,2 Alivia Fasso-Opie,3 Orla Galvin,4 Larissa S Moniz,5 Doug Earle,5 Todd Durham,6 Jason Menzo,6 Nan Li,7 Stephanie Duffy,7 Jill Dolgin,8 Mark S Shearman,8 Chiara Fiorani,9 Judit Banhazi,9 Avril Daly4 1Health Economics and Social Policy, Deloitte Access Economics, Melbourne, Victoria, Australia; 2Health Economics and Social Policy, Deloitte Access Economics, Sydney, New South Wales, Australia; 3Health Economics and Social Policy, Deloitte Access Economics, Canberra, Australian Capital Territory, Australia; 4Retina International, Dublin, D08 R9CN, Ireland; 5Fighting Blindness Canada, Toronto, Ontario, Canada; 6The Foundation Fighting Blindness, Raleigh, North Carolina, USA; 7The Janssen Pharmaceutical Companies of Johnson and Johnson, Raritan, New Jersey, USA; 8Applied Genetic Technologies Corporation, Cambridge, Massachusetts, USA; 9Novartis Pharma AG, Basel, SwitzerlandCorrespondence: Avril Daly Email avril.daly@retina-international.orgObjective: To estimate the annual cost of inherited retinal diseases (IRDs) in the United States of America (US) and Canada from a societal perspective – including costs to the health system, individual and family productivity costs, lost wellbeing and other societal economic costs – by setting and payer. Findings will inform the need for policy action to mitigate the impact of IRDs.Methods: The costs of IRDs were estimated using a cost-of-illness methodology, based on the prevalence of IRDs in each country. Intangible costs of reduced wellbeing were also estimated using disability-adjusted life years which were then converted to monetary values using the value of a statistical life.Results: Using base prevalence rates, total costs attributable to IRDs in the US were estimated to range between US$13,414.0 and US$31,797.4 million in 2019, comprising both economic costs (between US$4,982 and US$11,753.9 million; 37% of total costs) and wellbeing costs (between US$8,431.7 and US$20,043.6 million; 63%). Total costs attributable to IRDs in Canada were estimated to range between CAN$1637.8 and CAN$6687.5 million in 2019, comprising both economic costs (between CAN$566.6 and CAN$2,305.7 million; 34%) and wellbeing costs (between CAN$1,071.4 and CAN$4,381.9 million; 66% of total costs).Conclusion: The impact of IRDs in the US and Canada is substantial when considering both economic costs and reduced wellbeing. The wellbeing costs due to IRDs in the US and Canada are considerable, accounting for over 60% of total costs. Vision loss from IRDs often manifests in childhood, meaning some people live with vision impairment and blindness for their whole lives. Further research into current and emerging cost-effective therapies and interventions is required given the substantial economic burden faced by those living with vision loss.Keywords: genetic diagnosis, inherited retinal disease, cost-of-illness

Juan Jin,* Fengmei Qian,* Danna Zheng, Wenfang He, Jianguang Gong, Qiang He Department of Nephrology, Zhejiang Provincial People’s Hospital and Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianguang Gong; Qiang HeDepartment of Nephrology, Zhejiang Provincial People’s Hospital and Affiliated People’s Hospital, Hangzhou Medical College, 158 Shangtang Road, Xiacheng District, Hangzhou, Zhejiang, 310014, People’s Republic of ChinaEmail gojigu311@163.com; qianghe1973@126.comBackground: Renal fibrosis is a chronic and progressive process affecting kidneys in chronic kidney disease (CKD). Mesenchymal stem cells-derived exosomes (MSCs-Exo) have been shown to alleviate renal fibrosis and injury, but the mechanism of MSCs-Exo-induced renal protection remains unknown.Methods: In this study, MSCs were transfected with let-7i-5p antagomir (anti-let-7i-5p), and then exosomes were isolated from the transfected MSCs to deliver anti-let-7i-5p oligonucleotides to inhibit the level of let-7i-5p in kidney tubular epithelial cells (NRK-52E).Results: In both NRK-52E cells stimulated by TGF-β 1 and the mouse kidneys after unilateral ureteral obstruction (UUO), we demonstrated increased level of let-7i-5p. In addition, MSCs-Exo can deliver anti-let-7i-5p to reduce the level of let-7i-5p in NRK-52E cells and increase the expression of its target gene TSC1. Moreover, exosomal anti-let-7i-5p reduced extracellular matrix (ECM) deposition and attenuated epithelial–mesenchymal transition (EMT) process in transforming growth factor beta 1 (TGF-β 1)-stimulated NRK-52E cells and in the kidneys of UUO-treated mice. Meanwhile, mice received exosomal anti-let-7i-5p displayed reduced renal fibrosis and improved kidney function when challenged with UUO. Furthermore, exosomal anti-let-7i-5p promoted the activation the tuberous sclerosis complex subunit 1/mammalian target of rapamycin (TSC1/mTOR) signaling pathway in vivo and in vitro.Conclusion: In conclusion, exosomal anti-let-7i-5p from MSCs exerts anti-fibrotic effects in TGF-β 1-induced fibrogenic responses in NRK52E cells in vitro as well as in UUO-induced renal fibrosis model in vivo. These results provided a novel perspective on improving renal fibrosis by MSCs-Exo.Keywords: chronic kidney disease, renal fibrosis, mesenchymal stem cells, exosomes and microRNAs

