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Bo Jin,1 Kexin Lu,2 Wenna Gao,1 Yixian Liu,3 Mengfei Wang,2 Xiaojun Zhang,3 Huiping Chen,3 Liyun Zheng,3 Min Zou3 1Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Hennan, 450052, People’s Republic of China; 2BGI College, Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 3Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450052, People’s Republic of ChinaCorrespondence: Min Zou; Liyun Zheng, Email Minzou1980@126.com; zhengliyun@zzu.edu.cnBackground: At present, the few photothermal/chemotherapy studies about retinoblastoma that have been reported are mainly restricted to ectopic models involving subcutaneous implantation. However, eyeball is unique physiological structure, the blood-retina barrier (BRB) hinders the absorption of drug molecules through the systemic route. Moreover, the abundant blood circulation in the fundus accelerates drug metabolism. To uphold the required drug concentration, patients must undergo frequent chemotherapy sessions.Purpose: To address these challenges above, we need to develop a secure and effective drug delivery system (FA-PEG-PDA-DOX) for the fundus.Methods: We offered superior therapeutic efficacy with minimal or no side effects and successfully established orthotopic mouse models. We evaluated cellular uptake performance and targeting efficiency of FA-PEG-PDA-DOX nanosystem and assessed its synergistic antitumor effects in vitro and vivo. Biodistribution assessments were performed to determine the retention time and targeting efficiency of the NPs in vivo. Additionally, safety assessments were conducted.Results: Cell endocytosis rates of the FA-PEG-PDA-DOX+Laser group became 5.23 times that of the DOX group and 2.28 times that of FA-PEG-PDA-DOX group without irradiation. The fluorescence signal of FA-PEG-PDA-DOX persisted for more than 120 hours at the tumor site. The number of tumor cells (17.2%) in the proliferative cycle decreased by 61.6% in the photothermal-chemotherapy group, in contrast to that of the saline control group (78.8%). FA-PEG-PDA-DOX nanoparticles(NPs) exhibited favorable biosafety and high biocompatibility.Conclusion: The dual functional targeted nanosystem, with the effects of DOX and mild-temperature elevation by irradiation, resulted in precise chemo/photothermal therapy in nude mice model.Keywords: retinoblastoma, orthotopic model, nanoparticle, synergistic therapy

Jing Wang,1 Wenyue Gao,1 Hongbo Yu,1 Yuting Xu,1 Changchuan Bai,2 Qingwei Cong,1 Ying Zhu1 1Infectious Department, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116000, People’s Republic of China; 2Internal Department of Chinese Medicine, Dalian Hospital of Traditional Chinese Medicine, Dalian, Liaoning, 116013, People’s Republic of ChinaCorrespondence: Ying Zhu, Email zhuyingsh52@126.comAbstract: Hepatocellular carcinoma (HCC) stands as the prevailing form of primary liver cancer, characterized by a poor prognosis and high mortality rate. A pivotal factor in HCC tumorigenesis is epigenetics, specifically the regulation of gene expression through methylation. This process relies significantly on the action of proteins that modify methylation, including methyltransferases, their associated binding proteins, and demethylases. These proteins are crucial regulators, orchestrating the methylation process by regulating enzymes and their corresponding binding proteins. This orchestration facilitates the reading, binding, detection, and catalysis of gene methylation sites. Methylation ences the development, prolisignificantly influferation, invasion, and prognosis of HCC. Furthermore, methylation modification and its regulatory mechanisms activate distinct biological characteristics in HCC cancer stem cells, such as inducing cancer-like differentiation of stem cells. They also influence the tumor microenvironment (TME) in HCC, modulate immune responses, affect chemotherapy resistance in HCC patients, and contribute to HCC progression through signaling pathway feedback. Given the essential role of methylation in genetic information, it holds promise as a potential tool for the early detection of HCC and as a target to improve drug resistance and promote apoptosis in HCC cells.Keywords: methylation modifying proteins, biomarkers, methyltransferases, HCC tumorigenesis

Li An,1,2,* Xiaomei Ren,1,* Ye Pan,2 Wei Gao,1 Liqun Ren,1 Jing Wang,3 Yao Wang2 1Department of Geriatrics, ZhongDa Hospital, Southeast University School of Medicine, Nanjing, 210009, People’s Republic of China; 2Department of Endocrine, ZhongDa Hospital, Southeast University School of Medicine, Nanjing, 210009, People’s Republic of China; 3Yizheng Hospital of Nanjing Drum Tower Hospital Group, Yizheng, 211400, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing Wang; Yao Wang, Tel/Fax +86-25- 83272111, Email wang_yao100@163.com; yz3466599@hotmail.comBackground: The impact of inflammatory factors on the risk of diabetic nephropathy (DN) is inconsistent. Two-sample Mendelian randomization (MR) analyses were used to detect the causal role of inflammatory factors in DN risk.Methods: Inflammatory factor GWAS summary data were collected from a meta-analysis including 8,293 Finnish participants, and DN information was extracted from a GWAS of 213,746 individuals from FinnGen. The MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) outlier test was used for the removal of horizontal pleiotropic outliers. Multivariable MR analysis was also used to adjust for pleiotropy.Results: IFN-γ [ORIVW: 1.33; 95% CI: 1.09– 1.63; p=0.005] and SCF [ORIVW: 1.25, 1.02– 1.52; p = 0.027] were associated with an increased risk of DN. MIP1b [ORIVW: 0.92; 95% CI: 0.85– 0.98; p = 0.022] and IL-16 [ORIVW: 0.89, 0.81– 0.99; p = 0.043] showed negative associations with the risk of DN. We validated our MR results with MR-PRESSO analyses. Significant horizontal pleiotropy was not found. Moreover, in the multivariable MR analysis, the associations between cytokines and DN risk remained.Conclusion: Our MR results based on genetic data contribute to a better understanding of the pathogenesis of DN and provide evidence for a causal effect of inflammatory factors on DN. These findings support targeting specific inflammatory factors to alleviate DN risk.Keywords: causal association, diabetic nephropathy, inflammatory factors, Mendelian randomization

Gongxin Yang,1,* Jikai Xia,2,* Xiaoqing Dai,1,* Hongbo Zhao,1 Weiqing Gao,1 Weilong Ding,1 Xiaofeng Tao,1 Ling Zhu1 1Department of Radiology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200001, People’s Republic of China; 2Department of Radiology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, 264100, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaofeng Tao; Ling Zhu, Department of Radiology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200001, People’s Republic of China, Email cjr.taoxiaofeng@vip.163.com; zhuling011@126.comIntroduction: Magnetic resonance imaging (MRI) is an important tool for the accurate diagnosis of malignant tumors in clinical settings. However, the lack of tumor-specific MRI contrast agents limits diagnostic accuracy.Methods: Herein, we developed αv integrin receptor-targeting multi-crystalline manganese oxide (MCMO) as a novel MRI contrast agent for accurate diagnosis of tumors by coupling iRGD cyclopeptide PEGylation polymer onto the surface of MCMO (iRGD-pMCMO).Results: The MCMO consisted of numerous small crystals and exhibited an oval structure of 200 nm in size. The iRGD-pMCMO actively recognizes tumor cells and effectively accumulates at the tumor site, consequently releasing abundant Mn2+ ions in a weakly acidic and high-GSH-expressing tumor microenvironment. Subsequently, Mn2+ ions interact with cellular GSH to form Mn-GSH chelates, enabling efficient T1-weighted MR contrast imaging. In vivo experiments indicated that iRGD-pMCMO significantly improved T1-weighted images, achieving an accurate diagnosis of subcutaneous and orthotopic tumors. The results verified that the T1 contrast effect of iRGD-pMCMO was closely associated with the expression of GSH in tumor cells.Conclusion: Altogether, the novel tumor-targeting, highly sensitive MRI contrast agent developed in this study can improve the accuracy of MRI for tumor diagnosis. Keywords: multi-crystalline manganese oxide, MRI contrast agent, tumor targeting, tumor selectivity, accurate diagnosis

Weimin Bai,1,&ast; Taoke Huang,2,&ast; Xinying Li,3,&ast; Weiyang Gao,2 Ji Qin,2 Yongxin Bian,4 Weihao Xu,5 Juan Xu,6 Lijie Qin1 1Department of Emergency, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou, 463599, People’s Republic of China; 2Medical School of Chinese PLA, Beijing, 100853, People’s Republic of China; 3Faculty of Postgraduate Education, Shandong Sport University, Jinan, 250102, People’s Republic of China; 4The First School of Clinical Medicine, Binzhou Medical University, Yantai, 264003, People’s Republic of China; 5Haikou Cadre’s Sanitarium of Hainan Military Region, Haikou, 570203, People’s Republic of China; 6Department of General Surgery, Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou, 311202, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Juan Xu; Lijie Qin, Email sophia2932@163.com; qinlijie1819@163.comBackground: Frailty is a risk factor for acute myocardial infarction (AMI). This study examined the association between the modified frailty index (MFI) and adverse outcomes in patients with critical AMI.Methods: Data were obtained from the Medical Information Mart for Intensive Care IV database. Logistic and Cox regression models and a competing risk model were applied.Results: Of 5003 patients, 1496 were non-frail and 3507 were frail. Frailty was significantly associated with in-hospital mortality (per point, OR 1.13, 95% CI: 1.05– 1.21; frail vs non-frail, OR 1.31, 95% CI: 1.04– 1.65) and 1-year mortality (per point, HR 1.15, 95% CI: 1.11– 1.20; frail vs non-frail, HR 1.37, 95% CI: 1.20– 1.58). Frailty was significantly associated with post-discharge care needs (per point, OR 1.23, 95% CI: 1.14– 1.33; frail vs non-frail, OR 1.47, 95% CI: 1.22– 1.78). In the competing risk models, frailty was significantly associated with a lower probability of being discharged from the ICU (per point, HR 0.87, 95% CI: 0.85– 0.90; frail vs non-frail, HR 0.73, 95% CI: 0.68– 0.79) and hospital (per point, HR 0.82, 95% CI: 0.80– 0.85; frail vs non-frail, HR 0.62, 95% CI: 0.57– 0.68). Subgroup analyses showed the association of frailty with in-hospital and 1-year mortality was stronger in patients with a SOFA score ≤ 2 than in those with a SOFA score > 2 (both p< 0.05 for interaction).Conclusion: Frailty assessed by the MFI was an independent predictor of adverse outcomes in patients with critical AMI and may be helpful for prognostic risk stratification.Keywords: frailty, modified frailty index, acute myocardial infarction, critically ill patients, prognosis

Yi Zhou,1 Weina Gao,2 Shumin Gao,2 Xutong Guo,2 Meng Liu,2 Congjie Cao1 1School of Nursing, Langfang Health Vocational College, Langfang, Hebei, People’s Republic of China; 2Department of Orthopedics, Baoding No.1 Central Hospital, Baoding, Hebei, People’s Republic of ChinaCorrespondence: Weina Gao, Department of Orthopedics, Baoding No.1 Central Hospital, No. 320, Changcheng North Street, Lianchi District, Baoding, Hebei, 071000, People’s Republic of China, Tel/Fax +86 312-5975023, Email gaoweina984926@163.comPurpose: To examine whether exercise self-efficacy mediates the contributions of pain catastrophizing and kinesiophobia to exercise adherence in patients after total knee arthroplasty.Patients and Methods: A cross-sectional study design was conducted. A total 211 post-total knee arthroplasty patients were recruited from three orthopedics units of a tertiary hospital in China. Participants were invited to complete questionnaires on pain catastrophizing, kinesiophobia, exercise self-efficacy, and exercise adherence. Mplus 8.3 software was used to construct mediation models.Results: Pain catastrophizing and kinesiophobia were negatively correlated with exercise adherence (r = − 0.509, r = − 0.605, p < 0.001 respectively), while exercise self-efficacy were positively associated with exercise adherence (r = 0.799, p < 0.001). The results found exercise self-efficacy mediated the correlations of pain catastrophizing and kinesiophobia with exercise adherence after adjusting for demographic and clinical covariates. Pain catastrophizing indirectly affected patients’ exercise adherence through its effect on exercise efficacy (indirect effect: − 0.412), while Kinesiophobia is directly associated with exercise adherence and also indirectly through exercise self-efficacy (direct effect: − 0.184, indirect effect: − 0.415).Conclusion: Patients after total knee arthroplasty who have high levels of psychological distress (pain catastrophizing and kinesiophobia) are vulnerable to be non-adherent to exercise behaviors. Exercise self-efficacy explains the effects of pain catastrophizing and kinesiophobia on exercise adherence and may be a key target for measures to improve exercise behaviors in patients after total knee arthroplasty.Keywords: pain catastrophizing, kinesiophobia, self-efficacy, exercise, adherence, total knee arthroplasty

