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Xuyan Li,1 Lujia Guan,1 Dong Wang,1 Xiao Tang,1 Rui Wang,1 Ying Li,1 Zhaohui Tong,1 Bing Sun,1 Chen Wang2– 5 1Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China; 3National Clinical Research Center for Respiratory Diseases, Beijing, 100029, People’s Republic of China; 4Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China; 5Department of Respiratory Medicine, Capital Medical University, Beijing, 100069, People’s Republic of ChinaCorrespondence: Bing Sun; Chen Wang, Email sunbing20002023@163.com; birm2022@126.comBackground: Adjuvant corticosteroids are effective in patients with human immunodeficiency virus (HIV)-associated Pneumocystis jirovecii pneumonia (PCP) patients, but the effectiveness of adjuvant corticosteroids in non-HIV PCP remained controversial. This study aimed to evaluate the effectiveness of standard-dose compared with low-dose steroids in non-HIV PCP patients with acute respiratory distress syndrome (ARDS).Methods: This retrospective observational study included non-HIV PCP patients with ARDS admitted to the respiratory intensive care unit (RICU) of Beijing Chao-Yang Hospital from 2015 to 2022. Demographics, clinical characteristics, and outcomes were compared between patients receiving standard-dose and those receiving low-dose steroids. Survival times were assessed using Kaplan-Meier curves and compared with the Log rank test. Cox proportional hazards regression analysis was conducted to identify independent risk factors for 28-day and 60-day mortality.Results: A total of 105 non-HIV PCP with ARDS were included, with 48 patients in the standard-dose steroid group (66.7% male, 50.5± 12.6 years) and 57 in the low-dose steroid group (61.4% male, 55.5± 14.2 years). The 60-day mortality was lower in the standard-dose group than in the low-dose group (63.2% vs 48.3%, p=0.04), while 28-day mortality showed no significant difference (50.8% vs 35.4%, p=0.11). After adjusting for confounders, standard-dose steroids reduced 28-day mortality (aHR: 0.339, 95% CI: 0.147– 0.780) and 60-day mortality (aHR: 0.328, 95% CI: 0.152– 0.709), particularly in patients aged < 65 years, non-smokers, those requiring mechanical ventilation, with albumin< 30 g/L, or a PaO2/FiO2 ratio < 150 mmHg. No differences in co-infections or gastrointestinal bleeding were observed.Conclusion: The standard-dose steroid therapy significantly reduced 28-day and 60-day mortality without major complications in the non-HIV immunocompromised population with severe PCP with ARDS. These findings highlight the potential survival benefit of standard-dose corticosteroid regimen in this population.Keywords: adjuvant corticosteroids, Pneumocystis jirovecii pneumonia, acute respiratory distress syndrome, non-human immunodeficiency virus

Xiang He,1– 3,&ast; Qin Ran,2,3,&ast; Xiaolan Li,2,3,&ast; Anying Xiong,2,3 Lei Zhang,2,3 Manling Jiang,2,3 Lingling Bai,2 Dan Peng,2 Junyi Wang,2,3 Baoqing Sun,1 Guoping Li1– 3 1National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, People’s Republic of China; 2Laboratory of Allergy and Precision Medicine, Chengdu Institute of Respiratory Health, Affiliated Hospital of Southwest Jiaotong University, The Third People’s Hospital of Chengdu, Chengdu, 610031, People’s Republic of China; 3Department of Respiration, Chengdu third People’s hospital Branch of National Clinical Research Center for Respiratory Disease, Affiliated Hospital of ChongQing Medical University, Chengdu, 610031, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guoping Li; Baoqing Sun, Email lzlgp@163.com; sunbaoqing@vip.163.comIntroduction: Tumor-associated macrophages (TAMs) play a crucial role in the tumor microenvironment (TME), and their polarization state significantly influences patient outcomes. This study investigates the inhibitory effects of β-glucan extracted from Candida albicans on lung cancer progression, focusing on its impact on TAM polarization and the induction of ferroptosis, a form of regulated cell death.Methods: Utilizing both in vivo animal models and in vitro cellular assays, we assessed the impact of β-glucan on tumor growth, cellular proliferation, and migration. We evaluated TAM polarization by analyzing the expression of M1 and M2 markers and identified differentially expressed genes (DEGs) related to ferroptosis. The role of ferroptosis in TAM polarization was further confirmed by assessing the protein levels of ACSL4 and GPX4, intracellular ferrous ion levels, and lipid peroxides.Results: β-glucan treatment significantly reduced tumor size and weight, along with cellular proliferation and migration, suggesting a potent suppressive effect on lung cancer cell growth. β-glucan promoted an M1-like phenotype in TAMs, as evidenced by increased CD86 expression and decreased CD206 expression, and modulated cytokine mRNA levels. RNA sequencing analysis post β-glucan treatment identified a substantial number of DEGs enriched in the ferroptosis pathway. The induction of ferroptosis by β-glucan was further confirmed through the significant upregulation of ACSL4 and downregulation of GPX4, alongside increased intracellular ferrous ion levels and lipid peroxides. The ferroptosis inhibitor Fer-1 abrogated these effects, highlighting the specificity of β-glucan-mediated polarization.Conclusion: These results collectively provide novel insights into the immunotherapeutic potential of β-glucan from Candida albicans and its role in modulating TAM polarization and lung cancer growth, offering a promising avenue for cancer treatment strategies.Keywords: β-glucan, lung cancer, TAMs, macrophage polarization, ferroptosis, C. albicans

Shuang Lv,1 Yiming Li,2 Bojian Sun,1 Yu Jing,1 Xing Wang,3 Zhanqing Gu,1 Bailiang Wang,4 Cheng Xiao3 1Department of Rheumatology, the First Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Cardiovascular, the First Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 3Institute of Clinical Medicine, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 4Department of Orthopaedic Surgery, China-Japan Friendship Hospital, Beijing, People’s Republic of ChinaCorrespondence: Bailiang Wang; Cheng Xiao, Email orthopaedic_wang@126.com; xc2002812@126.comObjects: Rheumatoid arthritis (RA) is a systemic autoimmune disease with an obscure pathogenesis. This study aims to identify the susceptibility conferred by specific single nucleotide polymorphisms (SNPs), namely rs17548629 within the RIPK1 gene and rs10094579 within the RIPK2 gene, in RA. Additionally, it investigates the associations between inflammatory markers and biochemical parameters at various stages of the disease.Methods: We analyzed 394 patients with RA and 258 normal controls (NCs), examining SNPs within the RIPK1 (rs17548629) and RIPK2 (rs10094579) genes using polymerase chain reaction (PCR) and sequencing techniques. Profiles of RA patients were evaluated for inflammatory markers, including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), as well as biochemical parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, glucose, uric acid, and creatinine. Additionally, disease-specific indicators included cyclic citrullinated peptide (CCP), rheumatoid factor (RF), antinuclear antibodies (ANA), and anti-keratin antibodies. The Disease Activity Score 28 (DAS28), based on ESR, was used to categorize RA patients into groups of high, moderate, or low disease activity.Results: We found a significant association between the RIPK1 rs17548629 genotype and RA in the additive model (p < 0.001; OR = 3.23), over-dominant model (p < 0.001; OR = 0.27), and dominant model (p < 0.001; OR = 3.94). The frequency of the C allele at rs17548629 was significantly higher in NCs than in RA patients (p < 0.001; OR = 0.322). When compared with normal controls, the RIPK1 rs17548629 genotype demonstrated significant associations with both anti-CCP-positive RA patients (p < 0.001) and anti-CCP-negative RA patients (p < 0.001). Similarly, this genotype was associated with RF-positive RA patients (p < 0.001). Furthermore, the RIPK2 rs10094579 genotype was significantly associated with CRP levels in RA patients with low disease activity in the over-dominant model (p = 0.029; OR = 0.065, adjusted for age and sex).Conclusion: The presence of the RIPK1 rs17548629 genotype is associated with RA under additive, co-dominant, and dominant models. The T allele mutation at rs17548629 increases the risk of RA in the Chinese population. The RIPK1 rs17548629 genotype was identified as being associated with RF-positive RA patients, whereas no significant association was observed in RF-negative individuals. These findings suggest that this SNP may modulate the risk of RA in an RF-dependent manner. Furthermore, the RIPK2 rs10094579 genotype correlates with CRP levels in RA patients exhibiting low disease activity. This association underscores the necessity for caution when reducing the dosage of therapy in RA patients with low disease activity who carry the CA genotype at RIPK2 rs10094579. Additional research is warranted to explore other genotypes that may influence RA susceptibility and to refine potential treatment strategies.keywords: receptor-interacting protein kinase, rheumatoid arthritis, polymorphism, single nucleotide, biochemical parameters

Lanqi Yu,1,2 Xiaolu Wu,1,2 Qinhan Zhang,1,2 Binghai Sun1,2 1School of Psychology, Zhejiang Normal University, Jinhua, Zhejiang, People’s Republic of China; 2Intelligent Laboratory of Child and Adolescent Mental Health and Crisis Intervention of Zhejiang Province, Zhejiang Normal University, Jinhua, Zhejiang, People’s Republic of ChinaCorrespondence: Qinhan Zhang; Binghai Sun, School of Psychology, Zhejiang Normal University, 688 YingBin Road, Jinhua, Zhejiang, People’s Republic of China, Email Qinhanzhang@zjnu.edu.cn; jky18@zjnu.cnPurpose: Within the scope of secondary education, social adjustment among students signifies their ability to effectively engage in social activities and adapt to shifting social environments. Extensive research across diverse geographical and sociocultural landscapes has demonstrated a positive correlation between social support and social adjustment; nonetheless, the specific mechanisms that facilitate this correlation among secondary school students remain largely unexplored. This study examines the roles of subjective well-being and psychological resilience as potential mediators in the connection between social support and social adjustment.Participants and Methods: To achieve this, a descriptive correlation design was employed with four measures, including Social Support Scale, Social Adjustment Diagnosis Scale, Adolescent Students’ Life Satisfaction Scale, and the Chinese version of Mental Toughness Inventory (MTI). A total of 1537 valid responses from secondary school students across Zhejiang province (China) were collected, of which 786 were boys (51.1%) and 751 girls (48.9%), with average age of 16.89 years (SD = 0.79).Results: This research demonstrates that social support, along with subjective well-being and psychological resilience, significantly and positively influences social adjustment. It was observed that both subjective well-being and psychological resilience, whether occurring simultaneously or in succession, partially mediate the influence of social support on social adjustment.Conclusion: The implications of this research suggest that enhancing social adjustment among secondary school students can be achieved by increasing their levels of social support, thereby boosting subjective wellbeing and fortifying psychological resilience. Within the environment of secondary schools, augmenting social support leads to improved social adjustment; furthermore, enhancing subjective wellbeing and reinforcing psychological resilience are crucial for supporting students’ positive adaptation to dynamic social environments. Teachers and educational policymakers could implement training programmes, provide psychological counselling, and bolster home-school collaboration as strategies to foster better social adjustment among students. Keywords: social support, social adjustment, subjective well-being, psychological resilience, Chinese

