Search

Liang Chen,1,2 Zeqiang Xie,1,2 Jiyong Jian1,2 1Clinical Laboratory Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Key Laboratory of Urinary Cellular Molecular Diagnostics, Beijing, People’s Republic of ChinaCorrespondence: Jiyong Jian, Clinical Laboratory Medicine, Beijing Shijitan Hospital, Capital Medical University, NO. 10, Tie Yi Road, Yang Fang Dian, Beijing, Haidian District, People’s Republic of China, Email jianjiyong3137@bjsjth.cnPurpose: We investigated the Epidemiology, risk factors and outcomes of Candida bloodstream infection.Methods: The electronic laboratory records data of patients with candidemia (2015– 2022) were collected. We used univariate and multivariate logistic regression to determine the risk factors of candidemia.Results: Of the 134 patients with candidemia, the most prevalent species were Candida albicans (37.2%), followed by Candida glabrata (27.7%), Candida parapsilosis (18.9%), and others. The mean annual incidence was 0.33/1000 admissions. The overall resistance rate of Candida spp. against fluconazole and voriconazole were 4.9% (7/142) and 5.9% (6/101), while Candida tropicalis showed high resistance to fluconazole (38.8%) and voriconazole (27.8%). The 30-day mortality rate was 32.8%. On multivariate analysis, age ≥ 65 (odds ratio [OR] = 3.874, 95% confidence interval [CI]: 1.146, 13.092; P = 0.029), high Acute Physiology and Chronic Health Evaluation II (APACHE II) score (OR = 12.384, 95% CI: 2.963, 51.762; P = 0.001), shock (OR = 3.428, 95% CI: 1.097, 10.719; P = 0.034), initial antifungal therapy (OR = 0.057, 95% CI: 0.011, 0.306; P = 0.001) and White blood cells (OR = 1.129, 95% CI: 1.016, 1.255; P = 0.024) were the independent risk factors with mortality within 30 day in patients with candidemia.Conclusion: The incidence rate and the mortality rate of candidemia are high, and lower azole susceptibility was found in Candida tropicalis. Age≥ 65 years, Shock, high APACHE II score, Antifungal therapy and White blood cells count were independently associated with 30-day mortality.Keywords: Candidemia, Epidemiology, Antifungal susceptibility, Mortality, Risk factors

Kui Kang,1 Ying Wang,2 Bo Zhang,1 Zhengxing Xie,1 Sheng Qing,1 Yanan Di1 1Department of Gastroenterology, Beijing Aerospace General Hospital, Beijing, People’s Republic of China; 2Department of Endocrinology, Air Force Specialty Medical Center, Beijing, People’s Republic of ChinaCorrespondence: Yanan Di, Department of Gastroenterology, Beijing Aerospace General Hospital, 7 Wanyuan North Road, Fengtai District, Beijing, 100076, People’s Republic of China, Email diyanan4658@sina.comBackground: The biological function and prognostic significance of endothelial cell specific molecule 1 (ESM1) in various cancers have been validated. This study aimed to explore the expression and clinical diagnosis values in patients with stomach adenocarcinoma (STAD) and esophageal carcinoma (ESCA).Methods: Online database Gene Expression Omnibus was used to screen for abnormally expressed genes in STAD and ESCA. Besides, 36 STAD and 36 ESCA patients were enrolled, and their corresponding control groups were also 36 people each. Reverse transcription-quantitative polymerase chain reaction and Western blot were performed to analyze the expression of ESM1. Overall survival (OS) curve and receiver operating characteristics curve (ROC) analysis were used to assess the prognosis, and the sensitivity and specificity of ESM1 for the diagnosis of STAD and ESCA, respectively. Additionally, the effects of ESM1 on cell viability, migration, and invasion were analyzed by cell counting kit-8, transwell migration and invasion assays.Results: The results showed that the poor OS of STAD and ESCA patients was correlated with high ESM1. Besides, ESM1 was increased in ESCA and STAD in in vivo and in vitro studies. ESM1 has a high accuracy [area under the curve (AUC) > 0.79] at stage I and IV of STAD and ESCA. Knockdown of ESM1 suppressed the cell viability, migration, and invasion and increased the apoptosis rate of AGS and TE1 cells.Conclusion: Our study suggested that ESM1 might be used as a new indicator for the diagnosis and prognosis of early and advanced stage digestive tract cancers.Keywords: STAD, ESCA, ESM1, ROC, diagnosis, prognosis

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

Ziyi Xie,1 Zhizhuang Duan2 1Faculty of Humanities and Social Science, Macao Polytechnic University, Macao, People’s Republic of China; 2Xingzhi College, Zhejiang Normal University, Jinhua, People’s Republic of ChinaCorrespondence: Zhizhuang Duan, Xingzhi College, Zhejiang Normal University, Postal Address No. 3388 Yingbin Avenue, Jinhua, Zhejiang Province, People’s Republic of China, Email 105009342@qq.comAbstract: In response to the HIV/AIDS epidemic, China initiated the “Four Frees and One Care” policy in late 2003. This policy provided free counseling, testing, and antiretroviral treatment for people living with HIV, while also offering support to affected families. While instrumental in advancing HIV/AIDS prevention, the policy faces evolving challenges. This study aims to analyze this challenge from multiple dimensions and, based on this analysis, provide effective recommendations for the Chinese government to address it, promoting the sustainable development of the “Four Frees and One Care” policy. The research found that reduced government funding has led to the decline of grassroots organizations, creating a disconnect between administrative and treatment systems. Additionally, advancements in medical technology introduce new antiretroviral drugs, complicating their integration into the healthcare system. In the current healthcare reform, updating the list of free antiretroviral drugs proves challenging. Adapting the policy to contemporary HIV/AIDS prevention should be a priority for the Chinese government. Balancing financial constraints, organizational sustainability, and evolving medical technologies will be pivotal for the ongoing transformation of the “Four Frees and One Care” initiative.Keywords: Four Frees and One Care, ART, PLHIV, China, HIV/AIDS policy

Sijie Jiang,1– 4 Shaobing Xie,1– 4 Zhihai Xie,1– 4 Weihong Jiang,1– 4 Hua Zhang1– 4 1Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 2Hunan Province Key Laboratory of Otolaryngology Critical Diseases, Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 3National Clinical Research Center for Geriatric Disorders, Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 4Anatomy Laboratory of Division of Nose and Cranial Base, Clinical Anatomy Center of Xiangya Hospital, Central South University, Changsha, People’s Republic of ChinaCorrespondence: Weihong Jiang; Hua Zhang, Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital of Central South University, 87 Xiangya Road, Kaifu District, Changsha, 410008, People’s Republic of China, Tel/Fax +86731-89753045, Email jiangwh68@126.com; entxy@126.comBackground: Elevated serum uric acid is crucial in the pathophysiology of chronic inflammatory diseases. However, its impact on chronic rhinosinusitis (CRS) recurrence risk is unknown. This study investigates the association between elevated serum uric acid and the risk of CRS recurrence.Methods: A retrospective cohort study was conducted on 1004 CRS patients (including 638 males and 366 females) who received functional endoscopic sinus surgery. All patients were followed up for more than 2 years, and categorized into subgroups based on phenotype, gender, and postoperative recurrence. Cox regression analysis was performed to evaluate the associations between serum uric acid and the risk of CRS recurrence.Results: After categorization, 104 males had hyperuricemia, and 54 females presented hyperuricemia. The rate of recurrent CRS in the hyperuricemia group was significantly higher compared to the non-hyperuricemia group in both males and females (P< 0.05). In both male and female patients, the rate of hyperuricemia and uric acid levels were elevated in the recurrent CRS group in comparison with the non-recurrent CRS group (P< 0.05). Unadjusted and adjusted Cox regression analysis demonstrated that serum uric acid was an independent risk factor for CRS recurrence (P< 0.05). The receiver operator characteristic curve showed that serum uric acid was a potential biomarker for predicting the recurrence of CRS and its phenotypes in both genders (P< 0.05).Conclusion: There is a close relationship between elevated serum uric acid and the recurrence risk of CRS and its phenotypes, suggesting that serum uric acid may be a novel biomarker for predicting recurrent CRS.Keywords: chronic rhinosinusitis, uric acid, hyperuricemia, biomarker, recurrence

Zeyu Xie, Jia Hu, Mengting Li, Xiao Hu, Jisheng Chen Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, People’s Republic of ChinaCorrespondence: Jisheng Chen, Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510080, People’s Republic of China, Tel +86 20-87622305, Fax +86 20-61321967, Email cjslym@163.comPurpose: This study provides a reference for healthcare organizations in the selection and rational use of glucagon-like peptide-1 receptor agonists (GLP-1RAs), based on the Rapid Guide for Drug Evaluation and Selection in Chinese Medical Institutions (Second Edition).Methods: According to the Rapid Guide for Drug Evaluation and Selection in Chinese Medical Institutions (Second Edition) released in 2023, relevant databases such as PubMed, Cochrane, and Embase, drug labels, and clinical guidelines were searched for drug information. We systematically evaluated 7 GLP-1RAs marketed in China for safety, efficacy, economy, pharmacological properties, and other attributes using a percentage scoring method.Results: The final assessment result scores from highest to lowest were semaglutide (71.5 points), dulaglutide (68.9 points), liraglutide (68.7 points), exenatide (62.5 points), lixisenatide (59.9 points), polyethylene glycol loxenatide (55.9 points), and benaglutide (45.1 points).Conclusion: When a healthcare organization introduces GLP-1RAs to their hospital, they can refer to the assessment results and use the top three recommended medications: semaglutide, dulaglutide, and liraglutide.Keywords: glucagon-like peptide-1 receptor agonist, health technology assessment, type 2 diabetes mellitus, drug evaluation

Xin Zhao,1,2 Guijiang Huang,2 Zhenrong Xie,2 Yaxiong Mo,3 Hongxuan Zhu,2 Yajie Gao,2 Yanbing Han,4 Wei Tang2 1Department of Pharmacy, The Third Affiliated Hospital of Inner Mongolia Medical University, Baotou, People’s Republic of China; 2Department of Science and Education, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 3Department of Pediatrics, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 4Department of Neurology, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of ChinaCorrespondence: Wei Tang, Department of Science and Education, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, People’s Republic of China, Email tangw666@sina.com Yanbing Han, Department of Neurology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, People’s Republic of China, Email ynhyb@163.comIntroduction: Neuregulin-1 (NRG-1) appears to play a role in the pathogenesis of several neuropsychiatric disorders, including epilepsy. We conducted a study to investigate the effect of anti-seizure medication on NRG-1 mRNA and NRG-1 protein levels in patients with first-episode focal epilepsy.Methods: The levels of NRG-1 mRNA isoforms (type I, II, III, and IV) in peripheral blood mononuclear cells (PBMCs) of 39 healthy controls, 39 first-episode focal epilepsy patients before anti-seizure medication (ASM) therapy and four weeks after administration of ASM were measured by RT-qPCR, and the levels of NRG-1 protein in the serum of samples of each group were determined using ELISA. In addition the relationship between efficacy, NRG-1 mRNA expression, and NRG-1 protein expression was analyzed.Results: The levels of NRG-1 mRNA progressively increased in patients with first-episode focal epilepsy treated with ASM and were distinctly different from those before medication, but remained lower than in healthy controls (all P < 0.001). Before and after drug administration, NRG-1 protein levels were substantially higher in epileptic patients than in healthy controls, and no significant changes were detected with prolonged follow-up (P < 0.001). Patients with epilepsy who utilized ASM were able to control seizures with an overall efficacy of 97.4%. There was a negative correlation between NRG-1 mRNA levels and efficacy: as NRG-1 mRNA levels increased, seizures reduced (all P < 0.05).Conclusion: Our research indicated that NRG-1 may play a role in the pathophysiology of epilepsy. NRG-1 mRNA may provide ideas for the discovery of novel epilepsy therapeutic markers and therapeutic targets for novel ASM.Keywords: neuregulin-1, focal epilepsy, drug treatment, pathophysiology

