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Yanyan Li,1 Xia Deng,2 Xunan Wu,2 Ligang Zhou,1 Guoyue Yuan2 1Department of Endocrinology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Pudong, Shanghai, 201399 People’s Republic of China; 2Department of Endocrinology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, 210031, People’s Republic of ChinaCorrespondence: Guoyue Yuan, Department of Endocrinology, Affiliated Hospital of Jiangsu University, No. 438 Jiefang Road, Zhenjiang City, Jiangsu Province, 210031, People’s Republic of China, Email yuanguoyue@ujs.edu.cn Ligang Zhou, Department of Endocrinology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, 2800 Gongwei Road, Pudong, Shanghai, 201399, People’s Republic of China, Email zhouligang@yahoo.comObjective: Tsukushi is a newly identified hepatokine. Recent studies have shown that it relates to diabetes, lipid metabolism and fibrosis, but there is currently no investigation about whether Tsukushi is associated with diabetic kidney disease. Therefore, this study aimed to investigate the relationship between Tsukushi and diabetic kidney disease by characterizing Tsukushi levels in healthy subjects and type 2 diabetes with urinary albumin-creatinine ratio.Methods: Serum Tsukushi level was quantified by enzyme-linked immunosorbent assay in 167 normoalbuminuria, 80 microalbuminuria, and 31 macroalbuminuria patients with type 2 diabetes as compared with 53 healthy subjects. The correlation analysis was used to investigate the relationship between urinary albumin-creatinine ratio or Tsukushi level and other metabolic parameters. Multiple linear regression and logistic regression analysis were used to analyze the independent factors for urinary albumin-creatinine ratio and estimated glomerular filtration rate.Results: The Tsukushi level in the macroalbuminuria group was significantly higher than that in the normoalbuminuria or the microalbuminuria group. Multiple linear regression showed that the significantly independent factors for UACR included high Tsukushi quartile, systolic blood pressure, creatinine, homeostasis model assessment of insulin resistance, low 2-h post-oral glucose tolerance test c-peptide and female. Logistic regression demonstrated that the odds ratio of Tsukushi for glomerular filtration rate ≤ 90(mL/min/1.73m2) was 1.636 (95% CI 1.091– 2.452, P=0.017).Conclusion: The circulating Tsukushi increased in type 2 diabetes patients with albuminuria and was associated with urinary albumin-creatinine ratio, implying that Tsukushi may be involved in the pathogenesis of diabetic kidney disease, which deserves future studies.Keywords: type 2 diabetes, urinary albumin-creatinine ratio, hepatokine, Tsukushi

Luohang Ni,* Jianing Xu,* Quanpeng Li, Xianxiu Ge, Fei Wang, Xueting Deng, Lin Miao Medical Center for Digestive Diseases, Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xueting Deng; Lin Miao, Email xtdeng@njmu.edu.cn; linmiao@njmu.edu.cnAbstract: Biliary tract cancer (BTC) represents a challenging malignancy characterized by aggressive behavior, high relapse rates, and poor prognosis. In recent years, immunotherapy has revolutionized the treatment landscape for various cancers, but its efficacy in BTC remains limited. This article provides a comprehensive overview of the advances in preclinical and clinical studies of immunotherapy for BTC. We explore the potential of immune checkpoint inhibitors in reshaping the management of BTC. Despite disappointing results thus far, ongoing clinical trials are investigating the combination of immunotherapy with other treatment modalities. Furthermore, research on the tumor microenvironment has unveiled novel targets for immunotherapeutic interventions. By understanding the current state of immunotherapy in BTC and highlighting future directions, this article aims to fuel further exploration and ultimately improve patient outcomes in this challenging disease.Keywords: biliary tract cancer, cancer immunotherapy, tumor microenvironment, immune checkpoint inhibitors, clinical trials

Yongzhi Xu,1,2,* Yuanping Hao,2,* Muhammad Arif,3 Xiaodong Xing,4 Xuyang Deng,1 Danyang Wang,1 Yang Meng,2 Shuai Wang,1 Mohamed Sayed Hasanin,5 Wanchun Wang,2 Qihui Zhou3,6 1School of Stomatology, Qingdao University, Qingdao, People’s Republic of China; 2Department of Stomatology, Qingdao Stomatological Hospital Affiliated to Qingdao University, Qingdao, People’s Republic of China; 3Qingdao Key Laboratory of Materials for Tissue Repair and Rehabilitation, School of Rehabilitation Sciences and Engineering, University of Health and Rehabilitation Sciences, Qingdao, People’s Republic of China; 4School of Chemical Engineering, Nanjing University of Science and Technology, Nanjing, People’s Republic of China; 5Cellulose and Paper Department, National Research Centre, Dokki, Cairo, Egypt; 6Hubei Key Laboratory of Biomass Fibers and Eco-Dyeing & Finishing, Wuhan Textile University, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wanchun Wang; Qihui Zhou, Email kqwwch@126.com; qihuizhou@uor.edu.cnIntroduction: Persistent endodontic infections (PEIs) mediated by bacterial biofilm mainly cause persistent periapical inflammation, resulting in recurrent periapical abscesses and progressive bone destruction. However, conventional root canal disinfectants are highly damaging to the tooth and periodontal tissue and ineffective in treating persistent root canal infections. Antimicrobial materials that are biocompatible with apical tissues and can eliminate PEIs-associated bacteria are urgently needed.Methods: Here, ϵ-poly (L-lysine) derived carbon quantum dots (PL-CQDs) are fabricated using pyrolysis to remove PEIs-associated bacterial biofilms.Results: Due to their ultra-small size, high positive charge, and active reactive oxygen species (ROS) generation capacity, PL-CQDs exhibit highly effective antibacterial activity against Enterococcus faecalis (E. faecalis), which is greatly dependent on PL-CQDs concentrations. 100 μg/mL PL-CQDs could kill E. faecalis in 5 min. Importantly, PL-CQDs effectively achieved a reduction of biofilms in the isolated teeth model, disrupting the dense structure of biofilms. PL-CQDs have acceptable cytocompatibility and hemocompatibility in vitro and good biosafety in vivo.Discussion: Thus, PL-CQDs provide a new strategy for treating E. faecalis-associated PEIs. Keywords: carbon quantum dots, Enterococcus faecalis, bacterial biofilm, persistent endodontic infections

Yuanfei Li,1,* Yong Yang,1,* Yafeng Zheng,2,* Yang Gao,3 Guoliang Shu,4 Wei Gai,2 Yuxin Guo,2 Xianghui Deng1 1Department of Critical Care Medicine, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, People’s Republic of China; 2WillingMed Technology (Beijing) Co., Ltd, Beijing, People’s Republic of China; 3Department of Radiology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, People’s Republic of China; 4Department of General Surgery, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xianghui Deng, Department of Critical Care Medicine, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, People’s Republic of China, Tel +8613974833075, Email 853275395@qq.comAbstract: The liver receives blood from both the hepatic artery and portal vein. Hepatic infarction is rare in clinical practice as both the hepatic artery and portal vein can supply blood to the liver. Here, we reported a case of a 75-year-old man who underwent radical laparoscopic surgery for rectal cancer and subsequently developed hepatic infarction. The patient experienced severe infection, as well as circulatory and respiratory failure on the third day after surgery. The patient presented with high fever, chest tightness, shortness of breath, decreased blood oxygen saturation and blood pressure. The leukocyte count decreased from 8.10 × 10^9/L to 1.75 × 10^9/L. Procalcitonin (PCT) levels increased from 1.02 ng/mL to 67.14 ng/mL, and eventually reaching levels over 200 ng/mL. Enhanced abdominal computed tomography (CT) confirmed the presence of hepatic infarction, but no thrombosis was observed in the hepatic artery or portal vein. Metagenomic next-generation sequencing (mNGS) identified hypervirulent Klebsiella pneumoniae (hvKp) in the patient’s blood and ascites, one day earlier than the detection results using traditional culture methods. The patient was diagnosed with hepatic infarction combined with septic shock caused by hvKp. This case emphasizes that in the high-risk group of thrombosis, infection can trigger exacerbated hepatic infarction events, particularly in cases after surgical procedures. For severely ill patients with infectious diseases who are admitted to the ICU with worsening symptoms, it is important to collect appropriate samples and send them for pathogen detection using mNGS in a timely manner. This may aid in early intervention and improve clinical outcomes.Keywords: hepatic infarction, mNGS, hypervirulent Klebsiella pneumoniae, septic shock

Xiaoxi Deng,1,* Xiaofei Guo,1,* Xiaojie Chen,2 Xinyu Zeng,1 Jiamin Guo,1 Xin Bai,1 Ping Zhang,1 Yuan Wang1 1Department of Pathology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, 100102, People’s Republic of China; 2Department of Emergency, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, 100102, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuan Wang, Ping Zhang, Department of Pathology, Wangjing Hospital, China Academy of Chinese Medical Sciences, 6 Wangjing Zhonghuan South Road, Chaoyang District, Beijing, 100102, People’s Republic of China, Tel +86 010-84739040, Email yuanwangwwwy@126.com; zhang787ping@126.comBackground: Acute myocardial infarction (AMI) is a severe acute coronary syndrome, demonstrating a trend toward affecting younger individuals in recent years. The association between early-onset myocardial infarction and single nucleotide polymorphism necessitates further exploration and evaluation.Case description: We present a case of a patient experiencing early-onset and recurrent myocardial infarction. The patient underwent stent implantation for myocardial infarction at the age of 53 and subsequently encountered two more myocardial infarctions within a span of 16 years. Following interventional therapy, genetic testing was conducted to assess the efficacy of subsequent anti-heart failure medications, with the aim to preemptively address heart failure risks. Genetic testing revealed a mutation in the angiotensin-converting enzyme (ACE) gene (rs577350502, g.63488533C>A), characterized by an intron-deletion single nucleotide variant.Conclusion: While this variant has not been previously reported to be associated with any specific disease, we hypothesize that it may contribute to the susceptibility and risk of myocardial infarction and coronary heart disease in the patient under consideration. This observation underscores the significance of investigating the insertion/deletion polymorphisms of the ACE gene in the context of AMI and emphasizes the necessity for further validation of this variant and other genetic markers associated with AMI in related diseases.Keywords: ACE, case reports, gene mutations, myocardial infarction, SNV

Jia Chen,1– 4,&ast; Xiaoyu Deng,1– 4,&ast; Ting Lin,1– 4 Jiefeng Huang,1– 4 Yisong Yang,1– 4 Ningfang Lian1– 4 1Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 2Fujian Provincial Sleep-Disordered Breathing Clinic Center, Fuzhou, Fujian, People’s Republic of China; 3Institute of Respiratory Disease, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China&ast;These two authors contributed equally to this workCorrespondence: Ningfang Lian, Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Fujian Medical University, No. 20, Chazhong Road, Taijiang District, Fuzhou, Fujian Province, 350005, People’s Republic of China, Tel +86-591-87981698, Email 1533532863@qq.comPurpose: Chronic intermittent hypoxia (CIH) related arterial endothelium injury is a common cause of cardiovascular system injury. However, the mechanism still needs to be clarified. In this study, we aimed to clarify the role and mechanism of ferrostatin-1 (Fer-1) in CIH-related rat arterial endothelial cells (ROAEC) ferroptosis.Methods: ROAEC was divided into control group, CIH group, and CIH+ Fer-1 group. Cell viability was detected by cell counting kit 8 kits (CCK8). The apoptotic rate, reactive oxygen species (ROS) levels, Fe2+ levels, and lipid ROS levels were detected by flow cytometry. Malondialdehyde (MDA) levels and nicotinamide adenine dinucleotide (NAD+)/NADH ratio were detected via Elisa kits. The mRNA and protein levels of cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) were detected by qRT-PCR and Western blot. Mitochondrial structure and function were observed by transmission electron microscope (TEM) and mitochondrial membrane potential (MMP). Central carbon metabolism was measured to compare metabolites among each group.Results: After the CIH exposure, ROAEC cell viability decreased; The levels of cell apoptosis, ROS, Fe2+, MDA, and lip ROS increased; The levels of NAD+/NADP ratio decreased; The mRNA and protein levels of GPX4 and SLC7A11 decreased (all p< 0.05). Co-cultured with Fer-1 reversed the levels of apoptosis rate, cell viability, ROS, Fe2+, MAD, lipid ROS, NAD+/NADH ratio and the mRNA and protein expression of GPX4 and SLC7A11 (all p< 0.05). The TEM results showed that damaged mitochondrial membrane and the matrix spillover in the CIH group. The results of the JC-1 assay showed decreased MMP in the CIH group. Fer-1 treatment ameliorated the mitochondrial injury. The results of central carbon metabolism found that CIH altered the metabolites in the TCA cycle, which were reversed by Fer-1 treatment.Conclusion: CIH-induced ferroptosis in ROAEC, which were reversed by Fer-1 via reprogramming mitochondrial function.Keywords: obstructive sleep apnea, chronic intermittent hypoxia, arterial endothelium injury, ferroptosis, mitochondrial function

