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Zaifeng Si,1,2,&ast; Shengmei Zhao,3,&ast; Yingying Hao,3 Qian Wang,3 Yanfa Zhong,2 Yue Liu,3 Ran Chen,3 Yan Jin,3 Zhiming Lu1,3 1Department of Clinical Laboratory, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Clinical Laboratory, Dezhou Municipal Hospital of Traditional Chinese Medicine, Dezhou, Shandong, People’s Republic of China; 3Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Jin; Zhiming Lu, Email sdjinyan@163.com; luzhiming@sdu.edu.cnBackground: Enterobacter cloacae complex (ECC), which includes major nosocomial pathogens, causes urinary, respiratory, and bloodstream infections in humans, for which colistin is one of the last-line drugs.Objective: This study aimed to analyse the epidemiology and resistance mechanisms of colistin-resistant Enterobacter cloacae complex (ECC) strains isolated from Shandong, China.Methods: Two hundred non-repetitive ECC strains were collected from a tertiary hospital in Shandong Province, China, from June 2020 to June 2022. Whole-genome sequencing and bioinformatics analyses were performed to understand the molecular epidemiology of the colistin-resistant ECC strains. The nucleotide sequences of heat shock protein (hsp60) were analyzed by using BLAST search to classify ECC. The gene expression levels of ramA, soxS, acrA, acrB, phoP, and phoQ were assessed using RT-qPCR. MALDI-TOF MS was used to analyse the modification of lipid A.Results: Twenty-three colistin-resistant strains were detected among the 200 ECC clinical strains (11.5%). The hsp60 cluster analysis revealed that 20 of the 23 ECC strains belonged to heterogeneous resistance clusters. Variants of mgrB, phoPQ, and pmrAB, particularly phoQ and pmrB, were detected in the 23 ECC strains. The soxS and acrA genes were significantly overexpressed in all 23 colistin-resistant ECC strains (P < 0.05). Additionally, all 23 ECC strains contained modified lipid A related to colistin resistance, which showed five ion peaks at m/z 1876, 1920, 1955, 2114, and 2158. Among the 23 ECC strains, 6 strains possessed a phosphoethanolamine (pETN) moiety, 16 strains possessed a 4-amino-4-deoxy-L-arabinose (−L-Ara4N) moiety, and one strain had both pETN and −L-Ara4N moieties.Conclusion: This study suggests that diverse colistin resistance existed in ECC, including unknown resistance mechanisms, exist in ECC. Mechanistic investigations of colistin resistance are warranted to optimise colistin use in clinical settings and minimise the emergence of resistance.Keywords: Enterobacter cloacae complex, ECC, epidemiology, colistin, resistance mechanism

Yujie Hao, Runmin Liu, Hao Wang, Tao Rui, Junfang Guo Division of Cardiology, Department of Medicine, the Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of ChinaCorrespondence: Junfang Guo, Email zjyyxngjf@163.comAbstract: Sepsis is a syndrome of organ dysfunction caused by a dysregulated immune response to infection, with high morbidity and mortality. At present, there have been many advances in the study of its pathogenesis, especially the cardiac dysfunction caused by sepsis, namely sepsis-induced myocardial dysfunction, SIMD, which has received widespread attention. The mechanisms of SIMD mainly include excessive release of inflammatory mediators, impaired mitochondrial function, autophagy, apoptosis and myocardial dysfunction. This article reviews the pathogenesis of SIMD and elaborates on the progress in its treatment, aiming to improve the prognosis of patients with SIMD and sepsis.Keywords: sepsis, sepsis-induced myocardial dysfunction, pathogenesis, treatment

Yukai Hao,1 Baoling Zhao,1 Dongchao Wu,1 Xuejun Ge,1 Jianmin Han2 1Department of Endodontics, Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, People’s Republic of China; 2Central Laboratory, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing, 100081, People’s Republic of ChinaCorrespondence: Xuejun Ge, The Department of Endodontics, Shanxi Medical University School and Hospital ofStomatology, 63 Xinjian South Road, Yingze District, Taiyuan, 030001, People’s Republic of China, Tel +8613834568537, Email gxj19722003@163.com Jianmin Han, Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguan Cun South Street, Beijing, 100081, People’s Republic of China, Tel +8613810459668, Email hanjianmin@bjmu.edu.cnIntroduction: Recombinant humanized collagen, as a novel biomaterial, exhibits multiple excellent biological functions, such as inhibition of inflammation, promotion of cell proliferation and vascular proliferation, and promotion of tissue healing. However, there is a lack of conclusive evidence regarding the specific role of recombinant humanized collagen type 17 (rhCol 17) in oral ulcer healing. This study explored whether rhCol 17 could promote the proliferation of human gingival fibroblasts (HGFs) and inhibit its inflammation, and whether it could promote the healing of oral ulcers in rats by inhibiting inflammation and accelerating tissue healing.Methods: At the cellular level, we investigated the effect of rhCol 17 on the proliferation of (HGFs) by CCK8; HGFs were mixed with lipopolysaccharide (LPS) to investigate the effect of rhCol 17 on HGFs in an inflammatory state. Eighteen adult male Sprague-Dawley rats were randomly distributed into three groups: blank control group, carbomer group (carbomer sprayed only), and rhCol 17 group (carbomer containing rhCol 17 sprayed), 1 time/day. The samples were collected at D3 and D5. At completion, histological staining and PCR were carried out to study its effect on the healing of oral ulcers in rats.Results: Through cellular experiments, we found that rhCol 17 possesses good biocompatibility and anti-inflammatory properties, and can effectively promote the proliferation and migration of HGFs, as well as significantly reduce the inflammation level of the cells. The animal experimental results showed that rhCol 17 could significantly reduce the inflammation level, promote collagen deposition and angiogenesis at the ulcer site, thus effectively accelerating the healing of oral ulcers in rats.Conclusion: In summary, the collagen sprays containing rhCol 17 have excellent anti-inflammatory effects and could accelerate tissue healing and are expected to provide a new effective treatment for patients with recurrent oral ulcers.Keywords: oral ulcer, inflammation, wound healing, recombinant humanized collagen

Yanting Hao,1 Hua Zhang,2 Fan Zhang1 1Department of Geriatrics, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 2Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, 100191, People’s Republic of ChinaCorrespondence: Fan Zhang, Department of Geriatrics, Peking University Third Hospital, 49 North Garden Road, Beijing, 100191, People’s Republic of China, Email zfpuh3@126.comPurpose: It has been shown that lower Barthel’s index (BI) at admission is associated with a higher in-hospital mortality. There is a lack of evidence regarding the association between the change in BI during hospitalization and mortality after discharge. Our purpose was to determine whether the BI change during hospitalization is associated with all-cause mortality in older adults with COVID-19 pneumonia.Patients and Methods: We conducted a retrospective cohort study of 330 participants at Peking University Third Hospital during the COVID-19 pandemic period. In order to analyze the time to death data, a Kaplan-Meier survival curve was used. We used restricted cubic splines to analyze the association between BI change and all-cause mortality among COVID-19 pneumonia patients aged over 80 years old. Threshold effect analysis was used to assess the ability of BI change score to predict all-cause mortality.Results: Our study included 330 patients aged over 80 years with COVID-19 pneumonia. The Kaplan-Meier curve for mortality showed significantly worst survival with reduced BI among three groups (χ2= 6.896, P < 0.05). There was a non-linear association between the BI change and all-cause mortality (P for all over < 0.001). The effect sizes on the left and right sides of the inflection point were 0.958 (HR: 0.958, 95% CI 0.932– 0.958, P < 0.05) and 1.013 (HR: 1.013, 95% CI 0.967– 1.062, P > 0.05), respectively.Conclusion: Reduced BI during hospitalization was associated with the highest mortality risk. It is crucial to monitor BI change among COVID-19 pneumonia patients aged over 80 years old.Keywords: COVID-19 pneumonia, activities of daily living, mortality, older adult

Yongzhi Xu,1,2,&ast; Yuanping Hao,2,&ast; 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&ast;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, &epsiv;-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

Xin Huang,1,&ast; Meng Wang,1,&ast; Baochen Zhu,1,&ast; Yu Hao,2 Ruoyu Gao,2 Wenhui Liu,2 Jiaojiao Cheng,1 Guodong Hua,1 Chunmiao Xue1 1Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guodong Hua; Chunmiao Xue, Email zhaojhuagd@126.com; xuechunmiao9501@163.comIntroduction: Non-small cell lung cancer (NSCLC) stands as one of the most prevalent malignancies, and chemotherapy remains the primary treatment for advanced stages. However, the high expression of ABC binding cassette transporters, including MRP, P-gp, and LRP, along with multidrug resistance proteins, has been identified as a significant factor contributing to decreased chemotherapy drug sensitivity. This study aims to explore the impact and underlying mechanisms of Curculiginis Rhizoma [Hypoxidaceae; Curculigo orchioides Gaertn.] (CR) in combination with cisplatin on improving chemoresistance mediated by ABC binding cassette transporters and multidrug resistance proteins in NSCLC.Methods and Results: To unravel the relationship between JNK, MRP, P-gp, and LRP in NSCLC and gain insights into the regulatory mechanism of CR, this study employs an integrated approach encompassing bioinformatics, molecular docking, molecular dynamics, animal and cellular experiments. Bioinformatics analysis revealed a significant increase in the expression levels of JNK, MRP, P-gp, and LRP subtypes in multidrug-resistant non-small cell lung cancer. Subsequent animal experiments have shown that the combination of CR with cisplatin can improve the survival rate of lung cancer mice. Molecular docking and molecular dynamics analyses demonstrated favorable binding interactions between curculigoside and the aforementioned subtypes of JNK, MRP, P-gp, and LRP. In cellular experiments, the combination of cisplatin with both curculigoside and CR extract resulted in a notable decrease in cell viability and downregulation of the expression of JNK1, JNK2, MRP1, MRP2, MRP4, P-gp, and LRP1 in A549/cis cells.Conclusion: Remarkably, curculigoside exerted a significant downregulation effect on the expression levels of JNK1, MRP1, MRP2, MRP4, and LRP1. CR, particularly its main effective metabolite, curculigoside, has the potential to enhance the sensitivity of non-small cell lung cancer to cisplatin by regulating levels of JNK/MRP/LRP/P-gp and mitigating multidrug resistance.Keywords: non-small cell lung cancer, curculiginis rhizoma, CR, curculigoside, multidrug resistance, cisplatin resistance, ABC binding cassette transporter, multidrug resistance proteins

Wang L, Li D, Hao Y, et al. Int J Nanomedicine. 2017;12:3059-3075. The authors have advised Figures 9 and 11 on pages 3070 and 3071, respectively, are incorrect. The H&E staining image of tumor tissue in the PLGA/DTX@MnO2 group in Figure 9C and the X-ray CT images in Figure 11C were inadvertently misused during data acquisition. The correct Figure 9 is as follows. Figure 9 Inhibition of tumor growth in vivo by the drug delivery system.Abbreviations: H&E, hematoxylin and eosin; AuNR, gold nanorod; DTX, docetaxel; MnO2, manganese dioxide; PLGA, poly(lactic-co-glycolic acid); RF, radiofrequency.Notes: (A) Relative volumes of tumor-bearing mice; (B) body weight of the mice models (mean ± standard deviation; n=6); (C) H&E-stained tumor tissue sections: (a) control, (b) DTX, (c) PLGA/DTX@MnO2, (d) PLGA/DTX@MnO2 + RF, (e) PLGA/AuNR/DTX@MnO2, and (f) PLGA/AuNR/DTX@MnO2 + RF. The correct Figure 11 is as follows. Figure 11 Dual-mode imaging in vivo.Abbreviations: MR, magnetic resonance; CT, computed tomography.Notes: (A, B) T1-weighted MR images; (C) X-ray CT images: (a) control; (b) 4 h; (c) 8 h. The authors apologize for these errors and advise they do not affect the results and conclusions of the paper.