Zehang Xie, Zeyu Wang School of Media and Communication, Shanghai Jiao Tong University, Shanghai, People’s Republic of ChinaCorrespondence: Zeyu Wang, School of Media and Communication, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Minhang District, Shanghai, 200240, People’s Republic of China, Email zeyuwang@sjtu.edu.cnPurpose: As the interweaving of human interaction and Artificial Intelligence (AI) intensifies, understanding the psychological impact, especially regarding social anxiety, of engaging with AI-driven virtual companionship becomes crucial. While a substantial body of research on social anxiety has concentrated on interactions between individuals, both online and offline, there is a noticeable deficit in explorations concerning how human-computer interactions influence social anxiety. This study offers a comprehensive, longitudinal examination of this underinvestigated relationship, intricately dissecting the roles of emotional expression and mindfulness within the context of AI-based interactions.Methods: We use social support theory and emotion regulation theory as our theoretical foundation. Data were collected from 618 undergraduate students in Eastern China over two intervals (May 15, 2023 and September 15, 2023). We utilized SPSS 26.0 to conduct descriptive statistics, while AMOS 25.0 facilitated multi-group confirmatory factor analysis (CFA) and the cross-lagged panel modeling.Results: Our findings indicate that as the frequency of virtual companionship use increases, there’s a decline in online social anxiety but a rise in offline social anxiety. Emotional expression emerges as a significant mediator, with heightened emotional expression leading to reduced social anxiety in both contexts. Mindfulness serves as a potent moderator, suggesting its protective role against the potential pitfalls of frequent virtual interactions.Conclusion: This research not only deepens our theoretical understanding of the dynamics between virtual interactions and social anxiety but also serves as a cornerstone for future endeavors aimed at optimizing AI and devising therapeutic interventions tailored for the digital generation.Keywords: virtual companionship, social anxiety, emotional expression, mindfulness, longitudinal study

Li Che,1,2 Zhefan Xie,2,3 Guangshu Chen,4 Wei Zhang,2 Tingting Xia,2,3 Jiaxin Lin,2 Wenzhi Luo,2 Li Chen,2 Wenguang Yin,1 Xingdong Cai,2 Shengming Liu2 1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 3Affiliated Dongguan People’s Hospital, Southern Medical University, Donguan, People’s Republic of China; 4Department of Endocrinology, Guangzhou Red Cross Hospital, The Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of ChinaCorrespondence: Shengming Liu; Xingdong Cai, The First Affiliated Hospital of Jinan University, Guangdong, People’s Republic of China, Email tlsm@jnu.edu.cn; cxd19790920@sina.comBackground: The role of irreversible airway inflammatory damage in chronic obstructive pulmonary disease (COPD) progression is evident. Autophagy is an essential process in the cellular material metabolic cycle, and a family of resistant vegetative molecules may be involved in the COPD autophagic process. In this study, we investigated the mechanism of resistin-like molecule β (RELMβ) in COPD smoking-induced autophagy.Methods: Firstly, the expression differences of RELMβ and autophagy markers between COPD and control groups were analyzed in the Gene Expression Omnibus (GEO) datasets and clinical specimens. Secondly, in vitro and in vivo experiments were conducted using immunoblotting, immunofluorescence, immunohistochemistry, and other methods to investigate the mechanism by which RELMβ promotes airway inflammation through autophagy in a cigarette smoke extract-induced 16HBE cell inflammation model and a cigarette smoke-induced COPD-like mouse model. In addition, immunoprecipitation was used to analyze the binding of RELMβ to the membrane protein TLR4.Results: The expression of RELMβ and autophagy genes p62 and LC3B in lung tissue of COPD patients was significantly increased. RELMβ can mediate the activation of autophagy in 16HBE cells, and through autophagy, it increases the expression of inflammatory cytokines in a cigarette smoke extract-induced 16HBE cell inflammation model. RELMβ promotes cigarette smoke-induced COPD-like mouse airway inflammation through autophagy, and RELMβ can mediate signal transduction through the cell membrane receptor TLR4.Conclusion: The RELMβ binds to TLR4 to encourage signal transduction and that RELMβ can promote inflammation in smoky COPD lungs through autophagy.Keywords: autophagy, COPD, airway inflammation, cigarette smoke extract

Dingqi Lu,1,&ast; Xinchao Zhu,2,&ast; Tao Hong,2 Xinyi Yao,2 Zhiming Xie,3 Liying Chen,2 Yihan Wang,2 Kaiyuan Zhang,2 Yating Ren,2 Yi Cao,4 Xinchang Wang3 1First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310053, People’s Republic of China; 2Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310053, People’s Republic of China; 3The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310053, People’s Republic of China; 4The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310053, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinchang Wang, The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, People’s Republic of China, Tel +86 13065714635, Email ossani@126.comPurpose: Systemic lupus erythematosus is a heterogeneous autoimmune disease in which skin involvement is a common manifestation. It is currently thought that the photosensitivity of SLE skin involvement is associated with anti-SSA antibodies. This study aimed to expand the current state of knowledge surrounding the molecular pathophysiology of SLE skin photosensitivity through Serum metabolomics analysis.Patients and Methods: The serum metabolites of 23 cases of skin-involved SLE (SI) group, 14 cases of no SI (NSI) group, and 30 cases of healthy controls (HC) were analyzed by using UPLC-MS/MS technology, and subgroup analysis was performed according to the expression of anti-SSA antibodies in SI. MetaboAnalyst 5.0 was used for enrichment analysis and ROC curve construction, identifying serum metabolic markers of skin-involved SLE associated with anti-SSA antibodies.Results: We identified several metabolites and metabolic pathways associated with SLE photosensitivity. Two metabolites, SM (d18:1/24:0) and gamma-CEHC can distinguish between anti-SSA antibody-positive and negative SI, with AUC of 0.829 and 0.806. These two photosensitization-related substances may be potential markers of skin involvement in SLE associated with anti-SSA antibody.Conclusion: This study provides new insights into the pathogenesis of SI patients, and provides a new molecular biological basis for the association between anti-SSA antibodies and skin photoallergic manifestations of SLE.Keywords: systemic lupus erythematosus, metabolomics, biomarkers, anti-SSA antibodies, photosensitivity

Jun Ma,1,&ast; Deep K Vaishnani,2,&ast; Mansi,2 Jing Zeng,3 Zhenwen Xie,3 Xuanchen Jin,3 Haixia Zhang,3 Khaing Wut Yi Hla,2 Furong Ying4 1Department of Pathology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China; 2School of International Studies, Wenzhou Medical University, Wenzhou, Zhejiang Province, 325035, People’s Republic of China; 3School of Clinical Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, 325035, People’s Republic of China; 4Department of Clinical Laboratory, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Furong Ying, Department of Clinical Laboratory, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China, Tel/Fax +86 57755579738, Email 764741293@qq.comPurpose: The objective of this study was to evaluate the therapeutic efficacy of the curcumin analogue L6H4 in attenuating liver fibrosis and alleviating insulin resistance in streptozotocin-induced diabetic rats.Methods: Male Sprague-Dawley rats were fed a high-fat diet to induce insulin resistance, followed by streptozotocin injection to induce diabetes. The rats were then treated with L6H4 for eight weeks. Body weight, metabolic parameters, liver function, and liver histopathology were evaluated. Immunohistochemistry was performed to assess the expression of TGF-β 1, TIMP-2, and MMP-2 in liver tissues. Statistical analysis was conducted using one-way ANOVA and Spearman rank correlation test.Results: L6H4 treatment effectively reversed the weight gain associated with a high-fat diet and improved metabolic parameters in diabetic rats. Liver function markers, such as ALT and AST, were reduced after L6H4 treatment. Histological analysis showed improved liver morphology and reduced fibrosis in L6H4-treated rats. Electron microscopy revealed improved ultrastructural features of hepatocytes. Immunohistochemistry demonstrated downregulation of TGF-β 1 and TIMP-2 expression and restoration of MMP-2 expression in the liver tissue of L6H4-treated rats. Correlation analysis showed a significant positive correlation between TGF-β 1 and TIMP-2 expression.Conclusion: The findings suggest that L6H4 has therapeutic potential in attenuating liver fibrosis and alleviating insulin resistance in streptozotocin-induced diabetic rats. The hepatoprotective effect of L6H4 may be attributed to its anti-inflammatory properties and its ability to target molecules involved in fibrosis. Further research is warranted to explore the potential of L6H4 as a treatment option for nonalcoholic fatty liver disease and type 2 diabetes.Plain Language Summary: The versatile curcumin, derived from turmeric, has shown potential in treating type 2 diabetes (T2D) and its complications. However, its bioavailability is limited. This study evaluated the efficacy of L6H4, a curcumin analogue, in treating T2D-induced hepatic fibrosis in rats. The rats were fed a high-fat diet and injected with streptozotocin to induce T2D. L6H4 treatment for eight weeks reversed weight gain, abnormal liver function, and histological changes. The analogue reduced markers of T2D severity, including blood glucose, insulin levels, and insulin resistance. L6H4 also decreased liver fibrosis by reducing the expression of TGF-β 1 and TIMP-2 and increasing MMP-2 expression. These changes in protein expression were consistent with previous studies on liver fibrosis. The effects of L6H4 on MMP-2 and TIMP-2 expression in the liver of diabetic rats had not been observed before. Additionally, L6H4 exhibited anti-inflammatory properties and regulated the expression of key fibrosis-related proteins. The study suggests that L6H4 has the potential as a therapeutic candidate for treating diabetic hepatopathy. Further research is needed to elucidate the molecular mechanisms of action of L6H4 and other curcumin analogues in T2D and liver fibrosis. In conclusion, L6H4 shows promise as a curcumin analogue with hepatoprotective effects and the ability to modulate protein expression involved in liver fibrosis in T2D.Keywords: type 2 diabetic rats, curcumin analogue, L6H4, TIMP– 2, MMP– 2, TGF-β 1

Song Deng,1,&ast; Kaiwei Cai,1,&ast; Chaoying Pei,1 Xingyuan Zhang,1 Xiaoyi Xiao,1 Ye Chen,1 Ying Chen,1 Rongyao Liang,1 Yanlong Chen,1 Pei Li,1 Zhiyong Xie,2 Qiongfeng Liao1 1School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiongfeng Liao, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, People’s Republic of China, Tel/Fax +86 02039358081, Email zyfxliao@gzucm.edu.cn Zhiyong Xie, School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou, 510006, People’s Republic of China, Tel/Fax +86 075523260207, Email xiezhy@mail.sysu.edu.cnPurpose: This study aimed to investigate the underlying treatment mechanism of Radix Astragali (RA) in hyperuricemia from the perspective of microbiota and metabolomics.Methods: We used potassium oxyazinate (PO) to induce hyperuricemia mice, and we determined serum alanine aminotransferase/aspartate aminotransferase (ALT/AST), xanthine oxidase (XOD), creatinine (CRE), uric acid (UA), blood urea nitrogen (BUN) levels, liver XOD levels and assessed the kidney tissue histopathology. The therapeutic mechanism of RA in hyperuricemic mice was studied by 16S rRNA, metagenomic sequencing and metabolomics.Results: Our research showed that RA has therapeutic effect in hyperuricemia mice, such as slow the weight loss, repair kidney damage, and downregulate serum UA, XOD, CRE, ALT/AST, BUN, and liver XOD levels. RA restored the disturbance structure of the microbiota in hyperuricemia mice by increasing the relative abundances of beneficial bacteria (Lactobacillaceae and Lactobacillus murine) but decreasing the relative abundances of pathogenic bacteria (Prevotellaceae, Rikenellaceae and Bacteroidaceae). Meanwhile, we found that RA directly regulated the metabolic pathway (such as linoleic acid metabolism and glycerophospholipid metabolism) and indirectly regulated bile acid metabolism by mediating microbiota to ameliorate metabolic disorders. Subsequently, there was a robust correlation between specific microbiota, metabolites and the disease index.Conclusion: The ability of RA to protect mice against hyperuricemia is strongly linked to the microbiome-metabolite axis, which would provide evidence for RA as a medicine to prevent or treat hyperuricemia.Graphical Abstract: Keywords: Radix Astragali, hyperuricemia, microbiota, metabolism, bile acid