Jing Gong,1 Youxiu Yao,2 Yanbiao Wang3 1Department of Anesthesiology, The 960th Hospital of the People’s Liberation Army Joint Logistical Support Force, Jinan, Shandong, People’s Republic of China; 2Department of Anesthesiology, Peking University Third Hospital, Beijing, People’s Republic of China; 3Department of Orthopaedics, The 960th Hospital of the People’s Liberation Army Joint Logistical Support Force, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Youxiu YaoDepartment of Anesthesiology, Peking University Third Hospital, Beijing, People’s Republic of ChinaTel +8618810488772Email yaoqing2008.happy@163.comBackground: The aim of this study is to evaluate the effect of ultrasound-guided bilateral cervical plexus block on general anesthesia, postoperative analgesia, and surgical outcomes in patients undergoing total parathyroidectomy with autotransplantation.Patients and Methods: Forty-eight ASA III–IV patients with hyperparathyroidism secondary to renal failure were included: 24 patients received ultrasound-guided bilateral superficial and deep cervical plexus block combined with general anesthesia (group A), and 24 patients received general anesthesia alone (group B). Postoperative patient-controlled intravenous analgesia was provided with sufentanil 2 μg/kg. The primary outcome is the postoperative pain scores. Secondary outcomes include intraoperative remifentanil dosage, changes in hemodynamics, extubation time, and sufentanil consumption. Surgical outcomes regarding calcium, phosphorus and parathormone values were also noted.Results: The patients in group A required less remifentanil than group B (2.56± 0.92mg vs 3.38± 0.84mg, P=0.002) and lower VAS scores at 1, 3, 10, 24, and 48h postoperatively (P < 0.001). While the systolic blood pressure in group A patients was significantly greater than that in group B at T3 (immediately after extubation, [138.33± 11.36 vs 129.08± 17.06 mmHg; P=0.032]), heart rates in group A were lower than in group B at 1 min before induction (T1 [89.46 ± 9.14 vs 96.71± 14.19, P=0.042]) and 1 min after intubation (T2 [70.08 ± 5.35 vs 79.25 ± 11.81, P=0.002]). The extubation time in group A was shorter than that in group B (P < 0.001). There was no difference in calcium, phosphorus and parathormone values, nor in sufentanil consumption between the groups.Conclusion: Ultrasound-guided bilateral superficial and deep cervical plexus block combined with general anesthesia for TPTA is an effective strategy to improve anesthesia management and achieve better postoperative analgesia, and has no impact on surgical outcomes.Keywords: ultrasound guidance, cervical plexus block, hyperparathyroidism, renal failure

Jianming Gong,* Xiangdong Kong,* Jinhui Qi, Jiangkun Lu, Shaofeng Yuan, Ming Wu Department of Surgery, Tinglin Hospital of Jinshan District, Shanghai 201505, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ming WuDepartment of Surgery, Tinglin Hospital of Jinshan District, No. 80 Siping North Road, Jinshan District, Shanghai 201505, People’s Republic of ChinaTel + 86-18121367005Email wum7005@126.comBackground: Thyroid cancer is one of the most common cancers with rising incidence worldwide, and papillary thyroid carcinoma (PTC) accounts for 80– 85% of thyroid malignancy. Although it has been reported that many genes relate to the carcinogenesis of PTC, the molecular mechanisms remain mostly unclear.Methods: QRT-PCR assay was performed to detect circRNA_104565, miR-134 and ELF2 expression. CCK8 assay was exercised to examine cell proliferation. Western blot was used to detect ELF2 expression.Results: We found that circRNA_104565 was highly expressed in PTC tissue and cell and promoted cell proliferation in vitro and in vivo. In addition, circRNA_104565 promoted cell proliferation in PTC by regulating the miR-134/ELF2 axis.Conclusion: Hence, revealing the function of circRNA_104565 in PTC is important for understanding the molecular mechanism of carcinogenesis and providing new biomarkers or therapeutic targets for PTC.Keywords: circRNA_104565, cell proliferation, PTC, miR-134, ELF2

Jinchun Cong,1,* Jian Gong,2,* Chuanjia Yang,3 Zhixiu Xia,1 Hong Zhang1 1Department of Colorectal Tumor Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, People’s Republic of China; 2Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People’s Republic of China; 3Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang 110016, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong Zhang Email zhanghong7919@outlook.comPurpose: This study aimed to investigate the effects of microRNA (miR)-22 on biological behaviors of colon cancer cells and to explore the relationship between miR-22 and NLRP3.Materials and Methods: First, human colon cancer HCT116 cells were transfected with a miR-22 mimic, miR-22 inhibitor, control mimic, and control inhibitor, respectively. CCK8, colony formation, and transwell assays were performed to observe cell proliferation, migration, and invasion. Western blotting was used to analyze the expression of recombinant NLRP3 (NLR family, pyrin domain-containing protein 3) and epithelial–mesenchymal transformation (EMT)-related proteins. The target relationship between miR-22 and NLRP3 was verified by double luciferase report. Second, an NLRP3 inhibitor and NLRP3 mimic were transfected into HCT116 cells, and the biological behaviors and EMT-related proteins were again observed. Finally, a nude mouse xenograft model was constructed to verify the above results.Results: In vitro, compared with the control group, administration of the miR-22 mimic significantly decreased proliferation, migration, and invasion of HCT116 cells, whereas the miR-22 inhibitor markedly increased their proliferation and invasion (p< 0.05). Levels of NLRP3, interleukin-1β (IL-1β), matrix metalloproteinase-9 (MMP-9), MMP-2, N-cadherin, and vimentin were significantly reduced after miR-22 mimic transfection (p< 0.05). Furthermore, silencing of NLRP3, a downstream gene of miR-22 in HCT116 cells, suppressed proliferation, migration, and invasion of HCT116 cells. However, overexpression of NLRP3 weakened the effects of the miR-22 mimic. In vivo, overexpression of miR-22 slowed the growth rate of tumors and reduced Ki-67 expression in tumor tissues compared with the model group (p< 0.05). In tumor tissues, overexpression of miR-22 also decreased expression of NLRP3, IL-1β, MMP-9, MMP-2, N-cadherin, and vimentin compared with the model group (p< 0.05). Overexpression of NLRP3 weakened the role of miR-22 overexpression in vivo.Conclusion: miR-22 suppresses cell proliferation, migration, and invasion in colorectal cancer by targeting NLRP3.Keywords: miR-22, NLRP3, colorectal cancer, epithelial–mesenchymal transformation, invasion

