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Yuanchun Li,1,&ast; Zhengrong Yang,1,&ast; Qiping Ge,2 Yueqiu Zhang,1 Mengqiu Gao,2 Xiaoqing Liu,1,3,4 Lifan Zhang1,3,4 1Division of Infectious Diseases, Department of Internal Medicine, State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People’s Republic of China; 3Clinical Epidemiology Unit, Peking Union Medical College, International Clinical Epidemiology Network, Beijing, People’s Republic of China; 4Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lifan Zhang; Xiaoqing Liu, Email lifanzhang1982@126.com; liuxq@pumch.cnIntroduction: Current immunologic methods cannot distinguish Mycobacterium tuberculosis (Mtb) infection statuses, especially to discriminate active tuberculosis (ATB) from latent tuberculosis infection (LTBI). This study explored the potential of latency-associated antigens (Rv1733cSLP and Rv2028c) and multifactorial cytokine detection to distinguish tuberculosis infection states.Methods: ATB patients (20), LTBI healthcare workers (25), fever patients (11), and healthy controls (10) were enrolled. Cytokine levels (IFN-γ, TNF-α, IL-2, IL-6, IP-10, IL-1Ra, CXCL-1, and MCP-1) were measured using Luminex with/without MTB-specific virulence factor and latency-associated antigens stimulation.Results: Without antigen stimulation, IL-6, IP-10, MCP-1, and IL-1Ra were higher in the ATB group than in the LTBI group (p< 0.05), but no significant differences between the ATB group and the fever group. Stimulated with the four antigens, respectively, the cytokines, including IP-10Esat− 6, IP-10CFP− 10, IFN-γRv1733cSLP, IFN-γRv2028c, IL-6Esat− 6, IL-6Rv1733cSLP, IL-6Rv2028c, IL-2Rv1733cSLP, IL-2 Rv2028c, IL-1RaEsat− 6, IL-1RaCFP− 10, IL-1RaRv2028c, CXCL-1Esat− 6, CXCL-1CFP− 10, CXCL-1Rv1733cSLP, CXCL-1Rv2028c, MCP-1Esat− 6 and MCP-1CFP− 10, demonstrated accurate discrimination between ATB and LTBI (p< 0.05). Additive concentrations demonstrated significant secretion differences of IFN-γ, IP-10 and IL-2, primarily by virulence factors in ATB and latency-associated antigens in LTBI. Latency-associated antigens synergized with virulence factors, enhancing TH1-type cytokine diagnostic efficacy for discriminating ATB from LTBI, the AUC for TNF-α increased from 0.696 to 0.820 (p=0.038), IFN-γ increased from 0.806 to 0.962 (p=0.025), and IL-2 increased from 0.565 to 0.868 (p=0.007). Model selected by forward likelihood method indicated combined detection of IFN-γCFP− 10, IFN-γRv1733cSLP, IP-10Rv1733cSLP, and CXCL-1Rv1733cSLP achieved ATB diagnosis (AUC=0.996) and ATB-LTBI differentiation (AUC=0.992). Combined detection of IFN-γCFP− 10 and IFN-γRv1733cSLP achieved tuberculosis infection diagnosis (AUC=0.943).Conclusion: Latency-associated antigens enhance multiple cytokine discriminatory ability, particularly TH1-type cytokines, for differentiating Mtb infection statuses.Keywords: active tuberculosis, cytokine, latent tuberculosis infection, latency-associated antigen, Mycobacterium tuberculosis, virulence factor

Xinzuo Qin,1,&ast; Xu Guo,2,&ast; Yijiang Liu,1,3,&ast; Zijian Wang,1 Xinyu Wang,1 Qi Wan,4 Mingjie Gao,5 Juexian Song1 1Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing, People’s Republic of China; 3School of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 4No. 904 Hospital of Joint Logistics Unit, Jiangsu, Wuxi, People’s Republic of China; 5Department of Ultrasonography, Beijing Luhe Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingjie Gao; Juexian Song, Email mingjie.gao@xwh.ccmu.edu.cn; songjuexian@vip.163.comPurpose: Asymptomatic cerebral carotid artery stenosis (ACCAS) benefits from secondary prevention via statins and antiplatelets; nonetheless, the impact of medication alone is often limited. Evidence has suggested enhanced therapeutic outcomes when Chinese patent medicine—specifically, compound dilong capsules (CDC)—is integrated with conventional secondary prevention measures.Patients and Methods: We retrospectively analyzed 319 ACCAS patients from January 2018 to December 2022 at Xuanwu Hospital, Capital Medical University. Depending on the clinical outcomes—improvement or stabilization versus progression—patients were classified into effective or ineffective treatment groups. Patient medical records and questionnaire responses were the primary data sources. The study accounted for demographic variables, clinical history, and medication details, with the primary focus on CDC use and its duration. Treatment outcomes were gauged alongside Transcranial color-coded sonography and Carotid Doppler ultrasonography findings. We employed both univariate and multivariate statistical methods to assess the data.Results: CDC administration (aOR=2.51, 95% CI 1.39– 4.54, P=0.002) and extended usage beyond six months (aOR=3.54, 95% CI 1.71– 7.32, P=0.001) demonstrate a statistically significant correlation with treatment efficacy. Gender (aOR=2.54, 95% CI 1.30– 5.00, P=0.007), hypertension management (aOR=0.56, 95% CI 0.33– 0.95, P=0.031), and antiplatelet therapy with aspirin (aOR=9.53, 95% CI 1.15– 78.89, P=0.037) or clopidogrel (aOR=9.97, 95% CI 1.10– 90.12, P=0.041) also influenced the therapeutic outcome significantly.Conclusion: Incorporating CDC as part of a secondary prevention strategy for over six months can beneficially modulate and limit the progression of vascular stenosis in ACCAS. These findings underscore the value of combining traditional Chinese medicine with modern pharmacological interventions in ACCAS management.Keywords: asymptomatic cerebral carotid artery stenosis, case-control study, secondary prevention, compound dilong capsules

Menglin Liu,1 Mingyang Gao,1 Yufei Hu,1 Xiaoqin Ren,1 Yanan Li,1 Fang Gao,1 Jianglong Dong,1 Jiangtao Dong,2 Qiujun Wang1 1Department of Anesthesiology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, People’s Republic of China; 2Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, People’s Republic of ChinaCorrespondence: Qiujun Wang, Third Hospital of Hebei Medical University, No. 139, Ziqiang Road, Shijiazhuang City, Hebei, People’s Republic of China, Tel/Fax +86-311-8860-2072, Email wangqiujunsy@163.comPurpose: Patients undergoing arthroscopic hip surgery (AHS) require good analgesia and early rehabilitation after surgery, and there is no consensus on the optimal nerve block. We aimed to compare the efficacy of the pericapsular nerve group (PENG) block with lateral femoral cutaneous nerve (LFCN) block compared to fascia iliaca compartment block (FICB) in patients with AHS.Patients and Methods: A total of 80 patients receiving AHS under general anesthesia were randomized to receive either FICB (group F) or PENG block in combination with LFCN block (group P). The primary outcomes were the rate of quadriceps weakness after block on the afflicted side, as well as muscle strength grading and pain score after block, and the quality of recovery on the second postoperative day.Results: Compared with group F, group P had a lower incidence of quadriceps weakness 48 h after block (76.9% vs 28.2%, P < 0.001), and had less impact on muscle strength grade and lower static pain score at 6, 12, 18, 24, 36, and 48 h after block (P < 0.001), and a lower dynamic pain score at 6 and 12 h after block in group P (p < 0.05). The quality of recovery on the second postoperative day improved (p < 0.05).Conclusion: In comparison to FICB, PENG block in combination with LFCN block can affect less quadriceps muscle strength and reduce the use of postoperative analgesics, which is beneficial for the postoperative recovery of AHS patients.Keywords: analgesia, fascia iliaca compartment block, hip arthroscopy, nerve group block, pericapsular, postoperative pain

Tingting Wang,1– 3,&ast; Xia Wu,4,&ast; Xiaoli Zhao,2,3,&ast; Jiaqi Li,5,&ast; Jian Yu,4 Maozheng Sheng,4 Mingyuan Gao,4 Yutang Cao,5 Jiawen Wang,6 Xiaozhen Guo,5 Kai Zeng1 1Department of Anesthesiology, Anesthesiology Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 2Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Department of Anesthesiology, Changning Maternity and Infant Health Hospital, Shanghai, People’s Republic of China; 4Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, People’s Republic of China; 5State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People’s Republic of China; 6College of Life Sciences, Wuhan University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kai Zeng; Xiaozhen Guo, Email fymzk6822@163.com; guoxz@simm.ac.cnPurpose: Postoperative cognitive dysfunction (POCD) is a central nervous system complication that occurs after anesthesia, particularly among the elderly. However, the neurological pathogenesis of postoperative cognitive dysfunction remains unclear. The aim of this study was to evaluate the effects of sevoflurane exposure on serum metabolites and hippocampal gene expression in elderly patients and aging mice by metabolomics and transcriptomic analysis and to explore the pathogenesis of sevoflurane induced POCD.Patients and Methods: Human serum samples from five patients over 60 years old were collected before sevoflurane anesthesia and 1 hour after anesthesia. Besides, mice aged at 12 months (n=6 per group) were anesthetized with sevoflurane for 2 hours or with sham procedure. Subsequently, serum and hippocampal tissues were harvested for analysis. Further investigation into the relationship between isatin and neuroinflammation was conducted using BV2 microglial cells.Results: Sevoflurane anesthesia led to the activation of inflammatory pathways, an increased presence of hippocampal astrocytes and microglia, and elevated expression of neuroinflammatory cytokines. Comparative analysis identified 12 differential metabolites that exhibited changes in both human and mouse serum post-sevoflurane anesthesia. Notably, isatin levels were significantly decreased after anesthesia. Notably, isatin levels significantly decreased after anesthesia, a factor known to stimulate proliferation and proinflammatory gene expression in microglia—the pivotal cell type in inflammatory responses.Conclusion: Sevoflurane-induced alterations in serum metabolites in both elderly patients and aging mice, subsequently contributing to increased inflammation in the hippocampus.Keywords: sevoflurane, hippocampus, neuroinflammation, RNA-seq, metabolomics, isatin