Ying Wang,1,&ast; Xuanzhi Huang,1,&ast; Gaoshi Zhou,1 Jing Han,1 Zhuo Xie,1 Mudan Zhang,1 Xiaoling Li,1 Qi-rui Wu,1 Li Li,1 Ziyin Ye,2 Minhu Chen,1 Yun Qiu,1 Shenghong Zhang1 1Department of Gastroenterology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, People’s Republic of China; 2Department of Pathology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shenghong Zhang; Yun Qiu, Department of Gastroenterology, First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Road 2, Guangzhou Province, 510080, People’s Republic of China, Tel/Fax +86-20-87332916, Email zhshh3@mail.sysu.edu.cn; qyun@mail2.sysu.edu.cnBackground: Treatment failures (TFs) generally exist in the course of ulcerative colitis (UC), while early reliable predictors of TFs are still lacking. We aimed to generate nomograms for the prediction of TFs.Methods: In this retrospective case–control study, the endpoint was the occurrence of TFs, which included medically associated treatment failures and surgery-associated treatment failures (colectomy). Clinical features and mucus integrity evident by goblet cells (GCs) number, expression levels of MUC2 and SLC26A3 were enrolled in the univariate analysis. Nomogram performance was evaluated by discrimination and calibration.Results: We identified 256 UC patients at our center from January 2010 to June 2022. Fourteen variables for TFs and 9 for colectomy were identified by univariate analysis. Five baseline indices were incorporated into the nomogram for the prediction of TFs: area of GCs, age at diagnosis, disease duration, hemoglobin, and Mayo score. The model was presented with decent discrimination (C index of 0.822) and well calibration. In addition, the colectomy predictive nomogram was built using MUC2 intensity, age at onset, and Mayo score with a good discrimination (C index of 0.92).Conclusion: Nomograms based on comprehensive factors including mucus barrier function were developed to predict TFs in UC patients with great discrimination, which may serve as practical tools aiming to identify high-risk subgroups warrant timely intervention.Keywords: ulcerative colitis, treatment failure, nomogram, mucus barrier

Zhenghua Zhu,1,&ast; Xiang Wang,1,&ast; Jinhong Zhao,1 Zuozhou Xie,1 Chen Yang,1 Lingyi Li,2 Yi Liu1 1Department of Respiration, The Second People’s Hospital of Kunming, Kunming, People’s Republic of China; 2Department of Medical, Hangzhou Matridx Biotechnology Co., Ltd, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lingyi Li, Department of Medical, Hangzhou Matridx Biotechnology Co., Ltd, No. 2073 Jinchang Road, Yuhang District, Hangzhou, Zhejiang Province, 311100, People’s Republic of China, Tel +8613888173009, Email 001lly@sina.com Yi Liu, Department of Respiration, the Second People’s Hospital of Kunming, No. 871 Longquan Road, Panlong District, Kunming City, Yunnan Province, 650051, People’s Republic of China, Tel +8613648898773, Email 13648898773zzh@sina.comAbstract: The incidence of psittacosis infection has gradually increased in recent years. Metagenomic next-generation sequencing (mNGS) can be used to comprehensively identify the total DNA and RNA content of the microbiome, as well as identify both known and unexpected pathogens within 24 hours. We diagnosed and treated six patients with psittacosis infection using mNGS, two of whom developed severe disease and most of whom presented with pulmonary symptoms. One of the young female patients also presented with irregular vaginal bleeding and myocarditis. Patients with underlying gastric disorders first showed gastrointestinal symptoms, which is a rare manifestation in patients with psittacosis. Older patients with underlying disease usually showed more severe symptoms. However, rare complications can also occur in immunocompetent young people and develop into severe disease. All patients showed significant congestion at bronchial lumen lesions, which may be associated with a severe inflammatory response to mucosal Chlamydia psittaci (C. psittaci) infection. Overall, mNGS is a rapid and effective tool for the clinical diagnosis of psittacosis caused by C. psittaci, and early diagnosis and treatment can prevent psittacosis from developing into a serious illness.Keywords: Chlamydia psittaci, diagnosis, evolutionary tree, metagenomic next-generation sequencing, serotype

Qingbin Wang,1,2,&ast; Bingkun Wang,1,2,&ast; Xiaowu Ma,1,2 Hongkai Zhuang,1,2 Zhiqin Xie,1,2 Chenwei Tang,1,2 Wenliang Tan,1,2 Lei Yang,1,2 Changzhen Shang,1,2 Yajin Chen1,2 1Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Changzhen Shang; Yajin Chen, Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China, Tel +86 13711279678, Email shangcz_sysu@163.com; chenyaj@mail.sysu.edu.cnPurpose: Ferroptosis has been reported to regulate multiple biological behaviors. However, the prognostic and oncologic values of ferroptosis-related genes (FRGs) have not been comprehensively elucidated in hepatocellular carcinoma (HCC). Here, we aimed to construct FRGs-associated signature for stratification of the prognosis of HCC patients.Methods: A list of FRGs was generated from FerrDb. Public databases were used to extract expression matrices and clinical information. TCGA cohort was randomly divided into a training set and a validation set. Prognostic signature for Overall Survival (OS) was established in training set and validated in internal cohorts (TCGA validation set and entire set) and external cohort (ICGC cohort). Additionally, the role of signature in HCC was well investigated by analysis of mutations, gene set enrichment analysis (GSEA), analysis of immune infiltrates, and analysis of response to immune checkpoint blockade (ICB) treatment. The oncogenic effects of ZFP69B on HCC were also investigated in vitro.Results: We identified 12 FRGs-based signature for OS with LASSO regression. Patients were partitioned into different risk groups based on the signature. Overall, patients in different groups had different prognosis. The signature independently predicted OS in multivariate Cox regression analyses. Anti-tumor immune cells including activated CD8 T cells, cytolytic activity, and Th1 cells were negatively correlated with risk score in both TCGC and ICGC cohorts. Furthermore, low-risk patients responded better to ICB than high-risk patients. In addition, knockdown of ZFP69B reduced proliferation, migration, and invasion, and promoted erastin-induced ferroptosis of HCC cells.Conclusion: We developed a prognostic signature based on FRGs to predict OS of HCC patients. And the signature may facilitate clinicians in identifying those who are likely to benefit from ICIs. The results also indicated that ZFP69B might regulate the process of ferroptosis and could be used as a novel potential target for HCC.Keywords: ferroptosis, hepatocellular carcinoma, immunotherapy, overall survival, signature

Zeyu Xie, Sensen Yang, Weishang Deng, Jinjian Li, Jisheng Chen Key Specialty of Clinical Pharmacy, the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, People’s Republic of ChinaCorrespondence: Jisheng Chen, Key Specialty of Clinical Pharmacy, the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510080, People’s Republic of China, Tel +86+20-87622305, Fax +86+20-61321967, Email cjslym@163.comPurpose: The effect and safety of Semaglutide and Liraglutide on weight loss in people with obesity or overweight were evaluated by a Network Meta-Analysis system to provide an evidence-based reference for clinical treatment.Methods: Computer searched PubMed, Embase, and Cochrane Library databases to collect Liraglutide and Semaglutide injection monotherapy RCTs until April 2022, using Stata 16 software for Network Meta-Analysis.Results: Twenty-three RCTs study with 11,545 patients and 4 interventions (semaglutide 2.4mg, semaglutide 1.0mg, liraglutide 3.0mg and liraglutide 1.8 mg) were finally included. In terms of efficacy, semaglutide 2.4mg (− 12.47 kg) had the best weight loss, followed by liraglutide 3.0mg (− 5.24 kg), semaglutide 1.0mg (− 3.74 kg) and liraglutide 1.8mg (− 3.29 kg). In terms of decreased HbA1c, semaglutide 2.4mg (MD=− 1.48%, 95% CI [− 1.93, − 1.04]), semaglutide 1.0mg (MD=− 1.36%, 95% CI [− 1.72, − 1.01]), liraglutide 1.8mg (MD=− 1.23%, 95%Cl [− 1.66, − 0.80]) more effective than placebo. In terms of safety, the total incidence of adverse events was semaglutide 2.4mg > liraglutide 3.0mg > liraglutide 1.8mg > semaglutide 1.0mg compare to placebo, the incidence of serious adverse events was liraglutide 3.0mg > liraglutide 1.8mg > semaglutide 2.4mg > semaglutide 1.0mg, the incidence of hypoglycemic events was semaglutide 2.4mg > liraglutide 3.0mg > semaglutide 1.0mg > liraglutide 1.8mg.Conclusion: This meta-analysis indicates that all GLP-1RAs were more efficacious than placebo in people with obesity or overweight on efficacy. Semaglutide 2.4mg has an absolute advantage in weight loss and decreased HbA1c, but the incidence of total adverse events is also the highest and can cause hypoglycemia. In addition, although liraglutide 3.0mg was less effective than semaglutide 2.4mg, serious adverse events were still the most elevated.Keywords: glucagon-like peptide-1 receptor agonists, weight loss, systematic review, liraglutide, semaglutide

Shiting Tang,1,&ast; Liuyu Liu,1,&ast; Zhouhua Xie,2 Yaoqin He,2 Yunli Zhang,3 Yiju Xie,4 Shijian Chen,1 Yayuan Liu,1 Yunfei Wei,1,5 Zhijian Liang1 1Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Key Laboratory of Precision Medicine in Cardio-Cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-Cerebrovascular Diseases, Nanning, People’s Republic of China; 2Department of Tuberculosis, The Fourth People’s Hospital of Nanning City, Nanning, People’s Republic of China; 3Department of Neurology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, People’s Republic of China; 4Department of Neurology, Wuming Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 5Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhijian Liang, Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Key Laboratory of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-cerebrovascular Diseases, Nanning, People’s Republic of China, Email liangzhijian@gxmu.edu.cn Yunfei Wei, Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China, Email danggege@163.comObjective: Ischemic stroke is a common complication in patients with tubercular meningitis (TBM). However, the risk factors for Ischemic stroke in TBM patients are not fully understood, especially in those patients without conventional vascular risk factors. The aim of the present study was to explore the clinical features and independent risk factors for tubercular meningitis-related Ischemic stroke (TBMRIS).Methods: Tubercular meningitis patients with acute Ischemic stroke without conventional vascular risk factors were recruited between July 2010 and July 2020 as the TBMRIS group. Patients who solely had tubercular meningitis were recruited as the control group (TMB group). Demographic characteristics, clinical presentations, and cerebrospinal fluid (CSF) examinations were collected, and multiple logistic regression analysis was applied to analyse the independent risk factors for TBMRIS.Results: A total of 70 TBMRIS patients and 70 TMB patients were enrolled. Most (82.86%) of the TBMRIS patients experienced Ischemic stroke events within 3 months after the diagnosis of tubercular meningitis. The multiple logistic regression analysis revealed that variation in red blood cell distribution width (RDW-CV), mean platelet volume (MVP), C-reactive protein (CRP), CSF glucose and Modified Research Council Grade II (MRC Grade II) were independent risk factors for TBRIS. The AUC of the identification model was 0.808, with a sensitivity of 68.60% and a specificity of 84.30%.Conclusion: This study revealed that RDW-CV, MVP, CRP, CSF glucose and MRC Grade II are potential independent risk factors for TBMRIS. The identification model established in this study may help monitor TBM patients who are at high risk of developing TBMRIS.Keywords: tubercular meningitis, Ischemic stroke, tubercular meningitis-related Ischemic stroke, independent risk factor