Heli Li,1,&ast; Jinru Cui,1,&ast; Cong Hu,1 Hao Li,2 Xiaoping Luo,3 Yan Hao1 1Division of Child Healthcare, Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 3Department of Pediatrics, 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: Yan Hao, Email haoyaner@163.comObjective: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with significant genetic heterogeneity. The ZIC gene family can regulate neurodevelopment, especially in the cerebellum, and has been implicated in ASD-like behaviors in mice. We performed bioinformatic analysis to identify the ZIC gene family in the ASD cerebellum.Methods: We explored the roles of ZIC family genes in ASD by investigating (i) the association of ZIC genes with ASD risk genes from the Simons Foundation Autism Research Initiative (SFARI) database and ZIC genes in the brain regions of the Human Protein Atlas (HPA) database; (ii) co-expressed gene networks of genes positively and negatively correlated with ZIC1, ZIC2, and ZIC3, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and receiver operating characteristic (ROC) curve analysis of genes in these networks; and (iii) the relationship between ZIC1, ZIC2, ZIC3, and their related genes with cerebellar immune cells and stromal cells in ASD patients.Results: (i) ZIC1, ZIC2, and ZIC3 were associated with neurodevelopmental disorders and risk genes related to ASD in the human cerebellum and (ii) ZIC1, ZIC2, and ZIC3 were highly expressed in the cerebellum, which may play a pathogenic role by affecting neuronal development and the cerebellar internal environment in patients with ASD, including immune cells, astrocytes, and endothelial cells. (iii) OLFM3, SLC27A4, GRB2, TMED1, NR2F1, and STRBP are closely related to ZIC1, ZIC2, and ZIC3 in ASD cerebellum and have good diagnostic accuracy. (iv) ASD mice in the maternal immune activation model demonstrated that Zic3 and Nr2f1 levels were decreased in the immune-activated cerebellum.Conclusion: Our study supports the role of ZIC1, ZIC2, and ZIC3 in ASD pathogenesis and provides potential targets for early and accurate prediction of ASD.Keywords: autism, ZIC1, ZIC2, ZIC3, cerebellum, biomarkers

Xiaoqi Wang,1,2 Yuanjie Hao,3 Yujie Yin,4,5 Yunlong Hou,2,4,5 Ningxin Han,3 Yi Liu,3 Zhen Li,3 Yaru Wei,1 Kun Ma,1 Jiaojiao Gu,1 Yan Ma,1 Hui Qi,4,5 Zhenhua Jia1,4– 6 1Graduate School, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050090, People’s Republic of China; 2Hebei Yiling Pharmaceutical Research Institute, Shijiazhuang, 050035, People’s Republic of China; 3Graduate School, Hebei Medical University, Shijiazhuang, Hebei, 050017, People’s Republic of China; 4Hebei Academy of Integrated Traditional Chinese and Western Medicine, Shijiazhuang, Hebei, 050035, People’s Republic of China; 5National Key Laboratory for Innovation and Transformation of Luobing Theory, Shijiazhuang, 050035, People’s Republic of China; 6Department of Respiratory, Affiliated Yiling Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050091, People’s Republic of ChinaCorrespondence: Zhenhua Jia, Graduate School, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050090, People’s Republic of China, Email jzhjiazhenhua@163.com Hui Qi, Hebei Academy of Integrated Traditional Chinese and Western Medicine, Shijiazhuang, Hebei, 050035, People’s Republic of China, Email qihui_qh@163.comPurpose: Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD) is a sudden worsening of symptoms in patients with Chronic Obstructive Pulmonary Disease (COPD), such as cough, increased sputum volume, and sputum purulence. COPD and AECOPD are characterized by damage to cilia and increased mucus secretion. Mucociliary clearance (MCC) functions as part of the primary innate system of the lung to remove harmful particles and pathogens together with airway mucus and is therefore crucial for patients with COPD.Methods: AECOPD was induced by cigarette smoke exposure (80 cigarettes/day, 5 days/week for 12 weeks) and lipopolysaccharide (LPS) instillation (200 μg, on days 1, 14, and 84). Rats administered Lianhua Qingke (LHQK) (0.367, 0.732, and 1.465 g/kg/d) or Eucalyptol, Limonene, and Pinene Enteric Soft Capsules (ELP, 0.3 g/kg/d) intragastrically. Pulmonary pathology, Muc5ac+ goblet cell and β-tubulin IV+ ciliated cells, and mRNA levels of forkhead box J1 (Foxj1) and multiciliate differentiation and DNA synthesis associated cell cycle protein (MCIDAS) were assessed by hematoxylin and eosin staining, immunofluorescence staining, and RT-qPCR, respectively. Ciliary morphology and ultrastructure were examined through scanning electron microscopy and transmission electron microscopy. Ciliary beat frequency (CBF) was recorded using a high-speed camera.Results: Compared to the model group, LHQK treatment groups showed a reduction in inflammatory cell infiltration, significantly reduced goblet cell and increased ciliated cell proportion. LHQK significantly upregulated mRNA levels of MCIDAS and Foxj1, indicating promoted ciliated cell differentiation. LHQK protected ciliary structure and maintained ciliary function via increasing the ciliary length and density, reducing ciliary ultrastructure damage, and ameliorating random ciliary oscillations, consequently enhancing CBF.Conclusion: LHQK enhances the MCC capability of ciliated cells in rat with AECOPD by preserving the structural integrity and beating function of cilia, indicating its therapeutic potential on promoting sputum expulsion in patients with AECOPD.Keywords: goblet hyperplasia, ciliary density, ciliary length, ciliary ultrastructure, ciliary beat frequency, CBF

Xueping Ma, Zhengjun Zhang, Meihua Jin, Yu Hao, Hua Cheng, Ning Yan Heart Centre & Department of Cardiovascular Diseases, General Hospital of Ningxia Medical University, Yinchuan, 750004, People’s Republic of ChinaCorrespondence: Hua Cheng; Ning Yan, Heart Centre & Department of Cardiovascular Diseases, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China, Tel +86 15008617234 ; +86 15719591301, Email chenghzhp@126.com; yanning169@yahoo.comObjective: The study aims to reveal the association between family context and sleep trajectories in middle-aged and elderly Chinese adults.Methods: Subjects (n=7777) aged between 40 and 65 years were selected from the China Family Panel Studies (CFPS). Latent class analysis and the multi-trajectory method were used to identify the family context and sleep trajectories from 2010 to 2018. Multinomial (polytomous) logistic regression was performed to explore the relationship between family context and sleep trajectories.Results: Five family context classes were identified according to family demographic characteristics. Simultaneously, four sleep trajectories were determined based on three sleep-related indexes. Subjects from family that had only sons or multiple-child are liable to shorten or prolong sleep duration and increase midday nap ratios compare with subjects who from family that had one or more daughters, and in future public health prevention and control, more attention could be paid to such families.Conclusion: The study found that family context is associated with sleep trajectories among middle and old Chinese adults. Subjects from families with only girls seemed to have more stable sleep trajectories, while those with one or more boys’ families had unstable sleep trajectories. Further interventions would be carried out for sleep disorders, it is necessary to pay more attention to the family context, especially the number and gender of children.Keywords: family context, sleep trajectory, China Family Panel Studies, CFPS, sleep disorders

Yanan Hao,1,&ast; Xiaodan Yang,2,&ast; Weiwei Ma,1 Xiaoling Zhang,1 Yanping Wang,1 Shuxia Qian1 1Department of Neurology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, People’s Republic of China; 2Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Jiaxing University, Jiaxing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoling Zhang, Department of Neurology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, 314000, People’s Republic of China, Email zhaoxiaolingzz@126.comObjective: In this study, we assessed the awareness of cognitive dysfunction and the reasons for the lack of awareness among surgical practitioners in Jiaxing.Methods: Questionnaires were distributed to surgical practitioners covering all Class III and Class II hospitals in Jiaxing. Respondents were asked to make selections regarding the demographic data, clinical attitudes and practices of cognitive dysfunction based on Alzheimer’s Disease Assessment Scale (ADKS) of the Chinese version.Results: A total of 180 questionnaires were distributed, 12 of which were incomplete, with 168 being included for analysis. The respondents were generally under 50 years of age (150, 89.3%), predominantly males (146, 86.9%), and surgeons (153, 91.1%). They generally had a bachelor’s or master’s degrees (165, 98.2%), and served in Class III hospitals (127, 75.6%). The title of the practitioner was found to impact their attention toward their patients’ cognitive status during preoperative preparation (P< 0.05). Titles and hospital levels were found to influence decisions of surgical practitioners to invite specialist physicians for consultation and assessment when a patient was identified to have cognitive dysfunction (P< 0.05). Most surgical practitioners had little knowledge or training about Alzheimer’s disease and cognitive dysfunction. Among the 168 respondents, the mean ADKS score was 20.14± 2.40, and the awareness rate was 67.1%, indicating that the surgical practitioner’s title influenced ADKS score (P

Yanan Feng,1,2,&ast; Yongsheng Hao,3,&ast; Yuanyuan Wang,3 Weijian Song,1,4 Shanxin Zhang,1 Dong Ni,5 Fei Yan,3 Litao Sun1 1Cancer Center, Department of Ultrasound Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China; 2Department of Abdominal Ultrasound, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China; 3Center for Cell and Gene Circuit Design, CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, People’s Republic of China; 4Bengbu Medical College, Bengbu, 233030, People’s Republic of China; 5Medical Ultrasound Image Computing (MUSIC) Laboratory, Shenzhen University, Shenzhen, 518055, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Litao Sun; Fei Yan, Tel +86 13946037056, Email litaosun1971@sina.com; fei.yan@siat.ac.cnPurpose: Ultrasound molecular imaging (UMI) has proven promising to diagnose the onset and progression of diseases such as angiogenesis, inflammation, and thrombosis. However, microbubble-based acoustic probes are confined to intravascular targets due to their relatively large particle size, greatly reducing the application value of UMI, especially for extravascular targets. Extradomain B fibronectin (ED-B FN) is an important glycoprotein associated with tumor genesis and development and highly expressed in many types of tumors. Here, we developed a gas vesicles (GVs)-based nanoscale acoustic probe (ZD2-GVs) through conjugating ZD2 peptides which can specially target to ED-B FN to the biosynthetic GVs.Materials and Methods: ED-B FN expression was evaluated in normal liver and tumor tissues with immunofluorescence and Western blot. ZD2-GVs were prepared by conjugating ZD2 to the surface of GVs by amide reaction. The inverted microscope was used to analyze the targeted binding capacity of ZD2-GVs to MB49 cells (bladder cancer cell line). The contrast-enhanced imaging features of GVs, non-targeted control GVs (CTR-GVs), and targeted GVs (ZD2-GVs) were compared in three MB49 tumor mice. The penetration ability of ZD2-GVs in tumor tissues was assessed by fluorescence immunohistochemistry. The biosafety of GVs was evaluated by CCK8, blood biochemistry, and HE staining.Results: Strong ED-B FN expression was observed in tumor tissues while little expression in normal liver tissues. The resulting ZD2-GVs had only 267.73 ± 2.86 nm particle size and exhibited excellent binding capability to the MB49 tumor cells. The in vivo UMI experiments showed that ZD2-GVs produced stronger and longer retention in the BC tumors than that of the non-targeted CTR-GVs and GVs. Fluorescence immunohistochemistry confirmed that ZD2-GVs could penetrate the tumor vascular into the interstitial space of the tumors. Biosafety analysis revealed there was no significant cytotoxicity to these tested mice.Conclusion: Thus, ZD2-GVs can function as a potential UMI probe for the early diagnosis of bladder cancer.Graphical Abstract: Keywords: ultrasound contrast agents, gas vesicles, ultrasound molecular imaging, tumor diagnosis

Yijia Hao,1 Shaozhuang Liu,2 Teng Liu,2 Xin Huang,2 Mengshuang Xie,3 Dexiang Wang4 1Cheeloo College of Medicine, Shandong University, Jinan, 250033, People’s Republic of China; 2Division of Bariatric and Metabolic Surgery, Department of General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, People’s Republic of China; 3Department of Geriatrics & Key Laboratory of Cardiovascular Proteomics of Shandong Province, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, People’s Republic of ChinaCorrespondence: Dexiang Wang, Email wangdexiang@qiluhospital.comObjective: We explore risk factors related to severe obstructive sleep apnea (OSA) in obese patients, including pulmonary ventilation function, diffusion function, and impulse oscillometry (IOS) data.Methods: The medical records of 207 obese patients who were prepared to undergo bariatric surgery in a hospital from May 2020 to September 2021 were retrospectively reviewed. Polysomnography (PSG), pulmonary ventilation function, diffusion function, and IOS parameters were collected according to the ethical standards of the institutional research committee (registration number: KYLL-202008-144). Logistic regression analysis was used to analyze the related independent risk factors.Results: There were significantly statistical difference in a number of pulmonary ventilation and diffusion function parameters among the non-OSAHS group, the mild-to-moderate OSA group, and the severe OSA group. However, only airway resistance parameters R5%, R10%, R15%, R20%, R25%, and R35% increased with increasing OSA severity and were positively correlated with apnea hypopnea index (AHI). Age (P = 0.012, 1.104 (1.022, 1.192)), body mass index (P< 0.0001, 1.12 (1.057, 1.187)), gender (P = 0.003, 4.129 (1.625, 10.49)), and R25% (P = 0.007, 1.018 (1.005, 1.031)) were independent risk factors for severe OSA. In patients aged 35 to 60, RV/TLC (P = 0.029, 1.272 (1.025, 1.577)) is an independent risk factor for severe OSA.Conclusion: R25% was an independent risk factor for severe OSA in obese individuals, while RV/TLC was also an independent risk factor in those aged 35 to 60. Pulmonary function tests (PFTs), particularly IOS levels, are recommended to assess severe OSA in obese patients.Keywords: obstructive sleep apnea syndrome, obesity, pulmonary function