Zhisheng Huang,1,2 Zuowang Cheng,3 Xia Deng,4 Ying Yang,5 Na Sun,5 Peibin Hou,5 Ruyue Fan,5 Shuai Liu6,7 1Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, National Regional Center for Respiratory Medicine, Jiangxi Hospital of China-Japan Friendship Hospital, Nanchang, Jiangxi, People’s Republic of China; 3Department of Clinical Laboratory, Zhangqiu District People’s Hospital Affiliated to Jining Medical University, Jinan, Shandong, People’s Republic of China; 4School of Public Health, Shandong Second Medical University, Weifang, Shandong, People’s Republic of China; 5Shandong Center for Disease Control and Prevention, Jinan, Shandong, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 7Shandong Key Laboratory of Infectious Respiratory Disease, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Shuai Liu; Ruyue Fan, Email liushuai_sam@163.com; fanruyue2022@163.comBackground: Coronavirus disease 2019 (COVID-19) is a respiratory infectious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The objective of this study is to identify reliable and accurate biomarkers for the early stratification of disease severity, a crucial aspect that is currently lacking for the impending phases of the next COVID-19 pandemic.Methods: In this study, we identified important module and hub genes related to clinical severe COVID-19 using differentially expressed genes (DEGs) screening combing weighted gene co-expression network analysis (WGCNA) in dataset GSE213313. We further screened and confirmed these hub genes in another two new independent datasets (GSE172114 and GSE157103). In order to evaluate these key genes’ stability and robustness for diagnosing or predicting the progression of illness, we used RT-PCR validation of selected genes in blood samples obtained from hospitalized COVID-19 patients.Results: A total of 968 and 52 DEGs were identified between COVID-19 patients and normal people, critical and non-critical patients, respectively. Then, using WGCNA, 10 modules were constructed. Among them, the blue module positively associated with clinic disease severity of COVID-19. From overlapped section between DEGs and blue module, 12 intersected common differential genes were obtained. Subsequently, these hub genes were validated in another two new independent datasets as well and 9 genes that overlapped showed a highly correlation with disease severity. Finally, the mRNA expression levels of these hub genes were tested in blood samples from COVID-19 patients. In severe cases, there was increased expression of MCEMP1, ANXA3, CD177, and SCN9A. In particular, MCEMP1 increased with disease severity, which suggested an unfavorable development and a frustrating prognosis.Conclusion: Using comprehensive bioinformatical analysis and the validation of clinical samples, we identified four major candidate genes, MCEMP1, ANXA3, CD177, and SCN9A, which are essential for diagnosis or development of COVID-19.Keywords: COVID-19, differentially expressed genes, WGCNA, hub genes, neutrophil

Lei Qiang,1 Xianghui Deng,1 Yong Yang,1 Zhigan Wang,2 Wei Gai3 1Department of Critical Care Medicine, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, People’s Republic of China; 2Department of Pathology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, People’s Republic of China; 3WillingMed Technology (Beijing) Co., Ltd, Beijing, People’s Republic of ChinaCorrespondence: Xianghui Deng, Department of Critical Care Medicine, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, People’s Republic of China, Email dengxianghui1@zsszxyy2.wecom.workAbstract: Histoplasmosis is an endemic disease caused by Histoplasma capsulatum. This systemic disease can affect various organs beyond the lungs, such as the liver, spleen, adrenal gland, and lymph nodes. The clinical symptoms can range from asymptomatic to severe, life-threatening conditions, depending on the state of the patient’s immune system. This report describes a 40-year-old male who presented with reports of weight loss, low back pain, and progressively worsening movement disorder of the bilateral lower extremities for months. Computed tomography (CT) examination showed multiple lytic lesions of vertebral bodies, bilateral ribs, and pelvic bone, histopathological examination and tumor-related serum markers exclude tumors. mNGS was employed to identify H. capsulatum var. capsulatum as the etiological agent of the lesions in the bone biopsy. Through phylogenetic tree analysis, Histoplasma capsulatum var. Capsulatum (Hcc) was the main responsible pathogen, rarely reported in bone lesions. The patient underwent spinal surgery and was successfully treated with liposomal amphotericin B and itraconazole. Based on the diagnosis and treatment of this case, we discuss the epidemiologic status, clinical presentations, diagnostic criteria, and treatment guidelines of histoplasmosis to provide additional information about this disease. mNGS is utilized in this case, and it appears to be a reliable method for early and accurate diagnosis of this disease.Keywords: metagenomic next generation sequencing, disseminated histoplasmosis, multifocal osteolytic lesions, diagnosis, Histoplasma capsulatum var. capsulatum

Jia Chen,1– 3 Xiaoyu Deng,1– 3 Hansheng Xie,1– 3 Caiyun Wang,1– 3 Jiefeng Huang,1– 3 Ningfang Lian1– 3 1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 2Fujian Provincial Sleep-Disordered Breathing Clinic Center, Institute of Respiratory Disease, Fujian Medical University, Fuzhou, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, People’s Republic of ChinaCorrespondence: Ningfang Lian, Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University, No. 20, Chazhong Road, Taijiang District, Fuzhou, Fujian Province, 350005, People’s Republic of China, Tel +86-591-87981698, Email 1533532863@qq.comPurpose: Circular RNA (circRNA) plays an important role in various biological processes. However, their functions in cigarette smoke extract (CSE) induced human normal lung epithelial cells (BEAS-2B) injury remain vague. The study aimed to explore circRNA expression profiles and reveal their potential roles in CSE-treated BEAS-2B cells.Methods: 5% CSE exposure for 24 hours were used to build the BEAS-2B cells ferroptosis model. Differentially expressed circRNAs (DECs) were identified by next-generation RNA sequencing. Six randomly selected DECs were validated via quantitative reverse transcription polymerase chain reaction (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) analysis were conducted to clarify the potential functions of the DECs. Furthermore, the role of hsa_circ_0025843 in CSE-related BEAS-2B cells ferroptosis was confirmed.Results: 5% CSE exposure induced BEAS-2B cells ferroptosis. Fifty-one up-regulated cirRNAs and 80 down-regulated circRNAs were revealed in CSE-treated BEAS-2B cells. Hsa_circ_0003461, hsa_circ_0007548, hsa_circ_0025843, hsa_circ_0068896, hsa_circ_0005832, and hsa_circ_0053378 were selected randomly to validate the reliability of next-generation RNA sequencing by qRT-PCR. After KEGG pathway analysis, DECs were found to participate in the process of EGFR tyrosine kinase inhibitor resistance and glycerophospholipid metabolism. The knockdown of hsa_circ_0025843 significantly alleviated CSE-induced BEAS-2B cells ferroptosis.Conclusion: The study indicated the circRNA expression profiles in CSE-treated BEAS-2B cells. Hsa_circ_0025843 alleviated CSE induced BEAS-2B cells ferroptosis, which might be a potential therapeutic target of CSE related lung injury.Keywords: cigarette smoke extract, Circular RNA, next-generation RNA sequencing, lung injury, ferroptosis

Chun Wang,1 Xin Deng,1 Lei Li,2 Mei Li3 1Department of Integrated TCM & Western Medicine, Mengcheng County Second People’s Hospital, Anhui, 233500, People’s Republic of China; 2Department of Cardiology, Mengcheng County Second People’s Hospital, Anhui, 233500, People’s Republic of China; 3Department of Pharmacy, Mengcheng County Second People’s Hospital, Anhui, 233500, People’s Republic of ChinaCorrespondence: Chun Wang, Department of Integrated TCM & Western Medicine, Mengcheng County Second People’s Hospital, Anhui, 233500, People’s Republic of China, Tel +86-0558-7623307, Email chunwang0424@163.comBackground: Mitochondrial DNA (mtDNA) mutations are associated with essential hypertension (EH), but the molecular mechanism remains largely unknown.Objective: The aim of this study is to explore the association between mtDNA mutations and EH.Methods: Two maternally inherited families with EH are underwent clinical, genetic and biochemical assessments. mtDNA mutations are screened by PCR-Sanger sequencing and phylogenetic, and bioinformatics analyses are performed to evaluate the pathogenicity of mtDNA mutations. We also generate cytoplasmic hybrid (cybrid) cell lines to analysis mitochondrial functions.Results: Matrilineal relatives exhibit variable degree of clinical phenotypes. Molecular analysis reveals the presence of m.A14693G and m.A14696G mutations in two pedigrees. Notably, the m.A14693G mutation occurs at position 54 in the TψC loop of tRNAGlu, a position which is critical for post-transcriptionally modification of tRNAGlu. While the m.A14696G mutation creates a novel base-pairing (51C-64G). Bioinformatic analysis shows that these mutations alter tRNAGlu secondary structure. Additionally, patients with tRNAGlu mutations exhibit markedly decreased in mtDNA copy number, mitochondrial membrane potential (MMP) and ATP, whereas the levels of reactive oxygen species (ROS) increase significantly.Conclusion: The m.A14696G and m.A14693G mutations lead to failure in tRNAGlu metabolism and cause mitochondrial dysfunction that is responsible for EH.Keywords: EH, mt-tRNAGlu m.A14693G m.A14696G, mitochondrial dysfunction, Chinese families

Yiran Zhang,1– 4,&ast; Qingcheng Song,2,3,&ast; Yueyao Zhang,2,3,&ast; Jiheng Xiao,5 Xiangtian Deng,6 Xin Xing,2,3 Hongzhi Hu,5 Yingze Zhang1– 3 1School of Medicine, Nankai University, Tianjin, 300071, People’s Republic of China; 2Department of Orthopaedic Surgery, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050051, People’s Republic of China; 3NHC Key Laboratory of Intelligent Orthopaedic Equipment, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 4HeBei Ex&Invivo Biotechnology Co. Ltd, Shijiazhuang, Hebei, 050051, People’s Republic of China; 5Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 6Orthopaedics Research Institute, Department of Orthopaedics, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingze Zhang; Hongzhi Hu, Email yzling_liu@163.com; 13720105746@163.comBackground: Although systemic chemotherapy is a standard approach for osteosarcoma (OS) treatment, its efficacy is limited by the inherent or acquired resistance to apoptosis of tumor cells. Ferroptosis is considered as an effective strategy capable of stimulating alternative pathways of cancer cell demise. The purpose of this study is to develop a novel strategy boosting ferroptotic cascade for synergistic cancer therapy.Methods and Results: A novel nanovehicle composed of arginine-glycine-aspartate (RGD) modified mesoporous silica-coated iron oxide loading Fin56 was rationally prepared (FSR-Fin56). With the RGD-mediated targeting affinity, FSR-Fin56 could achieve selective accumulation and accurate delivery of cargos into cancer cells. Upon exposure to NIR light, the nanovehicle could generate localized hyperthermia and disintegrate to liberate the therapeutic payload. The released Fin56 triggered the degradation of GPX4, while Fe3+ depleted the intracellular GSH pool, producing Fe2+ as a Fenton agent. The local rise in temperature, in conjunction with Fe2+-mediated Fenton reaction, led to a rapid and significant accumulation of ROS, culminating in LPOs and ferroptotic death. The outstanding therapeutic efficacy and safety of the nanovehicle were validated both in vitro and in vivo.Conclusion: The Fin56-loaded FSR nanovehicle could effectively disturb the redox balance in cancer cells. Coupled with NIR laser irradiation, the cooperative CDT and PTT achieved a boosted ferroptosis-inducing therapy. Taken together, this study offers a compelling strategy for cancer treatment, particularly for ferroptosis-sensitive tumors like osteosarcoma. Keywords: chemodynamic therapy, photothermal therapy, Fenton reaction, Fin56, ferroptosis

Yinshan Lin,1,2,&ast; Xiaoling Guan,1,2,&ast; Jianfen Su,1,2,&ast; Sheng Chen,2 Xihua Fu,1 Xiaowei Xu,2 Xiaohua Deng,2 Jishuo Chang,2 Aiping Qin,2,&ast; Ao Shen,2,&ast; Lingmin Zhang1,2,&ast; 1Pharmacy Department & Panyu Institute of Infectious Diseases, Guangzhou Panyu Central Hospital, Guangzhou, Guangdong, 511400, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 511436, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lingmin Zhang, Guangzhou Panyu Central Hospital, No. 8 Fuyu East Road, Guangzhou, Guangdong, 511400, People’s Republic of China, Email zhanglm@gzhmu.edu.cn Ao Shen; Aiping Qin, Guangzhou Medical University, No. 1 Xinzao Road, Guangzhou, Guangdong, 511426, People’s Republic of China, Email shenao@gzhmu.edu.cn; qinaiping_2008@163.comAbstract: Nucleic acids have emerged as promising therapeutic agents for many diseases because of their potential in modulating gene expression. However, the delivery of nucleic acids remains a significant challenge in gene therapy. Although viral vectors have shown high transfection efficiency, concerns regarding teratogenicity or carcinogenicity have been raised. Non-viral vehicles, including cationic polymers, liposomes, and inorganic materials possess advantages in terms of safety, ease of preparation, and low cost. Nevertheless, they also face limitations related to immunogenicity, quick clearance in vivo, and lack of targeting specificity. On the other hand, bioinspired strategies have shown increasing potential in the field of drug delivery, yet there is a lack of comprehensive reviews summarizing the rapid development of bioinspired nanoparticles based on the cell membrane camouflage to construct the nucleic acids vehicles. Herein, we enumerated the current difficulties in nucleic acid delivery with various non-viral vehicles and provided an overview of bioinspired strategies for nucleic acid delivery. Keywords: nucleic acids, bioinspired nanoparticles, non-viral vehicles, gene therapy, cell membranes