Jie Hao,1– 3,&ast; Yu Liu,1,&ast; Fengli Guo,1,4 Guiming Fu,1,5 Junya Ning,2,3 Xianhui Ruan,1 Xiangqian Zheng,1 Ming Gao1– 3 1Department of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, People’s Republic of China; 2Department of Breast and Thyroid Surgery, Tianjin Union Medical Center of Nankai University, Tianjin, People’s Republic of China; 3Tianjin Key Laboratory of General Surgery in Construction, Tianjin Union Medical Center Nankai University, Tianjin, People’s Republic of China; 4Department of Thyroid and Breast Surgery, Binzhou Medical University Hospital, Binzhou, People’s Republic of China; 5Thyroid-Otolaryngology Department, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangqian Zheng; Ming Gao, Email xzheng05@tmu.edu.cn; headandneck2008@126.comBackground: We planned to explore the underlying mechanism and clinical significance of lnc-SNHG5 and RPS3 in hepatocellular carcinoma in this current study.Methods: The expression of Lnc-SNHG5 and RPS3 in HCC tissues and several cell lines were affirmed, respectively, using UALCAN, TIMER, TCGA and RT-qPCR assay. Cell proliferation ability was detected by colony formation assay and CCK8 assay. Cell apoptosis was monitored by flow cytometry assay. Next, the RPS3 expression levels and the related proteins in NFκB pathway were examined using Western blot analysis. The role of lnc-SNHG5 and RPS3 in vivo was identified by subcutaneous tumor bearing experiment.Results: Lnc-SNHG5 was significantly increased in hepatocellular carcinoma tissues and in hepatocellular carcinoma cells. Further investigation showed that up-regulated lnc-SNHG5 promoted cell viability and cell proliferation ability of SMMC-7721 cells by regulating the cell apoptosis, while down-regulation of lnc-SNHG5 revealed opposite results in QGY-7703 cells. In terms of mechanism, we found that lnc-SNHG5 interacted with RPS3. Lnc-SNHG5 regulated the NFκB pathway through RPS3 in vitro and in vivo.Conclusion: This study suggested that lnc-SNHG5 expression was signally up-regulated in hepatocellular carcinoma, and lnc-SNHG5 promoted the malignant phenotypes in vitro and in vivo via directly regulating RPS3-NFκB pathway. Lnc-SNHG5 might be a target for molecular targeted therapy, a potential and novel diagnostic marker for HCC patients.Keywords: long non-coding RNA, SNHG5, RPS3, HCC, NFκB pathway

Yanan Wang, Yuqiong Chai, Jieqiong Wang, Mingya Gao, Weiwei Zang, Yujie Chang Department of Genetics and Prenatal Diagnosis, Luoyang Maternal and Child Health Hospital, Luoyang, 471000, People’s Republic of ChinaCorrespondence: Yanan Wang, Department of Genetics and Prenatal Diagnosis, Luoyang Maternal and Child Health Hospital, No. 206 of Tongqu Street, Luolong District, Luoyang, 471000, People’s Republic of China, Tel +86-15896572343, Email Wangyanan_2023@yeah.netPurpose: The application value of ultrasound soft indicators in prenatal diagnosis was evaluated by copy number variation sequencing (CNV-seq).Methods: The authors conducted a retrospective analysis of 422 pregnant women who underwent CNV-seq testing at Luoyang Maternal and Child Health Hospital between January 2020 and November 2021. The women had presented with abnormal ultrasound soft markers; those identified as high-risk through non-invasive prenatal screening were excluded.Results: A total of 43 abnormal cases were detected in 422 pregnant women, including 24 aneuploidy (including chimerism) and 19 pathogenic or likely pathogenic copy number variations (CNVs). Based on the characteristics of ultrasound soft indicators, pregnant women were divided into five groups: isolated nuchal translucency (NT) group, combined NT group, isolated soft indicators group, combined soft indicators group and combined non-NT group. The abnormality detection rates in the five groups were 12.38% (13/105), 36.11% (13/36), 3.74% (4/103), 3.08% (2/63) and 10.09% (11/109), respectively. Statistical tests showed that the detection rate in the NT thickening combined with other abnormalities group was significantly higher than the other four groups, while there was no statistical difference in the detection rate among the other four groups.Conclusion: When NT thickening is combined with other abnormalities, it is more likely to indicate chromosome abnormalities or CNVs, so it should be regarded seriously upon finding, and pregnant women should be referred for prenatal diagnosis according to the examination results. In addition, NT thickening is an important indicator for prenatal diagnosis and should be considered regardless of whether it occurs independently. The authors recommend CNV-seq for prenatal diagnosis to prevent missing small fragments of CNVs during traditional karyotyping.Keywords: ultrasound soft indicators, isolated type, combined type, amniotic fluid, CNV-seq

YuJian He,1,2 XiaoYan Huang,1 Jingwen Zhang,1 Jinlan Liao,1 Huie Huang,1 Yan He,1 Min Gao,1 Yumei Liao,1 Zibo Xiong1 1Renal Division, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China; 2Renal Division, PKU-Shenzhen Clinical Institute of Shantou University Medical College, Shenzhen, People’s Republic of ChinaCorrespondence: Zibo Xiong, Renal Division, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China, Tel +86-13510880599, Fax +86-755-83089011, Email xiong0301@163.comPurpose: Peripheral blood lymphocyte counts is a pivotal parameter in assessing the host’s immune response during maladies and the equilibrium of the immune system which has been found to correlate with various diseases progression and prognosis. However, there was no study on patients with peritoneal dialysis-associated peritonitis (PDAP). We sought to investigate the prognostic value of baseline peripheral blood lymphocyte count in PDAP patients.Patients and methods: This retrospective study analyzed data from 286 PDAP patients over nine years. Episodes were categorized according to the tertiles of peripheral blood lymphocyte counts (Very Low Lymphocyte Count (VLLC) Group, < 0.72× 106/L; Low Lymphocyte Count (LLC) Group, 0.72– 1.11× 106/L; Normal Lymphocyte Count (NLC) Group, ≥ 1.11× 106/L). Demographic, laboratory, and infection-related variables were analyzed. Cox regression and generalized estimating equation (GEE) models were used to estimate the association between lymphocyte counts and PDAP treatment failure, which included PD catheter removal and death.Results: After adjusting for other potential predictors, decreased lymphocyte counts exhibited an incremental relationship with the risk of treatment failure. The VLLC group indicated a 270% (95% CI, 1.168– 6.247, P=0.020) and 273% (95% CI, 1.028– 7.269, P=0.044) increased venture of treatment failure in Cox regression and GEE analyses, respectively, compared with the NLC group. As a continuous variable, the restricted cubic spline showed a linear negative correlation between lymphocyte counts and the treatment failure risk (P for overall = 0.026). The multivariate model C (combined lymphocyte count with baseline age, sex, dialysis age, Charlson Comorbidity index (CCI), etiology of kidney failure, hemoglobin, albumin, total bilirubin and infection type) showed an area under the curve of 0.824 (95% CI, 0.767– 0.881, P=0.001) for the prediction of treatment failure.Conclusion: Lower lymphocyte counts are linked to increased PDAP treatment failure risk. This highlights lymphocyte count’s potential as a prognostic indicator for PDAP.Keywords: peritoneal dialysis-associated peritonitis, lymphocyte counts, prognosis, treatment failure

Min Gao,1,2,&ast; Wenhua Sang,1,3,4,&ast; Kun Mi,1,3,4 Jiancong Liu,1,3,4 Yudong Liu,1,3,4 Wenge Zhen,1,3,4 Bang An2 1Department of Affective Disorders II, Hebei Provincial Mental Health Center, Baoding, People’s Republic of China; 2Xianyang Central Hospital, Xianyang Mental Health Center, Xianyang, People’s Republic of China; 3Hebei Key Laboratory of Major Mental and Behavioral Disorders, Baoding, People’s Republic of China; 4The Sixth Clinical Medical College of Hebei University, Baoding, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenhua Sang, Department of Affective Disorders II, Hebei Provincial Mental Health Center, Hebei Key Laboratory of Major Mental and Behavioral Disorders, The Sixth Clinical Medical College of Hebei University, Baoding, People’s Republic of China, Email whsang997169@163.com Bang An, Xianyang Central Hospital, Xianyang Mental Health Center, Xianyang, People’s Republic of China, Email xyanbang@163.comObjective: Only about one-third of depressed patients respond to initial antidepressant treatment. Therefore, it is crucial to find effective predictors of antidepressants. The purpose of our study was to learn the relationship between EEG theta power, theta asymmetry, and the efficacy of escitalopram.Methods: The study included 34 patients with depression. Before and after each patient’s course of treatment, EEG data was gathered. Both the Hamilton Anxiety Scale (HAMA) and the 17-item Hamilton Depression Scale (HAMD-17) were evaluated simultaneously. The natural logarithm of right frontal theta power minus left frontal theta power was used to calculate inter-electrode theta asymmetry (AT).Results: First, our study found no statistically significant difference between intra-electrode theta power and inter-electrode AT before and after treatment (P ≥ 0.05). When we later looked at the data regarding treatment effects, the findings revealed that patients (n = 9) who did not respond to treatment had lower baseline theta power at C4 [6.190 (2.000, 12.990) vs 15.800 (7.255, 22.330), z = − 2.166, P = 0.030]. The two groups had no difference in other electrodes (P ≥ 0.05). The AT of C3/C4 in non-responders (n = 9) was lower [0.012 (0.795) vs 0.733 (0.539), t = − 3.224, P = 0.005]. However, there was no difference in inter-electrode AT between the two groups in F3/F4 and F7/F8 (P ≥ 0.05). We finally show that the theta power at C4 was negatively correlated with HAMD scores before treatment (r = − 0.346, P = 0.045).Conclusion: Our findings determined that increased theta power and positive asymmetry in the right frontal-central area correlate with favourable escitalopram treatment, providing a basis for finding predictive markers for antidepressants.Keywords: depression, EEG, theta power, theta asymmetry, treatment effect

