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Zhigao Xu,1 Lili Zhao,1 Lei Yin,2 Milan Cao,3 Yan Liu,4 Feng Gu,1 Xiaohui Liu,1 Guojiang Zhang5 1Department of Radiology, The Third People’s Hospital of Datong, Datong, 037046, People’s Republic of China; 2Graduate School, Changzhi Medical School, Changzhi, 046013, People’s Republic of China; 3Department of Science and Education, The Third People’s Hospital of Datong, Datong, 037046, People’s Republic of China; 4Department of Endocrinology, The Third People’s Hospital of Datong, Datong, 037046, People’s Republic of China; 5Department of Cardiovasology, The Third People’s Hospital of Datong, Datong, 037046, People’s Republic of ChinaCorrespondence: Guojiang Zhang, Department of Cardiovasology, The Third People’s Hospital, Pingcheng District, Datong, Shanxi, 037046, People’s Republic of China, Email yxkysjjys@163.comPurpose: To explore the potential of MRI-based radiomics in predicting cognitive dysfunction in patients with diagnosed type 2 diabetes mellitus (T2DM).Patients and Methods: In this study, data on 158 patients with T2DM were retrospectively collected between September 2019 and December 2020. The participants were categorized into a normal cognitive function (N) group (n=30), a mild cognitive impairment (MCI) group (n=90), and a dementia (DM) group (n=38) according to the Chinese version of the Montréal Cognitive Assessment Scale-B (MoCA-B). Radiomics features were extracted from the brain tissue except ventricles and sulci in the 3D T1WI images, support vector machine (SVM) model was then established to identify the CI and N groups, and the MCI and DM groups, respectively. The models were evaluated based on their area under the receiver operating characteristic curve (AUC), Precision (P), Recall rate (Recall, R), F1-score, and Support. Finally, ROC curves were plotted for each model.Results: The study consisted of 68 cases in the N and CI group, with 54 cases in the training set and 14 in the verification set, and 128 cases were included in the MCI and DM groups, with 90 training sets and 38 verification sets. The consistency for inter-group and intra-group of radiomics features in two physicians were 0.86 and 0.90, respectively. After features selection, there were 11 optimal features to distinguish N and CI and 12 optimal features to MCI and DM. In the test set, the AUC for the SVM classifier was 0.857 and the accuracy was 0.830 in distinguishing CI and N, while AUC was 0.821 and the accuracy was 0.830 in distinguishing MCI and DM.Conclusion: The SVM model based on MRI radiomics exhibits high efficacy in the diagnosis of cognitive dysfunction and evaluation of its severity among patients with T2DM.Keywords: cognitive dysfunction, radiomics, magnetic resonance imaging, support vector machine, diabetes mellitus, type 2

Rong Huang,1 Xiaoyan Huang,1 Hongmei Yang,1 Haixuan Wu,1 Fan Liu,1 Phei Er Saw,2,3 Minghui Cao1,4 1Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People’s Republic of China; 2Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People’s Republic of China; 4Department of Anesthesiology, Shenshan Medical Center, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Shanwei, 516600, People’s Republic of ChinaCorrespondence: Phei Er Saw; Minghui Cao, Email caipeie@mail.sysu.edu.cn; caomh@mail.sysu.edu.cnIntroduction: ATF3, a stress-induced transcription factor, has been implicated in the injury processes of various cell types, including neurons. It is recognized as a common marker for neuronal damage following neurotrauma. However, its role in other types of glial cells, particularly astrocytes, in response to ischemic injury remains unclear. Mitochondrial dysfunction is a key factor in the pathogenesis of ischemic stroke, and impaired mitochondrial function in astrocytes is associated with astrocyte activation. This study aimed to explore the relationship between mitochondrial damage and ischemic stroke and to investigate how ATF3 regulates mitochondrial dysfunction and astrocyte activation in the context of ischemic injury.Methods: In a transient middle cerebral artery occlusion (tMCAO) mouse model, we knocked down ATF3 and assessed infarct size, motor deficits, astrocyte activation, and mitochondrial damage. In vitro, we used oxygen-glucose deprivation and reoxygenation (OGD-R) to simulate ischemia and evaluated the impact of ATF3 knockdown on astrocyte activation and mitochondrial function.Results: ATF3 knockdown exacerbated infarct size, motor deficits, and astrocyte activation in vivo, with increased mitochondrial damage. In vitro, ATF3 depletion worsened mitochondrial dysfunction and astrocyte activation. ATF3 interacted with Drp1 via Akt2, inhibiting mitochondrial fission and protecting astrocytes.Conclusion: ATF3 regulates mitochondrial fission and protects astrocytes in ischemic stroke, highlighting its potential as a therapeutic target for stroke recovery.Keywords: activating transcription factor 3, ATF3, acute ischemic stroke, AIS, astrocytes, mitochondrial dysfunction, dynamics-related protein 1, Drp1, threonine/serine kinase 2, Akt2

Jaina Razbek,1 Yanggui Chen,2 Jiandong Yang,2 Yaying Zhang,1 Baofeng Wen,1 Junan Wang,1 Xiaomin Wang,1 Guliziba Kuerbanjiang,1 Abulikemu Aili,1 Mingqin Cao1 1Department of Epidemiology and Health Statistics, College of Public Health, Xinjiang Medical University, Urumqi, 830011, People’s Republic of China; 2Department of Prevention and Control of Tuberculosis, Urumqi Centre for Disease Control and Prevention, Urumqi, 830011, People’s Republic of ChinaCorrespondence: Mingqin Cao, Email cmq66@126.comPurpose: Latent tuberculosis infection (LTBI) is a critical stage in tuberculosis (TB)control, and few studies have addressed the role of vitamin D receptor(VDR) gene polymorphisms in differentiating between TB and late-onset TB from an immunogenetic perspective.Patients and Methods: Recruitment of tuberculosis patients and latently infected population in Urumqi, Xinjiang, and use of propensity score matching(PSM) to match the two groups and control confounding to further construct a Bayesian network to analyze causal associations between VDR polymorphisms and tuberculosis disease status.Results: 137 LTBI and 237 TB were obtained through PSM. Logistic regression showed that the VDR gene BsmI locus, TaqI locus, and ApaI locus were associated with a higher risk of TB in a codominant model (P< 0.05). Further Bayesian network construction showed that occupation and being a VDR gene BsmI locus were direct influences on TB disease status, and the VDR gene TaqI locus played an indirect role through the BsmI locus, and the probability of TB risk was highest in individuals with manual labour and BsmI locus of the C/T type, which was 84.15%.Conclusion: Bayesian network modelling intuitively revealed that individuals with a C/T type of BsmI locus and physical labour are at high risk of TB compared with TB infection, and they are key factors between with TB disease, providing reference evidence for controlling TB progression.Keywords: tuberculosis, disease state, vitamin D receptor, propensity score matching, Bayesian network