Xuchen Huang,1,2 Sainan Li,1,2 Wei Gao,1,2 Jiajie Shi,1,2 Meng Cheng,1,2 Yunzhe Mi,1,2 Yueping Liu,3 Meixiang Sang,4 Ziyi Li,4 Cuizhi Geng1,2 1Department of Breast Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Key Laboratory in Hebei Province for Molecular Medicine of Breast Cancer, Shijiazhuang, Hebei, People’s Republic of China; 3Department of Pathology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 4Research Center and Tumor Research Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Cuizhi Geng, Department of Breast Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China, Tel/Fax +86-311-66696313, Email gengcuizhisci@163.comPurpose: Our aim was to verify whether KIF20A has the potential to serve as a prognostic marker for female patients with estrogen receptor (ER)-positive breast cancer (BC) and treated with tamoxifen (TAM).Patients and Methods: Online tools were used to investigate the potential correlation between KIF20A gene expression and survival of patients with ER-positive BC and TAM treatment. Furthermore, immunohistochemistry (IHC) was conducted to assess the expression levels of KIF20A in patients included from our center. The prognostic value of KIF20A for disease-free survival (DFS) and overall survival (OS) was further evaluated using Cox regression analysis.Results: According to the results obtained from online tools, it was found that patients with low KIF20A expression exhibited significantly better survival outcomes in terms of relapse-free survival (RFS), distant metastasis-free survival (DMFS), and OS compared to those with high KIF20A expression (P < 0.001, P < 0.001, and P = 0.008, respectively). Additionally, significantly lower gene expression of KIF20A was found in patients who responded to TAM than in those who did not respond to TAM (P < 0.001). We further included 203 patients with adjuvant TAM therapy, and IHC for KIF20A was performed on sections from paraffin-embedded blocks. Patients with low KIF20A expression had significantly better DFS and OS (P = 0.001 and 0.002, respectively, log rank test), and the expression of KIF20A was identified as an independent factor for predicting both DFS and OS (P = 0.001 and 0.008, respectively).Conclusion: KIF20A expression is an independent prognostic factor for survival in patients with ER-positive BC who received adjuvant TAM therapy. In clinical practice, IHC evaluation of KIF20A expression in surgical samples before administering tamoxifen may assist in predicting the treatment outcomes of these patients.Keywords: KIF20A, breast carcinoma, biomarker, tamoxifen, survival, prognosis

Kennedy B Nkhoma,1 Lindsay Farrant,2 Olona Mzimkulu,2 Joy Hunter,2 Irene Higginson,1 Wei Gao,2 Matthew Maddocks,1 Liz Gwyther,2 Richard Harding1 1Cicely Saunders Institute of Palliative Care Policy and Rehabilitation, King’s College London, London, UK; 2Division of Interdisciplinary Palliative Care & Medicine, Department of Public Health and Family Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South AfricaCorrespondence: Kennedy B Nkhoma, Email kennedy.nkhoma@kcl.ac.ukBackground: Many deaths globally are attributable to non-communicable disease, and four-fifths of these deaths are in low- and middle-income countries. Globally, COPD is currently the third leading cause of mortality.Research Question: 1) To determine the prevalence and burden of symptoms and concerns, and 2) determine predicting factors of symptom burden among patients with COPD.Methods: A cross-sectional survey was conducted at eight primary care sites in Western Cape. We collected socio-demographic data (age, gender, smoking status, number of missed doses of prescribed medication in the last seven days) and clinical data (PEF and KPS). The Memorial Symptom Assessment Scale (MSAS), the Medical Outcomes Study, Social Support Survey (MOS-SSS), the London Chest Activity of Daily Living Scale (LCADLS) and the COPD Assessment Test (CAT) (impairment on person’s life) were administered to patients. We conducted ordered logistic regression analysis to assess factors associated with the burden of symptoms. MSAS subscales: 1) Global symptom distress index, 2) physical symptom distress and 3) psychological symptom distress were dependent outcomes. We constructed three ordinal logistic regression models for each of the three subscales. Covariates were MOS-SSS, LCADLS, CAT, demographic and clinical variables.Results: We recruited n=387 patients, mean age 59.5 years, 53.0% female. In multivariate analysis, each of the three models (ie, global, psychological and physical symptom distress) was positively associated with impairment on person’s life p< 0.001, difficulty to perform activities of daily living p< 0.001, and low social support p< 0.001. Old age was associated with lower global symptom distress (p=0.004), psychological and (0.014) physical distress (0.005). Missing 1 or more doses of medication was associated with higher levels of global (0.004) and physical (0.005) symptom distress.Interpretation: The high prevalence and burden of physical and psychological symptoms provides strong evidence of the need for integrating person-centred assessment and management of symptoms in primary care settings.Keywords: chronic lung disease, chronic obstructive pulmonary disease, symptom burden, symptom distress, symptom prevalence

Fengbing He,1,&ast; Wenzhong Hou,1,&ast; Yintao Lan,1,2 Weijian Gao,1 Mengyu Zhou,1 Jinghang Li,1 Shutong Liu,1 Bin Yang,1 Jian Zhang1 1Qingyuan People’s Hospital, The Sixth Affiliated Hospital of Guangzhou Medical University, School of Biomedical Engineering, Guangzhou Medical University, Guangdong, People’s Republic of China; 2Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Zhang, Email jianzhang@gzhmu.edu.cnBackground: Carotid artery thrombosis is the leading cause of stroke. Since there are no apparent symptoms in the early stages of carotid atherosclerosis onset, it causes a more significant clinical diagnosis. Photoacoustic (PA) imaging provides high contrast and good depth information, which has been used for the early detection and diagnosis of many diseases.Methods: We investigated thrombus formation by using 20% ferric chloride (FeCl3) in the carotid arteries of KM mice for the thrombosis model. The near-infrared selenium/polypyrrole (Se@PPy) nanomaterials are easy to synthesize and have excellent optical absorption in vivo, which can be used as PA contrast agents to obtain thrombosis information.Results: In vitro experiments showed that Se@PPy nanocomposites have fulfilling PA ability in the 700 nm to 900 nm wavelength range. In the carotid atherosclerosis model, maximum PA signal enhancement up to 3.44, 4.04, and 5.07 times was observed by injection of Se@PPy nanomaterials, which helped to diagnose the severity of carotid atherosclerosis.Conclusion: The superior PA signal of Se@PPy nanomaterials can identify the extent of atherosclerotic carotid lesions, demonstrating the feasibility of PA imaging technology in diagnosing carotid thrombosis lesion formation. This study demonstrates nanocomposites and PA techniques for imaging and diagnosing carotid thrombosis in vivo.Keywords: photoacoustic contrast agent, molecular imaging, Se@PPy nanocomposites, carotid artery thrombus

Shuo Zhang,1,&ast; Yishu Wang,1,&ast; Shuai Zhang,1 Chengqi Huang,1 Qiyang Ding,2 Ji Xia,2 Daocheng Wu,1 Wei Gao2 1The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, 710049, People’s Republic of China; 2Department of Anesthesiology & Center for Brain Science & Center for Translational Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710049, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Daocheng Wu, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, 710049, People’s Republic of China, Tel/Fax +86-29-82663941, Email wudaocheng@mail.xjtu.edu.cn Wei Gao, Department of Anesthesiology & Center for Brain Science & Center for Translational Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710049, People’s Republic of China, Tel +86 15209225834, Email gaowei2906@xjtufh.edu.cnAbstract: Anesthetics, which include both local and general varieties, are a unique class of drugs widely utilized in clinical surgery to alleviate pain and promote relaxation in patients. Although numerous anesthetics and their traditional formulations are available in the market, only a select few exhibit excellent anesthetic properties that meet clinical requirements. The main challenges are the potential toxic and adverse effects of anesthetics, as well as the presence of the blood-brain barrier (BBB), which makes it difficult for most general anesthetics to effectively penetrate to the brain. Loading anesthetics onto nanocarriers as anesthetic nanomedicines might address these challenges and improve anesthesia effectiveness, reduce toxic and adverse effects, while significantly enhance the efficiency of general anesthetics passing through the BBB. Consequently, anesthetic nanomedicines play a crucial role in the field of anesthesia. Despite their significance, research on anesthetic nanomedicines is still in its infancy, especially when compared to other types of nanomedicines in terms of depth and breadth. Although local anesthetic nanomedicines have received considerable attention and essentially meet clinical needs, there are few reported instances of nanomedicines for general anesthetics. Given the extensive usage of anesthetics and the many of them need for improved performance, emerging anesthetic nanomedicines face both unparalleled opportunities and considerable challenges in terms of theory and technology. Thus, a comprehensive summary with systematic analyses of anesthetic nanomedicines is urgently required. This review provides a comprehensive summary of the classification, properties, and research status of anesthetic nanomedicines, along with an exploration of their opportunities and challenges. In addition, future research directions and development prospects are discussed. It is hoped that researchers from diverse disciplines will collaborate to study anesthetic nanomedicines and develop them as a valuable anesthetic dosage form for clinical surgery.Keywords: anesthesia, nanocarriers, blood-brain barrier, drugs

Jing He,1,&ast; Youyuan Yao,1,&ast; Fei Quan,2 Zhongyu Lu,2 Jian Wang,1 Wen Gao1 1Medical Oncology Department, Jiangsu Province Hospital, Nanjing, Jiangsu, 210029, People’s Republic of China; 2The Medical Department, Jiangsu Simcere Diagnostics Co., Ltd, Nanjing, Jiangsu, 210021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wen Gao; Jian Wang, Medical Oncology Department, Jiangsu Province Hospital, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, People’s Republic of China, Tel +86 025 68305755, Fax +86 025 68305758, Email drgaowen@yeah.net; WJ20210205@126.comAbstract: Intergenic-gene fusion detected by DNA-seq is particularly confusing for drug selection since the function of the intergenic region located upstream is unknown. We reported a case of a 49-year-old male with advanced lung adenocarcinoma, who was detected FBXO11 (intergenic)-ALK (exon 20-29) by DNA-seq, and FISH analysis revealed a positive result. The patient was treated with crizotinib and achieved a PR. The canonical EML4 (exon 1-13)-ALK (exon 20-29) fusion verified by RNA-seq suggested a complex EML4 (exon 1-13)-FBXO11 (intergenic)-ALK (exon 20-29) tripartite rearrangement at the DNA level. Our case emphasized the necessity of RNA-seq for verifying intergenic-gene fusion. Simultaneously, the pathogenic germline SLX4 variant and extensive CNVs of DNA segment were detected by DNA-seq deserves our attention.Keywords: intergenic fusion, lung adenocarcinoma, ALK, SLX4, chromothripsis

Cuiping Xu, Feng Yang, Qimin Wang, Wei Gao Department of Respiratory and Critical Care Medicine, China Rehabilitation Research Center, Rehabilitation School of Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Wei Gao, Tel +86 10-87569070, Fax +86 10-67573428, Email rhhuxi@163.comPurpose: We aimed to evaluate whether high flow nasal cannula (HFNC) is an effective and safe method for adult patients with acute hypercapnic respiratory failure (AHRF).Methods: We searched the Cochrane Library, Embase, and PubMed databases from inception to August 2022 to obtain randomized controlled trials (RCTs) that compared HFNC with conventional oxygen treatment (COT) or non-invasive ventilation (NIV) in patients with AHRF, and then performed a meta-analysis.Results: A total of ten parallel RCTs with 1265 individuals were identified. Of them, two studies compared HFNC with COT and eight studies compared HFNC with NIV. In terms of intubation rate, mortality, and arterial blood gas (ABG) improvement, HFNC showed comparable effects to NIV and COT. However, HFNC was more comfortable (mean difference [MD] − 1.87, 95% confidence interval [CI] =− 2.59, − 1.15, P < 0.00001, I2 =0%) and resulted in fewer adverse events (odds ratio [OR] 0.12, 95% CI=0.06, 0.28, P< 0.00001, I2 = 0%), compared with NIV. In comparison to NIV, HFNC could significantly lower heart rate (HR) (MD − 4.66, 95% CI=− 6.82, − 2.50, P < 0.0001, I2 =0%), respiratory rate (RR) (MD − 1.17, 95% CI=− 2.03, − 0.31, P =0.008, I2 =0%), and hospital stay length (MD − 0.80, 95% CI=− 1.44, − 0.16, P =0.01, I2 =0%). NIV showed a decreased frequency in the treatment crossover rate, compared with HFNC in patients with pH< 7.30 (OR 5.78, 95% CI=1.50, 22.31, P = 0.01, I2: not applicable). Contrary to COT, HFNC could considerably reduce the need for NIV (OR 0.57, 95% CI=0.35, 0.91, P=0.02, I2=0%).Conclusion: HFNC was effective and safe in patients with AHRF. However, in patients with pH < 7.30, HFNC may result in a higher incidence of treatment crossover, compared with NIV. Compared to COT, HFNC may decrease the need for NIV in patients with compensated hypercapnia.Keywords: high-flow nasal cannula, non-invasive ventilation, conventional oxygen treatment, hypercapnic respiratory failure