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

Qingqing Li,1– 3 Ming Gao,4 Yanfang Deng,4 Zongkui Zhou,1– 3 Jing Wang1– 3 1Key Laboratory of Adolescent Cyberpsychology and Behavior (CCNU), Ministry of Education, Wuhan, People’s Republic of China; 2Key Laboratory of Human Development and Mental Health of Hubei Province, School of Psychology, Wuhan, People’s Republic of China; 3School of Psychology, Central China Normal University, Wuhan, People’s Republic of China; 4Beijing Dentons (Yichang) Law Office, Yichang, People’s Republic of ChinaCorrespondence: Jing Wang, School of Psychology, Central China Normal University, LuoYu Road 152, Hongshan Region, Wuhan, People’s Republic of China, Email jingwang888@ccnu.edu.cnIntroduction: Identifying risk and protective factors of aggressive behavior during adolescence is beneficial for the intervention and prevention treatments. Although studies show that attachment quality is closely related to aggression, the underlying psychological mechanisms remain unclear. This study aimed to investigate the links of parental attachment with proactive and reactive aggression and to examine the mediating role of perspective taking and self-control among Chinese adolescents.Methods: A cluster sampling method was used to recruit participants from several high schools located in the central regions of China. A total of 2982 participants (Mage = 17.28, SD = 0.83, range 15~20 years; 1602 girls, 1380 boys) were included in the final analysis.Results: Correlation analysis showed that participants possessing higher attachment security with parents were more likely to report lower levels of proactive and reactive aggression. And, self-control and perspective taking were positively associated with parental attachment, and negatively associated with both types of aggression. Moreover, structural equation models indicated that parental attachment directly, and indirectly predicted proactive and reactive aggression through self-control and perspective taking.Discussion: Overall, this study contributes to a more comprehensive understanding of the explanatory mechanisms that link adolescent-parent attachment and aggression, and suggest that high quality of adolescent-parent interactions may promote adolescents’ self-control and perspectives taking, which further reduces their aggression propensity.Keywords: attachment, aggression, self-control, perspective taking, adolescence

Jinling Ma, Suyan Bian, Meng Gao Department of Geriatric Cardiology, the Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of ChinaCorrespondence: Jinling Ma, Department of Geriatric Cardiology, the Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, No. 28, Fuxing Road, Haidian District, Beijing, 100853, People’s Republic of China, Email majinling1@163.comBackground: Chronic kidney disease (CKD) and coronary artery disease (CAD) are strongly associated. Cystatin C (Cys C) is a more sensitive marker of early renal insufficiency. This study aimed to evaluate the prognostic implications of combined of Cys C and cardiac troponin I (cTnI) on 90-day outcomes in elderly patients with type 2 myocardial infarction (MI).Methods: The data of consecutive type 2 MI patients aged 80 years and older who received Cys C and cTnI measurements within 24 h of admission were retrospectively reviewed. The endpoint was a 90-day all-cause and cardiac mortality.Results: A total of 4326 patients were included. During the 90-day follow-up period, a higher all-cause and cardiac mortality was observed in patients with Cys C ≥ 1.49mg/L than in patients with Cys C < 1.49 mg/L (P < 0.001). After the multivariate logistic regression adjustments, the higher CysC and cTnI levels remained independent predictors of the 90-day all-cause mortality and cardiac mortality. Moreover, the Kaplan–Meier all-cause and cardiac mortality event-free survival curves showed that the patients with the presence of elevated levels of both Cys C and cTnI had a significantly increased risk than those with Cys C or cTnI alone.Conclusion: Elevated Cys C level is an independent risk factor for all-cause and cardiac mortality in the elderly type 2 MI population. The predictive ability of the combined use of Cys C and cTnI in elderly type 2 MI patients is stronger than that of Cys C or cTnI alone.Keywords: myocardial infarction, cystatin C, elderly

Maoze Gao,1,&ast; Yaohui Fang,1,&ast; Zhangrui Liu,1 Xinpeng Xu,1,2 Hua You,1,2 Qifeng Wu1 1School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China; 2Institute of Healthy Jiangsu Development, Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinpeng Xu, School of Public Health, Nanjing Medical University, Nanjing, 211166, People’s Republic of China, Email xuxinpeng@njmu.edu.cnBackground: Effective healthcare utilization throughout pregnancy is essential in protecting mother and child health, but the maternal healthcare utilization and its associated factors among migrant women are still underexplored.Methods: The data came from the 2018 China Migrants Dynamic Survey. Our analysis included 6337 pregnant migrant women. Prenatal healthcare utilization comprises receiving at least 5 antenatal care (ANC) times and establishing the maternal health record within the first 12 weeks of pregnancy. Postnatal healthcare utilization refers to whether an individual received a postpartum visit and a physical health examination within 28 days and 42 days following delivery. A multivariate binary logit model was employed to investigate the factors related to maternal healthcare utilization.Results: 67.15% of the 6337 participants established health records within the first 12 weeks of pregnancy, and 88.35% received at least five ANC visits. 76.88% and 84.20% of migrant pregnant women received a postpartum visit and a health examination respectively. Age was positively correlated with receiving at least five ANC visits (OR:1.245, 95% CI: 1.038– 1.493), a postpartum visit within 28 days (OR: 1.272, 95% CI: 1.107– 1.460) and a physical examination within 42 days after delivery (OR=1.174, 95% CI: 1.002– 1.376). Education, household income, health insurance and maternal health education were positively associated with prenatal and postnatal healthcare utilization (P< 0.05). Number of Children negatively correlated with ANC times (OR: 0.742, 95% CI: 0.613– 0.898) and receiving health examination after delivery (OR: 0.720, 95% CI: 0.610– 0.849).Conclusion: There is still potential for improvement in the maternal healthcare utilization, particularly in postnatal healthcare. Strengthening the follow-up, focusing on those who are younger, have lower socioeconomic status, and are members of ethnic minorities, and continuing to strengthen maternal health education for them can promote the maternal healthcare utilization before and after delivery.Keywords: maternal healthcare utilization, prenatal and postnatal, migrant pregnant women, China

Min Gao,1,2,&ast; Yongwen Li,3,&ast; Hua Huang,4,&ast; Yaguang Fan,3 Ruifeng Shi,4 Lianchun Su,5 Chen Chen,3 Xuanguang Li,4 Guangsheng Zhu,4 Di Wu,4 Peijun Cao,4 Hongyu Liu,3 Jun Chen,3– 5 Shirong Kang1 1Department of Thoracic Surgery, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot, 010010, People’s Republic of China; 2Inner Mongolia Medical University, Hohhot, 010010, People’s Republic of China; 3Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 4Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, 300052, People’s Republic of China; 5Department of Thoracic Surgery, First Affiliated Hospital of Shihezi University School of Medicine, Shihezi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Chen; Shirong Kang, Email huntercj2004@qq.com; bssbzzk2013@163.comBackground: Genetic susceptibilities play a large role in the pathogenesis of lung cancer (LC). The polycomb repressive complex 2 (PRC2) is a conserved chromatin-associated complex that represses gene expression and is crucial for proper organismal development and gene expression patterns. Despite PRC2 dysregulation has been observed in various human cancers, the relationship between PRC2 genes variants and lung cancer risk remains largely unexplored.Methods: To investigate the association between single nucleotide polymorphisms (SNPs) in PRC2 genes and the risk of developing LC, we genotyped blood genomic DNA from 270 LC patients and 452 healthy individuals of Chinese Han ethnicity using the TaqMan™ genotyping technique.Results: We found that rs17171119T>G(adjusted odds ratio (OR) = 0.662, 95% CI: 0.467– 0.938, P < 0.05), rs10898459 T>C(adjusted OR = 0.615, 95% CI: 0.4– 0.947, P < 0.05), and rs1136258 C>T(adjusted OR = 0.273, 95% CI: 0.186– 0.401, P < 0.001) were significantly associated with a reduced risk of LC. Stratified analysis revealed a protective effect of rs17171119 in both male and female patients, specifically those with lung adenocarcinoma (LUAD). Additionally, rs1391221 showed a protective effect in both the LUAD and lung squamous cell carcinoma (LUSC) groups, while rs1136258 exhibited a protective effect in both females and males, as well as in both LUAD and LUSC groups. Furthermore, analysis of The Cancer Genome Atlas (TCGA) dataset revealed expression levels of EED and RBBP4 in both LUAD and LUSC.Conclusion: This study provides evidence that allelic variants in EZH2, EED, and RBBP4 may act as protective factors against LC development and could serve as genetic markers associated with susceptibility to LC.Keywords: the polycomb repressive complex 2, single nucleotide polymorphism, lung cancer