Chuangjia Huang,1,2,&ast; Yu Zhang,3,&ast; Jianfen Su,1,2,&ast; Xiaoling Guan,1,2 Sheng Chen,1,2 Xiaowei Xu,1,2 Xiaohua Deng,1,2 Lingmin Zhang,1,2 Jionghua Huang1 1Department of Cardiology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, People’s Republic of China; 2Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, People’s Republic of China; 3Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jionghua Huang; Lingmin Zhang, Email mdhjh2014@126.com; zhanglm@gzhmu.edu.cnBackground: High-level low-density lipoprotein cholesterol (LDL-C) plays a vital role in the development of atherosclerotic cardiovascular disease. Low-density lipoprotein receptors (LDLRs) are scavengers that bind to LDL-C in the liver. LDLR proteins are regulated by proprotein convertase subtilisin/kexin type 9 (PCSK9), which mediates the degradation of LDLR and adjusts the level of the plasma LDL-C. The low expression of PCSK9 leads to the up-regulation of liver LDLRs and the reduction of plasma LDL-C. Hepatocytes are attractive targets for small interfering RNA (siRNA) delivery to silence Pcsk9 gene, due to their significant role in LDL-C regulation.Methods: Here, a type of liver-specific ionizable lipid nanoparticles is developed for efficient siRNA delivery. This type of nanoparticles shows high stability, enabling efficient cargo delivery specifically to hepatocytes, and a membrane-active polymer that reversibly masks activity until an acidic environment is reached.Results: Significantly, the siPcsk9 (siRNA targeting to Pcsk9)-loaded nanoparticles (GLP) could silence 90% of the Pcsk9 mRNA in vitro. In vivo study showed that the improved accumulation of GLP in the liver increased LDLR level by 3.35-fold and decreased plasma LDL-C by 35%.Conclusion: GLP has shown a powerful effect on reducing LDL-C, thus providing a potential therapy for atherosclerotic cardiovascular disease. Keywords: ionizable lipid nanoparticles, bad cholesterol, PCSK9, small interfering RNA, liver-specific delivery

Chunran Pan,&ast; Wenjie Hou,&ast; Xiaofeng Deng, Jiawei Liu, Ruimin Chi, Xingru Shang, Tao Xu, Xiaoxia Hao Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoxia Hao, Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095&num;, Jie-Fang Avenue, Qiaokou District, Wuhan, 430030, People’s Republic of China, Tel +86 1-597-296-0593, Fax +86- 27-83662640, Email haoxiaoxia@hust.edu.cnAbstract: Intervertebral disc degeneration (IDD) is considered as a dominant contributor to low back pain (LBP), causing severe pain, limited range of lumbar motion, physical dysfunction, and restriction of social activity. However, the specific pathological mechanisms underlying IDD remain elusive, and effective strategies to delay the pathogenesis of IDD are still unclear and limited. In recent years, some studies have found that nuclear factor erythroid 2-related factor 2 (Nrf2), an important antioxidant transcription factor, may play crucial roles in the pathogenesis and progression of age-related diseases including IDD. Nrf2 can maintain redox homeostasis and protecting nucleus pulposus (NP) cells against oxidative stress, inflammatory response, extracellular matrix (ECM) catabolism, cell senescence and cell death involving in the progression of IDD. In this review, we aim to systematically describe the vital roles and pathological mechanism of Nrf2 signaling axis in the pathogenesis of IDD, which may put forward potential therapeutic strategies for the prevention and treatment of IDD by targeting Nrf2.Keywords: Nrf2, intervertebral disc degeneration, nucleus pulposus cells, oxidative stress

Yang Gou,&ast; Yongjie Tang,&ast; Shuiqing Liu, Siyu Cheng, Xiaojuan Deng, Qin Wen, Yimei Feng, Xiangui Peng, Ping Wang, Xi Zhang Medical Center of Hematology, Xinqiao Hospital of Army Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ping Wang, Medical Center of Hematology, The Xinqiao Hospital of Army Medical University, Chongqing, People’s Republic of China, Email wpii_2002@sina.comAbstract: The ETV6::PDGFRB fusion gene is commonly reported in chronic myelomonocytic leukemia with eosinophilia, yet patients with ETV6::PDGFRB presenting myeloid and lymphoid neoplasms successively have not been reported. Here, we report the first case of a 35-year-old man with myeloid and lymphoid neoplasms harboring an ETV6::PDGFRB fusion gene who demonstrated poor response to imatinib. The patient was diagnosed with an ETV6::PDGFRB fusion gene myeloid neoplasm on initial diagnosis at our hospital. After 5 months of treatment with imatinib, he was diagnosed with T-cell lymphoblastic lymphoma. ETV6::PDGFRB turned negative after increasing the dose of imatinib, but enlarged superficial lymph nodes reappeared the following year. Notably, the patient exhibited a worse response to imatinib treatment. This study describes this rare case and speculates on a possible mechanism.Keywords: ETV6, PDGFRB, fusion, myeloid/lymphoid neoplasms, imatinib

Lili Gao,1,2 Ying Lu,1 Na Zhang,3 Yi Wang,1,4 Weimin Yang,5 Xiaopeng Deng1 1Department of Construction and Real Estate, Southeast University, Nanjing, People’s Republic of China; 2Department of Architecture and Civil Engineering, City University of Hong Kong, Hong Kong, China; 3School of Civil Engineering and Architecture, Zhejiang University of Technology, Hangzhou, People’s Republic of China; 4College of Design and Engineering, National University of Singapore, Singapore, Singapore; 5School of Digital Commerce, Jiangsu Vocational Institute of Commerce, Nanjing, People’s Republic of ChinaCorrespondence: Ying Lu; Xiaopeng Deng, Department of Construction and Real Estate, Southeast University, No. 2 Southeast Road, Nanjing, 211100, People’s Republic of China, Email luying_happy@126.com; dxp@seu.edu.cnIntroduction: Expatriates are facing more stressors, such as cross-cultural adjustment, global political instability, family separation, health concern. The black swan events of the pandemic and the Russian-Ukrainian war have posed significant challenges in the current international environment. Adapting to an expatriate environment as soon as possible is critical to expatriate success. This study aims to examine the factors that affect expatriate adjustment through psychological resilience.Methods: Guided by person-environment (p-e) fit theory, an expatriate adjustment framework based on psychological resilience is proposed, and 309 valid sample data are used for structural equation model (SEM) analysis.Results: The results show that expatriate adjustment is a psychological process based on the development of resilience. Social support plays a buffering role in dealing with environmental deviations induced stressors. The person-environment transactional process is the most critical adjustment process.Discussion: The development of expatriate adjustment is divided into four stages (shock, buffer, adjustment, mastery) consistent with resilience development. Project managers can take different expatriate management strategies from multiple aspects. Finally, this study proposes the U-curve hypothesis of expatriates’ psychological resilience development aligned with the U-curve process of expatriate adjustment for future research.Keywords: international assignments, expatriate adjustment, psychological resilience, multifactorial framework

Li-Li Zheng,1 Sheng Wang,1 Ze-Geng Li,2 Lei Han,2 Chun-Dong Zhu,1 Chun-Ying Li,1 Xing-Xing Zhang,1 Xue Deng1 1Department of Respiratory Medicine of Geriatrics Center, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, 230000, People’s Republic of China; 2Anhui University of Traditional Chinese Medicine, Hefei, 230000, People’s Republic of ChinaCorrespondence: Sheng Wang, Department of Respiratory Medicine, Geriatrics Center, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, 117 Meishan Road, Shushan District, Hefei, 230000, People’s Republic of China, Tel +86 13855182043, Email wangs_sheng@163.comBackground: This study aims to explore the factors influencing the coagulation function of patients with chronic obstructive pulmonary disease (COPD) and its effects on thrombosis.Methods: A total of 155 COPD patients, including 118 patients with acute exacerbation of COPD (AECOPD) and 37 patients with stable COPD (SCOPD), were enrolled in this study. Meanwhile, 50 patients with gastrointestinal polyps found during physical examination and treated with surgery in the same period were enrolled as the control group. The basic data, routine blood tests, C-reactive protein (CRP), procalcitonin (PCT), and coagulation indexes of the three groups were collected, as well as arterial blood gas indexes of AECOPD patients.Results: The differences in erythrocyte count and hemoglobin among groups were not statistically significant. Compared with the SCOPD group and control group, white blood cell (WBC), neutrophil percentage, PCT, CRP, prothrombin time (PT), and fibrinogen (FIB) in the AECOPD group increased significantly, while the international normalized ratio (INR) decreased (P < 0.05). The differences in activated partial thromboplastin time (APTT) and D-dimer among groups were not statistically significant (P > 0.05). Thrombin time (TT) in the AECOPD group was shorter than that of the control group, and PT was longer than that of the SCOPD group (P < 0.05). Five patients with AECOPD and one patient with SCOPD had venous thrombosis.Conclusion: The abnormal coagulation function in AECOPD patients is related to the degree of infection and hypercapnia, which may be a risk factor for thrombosis.Keywords: acute exacerbation of chronic obstructive pulmonary disease, AECOPD, abnormal coagulation function, infection, thrombosis

Wei Jiang, Xiaofei Deng, Ting Zhu, Jing Fang, Jinyao Li Department of Ultrasound, Huazhong University of Science and Technology Union Shenzhen Hospital (Nanshan Hospital), Shenzhen, Guangdong province, People’s Republic of ChinaCorrespondence: Wei Jiang, Department of Ultrasound, Huazhong University of Science and Technology Union Shenzhen Hospital (Nanshan Hospital), No. 89 Taoyuan Road, Nanshan District, Shenzhen, Guangdong province, 518052, People’s Republic of China, Tel + 86- 13026628099, Email 2646748175@qq.comBackground: Neoadjuvant chemotherapy (NAC) plays a significant role in breast cancer (BC) management; however, its efficacy varies among patients. Current evaluation methods may lead to delayed treatment alterations, and traditional imaging modalities often yield inaccurate results. Radiomics, an emerging field in medical imaging, offers potential for improved tumor characterization and personalized medicine. Nevertheless, its application in early and accurately predicting NAC response remains underinvestigated.Objective: This study aims to develop an automated breast volume scanner (ABVS)-based radiomics model to facilitate early detection of suboptimal NAC response, ultimately promoting personalized therapeutic approaches for BC patients.Methods: This retrospective study involved 248 BC patients receiving NAC. Standard guidelines were followed, and patients were classified as responders or non-responders based on treatment outcomes. ABVS images were obtained before and during NAC, and radiomics features were extracted using the PyRadiomics toolkit. Inter-observer consistency and hierarchical feature selection were assessed. Three machine learning classifiers, logistic regression, support vector machine, and random forest, were trained and validated using a five-fold cross-validation with three repetitions. Model performance was comprehensively evaluated based on discrimination, calibration, and clinical utility.Results: Of the 248 BC patients, 157 (63.3%) were responders, and 91 (36.7%) were non-responders. Radiomics feature selection revealed 7 pre-NAC and 6 post-NAC ABVS features, with higher weights for post-NAC features (min > 0.05) than pre-NAC (max < 0.03). The three post-NAC classifiers demonstrated AUCs of approximately 0.9, indicating excellent discrimination. DCA curves revealed a substantial net benefit when the threshold probability exceeded 40%. Conversely, the three pre-NAC classifiers had AUCs between 0.7 and 0.8, suggesting moderate discrimination and limited clinical utility based on their DCA curves.Conclusion: The ABVS-based radiomics model effectively predicted suboptimal NAC responses in BC patients, with early post-NAC classifiers outperforming pre-NAC classifiers in discrimination and clinical utility. It could enhance personalized treatment and improve patient outcomes in BC management.Keywords: breast cancer, neoadjuvant chemotherapy, radiomics, automated breast volume scanner, prediction model, model validation comparison

Wan He,1,&ast; Changbu Wu,2,3,&ast; Guanping Chen,2– 4 Guili Zhang,2,3 Zihan Zhao,2,3 Shu’an Wen,2,3 Yuan Zhou,2,3 Xue Deng,2,3 Yu Feng,2,3 Lan-Lan Zhong,2,3 Guo-Bao Tian,2– 4 Min Dai1 1School of Laboratory Medicine, Chengdu Medical College, Chengdu, 610500, People’s Republic of China; 2Department of Immunology and Microbiology, Advanced Medical Technology Center, The First Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 3Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, 510080, People’s Republic of China; 4Department of Immunology, School of Medicine, Sun Yat-Sen University, Shenzhen, 518107, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min Dai, School of Laboratory Medicine, Chengdu Medical College, Chengdu, Sichuan Province, People’s Republic of China, Tel +86 28-62739128, Email daimin1015@163.com Guo-Bao Tian, Department of Immunology and Microbiology, Advanced Medical Technology Center, The First Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan 2nd Road, Guangzhou, 510080, People’s Republic of China, Tel/Fax +86 20 87335387, Email tiangb@mail.sysu.edu.cnBackground: The emergence and spread of hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) is a potential epidemiological threat that needs to be monitored. However, the transmission and pathogenic characteristics of hv-CRKP in China remain unclear. We investigated the epidemiological characteristics of gut colonized hv-CRKP in a hospital in Guangdong Province, China.Methods: A total of 46 gut colonized hv-CRKP isolates were collected from Sun Yat-Sen Memorial Hospital (Guangzhou, China) from August 31st to December 31st, 2021. Minimum inhibitory concentrations (MICs) were obtained for 15 antibiotics for 46 hv-CRKP isolates. BALB/C mice infection model and mucoviscosity assay was used to evaluate the virulence of the isolates. The characteristics of genome, phylogenetic relationship and the structure of the plasmid of 46 gut colonized hv-CRKP isolates were compared with pathogenic isolates from GeneBank based on whole-genome data.Results: The hv-CRKP isolation rate of all gut colonized carbapenem-resistant Klebsiella pneumoniae was 17% (46/270), and the intestinal colonization rate of hv-CRKP was irrelevant to the sex, age, department of hospitalization, and history of antibiotic use of the host. The gut colonized hv-CRKP showed pandrug resistance and hypervirulence. The gut colonized hv-CRKP and pathogenic hv-CRKP prevalent in China were mainly ST11 hv-CRKP and had two major epidemic clades. The similarities in genomic characteristics between gut colonized hv-CRKP and pathogenic hv-CRKP were consistent. The gut colonized hv-CRKP carried an incomplete structure pK2044 virulence plasmid from hypervirulent K. pneumoniae NTUH-K2044 by analyzing the virulence plasmid structure.Conclusion: Our results suggest that the gut colonized ST11 hv-CRKP may serve as a reservoir for the clinical pathogenic ST11 HV-CRKP. It is necessary to further strengthen the monitoring of gut colonized hv-CRKP and research the potential mechanism of infection caused by gut colonized hv-CRKP.Keywords: K. pneumoniae, intestinal colonization, hypervirulent, genomic characterization, carbapenemase