Yajuan Fu,1,2 Lingbo Xu,1– 3 Hui Zhang,1– 3 Ning Ding,1– 3 Juan Zhang,1– 3 Shengchao Ma,1– 3 Anning Yang,1– 3 Yinjv Hao,1– 3 Yujing Gao,1,2 Yideng Jiang1– 3 1National Health Commission Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan, People’s Republic of China; 2Ningxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan, People’s Republic of China; 3School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, People’s Republic of ChinaCorrespondence: Yujing Gao; Yideng Jiang, Email gaoyujing2004@126.com; jydeng@nxmu.edu.cnBackground: Atherosclerosis and type 2 diabetes mellitus contribute to a large part of cardiovascular events, but the underlying mechanism remains unclear. In this study, we focused on identifying the linking genes of the diagnostic biomarkers and effective therapeutic targets associated with these two diseases.Methods: The transcriptomic datasets of atherosclerosis and type 2 diabetes mellitus were obtained from the GEO database. Differentially expressed genes analysis was performed by R studio software, and differential analysis including functional enrichment, therapeutic small molecular agents prediction, and protein–protein interaction analysis were applied to the common shared differentially expressed genes. Hub genes were identified and further validated using an independent dataset and clinical samples. Furthermore, we measured the expression correlations, immune cell infiltration, and diagnostic capability of the three key genes.Results: We screened out 28 up-regulated and six down-regulated common shared differentially expressed genes. Functional enrichment analysis showed that cytokines and immune activation were involved in the development of these two diseases. Six small molecules with the highest absolute enrichment value were identified. Three critical genes (CD4, PLEK, and THY1) were further validated both in validation sets and clinical samples. The gene correlation analysis showed that CD4 was strongly positively correlated with PLEK, and ROC curves confirmed the good discriminatory capacity of CD4 and PLEK in two diseases.We have established the co-expression network between atherosclerosis lesions progressions and type 2 diabetes mellitus, and identified CD4 and PLEK as key genes in the two diseases, which may facilitate both development of diagnosis and therapeutic strategies.Keywords: small molecular agents, immune infiltration, atherosclerosis, diabetes mellitus, inflammation

Objective: to document patients’ antihypertensive agents, determine their medication adherence, and identify factors associated with the adherence. Material and Methods: A prospective study was performed on a group of hypertensive outpatients, with social health insurance, in Can Tho, Vietnam. The study included 330 patients over 18 years old, who agreed to participate and could listen, speak and answer questions in Vietnamese. The data collection method was based on prescriptions and patient interviews. Data were analyzed using descriptive statistics, and Generalized Estimating Equations with Poisson-log linear distribution. Results: Among the drug use characteristics, 76.1% were prescribed beta-blockers, 91.5% polytherapy, and 63.0% changed drugs at the third follow-up visit. The percentage of patients who adhered to medication ranged from 70.0% to 91.2%. Factors that improved drug adherence included: the academic level at high school or higher (39.0% increase), living in urban areas (15.0% increase), having a job related to social interaction (11.2%), and having a family history of hypertension (9.0% increase). Factors that reduced adherence included: advanced age (22.0% decrease), prolonged disease duration (16.0% decrease), prolonged treatment duration (11.0% decrease), and changes in at least one type of antihypertensive drug (8.0% decrease). Conclusion: The highlight of this study is the demonstration of an inverse relationship between the adherence rate and the number of follow-up visits: the higher the number of visits, the lower the adherence rate. The 3rd follow-up adherence rate was 70.0%, and the decreased adherence rate is related to older age, higher education levels, and a longer duration of treatment.

Dan Long,1 Ting Yang,1 Jie Chen,1 Ying Dai,1 Li Chen,1 Feiyong Jia,2 Lijie Wu,3 Yan Hao,4 Ling Li,5 Jie Zhang,6 Xiaoyan Ke,7 Mingji Yi,8 Qi Hong,9 Jinjin Chen,10 Shuanfeng Fang,11 Yichao Wang,12 Qi Wang,13 Chunhua Jin,14 Tingyu Li1 1Chongqing Key Laboratory of Child Nutrition and Health, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center of Child Health and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Developmental and Behavioral Pediatrics, The First Hospital of Jilin University, Changchun, People’s Republic of China; 3Research Center for Child Development and Behavior, Harbin Medical University, Harbin, People’s Republic of China; 4Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 5Department of Children Rehabilitation, Hainan Women and Children’s Medical Center, Haikou, People’s Republic of China; 6Children Health Care Center, Xi’an Children’s Hospital, Xi’an, People’s Republic of China; 7The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 8Department of Child Health Care, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 9Maternal and Child Health Hospital of Baoan, Shenzhen, People’s Republic of China; 10Department of Child Health Care, Shanghai Children’s Hospital, Shanghai, People’s Republic of China; 11Department of Child Health Care, Children’s Hospital Affiliated of Zhengzhou University, Zhengzhou, People’s Republic of China; 12National Health Commission Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Hospital, Changsha, People’s Republic of China; 13Deyang Maternal and Child Health Hospital, Deyang, People’s Republic of China; 14Department of Children Health Care, Capital Institute of Pediatrics, Beijing, People’s Republic of ChinaCorrespondence: Tingyu Li, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, People’s Republic of China, Tel +86 23 63630913, Fax +86 23 63622754, Email tyli@vip.sina.comPurpose: The present study investigated the age of diagnosis, treatment and demographic factors of Chinese children with autism spectrum disorders (ASD), to provide a scientific basis for the early detection, diagnosis, and intervention of ASD.Patients and Methods: A total of 1500 ASD children aged 2– 7 years old from 13 cities in China were administered questionnaires to examine their diagnosis, treatment, and basic family information. The Childhood Autism Rating Scale (CARS) was used to measure the symptoms and severity of ASD children, and the Children Neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016) was utilized to measure neurodevelopmental levels of ASD children.Results: We found that for children with ASD, the median (p25, p75) age for the initial detection of social behavioral developmental delay was 24 (18, 30) months, while the age for the initial diagnosis was 29 (24, 36) months and the age for the beginning of intervention was 33 (27, 42) months. Multiple linear regression (MLR) analysis suggested that in children with ASD whose parents were divorced, separated, or widowed, or whose mothers were engaged in physical work, the initial detection of social behavioral developmental delay happened later. For the children with ASD who lived in urban areas, had higher levels of ASD symptom severity or whose parents were not divorced or separated, the age for the initial diagnosis was earlier. For the children with ASD who lived in urban areas or whose mothers had received higher level of education, the earlier age for the beginning of intervention was observed, while for those with ASD whose mothers were engaged in physical work, the age for the beginning of training was later.Conclusion: It is recommended to actively carry out health education of ASD and strengthen the support for ASD families to enhance their rehabilitation level.Keywords: autism spectrum disorders, children, age, influencing factors, multicenter

Kaili Li, Sanle Jiang, Hongxue Fu, Yingting Hao, Shijing Tian, Fachun Zhou Department of Critical Care Medicine, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Shijing Tian; Fachun Zhou, Emergency Department, the First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong Qu, 17th Floor, Building 1, Chongqing, People’s Republic of China, Tel +86 023-89011756, Email doctortianshijing@163.com; cyzfc1966@126.com; zfc88@126.comBackground: To identify the risk factors and prognosis of carbapenem-resistant organisms (CRO) in patients with acute cholangitis.Methods: This retrospective observational study was conducted to explore the risk factors and prognosis of CRO infection in 503 acute cholangitis patients diagnosed between July 2013 and January 2022 at the First Affiliated Hospital of Chongqing Medical University, who were divided into a CRO group and non-CRO group based on the presence or absence of CRO. Univariate, multivariate analyses, and the proportional hazards model were used to compare the risk factors and prognosis of CRO suffering in patients with acute cholangitis.Results: We identified 35 patients colonized with CRO from 503 acute cholangitis patients. In the multivariate analysis, tumor (OR=7.09, 95% CI=1.11– 45.30, P=0.038) and chronic kidney disease (OR=8.70, 95% CI=2.11– 35.88, P=0.003) were ascertained as the risk factors of the occurrence on CRO infection under the background of acute cholangitis. CRO infection was identified as an independent risk factor for acute cholangitis patient death (HR=5.147, 95% CI=1.475– 17.595, P=0.01) by Cox proportional-hazards regression.Conclusion: Tumor and chronic kidney disease may be risk factors for CRO infection. Patients diagnosed with acute cholangitis further infected with CRO had a poor prognosis and a more severe mortality. Active screening for CRO is expected to facilitate early prevention, diagnosis, and treatment of high-risk patients.Keywords: CRO, acute cholangitis, risk factors, prognosis

Ao Li, Xiaozhao Zhang, Yihan Guo, Jingyi Wang, Yiran Hao, Yixuan Gu, Ying Jie Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Ying Jie, Tel +86-13693572296, Fax +861058265900, Email jie_yingcn@aliyun.comAbstract: Dry eye is a disease that severely affects patients’ quality of life, increasing the global burden on public health and finance. There is growing evidence that a poor lifestyle is a significant risk factor for dry eye. Along with the development of society, sleep, as a way of life, is also constantly changing. The main manifestations of sleep disorders are reduced sleep time, circadian rhythm disturbances, and sleep breathing disturbances. Sleep disorders and their secondary systemic diseases have attracted wide attention in recent years. This review mainly explored the correlation between sleep disorders and dry eye, and found that sleep-related problems and other factors potentially leading from sleep disorders could be critical factors for dry eye. These results suggest that ophthalmologists should pay attention to the sleep health problems in patients with dry eye, and we hope that this paper can provide help for future research in this field.Keywords: circadian rhythm, sleep, sleep disorders, dry eye

Guangshuo Li,1 Chuanying Wang,1 Shang Wang,1,2 Yahui Hao,2 Yunyun Xiong,1– 3,&ast; Xingquan Zhao1,&ast; 1Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2China National Clinical Research Center for Neurological Diseases, Beijing, People’s Republic of China; 3Chinese Institute for Brain Research, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xingquan Zhao, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No. 119 Nansihuanxilu, Fengtai District, Beijing, 100070, People’s Republic of China, Tel +86– 10– 59975549, Email zxq@vip.163.com Yunyun Xiong, National Clinical Research Center for Neurological Diseases, Beijing, People’s Republic of China, Email xiongyunyun@bjtth.orgObjective: The clinical significance of different glycemic parameters has been rarely investigated in ischemic stroke patients treated with intravenous tissue plasminogen activator (IV tPA). This study was aimed to investigate the association between different glycemic parameters and favorable functional outcome in patients treated with IV tPA.Methods: Patients with ischemic stroke who received IV tPA therapy at our stroke center were retrospectively enrolled. Four glycemic parameters were collected including admission glucose, HbA1c, stress hyperglycemia ratio (SHR) and glycemic gap (GG). Additional information was also recorded including demographics, medical history, stroke severity, imaging measures and mRS score at discharge. We used 5 machine learning models to investigate the predictive value of glycemic parameters.Results: Our study included 294 patients treated with IV tPA. SHR and GG were independently associated with favorable functional outcome (adjusted OR for SHR 0.03, 95% CI 0.01– 0.72, P = 0.03; adjusted OR for GG 1.024, 95% CI 1.00– 1.05, P = 0.04).Conclusion: SHR and GG were associated with functional outcomes in acute ischemic stroke patients with intravenous thrombolysis.Keywords: stroke, thrombolysis, tissue plasminogen activator, glucose, hyperglycemia