Taoying Lu,1– 3 Mingyue Fan,1 Jianxiong Cai,4 Aolin Liu,1 Qianwen Xie,2,3 Xiaowen Zhou,1 Bei Chang,1 Lingjia Yin,2,3,5 Guli Jiang,6 Bin Sun,7 Wenyi Tang,7 Darong Wu4 1The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Outcome Assessment Research Team in Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 3Outcome Assessment Research Team in Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China; 4State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 5Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden; 6Department of Scientific Research, Guangzhou Cadre Health Management Center, Guangzhou, People’s Republic of China; 7Department of Traditional Chinese Medicine, Guangzhou Cadre Health Management Center, Guangzhou, People’s Republic of ChinaCorrespondence: Darong Wu, State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, 111 Dade Road, Guangzhou, 510120, People’s Republic of China, Tel +86 13808869436, Email darongwu@gzucm.edu.cnBackground: Dampness syndrome is a basic syndrome of many major and chronic diseases. Early screening and identification of dampness syndrome are important. The Dampness Syndrome Scale of Chinese Medicine (DSSCM) was developed to measure the occurrence and severity of dampness syndrome. The measurement characteristics of the DSSCM should be further validated. The objective of this study is to evaluate the reliability and validity of the DSSCM based on a cross-sectional survey.Methods: The development of DSSCM was based on the traditional Chinese medicine (TCM) theory, expert consensus and clinical investigations. Participants were recruited from Guangdong Provincial Hospital of Chinese Medicine and Guangzhou Cadre Health Management Center in Guangdong Province, China. All participants completed the baseline questionnaire and DSSCM. The reliability of the DSSCM was evaluated by internal consistency reliability and test–retest reliability. The factor structure was tested with confirmatory factor analysis (CFA), while discriminant validity was evaluated by calculating the difference between the total score of the DSSCM and its four dimensions for participants with or without dampness syndrome. We used a clinician’s diagnosis of dampness syndrome as a criterion to evaluate the criterion validity. Multivariate regression analysis was used to analyze the associations among gender, age, height, and weight and dampness syndrome.Results: A total of 880 participants were enrolled for psychometric validation and 869 participants were included in the final analyses after exclusion. The mean age of the participants was 42.62± 12.86 years. The Cronbach’s alpha coefficients for the four dimensions of the DSSCM were 0.809, 0.891, 0.816 and 0.780. The ICCs for the four dimensions of the DSSCM were 0.806, 0.674, 0.780 and 0.760. For validity, the results showed that the DSSCM had good content validity, discriminant validity and criterion validity. For the CFA, the root mean square error of approximation (RMSEA) was 0.091; the standardized root mean square residual (SRMR) was 0.074; the comparative fit index (CFI) was 0.766; and the Tucker–Lewis index (TLI) was 0.745. Weight was found to be associated with the total scores of the DSSCM and its three dimensions.Conclusion: The DSSCM has good reliability and validity to support its use as a tool for assessing the severity of dampness syndrome. This study provides empirical evidence for future updates to the DSSCM.Keywords: dampness syndrome, dampness syndrome scale of Chinese medicine, reliability, validity

Mingtao Liu,1,&ast; Zhangkai J Cheng,1,&ast; Jiaxi Chen,2,&ast; Haiyang Li,1,3 Mingshan Xue,4,5 Xing Fu,1 Yanjun Li,2 Jiaxin Wang,2 Chenwei You,2 Haisheng Hu,1 Haojie Wu,1 Huimin Huang,1 Baoqing Sun1,4 1Department of Clinical Laboratory of the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, 510120, People’s Republic of China; 2KingMed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, 511495, People’s Republic of China; 3MRC Biostatistics Unit, University of Cambridge, Cambridge, CB2 0SR, UK; 4Guangzhou Laboratory, Guangzhou, 510005, People’s Republic of China; 5Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, 510440, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Baoqing Sun; Huimin Huang, Department of Clinical Laboratory of the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, 510120, People’s Republic of China, Tel +86 13824124015 ; +86 13631496651, Email sunbaoqing@vip.163.com; huanghuimin311@126.comBackground: While serum periostin and Krebs von den Lungen-6 (KL-6) have been acknowledged as independent markers in idiopathic pulmonary fibrosis (IPF) diagnosis, the clinical combinatory potential of these biomarkers combined with high-resolution computed tomography (HRCT) has yet to be fully explored.Methods: This retrospective study involved 78 participants, comprising 51 UIP-IPF patients and 27 healthy controls. All subjects underwent clinical and laboratory examinations, particularly the detection of periostin and KL-6 using ELISA with innovative HRCT fibrosis score evaluations at admission and discharge during hospitalization in UIP-IPF patients.Results: In our cohort of patients with IPF, predominantly male, over an average follow-up period of 195.27 days. Serum levels of periostin and KL-6 were significantly elevated in IPF patients compared to healthy controls (&ast;p < 0.05). Post-treatment, KL-6 levels decreased significantly, while periostin levels increased. Notably, periostin exhibited superior prognostic accuracy over KL-6, with a higher AUC of 0.875 than 0.639 in ROC analysis. An increase in periostin levels correlated with disease progression, as evidenced by worsened HRCT fibrotic scores and decreased survival probability. These findings underscore periostin’s potential as a reliable biomarker for assessing IPF severity and therapeutic response.Conclusion: Our findings underscore the preeminence of serum periostin over KL-6 in UIP-IPF diagnosis, particularly when conjoined with HRCT fibrosis score.Keywords: periostin, Krebs von den Lungen-6, idiopathic pulmonary fibrosis, HRCT fibrosis score, diagnostic hematology

Danwei Zhang,1 Yating Zeng,1 Bin Sun,2 Wei Li,2 Wenjuan Liu,2 Haiyan Gao,2 Yibing Zhu,2 Haibo Li,2,&ast; Qiang Chen1,&ast; 1Department of Cardiac Surgery, Fujian Children’s Hospital (Fujian Branch of Shanghai Children’s Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China; 2Division of Birth Cohort Study, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiang Chen, Department of Cardiac Surgery, Fujian Children’s Hospital (Fujian Branch of Shanghai Children’s Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, No. 966 Hengyu Road, Jinan District, Fuzhou, 350014, People’s Republic of China, Email chenqiang2228@163.com Haibo Li, Division of Birth Cohort Study, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, No. 18 Daoshan Road, Gulou District, Fuzhou, 350001, People’s Republic of China, Email haiboli89@163.comPurpose: Gestational diabetes mellitus (GDM) is a prevalent complication during pregnancy. This study aimed to explore the associations between inflammatory indices during pregnancy and the development of GDM.Methods: Data from the Fujian Birth Cohort Study between March 2019 and December 2022 were used. Participants who delivered a live-born singleton were included and categorized into GDM and non-GDM groups. Two inflammatory indices, the systemic immune-inflammation index (SII) and systemic inflammatory response index (SIRI), were calculated for each trimester of pregnancy via hematological parameters from complete blood count tests. The distributions of inflammatory indicators across trimesters were compared between the GDM and non-GDM groups. Additionally, multivariable logistic regression models were employed to investigate the associations between inflammatory indices and the incidence of GDM.Results: A total of 17297 participants were included, 21.2% of whom were diagnosed with GDM. In the first trimester, the median SIIs for the GDM and non-GDM groups were 817.7× 109/L and 756.9× 109/L, respectively, whereas the median SIRIs were 1.6× 109/L and 1.5× 109/L, respectively. In both groups, the SII increased to its peak in the second trimester before declining, whereas the SIRI progressively increased throughout pregnancy. The SII and SIRI were greater in the GDM group than in the non-GDM group during the first two trimesters but lower in the third trimester. Nonlinear positive associations between first-trimester SII and SIRI levels and GDM were observed, with extreme quartile odds ratios of 1.32 (95% CI: 1.19, 1.48) and 1.39 (95% CI: 1.24, 1.55), respectively.Conclusion: The SII and SIRI increased and reached their peak values in the second and third trimesters of pregnancy, respectively. Elevated levels of the SII and SIRI in early pregnancy were linked to an increased risk of GDM, suggesting their potential utility as screening tools for GDM.Keywords: gestational diabetes mellitus, GDM, systemic immune-inflammation index, SII, systemic inflammatory response index, SIRI

Rui Bai,1,2 Yuhang Sui,1,2 Tianqi Lu,1,2 Hua Chen,1,2 Gang Wang,1,2 Rui Kong,1,2 Hongtao Tan,1,2 Yongwei Wang,1,2 Guanqun Li,1,2 Bei Sun1,2 1Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People’s Republic of China; 2Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People’s Republic of ChinaCorrespondence: Guanqun Li; Bei Sun, Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Nangang District, Harbin, 150001, People’s Republic of China, Email liguanqun@hrbmu.edu.cn; sunbei70@hrbmu.edu.cnPurpose: The effects of the step-jump approach on the survival and prognosis of infected pancreatic necrosis (IPN) patients have not yet been determined.Patients and Methods: Between November 2018 and June 2023, 188 patients were included in this study. There were 144 patients in the step-up group (the SU group) and 44 in the step-jump group (the SJ group). In the SU group, patients successfully treated with percutaneous catheter drainage (PCD) alone were classified into the SU-1 group (n=101), while those requiring additional surgery after PCD were categorized into the SU-2 group (n=43). In the SJ group, patients who underwent minimally invasive necrosectomy (MIN) without PCD were assigned to the SJ-1 group (n=34), whereas those who initially underwent PCD followed by immediate open surgery were placed in the SJ-2 group (n=10). Propensity score matching (PSM) was used to mitigate bias.Results: After PSM, a total of 34 pairs were successfully matched. A comparison of the SU group with the SJ-1 group (upfront MIN without PCD) revealed similar mortality rates (P=0.239); however, the incidences of multiple drug-resistant organisms (MDROs) (P=0.029) and surgical complications (P< 0.001) were significantly lower in the SJ-1 group. After comparing the SU-2 and SJ-2 groups (patients who underwent direct open necrosectomy without MIN after PCD failure), the incidences of surgical complications and MDRO in the SJ-2 group were significantly lower (P< 0.05).Conclusion: Compared with the step-up approach, the step-jump approach is safer and more effective and can significantly reduce the incidence of MDRO and surgical complications.Keywords: infected pancreatic necrosis, step-up approach, step-jump approach, propensity score match