Hongtao Cheng,1,2,&ast; Xingwen Deng,3,&ast; Jieyao Li,4,&ast; Yonglan Tang,1,2 Shiqi Yuan,5 Xiaxuan Huang,5 Zichen Wang,1 Fuling Zhou,6 Jun Lyu1,7 1Department of Clinical Research, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 2School of Nursing, Jinan University, Guangzhou, People’s Republic of China; 3Department of Medical Information, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 4Department of Intensive Care Unit, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 5Department of Neurology, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 6Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 7Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Lyu, Department of Clinical Research, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, People’s Republic of China, Email lyujun2020@jnu.edu.cn Fuling Zhou, Department of Hematology, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuhan, 430071, People’s Republic of China, Email zhoufuling@whu.edu.cnBackground: Dysphagia is common in elderly patients with dementia and is one of the common clinical geriatric syndromes. It imposes a heavy burden on patients and their caregivers and is becoming an important public health problem. This study examined the association between dysphagia in older dementia patients in the ICU and the subsequent adverse health outcomes they experience.Patients and Methods: A retrospective analysis of adults (≥ 65 years) with dementia in ICUs of a Boston tertiary academic medical center was conducted. Using the International Classification of Diseases’ Ninth and Tenth Revisions, dementia patients were identified. The study cohort comprised 1009 patients, median age 84.82 years, 56.6% female, predominantly White (72.9%). Patients were grouped based on swallowing function: dysphagia (n=282) and no-dysphagia (n=727). Dysphagia was identified via positive bedside swallowing screening. Primary outcomes were 90- and 180-day mortality, secondary outcomes included aspiration pneumonia, pressure injury, and delirium. Cohort characteristics were compared using the Wilcoxon rank-sum and chi-square tests. Dysphagia and outcomes correlations were examined via Kaplan-Meier survival analysis, Cox proportional-hazards regression models, logistic regression models, and subgroup analysis.Results: After adjusting for covariates, the results from multivariate Cox proportional-hazards regression indicated that dysphagia was significantly associated with increased 90-day (HR=1.36, 95% CI=1.07– 1.73, E-value=1.78) and 180-day (HR=1.47, 95% CI=1.18– 1.82, E-value=1.94) mortality; the multifactorial logistic regression results indicated that dysphagia was associated with significant increases in pressure injury (OR=1.58, 95% CI=1.11– 2.23, E-value=1.83) and aspiration pneumonia occurrence (OR=4.04, 95% CI=2.72– 6.01, E-value=7.54), but was not significantly associated with delirium prevalence (OR=1.27, 95% CI=0.93– 1.74).Conclusion: Dysphagia is likely to increase the risk of adverse health outcomes in older adults with dementia in ICU, and these adverse outcomes mostly include 90- and 180-day mortality, aspiration pneumonia, and pressure injury.Keywords: dysphagia, dementia, older adults, mortality, intensive care unit, delirium

Yun Lan,1,&ast; Xuemei Ling,1,2,&ast; Xizi Deng,1,&ast; Yaqing Lin,1 Junbin Li,1,2 Liya Li,1 Ruiying He,1 Weiping Cai,1 Feng Li,1,&ast; Linghua Li,1 Fengyu Hu1 1Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, 510440, People’s Republic of China; 2Guangdong Center for Diagnosis and Treatment of AIDS, Guangzhou, 510060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fengyu Hu; Linghua Li, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, No. 8 Huaying Road, Baiyun District, Guangzhou, 510440, People’s Republic of China, Email gz8hhfy@126.com; llheliza@126.comBackground: Antiretroviral therapy (ART) efficiently reduces the morbidities and mortalities caused by HIV-1 infection and prevents the HIV epidemic. However, virologic failure (VF) occurs in some patients receiving ART experience, especially increases in those patients with intermittent or persistent low-level viremia (LLV). The presence of drug resistance mutations (DRMs) in LLV was a strong predictor of subsequent VF. The data on drug resistance (DR) or DRMs for HIV-1 infections at low-level viral load (LLVL) are limited in China.Objective: To monitor the prevalence of HIV-1 drug resistance and to evaluate the risk factors associated with drug resistance in LLVL HIV-1 infections during ART in Guangdong, China.Methods: Plasma samples with LLVL during ART in Guangdong Province between Jan 2011 and Dec 2022 were subjected to a modified reverse-transcription PCR with a pre-step of virus concentration by ultracentrifugation before extraction and the Sanger sequencing. Then, the genotypic resistance test was performed and DR was analyzed by the Stanford HIVDB program. Finally, DR-associated factors were identified by logistic regression analysis.Results: We found that CRF01_AE (53.57%) and CRF07_BC (25.07%) were the dominant HIV-1 genotypes in LLVL in Guangdong between 2011 and 2022 but that the percentage of CRF01_AE showed a trend of decrease over time. M46 (1.49%), M184 (30.91%), and K103 (21.46%) were the dominant PI-, NRTI-, and NNRTI-associated mutations, respectively. The total DR rate was 47.06%. Specifically, PI (3.71%) showed a significantly lower DR rate than NNRTI (40.74%) and NRTI (34.14%). Duration of ART, initial ART regimen, ethnicity, and WHO clinical stages were associated with DR.Conclusion: The drug resistance rate among the LLVL during ART in Guangdong, China is high. The risk factors associated with HIV drug resistance should be seriously considered for better control.Keywords: HIV, low-level viral load, drug resistance mutation, drug resistance

Xin Deng,1,&ast; Xin Zhong,1,&ast; Bin Nie,2 Ruochen Wang,1 Hao Lu,1 Lei Ge,1 Juying Qian,1 Jianying Ma,1 Junbo Ge1 1Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, National Clinical Research Center for Interventional Medicine, Shanghai, People’s Republic of China; 2The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junbo Ge; Jianying Ma, Email jbge@zs-hospital.sh.cn; ma.jianying@zs-hospital.sh.cnBackground: The septal collateral channel (CC) is the preferred channel in retrograde percutaneous coronary intervention (PCI) for chronic total occlusion (CTO). However, reports on the utilization of the ipsilateral septal CC are limited.Objective: To evaluate the feasibility and safety of the ipsilateral septal CC in retrograde CTO PCI.Methods: Twenty-five patients with successful wire CC tracking via the ipsilateral septal CC in retrograde CTO PCI were retrospectively analyzed. All procedures were performed by experienced CTO operators. Procedures were divided into the left descending coronary artery (LAD)-septal-LAD group and the LAD-septal-left circumflex coronary artery (LCX) group. Procedural complications and in-hospital outcomes were ascertained.Results: Both groups were similar with respect to risk factors and angiographic characteristics of the CTO, except for the collateral tortuosity (86.7% vs 20%, p=0.002). The success rate of microcatheter CC tracking was 96%. Both technical success and procedural success rates were 92%. Procedural complications were found in one case (septal perforation, 4%), which happened in the LAD-septal-LAD group (p=0.250). One postoperative adverse event (Q-wave myocardial infarction, 4%) was observed before discharge.Conclusion: The retrograde approach via the ipsilateral septal CC was feasible, with high success rates and acceptable complications, in the hands of experienced operators.Keywords: percutaneous coronary interventions, chronic total occlusions, ipsilateral septal collateral, left coronary artery

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

Min Sun,1,2 Lei Gao,1 Hongmei Bai,1 Weiwei Hu,1 Xiaofang Zhang,1 Jin Xiao,1 Xiangliang Deng,1 Hongmei Tao,1 Ping Ge,2 Yuhong Qin,1,&ast; Dongying Zhang1,&ast; 1Department of Cardiovascular Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Health Management Center, The First Branch of the Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongying Zhang; Yuhong Qin, Tel +86-23-13608398395 ; +86-23-13068357151, Email zhangdongying@cqmu.edu.cn; 798213639@qq.comPurpose: To investigate the association of visceral fat with arterial stiffness of heart failure patients with preserved ejection fraction (HFpEF) and to evaluate the extent to which this association is mediated by blood pressure (BP).Patients and Methods: This cross-sectional descriptive study (clinicaltrials.gov identifier: NCT04535726) recruited 94 patients with HFpEF totally from October to December 2020. The obesity-related measurements included visceral fat area (VFA), body mass index (BMI), waist circumference (WC), hip circumference (HC), waist–hip ratio (WC/HC), abdominal circumference (AC), body fat mass and fat percentage. Brachial-ankle pulse wave velocity (baPWV) was used to estimate the degree of arterial stiffness. Mediation analysis was performed to reveal whether the effect of visceral fat area on arterial stiffness can be mediated by BP in patients with HFpEF and the extent to which this association was mediated by BP.Results: About 93.6% of HFpEF patients were accompanied with abdominal obesity. Patients in baPWV ≥ 1800cm/s group were older, with a higher incidence of type 2 diabetes mellitus (T2DM), hypertension and abdominal obesity. VFA, systolic BP (SBP), diastolic BP (DBP) and pulse pressure (PP) were correlated with baPWV in total group. Adjusted for age ≥ 75 years old, gender, smoking, T2DM, calcium channel blocker and statins, the mediation effect of systolic SBP and PP on the VFA-baPWV association were 53.3% (indirect effect was 2.28, 95% CI 0.62– 4.73) and 48.4% (indirect effect was 2.07, 95% CI 0.51– 4.38), respectively. DBP failed to mediate the association between VFA and baPWV (indirect effect was 0.50, 95% CI − 0.41– 2.14).Conclusion: The association of visceral fat with baPWV in HFpEF patients may be partly accounted for SBP or PP. Elevated SBP and PP might be important potential targets for preventing arterial stiffness in HFpEF patients.Keywords: mediation analysis, blood pressure, visceral fat area, brachial-ankle pulse wave velocity, HFpEF

Li Ding,1,&ast; Xiaobin Deng,2,&ast; Kun Wang,1,&ast; Wentao Xia,1,&ast; Yang Zhang,1 Yan Zhang,1 Xianfeng Shao,1 Junqi Wang1 1Department of Urology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of China; 2Department of Urology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junqi Wang, Email wangjq_68@163.comIntroduction: Neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and lymphocyte/monocyte ratio (LMR) have been widely proposed to have predictive value for the patient prognosis of many malignancies, including bladder cancer. However, the predictive value of their combination in non-muscle-invasive bladder cancer (NMIBC) is unclear.Methods: Cases of NMIBC patients who underwent transurethral resection of the bladder tumor were recruited from two tertiary public medical centers. A systemic inflammatory marker (SIM) score was calculated based on comprehensive consideration of NLR, PLR, and LMR. Recurrence-free survival (RFS) and progression-free survival (PFS) were estimated by Kaplan-Meier analysis. The Log rank test was used to compare differences between the groups. Cox regression was used to screen risk factors affecting RFS and PFS. Nomogram models were established and validated, and patients were stratified based on the model scores.Results: The study dataset was grouped according to a 7:3 randomization, with the training cohort consisting of 292 cases and the validation cohort consisting of 124 cases. Cox regression analysis showed that SIM score is an independent predictor of RFS and PFS in NMIBC patients. The novel models were established based on the SIM score and other statistically significant clinicopathological features. The area under the curve (AUC) for predicting 1-, 2-, and 3-year RFS was 0.667, 0.689, and 0.713, respectively. The AUC for predicting 1-, 2-, and 3-year PFS was 0.807, 0.775, and 0.862, respectively. Based on the risk stratification, patients at high risk of recurrence and progression could be accurately identified. The established models were applied to the patient evaluation of the validation cohort, which proved the great performance of the novel models.Conclusion: The novel models based on the SIM score and clinicopathological characteristics can accurately predict the survival prognosis of NMIBC patients, and the models can be used by clinicians for individualized patient assessment and to assist in clinical decision-making.Keywords: systemic inflammatory markers, risk factor, bladder cancer, NMIBC, tumor recurrence, nomogram

Lingcan Tan,1 Hong Yu,1 Junyu Yan,2 Chunyuan Liu,3 Kun Xiao,4 Jin Yin,5 Yunxia Zuo,1 Tao Zhu,1 Xiaoqian Deng1 1Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of Anesthesiology, Karamay Hospital of Integrated Traditional Chinese and Western Medicine, Karamay, People’s Republic of China; 3Department of Anesthesiology, Chongqing Liangping District People’s Hospital, Chongqing, 405200, People’s Republic of China; 4School of Information and Software Engineering, University of Electronic Science and Technology of China, Chengdu, 610054, People’s Republic of China; 5West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of ChinaCorrespondence: Xiaoqian Deng, Department of Anesthesiology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, People’s Republic of China, Email d_xiaoqian@163.comPurpose: The National Remote Emergency System for Malignant Hyperthermia (MH-NRES) is an applet in China, designed to help anesthesiologists manage MH crisis. However, there is limited information about encountered difficulties in dealing with MH among Chinese anesthesiologists. The purpose of the study was to explore the current competency and encountered difficulties in the management of MH, as a key first step for assessing the potential user needs to develop the MH-NRES.Methods: The hospitals of different levels in different provinces across China were invited to participate in an online survey from November to December 2021. Anesthesiologists completed the online questionnaire containing four sections including demographic information, knowledge, competency, and continuing education about MH.Results: A total of 1357 valid questionnaires were completed from anesthesiologists, most respondents (66.7%, n = 905) correctly answered the MH trigger drugs included volatile anesthetics and succinylcholine. However, most respondents (77.0%, n = 1045) did not know that the recommended initial dose of domestic dantrolene. Up to 83.9% (n = 1138) stated that their hospitals did not store dantrolene for MH emergency. More than half of respondents thought that it would take more than one hour to obtain dantrolene in emergency. Less work experiences, lower levels of hospital and educations and professional titles were associated with lower competency scores in managing MH. Only 31.0% (n = 936) reported that their hospital had ever conducted MH continuing education curricula. Scenario simulation is the training method that most interests the participants (79.0%, n = 1072) but a whopping 46.9% (n = 637) never received simulation.Conclusion: The study indicated that difficulty in obtaining dantrolene, lack of competency in management of MH, difficulty in obtaining professional help, and poor teamwork were the main problems of most anesthesiologists in face of MH.Keywords: malignant hyperthermia, questionnaire, competency, dantrolene, education