Hang Dong, Meng Gao, Lu Lu, Rong Gui, Yunfeng Fu Department of Blood Transfusion, the Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Yunfeng Fu, Department of Blood Transfusion, the Third Xiangya Hospital, Central South University, Tongzipo Road 138, Changsha, Hunan, 410013, People’s Republic of China, Email fuyunfeng@csu.edu.cnIntroduction: Triple-negative breast cancer (TNBC) is a highly aggressive subtype with a poor prognosis. Current single-agent checkpoint therapy has limited effectiveness in TNBC patients. In this study, we developed doxorubicin-loaded platelet decoys (PD@Dox) for chemotherapy and induction of tumor immunogenic cell death (ICD). By combining PD-1 antibody, PD@Dox has the potential to enhance tumor therapy through chemoimmunotherapy in vivo.Methods: Platelet decoys were prepared using 0.1% Triton X-100 and co-incubated with doxorubicin to obtain PD@Dox. Characterization of PDs and PD@Dox was performed using electron microscopy and flow cytometry. We evaluated the properties of PD@Dox to retain platelets through sodium dodecyl sulfate-polyacrylamide gel electrophoresis, flow cytometry, and thromboelastometry. In vitro experiments assessed drug-loading capacity, release kinetics, and the enhanced antitumor activity of PD@Dox. The mechanism of PD@Dox was investigated through cell viability assays, apoptosis assays, Western blot analysis, and immunofluorescence staining. In vivo studies were performed using a TNBC tumor-bearing mouse model to assess the anticancer effects.Results: Electron microscopic observations confirmed that platelet decoys and PD@Dox exhibited a round shape similar to normal platelets. Platelet decoys demonstrated superior drug uptake and loading capacity compared to platelets. Importantly, PD@Dox retained the ability to recognize and bind tumor cells. The released doxorubicin induced ICD, resulting in the release of tumor antigens and damage-related molecular patterns that recruit dendritic cells and activate antitumor immunity. Notably, the combination of PD@Dox and immune checkpoint blockade therapy using PD-1 antibody achieved significant therapeutic efficacy by blocking tumor immune escape and promoting ICD-induced T cell activation.Conclusion: Our results suggest that PD@Dox, in combination with immune checkpoint blockade therapy, holds promise as a potential strategy for TNBC treatment.Keywords: drug delivery, doxorubicin, immunogenic cell death, immune checkpoint blockade therapy

Xufeng Yu,1,&ast; Zhan Gao,1,&ast; Mingzhou Gao,2 Mingqi Qiao1 1College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, People’s Republic of China; 2Innovation Research Institute of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingzhou Gao; Mingqi Qiao, Email gmingzhou@163.com; qmingqi@163.comBackground: GABA-A receptors are the primary mediators of brain inhibitory neurotransmission. In the past years, many studies focused on this channel to decipher the pathogenesis of related diseases but lacked bibliometric analysis research. This study aims to explore the research status and identify the research trends of GABA-A receptor channels.Methods: Publications related to GABA-A receptor channels were retrieved from the Web of Science Core Collection from 2012 to 2022. After screening, the VOSviewer 1.6.18 and Citespace 5.8 R3 were used for bibliometric analysis from journals, countries, institutions, authors, co-cited references and keywords.Results: We included 12,124 publications in the field of GABA-A receptor channels for analysis. The data shows that although there was a slight decrease in annual publications from 2012 to 2021, it remained at a relatively high level. Most publications were in the domain of neuroscience. Additionally, the United States was the most prolific country, followed by China. Univ Toronto was the most productive institution, and James M Cook led essential findings in this field. Furthermore, brain activation, GABAAR subunits expression, modulation mechanism in pain and anxiety behaviors and GABA and dopamine were paid attention to by researchers. And top research frontiers were molecular docking, autoimmune encephalitic series, obesity, sex difference, diagnosis and management, EEG and KCC2.Conclusion: Taken together, academic attention on GABA-A receptor channels was never neglected since 2012. Our analysis identified key information, such as core countries, institutions and authors in this field. Molecular docking, autoimmune encephalitic series, obesity, sex difference, diagnosis and management, EEG and KCC2 will be the future research direction.Keywords: GABA-A receptor, GABA, visual analysis, trends, CiteSpace, VOSviewer

Qian Qi,1,2,&ast; Jiawei Xu,1,2,&ast; Yujiao Wang,3,&ast; Jian Zhang,1 Mingxia Gao,1 Yu Li,4 Liang Dong1,2 1Department of Respiratory, the First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Institute of Respiratory Diseases, Jinan, Shandong Province, People’s Republic of China; 2Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong Province, People’s Republic of China; 3Department of Clinical Laboratory Medicine, the First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong Province, People’s Republic of China; 4Department of Respiratory, Qilu Hospital, Shandong University, Jinan, Shandong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liang Dong, Department of Respiratory, the First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, &num;16766, Jingshi Road, Jinan, Shandong Province, 250014, People’s Republic of China, Tel +86 13505401207, Email dl5506@126.comPurpose: To assess the metabolites associated with Pseudomonas aeruginosa infection by analyzing the microbial diversity and metabolomics in lower respiratory tract of bronchiectasis patients and to explore the therapeutic approaches for Pseudomonas aeruginosa infection.Methods: Bronchoalveolar lavage fluid samples from bronchiectasis patients and controls were analyzed by 16S rRNA and ITS sequencing, and metabolomic analysis was performed by liquid chromatography/mass spectrometry. A co-culture model of air-liquid interface cultured human bronchial epithelial cell with Pseudomonas aeruginosa was constructed to verify the correlation between sphingosine metabolism, acid ceramidase expression, and Pseudomonas aeruginosa infection.Results: After screening, 54 bronchiectasis patients and 12 healthy controls were included. Sphingosine levels in bronchoalveolar lavage fluid were positively correlated with lower respiratory tract microbial diversity and negatively correlated with the abundance of Pseudomonas spp. Moreover, sphingosine levels in bronchoalveolar lavage fluid and acid ceramidase expression levels in lung tissue specimens were significantly lower in bronchiectasis patients than in healthy controls. Sphingosine levels and acid ceramidase expression levels were also significantly lower in bronchiectasis patients with positive Pseudomonas aeruginosa cultures than in bronchiectasis patients without Pseudomonas aeruginosa infection. Acid ceramidase expression in air-liquid interface cultured human bronchial epithelial cell had significantly increased after 6 h of Pseudomonas aeruginosa infection, while it had decreased significantly after 24 h of infection. In vitro experiments showed that sphingosine had a bactericidal effect on Pseudomonas aeruginosa by directly disrupting its cell wall and cell membrane. Furthermore, adherence of Pseudomonas aeruginosa on bronchial epithelial cells was significantly reduced after sphingosine supplementation.Conclusion: Down-regulation of acid ceramidase expression in airway epithelial cells of bronchiectasis patients leads to insufficient metabolism of sphingosine, which has a bactericidal effect, and consequently weakens the clearance of Pseudomonas aeruginosa; thus, a vicious circle is formed. Exogenous supplementation with sphingosine aids bronchial epithelial cells in resisting Pseudomonas aeruginosa infection.Keywords: metabolomics, bronchiectasis, sphingosine, Pseudomonas aeruginosa, acid ceramidase

Yingli Wu,1– 3,&ast; Yu Yang,1– 3,&ast; Xiaolin Lv,1– 3 Menghan Gao,1 Xujin Gong,1– 3 Qingqiang Yao,1– 4 Yanna Liu1– 3 1School of Pharmacy and Pharmaceutical Sciences & Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, People’s Republic of China; 2NHC Key Laboratory of Biotechnology Drugs (Shandong Academy of Medical Sciences), Jinan, Shandong, 250117, People’s Republic of China; 3Key Laboratory for Rare & Uncommon Diseases of Shandong Province, Jinan, Shandong, 250117, People’s Republic of China; 4Jining Medical University, Jining, Shandong, 272067, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingqiang Yao, Jining Medical University, No. 133 HeHua Road, Jinan, Shandong, 272067, People’s Republic of China, Email qqyao@sdfmu.edu.cn Yanna Liu, Shandong First Medical University, No. 6699 Qingdao Road, HuaiYin District, Jinan, Shandong, 250117, People’s Republic of China, Email liuyanna@sdfmu.edu.cnAbstract: Ovarian cancer is one of the most common malignant tumors in gynecology with a high incidence. Combination therapy, eg, administration of paclitaxel followed by a platinum anticancer drug is recommended to treat ovarian cancer due to its advantages in, eg, reducing side effects and reversing (multi)drug-resistance compared to single treatment. However, the benefits of combination therapy are often compromised. In chemo and chemo/gene combinations, co-deposition of the combined therapeutics in the tumor cells is required, which is difficult to achieve due to dramatic pharmacokinetic differences between combinational agents in free forms. Moreover, some undesired properties such as the low-water solubility of chemodrugs and the difficulty of cellular internalization of gene therapeutics also hinder the therapeutic potential. Delivery of dual or multiple agents by nanoparticles provides opportunities to tackle these limits. Nanoparticles encapsulate hydrophobic drug(s) to yield aqueous dispersions facilitating its administration and/or to accommodate hydrophilic genes facilitating its access to cells. Moreover, nanoparticle-based therapeutics can not only improve drug properties (eg, in vivo stability) and ensure the same drug disposition behavior with controlled drug ratios but also can minimize drug exposure of the normal tissues and increase drug co-accumulation at targeted tissues via passive and/or active targeting strategies. Herein, this work summarizes nanoparticle-based combination therapies, mainly including anticancer drug-based combinations and chemo/gene combinations, and emphasizes the advantageous outcomes of nanocarriers in the combination treatment of ovarian cancer. In addition, we also review mechanisms of synergetic effects resulting from different combinations.Keywords: ovarian cancer, nanoparticles, combination therapy, chemotherapy, gene therapy