Dongdong Li,1 Lijun Bian,1 Lili Cui,2 Jingying Zhou,1 Gaotian Li,1 Xiaoyan Zhao,1 Liao Xing,1 Jiaxing Cui,1 Bo Sun,1 Chunlai Jiang,1,3,4 Wei Kong,1,3,4 Yong Zhang,1,3,4 Yan Chen1,3,4 1National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, People’s Republic of China; 2Beijing Institute of Drug Metabolism, Beijing, People’s Republic of China; 3Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, People’s Republic of China; 4NMPA Key Laboratory of Humanized Animal Models for Evaluation of Vaccines and Cell Therapy Products, Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Yan Chen; Yong Zhang, National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, 130012, People’s Republic of China, Tel +86-431-85167751, Fax +86-431-85167674, Email chen_yan0417@126.com; zhypharm@jlu.edu.cnPurpose: Heterologous immunization using different vaccine platforms has been demonstrated as an efficient strategy to enhance antigen-specific immune responses. In this study, we performed a head-to-head comparison of both humoral and cellular immune response induced by different prime-boost immunization regimens of mRNA vaccine and adjuvanted protein subunit vaccine against varicella-zoster virus (VZV) in middle-aged mice, aiming to get a better understanding of the influence of vaccination schedule on immune response.Methods: VZV glycoprotein (gE) mRNA was synthesized and encapsulated into SM-102-based lipid nanoparticles (LNPs). VZV-primed middle-aged C57BL/6 mice were then subjected to homologous and heterologous prime-boost immunization strategies using VZV gE mRNA vaccine (RNA-gE) and protein subunit vaccine (PS-gE). The antigen-specific antibodies were evaluated using enzyme-linked immunosorbent assay (ELISA) analysis. Additionally, cell-mediated immunity (CMI) was detected using ELISPOT assay and flow cytometry. Besides, in vivo safety profiles were also evaluated and compared.Results: The mRNA-loaded lipid nanoparticles had a hydrodynamic diameter of approximately 130 nm and a polydispersity index of 0.156. Total IgG antibody levels exhibited no significant differences among different immunization strategies. However, mice received 2×RNA-gE or RNA-gE>PS-gE showed a lower IgG1/IgG2c ratio than those received 2×PS-gE and PS-gE> RNA-gE. The CMI response induced by 2×RNA-gE or RNA-gE>PS-gE was significantly stronger than that induced by 2×PS-gE and PS-gE> RNA-gE. The safety evaluation indicated that both mRNA vaccine and protein vaccine induced a transient body weight loss in mice. Furthermore, the protein vaccine produced a notable inflammatory response at the injection sites, while the mRNA vaccine showed no observable inflammation.Conclusion: The heterologous prime-boost strategy has demonstrated that an mRNA-primed immunization regimen can induce a better cell-mediated immune response than a protein subunit-primed regimen in middle-aged mice. These findings provide valuable insights into the design and optimization of VZV vaccines with the potentials to broaden varicella vaccination strategies in the future.Keywords: varicella-zoster Virus, mRNA vaccine, glycoprotein E, lipid nanoparticles, heterologous prime-boost, cell-mediated immunity

Xiaojun Chen,1,&ast; Shushu Zuo,1,&ast; Chunhua Zhang,1 Bing Sun,1 Mengyue Zhang,1 Dandan Jiang,2 Yanyan Chen2 1School of Optometry and Ophthalmology, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People’s Republic of China; 2National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanyan Chen; Dandan Jiang, National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, No. 270, Xueyuan West Road, Lucheng District, Wenzhou, Zhejiang, 325027, People’s Republic of China, Tel +86 13858855689 ; +86 13506649289, Email cyy@eye.ac.cn; jiangdandan@eye.ac.cnObjective: This study aims to explore the effects of eye exercises on the accommodative ability of Chinese school-aged children.Methods: This study used a convenience cluster sampling and selected 149 students from grades 2– 5 in a Wenzhou primary school to participate in the intervention in June 2022. This study involved a one-month intervention teaching eye exercises using a composite feedback model. Assessments were made at 3 and 9 months post-intervention. Data collection occurred thrice, including a baseline and two follow-ups, measuring monocular and binocular accommodative facility, monocular and binocular accommodative amplitude, CISS scale, spherical equivalent refraction, and uncorrected visual acuity. Analysis used chi-square tests and generalized estimating equations to evaluate the exercises’ effectiveness, with a significance threshold of P < 0.05.Results: 134 students completed the follow-up, including 61 females (45.52%). After teaching intervention, students showed significant improvements in the accuracy of manipulation, rhythm, acupoint location, strength effectiveness and rhythm of acupressure eye exercises (all P < 0.05), with increases of 10.37%, 13.03%, 16.96%, and 25.17%, respectively. Follow-up assessments revealed both monocular and binocular accommodative amplitude at T3 were significantly higher than at T1 and T2. Moreover, the binocular accommodative amplitude in the high-quality eye exercise group remained significantly higher than that in the low-quality group even(B=1.39,1.46, P < 0.01). Eye exercises could improve monocular and binocular accommodative amplitude in the short term(P < 0.05). High-quality eye exercises could alleviate visual fatigue (B=− 2.00--3.49, both P < 0.05). However, eye exercises did not demonstrate any advantages in affecting spherical equivalent refraction or uncorrected visual acuity (P > 0.05).Conclusion: Eye exercises can alleviate myopia-related symptoms in Chinese children aged 7 to 11 years. However, this study did not find that eye exercises effectively reduce the degree of myopia in children.Trial Registration: The original trial (Registration site: https://www.chictr.org.cn/ Registration number: ChiCTR2300070903) was retrospectively registered on 26/04/2023.Keywords: Eye exercises, myopia, accommodative facility, accommodative amplitude, visual fatigue

Baojun Guo,1,2 Hui Gan,1 Mingshan Xue,1,3 Zhifeng Huang,1 Zhiwei Lin,1 Shiyun Li,1 Peiyan Zheng,1 Baoqing Sun1 1Department of Clinical Laboratory of the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, 510120, People’s Republic of China; 2School of Medicine, Henan University, Kaifeng, 475004, People’s Republic of China; 3Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, 510060, People’s Republic of ChinaCorrespondence: Baoqing Sun; Peiyan Zheng, Email sunbaoqing@vip.163.com; gdmcslxx@126.comBackground: This study analyzed the burden of chronic obstructive pulmonary disease (COPD) in China, the United States, and India from 1990 to 2019 and projected the trends for the next decade.Methods: This study utilized the GBD 2019 to compare the age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), age-standardized disability-adjusted life years (DALYs) rate, and the proportion attributed to different risk factors in China, the United States, and India. Joinpoint models and autoregressive integrated moving average (ARIMA) models were employed to capture the changing trends in disease burden and forecast outcomes.Results: From 1990 to 2019, China’s age-standardized COPD incidence and mortality rates decreased by 29% and 70%, respectively. In the same period, India’s rates decreased by 8% and 33%, while the United States saw an increase of 9% in COPD incidence and a 22% rise in mortality rates. Smoking and ambient particulate matter pollution are the two most significant risk factors for COPD, while household air pollution from solid fuels and low temperatures are the least impactful factors in the United States and India, respectively. The proportion of risk from household air pollution from solid fuels is higher in India than in China and the United States. Predictions for 2030 suggest that the age-standardized DALY rates, ASIR, and ASMR in the United States and India are expected to remain stable or decrease, while China’s age-standardized incidence rate is projected to rise.Conclusion: Over the past three decades, the incidence of COPD has been decreasing in China and India, while showing a slight increase in the United States. Smoking and ambient particulate matter pollution are the primary risk factors for men and women, respectively. The risk of household air pollution from solid fuels in India needs attention.Keywords: COPD, global burden of disease, risk factors, DALYs

Bo Sun,1 Xuewei Cao,2 Ming Xin,3 Ruiqian Guan4 1Neurology Department, The 962nd Hospital of the PLA Joint Logistic Support Force, Harbin, People’s Republic of China; 2Cardiopulmonary Department, Jiamusi Hospital of Traditional Chinese Medicine, Harbin, People’s Republic of China; 3Neurology Department, Xin Wanhe Acupuncture Clinic, Harbin, People’s Republic of China; 4Massage Department, The Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, People’s Republic of ChinaCorrespondence: Ruiqian Guan, Email 196224917@qq.comAbstract: Depression is a prevalent mental disorder and has a profound impact on an individual’s psychological and physical well-being. It is characterized by a persistently depressed mood, loss of interest, energy loss, and cognitive dysfunction. In recent years, more and more people have changed to mental diseases, such as depression, anxiety, mania and so on. In the incidence of depression, covering all ages, but still mainly young and middle-aged women. Traditional treatments for depression mainly rely on medication and psychotherapy, but these methods are not effective for all patients and are often accompanied by certain side effects. Therefore, finding safe and effective alternative or adjuvant treatments has become a priority. Here we highlight the research progress of acupuncture in the treatment of depression and to explore the mechanism of acupuncture in the treatment of depression. Acupuncture treatment of depression is an ancient and effective method, the mechanism involves multiple biological pathways, for example, by regulating neurotransmitter levels, regulating the neuroendocrine axis, improving neuroplasticity, anti-inflammatory and other effects, improving emotional state and play an antidepressant role. To provide evidence to support the widespread use of acupuncture in clinical practice. We hope to provide new treatment ideas and methods for patients with depression, and even reduce the incidence of depression.Keywords: acupuncture, depression, mechanism

Yunhong Ren,1,&ast; Yinhao Guo,2,&ast; Jing Tang,2 Ling He,1 Meiling Li,1 Xuemei Huang,1 Qin Lu,1 Baoxia Sun,1 Haixia Feng,1 Huan Liu,1 Juan Du,1 Jun Li1 1Mianyang Key Laboratory of Anesthesia and Neuroregulation, Department of Anesthesiology, Mianyang Central Hospital, Mianyang, Sichuan, 621000, People’s Republic of China; 2Department of Anesthesiology, North Sichuan Medical College, Nanchong, Sichuan, 637000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Li; Juan Du, Mianyang Key Laboratory of Anesthesia and Neuroregulation, Department of Anesthesiology, Mianyang Central Hospital, Mianyang, Sichuan, People’s Republic of China, Email lj89199@163.com; 1151941061@qq.comPurpose: This study aimed to investigate the effects of different psychological personalities and pain catastrophizing levels on postoperative analgesia in patients undergoing cesarean section.Patients and Methods: Puerperas who underwent cesarean section at our hospital between January and August 2023 were recruited into the study and assessed using the Eysenck Personality Questionnaire-Revised Short Scale (EPQRSC) and Pain Catastrophizing Scale (PCS). Data on the numerical pain intensity at rest and during activity 24 h after surgery, number and dosage of analgesia pumps, and satisfaction with analgesia were recorded. According to the numerical pain score during activity 24 h post-operation, the patients were divided into the analgesia incomplete group (≥ 4) and control group (< 4). Univariate analysis, Spearman correlation analysis, and binary logistic regression analysis were used to evaluate the influence of personality characteristics and PCS on postoperative analgesia.Results: A total of 778 women were included in the study. The incidence of inadequate analgesia was 89.8%. The satisfaction rate of analgesia was 66.8%. Univariate analysis showed that extraversion; neuroticism; PCS; numbers of previous cesarean delivery; ASA; analgesic satisfaction; and 24-h analgesia pump compressions and dosage were associated with postoperative analgesia after cesarean section (P< 0.05). Using binary logistic regression analysis, the first cesarean section (odds ratio [OR]=0.056, 95% confidence interval [CI]=1.913– 19.174), the number of 24-h analgesic pump compressions (OR=8.464, 95% CI=0.356– 0.604), extraversion (OR=0.667, 95% CI=0.513– 0.866), neuroticism (OR=1.427, 95% CI=1.104– 1.844), and PCS (OR=7.718, 95% CI=0.657– 0.783) were factors affecting postoperative analgesia.Conclusion: The incidence of inadequate analgesia after a cesarean section was high (89.8% on the first day after surgery). Formulating accurate analgesia programs for women undergoing cesarean section with extraversion, neuroticism personality characteristics, and pain catastrophizing behaviors is necessary for improving their postoperative analgesia effects and satisfaction and promoting postpartum comfort.Keywords: aftercare, anesthetics, breast feeding, fear, personal satisfaction, postpartum depression