Yingna Chen,1 Jieya Lu,2 Zhihao Xie,1 Jialing Tang,1 Xuejiao Lian,1 Xiuwen Li1 1School of Pharmacy, School of Medicine, Changzhou University, Changzhou, Jiangsu, People’s Republic of China; 2Department of Nephrology, Yixing Hospital of Traditional Chinese Medicine, Yixing, Jiangsu, People’s Republic of ChinaCorrespondence: Yingna Chen, School of Pharmacy, School of Medicine, Changzhou University, No. 21, Lake Gehu Road, Wujin District, Changzhou, Jiangsu, People’s Republic of China, Tel +86-13813661630, Email chenyingna@cczu.edu.cn Jieya Lu, Department of Nephrology, Yixing Hospital of Traditional Chinese Medicine, 128 Yangquan East Road, Yicheng Street, Yixing, Jiangsu, People’s Republic of China, Tel +86-15906153777, Email ljy7011645@sina.comBackground: Tumor microenvironment has attracted more and more attention in oncology. Alisol B23 acetate (AB23A) inhibits the proliferation of tumor cells including non-small cell lung cancer (NSCLC) cells. However, whether AB23A plays a role in the tumor microenvironment of NSCLC still remains obscure.Methods: After THP-1 cells were polarized to M0 type by PMA, M0 macrophages were differentiated into M1 by LPS and IFNγ, and were differentiated into M2 by IL-4 and IL-13. The differentiation of THP-1 cells was detected by flow cytometry. After AB23A was given to macrophage RT-qPCR and ELISA detected the expressions of IL-6, IL-1β, IL-10 and TGF-β. Western blot and RT-qPCR detected the expressions of CD11b and CD18 at both mRNA and protein levels. Lung cancer cell A549 cells were induced by above related macrophage culture medium. Cell proliferation was detected by CCK-8. Tunel, wound healing and Transwell detected the apoptotic, migration and invasion capabilities. Next, M0 and M1-type macrophages were cultured in the cell culture medium of conventional A549 cells, to which AB23A was added. Subsequently, cell differentiation and inflammatory response were measured. Finally, the expression of CD18 in A549 cells was knocked down to construct NSCLC tumor-bearing mice and AB23A was applied for intragastric administration. Immunohistochemistry detected the polarization of macrophages in tumor tissues. Western blot detected the expressions of CD11b, CD18, invasion-, migration- and apoptosis-related proteins.Results: AB23A promoted the polarization of macrophages towards M1, thus promoting the apoptosis and inhibiting the invasion and migration of A549 cells. The tumor cell culture medium induced M0 macrophages to M2, while AB23A reversed this effect. AB23A targeted CD11b/CD18 and improved the polarization of macrophages, thereby affecting tumor invasion, migration and apoptosis.Conclusion: AB23A affected the polarization of tumor-associated macrophages through the targeted regulation of CD11b/CD18, thus inhibiting the development of lung cancer.Keywords: Alisol B23 acetate, lung cancer, CD11b/CD18, tumor microenvironment

Yuanli Luo1 &ast;, Bin Qiao1 &ast;, Chao Yang2 &ast;, Ping Zhang,1 Zhuoyan Xie,1 Jin Cao,1 Anyu Yang,1 Qinyanqiu Xiang,1 Haitao Ran,1 Zhigang Wang,1 Lan Hao,1 Yang Cao,1 Zhiyi Zhou,3 Jianli Ren1 1Chongqing Key Laboratory of Ultrasound Molecular Imaging, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China; 2Radiology Department, Chongqing General Hospital, Chongqing, 400014, People’s Republic of China; 3General Practice Department, Chongqing General Hospital, Chongqing, 400014, People’s Republic of China&ast; These authors contributed equally to this workCorrespondence: Zhiyi Zhou; Jianli Ren, Email renjianli@cqmu.edu.cn; zzy16966@163.comBackground: Sonodynamic therapy (SDT) has been regarded as a novel therapeutic modality for killing tumors. However, the hypoxic tumor microenvironment, especially deep-seated tumors distant from blood vessels, severely restricts therapeutic efficacy due to the oxygen-dependent manner of SDT.Methods: Herein, we report a novel ultrasonic cavitation effect-based therapeutic modality that is able to facilitate the hypoxia-tolerant SDT for inducing hypoxic tumor death. A tLyP-1 functionalized liposomes is fabricated, composed of hematoporphyrin monomethyl ether gadolinium as the sonosentizer and perfluoropentane (PFP) as the acoustic environment regulator. Moreover, the tLyP-1 functioned liposomes could achieve active tumor homing and effective deep-penetrating into hypoxic tumors. Upon low intensity focused ultrasound (LIFU) irradiation, the acoustic droplet vaporization effect of PFP induced fast liquid-to-gas transition and quick bubbles explosion to generate hydroxyl radicals, efficiently promoting cell death in both normoxic and hypoxic microenvironment (acting as deep-penetration nanobomb, DPNB).Results: The loading of PFP is proved to significantly enhance the therapeutic efficacy of hypoxic tumors. In particular, these DPNB can also act as ultrasound, photoacoustic, magnetic resonance, and near-infrared fluorescence tetramodal imaging agents for guiding the therapeutic process.Conclusion: This study is the first report involving that liquid-to-gas transition based SDT has the potential to combat hypoxic tumors.Keywords: tetramodal imaging, low intensity focused ultrasound, sonodynamic therapy, deep-penetration, hypoxic tumors

Sijie Jiang,1– 3 Shaobing Xie,1– 3 Ruohao Fan,1– 3 Qingping Tang,4 Hua Zhang,1– 3 Fengjun Wang,1– 3 Shumin Xie,1– 3 Kelei Gao,1– 3 Junyi Zhang,1– 3 Zhihai Xie,1– 3 Weihong Jiang1– 3 1Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 2Hunan Province Key Laboratory of Otolaryngology Critical Diseases, Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 3National Clinical Research Center for Geriatric Disorders, Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 4Department of Rehabilitation, Brain Hospital of Hunan Province, Hunan University of Chinese Medicine, Changsha, People’s Republic of ChinaCorrespondence: Weihong Jiang, Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, People’s Republic of China, Tel +86-731-8975-3045, Email jiangwh68@126.comPurpose: Subcutaneous immunotherapy (SCIT) is an effective treatment for pediatric allergic rhinitis (AR), but its efficacy fluctuates among individuals. This study aims to identify the profile of serum exosomes derived microRNAs (miRNAs) and evaluate their capacities to early predict SCIT efficacy in pediatric AR.Patients and Methods: High-throughput sequencing was applied to identify the miRNA of serum exosomes in AR children. GO enrichment and KEGG pathway analysis were performed to enrich the biological annotations of target mRNAs of miRNAs. Then we validated differentially expressed miRNAs in two independent cohorts by RT-qPCR. Logistic regression and receiver operating characteristic curve (ROC) were applied to evaluate the abilities of identified miRNAs in predicting the efficacy of SCIT in AR children.Results: A total of 812 miRNAs were detected in the serum exosomes, including 16 upregulated and 14 downregulated. Differentially expressed genes are enriched in the biological process of developmental process and regulation of cellular process, and gathered in pathways such as the signaling pathways regulating pluripotency of stem cells and the Wnt signaling pathway. In the first validation cohort, hsa-miR-4669 (P=0.009) and hsa-miR-4686 (P=0.032) were significantly downregulated in the effective group than the ineffective group, while hsa-miR-3196 (P=0.015) was upregulated. In the second cohort, hsa-miR-4669 level (P< 0.0001) was downregulated in the effective group than the ineffective group. In addition, logistic regression revealed that hsa-miR-4669 level was correlated with the visual analogue scale (r=0.323, P=0.001) and total nasal symptoms score (r=0.269, P =0.007). ROC curve highlighted that hsa-miR-4669 level exhibited a reliable accuracy in predicting SCIT efficacy in pediatric AR (AUC=0.785).Conclusion: Serum exosomes derived miRNA were associated with the efficacy of SCIT. Serum exosomes derived hsa-miR-4669 might serve as a novel biomarker for early predicting the response of SCIT in AR children.Keywords: allergic rhinitis, subcutaneous immunotherapy, miRNA, exosome, children

Li Li,1 Rongjin Sun,1 Joseph Zenga,2 Heather Himburg,3 Lu Wang,1 Shengnan Duan,1 Jingwen Liu,1 Dinh Bui,1 Zuoxu Xie,1 Ting Du,4 Lijun Xie,1 Taijun Yin,1 Stu Wong,2 Song Gao,4 Ming Hu1 1Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, USA; 2Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, WI, USA; 3Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, USA; 4Department of Pharmaceutical Science, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX, USACorrespondence: Ming Hu, Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, USA, Email mhu@uh.edu Song Gao, Department of Pharmaceutical Science, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX, USA, Email Song.Gao@tsu.eduObjective: We aim to quantify the absolute protein expression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in various cells and tissues to determine the relative contribution of COX-1 and COX-2 to PGE2 production.Methods: An LC-MS method was developed and validated, then used for quantifying the absolute amounts of COX-1 and COX-2 in recombinant human COX-1 and COX-2, lysates from different cells, tissue microsomes of rodents and humans, Pirc rat colonic polyps, and biopsy specimens from squamous cell carcinoma (SCC) patients. The COX-1 and COX-2 turnover numbers were subsequently calculated based on apparent formation rates of PGE2.Results: A robust LC-MS method for quantification of COX-1 and COX-2 was developed and validated and then used to calculate their apparent turnover numbers. The results showed that COX-1 expression levels were much higher than that of COX-2 in all the tested tissues including the colonic epithelium of F344 (28-fold) and Pirc rats (20-fold), colonic polyps of Pirc rats (8-fold), and biopsy specimens of SCC patients (11– 17-fold). In addition, both COX-1 and COX-2 were higher in polyps when compared to adjacent mucosa of Pirc rats. The turnover number of recombinant human COX-2 was 14-fold higher than that of recombinant human COX-1. LPS stimulation increased COX-2 protein expression in three cell lines (Raw 264.7, SCC9 and EOMA) as expected but unexpectedly increased COX-1 protein expression (13.8-fold) in EOMA cells.Conclusion: In human oral cancer tissues and cells as well as Pirc rat colon, COX-1 plays an unexpectedly but more important role than COX-2 in abnormal PGE2 production since COX-1 expression is much higher than COX-2. In addition, COX-1 expression levels are inducible in cells, and higher in polyps than surrounding mucosa in Pirc rat colon. These results indicate that targeted suppression of local COX-1 should be considered to reduce colon-specific PGE2-mediated inflammation.Graphical Abstract: Keywords: cyclooxygenase-1, cyclooxygenase-2, turnover number, inflammation, absolute quantification, liquid chromatography with tandem mass spectrometry

Zhiman Xie,1,&ast; Jie Zhou,2,3,&ast; Fang Lu,2,3,&ast; Sufang Ai,1 Hao Liang,2– 4 Ping Cui,2,4 Jianyan Lin,1 Jiegang Huang2,3 1Nanning Infectious Disease Hospital Affiliated to Guangxi Medical University & The Fourth People’s Hospital of Nanning, Nanning, Guangxi, 530023, People’s Republic of China; 2Guangxi Key Laboratory of AIDS Prevention and Treatment & Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, Nanning, Guangxi, 530021, People’s Republic of China; 3School of Public Health, Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 4Life Science Institute, Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiegang Huang; Jianyan Lin, Email jieganghuang@gxmu.edu.cn; linjianyan@126.comAbstract: We reported an HIV-naïve patient from a resource-limited area who was detected with multiple resistance sites associated with nucleoside reverse transcriptase inhibitors (NRTIs) and integrase strand transfer inhibitors (INSTIs) after the failure of the initial antiviral regimen dolutegravir/lamivudine (DTG/3TC) and subsequent Bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). On May 8, 2021, a 53-year-old man was diagnosed with AIDS, Marneffei talaromycosis and fungal esophagitis, and was suspected of having tuberculosis (TB) in Guangxi, China. His baseline HIV RNA was 559,000 copies/mL and the CD4 count was 12 cells/μL, but resistance genotype testing was not performed. The patient remained immunosuppressed (CD4 count 3 cells/μL) after 12 weeks of initial antiviral treatment (ART) with DTG/3TC. After he was switched to BIC/FTC/TAF and started anti-TB treatment, the viral load (HIV RNA 163,200 copies/mL) was not effectively controlled, and there were multiple NRTIs drug-resistant mutations (D67N, K70R, M184V, T215V, K219Q) and INSTIs mutations (E138K, G140A, S147SG, Q148R). This suggested that in resource-limited areas, for HIV-naïve patients in advanced stages with active opportunistic infections, HIV RNA> 500,000 copies/mL, and low CD4 count, baseline resistance testing and increased HIV RNA testing frequency should be recommended, DTG/3TC was not recommended as initiation, and opportunistic infections should be treated promptly. In addition, switching to other INSTIs was not recommended in the absence of resistance testing and ineffective use of DTG.Keywords: HIV-naïve, DTG/3TC, BIC/FTC/TAF, resistance, resource-limited area