Zhibing Ou,1,* Hua Zhong,2,* Liang Zhang,2,3 Minghua Deng,2 Wenfeng Zhang,2 Jingyuan Wang,2 Huaguo Feng,2 Jianping Gong,2 Chunmu Miao,2 Zhujun Yi2 1Department of Hepatobiliary Surgery, Chenzhou No.1 People’s Hospital, Chenzhou, Hunan 410000, People’s Republic of China; 2Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 40000, People’s Republic of China; 3Institute of Ultrasound Imaging, Department of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 40000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhujun Yi; Chunmu MiaoDepartment of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 40000, People’s Republic of ChinaTel +86-15803630430Email 792937539@qq.com; luckmum@163.comPurpose: To investigate the effect and mechanism of macrophage membrane-coated nanoparticles (M-NPs) on hepatic ischemia-reperfusion injury (I/RI) caused by orthotopic liver transplantation. In addition, the advantages of TLR4+/M-NPs compared to M-NPs are discussed.Materials and Methods: We prepared biomimetic M-NPs and identified their characteristics. M-NPs were injected into an SD rat model of orthotopic liver transplantation, and the anti-inflammatory and anti-I/RI activities of M-NPs were studied in vivo and in vitro. In addition, we overexpressed macrophage membrane Toll-like receptor 4 (TLR4) in vitro and prepared TLR4+/M-NPs. Then, we assessed the characteristics and advantages of TLR4+/M-NPs.Results: The M-NPs neutralized endotoxin, inhibited the overactivation of Kupffer cells (KCs) and suppressed the secretion of inflammatory factors by inhibiting the endotoxin-mediated TLR4/MyD88/IRAK1/NF-κB signaling pathway. In an orthotopic liver transplantation model in SD rats, M-NPs showed significant therapeutic efficacy by neutralizing endotoxin and suppressing the secretion of inflammatory factors. Moreover, overexpression of TLR4 on the macrophage membrane by using a TLR4+-plasmid in vitro effectively reduced the amount of M-NPs needed to neutralize an equivalent dose of endotoxin, reducing the potential risks of NP overuse.Conclusion: This study indicates that M-NPs can effectively alleviate I/RI induced by liver transplantation.Keywords: biomimetic nanoparticle, endotoxin, Kupffer cell, liver transplantation, ischemia reperfusion injury

Yongbing Sun,1 Jianping Gong,1 Yi Cao2 1National Engineering Research Center for Solid Preparation Technology of Chinese Medicines, Jiangxi University of Traditional Chinese Medicines, Jiangxi, Nanchang 330006, People’s Republic of China; 2Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of Education, Laboratory of Biochemistry, College of Chemistry, Xiangtan University, Xiangtan 411105, People’s Republic of ChinaCorrespondence: Jianping GongNational Engineering Research Center for Solid Preparation Technology of Chinese Medicines, Jiangxi University of Traditional Chinese Medicines, Jiangxi, Nanchang 330006, People’s Republic of ChinaTel +86-0791-87119623Email gongjianping64@163.comPurpose: Physicochemical properties play a crucial role in determining the toxicity of multi-walled carbon nanotubes (MWCNTs). Recently we found that MWCNTs with longer length and smaller diameters could induce toxicity to human umbilical vein endothelial cells (HUVECs) through the activation of endoplasmic reticulum (ER) stress. In this study, we further investigated the possible contribution of hydroxylation and carboxylation to the cytotoxicity of MWCNTs.Methods: The HUVECs were exposed to pristine (code XFM19), hydroxylated (code XFM20; content of hydroxyl groups 1.76 wt%) and carboxylated (code XFM21; content of carboxyl groups 1.23 wt%) MWCNTs, respectively. Then, the internalization, cytotoxicity, oxidative stress and activation of apoptosis-ER stress pathway were measured.Results: In consequence, all types of MWCNTs could be internalized into the HUVECs, and the cellular viability was significantly reduced to a similar level. Moreover, the MWCNTs increased intracellular reactive oxygen species (ROS) and decreased glutathione (GSH) to similar levels, indicating their capacity of inducing oxidative stress. The Western blot results showed that all types of MWCNTs reduced BCL-2 and increased caspase-3, caspase-8, cleaved caspase-3 and cleaved caspase-8. The expression of ER stress gene DNA damage-inducible transcript 3 (DDIT3) and protein level of chop were only significantly induced by XFM20 and XFM21, whereas protein level of p-chop was promoted by XFM19 and XFM21. In addition, the pro-survival gene XBP-1s was significantly down-regulated by all types of MWCNTs.Conclusion: These results suggested that MWCNTs could induce cytotoxicity to HUVECs via the induction of oxidative stress and apoptosis-ER stress, whereas a low degree of hydroxylation or carboxylation did not affect the toxicity of MWCNTs to HUVECs.Keywords: multi-walled carbon nanotubes, MWCNTs, human umbilical vein endothelial cells, HUVECs, endoplasmic reticulum (ER) stress, hydroxylation, carboxylation, ER stress