Xiaoou Li,1 Wei Gao,2 Zhonglan Jia,3 Kaihu Yao,2 Jinyan Yang,1 Jingjing Tong,4 Yajuan Wang5 1Department of Neonatology, Haidian District Maternal and Child Health Care Hospital, Beijing, 100080, People’s Republic of China; 2Key Laboratory of Major Diseases in Children, Ministry of Education, National Key Discipline of Pediatrics (Capital Medical University), Laboratory of Dermatology, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, People’s Republic of China; 3Department of Clinical Laboratory, Haidian District Maternal and Child Health Care Hospital, Beijing, 100080, People’s Republic of China; 4Department of Neonatology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, 100026, People’s Republic of China; 5Department of Neonatology, Children’s Hospital, Capital Institute of Pediatrics, Beijing, 100020, People’s Republic of ChinaCorrespondence: Yajuan Wang, Department of Neonatology, Children’s Hospital, Capital Institute of Pediatrics, No. 2 Yabao Road, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel +86-10-85695631, Email cxswyj@vip.sina.comPurpose: We investigate the drug resistance, serotype and multilocus sequence typing (MLST) of Group B streptococcus (GBS) strains obtained from pregnant women and neonates in a hospital in Beijing.Patients and Methods: In this cross-sectional study, 1470 eligible pregnant women at a gestational age of 35– 37 weeks presented to our department between May 2015 and May 2016 were included. Vaginal and rectal samples from pregnant women together with sampling from neonatal samples were collected to screen GBS. GBS strains were subject to drug resistance and serotype analysis and MLST.Results: GBS strains were isolated from 111 pregnant women (7.6%) and 6 neonates (0.99%) from 606 matched neonates. 102 strains from pregnant women and 3 strains from neonates were included in the drug sensitivity test, serotyping and MLST typing. All these strains were susceptible to ampicillin, penicillin, ceftriaxone, vancomycin, linezolid, and meropenem. Sixty strains (58.8%) showed multi-drug resistance. Serious cross-resistance was seen between erythromycin and clindamycin. There were eight serotypes, and 37 strains (36.3%) showed a serotype of type III serving as the major type. All 102 GBS strains isolated from pregnant samples could be divided into 18 STs types. They belonged to five clonal complexes and five single clones, with the predominant type of ST19/III, ST10/Ib, and ST23/Ia, with CC19 as the most common type. Three GBS strains isolated from neonates covered two serotypes (ie type III and Ia) that were consistent with those of the mothers.Conclusion: Serotype III was the predominant serotype of GBS in this study. The predominant MLST type was ST19, ST10, and ST23, with ST19/III, ST10/Ib, and ST23/Ia serving as the most prevalent and CC19 as the most common clonal complex. GBS strains from neonates were consistent in the clonal complex, serotype, and MLST with these isolated from the mothers.Keywords: Group B streptococcus, multilocus sequence typing, drug resistance, molecular epidemiology

Guanru Chen,1,&ast; Wenfan Gao,2– 4,&ast; Yayun Xu,5 Huiying Chen,1 Heping Cai1 1Department of Clinical Pharmacy, Anhui Provincial Children’s Hospital, Hefei, Anhui, People’s Republic of China; 2Psychopharmacology Research Laboratory, Affiliated Psychological Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 3Department of Pharmacy, Hefei Fourth People’s Hospital, Hefei, Anhui, People’s Republic of China; 4Anhui Clinical Research Center for Mental Disorders, Anhui Mental Health Center, Hefei, Anhui, People’s Republic of China; 5Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guanru Chen, Department of Clinical Pharmacy, Anhui Provincial Children’s Hospital, 39 Wangjiang Road, Hefei, 230000, People’s Republic of China, Email albertandy@163.comObjective: Previous studies indicated that maternal thyroid dysfunction increase the offspring’s risk for attention deficit/hyperactivity disorder (ADHD). However, the relationship between thyroid function and symptoms in children with ADHD remains unclear.Methods: A total of 49 children with ADHD were enrolled. The Conners 3 scale was used to estimate the symptoms associated with ADHD. Correlation between thyroid hormones and the scores of the Conners 3 scale was evaluated by Pearson correlation analysis. Then, ADHD children were divided into two groups according to the hyperactivity index (HI) of the Conners 3 scale: ADHD children with hyperactivity behaviors (HB) (HI > 1.5) and ADHD children without HB (HI < 1.5). The demographic characteristics, thyroid hormones, and routine laboratory parameters between the two groups were collected. To distinguish HI-related factors, a univariate analysis and a binary logistic regression predictive model were used. The discriminative ability of thyroid stimulating hormone (TSH) in predicting ADHD children with HB from ADHD children without HB was investigated using the receiver operating characteristic (ROC) curve method.Results: The levels of TSH were positively correlated to the scores of the Conners 3 scale (r = 0.338, P = 0.033) and HI (r = 0.371, P = 0.019). Moreover, the levels of TSH, serum ferritin, and lactic acid were significantly increased in ADHD children with HB compared to ADHD children without HB (all P < 0.05). Furthermore, the results of binary logistic regression found that TSH (OR 2.243 (CL 1.052– 4.783)) and lactic acid (OR 1.018 (CI 1.003– 1.032)) were independently associated with HI. Additionally, ROC analysis indicated the potential diagnostic value of TSH in discriminating ADHD children with HB from ADHD children without HB with an AUC of 0.684.Conclusion: These results suggested that the serum TSH levels may be related to the HB in children with ADHD.Keywords: thyroid function, children, attention deficit/hyperactivity disorder, thyroid stimulating hormone, lactic acid, hyperactivity behaviors

Lisa Jane Brighton,1 Claire M Nolan,2,3 Ruth E Barker,2,4,5 Suhani Patel,2,4 Jessica A Walsh,2 Oliver Polgar,2 Samantha SC Kon,2,4,6 Wei Gao,1 Catherine J Evans,1,7 Matthew Maddocks,1 William DC Man2,4,8,9 1Cicely Saunders Institute of Palliative Care, Policy and Rehabilitation, King’s College London, London, UK; 2Harefield Respiratory Research Group, Royal Brompton and Harefield Hospitals, Guy’s and St Thomas NHS Foundation Trust, London, UK; 3Division of Physiotherapy, College of Health, Medicine and Life Sciences, Brunel University London, London, UK; 4National Heart and Lung Institute, Imperial College, London, UK; 5Insight Innovation, Wessex Academic Health Science Network, Southampton, UK; 6Department of Respiratory Medicine, The Hillingdon Hospital NHS Trust, London, UK; 7Brighton General Hospital, Sussex Community NHS Foundation Trust, Brighton, UK; 8Harefield Pulmonary Rehabilitation Unit, Guy’s and St Thomas NHS Foundation Trust, London, UK; 9Faculty of Life Sciences & Medicine, King’s College London, London, UKCorrespondence: Lisa Jane Brighton, Cicely Saunders Institute, Bessemer Road, Denmark Hill, London, SE5 9PJ, UK, Tel +44 020 7848 5041, Email lisa.brighton@kcl.ac.ukBackground: Identifying frailty in people with chronic obstructive pulmonary disease (COPD) is deemed important, yet comparative characteristics of the most commonly used frailty measures in COPD are unknown. This study aimed to compare how the Fried Frailty Phenotype (FFP) and Short Physical Performance Battery (SPPB) characterise frailty in people with stable COPD, including prevalence of and overlap in identification of frailty, disease and health characteristics of those identified as living with frailty, and predictive value in relation to survival time.Methods: Cohort study of people with stable COPD attending outpatient clinics. Agreement between frailty classifications was described using Cohen’s Kappa. Disease and health characteristics of frail versus not frail participants were compared using t-, Mann–Whitney U and Chi-Square tests. Predictive value for mortality was examined with multivariable Cox regression.Results: Of 714 participants, 421 (59%) were male, mean age 69.9 years (SD 9.7), mean survival time 2270 days (95% CI 2185– 2355). Similar proportions were identified as frail using the FFP (26.2%) and SPPB (23.7%) measures; classifications as frail or not frail matched in 572 (80.1%) cases, showing moderate agreement (Kappa = 0.469, SE = 0.038, p < 0.001). Discrepancies seemed driven by FFP exhaustion and weight loss criteria and the SPPB balance component. People with frailty by either measure had worse exercise capacity, health-related quality of life, breathlessness, depression and dependence in activities of daily living. In multivariable analysis controlling for the Age Dyspnoea Obstruction index, sex, BMI, comorbidities and exercise capacity, both the FFP and SPPB had predictive value in relation to mortality (FFP aHR = 1.31 [95% CI 1.03– 1.66]; SPPB aHR = 1.29 [95% CI 0.99– 1.68]).Conclusion: In stable COPD, both the FFP and SPPB identify similar proportions of people living with/without frailty, the majority with matching classifications. Both measures can identify individuals with multidimensional health challenges and increased mortality risk and provide additional information alongside established prognostic variables.Keywords: respiratory disease, chronic obstructive pulmonary disease, frailty, survival

Yaru Zou,1,2 Wei Gao,3 Huizhen Jin,2 Chenmei Mao,2 Yi Zhang,1 Xiaoling Wang,1 Dong Mei,1 Libo Zhao1,4 1Department of Pharmacy, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, People’s Republic of China; 2Department of Pharmacy, Children’s Hospital of Soochow University, Suzhou, Jiangsu, 215025, People’s Republic of China; 3Department of Pharmaceutical Sciences, College of Pharmacy, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, 48109, USA; 4Department of Pharmacy, Peking University Third Hospital, Beijing, 100191, People’s Republic of ChinaCorrespondence: Dong Mei; Libo Zhao, Email meidong11290926@126.com; libozhao2011@163.comBackground: Nanomedicines have significant advantages in enhancing the oral bioavailability of drugs, but a deeper understanding of the underlying mechanisms remains to be interpreted. Hence, the present study aims to explain the uptake and trafficking mechanism for 6-MP nanomedicines we previously constructed.Methods: 6-MP loaded poly(lactide-co-glycolide) (PLGA) nanomedicines (6-MPNs) were prepared by the multiple emulsion method. The transcytosis mechanism of 6-MPNs was investigated in Caco-2 cells, Caco-2 monolayers, follicle associated epithelium (FAE) monolayers and rats, including transmembrane pathway, intracellular trafficking, paracellular transport and the involvement of transporter.Results: Pharmacokinetics in rats showed that the area under the curve (AUC) of 6-MP in the 6-MPNs group (147.3 ± 42.89 μg/L·h) was significantly higher than that in the 6-MP suspensions (6-MPCs) group (70.31 ± 18.24 μg/L·h). The uptake of 6-MPNs in Caco-2 cells was time-, concentration- and energy-dependent. The endocytosis of intact 6-MPNs was mediated mainly through caveolae/lipid raft, caveolin and micropinocytosis. The intracellular trafficking of 6-MPNs was affected by endoplasmic reticulum (ER)-Golgi complexes, late endosome-lysosome and microtubules. The multidrug resistance associated protein 4 (MRP4) transporter-mediated transport of free 6-MP played a vital role on the transmembrane of 6-MPNs. The trafficking of 6-MPNs from the apical (AP) side to the basolateral (BL) side in Caco-2 monolayers was obviously improved. Besides, 6-MPNs affected the distribution and expression of zona occludens-1 (ZO-1). The transport of 6-MPNs in FAE monolayers was concentration- and energy-dependent, while reaching saturation over time. 6-MPNs improved the absorption of the intestinal Peyer’s patches (PPs) in rats.Conclusion: 6-MPNs improve the oral bioavailability through multiple pathways, including active transport, paracellular transport, lymphatic delivery and MRP4 transporter. The findings of current study may shed light on the cellular uptake and transcellular trafficking mechanism of oral nanomedicines.Keywords: nanomedicines, oral bioavailability, cellular uptake, transport mechanism

Ting-ting Yan,* Xin-lu Yang,* Shan Wang, Jia-qi Chen, Ji-cheng Hu, Ling Zhou, Wei Gao Department of Anesthesiology, First Affiliated Hospital of USTC (Anhui Provincial Hospital), University of Science and Technology of China, Hefei, Anhui, 230001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Gao; Ling Zhou, Department of Anesthesiology, First Affiliated Hospital of USTC (Anhui Provincial Hospital), University of Science and Technology of China, Hefei, Anhui, 230001, People’s Republic of China, Tel +86-15605690073 ; +86-13866702756, Fax +86-551-62283912, Email gaowei20100813@126.com; 13866702756@163.comPurpose: The present study aimed to explore the effects of continuous sacral block on the postoperative pain of children and the satisfaction of the nurses in post-anesthesia care unit (PACU). Also, the influence of the modified protocol of continuous sacral block was investigated.Patients and Methods: A total of 60 children undergoing laparoscopic surgery were randomly divided into two groups: GI and GC groups. The general anesthesia was induced with midazolam, propofol, sufentanil and succinylcholine in both groups. In addition, the patients were subjected to continuous sacral block with levobupivacaine in group GC. The modified protocol of continuous sacral block was divided into three steps: comprehensive lumbar and sacral vertebral canal scanning by ultrasound, catheterization and administration. The EVENDOL pain scales and pediatric anesthesia emergence delirium scales of the children were evaluated at 5 min after extubation (T3), 90 min (T4), and 4 h (T5) after the operation. The nurses’ satisfaction scores at T3 -T4 and adverse events, such as nausea and vomiting, were also recorded, after the operation.Results: After ultrasonic scanning, one patient in group GC was excluded due to the sacral hiatus atresia, which might lead to failure of catheterization. Data of 59 patients were collected for statistical analysis. Compared to the GI group, the EVENDOL scores and the pediatric anesthesia emergence delirium scales were reduced at T3, T4, and T5 (P < 0.05) in group GC. Furthermore, there was a higher rank of PACU nurses’ satisfaction in the GC group compared to the GI group (P < 0.05).Conclusion: Based on the modified protocol, continuous sacral block provides reliable and safety analgesia for children undergoing laparoscopic surgery, thereby improving the satisfaction of PACU nurses.Keywords: ultrasound-guided, lumbar and sacral vertebral canal scanning, postoperative pain, satisfaction of PACU nurses