Wenli Hui, Wenhua Mu, Cong Zhao, Dan Xue, Zihua Zhong, Yani Fang, Ming Gao, Xiao Li, Shihao Gao, Kaiyue Liu, Kunping Yan College of Life Science, Northwest University, Xi’an City, Shaanxi Province, 710069, People’s Republic of ChinaCorrespondence: Kunping Yan, Email kpyan@nwu.edu.cnIntroduction: A limitation of hemoglobin-based oxygen carriers (HBOCs) as oxygen therapeutics is unpolymerized hemoglobin, which induces vasoconstriction leading to hypertension. The removal of unpolymerized hemoglobin from polymerized hemoglobin (PolyHb) is complex, expensive, and time-consuming.Methods: Herein, we developed a method to completely polymerize hemoglobin almost without unpolymerized hemoglobin. Hemoglobin was adsorbed on the anion-exchange resin Q Sepharose Fast Flow or DEAE Sepharose Fast Flow, and acetal, a crosslinker prepared from glutaraldehyde and ethylene glycol, was employed to polymerize the hemoglobin. The polymerization conditions, including reaction time, pH, resin type, and molar ratios of glutaraldehyde to ethylene glycol and hemoglobin to acetal, were optimized. The blood pressure and blood gas of mice injected with PolyHb were monitored as well.Results: The optimal polymerization condition of PolyHb was when the molar ratio of glutaraldehyde to ethylene glycol was 1:20, and the molar ratio of 10 mg/mL hemoglobin adsorbed on anion-exchange resin to glutaraldehyde was 1:300 for 60 min. Under optimized reactive conditions, hemoglobin was almost completely polymerized, with < 1% hemoglobin remaining unpolymerized, and the molecular weight of PolyHb was more centrally distributed. Furthermore, hypertension was not induced in mice by PolyHb, and there were also no pathological changes observed in arterial oxygen, blood gas, electrolytes, and some metabolic indicators.Conclusion: The findings of this study indicate that the use of solid-phase polymerization and acetal is a highly effective and innovative approach to HBOCs, resulting in the almost completely polymerized hemoglobin. These results offer promising implications for the development of new methods for preparing HBOCs.Graphical Abstract: Keywords: polymerized hemoglobin, glutaraldehyde, acetal, solid-phase adsorption, hemoglobin-based oxygen carriers, HBOCs

Mingyang Gao,1,&ast; Yanan Li,1,&ast; Jiaxu Yu,1 Wei Li,1 Shiji Qin,2 Yahui Zhang,3 Lian Zhu,4 Zhiyong Hou,4 Qiujun Wang1 1Department of Anesthesiology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, People’s Republic of China; 2Department of Foot and Ankle Surgery, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 3Department of Nursing, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 4Department of Orthopaedics, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiujun Wang, Department of Anesthesiology, Third Hospital of Hebei Medical University, No. 139, Ziqiang Road, Shijiazhuang City, Hebei, People’s Republic of China, Tel/Fax +86-311-8860-2072, Email wangqiujunsy@163.comPurpose: A single-injection nerve block provides excellent analgesia in a short time, but rebound pain after the nerve block disappears has attracted researchers’ attention. The aim of this study is to evaluate the effect of intravenous dexamethasone on rebound pain after adductor canal block (ACB) and popliteal sciatic nerve block in patients with ankle fracture.Methods: We recruited 130 patients with ankle fractures scheduled for open reduction and internal fixation (ORIF), each of whom received ACB and popliteal sciatic nerve block. Patients were divided into two groups: C (ropivacaine only) and IV (ropivacaine with intravenous dexamethasone). The primary outcome was the incidence of rebound pain. Secondary outcomes included the following: pain scores at 6 h (T1), 12 h (T2), 18 h (T3), 24 h (T4), and 48 h (T5) after operation; duration of the nerve block; number of presses of the analgesia pump and rescue analgesic consumption in the three-day postoperative period; quality of recovery scale (QoR-15 score); postoperative sleep quality; satisfaction of patients; and levels of serum inflammatory markers (IL-1β, IL-6, and TNF-α) six hours after surgery.Results: Compared with group C, the incidence of rebound pain in group IV was significantly reduced, and the duration of nerve block was extended by approximately nine hours (P< 0.05). Moreover, patients in group IV had significantly lower pain scores at T2-T4, lower levels of serum inflammatory markers (IL-1β, IL-6, and TNF-α), higher QoR-15 score two days after the operation, and satisfactory sleep quality the night after surgery (P< 0.05).Conclusion: Intravenous dexamethasone can reduce the rebound pain after adductor block and sciatic popliteal nerve block in patients with ankle fracture surgery, prolong the duration of nerve block, and improve the quality of early postoperative recovery.Keywords: dexamethasone, nerve block, postoperative analgesia, ankle fracture, rebound pain

Wei Lu,1– 3 Zhaowei Teng,1,2 Jiayu Chen,1– 3 Rongmao Shi,4 Tiannan Zou,1– 3 Ming Gao,1– 3 Weichao Li,1– 3 Zhi Peng,1– 3 Long Wang,1– 3 Yonghui Zhao,1– 3 Sheng Lu1– 3 1Yunnan Key Laboratory of Digital Orthopedics, the First People’s Hospital of Yunnan Province, Kunming, People’s Republic of China; 2Department of Orthopedics, the First People’s Hospital of Yunnan Province, Kunming, People’s Republic of China; 3Department of Orthopedics, the Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650032, People’s Republic of China; 4Department of Orthopedics, Clinical College of the 920th Hospital of Joint Logistics Support Force of Kunming Medical University, Kunming, People’s Republic of ChinaCorrespondence: Sheng Lu, Department of Orthopedics, the First People’s Hospital of Yunnan Province, No. 157 Jinbi Road, Kunming, 650032, People’s Republic of China, Tel +86-0871-63633071, Fax +86-0871-63633071, Email drlusheng@163.comPurpose: The objective of this study was to analyze the clinical characteristics and the therapeutic effects of treatment at our spinal center in OVCF patients associated with referred pain. The underlying goals were to deepen the understanding of referred pain caused by OVCFs, improve the currently low early diagnosis rate of OVCFs, and improve the effectiveness of treatment.Methods: The patients who had referred pain from OVCFs and met the inclusion criteria were retrospectively analyzed. All patients were treated with percutaneous kyphoplasty (PKP). Visual analog scale (VAS) scores and Oswestry Disability Index (ODI) were used to evaluate the therapeutic effect at different time points.Results: There were 11 males (19.6%) and 45 females (80.4%). Their corresponding mean bone mineral density (BMD) value was − 3.3 ± 0.4. The regression coefficient of BMD in the linear regression equation was − 4.51 (P< 0.001). According to the classification system for referred pain in OVCFs, there were 27 cases of type A (48.2%), 12 cases of type B (21.2%), 8 cases of type C (14.3%), 3 cases of type D (5.4%), and 6 cases of type E (10.7%). All patients were followed up for at least 6 months, and both VAS scores and ODI were found to be significantly better postoperatively than preoperatively (P< 0.001). There was no significant difference in VAS scores and ODI between different types preoperatively or 6 months postoperatively (P > 0.05). Within each type, there were significant differences in VAS scores and ODI between the pre- and postoperative timepoints (P < 0.05).Conclusion: Attention should be paid to referred pain in OVCF patients, which is not uncommon in clinical practice. Our summary of the characteristics of referred pain caused by OVCFs can improve the early diagnosis rate of OVCFs patients and provide a reference for their prognosis after PKP.Keywords: referred pain, radicular pain, vertebral fracture, percutaneous kyphoplasty, osteoporosis, spinal fracture

Jie Pan,1 Qiuyan Li,1 Yan Sun,1 Yingying Gu,1 Yijie Ding,1 Nengzhi Pang,1 Yujia Zhou,1 Lei Pei,1 Mengqi Gao,1 Sixi Ma,1 Ying Xiao,1 Feilong Wu,1 De Hu,1 Yu-Ming Chen,2 Lili Yang1 1Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, People’s Republic of ChinaCorrespondence: Lili Yang, Department of Nutrition, School of Public Health, Sun Yat-sen University, No. 74, Zhongshan Road 2, Yuexiu District, Guangzhou, Guangdong, 510080, People’s Republic of China, Tel +86-20-87330625, Email yangll7@mail.sysu.edu.cnPurpose: A panel of international experts proposed a new definition of fatty liver in 2020, namely metabolic dysfunction-associated fatty liver disease (MAFLD). As an adipokine, adipsin is closely related to metabolic-related diseases. In this study, we aimed to evaluate the relationship among MAFLD, serum adipsin, and metabolic risk abnormalities.Methods: Our study was a cross-sectional study based on the first follow-up of the Guangzhou Nutrition and Health Study (GNHS). A total of 908 patients with hepatic steatosis were involved in our study. Detailed data of patients were collected based upon questionnaire information, physical examination, and blood biochemical test.Results: Among the 908 patients, 789 patients were diagnosed with MAFLD. The levels of serum adipsin in the MAFLD group and non-MAFLD group were (3543.00 (3187.94– 3972.50) ng/mL) and (3095.33 (2778.71– 3354.77) ng/mL) (P < 0.001), respectively. After adjusting for potential confounders, adipsin levels were found to be associated with MAFLD. The OR was 3.46 (95% CI: 1.57– 7.64) for adipsin when comparing subjects in the highest tertile with those in the lowest tertile. With the increase in the number of metabolic risk abnormalities, both the levels of serum adipsin and the proportion of moderate to severe fatty liver increased (all p-trend < 0.001).Conclusion: Increased serum adipsin correlates with MAFLD. Both adipsin levels as well as fatty liver severity increase with higher numbers of metabolic risk abnormalities.Keywords: metabolic dysfunction-associated fatty liver disease, adipsin, metabolic risk abnormalities, hepatic steatosis