Jian Gong,1 Yuxiang Wang,1 Buping Jiang,1 Bin Xu,1 Chuanzhen Hu2,31Department of Hepato-Biliary-Pancreatic Surgery, Shanghai Tenth People’s Hospital Affiliated to Tongji University, Shanghai 200072, People’s Republic of China; 2Department of Orthopaedic Surgery, Shanghai Tenth People’s Hospital Affiliated to Tongji University, Shanghai 200072, People’s Republic of China; 3Institute of Bone Tumor Affiliated to Tongji University School of Medicine, Shanghai 200072, People’s Republic of ChinaBackground: Tumor metastasis causes high mortality in patients with malignancies. In carcinomas, overexpression of high-mobility-group A2 (HMGA2) in cancer cells would lead to tumor development and epithelial to mesenchymal transition (EMT), promoting metastasis. This study evaluated HMGA2 overexpression for its effects on pancreatic cancer (PC).Methods: HMGA2 protein levels were immunohistochemically assessed in human PC tissue specimens and evaluated for associations with patients’ clinicopathological findings. In human PC CAPAN 1 cells after HMGA2 expression was silenced or overexpressed, Transwell migration and invasion assays were performed, and EMT marker levels (E-cadherin, N-cadherin and Vimentin) were determined by immunoblot.Results: HMGA2 and Vimentin were found in 43% and 45% of PC tissue samples, respectively, while E-cadherin was absent in 60%. HMGA2 expression, loss of E-cadherin and Vimentin expression were significantly associated with clinical stage, tumor differentiation and lymph node metastasis. More importantly, univariate and multivariate analysis demonstrated that HMGA2 expression is an independent prognostic factor for patients with pancreatic cancer. Meanwhile, HMGA2-silenced CAPAN 1 cells showed reduced migration and invasion ability while HMGA2-overexpressed CAPAN 1 cells showed increased migration and invasion ability. Increased E-cadherin (epithelial marker) and reduced N-cadherin and Vimentin (mesenchymal markers) were found in HMGA2-silenced cells, while reduced E-cadherin and increased N-cadherin and Vimentin were found in HMGA2-overexpressed cells. Furthermore, Snail and Zeb1 (transcriptional factors) were reduced in HMGA2-silenced cells and increased in HMGA2-overexpressed cells.Conclusion: Our findings demonstrate that HMGA2 expression correlates with advanced tumor grades, lymph node metastasis and poor prognosis and may be a novel prognosis/therapeutic marker for PC.Keywords: HMGA2, human pancreatic cancer, prognosis, EMT

Ruqing Yang,1 Minghua Jiang,2 Junzhao Zhao,1 Hui Chen,2 Jian Gong,2 Yaying You,3 Laiyue Song,3 Zhen Li,4 Qian Li2 1Reproductive Medicine Center, Department of Gynaecology and Obstetrics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; 2Department of Clinical Laboratory, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; 3The Second Clinical Medical College, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; 4Department of Traditional Chinese Medicine, The Third Affiliated Hospital of Guangzhou Medical University, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou, Guangdong 510150, China Background: Near-triploidy/tetraploidy is rarely found in acute leukemia. Only limited data are available to characterize this condition, and it remains largely unknown. Patients and methods: In our study, we performed karyotype analysis on 1,031 patients diagnosed with acute leukemia from 2006 to 2018. A total of 10 patients of near-triploidy/tetraploidy karyotype were enrolled. Two cases of near-triploidy (66–79 chromosomes) and eight cases of near-tetraploidy (84–100 chromosomes) were identified. Bone marrow samples of these 10 patients were analyzed by fluorescence in situ hybridization with 19 commercially available probes that detected a small portion of gene alterations and large regions of chromosome amplifications. Results: Of the six patients with acute myelocytic leukemia, we detected three cases of double t(8;21)(q22;q22) that have not been previously reported, and one of them demonstrated ins(21;8)(q22;q24q22). We also describe a novel pediatric case carrying double t(15;17)(q22;q21) and receiving targeted treatment with all-trans retinoic acid therapy. To date, this case has responded well to the regimen and has shown continuous complete remission. All patients received chemotherapy. One of them received allogeneic hematopoietic stem cell transplant (HSCT) and survived for 22 months. Eight of the 10 patients died, and the median overall survival was 11 months. Conclusion: Using fluorescence in situ hybridization, we identified the distinct complex karyotype of near-triploidy/tetraploidy and provided further prognostic information. Tetraploidy acute promyelocytic leukemia had favorable prognosis; thus, HSCT was not necessary. The case of insertion t(21;8)(q22;q24q22) in tetraploidy responded poorly to chemotherapy and achieved molecular remission with difficultly. Data from patients in this group indicated that near-triploidy/tetraploidy acute leukemia has poor prognosis and new therapy is urgently needed. Keywords: near-triploidy, tetraploidy karyotype, acute leukemia, fluorescence in situ hybridization, gene