Yanjiao Hao, Zhiyu Li, Mingzhi Chang, Xiaoli Zhang Department of Life Science Research Center, College of Basic Medicine, Hebei North University, Zhangjiakou, Hebei, 075000, People’s Republic of ChinaCorrespondence: Xiaoli Zhang, Department of Life Science Research Center, College of Basic Medicine, Hebei North University, Zhangjiakou, Hebei, 075000, People’s Republic of China, Tel +8618931316301, Email 894915208@qq.comBackground: Colorectal cancer (CRC) is a multifactorial disease and one of the most common malignancies worldwide. Salidroside (Sal) is a plant with a wide range of pharmacological effects and plays an important role in the treatment of many diseases, and is considered a new hope for the treatment of tumors. The purpose of this study was to investigate the effect of the combination of Sal and paclitaxel (Pac) on colorectal cancer cells and its mechanism of action.Methods: The effects of different mass concentrations of Sal, Pac, and the combination intervened in the cells for 48 h were examined using the CCK8 method. The inhibition rate was obtained, and the optimal concentration of the respective drug group was screened. The proliferative capacity of the respective group was obtained. Subsequently, the results of apoptosis, cloning, migration, invasion, and angiogenesis were observed through cell morphological analysis (shape observation and Hoechst staining), colony formation assay, cell scratching assay, Transwell, angiogenesis assay, and protein immunoblotting (Western blotting) to detect the expression of epithelial-mesenchymal transition (EMT)-associated proteins and PI3K pathway-associated proteins.Results: Different concentrations of Sal, Pac, and the combined application had significant effects in inhibiting cells in a concentration-dependent manner. Compared with the control group, the Sal group, the Pac group, and the combination group significantly inhibited the clonal number, migration, invasion, and tube-forming ability of colorectal cancer cells. Besides, the combined application had a better effect than the Sal and Pac groups. The apoptosis level was up-regulated in all drug groups, and the up-regulation was more significant in the combination group. The expression of E-cad protein was up-regulated, the expression of N-cad and Vim protein was down-regulated, and the expression of PI3K and AKT phosphorylation was down-regulated in the respective group, and the difference was more significant in the combination group compared with the group of individual drugs.Conclusion: The combined application of Sal and Pac significantly can decrease the survival rate of colorectal cancer cells, and the mechanism may be correlated with the blocking of the PI3K/AKT pathway, thus inhibiting EMT.Keywords: salidroside, paclitaxel, colorectal cancer, apoptosis, PI3K/AKT signaling pathway, EMT

Chao Yan,&ast; Ao Li,&ast; Yiran Hao, Xiaozhao Zhang, Yihan Guo, Yixuan Gu, Yinghui Wang, Ya Wen, Lei Tian, Ying Jie Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Jie; Lei Tian, Tel +86-13693572296 ; +86-18600166885, Fax +861058265900, Email jie_yingcn@aliyun.com; tianlei0131@163.comPurpose: To explore the relationship between symptomatic dry eye and circadian typology in college students.Methods: This study included 269 students from 3 Chinese universities. All participants completed the ocular surface disease index (OSDI) questionnaire, the morningness-eveningness questionnaire (MEQ), and the Pittsburgh sleep quality index (PSQI) questionnaire. Participants were grouped into 3 types by the reduced MEQ (rMEQ) score:E-Type, N-Type, and M-Type. All these parameters were then analyzed for the effect on the severity of dry eye.Results: The occurrence rates of poor sleep quality (PSQI> 5) and symptomatic dry eye (OSDI > 13) in the college students were 53.2% and 40.2%, respectively. The distribution of the circadian typology differed significantly among the college students with different dry eye severities (χ2 = 59.44, P = 0. 000), and E-type was associated with the most severe dry eye symptoms. The OSDI and PSQI scores were both significantly different among college students with different chronotypes (F = 22.14, P = 0.000; F = 15.21, P = 0.000; respectively). For both scores, the E-type scored the highest, followed by N-type, and M-type was the lowest. The circadian typology was an independent factor for dry eye. The risk of E-Type was 6.99 times higher than that of M-Type (P = 0.000), and the risk of N-types was 3.23 times higher than that of M-Type (P = 0.000). Sleep quality was also an independent risk factor for dry eye (P = 0.000). Gender and awareness of dry eye were not risk factors for dry eye.Conclusion: The severity of dry eye symptoms and sleep quality were associated with different circadian typologies. The more the circadian preference tended to be E-type, the worse the sleep quality and the more serious dry eye symptoms would appear.Keywords: circadian typology, college students, dry eye, sleep disorder

Guangshuo Li,1 Yahui Hao,2 Chuanying Wang,1 Shang Wang,1,2 Yunyun Xiong1– 3&ast;, Xingquan Zhao1 &#x002A1Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2China National Clinical Research Center for Neurological Diseases, Beijing, People’s Republic of China; 3Chinese Institute of Brain Research, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunyun Xiong, China National Clinical Research Center for Neurological Diseases, Beijing, People’s Republic of China, Email xiongyunyun@bjtth.org Xingquan Zhao, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No. 119 Nansihuanxilu, Fengtai District, Beijing, 100070, People’s Republic of China, Email zxq@vip.163.comObjective: Investigations on neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) in patients with ischemic stroke are insufficient. We aimed to investigate the relationship of NLR and LMR with in-hospital clinical outcomes at different time points in ischemic stroke patients treated with intravenous tissues plasminogen activator (IV tPA).Methods: We retrospectively enrolled patients who received IV tPA therapy within 4.5 hours from symptoms onset. Demographics, clinical characteristics, imaging measures, and the in-hospital clinical outcomes including early neurological improvement (ENI, defined as NIHSS score reduction within 24 hours ≥ 4 points or decreased to the baseline) and favorable functional outcome (defined as modified Rankin scale 0– 1) were collected. Multivariable logistic regression analyses were performed to test whether NLR or LMR was an independent predictor for the in-hospital clinical outcomes.Results: One hundred and two patients treated with IV tPA were included. NLR at 24 hours proved to be an independent predictor of ENI (adjusted OR=0.85, 95% CI=0.75– 0.95, P=0.04). NLR at 48 hours and LMR at 48 hours proved to be independent predictors of mRS 0– 1 at discharge (NLR at 48 hours: adjusted OR=0.64, 95% CI=0.49– 0.83, P=0.01; LMR at 48 hours: adjusted OR=1.50, 95% CI=1.08– 2.09, P=0.02). The AUC of NLR at 48 hours to predict favorable functional outcome at discharge was 0.79 (95% CI=0.70– 0.88, P< 0.001) and the optimal cut-off was 5.69 (sensitivity=0.52, specificity=0.63).Conclusion: In our study, NLR at 24 hours was correlated with ENI. Both NLR and LMR at 48 hours were closely associated with favorable functional outcomes at discharge.Keywords: stroke, thrombolysis, tissue plasminogen activator, neutrophil, inflammation

Xiaoxia Ding, Yu Wang, Bo Zou, Dongxiao Zang, Yi Hao Department of Ophthalmology, Fushun Eye Hospital, Fushun, Liaoning, People’s Republic of ChinaCorrespondence: Xiaoxia Ding, Fushun Eye Hospital, No. 1 Hupo Street, Xinfu District, Fushun, 113008, People’s Republic of China, Email 791151967@qq.comObjective: To evaluate the efficacy on best corrected visual acuity (BCVA) and microvascular structure changes of conbercept intravitreal injection for the treatment of macular edema (ME) secondary to different types of retinal vein occlusion (RVO) and to explore the baseline OCTA parameters which were related to the change of BCVA and CRT after the intravitreal conbercept injection to RVO.Methods: A retrospective observational study was conducted involving 67 eyes from 67 patients who were diagnosed with ME secondary to RVO between April 2019 to December 2020. The subjects were divided into branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO) according to the involved vessel, subsequently the subjects received intravitreal conbercept treatment. The BCVA and fundus microstructure were measured to identify predictors of effective outcomes.Results: BCVA, central retinal thickness (CRT), fovea avascular zone (FAZ), and foveal vascular density (FVD) in superficial capillary plexus (SCP) were significantly changed from baseline to 6-month follow-up in both CRVO and BRVO. In the BRVO group, age and baseline BCVA were correlated with changes of BCVA, while the baseline CRT, FVD in the DCP, and parafovea vascular density (PFVD) in DCP were associated with changes of CRT (P< 0.05). In the CRVO group, the baseline BCVA was correlated with changes of BCVA, while age, gender, baseline CRT, FVD in DCP, and PFVD in DCP were associated with changes of CRT (P< 0.05). There were no serious adverse events (SAEs) related to the drug or the injection procedure.Conclusion: Intravitreal injections of conbercept can improve BCVA and CRT and change the FVD in SCP effectively both in BRVO and CRVO groups. In addition, the baseline FVD and PFVD in the DCP were related to the change of CRT after intravitreal conbercept treatment.Keywords: conbercept, retinal vein occlusion, macular edema, microvascular structure, best-corrected visual acuity

Yuqi Hao,1 Yong’ang Jiang,1 Hafiz Muhammad Ishaq,2 Wenke Liu,1 Huajie Zhao,1 Mingyong Wang,3 Fan Yang1 1Xinxiang Key Laboratory of Pathogenic Biology, Department of Pathogenic Biology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, People’s Republic of China; 2Faculty of Veterinary and Animal Sciences, Muhammad Nawaz Shareef University of Agriculture, Multan, Pakistan; 3Xinxiang Key Laboratory of Immunoregulation and Molecular Diagnostics, School of Laboratory Medicine, Xinxiang Medical University,, Xinxiang, People’s Republic of ChinaCorrespondence: Fan Yang; Mingyong Wang, Email yangf77@163.com; wmy118@126.comBackground: In clinical practice, Klebsiella pneumoniae (K. pneumoniae) is a common opportunistic pathogen responsible for nosocomial infection. This study aimed to analyze the trend of antimicrobial susceptibility and virulent characteristics of K. pneumoniae isolated from sputum. In clinics, data of the current study will help in the clinical treatment of K. pneumoniae infection.Results: The current research showed the resistance rates of the 20 K. pneumoniae isolates against 13 antibiotics ranged from 15.0% to 80.0%. The detection rate of extended spectrum β-lactamases (ESBLs) was up to 55%, while blaSHV was the most prevalent ESBLs genes. Four strains (25.0%) of K. pneumoniae presented hypermucoviscous phenotype (HMV). Moreover, 18 strains (90.0%) showed the stronger biofilm-forming ability. wzi, wabG, fimH, mrkD were the most prevalent virulence genes in current research. Ten strains were found capsule typing and the higher genetic diversity of colonizing K. pneumoniae in this region. K19 exhibited a strong positive correlation with imipenem resistance, while K1 showed strong correlations with magA. Furthermore, HMV phenotype showed significantly negative correlations with multidrug-resistant.Conclusion: In the hospital, the antibiotic resistance of K. pneumoniae (isolated from sputum samples) has a serious concern. Additionally, strains of K. pneumoniae show the higher genetic diversity.Keywords: Klebsiella pneumoniae, antimicrobial resistance, resistant genes, virulent genes, biofilm-forming