Zhichao Lin,&ast; Wenhai Huang,&ast; Zehua Xie,&ast; Yongsheng Yi, Zumei Li Department of Thoracic Surgery, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-sen University, Jiangmen, 529030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhichao Lin, Department of Thoracic Surgery, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-sen University, No. 23 Haibang Street, Beijie, Jiangmen, 529030, People’s Republic of China, Tel +86 750-3989432, Email 230160549@qq.comBackground: Based on bioinformatics analysis and experimental validation, we investigated the expression, clinical significance, immune infiltration, and potential signaling pathways of miR-3940-5p in lung adenocarcinoma (LUAD).Methods: 521 LUAD tissue samples and 46 normal lung tissue samples from The Cancer Genome Atlas (TCGA) database. We evaluated the relationship between clinical features and miR-3940-5p expression using Kruskal–Wallis, Wilcoxon sign-rank, and logistic regression, explored the relationship between miR-3940-5p expression and the prognosis of LUAD patients using Kaplan–Meier survival curve analysis. Several databases were used to identify miRNA targets. MiR-3940-5p target genes were analyzed based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The significant role of miR-3940-5p in function was evaluated using immune infiltration analysis. LUAD cell lines were tested for miR-3940-5p expression using QRT-PCR.Results: There was a significant association between high miR-3940-5p expression in LUAD and T stage (P=0.005), pathologic stage (P=0.047), race (White vs Asian & Black or African American) (P=0.041), residual tumor (P=0.043), and anatomic neoplasm subdivision2 (P=0.030). MiR-3940-5p expression predicted poor overall survival (HR: 1.35; 95% CI: 1.01– 1.81; P=0.045), disease-specific survival (HR: 1.53; 95% CI: 1.05– 2.23; P=0.026), and progression-free survival (HR: 1.35; 95% CI: 1.03– 1.77; P=0.032). BAP1, BBS1, CCR2, KCNE3, PEBP1, and RABL2A were all associated with poor OS in LUAD patients with low miR-3940-5p expression levels. According to GO and KEGG analyses, miR-3940-5p may play a role in LUAD development by regulating pathways such as measles, PI3K-Akt signaling pathway, and p53 signaling pathway. There was a correlation between the expression level of miR-3940-5p and immune infiltration. LUAD cell lines showed significantly higher levels of miR-3940-5p than Beas-2B cells.Conclusion: A high expression of miR-3940-5p is significantly associated with a poor prognosis in patients with LUAD, suggesting that it could be used as a prognostic biomarker.Keywords: microRNA-3940-5p, lung adenocarcinoma, clinical significance, immune infiltration, regulation network

Zeyu Xie, Jinjian Li, Sensen Yang, Weishang Deng, Jisheng Chen Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, People’s Republic of ChinaCorrespondence: Jisheng Chen, Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangdong, 510080, People’s Republic of China, Tel +86 20-87622305, Fax +86 20-61321967, Email cjslym@163.comPurpose: According to the requirements of the “Quick Guide for Drug Evaluation and Selection in Chinese Medical Institutions”, this health technology assessment provides an evidence-based basis for drug selection and rational clinical use of glucagon-like peptide-1 receptor agonist drugs in medical institutions.Methods: We consult the drug instructions, clinical treatment guidelines and search relevant documents in databases such as China national knowledge infrastructure, Wanfang, PubMed, and government websites such as National Medical Products Administration, Food and Drug Administration, European Medicines Agency, and Pharmaceuticals and Medical Devices Agency to collect and sort out the relevant information of the indications, pharmacological effects, guideline recommendations, drug prices and other information of glucagon-like peptide-1 receptor agonists, using a percentile system systematically evaluate the five dimensions of glucagon-like peptide-1 receptor agonists in terms of pharmaceutical properties, efficacy, safety, economy, and other attributes.Results: The final scores of the evaluation results from high to low are semaglutide (71.00 points), dulaglutide (68.75 points), liraglutide (67.50 points), exenatide (67.00 points), lixisenatide (63.50 points), polyethylene glycol loxenatide (58.00 points) and benaglutide (49.00 points).Conclusion: In clinical practice, semaglutide and dulaglutide are the top two drugs that can be used as recommended drugs. This health technology assessment can provide an evidence-based basis for hospital selection and rational use of glucagon-like peptide-1 receptor agonists. Clinicians can rationally choose and use drugs according to the patient’s conditions and needs.Keywords: glucagon-like peptide-1 receptor agonist, hospital-based health technology assessment, drug selection and evaluation

Jiyong Jian,1– 3 Zeqiang Xie,1– 3 Liang Chen1– 3 1Clinical Laboratory Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Peking University Ninth School of Clinical Medicine, Beijing, People’s Republic of China; 3Beijing Key Laboratory of Urinary Cellular Molecular Diagnostics, Beijing, People’s Republic of ChinaCorrespondence: Liang Chen, Clinical Laboratory Medicine, Beijing Shijitan Hospital, Capital Medical University, NO. 10, Tie Yi Road, Yang Fang Dian, Haidian District, Beijing, 100038, People’s Republic of China, Email chenliang2254@bjsjth.cnObjective: Stenotrophomonas maltophilia (S. maltophilia) is an opportunistic and nosocomial pathogen with high mortality. And it has intrinsic resistance to a number of antibiotics classes. In this study, we investigated risk factors for death due to S. maltophilia bacteremia.Methods: A retrospective cohort study was conducted at a tertiary-care hospital in Beijing, China. The patients from the hospital database with S. maltophilia bacteremia between January 2011 and December 2020 were investigated. Univariate and multivariate analyses were performed to identify factors associated with mortality.Results: 51 patients with S. maltophilia bacteremia were identified. The mortality rate was 37.3%. Based on the univariate analysis, pulmonary disease (P=0.019), chronic kidney disease (P=0.014), shock (P=0.002), foley catheter (P=0.011), the Acute Physiology and Chronic Health Evaluation II (APACHE II) score (P< 0.001), procalcitonin (PCT) (P=0.045) and using antifungal agent (P=0.033) were significantly related to mortality. Based on the multivariate analysis, the APACHE II score (odds ratio [OR] =1.211; 95% confidence interval [CI]: 1.061, 1.382; P=0.005) was independent factor associated with mortality. S. maltophilia was the most susceptible to minocycline (94.7%), followed by trimethoprim and sulfamethoxazole (TMP/SMX, 92.2%).Conclusion: Our findings suggested that the APACHE II score was a significantly independent predictor in S. maltophilia bacteremia patients. The use of TMP/SMX or minocycline might be the first choice for the treatment of S. maltophilia bacteremia.Keywords: risk factor, Stenotrophomonas maltophilia, bacteremia, drug susceptibility

Yunfei Wei,1,2,&ast; Shiting Tang,1,&ast; Zhouhua Xie,3 Yaoqin He,3 Yunli Zhang,4 Yiju Xie,5 Shijian Chen,1 Liuyu Liu,1 Yayuan Liu,1 Zhijian Liang1 1Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Key Laboratory of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-cerebrovascular Diseases, Nanning, People’s Republic of China; 2Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 3Department of Tuberculosis, The Fourth People’s Hospital of Nanning City, Nanning, People’s Republic of China; 4Department of Neurology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, People’s Republic of China; 5Department of Neurology, Wuming hospital of Guangxi Medical University, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhijian Liang, Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Key Laboratory of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-cerebrovascular Diseases, Nanning, People’s Republic of China, Tel +86-771-5330705, Fax +86-771-5352627, Email liangzhijian@gxmu.edu.cnObjective: There have been only a few studies of ischemic stroke in patients with pulmonary tuberculosis (pTB). This study aimed to explore the clinical features and the underlying pathogenesis of pulmonary tuberculosis-related ischemic stroke (TBRIS).Methods: Active pulmonary tuberculosis patients with acute ischemic stroke (without conventional vascular risk factors) were recruited as the TBRIS group. Patients who solely had active pulmonary tuberculosis were recruited as the control group (pTB group). Clinical data were collected, and multiple logistic regression analysis was applied to analyze the independent risk factors for TBRIS.Results: A total of 179 TBRIS patients and 179 pTB patients were enrolled. Most (56.42%) of the TBRIS patients experienced the ischemic stroke events within 3 months after the diagnosis of tuberculosis. The multiple logistic regression analysis revealed that an increased mean platelet volume; elevated plasma D-dimer, C-reactive protein, and serum ferritin levels; and an increased monocyte percentage were independent risk factors for TBRIS. The AUC of the identification model was 0.778, with a sensitivity of 70.30% and a specificity of 78.90%.Conclusion: The findings in the present study suggested that most of the TBRIS patients experienced ischemic stroke within 3 months after the diagnosis of tuberculosis. And the more intensive immune response to the tuberculosis infection in the TBRIS group contributed to the initiation of platelet activation and to the development of a hypercoagulable state, which were attributed to the pathogenesis of TBRIS. Index of TBRIS equaling to 0.3234 facilitates clinicians to identify the pTB patients who were at higher risk for TBRIS, and allow physicians to take further effective measures to prevent ischemic stroke in patients with pTB. However, our findings will need to be confirmed by further studies.Keywords: pulmonary tuberculosis, ischemic stroke, tuberculosis-related ischemic stroke, independent risk factor, pathogenesis

Lin Chen,1 Zongxiao Xie,2 Jie Zhen,3 Kunxiang Dong4 1College of Humanities and Law, Shandong University of Science and Technology, Qingdao, 266590, People’s Republic of China; 2China Financial Certification Authority, Beijing, 100054, People’s Republic of China; 3School of Management Science and Engineering, Chongqing Technology and Business University, Chongqing, 400067, People’s Republic of China; 4School of Management Science and Engineering, Shandong University of Finance and Economics, Jinan, 250014, People’s Republic of ChinaCorrespondence: Zongxiao Xie, China Financial Certification Authority, 20-3, South Street of Caishikou, Xicheng District, Beijing, 100054, People’s Republic of China, Tel +86 18901086108, Email xiezongxiao@vip.163.comIntroduction: Information security policy (ISP) compliance of employees has a profound impact on organization. In the context of information technology innovation and information systems upgrade, employees’ information security behavior is one of the most crucial elements in the information security management of organizations. Based on the two-dimensional model of challenge−hindrance stressor theory and affective events theory, this study explores the mediating effects of emotions on the relationship between challenge information security stress and ISP compliance.Methods: A field quasi-experimental method was used in this study. Materials include the Challenge Information Security Stress Scale, Information System Security Policy Compliance Scale, and Emotions Scale, which were used to form the two-stage questionnaire surveys. Data of 217 employees from three Chinese companies in Shanghai and Beijing that had passed certifications for information security management system (GB/t22080-2008/ISO/IEC 27001:2005) were collected. Bootstrapping method for multiple mediation models and the Process 3.0 plug-in of SPSS 20.0 were used for data analysis.Results: The findings indicate that challenge information security stress has a positive effect on ISP compliance. Challenge information security stress has a positive effect on positive emotions and a negative effect on negative emotions. Positive emotions have mediating effect between challenge information security stress and ISP compliance, but negative emotions have no mediating effect.Conclusion: The research results expand the research scope of challenging stress in the two-dimensional model of challenge−hindrance stressor theory in the context of organizational information security. The findings reveal the mediating effect of positive emotions in challenge information security stress and ISP compliance relationship, which provides empirical support for the application of positive psychology in the field of management.Keywords: challenge information security stress, information security policy compliance, positive emotions, negative emotions