Peng Liu,1,2 Shan-Shan Zhang,1,2 Yun Liang,1,2 Zi-Jun Gao,1 Wei Gao,3 Bu-Huai Dong1 1Department of Anesthesiology, Xi’an Honghui Hospital, Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Xi’an Medical University, Xi’an, People’s Republic of China; 3Department of Anesthesiology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of ChinaCorrespondence: Bu-Huai Dong, Department of Anesthesiology, Xi’an Honghui Hospital, Affiliated Hospital of Xi’an Jiaotong University, No. 555, Youyi East Road, Nanqimen, Xi’an, 710054, People’s Republic of China, Tel +86 29-85260965, Email dongbuhuai@126.comObjective: To evaluate the efficacy and safety of esketamine + antidepressant in treatment-resistant depression.Methods: We searched PubMed, Web of Science, Embase, CNKI, and Wanfang databases to obtain published information on esketamine + antidepressant from inception to July 2022. We searched for randomized controlled studies on the treatment of depression with a double-blind induction phase. Outcome indicators included changes in Montgomery-Asberg Depression Rating Scale (MADRS) scores before and after treatment, effective response rate, remission rate, and changes in self-rating depression scale (SDS). We analyzed data using Review Manager 5.4 and assessed the quality of evidence using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) analysis.Results: A total of seven articles were included, including 701 patients in the esketamine + antidepressant group and 551 in the placebo group. Meta-analysis results showed that esketamine + antidepressant could improve the MADRS score in patients with treatment-resistant depression (MD = − 2.68, 95% CI − 3.98 to − 1.37, P < 0.0001), SDS (MD = − 2.9, 95% CI − 4.01 to − 1.79, P < 0.00001), response rate at the end of the double-blind induction period (RR = 1.28, 95% CI 1.12 to 1.46, P = 0.0002), remission rate at the end of the double-blind induction period (RR = 1.39, 95% CI 1.18 to 1.63, P < 0.0001), Five-Dimensional Health Scale (EQ-5D-5L) (MD = 0.05, 95% CI 0.02 to 0.08, P = 0.00009), Visual Analogue Scale of Health Status (EQ-VAS) (MD = 5.54, 95% CI 2.37 to 8.71, P = 0.0006).Conclusion: Esketamine + antidepressant has an obvious curative effect in treatment-resistant depression and can rapidly improve depression in patients, quality of life and satisfaction, but minor adverse reactions can occur.Keywords: esketamine, treatment-resistant depression, refractory depression, antidepressant, meta-analysis

Jingxia Wang,1,2,&ast; Qiangqiang Xiang,1,2,&ast; Silan Gu,1,&ast; Yudan Gu,3 Mingfei Yao,1 Weixin Huang,4,5 Wang Gao,4 Ling-Ling Tang1,2 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 2Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University, Shulan International Medical College, Hangzhou, People’s Republic of China; 3Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 4Jinan Microecological Biomedicine Shandong Laboratory, Jinan, People’s Republic of China; 5Shaoxing Tongchuang Biotechnology Co., Ltd, Shaoxing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling-Ling Tang, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University, Shulan International Medical College, Hangzhou, People’s Republic of China, Email lingling.tang@shulan.comBackground: Antibiotics are the first line of treatment for infectious diseases. However, their overuse can increase the spread of drug-resistant bacteria. The present study analyzed the impact of different types of antibiotics on the gut microbiome and cytokines level of mice.Methods: A total of five groups of 8-week-old male BALB/c mice (n = 35) were treated with piperacillin-tazobactam (TZP), ceftriaxone (CRO), tigecycline (TGC), levofloxacin (LEV) or normal saline (Ctrl), respectively, for up to 4 weeks. Fecal samples were analyzed by bacterial 16S rRNA gene sequencing for bacterial identification. Blood samples were used for the determination of 23 serum cytokines using multiplex immunoassay.Results: Exposure to antibiotics was shown to affect the normal weight gain of mice. Significant changes in gut composition caused by TZP, CRO and TGC treatment included the decreased abundance of Bacteroidetes (p < 0.01), Muribaculaceae (p < 0.01) and Lachnospiraceae (p < 0.01), and the increased abundance of Proteobacteria (p < 0.05), Enterobacteriaceae (including Klebsiella and Enterobacter) (p < 0.01) and Enterococcaceae (including Enterococcus) (p < 0.01). After 4-week treatment, the TZP, CRO and LEV groups had significantly lower concentrations of several serum cytokines. Correlation analysis of the top 30 bacterial genera and cytokines showed that Enterococcus and Klebsiella were strongly positively correlated with tumor necrosis factor-α (TNF-α), interleukins (IL) IL-12p70 and IL-1β. Desulfovibrio, Candidatus Saccharimonas, norank_f__norank_o__Clostridia_UCG-014, Lactobacillus, and Roseburia were strongly negatively correlated with these cytokines.Conclusion: This study demonstrates the effects of various antibiotics on the intestinal microflora and immune status of mice. Compared with TZP, CRO and TGC, LEV had minimal impact on the gut microbiota. In addition to TGC, long-term TZP, CRO and LEV intervention can lead to a decrease in serum cytokine levels, which may depend on the intestinal microflora, antibiotic used and the duration of treatment.Keywords: gut microbiota, piperacillin-tazobactam, ceftriaxone, tigecycline, levofloxacin, cytokine, immunity

Wenfan Gao,1– 4,&ast; Yayun Xu,5– 7,&ast; Jun Liang,1– 4 Yanhong Sun,1– 4 Yuanyuan Zhang,1– 4 Feng Shan,1– 4 Jinfang Ge,6– 8 Qingrong Xia1– 4 1Affiliated Psychological Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Department of Pharmacy, Hefei Fourth People’s Hospital, Hefei, People’s Republic of China; 3Psychopharmacology Research Laboratory, Anhui Mental Health Center, Hefei, People’s Republic of China; 4Anhui Clinical Research Center for Mental Disorders, Hefei, People’s Republic of China; 5Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, People’s Republic of China; 6Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, Anhui Medical University, Hefei, People’s Republic of China; 7The Key Laboratory of Anti-Inflammatory and Immune Medicines, Ministry of Education, Hefei, People’s Republic of China; 8School of Pharmacy, Anhui Medical University, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinfang Ge, School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, 230000, People’s Republic of China, Email gejinfang@ahmu.edu.cn Qingrong Xia, Department of Science and Education, Hefei Fourth People’s Hospital, Affiliated Psychological Hospital of Anhui Medical University, Anhui Mental Health Center, 316 Huangshan Road, Hefei, 230000, People’s Republic of China, Email ahmcxqr@163.comObjective: Evidence indicates a potential role of chemokines in depression-like behavior and depression-related pathophysiological processes. In the present study, we examined the serum levels of multiple chemokines, focusing on CC chemokines, in patients with major depressive disorder (MDD), with the aim to discover and identify serum chemokines-based biomarkers for MDD diagnosis.Methods: Participants included 24 patients with MDD and 24 healthy controls. The 24-item Hamilton Depression Rating Scale (HAMD-24) was administered to assess the disease severity of patients with MDD. A total of 9 serum CC chemokines including MCP-1 (CCL-2), MIP-1α (CCL-3), MIP-1β (CCL-4), eotaxin-1 (CCL-11), MCP-4 (CCL-13), TARC (CCL-17), MIP-3α (CCL-20), MDC (CCL-22), and Eotaxin-3 (CCL-26) were measured using electrochemiluminescence immunoassays. The levels of serum CC chemokines between MDD group and control group were compared, and diagnostic values of different CC chemokines were evaluated using the receiver operating characteristic (ROC) curve method for discriminating MDD patients from healthy controls. Correlations between the levels of serum CC chemokines and depression severity (HAMD-24 scores) were evaluated using Pearson’s correlation test.Results: Patients with MDD had higher levels of serum MIP-1α and MIP-1β and lower levels of serum MCP-1, MCP-4, TARC, MDC, and Eotaxin-3 compared to controls (all P < 0.05). Moreover, ROC curve analysis showed that the Area Under Curve (AUC) values of MIP-1α, MCP-4, TARC, and Eotaxin-3 were > 0.7 in discriminating patients with MDD from healthy controls. Furthermore, no significant relationship was found between the levels of serum CC chemokines and HAMD-24 scores in MDD group.Conclusion: These results suggested that circulating CC chemokines may hold promise in the discovery of biomarkers for diagnosing MDD.Keywords: chemokines, biomarker, diagnosis, serum, major depressive disorder

Dongting Zhang,1,&ast; Fengmei Tian,2,&ast; Wenjun Gao,2 Yvfeng Huang,3 Hui Huang,2 Liping Tan2 1Department of Nursing, the First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Department of Nursing, the Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 3School of Nursing, Soochow University, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Huang; Liping Tan, Department of Nursing, the Second Affiliated Hospital of Soochow University, No. 1055, Sanxiang Road, Suzhou, 215004, People’s Republic of China, Tel +86-15312187852 ; +86-13962514643, Email 15312187852@163.com; tlping67@126.comPurpose: To examine the reliability and validity of the Chinese short version of the Activities-specific Balance Confidence scale (ABC-6), and its predictive value for prospective falls in community-dwelling older adults.Patients and Methods: A total of 391 community older adults completed the prospective study. Internal consistency reliability, test-retest reliability, structural validity and discriminant validity were analyzed. To determine the accuracy of ABC-6 total score in predicting falls, a receiver operating characteristic curve analysis was performed, and comparisons with the Activities-specific Balance Confidence scale (ABC-16) and Berg Balance Scale (BBS) were made.Results: Excellent internal consistency (Cronbach’s α = 0.938) and test-retest reliability (ICC=0.964, 95% CI: 0.947– 0.977) were found for the ABC-6. Exploratory factor analysis suggested that ABC-6 had a one-factor structure (explained variance, 68.30%). The optimal cutoff value, sensitivity and specificity of ABC-6 to distinguish fallers from non-fallers was ≤ 60.00%, 70.83% and 84.26%, respectively, and there was no significant difference in the predictive value among the ABC-6, ABC-16, and BBS.Conclusion: The Chinese version of the ABC-6 scale was a valid and reliable tool for measuring self-perceived balance confidence in community-dwelling older adults, and can be used as an effective assessment tool to predict future falls.Keywords: activities-specific balance confidence scale, Chinese version, older adults, falls, predictive

Kai Bao,1,&ast; Jijun Chen,2,&ast; Ruifang Liu,1,3 Yuanyuan Xiang,1 Wenlong Gao1 1Institution of Epidemiology and Health Statistics, School of Public Health, Lanzhou University, Lanzhou, Gansu, People’s Republic of China; 2STD and AIDS Prevention and Control Institute, Lanzhou Municipal Center for Disease Control and Prevention, Lanzhou, Gansu, People’s Republic of China; 3Department of Science and Education, Xi’an No. 5 Hospital, Xi’an, Shanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenlong Gao, Lanzhou University, No. 222 South Tianshui Road, Lanzhou, Gansu, People’s Republic of China, Tel +8613919026975, Email gaowl2019@sina.comObjective: To investigate the prevalence of hepatitis C virus (HCV) infection among hemodialysis (HD) patients in Lanzhou of Northwestern China, we interviewed 565 patients from five randomly sampled HD centers in Lanzhou with a structured questionnaire including sociodemographic characteristics, past medical history and HD-related factors.Methods: The testing results of anti-HCV and HCV-RNA in a recent HD from clinical information system were collected. A generalized estimated equation (GEE) logistic regression model was used to identify the determinants of HCV infection among HD patients.Results: The prevalence of anti-HCV or HCV-RNA infection among HD patients was 1.77% or 1.42% respectively. GEE model showed that history of kidney transplantation (HCV-RNA: OR=19.79, 95%CI: 12.69– 30.85) could dramatically increase the risk of current HCV infection in dialysis patients. Compared with never using of blood products, using of blood products (anti-HCV: OR=2.38, 95%CI: 1.22– 4.64; HCV-RNA: OR=15.23, 95%CI: 1.79– 129.49) could increase the risk of HCV infection in dialysis patients. Moreover, with the increase of HD duration, the risk increased one time or so (anti-HCV: OR=1.83, 95%CI: 1.22– 2.72; HCV-RNA: OR=2.00, 95%CI: 1.11– 3.61). Furthermore, dialysis in multiple hospitals possessed more than three times risk of HCV infection (anti-HCV: OR=3.56, 95%CI: 3.11– 4.08; HCV-RNA: OR=3.35, 95%CI: 1.88– 5.96). Besides, HD patients having the history of acupuncture (HCV-RNA: OR=5.56; 95%CI: 1.16– 26.67) or surgery (HCV-RNA: OR=6.39; 95%CI: 2.86– 14.29) caused an about-six-times risk of current infections.Conclusion: It could be concluded that the prevalence of HCV infection was mild and using of blood products or kidney transplantation, long dialysis duration, dialysis in multiple hospitals, surgery or acupuncture treatment were some risk factors of HCV infection among HD patients in Lanzhou of Northwestern China.Keywords: hemodialysis, hepatitis C virus, generalized estimating equation introduction