Daidai Wang,1,&ast; Hua Zhang,2,&ast; Lanfang Du,1,&ast; Qiangrong Zhai,1 Guangliang Hu,1 Wei Gao,1 Anyi Zhang,1 Sa Wang,1 Yajuan Hao,1 Kaijian Shang,1,3 Xueqing Liu,1 Yanxia Gao,4 Nijiati Muyesai,5 Qingbian Ma1 1Department of Emergency Medicine, Peking University Third Hospital, Beijing, People’s Republic of China; 2Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, People’s Republic of China; 3Department of Emergency Medicine, Second hospital of Shanxi Medical University, Shanxi, People’s Republic of China; 4Department of Emergency Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 5Department of Emergency Medicine, Xinjiang Ulger Municipal People’s Hospital, Urumqi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingbian Ma; Nijiati Muyesai, Tel +86 15611908229, Email maqingbian@126.com; muyassar11@aliyun.comPurpose: Acute aortic syndrome is a constellation of life-threatening medical conditions for which rapid assessment and targeted intervention are important for the prognosis of patients who are at high risk of in-hospital death. The current study aims to develop and externally validate an early prediction mortality model that can be used to identify high-risk patients with acute aortic syndrome in the emergency department.Patients and Methods: This retrospective multi-center observational study enrolled 1088 patients with acute aortic syndrome admitted to the emergency departments of two hospitals in China between January 2017 and March 2021 for model development. A total of 210 patients with acute aortic syndrome admitted to the emergency departments of Peking University Third Hospital between January 2007 and December 2021 was enrolled for model validation. Demographics and clinical factors were collected at the time of emergency department admission. The predictive variables were determined by referring to the results of previous studies and the baseline analysis of this study. The study’s endpoint was in-hospital death. To assess internal validity, we used a fivefold cross-validation method. Model performance was validated internally and externally by evaluating model discrimination using the area under the receiver-operating characteristic curve (AUC). A nomogram was developed based on the binary regression results.Results: In the development cohort, 1088 patients with acute aortic syndromes were included, and 88 (8.1%) patients died during hospitalization. In the validation cohort, 210 patients were included, and 20 (9.5%) patients died during hospitalization. The final model included the following variables: digestive system symptoms (OR=2.25; P=0.024), any pulse deficit (OR=7.78; P< 0.001), creatinine (μmol/L)(OR=1.00; P=0.018), lesion extension to iliac vessels (OR=4.49; P< 0.001), pericardial effusion (OR=2.67; P=0.008), and Stanford type A (OR=10.46; P< 0.001). The model’s AUC was 0.838 (95% CI 0.784– 0.892) in the development cohort and 0.821 (95% CI 0.750– 0.891) in the validation cohort, and the Hosmer–Lemeshow test showed p=0.597. The fivefold cross-validation demonstrated a mean accuracy of 0.94, a mean precision of 0.67, and a mean recall of 0.13.Conclusion: This risk prediction tool uses simple variables to provide robust prediction of the risk of in-hospital death from acute aortic syndrome and validated well in an independent cohort. The tool can help emergency clinicians quickly identify high-risk acute aortic syndrome patients, although further studies are needed for verifying the prospective data and the results of our study.Keywords: acute aortic syndrome, risk prediction model, emergency department

Baohong Yuan, Danyan Liu, Zunyan Zhu, Yonggang Hao, Kaihua He, Shiyun Deng Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Danyan Liu, Tel/Fax +86 23 8901 1069, Email liudanyan0418@163.comPurpose: Ultrasound-guided thoracic paravertebral block (TPVB) has become increasingly popular for postoperative analgesia after thoracic surgery. We designed this prospective, randomized, double-blind, placebo-controlled trial to investigate the effect of TPVB on blood coagulation in patients after thoracoscopic lobectomy.Patients and Methods: Sixty patients scheduled for thoracoscopic lobectomy were randomly allocated to two groups. Patients underwent ultrasound-guided TPVB with 0.33% ropivacaine (T group) or 0.9% saline (C group) at the end of the surgery under general anesthesia. Patient-controlled intravenous analgesia (PCIA) was administered for both group after the surgery. The primary outcome was the thromboelastogram (TEG) parameters before anesthesia (T0), at the end of operation (T1) and in 1 day (T2) and 2 days (T3) after the operation, the second outcomes were the analgesic effect and the amount of intraoperative opioid consumption, operation time, infusion volume, blood loss and urine volume.Results: The visual analog scale (VAS) scores in group T were lower than group C (P < 0.05). In group T, compared with T0, the R value at T1 and T2 is significantly reduced, and the K value at T1 were significantly shortened, the α-angle and MA value at T1 were significantly increased (P < 0.05). In group C, compared with T0, the R value and K value were significantly shortened, the α-angle and MA value were significantly increased at all postoperative time points (P < 0.05). Compared with group C at the same time point, the R and K values of group T were significantly longer, and the α-angle and MA values were significantly reduced at T2 and T3 points, with statistically significant differences (P< 0.05).Conclusion: TPVB is beneficial to improve postoperative hypercoagulability and promote postoperative rehabilitation of patients after thoracoscopic lobectomy.Keywords: paravertebral nerve block, thoracoscopic lobectomy, thrombelastogram, blood coagulation

Xuejing Li,1– 3,&ast; Meiqi Meng,1– 3,&ast; Junqiang Zhao,4,5 Xiaoyan Zhang,1– 3 Dan Yang,1– 3 Jiaxin Fang,1– 3 Junxin Wang,1– 3 Liu Han,6 Yufang Hao1– 3 1School of Nursing, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Beijing University of Chinese Medicine Collaborating Center of Joanna Briggs Institute, Beijing, People’s Republic of China; 3Beijing University of Chinese Medicine Best Practice Spotlight Organization, Beijing, People’s Republic of China; 4School of Nursing, University of Ottawa, Ottawa, Ontario, Canada; 5Center for Research on Health and Nursing, University of Ottawa, Ottawa, Ontario, Canada; 6Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yufang Hao Liangxiang High Education Park, Fangshan District, Beijing, 102488, People’s Republic of ChinaTel +86-13552850210Email bucmnursing@163.comAbstract: For most breast cancer (BC) patients who have undergone a mastectomy, the decision whether to proceed with breast reconstruction (BR) is complicated and requires deliberation. Shared decision-making (SDM) helps to address those needs and promote informed value-based decisions. However, little is known about the SDM status for BR in BC patients. This scoping review describes: 1) basic characteristics of studies on BR SDM in BC patients; 2) factors influencing BR SDM in BC patients; 3) experience and perception of BR SDM in BC patients; and 4) outcome measures reported. This review was performed in accordance with the Arksey and O’Malley methodology. A total of 5 English and 4 Chinese databases were searched, as well as different sources from grey literature. The data extraction form was developed by referring to the objectives and the Ottawa Decision Support Framework (ODSF). Data was analyzed using thematic analysis, framework analysis and descriptive statistics, with findings presented in the tables and diagrams. A total of 1481 records were retrieved and 42 of these included after screening. In 21 (21/42, 50%) of the studies, patient decision aids (PDAs) were utilized, and in 17 (17/42, 40.48%) of the studies, the factors influencing the implementation of SDM were explored. Of these 17 studies, the factors influencing the implementation of SDM were categorized into the following: the patient level (17/17, 100%), the healthcare level (2/17, 11.76%) and the organizational and system level (7/17, 41.18%). A total of 8 (19.05%) of the 42 studies focused on patients’ experiences and perceptions of SDM, and all studies used qualitative research methods. Of these 8 studies, a total of 7 (7/8, 87.50%) focused on patients’ experiences of SDM participation, and 4 (4/8, 50.00%) focused on patients’ perceptions of SDM. A total of 24 studies (24/42, 57.14%) involved quantitative outcome measures, where 49 items were divided into three classifications according to the outcomes of ODSF: the quality of the decision (17/24, 70.83%), the quality of the decision-making process (20/24, 83.33%), and impact (13/24, 54.17%). Although researchers have paid less attention to other research points in the field of SDM, compared to the design and application of SDM interventional tools, the research team still presents some equally noteworthy points through scoping review. For instance, the various factors influencing BC patients’ participation in SDM for BR (especially at the healthcare provider level and at the organizational system level), patients’ experiences and perceptions. Systematic reviews (SRs) should be conducted to quantify the impact of these different factors on BR SDM. Implementation of scientific theories and methods can inform the exploration and integration of these factors.Keywords: shared decision-making, patients’ decisional aids, breast reconstruction, breast cancer, mastectomy, Ottawa Decision Support Framework

Xiaohua Ma,1 Yuanqiang Hao,1 Lin Liu1,2 1Henan Key Laboratory of Biomolecular Recognition and Sensing, Shangqiu Normal University, Shangqiu, Henan, 476000, People’s Republic of China; 2College of Chemistry and Chemical Engineering, Anyang Normal University, Anyang, Henan, 455000, People’s Republic of ChinaCorrespondence: Yuanqiang Hao; Lin Liu Email hao0736@163.com; liulin82414@aliyun.comAbstract: Exosomes with diameters of 30– 150 nm are small membrane-bound vesicles secreted by a variety of cells. They play an important role in many biological processes, such as tumor-related immune response and intercellular signal transduction. Exosomes have been considered as emerging and noninvasive biomarkers for cancer diagnosis. Recently, a large number of optical and electrochemical biosensors have been proposed for sensitive detection of exosomes. To meet the increasing demands for ultrasensitive detection, nanomaterials have been integrated with various techniques as powerful components. Because of their intrinsic merits of biological compatibility, excellent physicochemical features and unique catalytic ability, nanomaterials have significantly improved the analytical performances of exosome biosensors. In this review, we summarized the recent progress in nanomaterials-based biosensors for the detection of cancer-derived exosomes, including fluorescence, colorimetry, surface plasmon resonance spectroscopy, surface enhanced Raman scattering spectroscopy, electrochemistry, electrochemiluminescence and so on.Keywords: exosomes, nanomaterials, circulating tumor biomarkers, electrochemical biosensor, optical biosensor

Weixin Hou,1– 4 Yulin Hao,1,2 Wenlong Yang,1,2 Tian Tian,1,2 Peng Fang,1,2 Yuqiong Du,1,2 Lianyin Gao,1,2 Yanbin Gao,3,4 Qiuyun Zhang1,2 1Department of Hepatology, School of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 2Department of Hepatology, Beijing Key Laboratory of Traditional Chinese Medicine Collateral Disease Theory Research, Capital Medical University, Beijing, People’s Republic of China; 3Department of Endocrinology, School of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 4Department of Endocrinology, Beijing Key Laboratory of Traditional Chinese Medicine Collateral Disease Theory Research, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Qiuyun ZhangDepartment of Hepatology, School of Traditional Chinese Medicine, Capital Medical University, No. 10 You An Men Wai, Xi Tou Tiao, Feng Tai District, Beijing, 100069, People’s Republic of ChinaTel +86 10 8391 1638Email 19970059@ccmu.edu.cnYanbin GaoDepartment of Endocrinology, School of Traditional Chinese Medicine, Capital Medical University, No. 10 You An Men Wai, Xi Tou Tiao, Feng Tai District, Beijing, 100069, People’s Republic of ChinaTel +86 10 8391 1720Email gyb@ccmu.edu.cnBackground: Acute-on-chronic liver failure (ACLF) is a severe, complicated human disease. E2F1-mediated apoptosis plays an important role in ACLF development. Jieduan-Niwan (JDNW) formula, a traditional Chinese medicine (TCM), has shown remarkable clinical efficacy in ACLF treatment. However, the hepatoprotective mechanisms of the formula are barely understood.Purpose: This study aimed to investigate the mechanisms of JDNW formula in ACLF treatment by specifically regulating E2F1-mediated apoptotic signaling pathways in rats.Methods: The JDNW components were determined by high-performance liquid chromatography (HPLC) analysis. The ACLF rat model was established using human serum albumin immune-induced liver cirrhosis, followed by D-galactosamine and lipopolysaccharide joint acute attacks. The ACLF rat was treated with JDNW formula. Prothrombin time activity was measured to investigate the coagulation function. Liver pathological injury was observed by hematoxylin-eosin (HE) and reticular fiber staining. The hepatocyte apoptosis index and apoptosis rate were determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and flow cytometry, respectively. Additionally, the expression of key genes and proteins that regulate E2F1-mediated apoptosis was analyzed by quantitative real-time PCR and Western blot.Results: Seven major components of JDNW formula were detected. The formula ameliorated the coagulation function, decreased the hepatocyte apoptosis index and apoptosis rate, and alleviated liver pathological damage in ACLF rats. The down-regulation of the expression of genes and proteins from p53-dependent and non-p53-dependent apoptosis pathways and the up-regulation of the expression of genes from blocking anti-apoptotic signaling pathways indicated that JDNW formula inhibited excessive hepatocyte apoptosis in ACLF rats via E2F1-mediated apoptosis signaling pathways.Conclusion: The findings indicate that JDNW formula protects livers of ACLF rats by inhibiting E2F1-mediated apoptotic signaling pathways, implying that these pathways might be a potential therapeutic target for ACLF treatment.Keywords: traditional Chinese medicine, apoptosis, Jieduan-Niwan formula, acute-on-chronic liver failure rat model, E2F1, pharmacological effect