Purpose/objective(s)Radiographic MRI response following prostate radiotherapy, particularly stereotactic body radiotherapy (SBRT), remains poorly understood. Our objective was to describe radiographic changes to the prostate gland and prostate tumor following SBRT of men treated on a prospective, randomized trial.Materials/methodsMIRAGE (NCT04384770) is a single center, randomized phase III trial of patients receiving either CT or MRI guided SBRT for localized prostate cancer. Patients underwent pre-treatment and annual post-treatment MRIs, in addition to routine PSA surveillance. Outcomes reported include percent gland shrinkage, percent PSA response at one year, and presence of residual tumor based on radiographic interpretation. Patient characteristics were compared via two-sample t-test or Fischer's exact test. Both univariate and multivariable logistical analysis were employed to identify potential clinical predictors of residual tumor on 1-year follow up MRI.ResultsThis study cohort included 94 eligible patients with baseline characteristics in Table 1. Residual lesions were seen in 13 patients (14%), 5/27 (18.5%) treated without ADT and 8/67 (12%) with ADT. PSA ablation was deep, with a 79% median decrease without ADT and 98% median decrease with ADT. Patients receiving ADT showed more gland shrinkage (17% vs. 34% shrinkage, p = 0.0001), while radiographic non-responders and responders experienced similar gland shrinkage (median 21% vs 29% shrinkage, p > 0.05). No significant clinical predictors of residual tumor were identified on univariate and multivariate analysis. No patient had any clinical or biochemical evidence of failure.ConclusionA total of 14% of patients were found to have residual tumor detected on MRI one year after SBRT. These data highlight the protracted nature of radiographic tumor response to radiation therapy, even with ablative radiation techniques. The analysis is limited by the lack of biopsy data to quantify whether visualized residual tumor harbor active cancer.

Chenxi Li,1,&ast; Xiaolei Chen,2,&ast; Xiaowen Zhu,1 Mengjiao Cao,3 Qunfeng Tang,3 Wenjun Wu1,4 1Department of Endocrinology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, People’s Republic of China; 2Department of Neurology, Jiangnan University Medical Center, Wuxi No. 2 People’s Hospital, Wuxi, People’s Republic of China; 3Department of Radiology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, People’s Republic of China; 4Jinshan Branch of Shanghai Sixth People’s Hospital, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenjun Wu, Department of Endocrinology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, People’s Republic of China, Tel +86-15358008856, Fax +86-510-85737592, Email wuwenjung@163.comPurpose: Arterial stiffness is often increased in overweight or obese individuals before the development of hypertension (HT). This study aimed to determine the connection between pancreatic fat and atherosclerosis in overweight and obese people without HT.Patients and methods: We included 128 patients who were non-hypertensive and overweight or obese in a study between December 2019 and November 2022. Medical history was collected, and all participants underwent a physical examination and blood tests. Pancreatic fat content was measured by magnetic resonance imaging (MRI) and was grouped into quartiles based on pancreatic fat fraction (PFF). The upper three quartiles (PFF≥ 10.33%) were defined as non-alcoholic fatty pancreas disease (NAFPD) and the first quartile (PFF< 10.33%) as non-NAFPD. High baPWV (H-baPWV) and low baPWV (L-baPWV) were classified according to the median baPWV (1159 cm/s). The effect of NAFPD on baPWV was examined using binary logistic regression. The study population consisted of 96 NAFPD and 32 non-NAFPD cases.Results: Participants with NAFPD had significantly higher levels of baPWV than people without. The rates of NAFPD and the PFF values varied significantly in the L-baPWV and H-baPWV groups. Logistic regression analysis suggested that the presence of NAFPD was independently correlated with increased baPWV after adjusting for age, smoking, body mass index, blood pressure, lipid profiles, and glycemic index.Conclusion: NAFPD is an independent risk factor for increased baPWV in individuals with overweight and obesity but no HT, suggesting that the presence of NAFPD may be a warning signal of early atherosclerosis.Keywords: obesity, non-alcoholic fatty pancreas disease, overweight, arterial stiffness, brachial-ankle pulse wave velocity