Liangliang Ma,1 Xuelin Chen,1 Maolong Gao2 1Department of Infectious Diseases, Beijing Geriatric Hospital, Beijing, 100095, People’s Republic of China; 2Department of Science and Technology, Beijing Geriatric Hospital, Beijing, 100095, People’s Republic of ChinaCorrespondence: Liangliang Ma, Department of Infectious Diseases, Beijing Geriatric Hospital, No. 118 Wenquan Road, Haidian District, Beijing, 100095, People’s Republic of China, Tel +86-18610672953, Email gkdp29@163.comObjective: To explore the risk factors of malnutrition in type 2 diabetes mellitus combined with pulmonary tuberculosis (PTB-T2DM) patients and further to provide a clinical research basis for the identification and prevention of malnutrition.Methods: From January 2020 to February 2022, 307 adult patients diagnosed with PTB-T2DM were enrolled in this retrospective study. According to whether malnutrition occurred after 6 months of treatment, patients were divided into malnutrition group (n = 123) and non-malnutrition group (n = 184). The nutritional status of patients was evaluated according to the Micro-Nutrition Assessment Scale (MNA). Evaluation of indicators was performed, including general information, disease characteristics of PTB-T2DM and laboratory indicators.Results: Univariate logistic regression analysis showed that drinking, divorced, BMI < 18.5kg/m2, weight < 45kg, waist circumference < 79cm, hip circumference < 88cm, waist-to-hip ratio < 69.99, calf circumference < 26kg, grip strength < 28kg, NRS score ≥ 3, Hb < 106g/L, Alb < 29.00g/L, PA < 48.00μmol/L, GHB < 3.40%, serum transferrin < 1.37 mmol/L, serum potassium < 3.18mmol/L, serum sodium < 142.95 mmol/L, FEV1 ≥ 67.90% and RV < 2.89% were risk factors for malnutrition in PTB-T2DM patients (all P < 0.05). The results of multivariate logistic regression analysis showed that drinking, divorced, weight < 45kg, BMI < 18.5kg/m2, NRS score ≥ 3, Hb < 106g/L, Alb < 29.00g/L, PA < 48.00μmol/L, serum transferrin < 1.37mmol/L, FEV1 ≥ 67.90% and RV < 2.89% were independent risk factors for malnutrition in PTB-T2DM patients (all P < 0.05).Conclusion: Drinking, divorced, weight < 45kg, BMI < 18.5kg/m2, NRS score ≥ 3, Hb < 106g/L, Alb < 29.00g/L, PA < 48.00μmol/L, serum transferrin < 1.37mmol/L, FEV1 ≥ 67.90% and RV < 2.89% may be independent risk factors for malnutrition in PTB-T2DM patients, and timely identification of high-risk groups could improve the prognosis of PTB-T2DM patients.Keywords: risk factors, malnutrition, type 2 diabetes mellitus, pulmonary tuberculosis

Hongmei Chen,1,&ast; Shanshan Li,2,&ast; Weijie Zhao,3,&ast; Jiaheng Deng,4,&ast; Zhuohong Yan,5 Tingting Zhang,2 Shu’ an Wen,2 Haiping Guo,2 Lei Li,6 Jianfeng Yuan,6 Hongtao Zhang,5 Liping Ma,1 Jianhua Zheng,4,&ast; Mengqiu Gao,1 Yu Pang2 1Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, People’s Republic of China; 2Department of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, People’s Republic of China; 3Clinical Trial Agency Office, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, People’s Republic of China; 4Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, and Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 5Department of Central Laboratory, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, People’s Republic of China; 6Electral Safety Research & Development Center, Beijing Normal University, Zhuhai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu Pang, Department of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/ Beijing Tuberculosis & Thoracic Tumor Research Institute, No. 9, Beiguan Street, Tongzhou District, Beijing, 101149, People’s Republic of China, Tel +86 10 8950 9359, Email pangyupound@163.com Mengqiu Gao, Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University/ Beijing Tuberculosis & Thoracic Tumor Research Institute, No. 9, Beiguan Street, Tongzhou District, Beijing, 101149, People’s Republic of China, Tel +86 10 8950 9302, Email gaomqwdm@aliyun.comBackground: Here, we conducted a peptidomic study in murine model to identify novel antigen biomarkers for the diagnosis of tuberculosis (TB) with improved performance.Methods: Four recombinant proteins, including Mycobacterium tuberculosis protein 32 (MPT32), Mycobacterium tuberculosis protein 64 (MPT64), culture filtrate protein 10 (CFP10), and phosphate ABC transporter substrate-binding lipoprotein (PstS1) were expressed and intravenously injected into BALB/c mice. The serum were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The concentrations of candidate peptides in serum of suspected TB patients were determined using competitive enzyme-linked immunosorbent assay.Results: A total of 65 peptides from 4 MTB precursor recombinant proteins were identified in mouse serum by LC-MS/MS, of which 5 peptides were selected as candidates for serological analysis. The concentrations of peptides MPT64-2, CFP10-2 and PstS1-2 in TB patients were significantly higher than those in non-TB patients. MPT64-2 exhibited the most promising sensitivity (81.4%), followed by PstS1-2 and CFP10-2. In addition, PstS1-2 had the highest specificity (93.3%), followed by CFP10-2 and MPT64-2. According to the area under the curve (AUC), MPT64-2 (AUC = 0.863), PstS1-2 (AUC = 0.812) and CFP10-2 (AUC = 0.809) exhibited better diagnostic validity.Conclusion: We develop an effective approach to identify new antigen biomarkers via LC-MS/MS-based peptidomics. Multiple peptides exhibit promising efficacy in diagnosis of active TB patients.Keywords: tuberculosis, peptidomics, enzyme-linked immunosorbent assay, Mycobacterium tuberculosis protein 64, diagnostics

Liangliang Ma,1 Maolong Gao2 1Department of Infectious Diseases, Beijing Geriatric Hospital, Beijing, 100095, People’s Republic of China; 2Department of Science and Technology, Beijing Geriatric Hospital, Beijing, 100095, People’s Republic of ChinaCorrespondence: Liangliang Ma, Department of Infective Diseases, Beijing Geriatric Hospital, No. 118 Wenquan Road, Haidian District, Beijing, 100095, People’s Republic of China, Tel +86-18610672953, Email mlldr2021@sina.comObjective: To analyze the clinical characteristics and risk factors of drug resistance of newly-treated chronic obstructive pulmonary disease (COPD) complicated pulmonary tuberculosis (PTB).Methods: A total of 489 newly-treated PTB patients admitted to Beijing Geriatric hospital were retrospectively enrolled in this study. Of these, 138 patients with COPD were allocated to the study group, and the remaining 351 patients without COPD were allocated to the control group. The baseline information, clinical characteristics of PTB and drug resistance of Mycobacterium tuberculosis were compared between the two groups. Logistic regression was used to explore the correlation between drug resistance and COPD complications.Results: Patients complicated with COPD had a higher proportion of respiratory failure, cough, fever and night sweats, chest short breath, and emaciation between the study group and the control group (P< 0.05). In terms of medical history, patients complicated with COPD also had a higher proportion of childhood TB history, cough, tuberculosis exposure rate, dust exposure rate, and malnutrition (P< 0.05). There were significantly more patients with pulmonary cavities and a delayed diagnosis of TB in the study group than in the control group (P< 0.05). The single drug resistance rates of isoniazid, ethambutol, rifampicin, pyrazinamide, and rifapentine, and drug resistance with any two or more drugs in the study group were significantly higher than those in the control group (P< 0.05). Multivariate Logistic regression analysis showed that smoking, extrapulmonary tuberculosis, tuberculosis exposure history, malnutrition, pulmonary cavity, and delayed TB diagnosis were risk factors for drug resistance in newly-treated COPD complicated PTB patients.Conclusion: The symptoms of COPD complicated PTB were more serious. Smoking history, extrapulmonary tuberculosis, tuberculosis exposure history, malnutrition, pulmonary cavity, and delayed diagnosis of tuberculosis were risk factors for TB resistance in these patients.Keywords: chronic obstructive pulmonary disease, pulmonary tuberculosis, Mycobacterium tuberculosis, drug resistance, risk factors