Xiaofeng Zheng,1,&ast; Cong Xiao,1,&ast; Zhuocheng Xie,2 Lijuan Liu,1 Yinhua Chen1 1Department of Orthopedics, Third Hospital of Mianyang Sichuan Mental Health Center, Mianyang, Sichuan, 621000, People’s Republic of China; 2Department of Orthopedics, Sichuan Science City Hospital, Mianyang, Sichuan, 621000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yinhua Chen, Department of Orthopedics, Third Hospital of Mianyang Sichuan Mental Health Center, 190 East Jiannan Road, Youxian, Mianyang, Sichuan, 621000, People’s Republic of China, Tel +86-139-9014-7729, Email yhcdoc@outlook.comPurpose: To establish prediction models for 6-month prognosis in femoral neck–fracture patients receiving total hip arthroplasty (THA).Patients and Methods: In total, 182 computed tomography image pairs from 85 patients were collected and divided into a training set (n=127) and testing set (n=55). Least absolute shrinkage–selection operator regression was used for selecting optimal predictors. A random-forest algorithm was used to establish the prediction models, which were evaluated for accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC).Results: The best model in this study was constructed based on demographic data, preoperative laboratory indicators, and three preoperative radiomic features. In the random-forest model, activated partial thromboplastin time, a preoperative radiomic feature (maximum diameter), and fibrinogen were important variables correlating with patient outcomes. The AUC, sensitivity, specificity, PPV, NPV, and accuracy in the training set were 0.986 (95% CI 0.971– 1), 0.925 (95% CI 0.862– 0.988), 0.983 (95% CI 0.951– 1.016), 0.984 (95% CI 0.953– 1.014), 0.922 (95% CI 0.856– 0.988), and 0.953 (95% CI 0.916– 0.990), respectively. The AUC, sensitivity, specificity, PPV, NPV, and accuracy in the testing set were 0.949 (95% CI 0.885– 1), 0.767 (95% CI 0.615– 0.918), 1 (95% CI 1– 1), 1 (95% CI 1– 1), 0.781 (95% CI 0.638– 0.924), and 0.873 (95% CI 0.785– 0.961), respectively.Conclusion: The model based on demographic, preoperative clinical, and preoperative radiomic data showed the best predictive ability for 6-month prognosis in the femoral neck–fracture patients receiving THA.Keywords: prediction model, total hip arthroplasty, computed tomography, prognosis, femoral neck fracture

Haoqiang Zhang,1– 3,&ast; Shufang Yang,2,4,&ast; Wenwen Zhu,1,2 Tong Niu,1,2 Zheng Wang,1,2 Ke An,1,2 Zuoling Xie,1,2 Pin Wang,2 Xi Huang,1,2 Chenchen Wang,1,2 Haiyan Shangguan,2 Yang Yuan,1 Shaohua Wang1 1Department of Endocrinology, Affiliated Zhongda Hospital of Southeast University, Nanjing, People’s Republic of China; 2School of Medicine, Southeast University, Nanjing, People’s Republic of China; 3Department of Endocrinology, The First Affiliated Hospital of University of Science and Technology of China, Hefei, People’s Republic of China; 4Department of Endocrinology, Taizhou People’s Hospital, Taizhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaohua Wang; Yang Yuan, Department of Endocrinology, Affiliated Zhongda Hospital of Southeast University, No. 87 Dingjiaqiao Road, Nanjing, 210009, People’s Republic of China, Tel +86-25-83262815 ; +86-13814003661, Fax +86-25-83285132, Email gyjwsh@126.com; yang_yuan000@sina.comPurpose: We aim to determine the role of free triiodothyronine (FT3), the main active ingredient of thyroid hormones (THs), in type 2 diabetes mellitus (T2DM) patients with mild cognitive impairment (MCI).Patients and Methods: A total of 255 T2DM patients without diagnosed thyroid diseases were recruited and divided into MCI group and healthy cognition group. Neuropsychological functions were observed by multidimensional cognitive function scales in including MoCA, Digit Span Test (DST), Verbal Fluency Test (VFT), Clock drawing test (CDT), Trail Making Test (TMT) A and B, Instantaneously Recalled Auditory Verbal Learning Test (AVLT-IR), Delayed Recalled Auditory Verbal Learning Test (AVLT-DR) and Logical Memory Test (LMT). Correlation and logistic regression analyses were performed to explore the association between FT3 and diabetic cognitive dysfunction.Results: Compared with 147 normal cognition patients, 108 MCI patients exhibited lower FT3 and higher HOMA-IR. FT3 level was not only positively correlated with MoCA scores, but DST, VFT and LMT, while negatively associated with TMTB. Furthermore, there is a negative association between FT3 and HOMA-IR. Logistic regression showed that decreased FT3 is a risk factor of MCI in T2DM patients. Although FT3 is not the risk factor of MCI after homeostasis model assessment of insulin resistance (HOMA-IR) was entered as an independent variable, lower FT3 is associated with VFT and LMT adjusted by age, education, BMI, DM duration, HBP duration, smoking, HbA1c and HOMA-IR.Conclusion: Lower FT3 levels may involve in MCI, especially for executive function and scene memory in T2DM patients without diagnosed thyroid diseases.Keywords: free triiodothyronine, mild cognitive impairment, insulin resistance, type 2 diabetes mellitus

Zhaochen Zhu,1,2,* Renzhi Gao,1,2,* Teng Ye,1,2 Kai Feng,1,2 Juntao Zhang,2 Yu Chen,2 Zongping Xie,1 Yang Wang2 1Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, 200233, People’s Republic of China; 2Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, 200233, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zongping Xie, Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 600# Yishan Road, Shanghai, 200233, People’s Republic of China Email x91034@qq.comBackground: Tendinopathy is a common cause of tendon pain. However, there is a lack of effective therapies for managing tendinopathy pain, despite the pain being the most common complaint of patients. This study aimed to evaluate the therapeutic effect of small extracellular vesicles released from induced pluripotent stem cell-derived mesenchymal stem cells (iMSC-sEVs) on tendinopathy pain and explore the underlying mechanisms.Methods: Rat tendinopathy model was established and underwent the injection of iMSC-sEVs to the quadriceps tendon one week after modeling. Pain-related behaviors were measured for the following four weeks. Tendon histology was assessed four weeks after the injection. To further investigate the potential mechanism, tenocytes were stimulated with IL-1β to mimic tendinopathy in vitro. The effect of iMSC-sEVs on tenocyte proliferation and the expression of proinflammatory cytokines were measured by CCK-8, RT-qPCR, and ELISA. RNA-seq was further performed to systematically analyze the related global changes and underlying mechanisms.Results: Local injection of iMSC-sEVs was effective in alleviating pain in the tendinopathy rats compared with the vehicle group. Tendon histology showed ameliorated tendinopathy characteristics. Upon iMSC-sEVs treatment, significantly increased tenocyte proliferation and less expression of proinflammatory cytokines were observed. Transcriptome analysis revealed that iMSC-sEVs treatment upregulated the expression of genes involved in cell proliferation and downregulated the expression of genes involved in inflammation and collagen degeneration.Conclusion: Collectively, this study demonstrated iMSC-sEVs protect tenocytes from inflammatory stimulation and promote cell proliferation as well as collagen synthesis, thereby relieving pain derived from tendinopathy. As a cell-free regenerative treatment, iMSC-sEVs might be a promising therapeutic candidate for tendinopathy.Keywords: tendinopathy, pain relief, extracellular vesicles, iPSC derived MSC

Yafei Yuan,1 Wei Wang,1 Yue Zhang,1 Qiaohui Hong,1 Wenhui Huang,1 Lijuan Li,1 Zhanzhan Xie,1 Yixin Chen,1 Xu Li,2,3 Ying Meng1 1Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Emergency Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 3Ministry of Education, Key Laboratory of Hainan Trauma and Disaster Rescue, College of Emergency and Trauma, Hainan Medical University, Haikou, 571199, People’s Republic of ChinaCorrespondence: Ying Meng, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China, Tel/Fax +86 20-62787112, Email nfyymengy@163.com Xu Li, Department of Emergency Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China, Email mylx99@163.comPurpose: Acute lung injury (ALI) is a life-threatening condition with limited therapeutic options. Macrophage inflammation plays a key role in the development of ALI. Abnormal glycolysis of macrophages contributes to the inflammatory response. However, the role of macrophage glycolysis in ALI still requires investigation. Apelin-13 has been shown to protect against ALI, whereas the underlying mechanisms remain unclear. In this study, we explored the effect of apelin-13 on lipopolysaccharide (LPS)-induced inflammation and ALI via regulation of glycolysis by modulating redox homeostasis in macrophages.Methods: Serums from 34 patients with sepsis and 13 healthy volunteers were analyzed. In vivo, the protective effect of apelin-13 against LPS-induced ALI was evaluated using a mouse model of LPS-induced ALI. In vitro, mouse bone marrow macrophages (BMDMs) were pretreated with the antioxidant, NADPH oxidase (NOX) 4 (NOX4) small-interfering RNA (siRNA), the 6-phosphofructo-2 -kinase/fructose- 2,6-biphosphatase 3 (PFKFB3) siRNA, or the PFKFB3 overexpression plasmid before exposure to LPS.Results: Serum apelin-13 levels were significantly elevated in patients with sepsis and sepsis-associated acute respiratory distress syndrome (ARDS) (P< 0.0001). In vivo, apelin-13 suppressed LPS-induced ALI and inflammatory cytokine production (P< 0.05). Furthermore, apelin-13 reduced hydrogen peroxide (H2O2) content, NOX4 protein levels, and glycolysis. In vitro, LPS stimulation elevated NOX4 protein levels and reactive oxygen species (ROS) production (P< 0.05). These changes resulted in the accumulation of glycolysis in BMDMs. Treatment with antioxidant or NOX4 siRNA inhibited LPS-induced glycolysis and inflammatory cytokine production (P< 0.05). Moreover, in vitro experiments revealed that PFKFB3 regulates the release of pro-inflammatory cytokines by modulating glycolysis. In contrast, the action of apelin-13 opposed the effects of LPS.Conclusion: In conclusion, apelin-13 protects against LPS-induced inflammatory responses and ALI by regulating PFKFB3-driven glycolysis induced by NOX4-dependent ROS.Keywords: acute lung injury, inflammation, mice, apelin-13, NADPH oxidase 4, glycolysis, PFKFB3

Hua Zhang,1– 3,&ast; Shaobing Xie,1– 3,&ast; Ruohao Fan,1– 3 Fengjun Wang,1– 3 Zhihai Xie,1– 3 Weihong Jiang1– 3 1Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, People’s Republic of China; 2Hunan Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, Hunan, 410008, People’s Republic of China; 3National Clinical Research Center for Geriatric Disorders, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weihong Jiang, Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, People’s Republic of China, Email jiangwh68@126.comBackground: Chronic rhinosinusitis with polyps (CRSwNP) is characterized by high heterogeneity and postoperative recurrence rate. This study aimed to explore the clinical significance of activated leukocyte cell adhesion molecule (ALCAM) in endotyping CRSwNP and predicting its recurrence.Methods: We recruited 120 CRSwNP patients including 70 non-eosinophilic CRSwNP (neCRSwNP) and 50 eosinophilic CRSwNP (eCRSwNP) patients, and 40 healthy controls (HCs). Serum and tissue samples were collected. Serum ALCAM levels were detected by enzyme-linked immunosorbent assay (ELISA), and tissue ALCAM expression was assessed by reverse transcription-polymerase chain reaction (RT-PCR), Western blotting (WB) and immunohistochemistry (IHC). The predictive values of ALCAM expression for CRSwNP endotypes and postoperative recurrence were assessed.Results: The serum levels of ALCAM were significantly increased in CRSwNP patients in comparison with HCs and were correlated with the peripheral eosinophil count, tissue eosinophil counts, and percentage. Multivariate analysis and receiver operating characteristic (ROC) curve highlighted that serum ALCAM levels were associated with CRSwNP endotypes. Tissue ALCAM expression was significantly enhanced in CRSwNP patients, especially in eCRSwNP patients. At the end of the study, 110 patients completed the follow-up schedule, 78 patients were categorized into the non-recurrent group, and the other 32 patients were included in the recurrent group. The serum ALCAM levels were elevated in the recurrent group compared with the non-recurrent group, and ALCAM expression in the tissue was significantly elevated. The ROC curve exhibited a high predictive ability of serum ALCAM in predicting postoperative recurrence. Logistic regression and Kaplan–Meier curves demonstrated that serum ALCAM was an independent risk factor for postoperative recurrence.Conclusion: This is the first report suggesting that ALCAM expression was upregulated and associated with mucosal eosinophil infiltration and CRSwNP recurrence. Serum ALCAM could be a promising biomarker for distinguishing endotypes and predicting postoperative recurrence in CRwNP patients.Keywords: activated leukocyte cell adhesion molecule, chronic rhinosinusitis with nasal polyps, endotypes, recurrence, biomarker