Yan Zhang,1,&ast; Senlu Wang,1,&ast; Xinqi Wang,2 Nianqiang Liu,2 Le Wang,2 Xiaomin Wang,1 Zhichao Liang,1 Junan Wang,1 Abulikemu Aili,1 Mingqin Cao1 1Department of Epidemiology and Health Statistics, College of Public Health, Xinjiang Medical University, Urumqi, Xinjiang, 830011, People’s Republic of China; 2The Center for Disease Control and Prevention of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, 830002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingqin Cao, Department of Epidemiology and Health Statistics, College of Public Health, Xinjiang Medical University, No. 393 Xinyi Road, Urumqi, 830011, People’s Republic of China, Tel +86-13319912419, Email 573596229@qq.comObjective: To analyze the effectiveness of the “Xinjiang Model” for tuberculosis prevention and control in Kashgar Prefecture, Xinjiang, and to explore the determinants of the policy implementation effect.Methods: The registration data of pulmonary tuberculosis (PTB) patients in Kashgar Prefecture from 2012 to 2021 were collected to describe the temporal trend of registered incidence. A questionnaire survey was conducted among PTB patients registered and treated in the tuberculosis management information system in Zepu and Shache Counties from January 2022 to July 2023 to collect and analyze “Xinjiang model” determinants of effectiveness.Results: The PTB registered incidence in Kashgar Prefecture showed a significant increasing trend from 2012 to 2018 (APC=18.7%) and a significant decreasing trend from 2018– 2021 (APC=− 28.8%). Among the Kashgar Prefecture, compared with average registered incidence in 2012– 2017, registered incidence in 2021 in Shufu, Maigaiti, and Zepu Counties had a greater decline rate of 58.68%, 57.16%, and 54.02%, respectively, while the registered incidence in 2021 in Shache County increased by 6.32%. According to the comprehensive analysis of the factors affecting the effect of policy implementation, the proportion of PTB patients in Zepu County whose health status has now significantly improved compared with that before treatment was significantly greater than that in Shache County (P< 0.05); patients in Shache County were significantly less aware than those in Zepu County of how to take tuberculosis drugs, precautions, adverse reactions, and regular reviews during treatment; the factors that accounted for the greater proportion of heavy treatment burden in both Shache and Zepu Counties were discomfort caused by taking or injecting drugs, accounting for 12.8% and 8.7%, respectively.Conclusion: The “Xinjiang model” can effectively control the epidemic situation of tuberculosis in Kashgar, and the knowledge of tuberculosis treatment, adverse reactions to tuberculosis drugs, and treatment costs were the determinants of the effectiveness of policy implementation.Keywords: pulmonary tuberculosis, implementation effect, registered incidence, determinants, Xinjiang

Qiong Wu,1,&ast; Shiying An,1,&ast; RueyJyh Lee,1 Dongwen Gao,2 Yinyifan Zhou,1 Longping Peng,1 Chunrui Hu,1 Lei Yao,3 Chang Zhou,4 Li Zhou,5 Junjie Gao,6 Min Cao,1 Meijiao Mao,1 Guanghao Li,1 Bing Deng,1 Yingjia Xu,4 Youhua Wang1 1Department of Cardiology, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Ultrasound, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Department of Cardiology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Department of Cardiology, Shanghai Fifth People’s Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 5Department of Cardiology, Shanghai Jiading Nanxiang Hospital, Shanghai, People’s Republic of China; 6Department of Cardiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingjia Xu, Shanghai Fifth People’s Hospital, Fudan University, Minhang District, 128 Ruili Road, Shanghai, 200240, People’s Republic of China, Tel +862164308151, Email xuyingjia@5thhospital.com Youhua Wang, Department of cardiology, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Xunhui, 725 South Wan-Ping Road, Shanghai, 200032, People’s Republic of China, Tel +862164385700, Email doctorwyh@163.comBackground: Dilated cardiomyopathy (DCM) is a severe heterogeneous cardiomyopathy characterized by cardiac enlargement and declining heart function, often leading to refractory heart failure and life-threatening outcomes, particularly prevalent in China. The challenge lies in the scarcity of targeted therapies with substantial efficacy for DCM. Additionally, traditional anti-heart failure drugs are constrained due to hypotension propensity or limited symptom improvement. Kuoxin Formula (KXF), internally endorsed at Longhua Hospital, demonstrates clear biological evidence for enhancing cardiac function and myocardial remodeling. Previous clinical studies suggest its potential to enhance patients’ quality of life. This trial aims to further evaluate KXF’s safety and efficacy in managing DCM-related heart failure.Methods: This prospective, randomized, double-blind, placebo-controlled, multicenter trial aims to recruit 230 DCM patients from five centers. Participants will be randomly assigned to either KXF or placebo for 12 weeks, with careful monitoring of key indicators and adverse events. The primary outcome measures the proportion of patients with NT-proBNP reduction exceeding 30%. Secondary outcomes include New York Heart Association functional classification, Traditional Chinese Medicine syndrome scores, 6-minute walk test, Lee’s heart failure score, and Minnesota Heart Failure Quality of Life Scale score. Ventricular remodeling will be assessed using cardiac ultrasound and ELISA. Safety metrics and adverse events will be meticulously recorded.Discussion: This study will be the first multicentered research conducted in China that utilizes a randomized, double-blind, placebo-controlled design to investigate the use of TCM in the treatment of DCM. It seeks to develop new theoretical frameworks and provide solid clinical data to support the integration of TCM and modern medicine in treating heart failure in DCM patients.Trial Registration: China Clinical Trial Registry, ChiCTR2300068937. Registered on March 1, 2023. https://www.chictr.org.cn/bin/project/edit?pid=190926.Keywords: dilated cardiomyopathy, heart failure, Kuoxin Formula, traditional Chinese medicine, clinical trials