Mingde Gao1 &ast;, Qiuxing Yang2 &ast;, Haifei Xu,1 Zhigang Chen,1 Xiaolin Wang,1 Haifeng Guo1 1Department of Urology, Affiliated Tumor Hospital of Nantong University & Nantong Tumor Hospital, Nantong, 226361, People’s Republic of China; 2Department of Central Laboratory, Affiliated Tumor Hospital of Nantong University & Nantong Tumor Hospital, Nantong, 226361, People’s Republic of China&ast; These authors contributed equally to this workCorrespondence: Xiaolin Wang; Haifeng Guo, Department of Urology, Affiliated Tumor Hospital of Nantong University & Nantong Tumor Hospital, Nantong, 226361, People’s Republic of China, Tel +86 159 5086 8500 ; +86 138 1360 3975, Email cxhwyc2010@163.com; 13813603975@163.comIntroduction: Numerous studies, including bladder cancer (BLCA), have confirmed the relationship between conventional systemic inflammatory biomarkers and the prognosis of tumors. Leukocytes, as the most common factor in inflammatory indicators, have been reported to predict prognosis in other tumors. However, we have not seen this research in BLCA. Therefore, we aim to find new blood markers to predict the prognosis of patients with transurethral resection of bladder tumor (TURBT).Methods: Two cohorts from the two different hospitals were used for the specific study. The best cutoff values of leukocytes-related indicators were determined according to the ROC curve. Univariate and multivariate Cox regression analysis were used to explore the impact of indicators and clinical features on prognosis for patients with TURBT. The KM curve was used to show the impact of indicators on the prognosis. According to the consequence of multivariate method, a risk model was established to evaluate the prognosis of patients with bladder cancer.Results: The white blood cell-to-lymphocyte ratio (WLR), the white blood cell-to-hemoglobin ratio (WHR), the white blood cell-to-neutrophil ratio (WNR), the white blood cell-to-monocyte ratio (WMR) and the white blood cell-to-erythrocyte ratio (WRR) are related to the prognosis of BLCA. The new risk model consisted of WHR, WMR and platelet-to-lymphocyte ratio (PLR), and patients with TURBT in the high-risk group had a worse prognosis.Conclusions: Leukocyte-related preoperative indicators could predict the prognosis of the patients with TURBT and provided some guidance for clinical workers.Keywords: bladder cancer, BLCA, white blood cell-to-lymphocyte ratio, WLR, white blood cell-to-hemoglobin ratio, WHR, white blood cell-to-neutrophil ratio, WNR

Yifan Wang,1– 3 Shan Wang,1– 3 Liyun Zheng,1– 3 Xiuli Wang,1– 3 Hui Wang,1– 3 Zhenyu Zhong,1– 3 Siqi Liu,1– 3 Xiaodong Zheng,1– 3 Min Gao1– 3 1Department of Dermatology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, Anhui, People’s Republic of China; 3Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, People’s Republic of ChinaCorrespondence: Min Gao; Xiaodong Zheng, Department of Dermatology, the First Affiliated Hospital of Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui, 230032, People’s Republic of China, Tel/Fax +86-0551-62923042, Email ahhngm@126.com; zhengxiaodong.1234@163.comAbstract: SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome is a rare disease clinically characterized by a wide range of cutaneous and osteoarticular manifestations. Here, we report a case of SAPHO syndrome with cutis verticis gyrata (CVG) and investigated the genetic causes in the four members of this pedigree. After failure of conventional treatments, a recombinant human TNF-α receptor II:IgG Fc fusion protein (rhTNFR:Fc, YISAIPU®) achieved good control of the disease at the 2-year follow-up. We did not identify any pathogenic mutation in this pedigree. We also summarized the clinical and therapeutic characteristics of 83 patients with SAPHO syndrome through the China National Knowledge Infrastructure (CKNI) database from 2016 to 2021. Patients with acne were young and predominantly male. About 45.8% patients were treated with biological therapies or traditional Chinese medicine (TCM), 84.2% of which showed positive effects against cutaneous and osteoarticular manifestations. We report a case of SAPHO syndrome with CVG that was successfully treated with rhTNFR:Fc. Our results reveal the genetic heterogeneity involved. Biologics and TCM are likely alternative options for the treatment of SAPHO syndrome.Keywords: cutis verticis gyrata, gene mutation, SAPHO syndrome, treatment, whole-exome sequencing

Qiang Cai,1,&ast; Guoqing Liu,2,&ast; Linsheng Huang,3,&ast; Yuting Guan,2,&ast; Huixia Wei,4 Zhiqian Dou,5 Dexi Liu,6 Yang Hu,1 Meiling Gao4 1Department of Orthopedics, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, People’s Republic of China; 2Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 3Department of Hepatobiliary Surgery, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of China; 4Department of Anesthesiology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of China; 5Department of Obstetrics, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of China; 6Department of Stomatology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Meiling Gao, Department of Anesthesiology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of China, Tel +86-15971849819, Email mlgdoctor@163.com Yang Hu, Department of Orthopedics, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, 441000, People’s Republic of China, Tel +86-13995744850, Email huyang1983919@163.comAbstract: Dexmedetomidine, a specific α 2 adrenergic receptor agonist, is highly frequently used in the perioperatively for its favorable pharmacology, such as mitigating postoperative cognitive dysfunction. Increasing attention has been recently focused on the effect of whether dexmedetomidine influences cancer recurrence, which urges the discussion of the role of dexmedetomidine in tumor-progressive factors. The pharmacologic characteristics of dexmedetomidine, the tumor-progressive factors in the perioperative period, and the relationships between dexmedetomidine and tumor-progressive factors were described in this review. Available evidence suggests that dexmedetomidine could reduce the degree of immune function suppression, such as keeping the number of CD3+ cells, NK cells, CD4+/CD8+ ratio, and Th1/Th2 ratio stable and decreasing the level of proinflammatory cytokine (interleukin 6 and tumor necrosis factor-alpha) during cancer operations. However, dexmedetomidine exhibits different roles in cell biological behavior depending on cancer cell types. The conclusions on whether dexmedetomidine would influence cancer recurrence could not be currently drawn for the lack of strong clinical evidence. Therefore, this is still a new area that needs further exploration.Keywords: dexmedetomidine, cancer recurrence, surgery, immune, inflammation

Yu Pang,1 Rongmei Liu,2 Yanhua Song,2 Zizheng Lv,2 Mengqiu Gao,2 Lihui Nie,2 Qiping Ge,2 Xiaoguang Wu2 1Department of Science and Technology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, 101149, People’s Republic of China; 2Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, 101149, People’s Republic of ChinaCorrespondence: Lihui Nie; Xiaoguang Wu, Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, No. 9, Beiguan Street, Tongzhou District, Beijing, People’s Republic of China, Tel +86-10-8950 9322 ; +86-10-8950 9122, Email nielihui666@sohu.com; yuewxg@hotmail.comObjective: Cycloserine (CS) is a group B anti-tuberculosis (TB) drug endorsed by the World Health Organization (WHO) for the treatment of drug-resistant (DR)-TB. Despite CS widespread acceptance and known efficacy, the high potential of drug-associated psychiatric disorders is a major concern to multidrug-resistant (MDR)-TB patients. In this study, we investigated CS-associated psychiatric disorders in a cohort of MDR-TB patients in Beijing, China. Our aim was to determine psychiatric disorder prevalence rates and associated risk factors in this population.Methods: This MDR-TB cohort study was conducted at Beijing Chest Hospital between February 2018 and February 2021. All patients received individualized treatment regimens that included CS at some point during the full treatment course. Patient psychological status was assessed using the Symptom Checklist (SCL-90) questionnaire during the post-treatment follow-up period.Results: Two hundred and thirty-seven MDR-TB patients were included in the final analysis. Overall, psychiatric disorders were recorded in 22 (9.28%) of the 237 patients in our cohort, with severity grades of 1 or 2 observed for the majority (8.44%) of psychiatric adverse events. As compared to results obtained for control group patients who were ≥ 40 years of age, patients who were < 40 years of age (77.3%, 17/22) were more likely to experience psychiatric disorders [adjusted odds ratio (aOR) = 3.060; 95% CI (1.060– 8.828)]. Additionally, patients with body mass index (BMI)s of < 18.5 kg/m2 [aOR = 3.824; 95% CI (1.502– 9.739)] had significantly higher odds of being afflicted with psychiatric disorders as compared with patients with BMIs that were ≥ 18.5 kg/m2.Conclusion: Our results demonstrated that approximately one-tenth of Chinese MDR-TB patients experienced psychiatric disorders during CS treatment, with the majority of adverse events of moderate severity. In addition, low BMI and age < 40 years were identified as independent risk factors for psychiatric disorders in MDR-TB patients receiving CS therapy.Keywords: cycloserine, multidrug-resistant tuberculosis, incidence, risk factor, psychiatric disorder