Li-Jun Tian,1,* Hong-Zhi Liu,2,* Qiang Zhang,1 Dian-Zhong Geng,1 Yu-Qing Huo,1 Shou-Jian Xu,1 Yan-Zhang Hao1 1Department of Oncology, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China; 2Department of Orthopedics, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan-Zhang Hao HuangHe Two Road, Binzhou, 256603 Tel +8615506308710Fax +86 (0)543-3257792Email byfyhyz@bzmc.edu.cnPurpose: To evaluate the efficacy and safety of combined-modality therapy for elderly patients with locally advanced non-small-cell lung cancer (NSCLC) invading the chest wall.Patients and Methods: We retrospectively enrolled 21 elderly patients (aged ≥ 60 years) with locally advanced NSCLC invading the chest wall. For external beam radiotherapy (EBRT) of the primary tumor, 40Gy was applied and supplemented with iodine-125 seed implantation while 60Gy was applied to the lymph nodes of the mediastinum. Follow-up was conducted every 3 months postoperatively. The related analytic parameters were change in tumor size, the objective response rate (ORR), the disease control rate (DCR), the degree of pain relief, the improvement of physical status, and toxicity.Results: The combined-modality therapy significantly inhibited local growth of the tumor (from 7.84± 1.20 to 4.69± 1.90 cm) (P < 0.0001), with 71.4% ORR and 90.5% DCR at 1 year. The cancer-related pain was significantly relieved (P < 0.05) and physical status was significantly improved (P < 0.05). No procedure-associated death or grade > 2 irradiation-related adverse effects were reported in this study.Conclusion: The combined-modality therapy of EBRT with 40Gy and permanent iodine-125 seed implantation is an efficacious and safe treatment option for elderly patients with locally advanced NSCLC invading the chest wall.Keywords: iodine-125 seed implantation, external beam radiotherapy, combined therapy, NSCLC, elderly

Wenlu Zou,1– 3,&ast; Jie Lu,4,&ast; Yan Hao5 1Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, 250021, People’s Republic of China; 2Department of Infectious Disease; 3Department of Clinical Laboratory, Shandong University Qilu Hospital, Jinan, Shandong Province, 250012, People’s Republic of China; 4Department of Neurosurgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Medicine and Health Key Laboratory of Neurosurgery, Jinan, 250117, Shandong Province, People’s Republic of China; 5Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Hao Email haoyan02_09@sina.comAbstract: Under physiological conditions, immune checkpoint molecules downregulate the activation and effector function of myocardial antigen-reactive T cells through an immunosuppressive pathway, thus enabling myocardial T cells to maintain immune homeostasis under the action of central and peripheral tolerance mechanisms. The PD-1/PD-L1 signalling pathway is particularly important for limiting the ability of T cells to attack the heart. Immune checkpoint inhibitors (ICIs) specifically block this PD-1/PD-L1-mediated restriction of T cell activation and other immunosuppressive pathways by targeting immune checkpoints. In recent years, with the wide use of ICIs in cancer treatment, even though the incidence of immunomyocarditis is low, it has attracted increasing attention because of its complex clinical symptoms, rapid progression of disease and high mortality rates. The pathogenesis, genetic susceptibility factors and predictive biomarkers of immunomyocarditis still need to be understood, and multidisciplinary cooperation in the clinical treatment of this complication is necessary.Keywords: immunomyocarditis, immune checkpoint inhibitors, anti-PD-1/PD-L1, cancer

Jingyi Pan,* Xinyu Li,* Xinyang Wang, Lili Yang, Houlin Chen, Nana Su, Chenghua Wu, Yu Hao, Shengwei Jin, Hui Li Department of Anaesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hui Li; Shengwei JinDepartment of Anaesthesia and Critical Care, Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People’s Republic of ChinaEmail judy198406@sina.com; jinshengwei69@163.comPurpose: Pulmonary fibrosis (PF) is a progressing lethal disease, effective curative therapies remain elusive and mortality remains high. Maresin conjugates in tissue regeneration 1 (MCTR1) is a DHA-derived lipid mediator promoting inflammation resolution produced in macrophage. However, the effect of MCTR1 on PF remains unknown.Material and Methods: We established a lung fibrosis model in mice induced by intratracheal administration of bleomycin (BLM). On day 7 after lung fibrosis model establishment, treatment with MCTR1 up to day 21. The body weight of each mouse was recorded every day and survival curves were plotted. Histological staining was used to detect pulmonary inflammation and fibrosis. Lung sections were examined with transmission electron microscope to evaluate the ultrastructure of cells and deposit of collagen. Inflammatory cytokines in lung tissues were tested by ELISA. q-PCR and Western blot were used to evaluate the mRNA and the protein levels of EMT-related markers.Results: We found that MCTR1 intervention attenuated BLM-induced lung inflammatory and fibrotic response. Furthermore, MCTR1 protected BLM-induced epithelial cell destroy and reversed epithelial-to-mesenchymal transition phenotype into an epithelial one in lung fibrosis mice. Most importantly, post-treatment with MCTR1 restored BLM-induced lung dysfunction and enhanced survival rate significantly.Conclusion: Posttreatment with MCTR1 attenuated BLM-induced inflammation and fibrosis changes in mice, suggested MCTR1 may serve as a novel therapeutic strategy for fibrosis-related diseases.Keywords: pulmonary fibrosis, MCTR1, EMT, lung dysfunction

Xiaoxue Xu,1 Yuehan Hao,1 Jiao Wu,2 Jing Zhao,1 Shuang Xiong3 1Department of Neurology, The First Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of Neurology, The People’s Hospital of Liaoning Province, Shenyang, People’s Republic of China; 3Liaoning Academy of Analytic Science, Construction Engineering Center of Important Technology Innovation and Research and Development Base in Liaoning Province, Shenyang, People’s Republic of ChinaCorrespondence: Xiaoxue XuDepartment of Neurology, The First Hospital of China Medical University, No. 155, Nanjing Street, Heping District, Shenyang, Liaoning, People’s Republic of ChinaEmail xiaoxue80cn@sina.comPurpose: This study aimed to explore the key molecular pathways involved in Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) and thereby identify hub genes to be potentially used as novel biomarkers using a bioinformatics approach.Methods: Raw GSE109178 data were collected from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was conducted on the top 50% of altered genes. The key modules associated with the clinical features of DMD and BMD were identified. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using the DAVID website. A protein-protein interaction (PPI) network was constructed using the STRING website. MCODE, together with the Cytohubba plug-ins of Cytoscape, screened out the potential hub genes, which were subsequently verified via receiver operating characteristic (ROC) curves in other datasets.Results: Among the 11 modules obtained, the black module was predominantly associated with pathology and DMD, whereas the light-green module was primarily related to age and BMD. Functional enrichment assessments indicated that the genes in the black module were primarily clustered in “immune response” and “phagosome,” whereas the ones in the light-green module were chiefly enriched in “protein polyubiquitination”. Eleven essential genes were eventually identified, including VCAM1, TYROBP, CD44, ITGB2, CSF1R, LCP2, C3AR1, CCL2, and ITGAM for DMD, along with UBA5 and UBR2 for BMD.Conclusion: Overall, our findings may be useful for investigating the mechanisms underlying DMD and BMD. In addition, the hub genes discovered might serve as novel molecular markers correlated with dystrophinopathies.Keywords: Duchenne muscular dystrophy, Becker muscular dystrophy, WGCNA, biomarker, pathway

Yan Hao,1 Jie Miao,2 Wenjia Liu,1 Kangqin Cai,1 Xianli Huang,1 Li Peng1 1Department of Nephrology, The First People’s Hospital of Zigong, Zigong, 643000, Sichuan, People’s Republic of China; 2Department of Nephrology, The Health and Rehabilitation Vocational College of Sichuan, Zigong, 643000, Sichuan, People’s Republic of ChinaCorrespondence: Yan HaoDepartment of Nephrology, The First People’s Hospital of Zigong, No. 42, Shangyi Road, Daoshenghao Community, Ziliujing District, Zigong, 643000, Sichuan, People’s Republic of ChinaTel/Fax +86-13990087106Email haoyan12301@163.comBackground: Mesenchymal stem cell (MSC)-derived exosomes have seen great advances in human disease control in a minimally invasive manner. This research aimed to explore the function of MSC-derived exosomes in diabetic nephropathy (DN) progression and the molecules involved.Methods: A rat model with DN and rat glomerular mesangial cell (GMC) models treated with high glucose (HG) were established, which were treated with exosomes from adipose-derived-MSCs (adMSCs). The levels of blood glucose, serum creatinine, and urinary protein, the urine albumin-to-creatinine ratio (UACR), kidney weight/body weight, and mesangial hyperplasia and kidney fibrosis in rats were determined. The expression of interleukin-6 (IL-6), collagen I (Col. I), fibronectin (FN), Bax and Bcl-2 in HG-treated GMCs was assessed. The microRNA (miRNA) carried by adMSC-exosomes was identified, and the implicated down-stream molecules were analyzed.Results: adMSC-derived exosomes decreased levels of blood glucose, serum creatinine, 24-h urinary protein, UACR and kidney weight/body weight, and they suppressed mesangial hyperplasia and kidney fibrosis in DN rats. The exosomes also suppressed levels of IL6, Col. I and FN in HG-treated GMCs and promoted cell apoptosis. miR-125a was at least partially responsible for the above protective events mediated by adMSC-exosomes. miR-125a directly bound to histone deacetylase 1 (HDAC1), while HDAC1 further regulated endothelin-1 (ET-1) activation. Up-regulation of HDAC1 blocked the functions of adMSC-exosomal miR-125a.Conclusion: This study suggested that adMSC-derived exosomes inhibit DN progression and alleviate the symptoms by carrying miR-125a, during which HDAC1 and ET-1 were inhibited. This study may provide novel effects into DN treatment.Keywords: exosomes, miR-125a, HDAC1, ET-1, diabetic nephropathy

Yuan Zhang,1,2,* Xiaohang Chen,1,2,* Zilan Zhou,1,2 Yujia Hao,1,2 Huifei Li,1,2 Yongfeng Cheng,1,2 Xiuyun Ren,1,2 Xing Wang1,2 1Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, People’s Republic of China; 2Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xing Wang; Xiuyun RenShanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, People’s Republic of ChinaEmail tt1984621@163.com; rxy611@163.comAbstract: The extraction of impacted lower third molars (ILTM) is one of the most common procedures in oral-maxillofacial surgery. Being adjacent to lower second molars, most impacted lower third molars often lead to distal periodontal defects of adjacent second molars. Several symptoms may occur after extraction, such as periodontal pocket formation, loss of attachment, alveolar bone loss and even looseness of second molar resulting in extraction. The distal periodontal defects of second molars are affected by many factors, including periodontal conditions, age, impacted type of third molars, and intraoperative operations. At present, several studies have suggested that dentists can reduce the risk of periodontal defects of the second molar after ILTM extraction through preoperative evaluation, reasonable selection of flap design, extraction instruments and suture type, and necessary postoperative interventions. This review summarizes the research progress on the influence factors, interventions methods and some limitations of distal periodontal defects of adjacent second molar after extraction of impacted mandibular third molars, with the aim of opening up future directions for studying effects of ILTM extraction on periodontal tissue of the adjacent second molar.Keywords: impacted lower third molar, periodontal defect, alveolar bone defect, second molar, teeth extraction

Pan Gao,1,2,* Hongtao Liu,3,* Zhenzhen Yang,1,2 Yiran Hui,2,4 Zhuangzhuang Shi,2 Zhen Yang,2 Min Song,2 Menghui Yao,2 Wenfei Fan,1 Jinhua Yang,1 Yibin Hao,1 Tianli Fan2 1People’s Hospital of Zhengzhou, Zhengzhou, Henan, 450001, People’s Republic of China; 2Department of Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, Henan, 450001, People’s Republic of China; 3Laboratory for Cell Biology, College of Life Sciences of Zhengzhou University, Zhengzhou, Henan, 450001, People’s Republic of China; 4University of Chinese Academy of Sciences-Shenzhen Hospital, Shenzhen, Guangdong, 518106, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tianli FanDepartment of Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, Henan, 450001, People’s Republic of ChinaEmail fantianli@zzu.edu.cnPurpose: Increasing evidence has demonstrated that animal models are imperative to investigate the potential molecular mechanism of metastasis and discover anti-metastasis drugs; however, efficient animal models to unveil the underlying mechanisms of metastasis in esophageal squamous cell carcinoma (ESCC) are limited.Methods: ESCC cell EC9706 with high invasiveness was screened by repeated Transwell assays. Its biological characteristics were identified by flow cytometry as well as by the wound healing and CCK-8 assays. Besides, the levels of epithelial–mesenchymal transition-related markers were examined using Western blotting. Parental (EC9706-I0) and subpopulation (EC9706-I3) cells were employed to establish the renal capsule model. Next, the tumor growth was detected by a live animal imaging system, and hematoxylin and eosin staining was applied to evaluate the metastatic status in ESCC.Results: EC9706-I3 cells showed rapid proliferation ability, S phase abundance, and high invasive ability; obvious upregulation in N-cadherin, Snail, Vimentin, and Bit1; and downregulation in E-cadherin. EC9706-I3 cells were less sensitive to the chemotherapy drug 5-fluorouracil than EC9706-I0 cells; however, both cell lines reached a tumorigenesis rate of 100% in the renal capsule model. The live animal imaging system revealed that the tumors derived from EC9706-I0 cells grew more slowly than those from EC9706-I3 cells at weeks 3– 14. The EC9706-I3 xenograft model displayed a spontaneous metastatic site, including kidney, heart, liver, lung, pancreas, and spleen, with a distant metastatic rate of 80%.Conclusion: Our data suggested that the metastatic model was successfully established, providing a novel platform for further exploring the molecular mechanisms of metastasis in ESCC patients.Keywords: esophageal squamous cell carcinoma, renal capsule model, spontaneous metastasis, epithelial–mesenchymal transition process