Yao Cheng,1 Yaqiong Yan,2 Jie Gong,2,* Niannian Yang,2,* Shaofa Nie1,* 1Department of Epidemiology and Biostatistics, Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; 2Department of Chronic Disease Prevention and Control, Wuhan Centers for Disease Prevention and Control, Wuhan, China *These authors contributed equally to this work Purpose: Following the implementation of breast cancer (BC) control strategies for years in Central China, the outcome needs to be evaluated and further strategies based on long-term surveillance should be formulated. Therefore, we examined the trends of BC incidence and mortality during 1990–2014 and projected them to 2024 in Wuhan, Central China.Patients and methods: The incidence and mortality data of BC were extracted from the Wuhan Cancer Registry. The average annual percentage changes (AAPCs) of the age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) were analyzed using Joinpoint regression. The Nordpred R-package was used to project BC incidence and mortality between 2015 and 2024. The age–period–cohort analysis was applied to evaluate the age, period, and cohort effects on the trends of BC incidence and mortality.Results: Overall, the ASIR increased markedly from 20.01 to 44.26 per 100,000 (AAPC=3.3%, 95% CI: 1.7%, 5.0%) during 1990–2014, and it was projected to keep increasing in the next decade (AAPC=3.0%, 95% CI: 2.0%, 4.1%). The ASMR of BC leveled off during the study period (AAPC=0.4%, 95% CI: −0.2%, 0.9%). The BC mortality of the older group (aged 50–79 years) showed significant upward trends in both observed and projected periods. Strong age, period, and cohort effects were observed in BC incidence, and BC mortality was significantly driven by age and cohort effects.Conclusion: The ASIR in Wuhan was approaching those areas with the highest BC risk in China, and the evident increase in BC incidence suggested that prior strategies for BC control should be adopted. In particular, further strategies for reducing BC mortality in older age groups should be reinforced in Wuhan, Central China. Keywords: breast cancer, incidence, mortality, trend, rate projection

Zhiyi Li,1 Tao Xu,2 Zhaoai Li,3 Jian Gong,4 Qing Liu,5 Yulin Wang,6 Juntao Wang,7 Zhijun Xia,8 Lan Zhu1 1Department of Gynecology and Obstetrics, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Department of Epidemiology and Statistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Gynecology and Obstetrics, Children’s Hospital of Shanxi Province, Shanxi, People’s Republic of China; 4Department of Gynecology and Obstetrics, Maternal and Child Health Hospital of Wuxi, Jiangsu, People’s Republic of China; 5Department of Gynecology and Obstetrics, Maternal and Child Health Hospital of Gansu Province, Lanzhou, People’s Republic of China; 6Department of Gynecology and Obstetrics, Maternal and Child Health Hospital of Foshan, Guangdong, People’s Republic of China; 7Department of Gynecology and Obstetrics, Maternal and Child Health Hospital of Guiyang, Guizhou, People’s Republic of China; 8Department of Gynecology and Obstetrics, Sheng Jing Hospital of China Medical University, Liaoning, People’s Republic of China Background: The aim of this study was to investigate the prevalence and risk factors of symptomatic pelvic organ prolapse in obese Chinese women.Subjects and methods: We performed a secondary analysis of 3,105 obese women from an observational cross-sectional study conducted between February 2014 and March 2016 in Mainland China. The obesity standard in our study was the Chinese standard (body mass index ≥28). All the subjects were asked to complete a questionnaire which included age, job, parity, and so on. Symptomatic pelvic organ prolapse (POP) was characterized as being symptomatic and at stage II or higher. Multivariable logistic regression was used to assess the factors associated with symptomatic POP.Results: The prevalence of symptomatic POP was 15.84% in obese Chinese women, and there was a consistent increasing trend in the prevalence of POP with increasing age, ranging from 4.78% in women between 20 and 29 years of age to 28.21% in women aged 70 years or older (P3 weeks), and gynecological abnormalities. In addition, multiparity was not associated with symptomatic POP in multivariable analysis.Conclusion: Symptomatic POP affects nearly 16% of obese women in People’s Republic of China. The prevalence of symptomatic POP increases significantly with age. Keywords: epidemiology, pelvic organ prolapse, prevalence, risk factors, obese, China