Haiyao Huang,1,&ast; Lili Gao,1,2,&ast; Xiaopeng Deng,1 Hanliang Fu3 1Department of Construction and Real Estate, School of Civil Engineering, Southeast University, Nanjing, People’s Republic of China; 2Department of Architecture and Civil Engineering, City University of Hong Kong, Hong Kong, People’s Republic of China; 3Laboratory of Neuromanagement in Engineering, Xi’an University of Architecture and Technology, Xi’an, 710055, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaopeng Deng, Department of Construction and Real Estate, School of Civil Engineering, Southeast University, Nanjing, People’s Republic of China, Email dxp@seu.edu.cnPurpose: In the field of construction, it has been shown that individuals with higher emotional intelligence may perform better on the job. However, it is still a question worth exploring about how emotional intelligence affects expatriate performance in international construction projects. Therefore, this study aimed to verify the relationship between expatriates’ emotional intelligence and expatriate performance and explore the mediating role of self-efficacy and psychological resilience.Methods: A cross-sectional study was conducted in June 2021. A non-probability sampling method was used to obtain data. A total of 315 Chinese construction expatriates in 67 countries and regions around the world were evaluated using four scales: the Wong and Law Emotional Intelligence Scale, the General Self-Efficacy Scale, the Connor-Davidson Resilience scale, and the Kraimer’s expatriate’s performance scale. The hypothesis model was tested using Partial Least Squares Structural Equation Modeling (PLS-SEM).Results: The results of the data analysis indicated that self-efficacy (βIndirect effect = 0.175, p< 0.05) and psychological resilience (βIndirect effect = 0.112, p< 0.05) served as fully mediating variables (β Direct effect = 0.177, p=0.101), suggesting a way to explain how emotional intelligence affect the performance of contractor expatriates. The findings also suggest that self-efficacy and psychological resilience also play continuous and multiple mediating roles (βIndirect effect = 0.143, p< 0.05) between emotional intelligence and expatriate performance.Conclusion: This study attempted to investigate the mechanism of emotional intelligence’s influence on expatriate performance from the perspective of individual psychological resources. The results of the study suggest that the emotional intelligence of expatriates may bring about an increase in performance levels by improving self-efficacy and psychological resilience levels. This provides a practical way to improve the performance of expatriates and a new management perspective for human resource management in international construction projects.Keywords: expatriate performance, emotional intelligence, psychological resilience, self-efficacy, sequential mediation model

Lingcan Tan,1,&ast; Yi Teng,1,&ast; Hong Yu,1 Chunyuan Liu,2 Kun Xiao,3 Jin Yin,4 Yunxia Zuo,1 Tao Zhu,1 Xiaoqian Deng1 1Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of Anesthesiology, Chongqing Liangping District People’s Hospital, Chongqing, 405200, People’s Republic of China; 3School of Information and Software Engineering, University of Electronic Science and Technology of China, Chengdu, 610054, People’s Republic of China; 4West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoqian Deng, Department of Anesthesiology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, People’s Republic of China, Tel +86 885423592, Email d_xiaoqian@163.comPurpose: Malignant hyperthermia (MH) is a rare but fatal pharmacogenetic disorder, triggered by inhalational anesthetics or succinylcholine. Since the first nonprofit academic organization China Malignant Hyperthermia Emergency Assistance WeChat-based Group (CMHEA Group) was established in 2015, they have actively participated in the diagnosis and treatment of MH patients. Based on the CMHEA Group, the aim of the study was to retrospectively analyze the characteristics of suspected MH in China from 2015 to 2020.Methods: We conducted a retrospective analysis of the suspected MH patients from 2015 to 2020, for analyzing the current clinical diagnosis, treatment and prognosis of MH in China.Results: A total of 58 suspected MH cases occurred from 2015 to 2020, of these, 36 cases were collected with detailed data. The MH clinical grading score of 36 patients ranged from 33 to 73, with a median of 55. Abnormal hyperthermia and hypercarbia were the most common early signs of MH. Four patients were confirmed carrying six different potential MH-causative mutations. Of the total 58 cases, 14 patients (24.1%) received dantrolene and the whole mortality rate was 53.4%. Compared to the patients not receiving dantrolene treatment, the survival rate of patients receiving dantrolene treatment was significantly higher than that of patients not receiving dantrolene (78.6% vs 36.4%, p = 0.007).Conclusion: The current main diagnostic methods of suspected MH in China are still clinical diagnosis. Hence, it is critical to keep dantrolene for immediate accessibility with the introduction of domestic dantrolene to China. The WeChat group model has played an important but limited role in quick diagnosis and treatment of MH.Keywords: malignant hyperthermia, dantrolene, mortality, China

Yiran Zhang,1– 4,&ast; Hongzhi Hu,5,&ast; Xiangtian Deng,6,&ast; Qingcheng Song,2 Xin Xing,2,3 Weijian Liu,5 Yingze Zhang1– 3 1School of Medicine, Nankai University, Tianjin, 300071, People’s Republic of China; 2Department of Orthopaedic Surgery, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050051, People’s Republic of China; 3NHC Key Laboratory of Intelligent Orthopaedic Equipment, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 4HeBei Ex&Invivo Biotechnology Co. Ltd, Shijiazhuang, Hebei, 050051, People’s Republic of China; 5Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 6Orthopaedics Research Institute, Department of Orthopaedics, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingze Zhang; Weijian Liu, Email yzling_liu@163.com; xh_liuweijian@hust.edu.cnBackground: Although chemodynamic therapy (CDT) has attracted enormous attention in anti-tumor studies for converting endogenous hydrogen peroxide (H2O2) into toxic hydroxyl radicals (•OH) by Fenton-type reaction, the treating effects of using CDT alone is still unsatisfying. Recently, glucose oxidase (GOx) was reported to be co-delivered with Fenton agent for synergistic starvation therapy (ST) and CDT. However, the overexpressed glutathione (GSH) and hypoxia in tumor microenvironment (TME) restrict the therapeutic efficacy of ST/CDT.Methods and Results: In this work, a novel nanoplatform composed of GOx plus Fenton agent (Cu2+) encapsulated core and metformin (MET)-loaded manganese dioxide nanosheets (MNSs) shell was prepared and further functionalized by arginine-glycine-aspartate (RGD). With the RGD-mediated affinity with cancer cells, the nanocomposite (GOx-CuCaP@MNSs-MET@PEG-RGD, GCMMR) could accomplish targeting delivery and TME-activated release of cargos. The intracellular GSH was depleted by MnO2/Cu2+ and abundant H2O2 was generated along with the GOx-induced glucose deprivation, which process was further enhanced by MET-mediated hypoxia relief via inhibiting mitochondria-associated respiration. Subsequently generated •OH from Cu+-mediated Fenton-like reaction exerts severe intracellular oxidative stress and cause apoptosis. Moreover, significant inhibition of tumor growth was detected in a subcutaneous xenograft model of osteosarcoma (OS) after GCMMR treatment.Conclusion: The excellent therapeutic efficacy and biosafety of the nanoplatform were confirmed both in vitro and in vivo. Collectively, this study provides an appealing strategy with catalytic cascade enhancement on targeted ST/CDT for cancer treatment, especially for hypoxic solid tumors.Graphical Abstract: Keywords: chemodynamic therapy, starvation therapy, glucose oxidase, Fenton reaction, biomineralization, metformin

Xiaoqian Deng,1 Junyu Yan,2 Shaungwen Wang,3 Yifan Li,3 Yun Shi4 1Department of Anesthesiology, West China Hospital, Sichuan University and The Research Units of West China (2018RU012), Chinese Academy of Medical Sciences, Chengdu, People’s Republic of China; 2Department of Anesthesiology, Karamay Hospital of Integrated Traditional Chinese and Western Medicine, Karamay, People’s Republic of China; 3West China School of Medicine, Sichuan University, Chengdu, People’s Republic of China; 4Department of Anesthesiology, Children’s Hospital of Fudan University, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Yun Shi, Department of Anesthesiology, Children’s Hospital of Fudan University, Fudan University, 399 Wanyuan Road, Minhang District, Shanghai, 201102, People’s Republic of China, Email imulashi@yahoo.comPurpose: Inadvertent intraoperative hypothermia (IIH) is generally associated with several postoperative complications. Inspite of the existing guidelines, the global incidence of IIH remains unacceptably high. Understanding the conditions that influence temperature management is critical for developing future interventions to improve the postoperative patient outcomes. This study aimed to identify the major factors that hinder the implementation of IIH prevention practices.Methods: Through a literature research, pilot small-sample investigation, and expert suggestions, 11 factors that may hinder the implementation of IIH prevention practices were identified. A questionnaire was developed, and each question was used to assess each factor. After approval by the Research Ethics Board, the questionnaires were sent to the staff anaesthesiologists at two academic hospitals via WeChat. Each answer was coded according to the degree to which the factor was affected, as anticipated. Finally, the answers were analysed based on the 80/20 rule to identify the major barriers to effective temperature management.Results: We included 195 participants. Knowledge, memory, attention and decision processes, beliefs about consequences, and environmental context and resources were the major factors, with cumulative composition ratios of 24%, 43.4%, 57.7%, and 70.7%, respectively. Meanwhile, behavioural regulation and social influence were the secondary factors, with cumulative composition ratios of 80.4% and 87.5%, respectively. Reinforcement, confidence in capacity, duty realisation, skills, and intention were the general factors with cumulative composition ratios of 94.3%, 99.8%, 100%, 100%, and 100%, respectively.Conclusion: Four factors–knowledge, memory, attention and decision process, beliefs about consequences, and environmental context and resources–were the major factors that influence the effective hypothermia prevention practice.Relevance to Clinical Practice: These major factors will be used in further studies as a basis to develop the corresponding solutions and improve the patient outcomes in clinical practice.Keywords: intraoperative hypothermia, body temperature, temperature management, 80/20 rule

Rui Ma,1 Xiao-long Deng,2 Qi-qi-ge Aleteng,1 Lei Li,1 Jun Zhu3 1Department of Endocrinology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830054, People’s Republic of China; 2Department of Endocrinology, Shunde Hospital of Southern Medical University, Foshan, Guangdong, 528300, People’s Republic of China; 3Department of Endocrinology, People’s Hospital of Shenzhen Baoan District, Shenzhen, Guangdong, 518101, People’s Republic of ChinaCorrespondence: Jun Zhu, Department of Endocrinology, People’s Hospital of Shenzhen Baoan District, Shenzhen, 518101, Guangdong, People’s Republic of China, Tel +86 13899981212, Email zhujun_dr@outlook.comObjective: In this study, transcriptome sequencing was performed on patients with type 2 diabetes mellitus treated with different prognosis to explore the differential level genes of different hypoglycemic effects of sitagliptin.Methods: Patients with newly diagnosed T2DM (within six months of diagnosis) were selected as the study subjects. Patients were given sitagliptin 100 mg once a day orally. After 12 weeks of regular drug therapy, the reduction in glycated hemoglobin was compared before and after drug administration. The patients were then divided into two groups: the significantly effective group (M) and the less effective group (N). High-throughput sequencing of the transcriptome was conducted to detect the differential expression levels of genes in peripheral blood mononuclear cells. Expanded sample size validation of the candidate differential genes was conducted using reverse transcription-polymerase chain reaction (RT-PCR).Results: After 12 weeks of treatment with sitagliptin, high-throughput sequencing of the transcriptome found that expression of the following genes was different when comparing the significantly effective group (M) and the less effective group (N): ghrelin (GHRL), insulin-like growth factor-1 receptor (IGF1R), mitogen-activated protein kinase-3 (MAPK3), phosphatidylinositol-4,5-bisphosphonate 3-kinase, catalytic subunit delta (PIK3CD), and the suppressor of cytokine signaling-3 (SOCS3). The validation results of RT-PCR showed that, in the significantly effective group (M), the expression of IGF1R was significantly increased (P = 0.034), the expression of MAPK3 was significantly reduced (P = 0.002), and the expression of SOCS3 was also significantly reduced (P < 0.001).Conclusion: There was a significant difference in gene level between patients with significant hypoglycemic effect and patients with poor hypoglycemic effect, and the expression of IGF1R increased and the expression of MAPK3 and SOCS3 decreased.Keywords: sitagliptin, hypoglycemic effects, transcriptome sequencing, RT-PCR, SOCS3