Maria González-Cao,1 Xueting Cai,2 Jilian Wilhelmina Paulina Bracht,3 Xuan Han,2 Yang Yang,2 Carlos Pedraz-Valdunciel,4 Teresa Morán,5 Javier García-Corbacho,6 Andrés Aguilar,1 Reyes Bernabé,7 Pedro De Marchi,8,9 Luciane Sussuchi da Silva,8 Leticia Ferro Leal,8 Rui Manuel Reis,8,10,11 Jordi Codony-Servat,4 Eloisa Jantus-Lewintre,12– 14 Miguel Angel Molina-Vila,4 Peng Cao,2,15 Rafael Rosell1,16 1Translational Cancer Research Unit, Instituto Oncológico Dr Rosell, Dexeus University Hospital, Barcelona, Spain; 2Integrated Traditional Chinese and Western Medicine Department of Affiliated Hospital, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 3Amsterdam University Medical Center (UMC), Amsterdam, The Netherlands; 4Laboratory of Oncology, Pangaea Oncology, Quirón Dexeus University Hospital, Barcelona, Spain; 5Medical Oncology Department, Catalan Institute of Oncology (ICO), Germans Trias i Pujol Hospital, Badalona, Spain; 6Medical Oncology Department (Hospital Clinic)/Translational Genomics and Targeted Therapies in Solid Tumors (IDIBAPs), Barcelona, Spain; 7Medical Oncology Department, Hospital Universitario Virgen del Rocío, Sevilla, Spain; 8Molecular Oncology Research Center; Barretos Cancer Hospital, Barretos, Brazil; 9Oncoclinicas, Rio de Janeiro, Brazil; 10Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal; 11ICVS/3b’s – PT Government Associate Laboratory, Braga/Guimarães, Portugal; 12Valencian Community Foundation Principe Felipe Research Center, Laboratory of Molecular Oncology, Valencia, Spain; 13Centro de Investigación Biomédica en Red (CIBERONC), Madrid, Spain; 14Universitat Politècnica de Valencia, Biotechnology Department, Valencia, Spain; 15College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 16Laboratory of Molecular Biology, Germans Trias i Pujol Health Sciences Institute and Hospital (IGTP), Badalona, SpainCorrespondence: Rafael Rosell, Laboratory of Molecular Biology, Germans Trias i Pujol Health Sciences Institute and Hospital (IGTP), Camí de les Escoless/n, Badalona, Barcelona, 08916, Spain, Tel +34 930330520, Email rrosell@iconcologia.net Peng Cao, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China, Tel +86 85608666, Email cao_peng@njucm.edu.cnPurpose: High-mobility group box 1 protein (HMGB1) is subject to exportin 1 (XPO1)-dependent nuclear export, and it is involved in functions implicated in resistance to immunotherapy. We investigated whether HMGB1 mRNA expression was associated with response to immune checkpoint inhibitors (ICI) in non-small cell lung cancer (NSCLC).Patients and Methods: RNA was isolated from pretreatment biopsies of patients with advanced NSCLC treated with ICI. Gene expression analysis of several genes, including HMGB1, was conducted using the NanoString Counter analysis system (PanCancer Immune Profiling Panel). Western blotting analysis and cell viability assays in EGFR and KRAS mutant cell lines were carried out. Evaluation of the antitumoral effect of ICI in combination with XPO1 blocker (selinexor) and trametinib was determined in a murine Lewis lung carcinoma model.Results: HMGB1 mRNA levels in NSCLC patients treated with ICI correlated with progression-free survival (PFS) (median PFS 9.0 versus 18.0 months, P=0.008, hazard ratio=0.30 in high versus low HMGB1). After TNF-α stimulation, HMGB1 accumulates in the cytoplasm of PC9 cells, but this accumulation can be prevented by using selinexor or antiretroviral drugs. Erlotinib or osimertinib with selinexor in EGFR-mutant cells and trametinib plus selinexor in KRAS mutant abolish tumor cell proliferation. Selinexor with a PD-1 inhibitor with or without trametinib abrogates the tumor growth in the murine Lewis lung cancer model.Conclusion: An in-depth exploration of the functions of HMGB1 mRNA and protein is expected to uncover new potential targets and provide a basis for treating metastatic NSCLC in combination with ICI.Keywords: HMGB1, immunotherapy, non-small cell lung cancer, Lewis lung cancer murine model, K-Ras mutations

Hongmei Yang,1,&ast; Zhongqi Liu,1,&ast; Fan Liu,1,2,&ast; Haixuan Wu,1 Xiaoyan Huang,1 Rong Huang,1 Phei Er Saw,3,4 Minghui Cao1,2 1Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People’s Republic of China; 2Department of Anesthesiology, Shenshan Medical Center, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Shanwei, 516600, People’s Republic of China; 3Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People’s Republic of China; 4Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Phei Er Saw; Minghui Cao, Email caipeie@mail.sysu.edu.cn; caomh@mail.sysu.edu.cnBackground: Opioids are irreplaceable analgesics owing to the lack of alternative analgesics that offer opioid-like pain relief. However, opioids have many undesirable central side effects. Restricting opioids to peripheral opioid receptors could reduce those effects while maintaining analgesia.Methods: To achieve this goal, we developed Tet1-LNP (morphine), a neural-targeting lipid nanoparticle encapsulating morphine that could specifically activate the peripheral opioid receptor in the dorsal root ganglion (DRG) and significantly reduce the side effects caused by the activation of opioid receptors in the brain. Tet1-LNP (morphine) were successfully prepared using the thin-film hydration method. In vitro, Tet1-LNP (morphine) uptake was assessed in differentiated neuron-like PC-12 cells and dorsal root ganglion (DRG) primary cells. The uptake of Tet1-LNP (morphine) in the DRGs and the brain was assessed in vivo. Von Frey filament and Hargreaves tests were used to assess the antinociception of Tet1-LNP (morphine) in the chronic constriction injury (CCI) neuropathic pain model. Morphine concentration in blood and brain were evaluated using ELISA.Results: Tet1-LNP (morphine) had an average size of 131 nm. Tet1-LNP (morphine) showed high cellular uptake and targeted DRG in vitro. CCI mice treated with Tet1-LNP (morphine) experienced prolonged analgesia for nearly 32 h compared with 3 h with free morphine (p < 0.0001). Notably, the brain morphine concentration in the Tet1-LNP (morphine) group was eight-fold lower than that in the morphine group (p < 0.0001).Conclusion: Our study presents a targeted lipid nanoparticle system for peripheral neural delivery of morphine. We anticipate Tet1-LNP (morphine) will offer a safe formulation for chronic neuropathic pain treatment, and promise further development for clinical applications.Keywords: lipid nanoparticle, Tet1, peripheral nerve-targeted, pain management, chronic neuropathic pain