Huijuan Liang,1,2 Yancun Fan,1 Nan Zhang,1 Virasakdi Chongsuvivatwong,2 Qingchun Wang,3 Jing Gong,3 Hutcha Sriplung2 1Research Institute for Health Policy of Inner Mongolia, Inner Mongolia Medical University, Hohhot, Inner Mongolia, China; 2Epidemiology Unit, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand; 3Department of Medical Education, Hohhot First Hospital, Hohhot, Inner Mongolia, China Objective: This study explored women’s preference for cesarean section (CS) and the preference for cesarean sections’ influencing factors, particularly nonmedical factors.Methods: A cross-sectional study was conducted in four tertiary hospitals in Hohhot. We recruited 1,169 pregnant women at ≥28 gestational weeks and classified subjects into three groups by delivery mode preference: vaginal birth (VB), CS, and “no clear preference”. We identified the influencing factors of women’s choices by multinomial logistic regression. The adjusted relative-risk ratios (aRRRs) for the factors affecting the preference for CS and “no clear preference” categories and their 95% CIs were computed, using the preference for VB as the reference group.Results: VB was preferred by 80.3% of the subjects, 8.8% preferred CS, and 10.9% had not decided yet. In the multinomial logistic regression, pregnant women intending to have more than one child were less likely to prefer CS (aRRR: 0.37; 95% CI: 0.22–0.61); choosing a lucky day for baby birth was the strongest factor for CS preference (aRRR: 12.36; 95% CI: 6.62–23.08), and other factors for CS preference were being aged 40 years and above (aRRR: 4.21; 95% CI: 1.43–12.40), being ethnic minority (aRRR: 2.00; 95% CI: 1.17, 3.41), feeling difficulty in getting pregnant (aRRR: 2.23; 95% CI: 1.20, 4.13), and having husband’s preference for CS (aRRR: 7.62; 95% CI: 4.00–14.54). The top reasons for preferring CS were the belief that CS was safer (51.5%), associated with less pain (40.8%), and better for baby’s and woman’s health (24.3% and 22.3%, respectively).Conclusion: Less than one-tenth of the study subjects preferred CS. The cultural beliefs had the strongest influence on the decision of delivery mode. Those intending to have two or more children following the two-child policy were less likely to choose CS. Keywords: mode of delivery, vaginal birth, pregnant women, fertility intention

Jian Gong,1 Huiyan Wang,1 Wenwen Lou,1 Guiye Wang,1 Hongqun Tao,1 Huaikai Wen,1 Yu Liu,2 Qipeng Xie1 1Department of Laboratory Medicine, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, People’s Republic of China; 2Department of Cardiothoracic Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, People’s Republic of China Background: Lung cancer is the leading cause of cancer-related death worldwide and it is critical to discover specific biomarkers to provide better individualized treatment and subsequently better prognosis. The sirtuins (SIRT1–7) have been reported to be involved in cancers including non-small cell lung cancer (NCSLC), however, the results are not consistent and not all the seven sirtuins are explored and compared. Methods: TCGA data was downloaded and used to investigate and compare the associations of sirtuins mRNA levels with clinicopathological parameters and prognosis in NSCLC. Results: Our results suggested SIRT1, SIRT3, SIRT4, and SIRT7 were highly expressed in adenocarcinoma (ADC) patients and female patients while SIRT5 were highly expressed in squamous cell carcinoma (SCC) patients and male patients. Associations of high SIRT7 with younger onset age, high SIRT1 with distant metastasis and low T stage, and high SIRT4 with high T stage and TNM stage were also found. Kaplan-Meier plot curves and univariate Cox proportional regression analyses indicated that high SIRT2, SIRT4, and SIRT6 expressions were associated with longer overall survival (OS) time. Multivariate analyses indicated that SIRT2 and SIRT6 were still associated with OS. For recurrence-free survival (RFS), high SIRT1 expression was significantly associated with shorter RFS time while high SIRT2-3 and SIRT5-7 expressions were associated with longer RFS time in univariate analyses. After adjusting the confounding factors, significant associations were still found in SIRT1-2 and SIRT5-7 but not in SIRT3. We also stratified the patients by combining SIRT1 and SIRT2 and revealed that the combination of SIRT1 and SIRT2 was a better prediction model for RFS in NSCLC. To preliminarily understand the potential mechanisms of sirtuins in NSCLC carcinogenesis, the genes co-expressed with sirtuins were analyzed and annotated. Conclusion: sirtuins might be the potential therapy targets and prognostic biomarkers in NSCLC. Keywords: sirtuins, NSCLC, clinical features, overall survival, recurrence-free survival

Jun Gong,1,* Jessica Yan,2,* Charles Forscher,3 Andrew Hendifar4 1Department of Medical Oncology, City of Hope National Medical Center, Duarte, CA, USA; 2Department of Hematology and Oncology, Harbor-UCLA Medical Center, Torrance, CA, USA; 3Sarcoma Program, Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA; 4Gastrointestinal and Neuroendocrine Malignancies, Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA *These authors contributed equally to this work Abstract: Despite available therapies after initial systemic therapy, prognosis remains poor in relapsed or refractory soft tissue sarcomas (STS). The rational and clinical development of novel agents to improve outcomes in this area of high unmet need is desperately warranted. Aldoxorubicin is a prodrug of doxorubicin that binds to serum albumin immediately after administration through an acid-sensitive hydrazone linker and is subsequently transported to tumor tissues where the acidic environment cleaves the linker and facilitates delivery of a tumor-targeted drug payload. In clinical studies to date, there has been evidence of efficacy and mitigated cardiac toxicity. In this review, we comprehensively detail the clinical development of aldoxorubicin in STS to date. Specifically, we highlight available data on the pharmacokinetics and efficacy from Phase I, Phase II, and Phase III trials in advanced or metastatic STS. We conclude with considerations for future directions of investigation for this promising antitumor agent.Keywords: aldoxorubicin, albumin conjugate, soft tissue sarcomas, clinical trials, pharmacokinetics, cardiotoxicity