Yanli Li,1,&ast; Min Yi,1,&ast; Xiaoyi Deng,1 Wangen Li,1 Yimei Chen,2 Xiaodan Zhang1 1Department of Endocrinology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Health Examination Department, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaodan Zhang, Department of Endocrinology, The Second Affiliated Hospital of Guangzhou Medical University, 250 East Changgang Road, Haizhu District, Guangzhou, 510260, People’s Republic of China, Email sysuzhangxd@163.comBackground: Diabetes mellitus (DM) and thyroid dysfunction (TD) are two closely associated disorders. The objective of the present study was to investigate the thyroid status and the relationships between thyroid hormones, diabetic complications and metabolic parameters in hospitalized patients with newly diagnosed type 2 DM (T2DM).Methods: This was an observational cross-sectional study, conducting on 340 patients with newly diagnosed T2DM who were admitted to ward of endocrinology department and 120 matched individuals without diabetes. Anthropometric, clinical and biochemical data were collected. Spearman correlation coefficients were calculated to evaluate the correlations between thyroid hormones and other variables. Factors associated with diabetic nephropathy (DN) was analyzed with multivariate logistic regression.Results: Levels of free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) were significantly lower in patients with T2DM as compared to control group without diabetes. The prevalence of TD was 21.2% in patients with diabetes, higher than that in controls (4.2%). The low T3 syndrome was the most frequent TD, shown in 14.7% of patients. The presence of diabetic complications DN, diabetic ketosis or ketoacidosis), metabolic and demographic factors, including age, glycemic control and insulin resistance were factors significantly associated with levels of thyroid hormones. FT3 level was inversely correlated with the level of urinary total protein (mg/24h) and the presence of DN. Multivariate analysis indicated low FT3 level as a strong independent risk factor (OR = 0.364, P = 0.001) for DN.Conclusion: TD is not rarely seen in hospitalized patients with newly diagnosed T2DM. Diabetic complications and diabetes-related metabolic and demographic factors are related to thyroid hormone levels. Decreased FT3 is strongly correlated with the presence of DN.Keywords: type 2 diabetes mellitus, thyroid dysfunction, thyroid hormones, diabetic complication, diabetic nephropathy

Jiangbo Ren,1,2,&ast; Anli Ren,1,2,&ast; Xizhi Deng,2 Zhengrong Huang,1 Ziyu Jiang,1 Zhi Li,2 Yan Gong1,3 1Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Department of Ophthalmology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 3Human Genetics Resource Preservation Center of Wuhan University, Wuhan University, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Gong; Zhi Li, Tel +86 27 6781 1461; +86 27 6781 2622, Fax +86 27 6781 1471; +86 27 6781 3133, Email yan.gong@whu.edu.cn; 1103945483@qq.comAbstract: Age-related macular degeneration (AMD) is a blinding eye disease, whose incidence strongly increases with ages. The etiology of AMD is complex, including aging, abnormal lipid metabolism, chronic inflammation and oxidative stress. Long-chain polyunsaturated fatty acids (LCPUFA) are essential for ocular structures and functions. This review summarizes the regulatory effects of LCPUFA on inflammation in AMD. LCPUFA are related to aging, autophagy and chronic inflammation. They are metabolized to pro- and anti-inflammatory metabolites by various enzymes. These metabolites stimulate inflammation in response to oxidative stress, causing innate and acquired immune responses. This review also discusses the possible clinical applications, which provided novel targets for the prevention and treatment of AMD and other age-related diseases.Keywords: inflammation, long-chain polyunsaturated fatty acids, age-related macular degeneration

Huan Long,1,2,&ast; Xiaojuan Qin,3,&ast; Rui Xu,1,2 Chunlei Mei,4 Zhiyong Xiong,5 Xuan Deng,1 Kaiyao Huang,1,2 Huageng Liang5 1Key Laboratory of Algal Biology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei Province, 430072, People’s Republic of China; 2University of Chinese Academy of Sciences, Beijing, 100049, People’s Republic of China; 3Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 4Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 5Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kaiyao Huang; Huageng Liang Email leonard19800318@hust.edu.cn; huangky@ihb.ac.cnIntroduction: Ultrasonic molecular imaging (UMI) technology has attracted increasing interest because of its low cost and capability to evaluate changes rapidly and noninvasively at the cellular and molecular levels. The key material of this technology is ultrasound-responsive gas vesicles (GVs). GVs synthesized by conventional chemical methods have several limitations, such as high costs, low yields, and complex production processes. In comparison, biosynthesized GVs have the advantages of high stability, a low risk of toxicity, genetic engineering characterization, easy post modification and drug loading potential. However, translational studies of their biosynthesis are still in their infancy; in particular, the duration of GVs in the circulatory system is essential for the usage of UMI in biomedicine and the clinic.Results: Here, we report novel GVs biosynthesized by the cyanobacterium Microcystis, which have a moderate size, a negative zeta potential, a rod-like morphology, and a protein-shelled gas-contained structure. These GVs without any chemical modifications could be detected in the mice circulatory system for more than 10 hours by clinically used ultrasound scanners. In particular, GVs can accumulate in tumors via the enhanced permeation and retention (EPR) effect 11 hours post-injection, and lasting at least 2 hours, which might be a potential aid for tumor diagnosis. Furthermore, pathological and hematological study suggested that GVs are safe for the host.Conclusion: We concluded that the GVs synthesized by Microcystis without any modifications have UMI potential for systemic evaluation as well as tumoral diagnosis after intravenous injection.Keywords: ultrasonic molecular imaging, gas vesicles, biosynthesis

Yongqiang Yang, Xiaole Li, Pengcheng Zhou, Xiaoyu Deng, Yingyi Wang, Qianqian Dang, Yingjuan Zheng, Daoke Yang Department of Radiotherapy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Yingjuan Zheng; Daoke YangDepartment of Radiotherapy, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, Henan Province, People’s Republic of ChinaTel +86-15738872856; +86-15903650068Email zdyfyzlyy@163.com; 15903650068@163.comPurpose: To analyze the effects of radiotherapy and its timing on the survival and safety of patients with newly diagnosed distant metastatic NPC in non-high-incidence areas.Patients and Methods: We retrospectively analyzed 94 newly diagnosed NPC patients with distant metastatic admitted to our hospital from January 2011 to June 2018. They were divided into three groups: no radiotherapy group received chemotherapy alone, early radiotherapy group was combined with radiotherapy during 1 to 3 cycles of chemotherapy, and late radiotherapy group was combined with radiotherapy after 4– 6 cycles of chemotherapy were effective. The efficacy and side effects of the three groups were compared, and the prognostic factors were analyzed.Results: The 6-month, 1-year and 2-year PFS were 53.6%, 14.3% and 3.6% in no radiotherapy group, 71.0%, 38.7% and 19.4% in early radiotherapy group, 88.6%, 48.6% and 22.9% in late radiotherapy group; the radiotherapy groups were better than the no radiotherapy group, and the difference was statistically significant (P < 0.017). The 1-year, 2-year and 3-year OS were 75.0%, 32.1% and 0 in no radiotherapy group, 77.4%, 54.8% and 12.9% in early radiotherapy group, 85.7%, 71.4% and 31.4% in late radiotherapy group; the radiotherapy groups were better than the no radiotherapy group, and the differences were statistically significant (P < 0.017). There was no significant difference in OS and PFS between the two radiotherapy groups. Univariate and multivariate analysis showed that HBV (P = 0.031), number of metastases (P = 0.002), liver metastases (P = 0.038), radiotherapy (P < 0.001) and treatment response (P = 0.011) were related to OS. There was no significant difference in the incidence of adverse events (P > 0.017).Conclusion: Early and late combined radiotherapy had similar clinical efficacy and both prolonged PFS and OS for patients with newly diagnosed distant metastatic NPC in non-high-risk areas. If chemotherapy response is expected to be poor, radiotherapy can be received early.Keywords: radiotherapy, nasopharyngeal carcinoma, metastasis, non-high-incidence area, prognosis

Juan Jiang,1,2 Xia Wang,3 Jian He,3 Donglei Liao,3 Xiaolu Deng3 1Department of Respiratory Medicine (National Key Clinical Specialty), Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Hunan Provincial Clinical Research Center for Respiratory Diseases, Changsha, People’s Republic of China; 3Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, People’s Republic of ChinaCorrespondence: Xiaolu DengDepartment of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of ChinaTel +86 13786113654Email dengxiaolu1019@163.comBackground: Pneumocystis jirovecii pneumonia (PCP) is a serious opportunistic infection in immunocompromised children. Real-time polymerase chain reaction (PCR) is widely used for the diagnosis of PCP due to its good accuracy. However, the diagnostic performance of multiplex real-time PCR on sputum in children with PCP has never been explored.Methods: Medical records of 63 consecutive pediatric patients were analyzed retrospectively, including 13 cases with PCP and 50 with non-PCP pneumonia. Pneumocystis jirovecii (P. jirovecii) and other co-pathogens detected by multiplex real-time PCR in sputum samples were summarized. Using clinical composite diagnosis as the reference standard, we further compared the diagnostic performance of multiplex real-time PCR to combined serological markers (1,3)-β-D-glucan plus lactate dehydrogenase. Additionally, modifications of antimicrobial treatment for pediatric PCP patients after the report of multiplex real-time PCR results were reviewed.Results: In children with PCP, nonproductive cough and shortness of breath were more common, lymphocyte count in peripheral blood was markedly lower, and serum levels of (1,3)-β-D-glucan and lactate dehydrogenase were much higher than non-PCP group. Multiplex real-time PCR reached a sensitivity of 100% in diagnosing PCP, which was better than serum (1,3)-β-D-glucan plus lactate dehydrogenase (76.9%). Its specificity (98.0%) significantly surpassed serum (1,3)-β-D-glucan plus lactate dehydrogenase (84.4%). Furthermore, multiplex real-time PCR showed a good performance in identifying co-pathogens in sputum of pediatric PCP patients. Cytomegalovirus, Epstein–Barr virus and Streptococcus pneumoniae were the most common co-pathogens in these patients. Initial antimicrobial treatment was modified in 76.9% of children with PCP after the report of PCR results.Conclusion: Multiplex real-time PCR on sputum is a diagnostic tool with good performance for the identification of P. jirovecii as well as co-pathogens in children with PCP. Sputum may be an alternative to bronchoalveolar lavage fluid for PCR assay in children when bronchoscopic examination is not feasible.Keywords: immunocompromised population, children, Pneumocystis jirovecii pneumonia, multiplex real-time polymerase chain reaction, sputum

Yun Lan,&ast; Xizi Deng,&ast; Linghua Li, Weiping Cai, Junbin Li, Xiaoli Cai, Feng Li, Fengyu Hu, Chunliang Lei, Xiaoping Tang Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, 510030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunliang Lei; Xiaoping TangGuangzhou Eighth People’s Hospital, Guangzhou Medical University, 627 Dongfeng East Road, Yuexiu District, Guangzhou, 510030, People’s Republic of ChinaEmail gz8hlcl@126.com; tangxp@gzhmu.edu.cnBackground: Guangdong, located in South China, is one of the areas heavily affected by HIV-1 in China. The transmission of HIV-1 among men who have sex with men (MSM) has gradually been increasing in Guangdong.Objective: To investigate the characteristics of the HIV-1 drug resistance, and genetic transmission networks in MSM with antiretroviral therapy (ART) failure from 2014 to 2019 in Guangdong.Methods: HIV-1 pol gene sequences were amplified. An online subtyping tool was used to determine the genotype, and a maximum likelihood phylogenetic tree was reconstructed to confirm the genotype results. The Stanford University HIV Drug Resistance Database was used to analyse the sequences of drug resistance mutations (DRMs) and drug resistance profiles. A pairwise Tamura-Nei 93 genetic distance-based method was used to analyse the genetic transmission networks.Results: Of 393 sequences isolated from HIV-infected MSM with ART failure, CRF01_AE (47.3%), CRF07_BC (21.4%) and CRF55_01B (21.4%) were the top three strains. 55.2% individuals harboured NRTI DRMs, whereas 67.4% carried NNRTI DRMs. 96.8% cases harboured mutations resistance to NRTIs or NNRTIs at high-level. The most common DRMs were M184I/V (42.2%), followed by V179D/E (37.9%) and K65R (27.2%). Of the subtype B sequences, no sequence fell into a cluster. Of the CRF01_AE, CRF55_01B, and CRF59_01B sequences, 14.5%, 61.9%, and 33.3% fell into clusters, respectively. Of the CRF07_BC sequences, 39.3% fell into clusters. The majority of MSM in transmission networks were concentrated at age below 35 years old, with multiple links. Moreover, approximately 54.8% of MSM had more than 2 potential transmission partners.Conclusion: Drug resistance mutations more frequently occurred in NNRTIs among MSM with ART failure in Guangdong Province. Transmission network analysis revealed a complex transmission pattern, and more attention should be given to younger HIV-1-infected MSM with multiple links.Keywords: HIV-1, drug resistance, genetic transmission networks, MSM