Jaina Razbek,1 Mayisha Daken,2 Yanggui Chen,3 Li Ma,3 Yan Zhang,1 Wanting Xu,1 Baofeng Wen,1 Junan Wang,1 Xiaomin Wang,1 Mingqin Cao1 1Department of Epidemiology and Health Statistics, College of Public Health, Xinjiang Medical University, Urumqi, 830011, People’s Republic of China; 2Department of Epidemic Prevention, Karamay Centre for Disease Control and Prevention, Karamay, 834000, People’s Republic of China; 3Department of Prevention and Control of Tuberculosis, Urumqi Centre for Disease Control and Prevention, Urumqi, 830011, People’s Republic of ChinaCorrespondence: Mingqin Cao, Tel +86-13319912419, Email cmq66@126.comPurpose: Early recognition and treatment of latent tuberculosis infection(LTBI) is key to tuberculosis(TB) prevention. However, the emergence of LTBI is influenced by a combination of factors, of which the role of individual immune cytokines remains controversial. The aim of this study is to explore the influencing factors of LTBI and their effects with cytokines on LTBI.Patients and Methods: Close contacts of tuberculosis in Urumqi City from 2021 to 2022 were selected for the study to conduct a field survey. It used logistic regression model to analyse the influencing factors of LTBI, principal component analysis to extract a composite indicators of cytokines, and structural equation modelling to explore the direct and indirect effects of cytokines and influencing factors on LTBI.Results: LTBI infection rate of 33.3% among 288 TB close contacts. A multifactorial Logistic model showed that factors influencing LTBI included education, daily contact hours, eating animal liver, and drinking coffee (P< 0.05); After controlling for confounding factors and extracting composite indicators of cytokines using principal component analysis, CXCL5 and IFN-γ is a protective factor for LTBI(OR=0.572, P=0.047), IL-10 and TNF-α is a risk factor for LTBI(OR=2.119, P=0.010); Structural equation modelling shows drinking coffee, eating animal liver, daily contact hours, and IL-10 and TNF-α had direct effects on LTBI and educations had indirect effects on LTBI(P< 0.05).Conclusion: IL-10 and TNF-α are involved in the immune response and are directly related to LTBI. By monitoring the cytokine levels of TB close contacts and paying attention to their dietary habits and exposure, we can detect and intervene in LTBI at an early stage and control their progression to TB.Keywords: close contacts, latent tuberculosis infection, cytokines, structural equation modelling, association studies

Yueying Niu,1 Mengqing Cao,1 Shumin Li,1 Juanfen Mo,2 Ziyi Zhu,1 Haiqin Wang1 1Department of Respiratory Medicine, The Second Hospital of Jiaxing, Jiaxing, Zhejiang, People’s Republic of China; 2The Key Laboratory, The Second Hospital of Jiaxing, Jiaxing, Zhejiang, People’s Republic of ChinaCorrespondence: Haiqin Wang; Ziyi Zhu, Department of Respiratory Medicine, The Second Hospital of Jiaxing, 1518 Huanchen North Road, Jiaxing, Zhejiang, 314000, People’s Republic of China, Email w_haiqin@163.com; zhuziyi1986@163.comObjective: To retrospectively study the effects of budesonide inhalation combined with conventional symptomatic treatment on serum inflammatory factor expression levels and pulmonary function in patients with cough variant asthma (CVA) and to evaluate treatment efficacy.Methods: This retrospective cohort study included 200 patients diagnosed with CVA at the Second Hospital of Jiaxing between January 2022 and June 2023 and given conventional symptomatic treatment plus budesonide inhalation were included in this study. Patients were divided into a no remission group, a partial remission group and a complete remission group based on treatment effect. The expression levels of serum inflammatory factors, cough symptom scores, and small airway function indicators in the three groups of patients at different time points were compared.Results: In the three groups of CVA patients, after receiving budesonide inhalation combined with conventional symptomatic treatment, the expression levels of serum IL-5, IL-6, IL-8, TNF-α, TGF-β 1, and IgE and number of eosinophils significantly decreased (P < 0.05). There were statistically significant differences in the IL-6 and TGF-β 1 levels among the three groups of CVA patients at T1, T2 and T3. There were statistically significant differences in IgE levels, number of eosinophils, cough symptom scores, and small airway function indicators between T2 and T3 (P< 0.05). The receiver operating characteristic (ROC) curve prediction analysis revealed significant differences in the expression of IL-6 and TGF-β 1 at T1, T2, and T3.Conclusion: Budesonide inhalation combined with conventional symptomatic treatment can significantly reduce the levels of serum inflammatory factors in patients with CVA to reduce inflammation and the allergic response, thereby reducing the cough symptom score, improving pulmonary function, and improving therapeutic efficacy. In addition, IL-6 and TGF-β 1 can be used as early predictors of budesonide inhalation efficacy.Keywords: budesonide, cough variant asthma, cytokines, IL-6, TGF-β 1

Da Ke,1 Jian Ni,1 Yuan Yuan,1 Mingzhen Cao,1 Si Chen,2 Heng Zhou1 1Department of Cardiology, Renmin Hospital of Wuhan University, Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, 430060, People’s Republic of China; 2Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, 430060, People’s Republic of ChinaCorrespondence: Heng Zhou, Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China, Email hengzhou@whu.edu.cnPurpose: Studies have shown that neutrophil-mediated formation of neutrophil extracellular traps (NETs) leads to increased inflammatory response and cellular tissue damage during myocardial infarction (MI). We aimed to identify and validate possible hub genes in the process of NETs-mediated cell damage.Methods: We performed an immune cell infiltration analysis of the MI transcriptome dataset based on CIBERSORT and ssGSEA algorithms. Gene expression profiles of NETs formation (GSE178883) were used to analyze the physiological processes of peripheral blood neutrophils after phorbol myristate acetate (PMA) stimulation. Bioinformatics and machine learning algorithms were utilized to find candidate hub genes based on NETs-related genes and transcriptome datasets (GSE66360 and GSE179828). We generated the receiver operating curve (ROC) to evaluate the diagnostic value of hub genes. Next, the correlation between hub genes and immune cells was analyzed using CIBERSORT, ssGSEA and xCell algorithms. Finally, we used quantitative real-time PCR (qRT-PCR) and immunohistochemistry to verify gene expression.Results: Immune cell infiltration analysis revealed that inflammatory cells such as neutrophils were highly expressed in the peripheral blood of patients with MI. Functional analysis of differentially expressed genes (DEGs) in GSE178883 indicated that the potential pathogenesis lies in immune terms. Using weighted gene co-expression network analysis (WGCNA) and machine learning algorithms, we finally identified the seven hub genes (FCAR, IL1B, MMP9, NFIL3, CXCL2, ICAM1, and ZFP36). The qRT-PCR results showed that IL-1B, MMP9, and NFIL3 mRNA expression was up-regulated in the MI group compared to the control. Immunohistochemical results showed high MMP9, IL-1B, and NFIL3 expression in the infarcted area compared to the non-infarcted area and sham-operated groups.Conclusion: We identified seven hub genes associated with NETs-mediated cellular damage during MI. Our results may provide insights into the mechanisms of neutrophil-mediated cell injury during MI. Keywords: myocardial infarction, neutrophils, cell damage, neutrophil extracellular traps, bioinformatics, endothelial cells