Cheng Qin, Zhiping Qi, Su Pan, Peng Xia, Weijian Kong, Bin Sun, Haorui Du, Renfeng Zhang, Longchuan Zhu, Dinghai Zhou, Xiaoyu Yang Department of Orthopedic Surgery, the Second Hospital of Jilin University, Changchun, 130041, People’s Republic of ChinaCorrespondence: Xiaoyu Yang, Department of Orthopedic Surgery, the Second Hospital of Jilin University, Changchun, TX, 130041, People’s Republic of China, Email yangxiaoy@jlu.edu.cnAbstract: Spinal cord injury (SCI) treatment represents a major challenge in clinical practice. In recent years, the rapid development of neural tissue engineering technology has provided a new therapeutic approach for spinal cord injury repair. Implanting functionalized electroconductive hydrogels (ECH) in the injury area has been shown to promote axonal regeneration and facilitate the generation of neuronal circuits by reshaping the microenvironment of SCI. ECH not only facilitate intercellular electrical signaling but, when combined with electrical stimulation, enable the transmission of electrical signals to electroactive tissue and activate bioelectric signaling pathways, thereby promoting neural tissue repair. Therefore, the implantation of ECH into damaged tissues can effectively restore physiological functions related to electrical conduction. This article focuses on the dynamic pathophysiological changes in the SCI microenvironment and discusses the mechanisms of electrical stimulation/signal in the process of SCI repair. By examining electrical activity during nerve repair, we provide insights into the mechanisms behind electrical stimulation and signaling during SCI repair. We classify conductive biomaterials, and offer an overview of the current applications and research progress of conductive hydrogels in spinal cord repair and regeneration, aiming to provide a reference for future explorations and developments in spinal cord regeneration strategies. Keywords: neural tissue engineering, electrical stimulation, electrical signal, conductive biomaterials, spinal cord injury microenvironment

Xiaoyu Zhang,1– 3,&ast; Lan Ding,1– 3,&ast; Ling Sun,1– 3 Bingqing Sun,1– 3 Yangyi Huang,1– 3 Yishan Qian,1– 3,&ast; Xingtao Zhou1– 3,&ast; 1Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, People’s Republic of China; 2Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, 200031, People’s Republic of China; 3Shanghai Research Center of Ophthalmology and Optometry, Eye & ENT Hospital, Fudan University, Shanghai, 200031, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yishan Qian; Xingtao Zhou, Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, People’s Republic of China, Tel +86-21-64377134, Fax +86-21-64377151, Email thronebird31@hotmail.com; doctzhouxingtao@163.comPurpose: To investigate the relationship between corneal tomographic or biomechanical parameters and risk of keratoconus in very asymmetric ectasia (VAE).Methods: This retrospective case-control single-centre study included patients with VAE and normal controls. The VAE group had clinical ectasia in one eye and normal topography (VAE-NT) in the fellow eye; VAE-NT eyes were selected for analysis. The control group was selected from corneal refractive surgery candidates; the right eye was enrolled. Scheimpflug-based corneal tomography (Pentacam) and corneal biomechanical assessment (Corvis ST) were performed. Univariate and multivariable logistic regression were performed using Cox proportional hazards models to evaluate keratoconus-associated risk factors. A two-piecewise linear regression model was applied to examine the threshold effect of selected vital paragmeters on the risk of keratoconus according to a smoothing plot.Results: Threshold effect between tomographic integration and risk of keratoconus was observed. Discrepancy between the central corneal thickness and thinnest corneal thickness (discrepancy CCT vs TCT) greater than 5 μm, discrepancy between the apex corneal thickness and thinnest corneal thickness (discrepancy ACT vs TCT) greater than 3 μm, vector distance between CCT and TCT (distance CCT vs TCT) greater than 0.65 mm indicated a significant increased risk of keratoconus. Risk of keratoconus decreased when distance CCT vs TCT was less than 0.65 mm.Conclusion: Discrepancy CCT vs TCT, discrepancy ACT vs TCT, and distance CCT vs TCT can be used as indicators for risk assessment of early keratoconus.Keywords: keratoconus, corneal tomographic, corneal biomechanical, very asymmetric ectasia

Kai Yang,1 Beibei Sun,2 Shicheng Zhang,3 Ying Pan,1 Jun Fang4 1Department of Medical Technology, Anhui Medical College, Hefei, Anhui, 230601, People’s Republic of China; 2Department of Clinical Laboratory, the Second Hospital of Anhui Medical University, Hefei, Anhui, 230601, People’s Republic of China; 3School of Public Health and Health Management, Anhui Medical College, Hefei, Anhui, 230601, People’s Republic of China; 4Faculty of Pharmaceutical Science, Sojo University, Kumamoto, 860-0082, JapanCorrespondence: Jun Fang, Faculty of Pharmaceutical Science, Sojo University, Ikeda 4-22-1, Kumamoto, 860-0082, Japan, Email fangjun@ph.sojo-u.ac.jpPurpose: The clinical significance of the red blood cell distribution width (RDW)-coefficient of variation (RDW-CV) has been recognized in numerous diseases, but few studies have investigated the usefulness of RDW-standard deviation (RDW-SD). This study aimed to compare the utility of RDW-SD and RDW-CV in evaluating liver fibrosis stage in patients with chronic hepatitis B (CHB).Patients and Methods: In this retrospective study, we enrolled 720 treatment-naïve CHB patients and 578 healthy controls, and evaluated their clinical parameters. In CHB patients, the associations between RDW-CV and liver fibrosis stage were analyzed as compared to RDW-SD using one-way analysis of variance (ANOVA), Spearman’s rank correlation, student’s t-test, binary logistic regression, and receiver operating characteristic (ROC) curve.Results: RDW-SD, rather than RDW-CV was significantly elevated in CHB patients compared with healthy controls. Correlation analysis showed a stronger association between RDW-SD and liver fibrosis stage than RDW-CV in CHB patients. RDW-CV and RDW-SD are both independent predictors of significant fibrosis. For the diagnosis of significant fibrosis, the area under the receiver operating characteristic curve (AUC) for RDW-CV was 0.599, while for RDW-SD, it was 0.706. RDW-to-platelet ratio (RPR), a novel index for liver fibrosis calculated as RDW-CV/platelet, exhibited an AUC of 0.730. This AUC increased to 0.752 when RDW-CV in the RPR formula was replaced with RDW-SD. Additionally, subgroup analyses based on age, gender, and HBeAg status showed that the AUC for RDW-SD in diagnosing significant fibrosis was significantly greater than that for RDW-CV, with statistically significant differences.Conclusion: RDW-SD showed superiority in reflecting liver fibrosis stage and diagnosing liver significant fibrosis than RDW-CV in treatment-naïve CHB patients.Keywords: red blood cell distribution width, liver fibrosis, chronic hepatitis B

Yu Mao,1 Yuan Xie,1 Jiani Tang,1 Yujing Shen,2 Yang Liu,1 Bing Sun1 1Department of Cardiology, Tongji Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Department of Echocardiography, Tongji Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Bing Sun, Department of Cardiology, Tongji Hospital, Tongji University School of Medicine, No. 389, Xincun Road, Putuo District, Shanghai, 200065, People’s Republic of China, Tel +86 21-66111048, Email woowoocncn@163.comPurpose: The purpose of this study was to assess the left ventricular function effects of permanent left bundle branch pacing (LBBP) versus traditional right ventricular pacing (RVP).Patients and Methods: Consecutive patients receiving pacemaker implantation were included and divided into left bundle branch block (LBBB) group and right ventricular pacing (RVP) group. Baseline characteristics were collected, and they received 1-year follow-up. Electrocardiogram (ECG) characteristics and pacing parameters were assessed before and after implantation. Cardiac function parameters such as left ventricular ejection fraction (LVEF) and tricuspid regurgitation (TR) were recorded and compared.Results: Of 78 patients included, 45 patients received LBBP (mean age, 72.7 ± 12.2 years; male, 55.6%) and 33 patients underwent RVP (mean age 72.9 ± 11.8 years; male, 63.6%). The pacing parameters were satisfactory during the implantation and remained stable during mid-term follow-up. During the follow-up period, LBBP patients had a greater decrease in LVEDD and LVESD. The TR in the LBBP group was significantly improved as compared to the RVP group (P=0.016).Conclusion: Permanent LBBP achieves favorable cardiac hemodynamic effects with good stability and safety. LBBP may reduce severe TR at 1-year follow-up, and LBBP may be an option for patients with severe TR.Keywords: left bundle branch pacing, electrical synchrony, mechanical synchrony, left ventricular function, tricuspid regurgitation

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

Na Zhao,1,2,&ast; Bowen Sun,1,&ast; Yuan Cheng,1 Jianliu Wang1 1Department of Gynecology and Obstetrics, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China; 2Department of Obstetrics and Gynecology, Peking University International Hospital, Beijng, 102206, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianliu Wang; Yuan Cheng, Department of Gynecology and Obstetrics, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China, Tel +86-10-88324385 ; +86-10-88324474, Email wangjianliu1203@163.com; chengyuan@bjmu.edu.cnBackground: The role of immune checkpoint inhibitors in endometrial cancer is limited. At present, the anti-programmed cell death protein 1 (anti-PD-1) antibody is only used in patients with recurrence or metastasis. CD40 is an important immune checkpoint, which is expressed in tumor cells and immune cells, but its distribution characteristics in endometrial carcinoma have not been explored.Methods: Sixty-eight cases of primary endometrial carcinoma treated in Peking University People’s Hospital from January 2010 to December 2020 were collected, including 28 cases of poorly differentiated endometrioid adenocarcinoma, 23 cases of serous carcinoma and 17 cases of clear cell carcinoma. The relationship of CD40 expression and PD-L1 expression with their prognosis was analyzed by immunohistochemistry.Results: We found that CD40 had higher expression in non-endometrioid endometrial carcinoma, which lead to the worse prognosis. The effect of high expression of CD40 on the prognosis of endometrioid adenocarcinoma was not significantly different, and most patients with good prognosis. We found that the proportion of CD40 distribution in tumor cells and immune cells may be associated with this heterogeneity.Conclusion: The expression of CD40 in different endometrial cancers may indicate the difference prognosis, which may become a potential target for drug treatment of non-endometrioid endometrial carcinoma.Keywords: endometrial cancer, CD40, PD-L1, heterogeneity, immune checkpoint