Yangquan Hao, Chao Lu, Baogang Zhang, Zhaochen Xu, Hao Guo, Gaokui Zhang Department of Osteonecrosis and Joint Reconstruction, Honghui Hospital Xian Jiao Tong University Health Science Center, Xian, Shaanxi 710068, People’s Republic of ChinaCorrespondence: Yangquan HaoDepartment of Osteonecrosis and Joint Reconstruction, Honghui Hospital Xian Jiao Tong University Health Science Center, No. 555 Youyi East Road, Xian, Shaanxi 710068, People’s Republic of ChinaTel +86 13991038599Fax +86 29-87894724Email yangquan_haodoctor@163.comPurpose: Osteonecrosis of the femoral head is a common disease of the hip that leads to severe pain or joint disability. We aimed to identify potential differentially expressed miRNAs and mRNAs in osteonecrosis of the femoral head.Methods: The data of miRNA and mRNA were firstly downloaded from the database. Secondly, the regulatory network of miRNAs–mRNAs was constructed, followed by function annotation of mRNAs. Thirdly, an in vitro experiment was applied to validate the expression of miRNAs and targeted mRNAs. Finally, GSE123568 dataset was used for electronic validation and diagnostic analysis of targeted mRNAs.Results: Several regulatory interaction pairs between miRNA and mRNAs were identified, such as hsa-miR-378c-WNT3A/DACT1/CSF1, hsa-let-7a-5p-RCAN2/IL9R, hsa-miR-28-5p-RELA, hsa-miR-3200-5p-RELN, and hsa-miR-532-5p-CLDN18/CLDN10. Interestingly, CLDN10, CLDN18, CSF1, DACT1, IL9R, RCAN2, RELN, and WNT3A had the diagnostic value for osteonecrosis of the femoral head. Wnt signaling pathway (involved WNT3A), chemokine signaling pathway (involved RELA), focal adhesion and ECM-receptor interaction (involved RELN), cell adhesion molecules (CAMs) (involved CLDN18 and CLDN10), cytokine–cytokine receptor interaction, and hematopoietic cell lineage (involved CSF1 and IL9R) were identified.Conclusion: The identified differentially expressed miRNAs and mRNAs may be involved in the pathology of osteonecrosis of the femoral head.Keywords: osteonecrosis of the femoral head, miRNAs, mRNAs, signaling pathway

Xiang Zhang, Yarong Hao Department of Geriatrics, Renmin Hospital of Wuhan University, Hubei, People’s Republic of ChinaCorrespondence: Yarong HaoDepartment of Geriatrics, Renmin Hospital of Wuhan University, 99 Zhang Zhidong Road, Wuchang District, Wuhan, Hubei Province, People’s Republic of ChinaTel +86 18827688568Email 984022801@qq.comPurpose: In this study, we investigated the protective effects and mechanism of action of echinacoside (ECH) from cistanche tubulosa extract in cardiomyocytes of db/db diabetic mice.Methods: Twenty healthy male db/db mice aged 8 weeks were randomly divided into db/db+ECH (n=10, ECH, 300 mg/(kg/d)), db/db (n=10, saline), and db/m control groups (n=9). Mice were monitored weekly for diet and activity. Mice were injected with 2% of pentobarbital sodium in week 10 and executed. Weight and free blood glucose (FBG) were measured weekly. Echocardiographs were used to detect cardiac function. HE staining, Sudan II staining, Masson’s trichrome staining and Tunel assays were used to evaluate myocardial tissue pathological changes, collagen fiber deposition, lipid accumulation and apoptosis rates in cardiomyocytes, respectively. Western blot and RT-PCR analysis were used to detect the expression of components of the PPAR-α/M-CPT-1 and p53/p38MAPK signaling axis.Results: Compared to db/db mice, ECH groups showed lower blood glucose and lipid levels. Deterioration in cardiac function was also delayed following ECH treatment. Histopathological analysis showed that ECH significantly improved myocardial tissue in db/db mice, including reduced intercellular spaces, regular arrangements, improved extracellular matrix deposition, and reduced lipid accumulation. ECH also significantly reduced oxidative stress levels in myocardial tissue in db/db mice. Moreover, ECH inhibited PPAR-α/M-CPT-1 signaling, downregulated CD36, and upregulated glucose transporter type 4 (GLUT-4) expression in db/db mouse models of DCM. ECH also inhibited p53/p38MAPK signaling, downregulated caspase-3 and caspase-8, and upregulated Bcl-2/Bax in db/db mouse models of DCM.Conclusion: ECH displays protective effects in DCM, including the inhibition of cardiac apoptosis and oxidative stress, and improved lipid metabolism in cardiomyocytes. ECH also inhibits cardiac apoptosis through its regulation of p53/p38MAPK signaling, and prevents lipid accumulation through suppression of the PPAR-α/M-CPT-1 signaling axis.Keywords: diabetic cardiomyopathy, echinacoside, lipid metabolism disorders, PPAR-α, p53/p38MAPK signaling

Yu Hao,1,* Ting Li,1,2,* Chanfan Zheng,2 Shengwei Jin1 1Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2Clinical Research Unit, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shengwei Jin Email jinshengwei69@163.com

Hongna Dong,1,* Yuqiu Hao,1,* Dapeng Li,2 Zhenzhong Su,1 Wei Li,1 Bingqing Shi,1 Peng Gao1 1Department of Respiratory Medicine, Second Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China; 2Department of Respiratory Medicine, Affiliated Hospital of Jilin Medical College, Jilin, Jilin Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Peng GaoDepartment of Respiratory, Second Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of ChinaTel/Fax +86-43181136866Email gaopeng1234@sina.comBackground: The exacerbation of chronic obstructive pulmonary disease (COPD) seriously affects the patient’s quality of life and prognosis. This multicenter cross-sectional study investigated the characteristics of stable COPD and risk factors for acute exacerbation of COPD (AECOPD) in patients in Changchun, Jilin Province, China.Methods: The study included 400 outpatients admitted to four secondary hospitals and four tertiary hospitals in Jilin Province from March 2018 to March 2019. Data on the general condition of stable COPD patients, patient self-management, COPD Assessment Test (CAT) scores, number of acute exacerbations in the past 12 months, and medications received during the study period were collected using a questionnaire.Results: Sociodemographic characteristics and clinical data were obtained from 306 patients, and drug prescription data were obtained from 329 patients. Pearson correlation analysis revealed that CAT scores were positively correlated with the number of acute exacerbations. Age, education level, smoking history, disease duration, number of comorbidities, and the presence of ischemic heart disease (IHD) were associated with AECOPD. Moreover, the level of education, disease duration, and the presence of IHD were independent risk factors for AECOPD. Poor compliance due to the lack of understanding of the disease and the high cost of treatment is a risk factor for AECOPD. In addition, increased air pollution in industrial cities and vitamin D deficiency are closely related to AECOPD.Conclusion: Low education level, long disease duration, and the presence of IHD may promote the exacerbation and poor control of COPD in patients in Jilin Province.Keywords: COPD, exacerbation, risk factors, Jilin Province

Muhammad Fawad,1,2 Sumaira Mubarik,3 Saima Shakil Malik,4 Yangyang Hao,2 Chuanhua Yu,3 Jingli Ren1 1Henan Academy of Big Data, Zhengzhou University, Zhengzhou 450052, People’s Republic of China; 2School of Mathematics and Statistics, Zhengzhou University, Zhengzhou 450001, People’s Republic of China; 3Department of Epidemiology and Biostatistics, School of Health Sciences, Wuhan University, Wuhan, Hubei 430071, People’s Republic of China; 4Department of Zoology, University of Gujrat, Gujrat 50700, PakistanCorrespondence: Jingli RenHenan Academy of Big Data, Zhengzhou University, Zhengzhou 450052, People’s Republic of ChinaTel +86-13653827917Email renjl@zzu.edu.cnObjective: A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detected by researchers from a patient in Wuhan, Hubei province, China, in December 2019, and broke out in January 2020. Then, the pandemic was detected in countries around the world. Therefore, precise estimates of its current and future trends are highly required for future policy implications.Methods: We retrieved data from the Health Commission of Hubei, China. Logistic-S curve model was used to estimate the current and future trends of SARS-CoV-2-infected cases among 16 cities of Hubei, China from Jan-11 to Feb-24, 2020.Results: Out of 64,287 confirmed cases of SARS-CoV-2 infection in Hubei, higher percentage of cases were in Wuhan and Xiaogan. The highest death percentage was found in Wuhan and Qianjiang. A significant percentage of cures were found in Enshi Prefecture and Huanggang, while Wuhan showed the lowest percentage of cures. Rising trends in infected cases were observed throughout the study period, particularly in Wuhan, and a higher trend was observed after 12-Feb. Gradual decline trend of SARS-CoV-2 cases was observed during Feb-25 to Mar-15 in Hubei Province. Future forecast showed that the average number of SARS-CoV-2-infected cases might be decreased or stable in Hubei in the coming 20 days.Conclusion: The public must take precautionary measures in order to control and prevent disease spread and avoid extra travelling.Keywords: SARS-CoV-2, death, trends, cities, Wuhan, China

Yanhong Hao,1,* Junfeng Xi,1,* Yancai Peng,1 Burong Bian,2 Guangjun Hao,2 Yunfeng Xi,3 Zhibin Zhang1 1Department of Cardiothoracic Surgery, The First Hospital of Yulin, Yulin City, Shanxi Province, People’s Republic of China; 2Department of Oncology, The First Hospital of Yulin, Yulin City, Shanxi Province, People’s Republic of China; 3Department of Dermatological Surgery, The First Hospital of Yulin, Yulin City, Shanxi Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhibin Zhang Email r7mj90@163.comBackground: Patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) have a poor prognosis. Circular RNA circ_0016760 (circ_0016760) is associated with the development of NSCLC. At present, the role and regulatory mechanism of circ_0016760 in NSCLC have not been well explained.Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was executed to detect the expression of circ_0016760, miR-577, and Zinc finger and BTB domain containing 7A (ZBTB7A) mRNA in NSCLC tissues and cells. The colony formation, migration, invasion, and extracellular acidification rate (ECAR) of NSCLC cells were determined through colony formation, transwell, or ECAR assays. The relationship between circ_0016760 or ZBTB7A and miR-577 was analyzed via dual-luciferase reporter and RNA pull-down or RNA immunoprecipitation (RIP) assays. Protein level of ZBTB7A was evaluated with Western blot analysis. Xenograft assay was conducted to confirm the role of circ_0016760 in vivo.Results: Circ_0016760 and ZBTB7A were upregulated and miR-577 was downregulated in NSCLC tissues and cells. Circ_0016760 exhaustion curbed the colony formation, migration, invasion, and ECAR of NSCLC cells in vitro and impeded tumor growth in vivo. Mechanically, circ_0016760 modulated ZBTB7A expression via sponging miR-577 in NSCLC cells. MiR-577 downregulation abolished the repressive effects of circ_0016760 silencing on colony formation, migration, invasion, and ECAR of NSCLC cells. Also, ZBTB7A upregulation overturned the repressive impacts of miR-577 elevation on colony formation, migration, invasion, and ECAR of NSCLC cells.Conclusion: Circ_0016760 silencing impeded NSCLC advancement through regulation of the miR-577/ZBTB7A axis.Keywords: circ_0016760, miR-577, ZBTB7A, NSCLC, ECAR