Yan Zhang,1 Xinqi Wang,2 Nianqiang Liu,2 Senlu Wang,2 Xiaomin Wang,1 Mingqin Cao1 1Department of Epidemiology and Health Statistics, College of Public Health, Xinjiang Medical University, Urumqi, Xinjiang, 830011, People’s Republic of China; 2The Center for Disease Control and Prevention of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, 830002, People’s Republic of ChinaCorrespondence: Mingqin Cao, Department of Epidemiology and Health Statistics, College of Public Health, Xinjiang Medical University, No. 393 Xinyi Road, Urumqi, 830011, People’s Republic of China, Tel +86-13319912419, Email 573596229@qq.comObjective: To quantitatively evaluate the intervention effect of the “Xinjiang model” policy on pulmonary tuberculosis (PTB) incidence in Xinjiang, and to compare the difference of policy effect between areas with different tuberculosis burdens.Methods: We retrospectively collected data on the registered incidence of PTB patients in 14 prefectures of Xinjiang from January 2012 to December 2021 and used Joinpoint model to describe the time trend of registered incidence, single-group interrupted time series (ITS) model to analyze the dynamics of registered incidence before and after the policy intervention, and controlled interrupted time series (CITS) model to compare the differences in the effects of the policy in different tuberculosis burdened areas.Results: The areas with high registered incidence of PTB in Xinjiang were mainly located in the four prefectures of southern Xinjiang. The time trend of registered incidence of PTB in Xinjiang from 2012 to 2021 showed a general downward trend (AAPC=− 3.4%), an upward trend from 2012 to 2018 (APC=12.1%), and a rapid downward trend from 2018 to 2021 (APC=− 28.3%). Single-group ITS results showed that registered incidence in Xinjiang increased by 13.806/100,000 one month after policy was implemented (P< 0.001); the long-term effect of policy was a downward trend in registered incidence (β3< 0, P< 0.001), decreasing by 0.690/100,000 per month. In high-, medium-, and low-burden areas of PTB, the long-term effect of policy was a monthly decrease in registered incidence of 1.460/100,000, 0.227/100,000, and 0.064/100,000, respectively. The long-term effects of policy interventions in high- and medium-burden areas showed a faster decline in registered incidence than in low-burden areas (β7 was − 1.548 and − 0.194, respectively, P< 0.001).Conclusion: A dynamic causal relationship exists between “Xinjiang model” policy and registered incidence, and its continued implementation is effective in controlling the spread of tuberculosis.Keywords: pulmonary tuberculosis, interrupted time series, policy evaluation, active case finding, treatment

Ling Yang,1,2 Maolin Cao,3 Jing Tian,1 Peijin Cui,1 Ling Ai,3 Xue Li,4 Hua Li,5 Menghan Gao,1 Liang Fang,1,2,6 Libo Zhao,1,2 Fang Gong,2,6 Chanjuan Zhou1,3,4,6 1Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Key Laboratory of Cerebrovascular Disease Research, Chongqing, People’s Republic of China; 3Department of General Practice, Yongchuan Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Central Laboratory, Yongchuan Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 5Department of Ophthalmology, Yongchuan Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 6Chongqing Clinical Research Center for Geriatric Disease, Chongqing, People’s Republic of ChinaCorrespondence: Fang Gong; Chanjuan Zhou, Yongchuan Hospital of Chongqing Medical University, No. 439 Xuanhua Road, Yongchuan, Chongqing, 402160, People’s Republic of China, Email 1512367841@qq.com; chanjuanzhou@hospital.cqmu.edu.cnPurpose: The quality of life of worldwide adolescents has been seriously affected by depression. Notably, the inflammatory response is closely associated with the pathophysiology of depression. The present study applied a novel targeted proteomics technology, Olink proximity extension assay (PEA), to profile circulating immune-related proteins in adolescents with depression.Methods: In the present study, the expression levels of 92 inflammation-related proteins were compared between adolescents with depression (ADs) (n=15) and healthy controls (HCs) (n=15), using the OLINK PEA inflammation panel. We further validated 5 top proteins that were identified through KEGG and GO analyses between 40 HCs and 50 ADs, including CCL4, CXCL5, CXCL6, CXCL11, and IL-18 using enzyme linked immunosorbent assay (ELISA).Results: We identified 13 differentially expressed proteins between the two cohorts, including 5 up-regulated and 8 down-regulated proteins. Among them, the TRAIL protein levels were significantly negatively correlated with the HAMA-14 score (r=− 0.538, p= 0.038), and the levels of transforming growth factor α (TGF-α) were significantly associated with a change in appetite (r = -0.658, p = 0.008). After validation by ELISA, CCL4, CXCL5, CXCL11, and IL-18 showed significant changes between ADs and HCs (p < 0.05), while CXCL6 showed an up-regulated tendency in ADs (p=0.0673). The pooled diagnostic efficacy (area under the curve [AUC]) of these five inflammation markers in clinical diagnosis for adolescent depression was 0.819 (95% CI: 0.735– 0.904).Conclusion: We report a number of inflammation-related plasma biomarkers, which uncover a potential involvement of chemokines, cytokines, and cytokine receptors in adolescent depression. Their roles in the pathophysiology of depression need to be further elucidated.Keywords: olink proximity extension assay, biomarkers, adolescent depression, inflammation