Chao Tang,1,2,&ast; Xiaoqing Deng,1,&ast; Jingru Qu,1 Yahui Miao,1 Lei Tian,1 Man Zhang,1 Xiaoyu Li,1 Bei Sun,1 Liming Chen1 1NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, 300134, People’s Republic of China; 2The Affiliated Huzhou Hospital, Zhejiang University School of Medicine (Huzhou Central Hospital), Huzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liming Chen; Bei Sun, No. 6 North Huanrui Road, Beichen District, Tianjin, People’s Republic of China, Email xfx22081@vip.163.com; sun_peipei220@hotmail.comBackground: Diabetic kidney disease (DKD) is a major diabetic microvascular complication. Fatty acid-induced lipotoxicity and apoptosis were associated with the exacerbation of DKD. However, the association of lipotoxicity with renal tubular apoptosis and the effects of fenofibrate on DKD are not fully understood.Methods: Eight-week-old db/db mice were given fenofibrate or saline by gavage for 8 weeks. Human kidney proximal tubular epithelial (HK2) cells stimulated with palmitic acid (PA) and high glucose (HG) were used as a model of lipid metabolism disorders. Apoptosis was assessed with or without fenofibrate. The AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) and AMPK inhibitor Compound C were used to determine the involvement of AMPK and Medium-chain acyl-CoA dehydrogenase (MCAD) in the regulation of lipid accumulation by fenofibrate. MCAD silencing was achieved by small interfering RNA (siRNA) transfection.Results: Fenofibrate reduced triglyceride (TG) content and lipid accumulation in DKD. Importantly, renal function and tubular cell apoptosis were significantly improved by fenofibrate. Fenofibrate reduced apoptosis, accompanied by increased activation of the AMPK/FOXA2/MCAD pathway. MCAD silencing resulted in apoptosis and lipid accumulation despite fenofibrate treatment.Conclusion: Fenofibrate improves lipid accumulation and apoptosis through the AMPK/FOXA2/MCAD pathway. MCAD may be a potential therapeutic target of DKD, and the use of fenofibrate as a treatment for DKD warrants further study.Keywords: fenofibrate, diabetic kidney disease, renal tubular cell, apoptosis, lipid accumulation, MCAD

Zhifeng Huang,1,&ast; Hui Gan,1,&ast; Yiyun Huang,2,&ast; Huiqing Zhu,1 Tingting Liu,1 Tong Chen,1 Runpei Lin,1 Manrong Xie,2 Baoqing Sun1 1Department of Laboratory, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Helong Street Community Health Service Center, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Baoqing Sun; Manrong Xie, Department of Clinical Laboratory, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510180, People’s Republic of China, Tel +86 18816781502, Email sunbaoqing@vip.163.com; Xmr20041103@163.comPurpose: To investigate the lifestyle and stress of mothers during pregnancy to analyze the risk factors for the disease in early childhood.Patients and Methods: A cross-sectional survey was conducted from January 2022 to June 2022 in a sub-district in Guangzhou, China. A total of 3437 valid questionnaires were eventually collected. The questionnaire consisted of 56 questions in three sections included questions on child’s birth conditions and early life environment, questions on mother’s lifestyle during pregnancy, and questions about father.Results: 49.75% of the children were likely to have allergic diseases (suspected allergy group). There were more boys in the suspected allergy group (58% vs 50%), and the percentage of children born at first birth was also higher in the suspected allergy group (61% vs 51%). 67% to 69% of children had suspicious allergies when one parent claimed an allergy, and 80.1% when both parents reported an allergy. The results of the multifactorial logistic model showed that male had 1.49 (1.28 to 1.73) times the risk of allergic diseases than female, and preterm births increased the risk of allergic diseases by 1.53 (1.13– 2.07) times compared to full-term births. Both unplanned pregnancies and pregnancy complications increased the risk of allergic diseases in children before school age [1.34 (1.15– 1.55) and 1.82 (1.46– 2.26)]. Among pregnant women who reported regular passive smoking, the risk of the disease was increased 2.43 (1.71 to 3.50) times in preschool children. Reported allergies in all family members were significant risk factors for allergic diseases in children, especially mother [2.88 (2.41~3.46)]. In the prenatal period, maternal negative emotions are more common in children with suspected allergies.Conclusion: Nearly half of the children in the region suffer from allergic diseases. Sex, birth order and full-term delivery all contributed to early childhood allergy. Family history of allergy, especially maternal, was the most important risk factor, and the number of family members with allergy was significantly associated with the allergy in children. Maternal effects are also reflected in prenatal conditions such as unplanned pregnancy, smoke exposure, pregnancy complications, and prenatal stress.Keywords: cross-sectional, heritability, risk factor, questionnaire, allergic rhinitis

Mongolia experienced a nationwide measles outbreak during 1 March 2015–31 December 2016, with 49,077 cases reported to the WHO; many were among vaccinated young adults, suggesting a possible role of vaccine failure. Advanced laboratory methods, coupled with detailed epidemiological investigations, can help classify cases as vaccine failure, failure to vaccinate, or both. In this report, we conducted a study of cases to identify risk factors for breakthrough infection for a subset of laboratory-confirmed measles cases. Of the 193 cases analyzed, only 19 (9.8%) reported measles vaccination history, and 170 (88%) were uncertain. Measles-specific IgG avidity testing classified 120 (62%) cases as low IgG avidity, indicating no prior exposure to measles. Ten of these cases with low IgG avidity had a history of measles vaccination, indicating primary vaccine failure. Overall, sixty cases (31%) had high IgG avidity, indicating breakthrough infection after prior exposure to measles antigen through vaccination or natural infection, but the IgG avidity results were highly age-dependent. This study found that among young children aged 9 months–5 years, breakthrough infection was rare (4/82, 5%); however, among young adults aged 15–25 years, breakthrough infection due to secondary vaccine failure (SVF) occurred on a large scale during this outbreak, accounting for the majority of cases (42/69 cases, 61%). The study found that large-scale secondary vaccine failure occurred in Mongolia, which highlights the potential for sustained outbreaks in post-elimination settings due to “hidden” cohorts of young adults who may have experienced waning immunity. This phenomenon may have implications for the sustainability of measles elimination in countries that remain vulnerable to the importation of the virus from areas where it is still endemic. Until global measles elimination is achieved, enhanced surveillance and preparedness for future outbreaks in post- or peri-elimination countries may be required.

Tao Sun,1,2,&ast; Yanqiao Ren,1,2,&ast; Bo Sun,1,2,&ast; Lei Chen,1,2 Licheng Zhu,1,2 Lijie Zhang,1– 3 Chuansheng Zheng1,2 1Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Hubei Province Key Laboratory of Molecular Imaging, Wuhan, Hubei, People’s Republic of China; 3Department of Interventional Radiology, The Fifth Medical Center of Chinese, PLA General Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chuansheng Zheng, Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China, Tel +86-13329702158, Email hqzcsxh@sina.com Lijie Zhang, Department of Interventional Radiology, The Fifth Medical Center of Chinese, PLA General Hospital, Beijing, People’s Republic of China, Email zlj_1226@163.comObjective: To evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs: sorafenib, lenvatinib, and apatinib) plus camrelizumab (TACE-TKIs-C) vs TACE combined with TKIs (TACE-TKIs) for advanced hepatocellular carcinoma (HCC).Methods: In this two-center retrospective study, patients with advanced HCC treated with TACE-TKIs-C or TACE-TKIs were enrolled between January 1, 2018, to October 1, 2020. A total of 260 eligible patients received TACE-TKIs-C (N=70) or TACE-TKIs (N=190). The differences in overall survival (OS), progression-free survival (PFS) and tumor response were compared between two groups. Propensity score matching (PSM) analysis was applied to reduce patient selection bias. The risk factors affecting OS or PFS were analyzed.Results: Fifty-three pairs of patients were matched after PSM analysis. Before PSM analysis, the median OS and PFS of TACE-TKIs-C were significantly longer than those of the TACE-TKIs (OS: not reached vs 12.0 months, P< 0.0001; PFS: 10.0 months vs 6.0 months, P< 0.0001). After PSM analysis, the median OS and PFS of TACE-TKIs-C were significantly longer than those of the TACE-TKIs (OS: Not reached vs 13.0 months, P< 0.0001; PFS: 9.0 months vs 6.0 months, P< 0.0001); the uni- and multivariate analysis revealed that TACE-TKIs-C treatment was a protective factor of OS and PFS. Grade 3 or 4 hypertension occurred in 14.3% of patients in the TACE-TKIs-C group and other high-grade toxic effects were infrequent.Conclusion: In patients with advanced HCC, TACE-TKIs-C may improve overall and progression-free survival outcomes over TACE-TKIs with manageable safety profile.Keywords: hepatocellular carcinoma, transarterial chemoembolization, tyrosine kinase inhibitors, camrelizumab, propensity score matching

Jiaxin Cao,1,2 Huimin Zhang,1,2 Zhien He,2 Zhongwan Piao,1 Xianchun Zong,1 Baolin Sun1,2 1College of Life Science and Technology, Mudanjiang Normal University, Mudanjiang, People’s Republic of China; 2School of Life Science and Medicine, University of Science and Technology of China, Hefei, People’s Republic of ChinaCorrespondence: Baolin Sun; Zhongwan Piao, Email sunb@ustc.edu.cn; jwcpzw@126.comBackground: Staphylococcus aureus is a highly successful pathogen that can cause various infectious diseases, from relatively mild skin infections to life-threatening severe systemic diseases. The widespread pathogenicity of S. aureus is mainly due to its ability to produce many virulence factors that help destroy various host cells, causing disease. Our primary goal in this study was to explore the genes of highly virulent strains, to identify genes closely associated with high virulence, and to provide ideas for the treatment of infection by highly virulent clinical strains.Results: This study collected 221 clinical strains from The First Affiliated Hospital Of The University of Science and Technology of China (USTC); their hemolytic abilities were tested. Eight isolates were selected based on their highly hemolytic ability and tested their hemolytic activity again; their phenotypes and gene sequences were also explored. Whole-genome sequencing (WGS) showed six plasmids (pN315, pNE131, pSJH901, pSJH101, SAP106B, and MSSA476), eight antibiotic resistance genes [blaR1, blaI, blaZ, mecA, erm(C), erm(T), tet(38), and fosB-Saur] and seventy-two virulence related genes. Three highly virulent strains, namely X21111206, 21092239, and 21112607, were found according the Galleria mellonella infection model. Therefore, we selected 10 representative virulence genes for qRT-PCR: psmα, psmβ, hlgA, hlgB, hlgC, hla, clfA, clfB, spa, and sak. Among them, the expression levels of psmα and psmβ, the three isolates, were significantly higher than the positive control NCTC8325.Conclusion: Significant differences appear in the expression of virulence genes in the highly virulent strains, particularly the psmα and psmβ, It may be that the high expression of psm gene is the cause of the high virulence of Staphylococcus aureus. We can reduce the pathogenicity of Staphylococcus aureus by inhibiting the expression of psm gene, which may provide a strong basis for psm as a new target for clinical treatment of S. aureus infection.Keywords: Staphylococcus aureus, virulence factors, qRT-PCR, next-generation sequencing, psm