Olivier Belzile,1 Xianming Huang,2,3 Jian Gong,2,3 Jay Carlson,2,3 Alan J Schroit,1 Rolf A Brekken,1 Bruce D Freimark2,3 1Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX, 2Department of Preclinical Research, 3Department of Antibody Discovery, Peregrine Pharmaceuticals, Inc., Tustin, CA, USA Abstract: Phosphatidylserine (PS) is a negatively charged phospholipid in all eukaryotic cells that is actively sequestered to the inner leaflet of the cell membrane. Exposure of PS on apoptotic cells is a normal physiological process that triggers their rapid removal by phagocytic engulfment under noninflammatory conditions via receptors primarily expressed on immune cells. PS is aberrantly exposed in the tumor microenvironment and contributes to the overall immunosuppressive signals that antagonize the development of local and systemic antitumor immune responses. PS-mediated immunosuppression in the tumor microenvironment is further exacerbated by chemotherapy and radiation treatments that result in increased levels of PS on dying cells and necrotic tissue. Antibodies targeting PS localize to tumors and block PS-mediated immunosuppression. Targeting exposed PS in the tumor microenvironment may be a novel approach to enhance immune responses to cancer. Keywords: immunosuppression, tumor microenvironment, immunotherapy, imaging, phosphatidylserine, bavituximab

Zuojin Liu,1,* Dechao Niu,2,3,* Junyong Zhang,1 Wenfeng Zhang,1 Yuan Yao,2 Pei Li,2 Jianping Gong1 1Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 2Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, 3Lab of Low-Dimensional Materials Chemistry, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Efficient and targeted delivery approach to transfer exogenous genes into macrophages is still a great challenge. Current gene delivery methods often result in low cellular uptake efficiency in vivo in some types of cells, especially for the Kupffer cells (KCs). In this article, we demonstrate that amphiphilic core–shell nanoparticles (NPs) consisting of well-defined hydrophobic poly(methyl methacrylate) (PMMA) cores and branched polyethyleneimine (PEI) shells (denoted as PEI@PMMA NPs) are efficient nanocarriers to deliver microRNA (miRNA)-loaded plasmid to the KCs. Average hydrodynamic diameter of PEI@PMMA NPs was 279 nm with a narrow size distribution. The NPs also possessed positive surface charges up to +30 mV in water, thus enabling effective condensation of negatively charged plasmid DNA. Gel electrophoresis assay showed that the resultant PEI@PMMA NPs were able to completely condense miRNA plasmid at a weight ratio of 25:1 (N/P ratio equal to 45:1). The Cell Counting Kit-8 assay and flow cytometry results showed that the PEI@PMMA/miRNA NPs displayed low cytotoxicity and cell apoptosis activity against the KCs. The maximum cell transfection efficiency reached 34.7% after 48 hours, which is much higher than that obtained by using the commercial Lipofectamine™ 2000 (1.7%). Bio-transmission electron microscope observation revealed that the PEI@PMMA NPs were mainly distributed in the cytoplasm of the KCs. Furthermore, when compared to the control groups, the protein expression of target nuclear factor κB P65 was considerably inhibited (P

Hydrate is one of the critical precipitates which have to be controlled for subsea flow assurance. The induction time of hydrate is therefore a significant parameter. However, there have been few studies on the induction time of the natural gas hydrate formation in a flow loop system. Consequently, a series of experiments were firstly performed, including water, natural gas and Diesel oil, on the hydrate induction time under various conditions such as the supercooling and supersaturation degree, water cut, anti-agglomerant dosage, etc. The experiments were conducted in a high-pressure hydrate flow loop newly constructed in the China University of Petroleum (Beijing), and dedicated to flow assurance studies. Then, based on previous research, this study puts forward a method for induction time, which is characterized by clear definition, convenient measurement and good generality. Furthermore, we investigated the influences of the experimental parameters and analyzed the experimental phenomena for the hydrate induction time in a flowing system.

Akanand Singh,1 Yi Feng,1 Nisha Mahato,2 Jinzheng Li,1 Chuanxin Wu,1 Jianping Gong1 1Chongqing Key Laboratory of Hepatobiliary Surgery and Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China; 2Department of Prosthodontics, The Affiliated Hospital of Stomatology, Chongqing Medical University, Chongqing, People's Republic of China Background: High-mobility group box 1 (HMGB1) is a proinflammatory cytokine that plays an active role during the pathogenesis of inflammatory processes. The primary aim of this study was to detect whether HMGB1 is involved in the pathogenesis of acute obstructive suppurative cholangitis (AOSC). Methods: We collected peripheral blood samples from 23 patients with AOSC and 23 healthy volunteers who served as normal controls. All participants were tested for HMGB1 mRNA level, HMGB1 protein, tumor necrosis factor alpha (TNF-alpha), and interleukin 10 (IL-10). HMGB1 mRNA levels were tested using real-time polymerase chain reaction. HMGB1 protein expression was measured using Western blot. TNF-alpha and IL-10 were tested using enzyme-linked immunosorbent assay. Results: The expression of HMGB1 mRNA and HMGB1 protein was higher in the AOSC group than in the normal controls (P