Mingxin Cao,1,&ast; Enyu Shi,1,&ast; Hanping Wang,1 Lujia Mao,1 Qiqi Wu,1 Xinming Li,2 Yanjie Liang,1 Xiaoying Yang,3 Yinsong Wang,1,3 Changyi Li1 1School and Hospital of Stomatology, Tianjin Medical University, Tianjin, 300070, People’s Republic of China; 2Tianjin Stomatological Hospital, School of Medicine, Nankai University, Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin, 300041, People’s Republic of China; 3Tianjin Key Laboratory of Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, 300070, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yinsong Wang; Changyi Li, Email wangyinsong@tmu.edu.cn; lichangyi@tmu.edu.cnAbstract: Oral squamous cell carcinoma (OSCC) is the most common type of malignant tumor in the head and neck, with a poor prognosis mainly due to recurrence and metastasis. Classical treatment modalities for OSCC like surgery and radiotherapy have difficulties in dealing with metastatic tumors, and together with chemotherapy, they have major problems related to non-specific cell death. Molecular targeted therapies offer solutions to these problems through not only potentially maximizing the anticancer efficacy but also minimizing the treatment-related toxicity. Among them, the receptor-mediated targeted delivery of anticancer therapeutics remains the most promising one. As OSCC exhibits a heterogeneous nature, selecting the appropriate receptors for targeting is the prerequisite. Hence, we reviewed the OSCC-associated receptors previously used in targeted therapy, focused on their biochemical characteristics and expression patterns, and discussed the application potential in personalized targeted therapy of OSCC. We hope that a better comprehension of this subject will help to provide the fundamental information for OSCC personalized therapeutic planning.Keywords: oral squamous cell carcinoma, receptors, targeted therapy, active targeting, drug delivery

Fang Liu, Fei Qi, Xiuying Zhang, Mei Cao, Shiguang Peng Department of Dermatology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Fang Liu, Email roseliufang@qq.comAbstract: Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LTs) is a rare and the most aggressive type of the cutaneous B-cell lymphoma with poor prognosis and low therapeutic response. It mostly affects elderly women, with a 5-year survival rate of 50% if not efficiently treated. We present a 28-year-old male patient with indolent PCDLBCL-LT who reached nearly 100% clearance after six rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy sessions.Keywords: primary cutaneous diffuse large B-cell lymphoma, leg type, rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP), remission

Hongyang Qian,1,&ast; Yiqiu Wang,1,&ast; Zehua Ma,1,&ast; Lei Qian,1 Xiaoguang Shao,1 Di Jin,1 Ming Cao,1 Shupeng Liu,2 Haige Chen,1 Jiahua Pan,1 Wei Xue1 1Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, People’s Republic of China; 2Shanghai Institute for Advanced Communication and Data Science, Key Laboratory of Specialty Fiber Optics and Optical Access Networks, School of Communication and Information Engineering, Shanghai University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Xue; Jiahua Pan, Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, No. 1630 Dongfang Road, Shanghai, 200127, People’s Republic of China, Tel +86 21 6838 3375, Email xuewei@renji.com; panjiahua@renji.comObjective: To explore the value of surface-enhanced Raman spectroscopy analysis of pretreated plasma samples in prediction of bladder cancer (BCa) recurrence after neoadjuvant chemotherapy (NAC) and radical cystectomy (RC).Patients and Methods: SERS was used to analyze plasma samples collected before biopsy and treatment in BCa patients undergoing NAC and RC. The value of clinicopathological parameters and distinctive SERS peaks in the prediction of disease recurrence were analyzed in Cox regression proportional hazard analysis and Log rank test. Principal component analysis and linear discriminant analysis (PCA-LDA) were employed to process spectral data and construct diagnostic algorithms.Results: A total of 88 patients with 440 plasma SERS spectra were collected. The SRES spectra from recurrent patients were compared with patients who remained recurrence free. The SERS demonstrated higher levels of circulating free nucleic acid components in recurrent population, which is represented by significantly higher intensities at SERS peaks of 725 cm− 1, 1328 cm− 1 and 1455 cm− 1. The SERS also detected significantly lower levels of tryptophan shown as lower significantly intensities at the 1558 cm− 1, which is proved to be an independent predictor of BCa recurrence. The addition of SERS peaks of 1558 cm− 1 to classic clinicopathological predictors including pathological tumor stage, lymph node metastasis and pathological downstaging can significantly enhance the power of the predictive model from 0.66 to 0.76 in the area under curve (AUC) of receiver operating characteristic (ROC) curves. Meanwhile, the PCA-LDA diagnostic model based on SERS spectra reveals a high accuracy of 85.2% in prediction of disease recurrence and the AUC of 0.92 in the ROC curve. When validated in the leave-one-out cross-validation method, the accuracy of the model remained 84.1%.Conclusion: We show that SERS analysis of plasma before NAC treatment can accurately classify patients with different risks of disease recurrence after surgery and improve the power of clinicopathological predictive models, thus refining clinical decision-making.Keywords: Raman spectroscopy, bladder cancer, cancer recurrence, neoadjuvant chemotherapy, radical cystectomy

Miaomiao Cao, Bolin Li, Qian Li, Chaofeng Sun Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of ChinaCorrespondence: Chaofeng SunDepartment of Cardiovascular Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Xi’an, 710061, People’s Republic of China, Email cfsun123@126.comBackground: Rapid advancements in percutaneous coronary intervention (PCI) have improved the outcome of chronic coronary total occlusions (CTOs); however, data regarding the difference in long-term outcomes in stable coronary artery disease (CAD) patients with single and multiple CTOs who underwent PCI are scarce. This study aimed to compare the long-term outcomes of patients with multiple CTOs and single CTO after PCI.Methods: This study cohort included stable CAD patients who were diagnosed with CTO and treated with PCI from a single center. The primary endpoint was all-cause death.Results: We retrospectively reviewed 670 consecutive patients with CTO-PCI. Among them, 539 patients had a single CTO, and 131 (19.7%) patients had multiple (at least two) CTOs. CTO revascularization was achieved in 470 (70.1%) patients. After a median follow-up duration of 33.7 months, the cumulative all-cause mortality (p = 0.037) and cardiac mortality (p = 0.003) were higher in patients with multiple CTOs than in those with a single CTO. In the multivariable model, multiple CTOs and left ventricular ejection fraction (LVEF) less than 40% were independent predictors for cardiac death (adjusted hazard ratio (HR) 2.53; P = 0.013 and adjusted HR 3.95; P < 0.001), while age older than 65 and LVEF less than 40% were independent predictors for all-cause death in CTO-PCI patients (adjusted hazard ratio (HR) 1.84; P = 0.035 and adjusted HR 2.54; P = 0.001).Conclusion: In CTO-PCI patients, long-term survival was associated with multiple CTOs, age and LVEF, but not with CTO revascularization.Keywords: coronary chronic total occlusion, percutaneous coronary intervention, clinical outcomes, cardiac death