Jia-qi Chen,&ast; Jie-ru Chen,&ast; Sheng Wang, Wei Gao, Hai Gu, Xin-lu Yang, Ji-cheng Hu, Xiao-qing Chai, Di Wang Pain Clinic, Department of Anesthesiology, The First Affiliated Hospital of USTC (Anhui Provincial Hospital), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Di Wang; Xiao-qing Chai, Department of Anesthesiology, The First Affiliated Hospital of USTC (Anhui Provincial Hospital), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, People’s Republic of China, Tel/Fax +86-551-62283963 ; +86-551-62283912, Email di.wang@ustc.edu.cn; xiaoqingchai@ustc.edu.cnPurpose: The goal of this study was to evaluate the analgesic efficiency of dexamethasone with ropivacaine in continuous serratus anterior plane block (cSAPB) after video-assisted thoracoscopic surgery (VATS).Patients and Methods: Sixty-six patients who underwent VATS were randomized into two groups. All patients received cSAPB postoperatively, and patients in Group RD received 20 mL of 0.375% ropivacaine plus 0.1 mg/kg dexamethasone followed by an infusion of 0.2% ropivacaine plus 0.02 mg/kg/hour dexamethasone at a rate of 5 mL/h in patient-controlled analgesia (PCA) pump. Patients in Group R received 20 mL of 0.375% ropivacaine with normal saline followed by an infusion of 5 mL/h of 0.2% ropivacaine in PCA pump. Fifty milligrams of tramadol was given as rescue medication when the visual analog scale (VAS) score was ≥ 4 at rest. The primary outcomes were the sum of pressing number within 48 hours postoperatively and the time to the first patient-controlled bolus. The secondary outcomes were VAS scores, the incidence of rescue analgesia, wound infection and nausea/vomiting.Results: Within 48 hours postoperatively, the sum of pressing number was more in Group R (18.33 ± 3.149 vs 16.09 ± 3.292, P = 0.006), and the Log Rank Test showed a significant difference in time to the first patient-controlled bolus (P = 0.006). After the PCA infusion finished, there were significantly lower VAS scores in Group RD at 60 and 72 hours postoperatively (P < 0.001). Additionally, the incidence of rescue analgesia in Group R was significantly more than that in Group RD (P < 0.001). No incision infection was observed in any patient.Conclusion: The cSAPB with ropivacaine plus dexamethasone prolonged the duration of analgesia and motor blockade, reduced pain intensity and rescued analgesia requirements after the end of PCA infusion for patients undergoing VATS, which provide further improvement to continuous perineural block.Keywords: continuous serratus anterior plane block, video-assisted thoracoscopic surgery, dexamethasone, levobupivacaine

Jiapeng Fu,1– 3,&ast; Jian Li,1– 3,&ast; Zhi Liu,1– 3 Shasha Zheng,1– 3 Xue Li,1– 3 Xianjia Ning,4,5 Jinghua Wang,4,5 Wenying Gao,1– 3 Guobao Li1– 3 1Department of the Third Pulmonary Disease, The Third People’s Hospital of Shenzhen, Shenzhen, Guangdong, People’s Republic of China; 2The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, People’s Republic of China; 3National Clinical Research Center for Infectious Diseases, Shenzhen, Guangdong, People’s Republic of China; 4Center of Clinical Epidemiology, The Third People’s Hospital of Shenzhen, Shenzhen, Guangdong, People’s Republic of China; 5Laboratory of Epidemiology, Tianjin Neurological Institute, Tianjin, 300052, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guobao Li; Wenying Gao, Department of the Third Pulmonary Disease, The Third People’s Hospital of Shenzhen, 29 Bulan Road, Longgang District, Shenzhen, Guangdong Province, 518112, People’s Republic of China, Tel +86-755-61238942, Fax +86-755-61238928, Email Lgb062112@163.com; jmjtgwy@126.comPurpose: Tracheobronchial tuberculosis (TBTB) has been proposed to occur more commonly in female patients. However, to date, studies that systematically delineate differences between female and male patients with TB infection are lacking. We aimed to comprehensively assess the sex-specific differences in clinical manifestation, bronchoscopy performance, bacteriological examination, and imaging of TBTB in Shenzhen, China.Methods: All patients with diagnosed TBTB from August 1, 2018 to July 31, 2021 at The Third People’s Hospital of Shenzhen were enrolled in the present study. Demographic information, clinical manifestations, blood tests, chest computed tomography, and bronchoscopic findings were collected, and assessed their sex-specific differences.Results: Of these 331 patients, 238 patients (71.9%) were female, and 93 patients (28.1%) were male, with an overall average age of 37.3 years. The average age of male patients with TBTB was more than 5 years older than that of female patients. The prevalence of lymph fistula and diabetes mellitus was significantly higher in male patients than female patients (8.6% vs 1.7%, P = 0.005; 17.2% vs 2.1%, P < 0.001). The positive proportion of sputum smear was higher in male patients (27.9%) than in female patients (16.7%, P = 0.026). Moreover, the mean monocyte-to-lymphocyte ratio, serum CRP, and IL-6 levels were significantly higher in male patients than in female patients (P < 0.05).Conclusion: In summary, in patients with TBTB diagnosis, male sex was associated with a high prevalence of diabetes mellitus, lymph fistula, and smear-positive ratio, as well as high inflammation levels. The management of young female and male patients with diabetes mellitus and high inflammation levels should be strengthened. Furthermore, to reduce the burden of TBTB, we must pay attention to the risk of TBTB in past tuberculosis patients, especially male patients under 45 years old and female patients over 45 years old.Keywords: sex difference, tracheobronchial tuberculosis, inflammation

Xinqiao Liu,1 Xiaojie Cao,2 Wenjuan Gao3 1School of Education, Tianjin University, Tianjin, 300350, People’s Republic of China; 2Graduate School of Education, Peking University, Beijing, 100871, People’s Republic of China; 3Institute of Higher Education, Beihang University, Beijing, 100191, People’s Republic of ChinaCorrespondence: Xinqiao Liu, School of Education, Tianjin University, No. 135 Tongyan Road, Jinnan District, Tianjin, 300350, People’s Republic of China, Email xinqiaoliu@pku.edu.cnPurpose: This study aimed to investigate the longitudinal relationship between anxiety and self-esteem among college students.Participants and methods: A total of 2473 Chinese college students were tracked, with their anxiety and self-esteem levels collected annually over the four academic years. The study employed a four-wave random intercept cross-lagged panel model to examine the prospective relationship between anxiety and self-esteem.Results: The anxiety levels were negatively associated with self-esteem over campus life. Results of the four-wave cross-lagged panel model revealed that low self-esteem maintained having subsequent negative impacts on students’ anxiety levels, while the effects became progressively stronger over the four academic years. Meanwhile, no significant prospective effects were identified of anxiety levels on self-esteem.Conclusion: The study confirmed self-esteem as one of the leading contributors to anxiety for college students and emphasized the importance of nourishing the self-esteem of students to alleviate their anxiety issues and improve their mental health at college.Keywords: mental health, longitudinal study, reciprocal relationships, student development

Hui Wang,1,&ast; Huaiming Peng,1,&ast; Linlin Zhang,1 Wei Gao,1 Jingya Ye2,3 1Department of Endocrinology, Yancheng City No.6 People’s Hospital, Yancheng, Jiangsu Province, People’s Republic of China; 2Department of Endocrinology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital), Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingya Ye, Department of Endocrinology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, People’s Republic of China, Tel +011-86-571-87783882, Fax +011-86-571-87022776, Email yezi88999@163.comObjective: Decreased bone mineral density (BMD) is a common complication in individuals with type 2 diabetes mellitus (T2DM). Body weight, mainly consisting of muscle and fat, is the main determinant of BMD and fracture risks but does not accurately describe nutritional status. Most studies suggest that skeletal muscle mass (SMM) promotes BMD, while body fat mass (BFM) decreases BMD. However, the combined effect of SMM and BFM on BMD is elusive. Thus, the study aims to explore the combined effect of fat and muscle by the ratio index SMM/BFM on BMD in T2DM.Methods: BFM and SMM were measured by the bioelectrical impedance analysis (BIA) method among 593 T2DM individuals ranging from normal weight and obesity. BMD was analyzed by DXA. Novel non-linear generalized additive models (GAMs) were used as the statistical analysis method.Results: The results demonstrated that BMD T score/Z score of both femur and lumbar vertebrae were significantly higher and waist–hip ratio (WHR) was significantly lower in the high SMM/BFM group of both normal weight and overweight groups in T2DM individuals. Hence, SMM/BFM might be a good factor indicating BMD in different weight ranges. Additionally, the relationship between muscle fat and BMD was not linear. Notably, this correlation was not influenced by hyperglycemia in T2DM since different analytic models adjusted with the age, gender, BMI and HbA1c were adopted in this study. Furthermore, the impact of trunk fat (central, visceral fat most) and non-trunk fat (peripheral, the sum of subcutaneous limb fat most) on BMD was inconsistent. BMD presented unlimited reduction with trunk BFM increasing, while sustaining minimal diminishment with non-trunk BFM accumulation.Conclusion: Our study provided a novel viewpoint relationship between muscle-fat and bone, and SMM/BFM might be a potential biomarker for bone health and clinical treatments of diabetes and related metabolic syndromes.Keywords: bone mineral density, skeletal muscle mass, body fat mass, type 2 diabetes, non-linear correlation

Wenqing Gao,1,&ast; Yuanyuan Li,1,&ast; Teng Zhang,1 Jianglong Lu,2 Jiasong Pan,1 Qi Qi,1 Siqi Dong,3 Xiangjun Chen,3,4 Zhipeng Su,2 Jixi Li1,4 1State Key Laboratory of Genetic Engineering, Department of Neurology, Huashan Hospital and Institute of Neurology, School of Life Sciences, Shanghai Engineering Research Center of Industrial Microorganisms, Fudan University, Shanghai, 200438, People’s Republic of China; 2Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 3Department of Neurology, Huashan Hospital and Institute of Neurology, Fudan University, Shanghai, 200040, People’s Republic of China; 4National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhipeng Su; Jixi Li, Email drsuzhipeng@wmu.edu.cn; lijixi@fudan.edu.cnBackground: Glioblastoma (GBM) is the most common and aggressive brain tumor in adults, in which chemokines are often upregulated and may play pivotal roles in their development and progression. Chemokines are a large subfamily of cytokines with leukocyte chemotactic activities involved in various tumor progression. However, gene expression patterns of the chemokines on a global scale were not known in GBM.Methods: Differentially expressed chemokine genes in glioma and normal samples were screened by using The Cancer Genome Atlas (TCGA) database. Cox regression identified the prognosis-related genes in each glioma subtype. The protein expression levels of chemokines in 72 glioma tissues were detected by ELISA.Results: We found that the transcripts of seven chemokines, including CCL2, CCL8, CCL18, CCL28, CXCL1, CXCL5, and CXCL13, were highly expressed in GBM that evidenced by involving immune cell infiltration regulation and accompanied with worse outcomes of GBM patients. The prognostic nomogram construction demonstrated that CCL18 held the highest risk score in patients with GBM. Furthermore, experiments on 72 glioma tissue samples confirmed that CCL18 protein expression was positively associated with tumor grade and IDH1 status but inversely with glioma patients’ overall survival (OS).Conclusion: Our study reveals comprehensive and comparable roles of chemokine members in glioblastoma, and identified CCL18 as a critical driver of GBM malignant behaviors, therefore providing a potential target for developing prognosis and therapy in human glioblastoma.Keywords: chemokines, GBM, biomarker, overall survival, prognosis

Yong Gao,1,&ast; Baobao Cai,1,&ast; Lingdi Yin,1,&ast; Guoxin Song,2 Zipeng Lu,1 Feng Guo,1 Jianmin Chen,1 Chunhua Xi,1 Jishu Wei,1 Junli Wu,1 Wentao Gao,1 Kuirong Jiang,1 Yi Miao1,3 1Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China; 2Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China; 3Pancreas Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Miao, Email miaoyi@njmu.edu.cnBackground: Undifferentiated carcinoma of pancreas with osteoclast-like giant cells is an extremely rare tumor in pancreas. It is relatively difficult to have preoperative diagnosis due to the lack of specific tumor markers and pre-operative images.Methods: In the present study, database of the pancreas center in the First Affiliated Hospital of Nanjing Medical University was retrospectively screened. A total of thirteen cases diagnosed as undifferentiated carcinoma of pancreas with osteoclast-like giant cells were included. Their clinical data and treatments were collected.Results: Thirteen patients include eight males and five females, and the median age was 67 (60– 72) years old. The lesions were found in more than half patients through health examination with no symptoms. NSE was elevated in eight cases (66%). CT scan revealed that cystic and solid lesions often had thick (4/5), contrast-enhanced (5/5) wall with smooth edges (5/5) and the boundary of lesions mainly with solid composition (4/10) is not well demarcated with normal pancreatic parenchyma. All patients received surgical resection. Eight patients had adjuvant chemotherapy and only one patient had adjuvant radiotherapy. The median survival time was 13 months. Five patients had postoperative metastasis or recurrence of tumor and four of them had died of this disease during follow-up.Conclusion: Our data showed that elevated level of NSE and characteristic pre-operative images might provide aid with the pre-operative diagnosis for undifferentiated carcinoma of pancreas with osteoclast-like giant cells. Patients with suspected diagnosis should receive surgical intervention as soon as possible, supplemented with postoperative chemotherapy, in order to prolong the survival of patients.Keywords: pancreatic cancer, undifferentiated carcinoma of pancreas, osteoclast-like giant cells, retrospective, pre-operative image