Huimin Zhang,1 Jiaxin Cao,1 Zhien He,2,3 Xianchun Zong,1 Baolin Sun2,3 1College of Life Science and Technology, Mudanjiang Normal University, Mudanjiang, People’s Republic of China; 2Department of Oncology, The First Affiliated Hospital, University of Science and Technology of China, Hefei, People’s Republic of China; 3School of Life Science and Medicine, University of Science and Technology of China, Hefei, People’s Republic of ChinaCorrespondence: Baolin Sun, Email sunb@ustc.edu.cnPurpose: This study aimed to investigate the molecular characteristics, antimicrobial resistance and hemolytic phenotype of Staphylococcus aureus isolated from Anhui, China.Results: From August 2021 to January 2022, 214 S. aureus isolates were collected from the Anhui Provincial Hospital. This study identified 117 methicillin-resistant S. aureus and 97 methicillin-sensitive S. aureus isolates, and the detection rate of methicillin-resistant isolates was 1.8-fold higher than the average isolates reported in China (53.9% vs 30.5%). S. aureus isolates share identity at five or more of the seven MLST-based housekeeping loci, referred to as the clonal complex (CC). Forty ST types were found in 214 clinical S. aureus isolates, with the most extensive distribution of ST59 and ST6697 typing numbers and higher CC5 detection rates than any other clonal group. (The ST typing is the result of the MLST typing website query.) To detect the virulence of ST types of S. aureus, hemolysis experiments were performed on 214 clinical isolates, and it was concluded that ST59 had a relatively robust hemolytic capacity.Conclusion: Anhui S. aureus isolates have unique molecular and antibiotic resistance profiles. The antibiotic resistance profile may be related to the random use of antibiotics.Keywords: Staphylococcus aureus, epidemiological analysis, multilocus sequence typing, phenotype, hemolytic

Bao Sun,1,2,&ast; Yingshuang Tang,2,&ast; Dan Chen,3 Yanning Bai,4 Yuanyuan Zhang,5 Suning Chen,2 Yi Qiao,2 Jingwen Wang2 1Department of Pharmacy, The Second Affiliated Hospital of Xi’an Medical University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Pharmacy, Xijing Hospital, Fourth Military Medical Unversity, Xi’an, Shaanxi, People’s Republic of China; 3Department of pharmacy, 404 Hospital of Mianyang, Mianyang, Sichuan, People’s Republic of China; 4Department of Clinical Pharmacy, Yan’ an University Affiliated Hospital, Yan’an, Shaanxi, People’s Republic of China; 5Department of Pharmacy, The Second Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Qiao; Jingwen Wang, Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, 127 Changle West Road, Xi’an, Shaanxi, People’s Republic of China, Email 694305040@qq.com; wangjingwen8021@163.comAbstract: Biliary cryptococcosis infection is extremely rare and difficult for preoperative diagnosis. We report a rare case of 61-year-old woman with biliary cryptococcal infection. To explore the general rule and case characteristics of biliary cryptococcal infection and provide a reference for future diagnosis and treatment, we consulted the PubMed database for reported biliary cryptococcal infection from 1985 to 2021. Including the present one, we collected 12 reports, among which half were male and five were younger than 18 years old. Clinical manifestations were mainly jaundice, while in vitro examination revealed bile duct dilatation and bile duct stenosis. In 8 cases (66.67%), symptoms improved or healed after antifungal treatment. Although preoperative misdiagnosis of cryptococcal infection is high, the antifungal treatment is quite effective. Thus, early accurate diagnosis can effectively improve the cure rate of biliary cryptococcosis infected patients.Keywords: biliary cryptococcosis, obstructive jaundice, Cryptococcus neoformans, literature analysis

Huiqing Zhu,1,&ast; Zhifeng Huang,1,&ast; Tingting Liu,1 Nairui An,1 Hui Gan,1 Dongming Huang,2 Chuangli Hao,3 Wenting Luo,1 Baoqing Sun1 1Department of Allergy and Clinical Immunology, Department of Laboratory, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, People’s Republic of China; 2Department of Pediatrics, Boai Hospital of Zhongshan City, Zhongshan, 528400, People’s Republic of China; 3Department of Respirology, Children’s Hospital, Soochow University, Suzhou, 215025, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Baoqing Sun; Wenting Luo, Department of Allergy and Clinical Immunology, Department of Laboratory, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiangxi Road, Guangzhou, 510120, Guangdong, People’s Republic of China, Tel +86 20 8306 2865, Fax +86 20 8306 2729, Email sunbaoqing@vip.163.com; 348307379@qq.comPurpose: An objective of this study was to investigate the allergen sensitization characteristics of cat, dog and horse dander in patients with suspected allergic diseases in different geographical regions of Chinese mainland.Patients and Methods: We invited 2377 patients aged 0– 86 years with suspected allergic diseases to participate in a cross-sectional survey in 11 provinces in China. Combined with the questionnaires and animal-specific IgE levels, we analyzed the epidemiological characteristics and risk factors of furry animal sensitization in different regions and populations of Chinese Mainland.Results: Among the 2377 patients with suspected allergic diseases, 14.9% were sensitized to cat dander, 9.3% to dog dander and 5.5% to horse dander. Animal allergens mainly cause low-level sensitization (class 1– 3). There was a significant correlation between cat, dog and horse dander allergen sIgE, with correlation coefficients (rs) all greater than 0.750. The majority (46.5%) of sIgE-positive patients were sensitized to at least two animal allergens simultaneously. The prevalence of these animals all showed a trend of increasing first and then decreasing with age, and all reached the peak in young adolescence. As for the geographical factors, the sensitization rate of cats and dogs in Western was significantly higher than that in Eastern (cat: 18.4% vs 9.2%, dog: 11.6% vs 5.5%, all P < 0.001), however, no significant differences were found in horses. Aged ≤ 6 years, living in Western, and high animal allergen exposure elevated the risk of cat or dog sensitization. Living on a lower floor (aOR: 0.56) was a protective factor for horse sensitization.Conclusion: In this representative sample of Chinese patients with suspected allergic diseases, there was an apparent geographic variation in sensitization to cats and dogs. Age factor and living in Western also had a significant impact on animal allergen sensitization rate.Keywords: animal allergen, specific immunoglobulin E, cross-sectional survey, suspected allergic patient

Zhao Zhou,1,2,&ast; Xiaohan Cui,1,2,&ast; Peng Gao,2 Xudong Zhang,2 Chunfu Zhu,2 Beicheng Sun1 1Department of Hepatobiliary Surgery of Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, People’s Republic of China; 2The Affiliated Changzhou NO.2 People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunfu Zhu, The Affiliated Changzhou NO.2 People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of China, Email zcfmlm@njmu.edu.cn Beicheng Sun, Department of Hepatobiliary Surgery of Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, People’s Republic of China, Email sunbc@nju.edu.cnObjective: Recently, emerging studies have validated that circular RNAs participate in multiple biological progresses in various human malignant tumors, including hepatocellular carcinoma (HCC). However, until now, the elucidated mechanism of circular RNAs is only the tip of the iceberg. In this study, we firstly identify a novel circular RNA circRASSF5 (the only circular RNA derived from the RASSF5 gene), and attempt to investigate its biological function and underlying mechanism in HCC.Methods: qRT-PCR, Western blotting and IHC were applied to detect the expression of related genes. CCK-8 assay, EdU staining, wound healing and transwell assays were used to investigate HCC proliferation, migration and invasion abilities. Animal model studies were included to investigate the function of circRASSF5 in HCC tumorigenesis and metastasis. RNA pull-down assay, luciferase reporter assay and FISH (fluorescence in situ hybridization) assay were performed to explore the potential biological mechanism underlying circRASSF5 function in HCC.Results: CircRASSF5 is obviously downregulated in both HCC tissues and cell lines. Low level of circRASSF5 is negatively associated with larger tumor size, severe vascular invasion, more portal vein tumor embolus and unfavorable prognosis. Loss-of-function assay reveals that circRASSF5 remarkably impedes the growth and metastasis of HCC cells in vitro and in vivo. Mechanistically, circRASSF5 directly interacts with miR-331-3p as a sponge, and then enhances the expression of PH domain and leucine-rich repeat protein phosphatase (PHLPP), thus restraining the progression of HCC cells.Conclusion: Altogether, we validate that circRASSF5 is a tumor suppressor in HCC, which competitively sponges with miR-331-3p and then enhances the tumor inhibitory effect of PHLPP, indicating the potential application value of circRASSF5 for HCC diagnosis and clinical treatment.Keywords: circRASSF5, miR-331-3p, PHLPP, HCC

Antony Fute, Binghai Sun, Mohamed Oubibi College of Teacher Education, Zhejiang Normal University, Jinhua, People’s Republic of ChinaCorrespondence: Binghai Sun, Email jky18@zjnu.cn Mohamed Oubibi, Email liby478@nenu.edu.cnIntroduction: Teachers’ mental health is an imperative aspect in ensuring their appropriate cognition, behaviors and perception. Studies have reported mixed results on work engagement and compassion fatigue among employees in different time and cultures. This study assesses and examines the correlation between Chinese teachers’ work engagement and compassion fatigue during the pandemic.Methods: An online questionnaire was designed through a Chinese data collection platform (Credamo), and the sample of 3147 teachers in Zhejiang province (China) completed the survey online. The Utrecht Work Engagement Scale (UWES) was used to measure teachers’ work engagement (WE), while the Professional Quality of Life Scale version 5 (ProQoL-5) was used to measure teachers’ compassion fatigue (CF). SPSS 25, PROCESS Macro of SPSS, and JASP were used to analyze the data.Results: The results indicated a negative correlation between teachers’ work engagement and compassion fatigue in general, while particularly, vigor, dedication, and absorption negatively correlated with burnout (r = − 0.370, r = − 0.243, and r = − 0.220 respectively), but positively correlating with secondary traumatic stress (r = 0.489, r = 0.343, and r = 0.319).Discussion: Teachers’ working experience positively correlates with their work engagement but negatively correlates with their compassion fatigue.Conclusion: Teachers’ work engagement (ie, dedication) is important in reducing compassion fatigue and maintaining compassion satisfaction.Keywords: work engagement, compassion fatigue, vigor, dedication, absorption, burnout