Xiaowu Ma,1,2,&ast; Hongkai Zhuang,1,2,&ast; Qingbin Wang,1,2 Lei Yang,1,2 Zhiqin Xie,1,2 Ziyu Zhang,1,2 Wenliang Tan,1,2 Chenwei Tang,1,2 Yajin Chen,1,2 Changzhen Shang1,2 1Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yajin Chen; Changzhen Shang, Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China, Tel +86-2034070701, Email cyj0509@126.com; shangcz_sysu@163.comBackground: Solute carrier family 39 member 1 (SLC39A1) has been identified as a zinc ion transport protein that possesses oncogenic properties in various types of cancers. However, its potential function in hepatocellular carcinoma (HCC) remains unknown. This study aimed to investigate the expression profile and potential mechanisms of SLC39A1 in HCC.Methods: SLC39A1 expression was analyzed using multiple databases. The clinical significance and associated biological pathways of SLC39A1 were investigated using bioinformatics analysis. Potential correlations between SLC39A1 expression and tumor immunity in HCC were also evaluated using single-sample gene set enrichment analysis (GSEA). Sixty paired HCC samples were used to verify the expression pattern of SLC39A1. In vitro studies were performed to investigate the oncogenic effects of SLC39A1 in HCC. Western blot analysis was conducted to further investigate the possible involved signaling pathways.Results: The overexpression of SLC39A1 in HCC was determined by bioinformatics analysis and was confirmed in tissues from our center. SLC39A1 overexpression was also significantly correlated with worse prognosis, advanced TNM stage, and histological grade. GSEA analysis demonstrated that SLC39A1 overexpression was involved in various tumor-related pathways, such as the cell cycle and Wnt signaling pathway. SLC39A1 knockdown repressed the proliferation, invasion, and migration abilities of HCC cells. Furthermore, SLC39A1 knockdown decreased the expression of the tumor progression-related proteins (eg, cyclin D1 and MMP2) and Wnt signaling pathway-related proteins (eg, Wnt3A and β-catenin). In addition, SLC39A1 overexpression may be associated with impaired tumor immunity in HCC, as evidenced by the increased infiltration of Th2 cells and reduced infiltration of cytotoxic cells.Conclusion: These findings preliminarily suggested the crucial effect of SLC39A1 overexpression on HCC tumor progression and immunosuppression, suggesting its potential as a novel prognostic and therapeutic target in HCC.Keywords: SLC39A1, hepatocellular carcinoma, prognosis, Wnt signaling pathway, immune infiltration

Yuehui Jia,1,&ast; Shuli Ma,1,&ast; Lianjie Bai,2 Qiong Xiao,3 Yu Wu,3 Ying Gao,4 Yunfeng Han,1 Zhiping Xie,1 Xiaowei Tang,5 Jie Ge1 1School of Public Health, Qiqihar Medical University, Qiqihar, Heilongjiang, People’s Republic of China; 2The Second Affiliated Hospital, Qiqihar Medical University, Qiqihar, Heilongjiang, People’s Republic of China; 3School of Nursing, Qiqihar Medical University, Qiqihar, Heilongjiang, People’s Republic of China; 4School of Mental Health, Qiqihar Medical University, Qiqihar, Heilongjiang, People’s Republic of China; 5Sanitary Analysis Center, Scientific Research Office, Qiqihar Medical University, Qiqihar, Heilongjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie GeSchool of Public Health, Qiqihar Medical University, 333 Bukui Street, Jianhua District, Qiqihar, 161000, People’s Republic of ChinaTel +86452-2663409Fax +86452-2663755Email gejieqiao@126.comPurpose: This study aimed to assess the knowledge, attitude and practice (KAP) towards COVID-19 of Chinese college students during the COVID-19 outbreak and identify the determinants considerably associated with KAP.Methods: An online cross-sectional questionnaire survey was conducted in February 2020 in China to recruit participants on the Wen-Juan-Xing online platform. A self-made questionnaire was used to assess the KAP towards COVID-19.Results: The average scores of COVID-19-related KAP among college students were 32.16 ± 4.09, 16.84 ± 3.18 and 15.36 ± 1.83, respectively. The average correct response rate of COVID-19-related knowledge was 84.62%. 94.59% of the respondents believed China could control and conquer the pandemic; 98.92% of the respondents wore a mask when they went out. The multiple linear regression showed that the female students had higher scores of COVID-19-related knowledge than male students (β = 0.79, P = 0.01), and the students from 985 or 211 universities (β = − 2.22, P < 0.01) were significantly associated with higher knowledge scores. Furthermore, a significantly positive correlation was found between the scores of COVID-19-related KAP among students.Conclusion: The college students had a good KAP towards the COVID-19 pandemic. The present study was able to access the COVID-19-related KAP among college students during the pandemic and identify their weaknesses in pandemic prevention. Consequently, the results of this study provide theoretical basis for implementing precision health education among college students and reference for campuses to conduct scientific prevention and control during a pandemic. Results also provide beneficial experience to curb similar major public health emergencies in the future.Keywords: COVID-19, knowledge, attitude, practice, college students

Yixiu Zhong, Kaiwen Qin, Leqian Li, Huiye Liu, Zhiyue Xie, Kang Zeng Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Kang Zeng Tel +862062787322Email npfkzk1@126.comPurpose: Atopic dermatitis (AD) is a common chronic inflammatory skin disorder associated with immune dysregulation and barrier dysfunction. In this study, we investigated immunological biomarkers for AD diagnosis and treatment using CIBERSORT to identify immune cell infiltration characteristics.Patients and Methods: Common differentially expressed genes (DEGs) of lesioned (LS) vs non-lesioned (NL) groups were obtained from public datasets (GSE140684 and GSE99802). We performed functional enrichment analysis and selected hub genes from the protein–protein interaction (PPI) network. The hub genes were then subjected to transcription factor (TF), microRNA (miRNA), long non-coding RNA (lncRNA), drug interaction, and protein subcellular localization analyses. We also performed correlation analysis on differentially expressed immune cells, TFs, and hub genes. Receiver operating characteristic (ROC) curve analysis and binomial least absolute shrinkage and selection operator (LASSO) regression analysis were employed to assess the expression of hub genes in the GSE99802, GSE140684, GSE58558, GSE120721, and GSE36842 datasets.Results: We identified 238 common DEGs and 25 hub genes. Additionally, we predicted TFs, miRNAs, lncRNA, drugs, and protein subcellular localizations. The proportions of activated dendritic cells (DCs) and CD4+ memory T cells were relatively high in the LS skin. Expression levels of the TF FOXC1 were negatively correlated with target genes and the abundance of two immune cell types. The LASSO model showed that GZMB, CXCL1, and CD274 are candidate diagnostic biomarkers.Conclusion: Our study suggests that downregulated expression of FOXC1 expression may enhance the levels of chemokines, chemokine receptors, T cell receptor signaling molecules, activating CD4+ memory T cells and DCs in AD.Keywords: atopic dermatitis, CIBERSORT, immune infiltration, transcription factors, biomarkers

Zhichao Lin,1,&ast; Wenhai Huang,1,&ast; Yongsheng Yi,1,&ast; Dongbing Li,2,&ast; Zehua Xie,1 Zumei Li,1 Min Ye1 1Department of Thoracic Surgery, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-sen University, Jiangmen, 529030, Guangdong, People’s Republic of China; 2MyGene Diagnostics Co., Ltd., Guangzhou, 510000, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhichao Lin; Min YeDepartment of Thoracic Surgery, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-sen University, No. 23 Haibang Street, Beijie, Jiangmen, 529030, Guangdong, People’s Republic of ChinaTel +86-750-3989432Email 230160549@qq.com; Yeminzhangcuiyuan@126.comBackground: The role of long noncoding RNA (LncRNA) ADAMTS9 antisense RNA 2 (ADAMTS9-AS2) is unclear in lung adenocarcinoma (LUAD). The aim of this study was to explore the relationship between ADAMTS9-AS2 and LUAD, based on The Cancer Genome Atlas (TCGA) database and bioinformatics analysis.Methods: Various statistical methods, Kaplan–Meier method, Cox regression analysis, GSEA, and immune infiltration analysis were used to evaluate the relationship between clinical features and ADAMTS9-AS2 expression, prognostic factors, and the significant involvement of ADAMTS9-AS2 in function.Results: In LUAD patients, low expression of ADAMTS9-AS2 was associated with N stage (P=0.011), gender (P=0.002), number of packs smoked (P=0.024) and smoker (P< 0.001). Low ADAMTS9-AS2 expression predicted a poorer overall survival (OS) (HR: 0.68; 95% CI: 0.51– 0.91; P=0.01). And ADAMTS9-AS2 expression (HR: 0.626; 95% CI: 0.397– 0.986; P=0.043) was independently correlated with OS in LUAD patients. Unwinding of DNA, extrinsic pathway, polo-like kinase-mediated events, cori cycle, MCM pathway, proteasome pathway, lagging strand synthesis and PCNA-dependent long patch base excision repair were differentially enriched in ADAMTS9-AS2 high expression phenotype. ADAMTS9-AS2 expression was correlated with certain immune infiltrating cells.Conclusion: In LUAD patients, ADAMTS9-AS2 expression was significantly associated with poor survival and immune infiltration. ADAMTS9-AS2 may be a promising biomarker of prognosis and response to immunotherapy for LUAD.Keywords: lung adenocarcinoma, ADAMTS9-AS2 antisense RNA 2, prognosis, immune infiltration, biomarker

Sihui Wen,&ast; Shenghao Cheng,&ast; Shaobing Xie, Hua Zhang, Zhihai Xie, Weihong Jiang Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University & Hunan Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, Hunan, 410008, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhihai Xie; Weihong JiangDepartment of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University & Hunan Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, Hunan, 410008, People’s Republic of ChinaEmail xiedoctor@csu.edu.cn; jiangwh68@126.comBackground: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a global health concern with high heterogeneity and rate of postoperative recidivation. YKL-40 is a pivotal pro-inflammatory mediator to promote Th2 immune response which is involved in many inflammatory diseases. This study aimed to investigate the predictive value of serum YKL-40 in CRSwNP endotypes and postoperative recurrence.Methods: We recruited 80 primary CRSwNP, 40 recurrent CRSwNP patients and 40 healthy controls (HCs) in this study, and the serum and tissue specimens were collected. The middle turbinate mucosa tissue collected from patients undergoing septoplasty was used as control. Serum YKL-40 concentrations were detected by enzyme-linked immunosorbent assay (ELISA), and tissue YKL-40 mRNA and protein levels were examined using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). The difference of YKL-40 expression was compared among different group. Multivariate analysis and receiver operating characteristic (ROC) curve were performed to evaluate the value of serum YKL-40 in discriminating eosinophilic CRSwNP (eCRSwNP) and predicting postoperative recurrence.Results: The serum YKL-40 levels in CRSwNP patients were higher than HCs, especially in eCRSwNP patients (p < 0.05). The elevated YKL-40 levels positively correlated with blood eosinophil percentage, tissue eosinophil counts and percentages (p < 0.05). The serum YKL-40 levels in recurrent CRSwNP patients were markedly enhanced than primary CRSwNP patients (p < 0.05). The YKL-40 mRNA and protein levels were significantly elevated in CRSwNP patients compared to HCs, especially in eCRSwNP and recurrent CRSwNP group. Multivariate analysis and ROC curve exhibited that serum YKL-40 might be a promising indicator in distinguishing CRSwNP endotypes and predicting postoperative recurrence.Conclusion: Our data suggested that YKL-40 might be unregulated in CRSwNP and associated with mucosal eosinophilia and recurrence. Serum YKL-40 appeared to a novel biomarker for predicting CRSwNP endotypes and postoperative recurrence of CRSwNP.Keywords: YKL-40, chronic rhinosinusitis with nasal polyps, endotypes, recurrence