Ganlu Ouyang,1 Xibiao Yang,2 Xiangbing Deng,3 Wenjian Meng,3 Yongyang Yu,3 Bing Wu,2 Dan Jiang,4 Pei Shu,1 Ziqiang Wang,3 Jin Yao,2 Xin Wang1 1Department of Radiation Oncology/Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of Radiology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 3Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 4Department of Pathology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of ChinaCorrespondence: Xin WangDepartment of Radiation Oncology/Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, No. 37 of Wainan Guoxue Lane, Wuhou District, Chengdu, 610041, People’s Republic of ChinaTel +86 18980602291Email wangxin213@sina.comPurpose: To investigate the potential value of magnetic resonance imaging (MRI) in predicting response relevance to total neoadjuvant treatment (TNT) in locally advanced rectal cancer.Methods: We analyzed MRI of 71 patients underwent TNT from 2015 to 2017 retrospectively. We categorized the response of TNT as CR (complete response) vs non-CR, and high vs moderate vs low sensitivity. Logistic regression analysis was used to identify the best predictors of response. Diagnostic performance was assessed using receiver operating characteristic curve analysis.Results: Post-ICT (induction chemotherapy) ∆TL (tumor length), post-CRT (concurrent chemoradiotherapy) ∆LNN (the numbers of lymph node metastases), post-CCT (consolidation chemotherapy) ∆SDWI (maximum cross-sectional area of tumor on diffusion-weighted imaging), post-CCT ADCT (the mean apparent diffusion coefficient values of tumor) and post-CCT ∆LNV (volume of lymph node) were the best CR predictors. Post-ICT ∆TL, post-CRT EMVI (extramural vascular invasion) and post-CCT ∆ST2 (S on T2-weight) were the best significant factors for high sensitivity.Conclusion: Post-ICT ∆TL may be an early predictor of CR and high sensitivity to TNT. Dynamic analysis based on MRI between baseline and post-CCT could provide the most valuable prediction of CR. The grouping modality of CR vs non-CR may be more suitable for treatment response prediction than high vs moderate vs low sensitivity.Keywords: rectal cancer, total neoadjuvant treatment, MRI, response, TRG

Xingyue He,1 Xin Luo,2 Junjun Dong,1 Xing Deng,1 Feng Liu,1,2 Guanghui Wei1,2 1Department of Urology, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, People’s Republic of China; 2Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering; Chongqing Key Laboratory of Pediatrics, Chongqing, People’s Republic of ChinaCorrespondence: Feng Liu; Guanghui WeiDepartment of Urology, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, 136, Zhongshan 2nd Road, Yuzhong District, Chongqing, 400014, People’s Republic of ChinaTel +8613983693965; +8613883617398Email liuu_ff@163.com; u806806@cqmu.edu.cnPurpose: Although the long non-coding RNA (lncRNA) X inactive-specific transcript (XIST) has been reported to have an anti-tumor effect in multiple malignant tumors, its role in Wilms tumor (WT) progression has not been characterized. Thus, we investigated the underlying mechanism by which XIST regulates WT progression.Patients and Methods: We performed microarray analysis and real-time quantitative PCR (RT-qPCR) to detect the expression levels of XIST lncRNA, microRNA-194-5p (miR-194-5p), and YAP (yes-associated protein in Hippo pathway) in tumor and matched adjacent normal tissues and blood collected from 49 WT patients. We also conducted bioinformatics analyses to identify differentially expressed genes. We measured the effects of XIST overexpression and knockdown on cell proliferation, apoptosis, migration, and invasion, and its association with the miR-194-5p/YAP pathway in the rhabdoid G401cell line using flow cytometry, transwell assays, immunohistochemistry, Western blot analysis, and the dual luciferase reporter gene assay.Results: We found that XIST lncRNA levels were increased in blood and tissue samples of WT patients, and this upregulation was significantly correlated with TNM staging and shorter survival time. Notably, we found that XIST upregulation correlated with miR-194-5p downregulation and YAP upregulation in WT tissues, suggesting that XIST regulates the miR-194-5p/YAP pathway. Conversely, XIST downregulation inhibited WT cell proliferation, migration, and invasion and induced apoptosis. Our study revealed the oncogenic role of the lncRNA XIST in WT and demonstrated its role as a competitive endogenous RNA that regulates the miR-194-5p/YAP pathway.Conclusion: Our study demonstrates XIST’s potential as a clinical prognostic biomarker and therapeutic target for WT.Keywords: lncRNA, XIST, Wilms tumor, YAP

Wenjuan Feng,1,2 Longyun Nie,3 Xiaoyu Wang,4 Fang Yang,1 Pan Pan,5 Xiaohui Deng1 1Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 2Department of Reproductive Medicine, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250013, People’s Republic of China; 3Department of Obstetrics and Gynecology, Shenzhen University General Hospital, Shenzhen, Guangdong, 518055, People’s Republic of China; 4Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Beijing, 100730, People’s Republic of China; 5Department of Pathology, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250013, People’s Republic of ChinaCorrespondence: Xiaohui Deng Tel +86 185 60082026Email dxh@sdu.edu.cnPurpose: This study aimed to assess the efficacy of vaginally versus orally administered estradiol (E2) and dydrogesterone (DG) on the proliferative and secretory transformation of endometrium in patients with premature ovarian failure (POF) and preparing for assisted reproductive technology.Methods: Twenty patients with POF who were awaiting oocyte donation were included in the study; they were randomly assigned to two groups to receive E2 and DG either orally or vaginally. Treatment efficacy was compared between the two groups regarding blood E2 concentrations, endometrial thickness, histology using hematoxylin and eosin staining, immunohistochemical analysis of ER expression, and PR and pinopodes morphology using scanning electron microscopy.Results: E2 concentrations differed significantly between oral and vaginal E2 and DG administration for 14 days (82.3 vs 1015.6 pg/mL; P < 0.001) and 21 days (85.0 vs 809.8 pg/mL; P < 0.001). Endometrial thickening was more pronounced in the vaginal treatment group, and also ER staining was stronger on days 14 and 21 in the vaginal treatment group. PR staining in the endometrium appeared more intense in the oral treatment group, which was, however, not significant. The abundance of developing pinopodes was higher in the vaginal treatment group (P = 0.04).Conclusion: Vaginal administration of E2 and DG is more effective than oral administration regarding proliferative and secretory transformation of the endometrium in POF patients and preparing for assisted reproductive technology.Keywords: micronized estradiol, vaginal administration, oral administration, pinopodes, premature ovarian failure

Qihua Gu,1,2 Xinhao Deng,1,2 Zhao Li,1,2 Jing Wang,3 Chengping Hu,1,2 Shuhua Lei,1,2 Xiaoling Cai1,2 1Department of Respiratory Medicine, Xiangya Hospital Affiliated to Central South University, Changsha, Hunan Province, 410008, People’s Republic of China; 2Key Cite of National Clinical Research Center for Respiratory Disease, Changsha, Hunan Province, 410008, People’s Republic of China; 3Department of Pathology, Xiangya Hospital Affiliated to Central South University, Changsha, Hunan Province, 410008, People’s Republic of ChinaCorrespondence: Qihua Gu Tel +86 15973196025Email guqh06@163.comBackground: Simple signs of local pleural adhesion are often found in people during a physical examination. In the present study, we aimed to clarify whether the merely localized pleural adhesion was just caused by previous pleural inflammation or physiological variation.Materials and Methods: Chest X-ray image materials were collected to analyze the incidence of simple pleural adhesions. Moreover, the causes of these simple pleural adhesions were further analyzed using thoracoscopy under direct vision and biopsy data.Results: In all 2218 chest X-ray images, 68 cases were found to have pleural lesions (3.07%), including 15 cases of localized pleural adhesion only. Subsequently, we analyzed the characteristics of 70 cases of pleural lesions using thoracoscopy. In two lung cancer patients with pleural metastasis, we found an unusual pleural junction. This connective strip was smooth and free of inflammation, resembling the normal pleura.Conclusion: Some of these purely localized pleural adhesions might be attributed to previous inflammation. However, there was still at least a possibility that there must be a physiological pleural junction, which could be the cause of the purely localized pleural adhesion shown in the chest radiograph.Keywords: pleural adhesion, bridge connection, physiological variation, image, thoracoscope

Xiangming Deng,1 Jinlong Teng,1 Xiucheng Nong,1 Bihan Yu,1 Liying Tang,2,* Jinsong Liang,3 Zhuocheng Zou,1,* Qiang Liu,2,* Lu Zhou,4 Qirong Li,5 Lihua Zhao1 1Department of Acupuncture and Moxibustion, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, 530023, People’s Republic of China; 2The Xinhu Outpatient Clinic of the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, People’s Republic of China; 3Department of Clinical Laboratory of the First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, 530023, People’s Republic of China; 4Medical Examination Center of the First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, 530023, People’s Republic of China; 5Renai Branch of the First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, 530023, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lihua ZhaoDepartment of Acupuncture and Moxibustion, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Dongge Road & 89-9, Nanning, 530023, People’s Republic of ChinaTel +86 130 06913108Email zhaolh67@163.comQirong LiDepartment of Acupuncture and Moxibustion, Renai Branch of the First Affiliated Hospital of Guangxi University of Chinese Medicine, Mingxiu East Road & 179, Nanning, 530023, People’s Republic of ChinaTel +86 136 07717755Email 632481428@qq.comIntroduction: The incidence of Alzheimer’s disease is on the rise, early detection of cognitive impairment of the elderly is very important. In traditional Chinese medicine, constitution is related to the susceptibility of the human body to diseases. Based on the theory of constitution of traditional Chinese medicine (TCM), the human population can be classified into 9 constitutions. However, little is known about the characteristics of medical constitution and related biomarkers in subjects with mild cognitive impairment (MCI).Methods: We measured the TCM Constitution of 214 subjects by using the Constitution in Chinese Medicine Questionnaire (CCMQ). MMSE and MoCA were used to assess cognitive function. The subjects were divided into mild cognitive impairment group (MCI, n = 152) and normal control group (NC, n = 62). The levels of serum Hcy and serum/urine 8-iso-PGF 2α were determined.Results: 1) It was found that there was a significant difference in constitution types between MCI and NC. There were significant differences in MMSE and MoCA score, serum Hcy and serum/urine 8-iso-PGF 2a levels between the two groups. 2) In logistic regression analysis, the variables with statistical significance were TCM Constitution of Yang-Deficient, Phlegm-Dampness, Blood-Stasis and abnormal increase of Hcy (OR> 1). 3) The MoCA scores had a positive correlation with the MMSE. A statistically significant inverse association was found between serum Hcy, blood and urine 8-iso-PGF 2a and scores of cognitive assessment in MCI.Conclusion: Constitution types (Yang-Deficient, Phlegm-Dampness and Blood-Stasis) and abnormal serum Hcy elevation can be used as risk factors for MCI. MoCA scores can serve to detect MCI at early stage. Serum/urine 8-iso-PGF 2α has a certain relationship with MCI. Higher levels of serum/urine 8-iso–PGF 2α are more likely to be associated with MCI risk.Keywords: cognitive impairment, constitutions of traditional Chinese medicine, biomarkers, MoCA score

Qianyu Yue,* Yanyan Xu,* Xiaoli Deng, Shenglan Wang, Jingman Qiu, Baojiang Qian, Yunhui Zhang Department of Pulmonary and Critical Care Medicine, The First People’s Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, 650032, Yunnan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yunhui Zhang; Xiaoli DengDepartment of Pulmonary and Critical Care Medicine, The First People’s Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), No. 157, Jinbi Road, Kunming, 650032, Yunnan, People’s Republic of ChinaTel +86 871-63638515Email Yueqianyu2020@163.com; xeygyc@163.comBackground: Circular RNA (circRNA) is a key regulator of cancer, and it has been proved to be involved in the regulation of cancer progression including non-small cell lung cancer (NSCLC). Circ-PITX1 was found to be a significantly upregulated circRNA in NSCLC, and its role and potential mechanism in NSCLC progression deserve further investigation.Methods: The expression levels of circ-PITX1, microRNA (miR)-1248 and cyclin D2 (CCND2) were examined by quantitative real-time PCR (qRT-PCR). Cell proliferation, apoptosis, cell cycle process, migration and invasion were determined using cell counting kit 8 (CCK8) assay, colony formation assay, flow cytometry, wound healing assay and transwell assay. Xenograft models were built to explore the role of circ-PITX1 in NSCLC tumor growth in vivo. The glycolysis and glutamine metabolism of cells were assessed by detecting the consumptions of glucose and glutamine, cell extracellular acidification rate (ECAR), and the productions of lactate, α-ketoglutaric acid (α-KG) and ATP. The protein levels of hexokinase 2 (HK-2), glutaminase 1 (GLS1) and CCND2 were tested by Western blot (WB) analysis. Dual-luciferase reporter assay and RIP assay were employed to verify the interaction between miR-1248 and circ-PITX1 or CCND2.Results: Circ-PITX1 was upregulated in NSCLC and its silencing could inhibit the proliferation, migration, invasion, cell cycle process, glycolysis, glutamine metabolism, and promote the apoptosis of NSCLC cells in vitro, as well as reduced tumor growth in vivo. In the terms of mechanism, we found that circ-PITX1 could act as a sponge of miR-1248, and miR-1248 could target CCND2. In addition, miR-1248 inhibitor reversed the inhibitory effect of circ-PITX1 knockdown on NSCLC progression. Similarly, CCND2 overexpression also reversed the suppressive effect of miR-1248 on NSCLC progression. Moreover, circ-PITX1 positively regulated CCND2 expression by sponging miR-1248.Conclusion: Circ-PITX1 served as a sponge of miR-1248 to promote NSCLC progression by upregulating CCND2.Keywords: non-small cell lung cancer, circ-PITX1, miR-1248, CCND2