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

Guodai Hong,1 Silun Xie,2 Zikuan Guo,3 Diping Zhang,2 Sihai Ge,2 Suqin Zhang,1 Wenbin Gao1 1Department of Oncology, The Third Affiliated Hospital of Shenzhen University (Shenzhen Luohu People’s Hospital), Shenzhen, 518002, People’s Republic of China; 2Shenzhen Cell Biotechnology Co., Ltd, Shenzhen, 518054, People’s Republic of China; 3Beijing Clin- Biotechnology Co., Ltd, Beijing, 100070, People’s Republic of ChinaCorrespondence: Wenbin Gao, Department of Oncology, The Third Affiliated Hospital of Shenzhen University (Shenzhen Luohu People’s Hospital), Luohu District, Shenzhen, 518002, People’s Republic of China, Tel +86 132 6677 8968, Email drwenbingao@163.comAbstract: Adoptive cell therapy (ACT) is a promising treatment that is considered safe and efficient. Natural killer (NK) cells play an important role in the innate immune system and destroy target cells such as tumor cells without prior sensitization. Here, we report a 59-year-old man with advanced diffuse hepatocellular carcinoma (HCC) who underwent 17 courses of NK cell treatment from March 2017 to July 2018. Although he presented with progressive disease, his hydrothorax and ascites decreased, and his state of mind, appetite and quality of life were markedly improved after treatment versus at admission. To date, his survival time is > 48 months. Here, we provide evidence that NK cell adoptive therapy has no adverse effects, enhances immune function, and improves the quality of life of patients with HCC.Keywords: hepatocellular carcinoma, natural killer cell therapy, prolonged survival

Wenbo Gao, Ming Li, Yunhao Zhang Department of Oncology Surgery, Jiamusi Central Hospital, Jiamusi, 154002, People’s Republic of ChinaCorrespondence: Wenbo GaoDepartment of Oncology Surgery, Jiamusi Central Hospital, Jiamusi, 154002, People’s Republic of ChinaEmail Wenbogaojms@163.comObjective: To investigate the potential prognostic significance of fibrinogen/albumin ratio (FAR) in triple negative breast cancer (TNBC) patients and its relationship with epidermal growth factor receptor (EGFR) expression.Methods: There were 164 patients with TNBC enrolled in this study in our hospital from January 2010 to December 2015. The optimal cutoff value of FAR was evaluated by the receiver operating characteristic curve (ROC). The associations between TNBC and clinicopathological variables by FAR were performed by Chi-square test. Kaplan–Meier method and Log rank test were used for survival analysis. The independent prognostic factors were determined by univariate and multivariate Cox’s proportional hazards regression model. The EGFR expression was analyzed by the immunohistochemistry assay.Results: One hundred and sixty-four TNBC patients were divided into: low FAR group (FAR < 0.08) and high FAR group (FAR ≥ 0.08) by ROC. The preoperative FAR was associated to BMI, menopause, red blood cell, albumin, fibrinogen (P < 0.05). FAR was an independent prognostic factor for TNBC. In low FAR group, the mean disease-free survival (DFS) and overall survival (OS) were 33.62 months and 52.99 months; in high FAR group, the mean DFS and OS were 30.18 months and 48.27 months, respectively. The DFS and OS survival curve were performed by Log rank assay and were statistically significant (P < 0.05). The mean DFS and OS after operation in patients with EGFR negative expression were longer than that in patients with EGFR positive expression. In EGFR positive group, the mean DFS and OS of low FAR group were higher than that of high FAR group, and the difference was statistically significant (P < 0.05).Conclusion: Pretreatment FAR is the independent prognostic factor in TNBC, and with low cost, strong repeatability, and high safety. It can be acted as an effective indicator to predict the prognosis of TNBC.Keywords: fibrinogen/albumin ratio, epidermal growth factor receptor, triple negative breast cancer, prognosis

Yilin Xiong,1,&ast; Yuqiao Han,1,&ast; Zinan Zhao,1,&ast; Wenting Gao,2 Yong Ma,2 Shiyu Jiang,1 Mengyao Wang,1 Qingqing Zhang,3 Yun Zhou,4 Yang Chen1 1Department of Biotechnology, College of Basic Medical Sciences, Dalian Medical University, Dalian, People’s Republic of China; 2Institute of Genome Engineered Animal Models for Human Disease, Dalian Medical University, Dalian, People’s Republic of China; 3Laboratory of Pathogenic Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, People’s Republic of China; 4Department of Clinical Nutrition, Second Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang ChenDepartment of Biotechnology, College of Basic Medical Sciences, Dalian Medical University, 9 West Section of Lvshun South Road, Dalian, 116044, People’s Republic of ChinaTel/Fax +86 411 86110350Email yangchen@dmu.edu.cnYun ZhouDepartment of Clinical Nutrition, Second Affiliated Hospital of Dalian Medical University, 467 Zhongshan Road, Dalian, 116023, People’s Republic of ChinaTel +86 411 84690722Fax +86 411 84672130Email dmu_yunzhou@yeah.netPurpose: Antibiotic resistance is a growing health crisis that is further complicated by treatment failures caused by bacteria that exhibit heterogeneous susceptibility to antibiotics. The aim of this study was to describe imipenem (IPM)-heteroresistant strains among multidrug-resistant (MDR) ESBL/AmpC-producing Klebsiella pneumoniae clinical isolates, investigate their molecular phenotypic characteristics, and elucidate the outcome of antibiotic treatment in mice infected with the heteroresistant isolates.Materials and Methods: Antimicrobial susceptibility of K. pneumoniae isolates was determined by the disk diffusion and E-test methods. Heteroresistance to IPM was confirmed by population analysis profile (PAP) assays. PCR and sequencing were employed to detect MDR determinants. Molecular differences between the susceptible and resistant subpopulations were evaluated by sequencing and quantitative real-time reverse transcription PCR (qRT-PCR) analysis. The effect of the carbapenem-heteroresistant strains on antibiotic treatment was assessed using a mouse model of peritonitis with heteroresistant K. pneumoniae and subsequent treatment with IPM.Results: In total, 37 MDR ESBL/AmpC-producing clinical isolates of K. pneumoniae were identified between September 2018 and December 2019. These strains were notably resistant to conventional antimicrobials other than carbapenems. Among the isolates, three strains exhibited heteroresistance to IPM and carried several ESBL and/or AmpC genes. Mice infected with a lethal dose of any of the three heteroresistant isolates were unable to survive in the presence of IPM treatment, as the percentage of the IPM-resistant subpopulation of each strain was increased in the peritoneum of these mice at 24 h after infection. The resistant subpopulation of the strains presented pulsed-field gel electrophoresis (PFGE) profiles that were identical to those of the susceptible subpopulation, but ompK36 porin showed a reduction in gene expression (0.09- to 0.50-fold) in the resistant subpopulation.Conclusion: Carbapenem-heteroresistant strains were present among the MDR K. pneumoniae isolates producing ESBL/AmpC β-lactamases, and these heteroresistant strains failed IPM therapy in experimentally infected mice.Keywords: Enterobacteriaceae, imipenem, heterogeneous susceptibility, treatment failure, OmpK porin, in vivo

Sujuan Zeng,1,&ast; Shiqi Liu,1,2,&ast; Yintao Lan,3 Ting Qiu,3 Mengyu Zhou,3 Weijian Gao,3 Wenyan Huang,1 Lihong Ge,1,4 Jian Zhang1,3 1Department of Pedodontics, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangdong, People’s Republic of China; 2Department of Stomatology, Taihe Hospital, Institute of Oral Diseases, School of Dentistry, Hubei University of Medicine, Hubei, People’s Republic of China; 3Department of Biomedical Engineering, School of Basic Medical Sciences, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Guangzhou Medical University, Guangdong, People’s Republic of China; 4Department of Pediatric Dentistry, Stomatology Hospital of Peking University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Zhang; Lihong Ge Email jianzhang@gzhmu.edu.cn; gelh0919@126.comBackground: Squamous cell carcinoma of the head and neck is the sixth most common cancer worldwide, with 40% occurring in the oral cavity. Although the level of early diagnosis and treatment of OSCC has improved significantly, the five-year survival rate of advanced patients remains unsatisfactory. However, the main challenges before us are how to get an early and accurate diagnosis and how to formulate effective treatment. Nanoparticle-based chemo-photothermal therapy has proven to be a promising non-invasive approach to treating oral squamous cell carcinoma treatment.Methods: In this study, we tried to design and synthesize multifunctional hyaluronic acid (HA) modified gold nanorods/mesoporous silica-based nanoparticles loaded with doxorubicin hydrochloride (DOX) for photoacoustic imaging (PAI) guided cooperative chemo-photothermal therapy.Results: The resultant nanocomposite shows favorable biocompatibility, relatively low cytotoxicity, ideal drug loading capability and strong PAI signals. In addition, they showed an excellent photothermal conversion efficiency of 49.02% for photothermal therapy (PTT). Moreover, in vivo and in vitro experiments have shown that synergistic chemo-photothermal therapy has better therapeutic effects than chemotherapy alone or PTT (P < 0.05). After being injected into the CAL-27 tumor-bearing mice, the DOX-AuNRs@mSiO2-HA nanoparticles could accumulate rapidly at the tumor sites and achieve complete ablation of tumors when combined with near-infrared laser irradiation, without obvious side effects on normal tissues.Conclusion: Our research provides a solid demonstration of the potential of DOX–AuNRs@mSiO2-HA as a multifunctional platform in PAI-guided photothermal chemotherapy for oral squamous cell carcinoma.Keywords: mesoporous silica coated gold nanorods, photoacoustic imaging, chemo-photothermal therapy, oral squamous cell carcinoma

Sheng Yin,1,&ast; Wen Gao,2,&ast; Peipei Shi,1 Meili Xi,1 Wenbin Tang,1 Jiarong Zhang1 1Department of Obstetrics and Gynecology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 2Department of Gynaecologic Oncology, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiarong ZhangDepartment of Obstetrics and Gynecology, Zhongshan Hospital, Fudan University, Fenglin Road, 180#, Xuhui District, Shanghai, 200032, People’s Republic of ChinaTel +86 21-64041990Email zhang.jiarong@zs-hospital.sh.cnPurpose: Minimally invasive surgery (MIS) is performed frequently in early-stage ovarian cancer patients, especially in ovarian clear cell carcinoma (OCCC). The aim of this study was to investigate whether primary laparoscopic surgery influences prognosis in patients with early-stage OCCC.Patients and Methods: Patients with International Federation of Gynecology and Obstetrics (FIGO) stage I OCCC were retrospectively reviewed in two hospitals between April 2010 and August 2020. Clinical data were abstracted, and patients were followed up until February 2021. Patients were divided into open surgery (laparotomy) and laparoscopy groups, and the Kaplan–Meier method was applied to compare progression-free survival (PFS) and overall survival (OS) between the groups. Statistical differences were determined by the Log rank test.Results: Eighty-nine patients were included in the study; 20 (22.5%) and 69 (77.5%) patients underwent laparoscopic and open surgery, respectively. The patients’ characteristics were well-balanced except that patients in the laparoscopy group tended to have smaller tumors and lower frequency of omentectomy and lymphadenectomy compared with the open surgery group. The median follow-up duration was 42.6 and 36.5 months in the laparoscopy and open surgery groups, respectively. Nine (10.1%) patients developed recurrence, and 4 (4.5%) died of the disease; all in the open surgery group. The estimated 2-year PFS rates were 100.0% and 90.1%, and the estimated 5-year OS rates were 100.0% and 91.9% in the laparoscopy and open surgery groups, respectively. No significant survival differences were found between the groups.Conclusion: Survival was not compromised when primary laparoscopic surgery was performed in early-stage OCCC patients. A well-designed randomized controlled trial is warranted.Keywords: laparoscopic surgery, early-stage ovarian clear cell cancer, prognosis

Yan Sun,1,2 Lixin Yu,1,2 Wei Gao,1,2 Jinzhen Cai,1,2 Wentao Jiang,1,2 Wei Lu,3 Yihe Liu,1,2 Hong Zheng1,2 1Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, 300192, People’s Republic of China; 2Tianjin Key Laboratory for Organ Transplantation, Tianjin, People’s Republic of China; 3Liver Cancer Treatment Centre, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People’s Republic of ChinaCorrespondence: Yihe Liu; Hong ZhengOrgan Transplantation Center, Tianjin First Central Hospital, No. 24 of Fukang Street, Nankai District, Tianjin, 300192, People’s Republic of ChinaTel/Fax +8602223627027Email limyihe@163.com; zhemghomgi@21cn.comObjective: This study aimed to investigate the colonization and prevalence of carbapenem-resistant Enterobacteriaceae (CRE) in pediatric liver transplant recipients and analyze the high-risk factors and prognosis of CRE infection.Methods: A prospective study involving 152 pediatric patients undergoing liver transplantation was carried out. Anal swab bacteria cultures were collected when the patients entered the intensive care unit (ICU) and when they left in order to screen for intestinal CRE colonization. The results were grouped according to the occurrence of CRE infection following surgery, and the patients were divided into two groups: a CRE infection group and a non-CRE infection group. Univariate analysis and multiple logistic regression analysis were conducted to determine the independent risk factors of CRE infection and analyze the survival rate.Results: Of the 152 pediatric liver transplant recipients enrolled in the study, there were 13 cases of postoperative CRE infection and 139 cases of non-CRE infection. The incidence of preoperative CRE infection, preoperative cytomegalovirus (CMV) infection, and preoperative sepsis in the CRE infection group was significantly higher than in the non-CRE infection group (P < 0.005). Intraoperative bleeding volume and operation times in the CRE infection group were also significantly higher than in the non-CRE infection group (P < 0.05). Furthermore, postoperative ICU treatment time, postoperative occurrence of unplanned surgery, postoperative mechanical ventilation of more than 24 hours, and the incidence of pre-ICU CRE colonization in the CRE infection group were significantly higher than in the non-CRE infection group (P < 0.05). Finally, the difference between the CRE infection group and the non-CRE infection group in six-month survival rate following surgery was significant (P < 0.001).Conclusion: The independent risk factors of CRE infection following pediatric liver transplantation include preoperative CRE infection and pre-ICU CRE colonization. CRE infection progresses quickly, with a poor prognosis and a high mortality rate. The CRE screening of anal swabs is crucial for the early detection of CRE infection.Keywords: carbapenem-resistant Enterobacteriaceae, CRE, liver transplantation, intestinal colonization, CT screening, anal swabs