Yunsheng Dong,1 Huahong Zhuang,1 Yan Hao,1 Lin Zhang,1 Qiang Yang,2 Yufei Liu,1 Chunxiao Qi,1 Shufang Wang1 1State Key Laboratory of Medicinal Chemical Biology, The Key Laboratory of Bioactive Materials, The College of Life Science, Nankai University, Tianjin, People’s Republic of China; 2Department of Spine Surgery, Tianjin Hospital, Tianjin, People’s Republic of ChinaCorrespondence: Qiang Yang No. 406 Jiefang Nan Road, Tianjin 300211, People’s Republic of ChinaEmail yangqiang1980@126.comShufang Wang No. 94 Weijin Road, Nankai District, Tianjin 300071, People’s Republic of ChinaEmail wangshufang@nankai.edu.cnIntroduction: Chronic trauma repair is an important issue affecting people’s healthy lives. Thermo-sensitive hydrogel is injectable in situ and can be used to treat large-area wounds. In addition, antioxidants play important roles in promoting wound repair.Methods: The purpose of this research was to prepare a novel thermo-sensitive hydrogel-poly(N-isopropyl-acrylamide)/poly(γ-glutamic acid) (PP) loaded with superoxide dismutase (SOD) to improve the effect for trauma treatment. The micromorphology of the hydrogel was observed by scanning electron microscope and the physical properties were measured. The biocompatibility of hydrogel was evaluated by MTT experiment, and the effect of hydrogel on skin wound healing was evaluated by in vivo histological staining.Results: Gelling behavior and differential scanning calorimeter outcomes showed that the PP hydrogels possessed thermo-sensitivity at physiological temperature and the phase transformation temperature was 28.2°C. The high swelling rate and good water retention were conducive to wound healing. The activity of SOD in vitro was up to 85% at 10 h, which was advantageous to eliminate the superoxide anion. MTT assay revealed that this hydrogel possessed good biocompatibility. Dressings of PP loaded with SOD (SOD-PP) had a higher wound closure rate than other treatments in vivo in diabetic rat model.Discussion: The SOD-PP thermo-sensitive hydrogels can effectively promote wound healing and have good application prospects for wound repair.Keywords: thermo-sensitive hydrogels, wound dressing, superoxide dismutase, poly(γ-glutamic acid)

Chunyan Liu, Yanan Hao, Fei Yin, Jianhui Liu Chongqing Key Laboratory of Medicinal Chemistry & Molecular Pharmacology, Chongqing University of Technology, Chongqing 400054, People’s Republic of ChinaCorrespondence: Jianhui Liu; Fei YinChongqing Key Laboratory of Medicinal Chemistry & Molecular Pharmacology, Chongqing University of Technology, Hongguang Road 69, Ba’nan District, Chongqing 400054, People’s Republic of ChinaTel/Fax +86-23-6256-3182Email jhliu@cqut.edu.cn; fyin@cqut.edu.cnPurpose: To investigate the effect of geniposide on the biosynthesis of insulin and the expression protein disulfide isomerase (PDI) and endoplasmic reticulum oxidoreductin 1 (ERO1) in the presence of low (5 mM) and high (25 mM) glucose in pancreatic β cells.Methods: The content of insulin was measured by ELISA, the number of SH groups was determined with the classical chromogenic reagent, 5,5ʹ-dithiobis-(2-nitrobenzoic) acid (DTNB; also known as Ellman’s reagent), the expressions of PDI and ERO1 were analyzed by Western blot.Results: Geniposide played contrary roles on the accumulation of H 2O 2, the ratio of GSH/GSSG and the thiol–disulfide balance in the presence of low (5 mM) and high (25 mM) glucose in rat pancreatic INS-1 cells. Geniposide also regulated the protein levels of protein disulfide isomerase (PDI) and endoplasmic reticulum oxidoreductin1 (ERO1), the two key enzymes for the production of H 2O 2 during the biosynthesis of insulin in INS-1 cells.Conclusion: Geniposide affects glucose-stimulated insulin secretion by modulating the thiol–disulfide balance that is controlled by the redox signaling in pancreatic β cells.Keywords: endoplasmic reticulum oxidoreductin1, ERO1, geniposide, protein disulfide isomerase, PDI, glucose-stimulated insulin secretion, GSIS, type 2 diabetes mellitus, T2DM

Abstract We argue that global F-theory compactifications to four dimensions gener- ally exhibit higher rank Yukawa matrices from multiple geometric contributions known as Yukawa points. The holomorphic couplings furthermore have large hierarchies for generic complex structure moduli. Unlike local considerations, the compact setup realizes these features all through geometry, and requires no instanton corrections. As an example, we consider a concrete toy model with SU(5) × U(1) gauge symmetry. From the geometry, we find two Yukawa points for the 1 0 − 2 5 ¯ 6 5 ¯ − 4 $$ \mathbf{1}{\mathbf{0}}_{-2}{\overline{\mathbf{5}}}_6{\overline{\mathbf{5}}}_{-4} $$ coupling, producing a rank two Yukawa matrix. Our methods allow us to track all complex structure dependencies of the holomorphic couplings and study the ratio numerically. This reveals hierarchies of O $$ \mathcal{O} $$ (105) and larger on a full-dimensional subspace of the moduli space.

Yanli Hao,1 Yuanyuan Hu,2 Haili Wang,3 Dhirendra Paudel,4,5 Yan Xu,4–6 Bin Zhang4–6 1Department of Human Anatomy, Guangzhou Medical University, Guangzhou 511436, People’s Republic of China; 2Zhongshan Third People’s Hospital, Zhongshan, People’s Republic of China; 3Ganzhou Third People’s Hospital, Ganzhou, People’s Republic of China; 4Department of Psychiatry, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 5Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangzhou, People’s Republic of China; 6Guangdong Provincial Mental Health Institute, Guangzhou, People’s Republic of ChinaCorrespondence: Bin ZhangDepartment of Psychiatry, Nanfang Hospital, Southern Medical University, No 1838, Guangzhou Northern Road, Guangzhou 510515, People’s Republic of ChinaTel/fax +8620-62786731Email zhang73bin@hotmail.comBackground and aims: Fluvoxamine can markedly increase the serum melatonin level, which regulates human circadian rhythm. However, only limited research has evaluated the effects of fluvoxamine on sleep architecture. Thus, the current study aims to investigate the effect of fluvoxamine on PSG characteristics and the impact of persistent insomnia on the prognosis of depression in the depressed individual with insomnia over the course of 8 weeks.Methods: Thirty-one clinically depressed patients with insomnia were enrolled in this 8-week, open-label, baseline-controlled study, and 23 patients completed the study. All participants were assigned to receive fluvoxamine for 8 weeks. They were assessed by the PSG, Hamilton Rating Scale for Depression (17 items) (HRSD-17), Clinical Global Index, Pittsburgh Sleep Quality Index, and Epworth Sleepiness Scale at baseline and the following visits, which were at day 14, day 28, and day 56. A patient with an ≥4 HRSD-17 sleep disturbance factor score at both baseline and endpoint (day 56) was defined as a patient with persistent insomnia.Results: Compared with baseline, the percentage of stage 3 sleep had significantly (F=11.630, P=0.001) increased in all 3 visits. Moreover, the percentage of rapid eye movement sleep was reduced during the study, with only a significant difference (F=3.991, P=0.027) between baseline and day 14. Finally, 47.8% (11/23) of the participants were in remission, and 60.9% (14/23) of them did not report insomnia. The clinical remission ratio of the persistent insomnia group (11.1% [1/9]) (χ2=8.811, P=0.004) was significantly lower than that of the non-insomnia group (71.4% [10/14]) at the endpoint. Additionally, during the first clinical evaluation (day 14), patients without insomnia had significantly higher final remission ratios than patients with insomnia (80% [8/10] versus 30.8% [4/13]; χ2=5.79; P=0.016).Conclusion: Fluvoxamine improved PSG parameters and ameliorated complaints of insomnia simultaneously during this 8-week study. Moreover, depressed individuals who reported persistent insomnia were at higher risk of remaining depressed by the end of the trial, which might be forecasted by the sleep status on day 14.Trial registration: The Effect of Fluvoxamine on Polysomnogram in Depressed Patients with Insomnia; https://clinicaltrials.gov/ct2/show/NCT02442713. Registry identifier: NCT02442713. Registry date: May 13, 2015.Keywords: fluvoxamine, depression, insomnia, polysomnogram

Yuxing Cai,1 Yi Hao,2 HaiFeng Ren,3 ZhiGuo Dang,3 Hui Xu,1 Xiangfei Xue,1 Yan Gao3 1Department of Respiratory Medicine, Baoji Central Hospital, Baoji, 721008, People’s Republic of China; 2Department of Pediatric Surgery, Baoji Maternal and Child Health Hospital, Baoji, 721008, People’s Republic of China; 3Department of Respiratory Medicine, People Hospital BaoJi City, Baoji, 721001, People’s Republic of ChinaCorrespondence: Yan GaoDepartment of Respiratory Medicine, People Hospital BaoJi City, No. 24 Xinhua Street, Weibin District, Baoji City, Shanxi Province 721001, People’s Republic of ChinaEmail zhungao703730393@126.comBackground: Increasing evidence has suggested the critical implication of microRNAs (miRNAs) in the initiation and progression of non-small cell lung cancer (NSCLC). Previous studies have shown the tumor-suppressive function of miR-1305 in cancer; however, the role of miR-1305 in NSCLC has not been fully understood.Methods: The expression of miR-1305 in NSCLC was detected by RT-qPCR. The influence of miR-1305 on the growth of NSCLC cells was determined via Cell Counting Kit 8 (CCK-8), colony formation and FACS analysis. The targets of miR-1305 were predicted with the miRDB database. Luciferase reporter assay was performed to investigate the binding between miR-1305 and 3ʹ-UTR of MDM2. Western blot was applied to check the expression of MDM2 with miR-1305.Results: Here, we found that miR-1305 was down-regulated in NSCLC tissues and cell lines. Decreased miR-1305 was significantly correlated with the metastasis and poor prognostics of NSCLC patients. Overexpression of miR-1305 inhibited the proliferation and migration and promoted the apoptosis of NSCLC cells. Bioinformatics and luciferase assay uncovered that the mouse/murine double minute 2 (MDM2) was a target of miR-1305. miR-1305 bound the 3ʹ-untranslated region (UTR) of MDM2 and decreased the expression of MDM2 in NSCLC cells. As MDM2 was a negative regulator of p53, decreased MDM2 by miR-1305 up-regulated the abundance of p53 in NSCLC cells. Restoration of MDM2 markedly attenuated the suppressive role of miR-1305 in the proliferation and migration of NSCLC cells.Conclusion: The findings provided novel mechanism of miR-1305/MDM2 signaling in regulating the progression of NSCLC, suggesting miR-1305 as a promising target for the treatment of NSCLC.Keywords: NSCLC, miR-1305, MDM2, p53

Zhao Z, Wu C, Zhao Y, Hao Y, Liu Y, Zhao W. Int J Nanomedicine. 2015;10:1691–1701. The authors have advised due to an error at the time of figure assembly, Figure 1B on page 1694 is incorrect. The correct Figure 1 is shown in Download Article. The authors apologize for this error and advise it does not affect the results of the paper. Read the original article

BackgroundThe lack of understanding of molecular pathologies of the solitary functioning kidney makes improving and strengthening the continuity of care between pediatric and adult nephrological patients difficult. Copy number variations (CNVs) account for a molecular cause of solitary functioning kidney, but characterization of the pathogenic genes remains challenging.MethodsIn our prospective cohort study, 99 fetuses clinically diagnosed with a solitary functioning kidney were enrolled and evaluated using chromosomal microarray analysis (CMA). The genetic drivers for the pathogenic CNVs were analyzed. We characterized QPRT localization in fetal kidneys using immunohistochemistry and its expression in adult kidneys using quantitative RT-PCR. Further, QPRT was knocked down using siRNA in human embryonic kidney (HEK293T) cells, and the cell cycle and proliferation were tested.ResultsBesides one Triple X syndrome and one Down syndrome, we identified a total of 45 CNVs out of 34 subjects. Among the 14 pathogenic CNVs, CNV 16p11.2 reached the highest number of records with the phenotype of kidney anomalies in the Decipher database. Among the 26 genes within the 16p11.2 region, as a key enzyme for nicotinamide adenine dinucleotide (NAD+) biosynthesis, QPRT was distinctly localized in renal tubules but was barely observed in renal interstitial and glomeruli in fetal kidneys. The loss of QPRT prevented cells’ efficient transition into S phase, affected cell-cycle progression, and abrogated proliferation of human embryonic kidney cells.ConclusionOur data suggest that QPRT is a candidate gene associated with susceptibility for solitary functioning kidney. The CNVs discovered in our study exhibit great potential for future applications in genetic counseling and pregnancy management.