Pan Zhang,1 Fang Liu,1 Yin Cha,2 Xiuying Zhang,1 Mei Cao1 1Department of Dermatology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Dermatology, Dali Bai Autonomous Prefecture People’s Hospital, Dali, Yunnan Province, People’s Republic of ChinaCorrespondence: Fang LiuDepartment of Dermatology, Beijing Chaoyang Hospital, Capital Medical University, 8 Gongti South Road, Chaoyang District, Beijing, 100020, People’s Republic of ChinaTel +86-10-85231688Fax +86-10-85231217Email roseliufang@qq.comAbstract: Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy (SHML), is a rare, benign, and self-limiting disease. Cutaneous Rosai-Dorfman disease (CRDD) is an exceedingly rare extranodal variant, which is strictly limited to the skin and is easily misdiagnosed. We present the case of a 47-year-old Chinese woman with primary CRDD and a review of relevant literature. The patient had red-yellow papules on her left cheek and chest for more than three months with occasional tenderness. Histopathology showed phagocytic histiocytes in the dermis with the typical presentation of emperipolesis. Immunohistochemistry (IHC) staining showed S100 (+), CD68 (+), and CD1a (-). Based on these findings and the negative systemic presentation, the patient was diagnosed with primary papulonodular-type CRDD, and no treatment regimen was initiated. After three months, the skin lesions partially disappeared, confirming the spontaneous regression of CRDD.Keywords: primary cutaneous Rosai-Dorfman disease, sinus histiocytosis with massive lymphadenopathy, diagnosis, histopathology, immunohistochemistry, treatment, gene mutation

Huaqi Wang,1,&ast; Zhiwei Wang,1,&ast; Zhenyu Hou,1 Xuejiao Yang,1 Keyun Zhu,1 Manqing Cao,2 Xiaolin Zhu,1 Huikai Li,1 Ti Zhang1,3 1Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital; Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060, People’s Republic of China; 2Department of Breast Surgery, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of China; 3Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ti ZhangDepartment of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of ChinaTel/Fax +86-21-6417-5590Email zhangti@shca.org.cnHuikai LiDepartment of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, 24 Bin Shui Road, Hexi District, Tianjin, 300060, People’s Republic of ChinaTel/Fax +86-22-2335-9984Email tjchlhk@126.comPurpose: Patients with hepatocellular carcinoma (HCC) who might benefit most from anti-angiogenesis therapy remain unknown. In recent years, neutrophil-to-lymphocyte ratio (NLR), an indicator of inflammatory response, has received particular attention in HCC. Herein, we explored the prognostic value of pre-treatment NLR in individuals with unresectable intermediate and advanced hepatocellular carcinoma treated with apatinib, a second-line angiogenesis inhibitor. The findings of this study would assist in precision medicine and provide clinical decision support.Patients and Methods: This is a retrospective study in which 171 HCC patients attending Tianjin Medical University Cancer Institute and Hospital and treated with apatinib between January 2016 and July 2018 were enrolled. The prognosis of the patients based on NLR signatures was then analyzed.Results: Patients with a low pre-treatment NLR (NLR < 2.49) presented a significantly longer overall survival (OS) (P < 0.001) and progression-free survival (PFS) (P = 0.043). Furthermore, a low pre-treatment NLR level could be used to predict a longer OS in patients with non-macrovascular invasion (P < 0.001). Independent of serum alpha-fetoprotein (AFP) levels, a low NLR level in this cohort of patients is associated with a longer OS.Conclusion: Pre-treatment NLR predicts the prognosis of patients with unresectable intermediate and advanced HCC treated with apatinib.Keywords: hepatocellular carcinoma, vascular endothelial growth factor receptor - 2, neutrophil to lymphocyte ratio, tyrosine protein kinases inhibitor

Fang Liu, Fei Qi, Xiuying Zhang, Mei Cao Department of Dermatology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Fang LiuDepartment of Dermatology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of ChinaTel +86-10-85231688Fax +86-10-85231217Email roseliufang@qq.comAbstract: Sebaceous carcinoma (SC) is a rare, aggressive malignancy. Most lesions occur in the periocular region, with few cases presenting with extraocular lesions. Here, we report a case of an 89-year-old woman with a 3-month history of a rapidly growing giant extraocular SC. The diagnosis was based on skin biopsy findings. We advised the patient to undergo surgical excision of the carcinoma. However, the patient and her family rejected our proposed surgical treatment, opting for topical traditional Chinese medicine as alternative treatment. The patient subsequently died of unknown causes at home, four months after the first visit. This case of treatment failure emphasizes the importance of early detection and treatment for these aggressive tumors.Keywords: sebaceous carcinoma, extraocular, skin neoplasms, malignancy, Muir-Torre syndrome

Although educators are excited about the potential of social network sites for language learning (SNSLL), there is a lack of understanding of how SNSLL can be used to facilitate teaching and learning for English as Second language (ESL) instructors and students. The purpose of this study was to examine the affordances of four selected SNSLL (LingQ, Lang-8, italki, and Polyglotclub) through site design and user experience from two perspectives: using the sites as a language teacher through site analyses; and using the sites as a language learner through usability testing. The findings showed that these sites have the potential to facilitate language learning. The learning tasks created using the social networking features of these sites are to provide examples of how to use these SNSLL as teaching tools under a socio-constructivist learning framework. In addition, the results of the usability testing highlighted the importance of considering the website's information, interface, and interaction designs. SNSLL should be as easy to use and as intuitive to navigate as possible. We hope the findings will provide valuable insights regarding how SNSLL can be used as teaching and learning tools, and how they should be designed to facilitate pedagogical goals.