Lili Long,1 Yanmin Song,1 Linlin Zhang,2 Chongyu Hu,3 Jian Gong,2 Lin Xu,1 Hongyu Long,1 Luo Zhou,1 Yunci Zhang,2 Yong Zhang,2 Bo Xiao1 1Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan Province, People’s Republic of China; 2The People’s Hospital of Fuyang, Anhui Province, People’s Republic of China; 3Department of Neurology, Hunan Provincial People’s Hospital, People’s Republic of China Background: Benign adult familial myoclonic epilepsy (BAFME) is a rare form of epilepsy syndrome. The pathogenesis of BAFME remains unclear, though it seems to involve dysfunction of the cerebellum. Objectives: The purpose of this study was to use proton magnetic resonance spectroscopy (1H-MRS) to investigate whether neurochemical changes underlie abnormal brain function in BAFME. Methods: Twelve BAFME patients from one family and 12 age- and sex-matched healthy controls were enrolled in this study. The ratios of NAA/Cr, NAA/Cho, Cho/Cr, and NAA/(Cr+Cho) were analyzed. Results: The BAFME patients exhibited a decreased N-acetylaspartate (NAA)/choline (Cho) ratio in the cerebellar cortex, whereas there were no significant differences in the NAA/creatine (Cr), Cho/Cr, and NAA/(Cr+Cho) ratios compared with healthy controls. There were no significant differences in 1H-MRS values in the frontal cortex or thalamus between the BAFME patients and controls. No correlation was detected between the NAA/Cho ratio in the cerebellar cortex and disease duration, myoclonus severity, or tremor severity. Conclusion: Our results indicate clear cerebellar dysfunction in BAFME. 1H-MRS is a useful tool for the diagnosis of BAFME in combination with family history and electrophysiological examination. Keywords: benign adult familial myoclonic epilepsy (BAFME), proton magnetic resonance spectroscopy (1H-MRS), cerebellum, cortical tremor, myoclonus

In the simulation of oil-gas pipeline multiphase flow, thermodynamic computation is an important process interacting with the hydraulic calculation and it influences the convergence of the program and the accuracy of the results. The form of the energy equation is the key to the thermodynamic computation. Based on the energy equation of oil-gas flow in pipeline, the Explicit Temperature Drop Formula (ETDF) is derived for oilgas steady state temperature calculation. This new energy equation has considered many factors, such as Joule-Thomson effect, pressure work, friction work and impact of terrain undulation and heat transfer Oil & Gas Science and Technology – Rev. IFP Energies nouvelles with the surroundings along the line. So it is an overall form of energy equation, which could describe the actual fact of multiphase pipeline accurately. Therefore, some standpoints in literatures on the temperature calculation of oil-gas two-phase flow in pipelines are reviewed. Elimination of temperature iteration loop and integration of the explicit temperature equation, instead of enthalpy energy equation, into the conjugated hydraulic and thermal computation have been found to improve the efficiency of algorithm. The calculation applied to both the component model, also applied to the black-oil model. This model is incorporated into the component model and black-oil model, respectively, and two simulations are carried out with two practical pipeline Yingmai-Yaha and Lufeng multiphase pipeline and the temperature results are compared with the simulation calculated by the OLGA and the measured. It is shown that this model has simulated the temperature distribution very well. Finally, we analyzed the influence of the specific heat capacity of oil and gas on the temperature of the mixture of fluids and the influence of the Joule-Thomson effect on the temperature distribution on the pipeline. It is shown that the Joule-Thomson coefficient is a key factor to well describe the oil-gas two-phase flow. Lors de la simulation d’un écoulement multiphasique huile-gaz dans une conduite, le calcul thermodynamique représente un processus important en interaction avec le calcul hydraulique; il influence la convergence du programme et la précision des résultats. La forme de l’équation d’énergie constitue la clef du calcul thermodynamique. Basée sur l’équation d’énergie de l’écoulement huile-gaz dans un pipeline, la formule de chute de température explicite (ETDF; Explicit Temperature Drop Formula) est dérivée pour un calcul de température d’état stable huile-gaz. Cette nouvelle équation d’énergie prend en compte de nombreux facteurs, tels que l’effet Joule-Thomson, le travail de pression, le travail de frottement, ainsi que l’incidence des ondulations de terrain et le transfert de chaleur avec le milieu extérieur le long de la ligne. Ainsi, il s’agit d’une forme globale de l’équation d’énergie, laquelle pourrait décrire précisément la réalité d’un pipeline à phases multiples. Pour cette raison, un certain nombre de points de vue de la littérature à propos du calcul de température d’un écoulement diphasique huile-gaz dans des pipelines sont passés en revue. L’élimination de la boucle d’itération de température et l’intégration de l’équation de température explicite, au lieu de l’équation d’énergie d’enthalpie, dans le calcul conjugué hydraulique et thermique, se sont avérées améliorer l’efficacité de l’algorithme. Le calcul a été appliqué non seulement au modèle de composants mais aussi au modèle Black-Oil. Ce modèle est incorporé respectivement dans le modèle de composants ainsi que le modèle Black-Oil et deux simulations sont effectuées sur deux pipelines en service, les pipelines multiphasiques Yingmai-Yaha et Lufeng; les résultats de température sont comparés à la simulation calculée par OLGA et aux résultats mesurés. Il est montré que ce modèle a très bien simulé la distribution de températures. Enfin, on a analysé l’influence de la capacité thermique spécifique du pétrole et du gaz sur la température du mélange des fluides et l’influence de l’effet Joule-Thomson sur la répartition de température sur le pipeline. Il est montré que le coefficient de Joule-Thomson représente un facteur clef pour décrire correctement un écoulement diphasique huile-gaz.

The durability damage of concrete structures in the actual engineering environment is often the result of the interaction of the load and the environment, climate and other multiple factors. In this paper, the test researches were carried out on the concrete mass and dynamic elastic modulus under the effects of sustained loading, sulfate attack and dry-wet circulation, and the test phenomenon and results were discussed and analyzed. Then this paper proposed the durability damage model of the concrete under the effects of sustained loading, sulfate attack and dry-wet circulation considering the compressive stress level, the sulfate solution concentration and the age of corrosion as test factors, and the rationality of the model was discussed.