JingTong Tang,1 Wei Gao,1 Gang Liu,1 WeiWei Sheng,1 JianPing Zhou,1 Qi Dong,2 Ming Dong1 1Department of Gastrointestinal Surgery & Hernia and Abdominal Wall Surgery, The First Hospital, China Medical University, Shenyang, 110001, Liaoning, People’s Republic of China; 2Department of General Surgery, The People’s Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: JianPing Zhou Fax +86 24-83282886Email zjphama@163.comBackground: miR-944 belongs to the MicroRNAs family, as shown in our previous study, and is essential in the colorectal cancer (CRC) progression. It is negatively associated with invasion depth and lymph node status. Epithelial-mesenchymal transition (EMT) is essential in tumor invasion and metastasis. However, the relationship between miR-944 and EMT in CRC is unknown and should be further investigated.Methods: Epithelial–mesenchymal transition (EMT) progression in CRC cell lines was detected with Cell morphology and Western blotting. CRC cell migration and invasion were examined using Transwell assays. Transcriptome and clinical data were obtained from The Cancer Genome Atlas (TCGA) database. The potential pathway of miR-944 and GATA6 were predicted using KEGG analysis. Colocalization was validated using immunofluorescence and Immunohistochemistry. Nuclear and Cytoplasmic Protein Extraction assays were conducted to determine the effects of miR-944 on Wnt/β-catenin signaling.Results: We found that miR‑944 influences EGF-induced EMT malignant phenotype in vitro. KEGG analyses showed that miR-944 and GATA6 are associated with EMT related pathways, wnt signaling pathways. On the other hand, Western Blot analyses showed that miR-944 can regulate EMT and wnt-β-catenin pathway-related protein, including β-catenin, ZEB1, snail1 via GATA6 regulation. miR-944 also abrogates E-ca after EGF induction. Immunohistochemistry (IHC) and Immunofluorescence (IF) co-expression showed that GATA6 expression is positively associated with β-catenin and ZEB1. GATA6 silencing can reverse EMT malignant phenotype and alterations of related protein induced by miR-944. Quantitative polymerase chain reaction analysis results showed that miR-944 is negatively associated with the UICC stage (P= 0.02), lymph nodes (p=0.04), and liver metastasis (p=0.03). Moreover, patients with high miR-944 expression have better survival (p=0.045). We finally combined miR-944 and GATA6 and found that miR-944/GATA6 ratio could be a novel prognostic biomarker in the TCGA dataset and it is an independent risk prognosis factor (p=0.045).Conclusion: Our results suggest that miR-944 suppresses the aggressive biological processes by directly repressing GATA6 expression and could be a potential candidate for therapeutic applications in CRC.Keywords: miR-944, colorectal cancer, GATA6, epithelial-mesenchymal transition

Chunxiao Liao,1 Wenjing Gao,1 Weihua Cao,1 Jun Lv,1 Canqing Yu,1 Shengfeng Wang,1 Zengchang Pang,2 Liming Cong,3 Hua Wang,4 Xianping Wu,5 Liming Li1 1Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, 100191, People’s Republic of China; 2Qingdao Center for Diseases Control and Prevention, Qingdao, 266033, People’s Republic of China; 3Zhejiang Center for Disease Control and Prevention, Hangzhou, 310051, People’s Republic of China; 4Jiangsu Center for Disease Control and Prevention, Nanjing, 210009, People’s Republic of China; 5Sichuan Center for Disease Control and Prevention, Chengdu, 610041, People’s Republic of ChinaCorrespondence: Liming Li; Wenjing GaoDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University, 38 XueYuan Road, HaiDian District, Beijing, 100191, People’s Republic of ChinaTel +86 10 82801528Fax +86 10 82801528 Ext. 322Email lmlee@vip.163.com; wenjinggao@bjmu.edu.cnBackground: Obesity is a heterogeneous condition in terms of metabolic status. Different obesity phenotypes have various health risks. The aim of this work was to define different subtypes of obesity and investigate their relationship with inflammatory-cardiometabolic abnormalities among Chinese adult twins.Methods: The analyses used data from 1113 adult twins in 4 provinces (Shandong, Zhejiang, Jiangsu and Sichuan) from Chinese National Twin Registry (CNTR) which collected detailed information. We defined those with 0 or 1 metabolic syndrome (MetS) components excluding waist circumference as metabolically healthy, and those with waist circumference ≥ 90 cm (for men) and ≥ 85 cm (for women) as obese. The two-category obesity status and metabolic states are combined to generate four metabolic/obesity phenotypes. High sensitivity C reactive protein (hsCRP) was measured to assess underlying inflammation and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated as surrogate measure of insulin resistance. Mixed-effect linear regression models and fixed-effect linear regression models were used to analyse the correlation between HOMA-IR, hsCRP and different metabolic/obesity phenotypes.Results: In cross-sectional analyses of 1113 individuals (mean [SD] age, 46.6 [12.9] years; 463 obese [41.6%]), 20.3% obese twins were metabolic healthy and 64.2% non-obese twins were metabolic unhealthy. Serum HOMA-IR level was higher in metabolically unhealthy non-obesity (MUNO) (β=0.42, 95% CI: 0.21– 0.64), metabolically healthy obesity (MHO) (β=0.68, 95% CI: 0.36– 1.00) and metabolically unhealthy obesity (MUO) (β=0.69, 95% CI: 0.46– 0.91) twins, compared with their metabolically healthy non-obesity (MHNO) counterparts. HsCRP was similar between MHO and MUO, which differed significantly to metabolic healthy non-obesity (MHNO).Conclusion: MHO and MUNO phenotypes were common in Chinese twin population. Both phenotypes were associated with elevated IR and hsCRP which may not be benign and need to be concerned.Keywords: metabolic status, insulin resistance, chronic inflammation, twin study

Li Song,1,* Yuanjing Lyu,1,* Ling Ding,1 Xiaoxue Li,1 Wen Gao,1 Ming Wang,1 Min Hao,2 Zhilian Wang,2 Jintao Wang1 1Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030000, People’s Republic of China; 2Department of Obstetrics and Gynecology, Second Hospital of Shanxi Medical University, Taiyuan 030000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jintao WangDepartment of Epidemiology, School of Public Health, Shanxi Medical University, 56 Xinjian Nan Road, Taiyuan 030000, People’s Republic of ChinaTel +86 0351-413-5245Email wangjt59@163.comPurpose: High-risk human papillomavirus (HR-HPV) infection is widely known as the major cause of cervical cancer and there are notable differences in HR-HPV prevalence and genotype distribution in different populations. Women with abnormal cervical cytology are at increased risk of cervical cancer; however, the genotype distribution of HR-HPV in women with abnormal cervical cytology remains unclear.Methods: A total of 2,300 women with abnormal cervical cytology (from 39,988 women completing a baseline survey in a cohort established during June 2014 to December 2014) were enrolled in this study. All participants gave informed consent and completed a questionnaire about characteristics related to HPV infection. HPV genotypes were identified using flow-through hybridization, and cytology was assessed by the ThinPrep cytological test. Data were analyzed using SPSS 22.0 for Windows.Results: The overall prevalence of HR-HPV in the 2,300 women with abnormal cervical cytology was 32%, with single and multiple HR-HPV infections making up 70.2% and 29.8%, respectively. The top-five HR-HPV genotypes were HPV16 (13.5%), HPV58 (5.7%), HPV52 (4.9%), HPV53 (2.5%), and HPV51 (2.3%). The prevalence of HR-HPV in atypical squamous cells of undetermined significance, low-grade squamous intraepithelial lesions, and high-grade squamous intraepithelial lesions or higher was 30.8%, 36.5%, and 54.9%, respectively, showing an increasing trend with severity of cervical cytology (χ2trend=13.952, p< 0.001). The prevalence of HPV16 and HPV33 increased significantly with the degree of cytological abnormality. HR-HPV infection risk was statistically higher in women aged 35– 45 years, with low education, infrequent bathing, multiple gravidity, multiple parity, history of gynecological diseases, and premenopause.Conclusion: HR-HPV infection in women with abnormal cervical cytology was 32%, and the top-five HR-HPV genotypes were HPV16, HPV58, HPV52, HPV53, and HPV51 in Shanxi Province, China. These results shed light on demographic and behavioral characteristics related to HR-HPV infection in women with abnormal cervical cytology and provide an insight for the development of HPV vaccines.Keywords: cervical cancer, high-risk human papillomavirus, genotype distribution, abnormal cervical cytology

Wenjuan Zhu,1,* Wenzhe Gao,2,* Yanyao Deng,3 Xiao Yu,2 Hongwei Zhu2 1Division of Nephrology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, People’s Republic of China; 2Department of Hepatopancreatobiliary Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 3Department of Neurology, The First Hospital of Changsha, Changsha, Hunan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiao Yu; Hongwei ZhuDepartment of Hepatopancreatobiliary Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of ChinaEmail yuxiaoyx4@126.com; zhw_0509@csu.edu.cnBackground and Aims: Pancreatic adenocarcinoma (PAAD) is the most lethal cancer type around the world. With the in-depth exploration of the function of long non‐coding RNAs (lncRNAs), the competing endogenous RNA (ceRNA) mechanism has shown its potential to partially reveal the pathogenesis of PAAD. This study aimed to construct a lncRNA‐associated ceRNA network and explore ceRNA regulatory axes with experimental and prognostic value in PAAD.Methods: First, we applied differential expression analysis in the TCGA_PAAD dataset. Then, interaction analysis and survival analysis in multiple RNA interaction databases were conducted to construct a ceRNA network. Finally, a potential regulatory axis was validated using clinical samples and cell lines by quantitative realtime PCR (qRT‐PCR).Results: A ceRNA network comprising 13 lncRNAs, 96 miRNAs, and 30 mRNAs was successfully constructed. Survival analysis further narrowed this network to five lncRNAs, three miRNAs, and seven mRNAs, which were significantly associated with patients’ overall survival. A potential regulatory axis CASC8-miR-129-5p-TOB1 was further experimentally validated. The expression of these genes was associated with clinicopathological factors and their expression trend was consistent with ceRNA mechanism. Specifically, knockdown of lncRNA-CASC8 led to the overexpression of miR-129-5p and down-regulation of TOB1, while overexpression of CASC8 showed opposite effects.Conclusion: This novel ceRNA regulatory network could provide new insight into the pathogenesis of PAAD. The new regulatory axis CASC8-miR-129-5p-TOB1 might serve as a potential therapeutic target for patients.Keywords: pancreatic adenocarcinoma, competing endogenous RNA, long non‐coding RNA, The Cancer Genome Atlas, bioinformatics analysis

Lian Liu,1 Bingyu Li,1 Quan Cao,2 Bo Zhao,1 Wenwei Gao,3 Yuan Chen,4 Shihua Yu5 1Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, People’s Republic of China; 2Department of Ultrasound Imaging, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, People’s Republic of China; 3Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, People’s Republic of China; 4Department of Academic Research, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, People’s Republic of China; 5Department of Anesthesiology, Renmin Hospital of Hannan District, Wuhan, Hubei 430090, People’s Republic of ChinaCorrespondence: Yuan ChenDepartment of Academic Research, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, People’s Republic of ChinaEmail chenyuan_rmyy@whu.edu.cnShihua YuDepartment of Anesthesiology, Renmin Hospital of Hannan District, Wuhan, Hubei 430090, People’s Republic of ChinaEmail 1912840405@qq.comPurpose: Although pain after laparoscopic surgery is assumed to be minor, many women still suffer from unexpected postoperative pain. Thus, we aimed to assess whether additional intraoperative administration of sufentanil could help to improve postoperative pain and related agitation, stress, and inflammation response in patients undergoing laparoscopic myomectomy.Patients and Methods: Forty female patients with uterine myoma scheduled for laparoscopic myomectomy under general anesthesia were randomized to receive sufentanil (group T, n=20) or normal saline (group C, n=20) 1h before the end of the surgery. The postoperative pain, agitation, stress, inflammation, and adverse effects were measured.Results: As the primary outcome, the visual analog scale (VAS) pain score was significantly reduced in group T as compared with group C at each measured time point in a post-anesthesia care unit (PACU), VAS 5 min (31.5 ± 2.7 vs 40.6 ± 5.6) (P< 0.001), VAS 30 min (36.5 ± 4.5 vs 46.0 ± 2.9) (P< 0.001), VAS 1h (37.8 ± 4.0 vs 48.6 ± 5.5) (P< 0.001). The secondary outcomes, including the sedation agitation scale (SAS) scores, plasma concentrations of epinephrine and norepinephrine, and the levels of plasma interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-α) in group T were remarkably lower than those in group C (P < 0.001). The cough cases in group T also showed a significant reduction in comparison with group C (P < 0.05). In addition, the anesthetic recovery time, including the spontaneous breathing recovery time and extubation time, were not significantly different between the two groups, as were the cases of respiratory depression and postoperative delirium (P > 0.05).Conclusion: For patients undergoing laparoscopic myomectomy, administration of sufentanil 1 h before the end of surgery shows excellent analgesic and sedative effects, alleviated postoperative stress and inflammatory responses, reduced incidence of cough, without prolonging anesthetic recovery time and increasing adverse reactions.Keywords: anesthesia, laparoscopic myomectomy, postoperative outcomes, sufentanil