Lei Chen,1– 3,&ast; Weihua Zhang,1– 3,&ast; Tao Sun,1– 3,&ast; Yanqiao Ren,1– 3 Bo Sun,1– 3 Licheng Zhu,1– 3 Huangxuan Zhao,1,3 Chuansheng Zheng1– 3 1Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Hubei Province Key Laboratory of Molecular Imaging, Wuhan, People’s Republic of China; 3Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chuansheng Zheng, Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan City, Wuhan, 430022, People’s Republic of China, Tel +027-85726432, Email hqzcsxh@sina.com Huangxuan Zhao, Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan City, Wuhan, 430022, People’s Republic of China, Tel +18971676985, Email zhao_huangxuan@sina.comBackground: The efficacy of the transarterial chemoembolization (TACE) process combined with percutaneous ethanol injection (PEI, TACE-P) or the radiofrequency ablation (RFA, TACE-R) process was found to be good when used for the treatment of patients suffering from early or intermediate hepatocellular carcinoma (eiHCC). The study was conducted to compare the efficacy and safety of the TACE-P with TACE-A processes followed during the treatment of patients with eiHCC.Methods: A total of 241 patients suffering from eiHCC, subjected to TACE-P (147 patients) or TACE-R (94 patients) processes from January 1, 2014, to December 31, 2018, were retrospectively reviewed and included. The propensity score matching (PSM) method was used to reduce selection bias.Results: The median overall survival (mOS) and progression-free survival (mPFS) of the TACE-P group were similar to those recorded for the TACE-R group (P> 0.05) before using the PSM technique. Similar results were obtained post the use of the PSM technique. In the subgroup analysis after PSM, patients with single tumor (dimension: ≤ 5 cm), who were subjected to TACE-P-based treatment methods, exhibited worse tumor response than patients subjected to TACE-R-based methods (HR: 1.804, 95% CI: 1.083– 3.005, P=0.023). Seven adverse events were reported. A statistically significant difference for all grades of adverse events (and grade III or IV adverse events) between the two groups (all P> 0.05) was not reported.Conclusion: The benefits and advantages of using the TACE-P based method was similar was those obtained using the TACE-R in patients with eiHCC, especially for patients with a single large tumor or multiple tumors.Keywords: early or intermediate hepatocellular carcinoma, transarterial chemoembolization, percutaneous ethanol injection, radiofrequency ablation, efficacy

Min Jiang,&ast; Bin Sun,&ast; Yong Huang, Chengyang Liu, Yan Wang, Yanli Ren, Yuhong Zhang, Yunying Wang, Di Mu Department of Laboratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Di Mu; Yunying Wang, Department of Laboratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, No. 74 Linjiang Road, Yuzhong District, Chongqing, People’s Republic of China, Tel/Fax +86 23-62887386, Email 303921@hospital.cqmu.edu.cn; Wangyunying@hospital.cqmu.edu.cnPurpose: The aim of this study was to understand the resistance mechanism of ceftazidime/avibactam (CZA) in carbapenem-resistant Klebsiella pneumoniae under antibiotic selection pressure.Patients and Methods: Four CZA-resistant Klebsiella pneumoniae strains were isolated from two patients, and six CZA-resistant strains that were produced in vitro were screened from 25 carbapenem-resistant Klebsiella pneumoniae strains. The mechanisms of resistance to CZA of these strains were characterized by PCR and Sanger sequencing.Results: CZA-resistant Klebsiella pneumoniae with different resistance mechanisms (including upregulation of the expression of efflux pumps and KPC variants (KPC-14, KPC-44)) were isolated from the same patient (patient 1). In patient 2, the resistance mechanism of CZA-resistant Klebsiella pneumoniae was the mutation of KPC-2 to KPC-33. In addition, among the CZA-resistant Klebsiella pneumoniae that were produced in vitro, we found 3 new KPC variants: KPC-86 (D179G), KPC-87 (GT241A) and KPC-88 (G523T).Conclusion: In this study, although the CZA-resistant bacteria originated from only two clinical patients, four different mechanisms of CZA resistance were detected. In the in vitro induction experiment, the mechanisms of resistance to CZA in strains from different patients were also different. The above result implies that the mechanisms of resistance to CZA are generally random and diverse. Therefore, elucidating the mechanism of resistance to CZA can provide a certain theoretical basis for the effective response of CZA-resistant strains and the selection of antibiotics.Keywords: ceftazidime/avibactam-resistance, KPC mutants, antibiotic pressure, Klebsiella pneumoniae, resistance mechanisms

Feng Qian,1– 3,&ast; Song Hu,4,&ast; Yueping Zhu,2,3 Yinling Wang,2,3 Jin Liu,2,3 Jialu Qiao,4 Xiji Shu,4 Yong Gao,5 Binlian Sun,4 Chuanwu Zhu1– 3 1Department of Infectious Diseases, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, People’s Republic of China; 2Department of Infectious Diseases, The Affiliated Infectious Disease Hospital of Soochow University, Suzhou, 215131, People’s Republic of China; 3Department of Infectious Diseases, The Fifth People’s Hospital of Suzhou, Suzhou, 215131, People’s Republic of China; 4Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan, 430056, People’s Republic of China; 5The First Affiliated Hospital, Department of Life Science and Medicine, University of Science and Technology of China, Hefei, 230001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chuanwu Zhu; Binlian Sun, Tel/Fax +86 512 87806206 ; +86 27 84225149, Email zhuchw@126.com; binlian17@jhun.edu.cnPurpose: To investigate factors involved in T-cell depletion in combination antiretroviral therapy (cART)-treated human immunodeficiency virus 1 (HIV-1)-positive patients.Patients and Methods: 29 HIV-1-positive patients were enrolled. The CD4+, CD8+ T cell subsets and CD56dim NK cells were detected by flow cytometry. The concentrations of cytokines were measured by enzyme-linked immunosorbent assay. Extraction, amplification, and viral load quantification of specimens were performed using the Roche Cobas Ampliprep/Cobas TaqMan HIV-1 test.Results: Compared with IR group, the total number of red blood cells (RBCs) and lymphocytes (LCs) in INR group was significantly reduced, and there was a significant positive correlation between the number of RBCs and that of LCs. The overall production rates of T cells-related cytokines were lower in INR group. However, the cell-surface expression of programmed death-1 (PD-1) on CD4+ T and CD8+ T cells were markedly elevated in INR group. Moreover, it was found that the proportion and the killing ability of CD56dim NK cells significantly increased in INR patients, and significantly correlated with apoptosis of T lymphocytes.Conclusion: A poor immune reconstitution in HIV-positive patients might result from multiple factors, including bone marrow suppression, high PD-1 expression on the surface of CD4+ T cells, and over-activation of T and NK cells. Besides, the activity of NK cells and RBCs count might be important auxiliary indicators for immune reconstitution and provided a reliable guidance for developing strategies to improve immune reconstitution.Keywords: AIDS, T-cells, CD56dim NK cells, antiretroviral therapy, immune reconstitution

Xiao-Yuan Li,1,&ast; Yang Rao,2,&ast; Bing Sun,3 Xue-Mei Mao4 1Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China; 2Department of Gynecological Oncology, Tianjin Central Obstetrics and Gynecology Hospital, Tianjin, 300199, People’s Republic of China; 3Department of Radiation Oncology, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, 100071, People’s Republic of China; 4Department of Obstetrics and Gynecology, Tianjin Integrated Traditional Chinese and Western Medicine Hospital (Nankai Hospital), Tianjin, 300102, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xue-Mei Mao; Bing Sun, Tel +86 13820312420 ; +86 13810193881, Email mxm0206@163.com; sunice116@163.comPurpose: This study was to investigate the efficacy and safety of anlotinib combined with programmed cell death protein 1 (PD-1) blockades for patients with previously treated advanced epithelial ovarian cancer (EOC).Patients and Methods: Present study was designed as a retrospective study, a total of 32 patients with advanced EOC who progressed after at least two lines previously available standard therapy were included in this study. All the patients were administered with anlotinib combined with PD-1 blockades administration. Clinical activity was implemented and analyzed, which was assessed according to the change of target lesion by imaging evidence and all the subjects were followed up regularly. Safety profile were collected and documented during the treatment. Univariate analysis was carried out using log rank test and multivariate analysis were adjusted by Cox regression analysis.Results: The best overall response suggested that partial response was noted in 12 patients, stable disease was observed in 14 patients, progressive disease was found in 6 patients. Therefore, the objective response rate (ORR) of the 32 patients was 37.5% (95% CI: 21.1– 56.3%), disease control rate (DCR) of the patients was 81.3% (95% CI: 63.6– 92.8%). The median follow-up duration of this study was 17.5 months (follow-up range: 0.9– 33.5 months). And the median PFS and OS of the 32-patient cohort was 6.8 months (95% CI: 2.64– 10.96) and 18.5 months (95% CI: 14.08– 22.92), respectively. The most common treatment-related adverse reactions were fatigue (68.8%), nausea and vomiting (56.3%), hypertension (50.0%) and diarrhea (40.6%). Multivariate Cox regression analysis for PFS indicated that ECOG performance status and FIGO stage were independent factors to predict PFS of patients with previously treated EOC.Conclusion: Anlotinib combined with PD-1 blockades demonstrated promising efficacy and tolerable safety profile for patients with previously treated advanced EOC preliminarily. The conclusion should be confirmed in more patients with advanced EOC subsequently.Keywords: epithelial ovarian cancer, anlotinib, PD-1 blockade, efficacy, safety

Changkang Sun,1,&ast; Binghai Sun,1,&ast; Yishan Lin,1 Hui Zhou2 1College of Teacher Education, Zhejiang Normal University, Jinhua, 321004, People’s Republic of China; 2Jinhua Advanced Research Institute, Jinhua, 321004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yishan LinCollege of Education and Human Development, Zhejiang Normal University, 688 Ying bin Road, Jinhua, Zhejiang, People’s Republic of ChinaEmail psy013@163.comHui ZhouJinhua Advanced Research Institute, Jinhua, 321004, People’s Republic of ChinaEmail zhouhui102@163.comIntroduction: Mobile phones bring much convenience to college students’ lives, but they also cause problems. Few studies have explored the effect of the fear of missing out (FoMO) on problematic mobile phone use among college students. This study tested the mediating effect of self-control in the relationship between FoMO and problematic mobile phone use. It also explored the moderating roles of perceived social support and future orientation in the relationship between these variables.Methods: A cross-sectional design was used in this study. Materials include the Fear of Missing Out Scale, Perceived Social Support Scale, Self-control Scale (Chinese version), Mobile Phone Addiction Index, and Consideration of Future Consequences Scale. Of 3606 participants, 3189 completed the questionnaire. SPSS 21 was used to analyze the mediation and moderation effects.Results: The results showed that problematic mobile phone use was positively predicted by FoMO. The relationship between FoMO and problematic mobile phone use was partially mediated by self-control. When the scores of perceived social support and future orientation were high, the negative effect of FoMO on problematic mobile phone use was reduced.Conclusion: The negative effect of FoMO on problematic mobile phone use through self-control was moderated by perceived social support and future orientation.Keywords: fear of missing out, self-control, perceived social support, future orientation, problematic mobile phone use