Xianzhao Deng, Bomin Guo, Youben Fan Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, People’s Republic of ChinaCorrespondence: Youben FanDepartment of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 600 Yishan Road, Shanghai 200233, People’s Republic of ChinaTel +86-21-24058410Email dryouben_f123@163.comPurpose: The aim was to research the role of miR-153-3p and E2F3 in the development of thyroid tumors.Methods: A total of 91 thyroid cancer patients were involved. The role of miR-153-3p in THCA cell lines and Nthy-ori3-1 cell line was researched. qPCR was used to detect miR-153-3p and E2F3 expression. MiR-153-3p mimic, inhibitor, siE2F3 or corresponding controls were transfected in cells. CCK8 was used to verify the proliferation. Cell cycle and apoptosis was detected by flow cytometry. Transwell assay was applied for migration and invasion, and glycolysis was monitored. The binding of miR-153-3p and E2F3 was predicted by targetscan database, and verified by luciferase reporter and RNA-pull down assay. Western blot was used to detect E2F3 expression. Rescue assay was undertaken to verify the effect of siE2F3 on miR-153-3p inhibitor. Moreover, the effect of miR-153-3p mimic on tumor volume and weight was measured. IHC assay was processed to E2F3 and Ki67 expression, and TUNEL assay was used for apoptosis.Results: MiR-153-3p expressed lower in thyroid tumors and cells. The level of miR-153-3p was negatively related with TNM stage. MiR-153-3p inhibited cell proliferation, invasion migration, and induced cycle arrest and apoptosis. Moreover, it negatively regulated E2F3. siE2F3 rescued effects of miR-153-3p inhibitor in all above biological processes in thyroid cancer cells. MiR-153-3p inhibited tumor growth. Moreover, it inhibited E2F3 and Ki67 expression, and also increased apoptosis in vivo.Conclusion: MiR-153-3p suppresses cell proliferation, invasion and glycolysis of thyroid cancer through inhibiting E3F3 expression, which may be a biomarker for thyroid cancer diagnose.Keywords: thyroid cancer, MiR-153-3p, E3F3, proliferation, invasion, glycolysis

Nb–Si based alloys have drawn continuously increasing attention due to their excellent high-temperature mechanical properties. The addition of element Fe could improve their poor high-temperature oxidation resistance which largely restricts their application. With the aim to study the effect of Fe addition on the Nb–Si system and to design appropriate alloy composition, the Fe–Nb–Si ternary system was thermodynamically investigated using the CALPHAD (CALculation of PHAse Diagrams) approach aided with the formation enthalpies for ternary compounds at 0 K computed via ab initio calculations. A self-consistent thermodynamic description of the Fe–Nb–Si system was obtained in this work. Key isothermal sections and liquidus projection were presented, and the calculation results showed a good agreement with available experimental data.

Yuan Nie,* Xizi Deng,* Yun Lan, Linghua Li, Feng Li, Fengyu Hu Research Institute, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fengyu Hu; Feng LiResearch Institute, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, No. 627, Dongfeng Road, Yuexiu District, Guangzhou, Guangdong 510030, People’s Republic of ChinaEmail gz8hhfy@126.com; gz8h_lifeng@126.comBackground: Human immunodeficiency virus (HIV)/hepatitis B virus (HBV) co-infection can accelerate HBV-induced liver disease. A previous study showed that variation in the HBV pre-S region and quasispecies heterogeneity (Sn, mean genetic distance, dS, dN, and dS/dN) are both related to HBV-induced terminal liver disease in HBV mono-infection. Currently, data are lacking on quasispecies variation of the HBV pre-S region in HIV/HBV co-infection. Investigating the quasispecies variation of the HBV pre-S region and its related factors in HIV/HBV co-infection will help to better explore the pathogenic mechanism of HIV/HBV co-infection.Methods: According to the HIV antibody results obtained before treatment, chronic HBV-infected patients were divided into HIV/HBV co-infected and HBV mono-infected groups. The clinical characteristics of all patients were collected, and DNA was extracted from the serum. The HBV pre-S region was amplified by nested PCR and was further TA cloned. BioEdit software 7.0 was used for sequence alignment with reference to the standard sequence of the matched HBV genotype. We used 1:1 propensity score matching (PSM) to control for baseline confounding factors between the two groups.Results: After 1:1 PSM, we identified 100 patients with similar propensities: 50 HIV/HBV co-infected patients and 50 HBV mono-infected patients. HBV quasispecies indices were lower in the HIV/HBV co-infected group than those in the HBV mono-infected group. A significant correlation was observed between all quasispecies indices and soluble cluster of differentiation 163 (sCD163) and interleukin-18 (IL-18) in the HIV/HBV co-infected group; however, this phenomenon was not found in the HBV mono-infected group.Conclusion: Combined HIV infection reduces quasispecies heterogeneity in the HBV pre-S region, and the quasispecies heterogeneity is related to the sCD163 and IL-18 levels.Keywords: HIV, HBV, quasispecies, pre-S region, inflammation

Yun Lan,1,* Linghua Li,2,* Weilie Chen,1,* Xizi Deng,1 Junbin Li,2 Qinghong Fan,1 Xiaoli Cai,1 Weiping Cai,2 Fengyu Hu1 1Institute of Infectious Disease, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Infectious Disease Center, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weiping CaiInfectious Disease Center, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, 627 Dongfeng East Road, Yuexiu District, Guangzhou 510030, People’s Republic of ChinaTel +86-20-83710825Email gz8hcwp@126.comFengyu HuInstitute of Infectious Disease, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, 627 Dongfeng East Road, Yuexiu District, Guangzhou 510030, People’s Republic of ChinaTel +86-20-83710851Email gz8hhfy@126.comBackground: Antiretroviral therapy (ART) containing an integrase strand transfer inhibitor (INSTI) plus two nucleoside reverse-transcriptase inhibitors has been recommended as a first-line regimen for ART-naïve HIV-1-infected patients in the latest Chinese Guidelines for Diagnosis and Treatment of HIV/AIDS.Objective: To determine the prevalence of INSTI-related mutations among ART-naïve HIV-1-infected adults in Guangdong, China, in 2018.Methods: The entire integrase gene was amplified from blood plasma. Demographic and epidemiological information was collected. INSTI mutations and antiretroviral susceptibility were interpreted using the Stanford University HIV Drug Resistance Database HIVdb program.Results: Of 927 samples, 827 integrase sequences were successfully obtained. Among them, no major resistance mutations to INSTIs were identified, and four accessory mutations, including T97A (0.12%, 1/827), A128T (0.24%, 2/827), E157Q (0.85%, 7/827), and G163R (0.24%, 2/827), were found in twelve individuals. Two patient samples contained the G163R mutation conferring low-level resistance to elvitegravir and raltegravir.Conclusion: The overall prevalence of INSTI mutations remains low. Drug resistance mutation testing for the detection of INSTI drug resistance mutations in HIV treatment-naïve patients should be considered due to the circulation of polymorphisms contributing to INSTI resistance and the expected increasing use of this class of drugs.Keywords: HIV-1, integrase inhibitor, drug resistance mutation, Guangdong

Hongzhi Hu,1,2,* Xiangtian Deng,2,3,* Qingcheng Song,2,* Hongzhi Lv,2 Wei Chen,2 Xin Xing,2 Jian Zhu,2,3 Zhanchao Tan,2 Xiaodong Cheng,2 Baichuan Wang,1 Zengwu Shao,1 Yingze Zhang1,2 1Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People’s Republic of China; 2Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijazhuang 050051, People’s Republic of China; 3School of Medicine, Nankai University, Tianjin 300071, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yingze Zhang; Zengwu Shao Tel +86 18533112888; 86 13971021748Email yzling_liu@163.com szwpro@163.comPurpose: Growing evidence indicates that preoperative biomarkers could be identified as independent prognostic factors in various cancers. The purpose of this study was to assess prognostic value of the preoperative lymphocyte-to-C-reactive protein ratio (LCR), albumin-to-globulin ratio (AGR), lymphocyte–monocyte ratio (LMR), and C-reactive protein to albumin ratio (CAR) in patients with osteosarcoma.Methods: A total of 137 osteosarcoma patients treated at our hospital between 2011 and 2019 were enrolled in the study. Patient demographics, clinical characteristics, and laboratory data were collected and analyzed. The optimal cutoff values of LCR, AGR, LMR, and CAR were assessed with receiver operating characteristic (ROC) analysis. Kaplan–Meier analysis was performed to estimate overall survival (OS). Univariate and multivariate Cox regression models were employed to determine the independent prognostic factors. The hazard ratios (HR) and 95% confidence intervals (95% CI) were calculated to evaluate relative risk.Results: The optimal cutoff values of LCR, AGR, LMR, and CAR were 0.14, 1.79, 3.05 and 0.24, respectively. According to the univariate analysis, OS was remarkably associated with neoadjuvant chemotherapy (P < 0.001), pathological fracture (P < 0.001), local recurrence (P = 0.020), metastasis (P < 0.001), LCR (P = 0.035), AGR (P = 0.028), LMR (P = 0.010), and CAR (P = 0.004). In multivariate analyses, pathological fracture (P = 0.025), metastasis (P < 0.001), LCR (P = 0.012), and AGR (P = 0.001) were identified as independent risk predictors for OS.Conclusion: The present study provides new evidence that the preoperative LCR and AGR could serve as independent prognostic factors for patients with osteosarcoma. These findings will help physicians to stratify patients for appropriate treatment protocols and facilitate decision-making so as to improve the patients’ survival condition.Keywords: osteosarcoma, biomarker, albumin-to-globulin ratio, C-reactive protein, lymphocyte, prognosis

Xiaolu Deng, Fang He, Ciliu Zhang, Fei Yin, Jing Peng Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, People’s Republic of ChinaCorrespondence: Jing PengDepartment of Pediatrics, Xiangya Hospital, Central South University, No. 87, Road Xiangya, Changsha, Hunan 410008, People’s Republic of ChinaTel +86 13548966986Fax +86 731-84327922Email pengjing627@126.comPurpose: Seizure is a serious neurological symptom in the pediatric intensive care unit (PICU), yet data on etiologies of non-traumatic childhood seizures in China are scarce. We aimed to investigate the etiological trends of seizures in children admitted to the PICU in our tertiary center.Patients and Methods: We performed a retrospective analysis of all patients (aged 29 days to 14 years) with non-traumatic seizures, admitted to the PICU of Xiangya Hospital from 2010 to 2017. Etiological analysis was performed to compare data between 2010– 2013 and 2014– 2017.Results: The study included 318 patients (male: female = 1.27:1) with mean age of 5.4 ± 4.0 years. The most frequent causes observed were CNS infections (109/318, 34.3%), unknown reason epilepsy (96/318, 30.2%), and immune (56/318, 17.6%). Comparison of the 2010– 2013 and 2014– 2017 periods revealed a significant decrease in the percentage of CNS infections [48.8% (59/121) vs 25.4% (50/197), p < 0.001] and a significant increase in the incidence of unknown reason epilepsy [(24/121, 19.8%) vs (72/197, 36.5%), p < 0.001] and immune causes [(12/121, 9.9%) vs (44/197, 22.3%), p = 0.005].Conclusion: CNS infections were the most common cause of seizures during 2010– 2013, while non-infectious diseases such as epilepsy and immune disorders represented the leading causes during 2014– 2017. Continuous improvement in medical technology and understanding of disease patterns would greatly improve early diagnosis and therapeutic management of such conditions.Keywords: epilepsy, autoimmune encephalitis, CNS infections, pediatric

Yue Qiu, Xia Deng, Yujing Sha, Xunan Wu, Panpan Zhang, Ke Chen, Zhicong Zhao, Weiping Wei, Ling Yang, Guoyue Yuan, Li Zhao, Dong Wang Department of Endocrinology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, People’s Republic of ChinaCorrespondence: Dong Wang; Li ZhaoDepartment of Endocrinology, Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang, Jiangsu 212001, People’s Republic of ChinaTel +86-13605282460; +86-15800578209Email zjdongdonghao@aliyun.com; zhaoli863@163.comBackground: This study was conducted in patients with type 2 diabetes mellitus (T2DM) to assess the association between visceral fat area (VFA) and cardiac hemodynamics.Methods: A total of 568 patients with type 2 diabetes (mean age 54± 12 years; 40.8% of women) were enrolled. Visceral fat area (VFA, m2) and subcutaneous fat area (SFA, m2) were evaluated by a bioelectrical impedance analyzer. Cardiac hemodynamics were measured by echocardiography, and other clinical and laboratory variables were also assessed and recorded. Patients were divided into those with VFA ≤ 100 (n=369) and those with VFA > 100 (n=199).Results: VFA, SFA, LVMI (left ventricular mass index), left atrial diameter, left ventricular diastolic diameter (LvDd), interventricular septal thickness (IVST), left ventricular systolic diameter (LvSd), and posterior wall thickness (PWT) levels in high-V groups were significantly higher than those in low-V groups. Correlation analysis showed that VFA was positively correlated with LVMI (r=0.120, p=0.004), LVM (r=0.249, p< 0.0001), left atrial diameter (r=0.375, p< 0.0001), aortic root diameter (r=0.243, p< 0.0001), left ventricular systolic diameter (LvSd) (r=0.211, p< 0.0001) and negatively correlated with LVEF (r=− 0.107, p=0.011). In multivariate linear regression analysis, VFA was the strongest independent determinant of LVMI (β=0.04, p=0.016), LVEF (β=− 0.01, p=0.023), and left atrial diameter (β=0.035, p< 0.0001), Internal diameter of the aortic root (β=0.014, p< 0.0001) and LvSd (β=0.017, p< 0.0001). In addition, the VFA also better predicted cardiovascular disease risk with AUC of 0.609 (95% CI:0.563– 0.656), compared with SFA, waist–hip ratio (WHR), in a statistically significant manner.Conclusion: We found a significant correlation between VFA (but not SFA) and cardiac hemodynamic parameters. The VFA has advantages as a predictor of visceral obesity and is significantly associated with the development of cardiovascular risk factors (CVD) in T2DM patients.Keywords: cardiac hemodynamics, left ventricular mass index, type 2 diabetes mellitus, visceral fat area