Chenchen Wang,1,2 Demei Ye,1 Zuoling Xie,1,2 Xi Huang,1 Zheng Wang,2 Haiyan Shangguan,2,3 Wenwen Zhu,2 Shaohua Wang1 1Department of Endocrinology, The Affiliated ZhongDa Hospital of Southeast University, Nanjing, 210009, People’s Republic of China; 2School of Medicine, Southeast University, Nanjing, 210009, People’s Republic of China; 3Nanjing Central Hospital, Nanjing, 210008, People’s Republic of ChinaCorrespondence: Shaohua WangDepartment of Endocrinology, The Affiliated ZhongDa Hospital of Southeast University, Nanjing, 210009, People’s Republic of ChinaTel +86 25 83262810Fax +86 25 83285132Email gyjwsh@126.comPurpose: In addition to hyperglycemia and hyperlipidemia, obesity and hypertension are important cardiovascular risk factors for coronary heart disease (CHD) in patients with type 2 diabetes mellitus (T2DM). This study aims to explore the interaction of these risk factors.Patients and Methods: Data of hospitalized patients with T2DM from 2013 to 2018 were collected. A multivariate logistic regression model was established. Patients with normal weight and blood pressure were recruited as controls. The interaction on the risk of CHD was evaluated by relative excess risk due to interaction (RERI).Results: Among the 30,693 patients with T2DM, 7202 (23.5%) had CHD. In the low weight group, the prevalence of CHD in patients with hypertension was nearly four times higher than that in patients without hypertension (42.7% vs 11.3%, P < 0.01). The OR value of hypertension alone on CHD increased from 1.29 (95% CI 1.06– 1.56) in the body mass index (BMI) 30.0– 34.9 kg/m2 group to 1.35 (95% CI 1.11– 1.62) in the BMI ≤ 18.5 kg/m2 group. Additive interaction was observed between hypertension and BMI in CHD risk, especially in the low weight group (RERI:2.2, 95% CI 0.9– 3.5). BMI and CHD risk showed a smile curve relationship. The attributive proportion in the low weight group was higher than that in the severe obesity group, that is, 0.52 (95% CI 0.35– 0.69) vs 0.18 (95% CI − 0.59 to 0.95).Conclusion: Maintaining normal weight and avoiding low weight are particularly important for patients with co-occurring diabetes and hypertension to prevent the risk of CHD.Keywords: type 2 diabetes, cardiovascular, hypertension, body mass index, interaction

Li Che,1 Chao Yu,2 Guangshu Chen,3 Jiaxin Lin,1 Zhefan Xie,1 Tingting Xia,1 Wenzhi Luo,1 Xingdong Cai,1 Shengming Liu1 1Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Lu’an People’s Hospital of Anhui Province, Lu’an, 237016, People’s Republic of China; 3Department of Endocrinology, Guangzhou Red Cross Hospital, The Affiliated Hospital of Jinan University, Guangzhou, 510220, People’s Republic of ChinaCorrespondence: Shengming Liu; Xingdong CaiDepartment of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Jinan University, The West of Huangpu Road 613, Tianhe District, Guangzhou, Guangdong, People’s Republic of ChinaTel +86 20 38688628Email tlsm@jnu.edu.cn; cxd19790920@sina.comPurpose: Chronic obstructive pulmonary disease (COPD) is associated with a complex inflammatory regulatory network. Resistin-like molecule β (RELMβ) is highly expressed in the lungs of COPD patients. We aimed to investigate the proinflammatory effect of RELMβ on airway epithelial cells in COPD.Methods: First, a GEO dataset was used to analyze the expression of the RELMβ gene in the COPD and control groups as well as the protein levels of RELMβ in the sera of outpatients with COPD and normal control subjects in our hospital. We also stimulated 16HBE bronchial epithelial cells with recombinant RELMβ protein and analyzed the expression of IL-8 and IL-1β. We upregulated and downregulated the gene expression of RELMβ in 16HBE cells and analyzed the expression of the inflammatory cytokines IL-8 and IL-1β. In addition, we also examined the mechanism by which the p38 MAPK signaling pathway contributed to the regulation of IL-8 and IL-1β expression by RELMβ.Results: RELMβ expression was increased in COPD tissues in different data sets and in the serum of COPD patients in our hospital. IL-8 and IL-1β expression was also increased in COPD tissues with high RELMβ gene expression in different data sets. The RELMβ gene was mainly related to inflammatory factors and inflammatory signaling pathways in the PPI regulatory network. Experiments at the cellular level showed that RELMβ promoted the expression of the inflammatory cytokines IL-8 and IL-1β, and this regulation was mediated by the p38 MAPK signaling pathway.Conclusion: RELMβ can promote the expression of the inflammatory cytokines IL-8 and IL-1β in bronchial epithelial cells of patients with COPD and exert inflammatory effects. RELMβ may be a potential target for the treatment of COPD.Keywords: resistin-like molecule beta/RELMβ, chronic obstructive pulmonary disease, p38 MAPK, IL-8, IL-1&#x03B2

Yanyan Zhou,1 Zihe Hu,1 Mingjie Ge,1 Wenjing Jin,1 Ruikang Tang,2 Qi Li,1 Weijian Xu,1 Jue Shi,1 Zhijian Xie1 1Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, 310006, People’s Republic of China; 2Center for Biomaterials and Biopathways, Department of Chemistry, Zhejiang University, Hangzhou, 310027, People’s Republic of ChinaCorrespondence: Zhijian Xie; Jue Shi Email xzj66@zju.edu.cn; dentistsj@zju.edu.cnPurpose: Osteoporosis, due to bone loss and structural deterioration, is a risk factor for dental implant failure, as it impedes initial stability and osseointegration. We aim to assess the effects of calcium phosphate polymer-induced liquid precursor (CaP-PILP) treatment, which significantly increases bone density and improves early implant osseointegration in ovariectomized rats.Methods: In this study, CaP-PILP was synthesized and characterized through TEM, FTIR and XRD. A rat model of osteoporosis was generated by ovariectomy. CaP-PILP or hydroxyapatite (HAP, negative control) was injected into the tibia, and the resulting changes in bone quality were determined. Further, implants were installed in the treated tibias, and implantation characteristics were assessed after 4 weeks.Results: The CaP-PILP group had superior bone repair. Importantly, CaP-PILP had excellent properties, similar to those of normal bone, in terms of implant osseointegration. In vivo experiment displayed that CaP-PILP group had better bone contact rate (65.97± 3.176) than HAP and OVX groups. Meanwhile, a mound of mature and continuous new bone formed. Moreover, the values of BIC and BA showed no significant difference between the CaP-PILP group and the sham group.Conclusion: In summary, CaP-PILP is a promising material for application in poor-quality bones to improve implant success rates in patients with osteoporosis. This research provides new perspectives on the application of nano-apatite materials in bone repair.Keywords: polymer-induced liquid precursor, calcium phosphates, nanocluster, osteoporosis, oral implant

Xuan Wang, Dongyu Hua, Xiaole Tang, Shan Li, Rao Sun, Zheng Xie, Zhiqiang Zhou, Yilin Zhao, Jintao Wang, Shiyong Li, Ailin Luo Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, People’s Republic of ChinaCorrespondence: Shiyong Li; Ailin Luo Email shiyongli@hust.edu.cn; alluo@tjh.tjmu.edu.cnAbstract: Postoperative neurocognitive disorder (PND) increases the length of hospital stay, mortality, and risk of long-term cognitive impairment. Perioperative sleep disturbance is prevalent and commonly ignored and may increase the risk of PND. However, the role of perioperative sleep disturbances in PND remains unclear. Nocturnal sleep plays an indispensable role in learning, memory, and maintenance of cerebral microenvironmental homeostasis. Hospitalized sleep disturbances also increase the incidence of postoperative delirium and cognitive dysfunction. This review summarizes the role of perioperative sleep disturbances in PND and elucidates the potential mechanisms underlying sleep-deprivation-mediated PND. Activated neuroinflammation and oxidative stress; impaired function of the blood-brain barrier and glymphatic pathway; decreased hippocampal brain-derived neurotrophic factor, adult neurogenesis, and sirtuin1 expression; and accumulated amyloid-beta proteins are associated with PND in individuals with perioperative sleep disorders. These findings suggest that the improvement of perioperative sleep might reduce the incidence of postoperative delirium and postoperative cognitive dysfunction. Future studies should further investigate the role of perioperative sleep disturbance in PND.Keywords: perioperative sleep disturbance, cognitive impairment, postoperative delirium, postoperative cognitive dysfunction, neuroinflammation

Zhiping Xie,1 Chengcai Li,1 Zelong Xing,1 Wu Zhou,1 Shenke Xie,1 MeiHua Li,1 Yujuan Zhou2 1Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, People’s Republic of China; 2Department of Orthopaedics, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330006, People’s Republic of ChinaCorrespondence: MeiHua LiDepartment of Neurosurgery, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Nanchang, 330006, Jiangxi, People’s Republic of ChinaEmail limeihua2000@sina.comYujuan ZhouDepartment of Orthopaedics, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Nanchang, 330006, Jiangxi, People’s Republic of ChinaEmail 2669174039@qq.comPurpose: Depression is associated with an inflammatory immune response. There are minimal data regarding the association of inflammatory markers with depression in patients with spinal cord injury (SCI). We aimed to investigate the association of inflammatory markers with depression in middle-aged and elderly SCI patients.Methods: Data were obtained from the Midlife in the United States (MIDUS) study, a longitudinal study of a representative sample of the adult population. We analyzed the associations of serum levels of fibrinogen, interleukin-6, tumor necrosis factor-ɑ, and C-reactive protein with depressive symptoms.Results: The median participant age was 52.5 years; 44.9% of participants were men. Multivariate linear regression analyses showed that an increased serum fibrinogen level (Sβ = 0.114, p = 0.005) was associated with higher Centre for Epidemiological Studies-Depression (CES-D) scores after adjustment for age, sex, body mass index (BMI), ethnicity, education, marital status, smoking, alcohol use, exercise, perceived stress score, and cardiovascular disease (CVD). Multivariate logistic regression analysis showed that an increased serum fibrinogen level was independently associated with a history of depression (odds ratio [OR] = 1.240, 95% confidence interval [CI] = 1.103– 1.997, p = 0.012) and depressive symptoms (OR = 1.884, 95% CI = 1.165– 2.499, p < 0.001; CES-D score ≥ 16) after adjustment for confounding factors. Stratified analysis revealed that the association between serum fibrinogen level and depressive symptoms was affected by antidepressant use.Conclusion: Serum fibrinogen level had a significantly positive association with depressive symptoms in middle-aged and elderly patients with SCI. Future longitudinal cohort studies should evaluate the possible use of serum &filig;brinogen for diagnosis of depression in SCI patients.Keywords: fibrinogen, depression, spinal cord injury, cross-sectional study