Liting Wu,1,&ast; Wenting Luo,1,&ast; Haisheng Hu,1 Xianhui Zheng,1 Zhangkai J Cheng,1 Dongming Huang,2 Xiaowen Huang,2 Hong Zhang,3 Yang Liu,3 Rongfang Zhang,4 Hui Yang,4 Yun Sun,5 Yi Wang,5 JinHai Ma,6 Jing Liu,6 Xin Sun,7 Huajie Wu,7 Chunhua Wei,8 Shuping Zhang,8 Xiaoluan Li,9 Shuang Ren,9 Chuangli Hao,10 Baoqing Sun1 1Department of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, National Clinical Research Center of Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, People’s Republic of China; 2Department of Pediatrics, Boai Hospital of Zhongshan City, Zhongshan, 528400, People’s Republic of China; 3Gansu Provincial Hospital, Lanzhou, 730000, People’s Republic of China; 4Gansu Provincial Maternity and Child Care Hospital, Lanzhou, 730000, People’s Republic of China; 5Yinchuan Maternal and Child Health Care Hospital, Yinchuan, 750000, People’s Republic of China; 6Ningxia Medical University General Hospital, Yinchuan, 750000, People’s Republic of China; 7Department of Pediatrics, Xijing Hospital, the Fourth Military Medical University, Xian, 710032, People’s Republic of China; 8Weifang Weien Hospital, Weifang, 261000, People’s Republic of China; 9The First Hospital of Hebei Medical University, Shijiazhuang, 050000, People’s Republic of China; 10Department of Respirology, Children’s Hospital, Soochow University, Suzhou, 215025, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Baoqing SunFirst Affiliated Hospital of Guangzhou Medical University, 151 Yanjiangxi Road, Guangzhou, 510120, Guangdong, People’s Republic of ChinaTel +86 20 8306 2865Fax +86 20 8306 2729Email sunbaoqing@vip.163.comChuangli HaoDepartment of Respirology, Children’s Hospital, Soochow University, Suzhou, 215025, Jiangsu, People’s Republic of ChinaTel +86-51280693588Fax +86-512-80696309Email hcl_md@163.comBackground: Up to now, epidemiological studies on allergy rhinitis (AR) have primarily focused on determining the risk of disease in Chinese adults, with the majority of them designed by single centers, while cross-sectional and epidemiological data describing allergic sensitization in children with self-reported AR are scarce.Objective: This study was estimating of the latest information about the sensitization patterns and risk factors of clinical AR to develop effective strategies for the prevention and treatment of AR.Methods: We conducted a cross-sectional survey between January 2020 and June 2021 involving children from seven cities in China who reported AR. A total of 762 children participated in this survey. To evaluate the risk factors and specific sensitization patterns of clinical AR through questionnaires and specific immunoglobulin E to 11 aeroallergens.Results: Of the 762 patients, 593 (77.8%) had at least one positive IgE level. Aged 7– 14 years (OR 1.503, (95% CI 1.058– 2.136), P = 0.023); With allergic conjunctivitis (OR 1.843, (95% CI 1.297– 2.620), P = 0.001) and living in the Eastern (OR 1.802, (95% CI 1.263– 2.573), P = 0.001) all elevated the risk of clinical AR associated with aeroallergens. The sensitization rates of D. pteronyssinus and D. farinae were higher than those of other allergens in the 0– 6 and 7– 14 years old age groups. The most common aeroallergens among self-reported children with AR in the eastern were D. farinae (74.9%) and D. pteronyssinus (74.3%), while in the western were mugwort (60.0%) and marguerite (56.6%). Majority of sIgE-positive subjects were sensitized to three or more of the tested pollen allergens in the Western (52.1%), compared with 5.7% in the Eastern.Conclusion: There was an apparent geographic variation in childhood allergies in China. Age factors also had strong impacts on the allergen sensitization rate of children, but these impacts differed across regions.Keywords: allergic rhinitis, specific immunoglobulin E, cross-sectional survey, aeroallergen, children

Zili Meng,1,&ast; Bing Sun,1,&ast; Wei Chen,1,&ast; Xilong Zhang,2 Mao Huang,2 Jing Xu1 1Department of Respiratory and Critical Care Medicine, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huaian, Jiangsu, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing XuDepartment of Respiratory and Critical Care Medicine, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, 6 Beijing Road West, Huaian, Jiangsu, 223300, People’s Republic of ChinaTel +86-13912080023Fax +86-517 83724440Email xj680390@126.comPurpose: Simultaneous occurrence of hypertension and excessive daytime sleepiness (EDS) is very common in obstructive sleep apnea syndrome (OSAS), although no study has specifically addressed this issue. The present study explored the risk factors for co-occurrence of OSAS-related EDS and hypertension.Patients and Methods: A total of 161 OSAS patients were studied after undergoing an eight-hour in-laboratory polysomnography for one night. The OSAS severity assessment depends on the number of breathing disturbances per hour of sleep. EDS was defined using the Epworth Sleepiness Scale (ESS) scores of ≥ 13. Hypertension was defined according to direct cuff blood pressure (BP) measurements. Beat-to-beat R-R interval data were incorporated in polysomnography for heart rate variability analysis. The low-frequency/high-frequency band ratio was used to reflect sympathovagal balance. The study participants were divided into four groups based on the presence of EDS and/or hypertension: EDS with hypertension (n = 53), EDS without hypertension (n = 27), no EDS with hypertension (n = 38), and no EDS or hypertension (n = 43). Clinical, polysomnographic and heart rate data were compared and studied among the four groups. Plasma acetylcholine (ACh) levels were assessed to explore the effects of the non-neuronal cholinergic system and the co-occurrence of EDS and hypertension.Results: Patients with EDS and hypertension had more severe OSAS severity indices compared to control patients. Increased cardiac sympathovagal imbalance and nocturnal hypoxemia regulated the presence of EDS and hypertension. Further plasma biomarker analysis revealed that both ESS scores and BP levels were associated with significantly elevated plasma norepinephrine, interleukin-6 and superoxide dismutase levels and significantly decreased ACh levels. Logistic regression analyses showed that ACh was the only factor significantly associated with co-occurrence of EDS and hypertension after controlling for confounders using odds ratio of 0.932, with a 95% confidence interval of 0.868 to 1.000 (P = 0.049).Conclusion: The results suggested that OSAS coupled with both EDS and hypertension is a more severe phenotype of the respiratory disorder. The presence of EDS and hypertension was accompanied by sympathovagal imbalance, and co-occurrence of these two conditions may be related to decreased plasma ACh levels.Keywords: acetylcholine, subjective excessive daytime sleepiness, hypertension, obstructive sleep apnea

Xuhui Yuan, Zirong Ren, Zhengjie Liu, Weijian Li, Binghai Sun School of Teacher Education, Zhejiang Normal University, Jinhua, 321004, People’s Republic of ChinaCorrespondence: Weijian Li; Binghai SunCollege of Teacher Education, Zhejiang Normal University, 688 Yingbin Avenue, Jinhua, 321004, People’s Republic of ChinaEmail xlxh@zjnu.cn; jky18@zjnu.cnPurpose: Since it is practically significant to explore how to repair the public’s trust in charities during accidental crisis, this study explored the crisis response strategies that charitable organizations with and without crisis histories could adopt when facing a current accidental crisis.Participants and Methods: Study 1 (N = 177) used a 2 × 2 between-subjects design to examine the effects of crisis history (no crisis history vs. crisis history) and crisis response strategies (diminish vs. rebuild) on charity trust repair during an accidental crisis. Study 2 adopting a 3 × 2 between-subjects design examined the effects of crisis history (victim crisis history vs. accidental crisis history vs. preventable crisis history) and crisis response strategies (diminish vs. rebuild) on charity trust repair during an accidental crisis.Results: The results of Study 1 showed that the diminish strategy adopted by charities in an accidental crisis can enhance public trust. However, if the charity has a crisis history, the rebuild strategy will enhance public trust. The results of Study 2 showed that, under the victim crisis history condition, participants’ charity trust was borderline significantly higher than their pre-test charity trust when the diminish strategy was used. However, rebuild strategies did not significantly increase trust. Under the accidental crisis history condition, diminish strategies improved trust after the accidental crisis, while rebuild strategies did not. Under the preventable crisis history condition, diminish strategies did not improve trust after an accidental crisis, while rebuild strategies did.Conclusion: Charities should adopt a diminish strategy when experiencing their first accidental crisis. Charities with a victim or accidental crisis history should adopt a diminish strategy when facing a current accidental crisis. However, if a charity has a preventable crisis history, rebuild strategies are the most appropriate response to a current accidental crisis.Keywords: situational crisis communication theory, SCCT, crisis history, crisis response strategy, trust repair, charity

Qingqing Chen,1,2 Xinxin Han,2 Meihua Chen,2,3 Bingjiao Zhao,1,2 Bingjing Sun,1,2 Liangyan Sun,1,2 Weihua Zhang,1,2 Liming Yu,1,2 Yuehua Liu1,2 1Department of Orthodontics, Shanghai Stomatological Hospital, Fudan University, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, People’s Republic of China; 3Department of Periodontology, Shanghai Stomatological Hospital, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Yuehua Liu; Liming YuShanghai Stomatological Hospital, Fudan University, No. 356 East Beijing Road, Shanghai, 200001, People’s Republic of ChinaTel +86 2163298475Fax +86 2163614515Email liuyuehua@fudan.edu.cn; ylmphoebe@126.comPurpose: Obesity is a worldwide metabolic disease and a critical risk factor for several chronic conditions. Obstructive sleep apnea (OSA) is an important complication of obesity. With the soaring morbidity of obesity, the prevalence of OSA has markedly increased. However, the underlying mechanism of the high relevance between obesity and OSA has not been elucidated. This study investigated the effects of obesity on the structure and function of the genioglossus to explore the possible mechanisms involved in OSA combined with obesity.Methods: Six-week-old male C57BL/6J mice were fed high-fat diet (HFD, 60% energy) or normal diet (Control, 10% energy) for 16 weeks. The muscle fibre structure and electromyography (EMG) activity of genioglossus were measured. The ultrastructure and function of mitochondrial, oxidative damage and apoptosis in genioglossus were detected by transmission electron microscopy (TEM), qPCR, Western blotting, immunohistochemistry and TUNEL staining. We further studied the influence of palmitic acid (PA) on the proliferation and myogenic differentiation of C2C12 myoblasts, as well as mitochondrial function, oxidative stress, and apoptosis in C2C12 myotubes.Results: Compared with the control, the number of muscle fibres was decreased, the fibre type was remarkably changed, and the EMG activity had declined in genioglossus. In addition, a HFD also reduced mitochondria quantity and function, induced excessive oxidative stress and increased apoptosis in genioglossus. In vitro, PA treatment significantly inhibited the proliferation and myogenic differentiation of C2C12 myoblasts. Moreover, PA decreased the mitochondrial membrane potential, upregulated mitochondrial reactive oxygen species (ROS) levels, and activated the mitochondrial-related apoptotic pathway in myotubes.Conclusion: Our findings suggest that a HFD caused genioglossus injury in obese mice. The mitochondrial dysfunction and the accompanying oxidative stress were involved in the genioglossus injury, which may provide potential therapeutic targets for OSA with obesity.Keywords: obesity, obstructive sleep apnea, genioglossus, muscle, mitochondria

Wang D, Xu X, Zhang K, et al. Int J Nanomedicine. 2018;13:187–198. The authors have advised due to an error at the time of figure assembly, Figure 5 on page 195 is incorrect. The correct Figure 5 is shown in Download Article. The authors apologize for this error and advise it does not affect the results of the paper. Read the original article