Fuyan Shi,1 Changlan Yu,2 Liping Yang,3 Fangyou Li,2 Jiangtao Lun,4 Wenfeng Gao,5 Yongyong Xu,6 Yufei Xiao,1 Sravya B Shankara,7 Qingfeng Zheng,8 Bo Zhang,9 Suzhen Wang1 1Department of Health Statistics, School of Public Health and Management, Weifang Medical University, Weifang, Shandong, People’s Republic of China; 2Anqiu City Center for Disease Control and Prevention, Anqiu, Shandong, People’s Republic of China; 3Health and Medical Center, Xijing Hospital, Air Force Military Medical University, Xi’an, Shannxi, People’s Republic of China; 4Anqiu Meteorological Bureau, Anqiu, Shandong, People’s Republic of China; 5Department of Immunology and Rheumatology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, People’s Republic of China; 6Department of Health Statistics, School of Military Preventive Medicine, Air Force Military Medical University, Xi’an, Shannxi, People’s Republic of China; 7Program in Health: Science, Society, and Policy, Brandeis University, Waltham, MA, USA; 8Institute for Hospital Management of Tsinghua University, Tsinghua Campus, Shenzhen, People’s Republic of China; 9Department of Neurology and ICCTR Biostatistics and Research Design Center, Boston Children’s Hospital and Harvard Medical School, Boston, MA, USACorrespondence: Bo Zhang; Suzhen Wang Email bo.zhang@childrens.harvard.edu; wangsz@wfmc.edu.cnObjective: The purpose of this study was to explore the dynamics of incidence of hemorrhagic fever with renal syndrome (HFRS) from 2000 to 2017 in Anqiu City, a city located in East China, and find the potential factors leading to the incidence of HFRS.Methods: Monthly reported cases of HFRS and climatic data from 2000 to 2017 in the city were obtained. Seasonal autoregressive integrated moving average (SARIMA) models were used to fit the HFRS incidence and predict the epidemic trend in Anqiu City. Univariate and multivariate generalized additive models were fit to identify and characterize the association between the HFRS incidence and meteorological factors during the study period.Results: Statistical analysis results indicate that the annualized average incidence at the town level ranged from 1.68 to 6.31 per 100,000 population among 14 towns in the city, and the western towns exhibit high endemic levels during the study periods. With high validity, the optimal SARIMA(0,1,1,)(0,1,1)12 model may be used to predict the HFRS incidence. Multivariate generalized additive model (GAM) results show that the HFRS incidence increases as sunshine time and humidity increases and decreases as precipitation increases. In addition, the HFRS incidence is associated with temperature, precipitation, atmospheric pressure, and wind speed. Those are identified as the key climatic factors contributing to the transmission of HFRS.Conclusion: This study provides evidence that the SARIMA models can be used to characterize the fluctuations in HFRS incidence. Our findings add to the knowledge of the role played by climate factors in HFRS transmission and can assist local health authorities in the development and refinement of a better strategy to prevent HFRS transmission.Keywords: hemorrhagic fever with renal syndrome, meteorological factors, autoregressive integrated moving average model, generalized additive model, prediction

Jie Zhou,1,2 Jing Hou,1,2 Jun Rao,2,3 Conghui Zhou,2,4 Yunlong Liu,5 Wenxi Gao1,2 1Department of Urology, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, Hubei, People’s Republic of China; 2Hubei Province Academy of Traditional Chinese Medicine, Wuhan, Hubei, People’s Republic of China; 3Clinical Laboratory, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, Hubei, People’s Republic of China; 4Department of Pharmaceutical Sciences, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, Hubei, People’s Republic of China; 5Department of Urology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Jie Zhou Email zhoujieuser@163.comBackground: β-Glucosidase (β-Glu) can activate amygdalin to kill prostate cancer cells, but the poor specificity of this killing effect may cause severe general toxicity in vivo, limiting the practical clinical application of this approach.Materials and Methods: In this study, starch-coated magnetic nanoparticles (MNPs) were successively conjugated with β-Glu and polyethylene glycol (PEG) by chemical coupling methods. Cell experiments were used to confirm the effects of immobilized β-Glu on amygdalin-mediated prostate cancer cell death in vitro. Subcutaneous xenograft models were used to carry out the targeting experiment and magnetically directed enzyme/prodrug therapy (MDEPT) experiment in vivo.Results: Immobilized β-Glu activated amygdalin-mediated prostate cancer cell death. Tumor-targeting studies showed that PEG modification increased the accumulation of β-Glu-loaded nanoparticles in targeted tumor tissue subjected to an external magnetic field and decreased the accumulation of the nanoparticles in the liver and spleen. Based on an enzyme activity of up to 134.89 ± 14.18mU/g tissue in the targeted tumor tissue, PEG-β-Glu-MNP/amygdalin combination therapy achieved targeted activation of amygdalin and tumor growth inhibition in C57BL/6 mice bearing RM1 xenografts. Safety evaluations showed that this strategy had some impact on liver and heart function but did not cause obvious organ damage.Conclusion: All findings indicate that this magnetically directed enzyme/prodrug therapy strategy has the potential to become a promising new approach for targeted therapy of prostate cancer.Keywords: magnetic nanoparticles, β-glucosidase, amygdalin, prostate cancer, magnetically directed enzyme/prodrug therapy

Shang Qiao, Wen Gao, Shujun Guo Department of Cardiology, Bayan Nur Hospital of the Nei Monggol Autonomous Region, Bayan Nur City 015000, People’s Republic of ChinaCorrespondence: Shujun GuoDepartment of Cardiology, Bayan Nur Hospital of the Nei Monggol Autonomous Region, Bayan Nur Hospital, No. 98 Wulanbuhe Road, Linhe District, Bayan Nur City 015000, People’s Republic of ChinaEmail zuiailicip@126.comBackground: Cardiovascular diseases (CVD) combined with Type 2 diabetes mellitus (T2DM) frequently occurred. In this study, we aimed at exploring the prognostic significance of blood neutrophil–lymphocyte ratio (NLR) in these types of patients.Patients and Methods: Between June 30, 2010 and August 30, 2017, 1454 patients with CVD were enrolled in this study. Kaplan and Meier methodology was used for survival analysis. We also used propensity score matching (PSM) to further compare survival in patients with or without T2DM.Results: Among all patients, we applied ROC curve analysis to stratify all patients into two different groups including NLR > 2.5 (n=432) and NLR≤ 2.5 (n=1022) groups. After that, we further performed survival analysis between different groups. We found that patients with NLR ≤ 2.5 had significantly favorable OS compared with the overall survival in patients with NLR > 2.5. We further built the PSM using 242 pairs of patients who have CVD and with or without T2DM. After adjusting for competing risk factors, we performed Cox proportional hazards models to identify the independent prognostic factors in multivariable adjustment. We found that NLR ≤ 2.5 (HR: 2.576, 95% CI: 1.241– 4.583, P =0.001) and extent of coronary artery disease (HR: 2.432, 95% CI: 1.189– 4.392, P =0.005) remained independent predictors of OS.Conclusion: In conclusion, we have established an PSM model and found that a high NLR value was an independent prognostic factor for survival, predicting in patients with both CAD and T2DM. The NLR value would be a valuable biomarker to evaluate the outcomes of patients and give them opportunities for choosing alternative therapies.Keywords: neutrophil–lymphocyte ratio, NLR, cardiovascular diseases, CVD, type 2 diabetes mellitus, T2DM

Muyun Wang,1,* Kun Wang,1,* Guoying Deng,2,* Xijian Liu,3 Xiaodong Wu,1 Haiyang Hu,4 Yanbei Zhang,5 Wei Gao,1 Qiang Li1 1Department of Pulmonary and Critical Care Medicine, Shanghai East Hospital, Tongji University, Shanghai 200120, People’s Republic of China; 2Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, People’s Republic of China; 3College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai 201620, People’s Republic of China; 4Department of Cardiothoracic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, People’s Republic of China; 5Department of Geriatric Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Anhui 230022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Gao; Qiang Li Email grace19881118@126.com; liqressh2@hotmail.comBackground: Mitochondrial dysfunction played a vital role in the pathogenesis of various diseases, including acute lung injury (ALI). However, few strategies targeting mitochondria were developed in treating ALI. Recently, we fabricated a porous Se@SiO2 nanoparticles (NPs) with antioxidant properties.Methods: The protective effect of Se@SiO2 NPs was assessed using confocal imaging, immunoblotting, RNA-seq, mitochondrial respiratory chain (MRC) activity assay, and transmission electron microscopy (TEM) in airway epithelial cell line (Beas-2B). The in vivo efficacy of Se@SiO2 NPs was evaluated in a lipopolysaccharide (LPS)-induced ALI mouse model.Results: This study demonstrated that Se@SiO2 NPs significantly increased the resistance of airway epithelial cells under oxidative injury and shifted lipopolysaccharide-induced gene expression profile closer to the untreated controls. The cytoprotection of Se@SiO2 was found to be achieved by maintaining mitochondrial function, activity, and dynamics. In an animal model of ALI, pretreated with the NPs improved mitochondrial dysfunction, thus reducing inflammatory responses and diffuse damage in lung tissues. Additionally, RNA-seq analysis provided evidence for the broad modulatory activity of our Se@SiO2 NPs in various metabolic disorders and inflammatory diseases.Conclusion: This study brought new insights into mitochondria-targeting bioactive NPs, with application potential in curing ALI or other human mitochondria-related disorders.Keywords: mitochondrial dysfunction, porous Se@SiO2 nanoparticles, acute lung injury, anti-oxidative injury, anti-inflammation

Biaoxue Rong,1 Tian Fu,2 Wenlong Gao,3 Min Li,4 Congxue Rong,5 Wen Liu,6 Hua Liu7 1Department of Oncology and Gerontology, First Affiliated Hospital, Xi’an Medical University, Xi’an, People’s Republic of China; 2Department of Respiratory Medicine, Jining No.1 People’s Hospital, Jining, People’s Republic of China; 3Institute of Epidemiology and Health Statistics, School of Public Health, Lanzhou University, Lanzhou, People’s Republic of China; 4Nursing Department, Binhe New District Branch, Shenmu Hospital, Yulin City, Shaanxi, People’s Republic of China; 5Comprehensive Medical Department, Zhangye Second People Hospital, Zhangye, People’s Republic of China; 6Department of Respiratory Medicine, Minqin County People’s Hospital, Minqin, People’s Republic of China; 7Department of Respiratory Medicine, Gansu Provincial Hospital, Lanzhou, People’s Republic of ChinaCorrespondence: Biaoxue RongDepartment of Oncology and Gerontology, First Affiliated Hospital, Xi’an Medical University, 48 Fenghao West Road, Xi’an 710077, People’s Republic of ChinaTel +86 29-87679300Email research568rbx@yeah.netBackground: The aim of this study was to reveal the correlations between serum concentration of Clara cell secretory protein (CC16) and clinical parameters of stable chronic obstructive pulmonary disease (COPD).Patients and Methods: Serum concentration of CC16 was determined by enzyme-linked immunosorbent assay (ELISA). The correlations between serum concentration of CC16 and clinical parameters was performed by linear correlation analysis and multiple linear regression analysis. The sensitivity and specificity of serum CC16 for differential diagnosis of COPD were determined by receiver operator characteristic curve (ROC).Results: The serum concentration of CC16 was down-regulated in stable COPD patients compared with healthy control group (p < 0.05). The decreased serum CC16 was negatively related to smoking (p < 0.05), GOLD grading (p < 0.005), mMRC score (p < 0.05) and medical history (p < 0.05) of patients, but positively correlated with pulmonary function (p < 0.05). The smoking, FEV1/FVC values, COPD grading and mMRC scores all affected the concentration of CC16 (p < 0.05). The decreased CC16 was an independent risk factor in the process of deterioration of lung function. The sensitivity and specificity of serum CC16 for identifying COPD reached to 65.3% and 75%.Conclusion: Decreased serum concentration of CC16 correlated with the disease progression of COPD, suggesting that it can be used as an indicator contributing to the diagnosis and assessment of COPD.Keywords: chronic obstructive pulmonary disease, COPD, Clara cell secretory protein 16, CC16