Ming Gao,1 Haisheng Lin,2 Bingxiao Li,3 Junjie Wen,3 Yingying Wang,1 Zhanhui Zhang,4,&ast; Wenxiong Chen2,&ast; 1Department of Neurology, First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, 510630, People’s Republic of China; 2Department of Neurology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, 510120, People’s Republic of China; 3Department of Pediatrics, First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, 510630, People’s Republic of China; 4Clinical Medicine Research Institute, First Affiliated Hospital, Jinan University, Guangzhou, 510630, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhanhui ZhangFirst Affiliated Hospital, Jinan University, 613 West Huangpu Avenue, Tianhe, Guangzhou 510630, Guangdong, People’s Republic of China, Tel +86-20-3868-8749, Email zzhaddress@126.comObjective: Tic disorders (TDs) are highly polygenic and heritable neurodevelopmental disorders characterized by the presence of movements (motor tics) and/or vocalizations (phonic tics). SLITRK1 is a pathogenic variation of TD, and in a recent genome-wide association study in those of European ancestry, a single-nucleotide polymorphism (rs2504235) in the FLT3 gene was significantly associated with TDs/Tourette’s syndrome. However, these results need to be proved in different populations. This study aimed to determine whether these two genetic variants were also associated with TD patients in south China.Methods: A total of 116 child TD patients and 114 healthy controls were included. All children underwent peripheral blood sampling for genomic DNA extraction. Gene fragments with two single-nucleotide polymorphisms were amplified by PCR and sequenced by Sanger chain termination before genotype analysis.Results: SLITRK1 var321 was not observed in any of the TD patients or controls. No significant difference was observed in allelic frequencies or genotypic distributions of rs2504235 between TD patients and controls.Conclusion: Our results provide no evidence to support the previous conclusion that SLITRK1 var321 plays a major role in TDs, and FLT3 rs2504235 was not significantly associated with TDs in our cohort.Keywords: tic disorders, Tourette’s syndrome, SLITRK1, SLIT and NTRK like family member 1, FLT3, Fms related receptor tyrosine kinase 3

Miaozi Gao,1,2 Xiaowei Peng,3 Junrong Tang,1 Jia Deng,1 Fang Wang,1 Yingjun Zhang,4 Ping Zhao,1,2 Huan Kan,1,3 Yun Liu1,3 1Key Laboratory of Forest Resources Conservation and Utilization in the Southwest Mountains of China Ministry of Education, Southwest Forestry University, Kunming, People’s Republic of China; 2Key Laboratory of State Forestry and Grassland Administration on Highly-efficient Utilization of Forestry Biomass Resources in Southwest China, Southwest Forestry University, Kunming, People’s Republic of China; 3School of Life Science, Southwest Forestry University, Kunming, People’s Republic of China; 4State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, People’s Republic of ChinaCorrespondence: Ping Zhao; Yun LiuKey Laboratory of Forest Resources Conservation and Utilization in the Southwest Mountains of China Ministry of Education, Southwest Forestry University, #300, Bailong Road, Kunming, 650224, People’s Republic of China, Email hypzhao@yahoo.com; liuyun@swfu.edu.cnPurpose: Plant polyphenols possess beneficial functions against various diseases. This study aimed to identify phenolic ingredients in Camellia fascicularis (C. fascicularis) and investigate its possible underlying anti-inflammatory mechanism in lipopolysaccharide (LPS)-induced human monocytes (THP-1) macrophages.Methods: C. fascicularis polyphenols (CFP) were characterized by ultra-performance liquid chromatography (UPLC) combined with quadrupole-time-of-flight mass/mass spectrometry (Q-TOF-MS/MS). The THP-1 cells were differentiated into macrophages under the stimulation of phorbol 12-myristate 13-acetate (PMA) and then treated with LPS to build a cellular inflammation model. The cell viability was detected by CCK-8 assay. The levels of reactive oxygen species (ROS) were assessed by flow cytometry. The secretion and expression of inflammatory cytokines were tested by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR). In addition, the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways were analyzed by Western blotting.Results: Twelve phenolic constituents including (–)-epicatechin, casuariin, agastachoside, etc. in CFP were identified. The CCK-8 assay showed that CFP exhibited no significant cytotoxicity between 100 and 300 μg/mL. After treated with CFP, the release of ROS was significantly suppressed. CFP inhibited inflammation in macrophages by attenuating the polarization of LPS-induced THP-1 macrophages, down-regulating the expression of the pro-inflammatory cytokines IL-6, IL-1β and TNF-α, and up-regulating the expression of the anti-inflammatory cytokine IL-10. Western blotting experiments manifested that CFP could markedly inhibit the phosphorylation of p65, ERK and JNK, thereby suppressing the activation of NF-κB and MAPK signaling pathways.Conclusion: These findings indicated that CFP exerted anti-inflammatory activity by inhibiting the activation NF-κB and MAPK pathways which may induce the secretion of pro-inflammatory cytokines. This study offers a reference for C. fascicularis as the source of developing natural, safe anti-inflammatory agents in the future.Keywords: Camellia fascicularis, polyphenols, anti-inflammatory activity, NF-κB, MAPK

Kangjun Fan,1 Liang Chen,1 Fei Liu,2 Xiaohang Ding,1 Pengyun Yan,1 Mingxin Gao,1 Wenyuan Yu,1 Hongli Liu,1 Yang Yu1 1Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, People’s Republic of China; 2Department of Biology, Faculty of Science, Hong Kong Baptist College, Kowloon Tong, Hong Kong, People’s Republic of ChinaCorrespondence: Yang Yu, Tel +86-10-64456868, Fax +86-10-84005030, Email heartyuyang@hotmail.comObjective: To select variables associated with new-onset postoperative atrial fibrillation (POAF) following isolated coronary artery bypass grafting (CABG) and develop a nomogram for risk prediction in a Chinese population.Methods: The study retrospectively enrolled 4854 consecutive patients undergoing isolated CABG from February 2018 to September 2019, they were divided into derivation cohort and validation cohort with a 3:1 ratio according to the order of operation date. In the derivation cohort, significant variables were selected by use of the multivariate logistic backward stepwise regression analysis and a nomogram model was built on the strength of the results. The model performance was assessed in terms of discrimination and calibration. Besides, we compared the discriminative ability for POAF of the nomogram with established prediction models (CHA2DS2-VASc and HATCH scores) in the two cohorts.Results: POAF occurred in 1025 (28.2%) out of 3641 patients in the derivation cohort, and in 337 (27.8%) out of 1213 patients in the validation cohort. A nomogram, composed of eight prognostic variables, namely age, sex, heart rate, hypertension, left ventricular ejection fraction (LVEF) < 50%, left atrial diameter (LAD) > 40mm, estimated glomerular filtration rate (eGFR) level, and on-pump surgery, was constructed from the derivation cohort. The nomogram had substantial discriminative ability in derivation and validation cohorts with the area under the receiver operating characteristic curves (AUCs) of 0.661 (95% confidence interval, 0.642– 0.681) and 0.665 (95% confidence interval, 0.631– 0.699), respectively, and showed well-fitted calibration curves. Compared with CHA2DS2-VASc, HATCH and POAF scores, respectively, the nomogram had superior discrimination performance.Conclusion: We constructed a novel nomogram with improved accuracy for predicting the risk of POAF following isolated CABG, which might help clinicians predict individual probability of POAF and achieve effective prophylaxis.Keywords: coronary artery bypass grafting, atrial fibrillation, high-risk patients, prediction, nomogram

Yu Liu,1 Ying Liang,1 Min Gao,1 Yingchun Li,1 Tingting Zhao,2 Yani Zhao1 1Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, Shanxi, 030032, People’s Republic of China; 2Shaanxi University of Traditional Chinese Medicine, Xi’an, Shaanxi, 712046, People’s Republic of ChinaCorrespondence: Ying LiangThird Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, No. 99, Longcheng Street, Xiaodian District, Taiyuan, Shanxi, 030032, People’s Republic of ChinaTel +86-13934225687Email sx.liangying@126.comAbstract: Complex regional pain syndrome (CRPS) is a chronic pain disorder characterized by spontaneous or evoked regionally-confined pain which is out of proportion to the initial trauma event. The disease can seriously affect the quality of the patients’ life, increase the psychological burden, and cause various degrees of disability. Despite the awareness of CRPS among medical practitioners for over a century, its pathogenesis remains unclear, and the available treatment is still unsatisfactory. Effective animal models are the foundation of disease research, which is helpful in understanding the pathogenesis and an in-depth exploration of the appropriate therapeutic approaches. Currently, researchers have established a series of animal models of the disease. There are four main CRPSI animal models: chronic post-ischemic pain (CPIP) model, tibial fracture/cast immobilization model, passive transfer-trauma model, and the needlestick-nerve-injury (NNI) model. The modeling methods of these models are constantly improving over time. In preclinical studies, the interpretation of experimental results and the horizontal comparison between similar studies may be affected by the nature of the experimental animal breeds, sex, diet, and psychology. There is need to facilitate the choice of appropriate animal models and avoid the interference of the factors influencing animal models on the interpretation of research results. The review will provide a basic overview of the influencing factors, modeling methods, and the characteristics of CRPSI animal models.Keywords: CRPS, reflex sympathetic dystrophy, animal model, mouse, rat, sex, diet, psychology

Jidong Guo,1,2,&ast; Qiang Li,1,&ast; Xuxia Zhang,2 Cong Yao,2 Rongmei Liu,1 Yu Pang,2 Mengqiu Gao1 1Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, 101149, People’s Republic of China; 2Department of Bacteriology and Immunology, Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, 101149, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: : Yu PangDepartment of Bacteriology and Immunology, Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, No. 9, Beiguan Street, Tongzhou District, Beijing, 101149, People’s Republic of ChinaTel/Fax +86-10-8950 9162Email pangyupound@163.comMengqiu GaoDepartment of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, No. 9, Beiguan Street, Tongzhou District, Beijing, 101149, People’s Republic of ChinaTel/Fax +86-10-8950 9322Email gaomqwdm@aliyun.comIntroduction: Interferon-γ release assays (IGRAs) can have high false-negative rates for active tuberculosis (TB) cases. Here we investigated factors, including potential anti-inflammatory mechanisms, that contributed to false-negative IGRA results.Methods: We established two cohorts. In the first cohort, we reviewed IGRA results for confirmed TB cases diagnosed in our hospital in 2018. Cases with false-negative IGRA results were analysed to identify factors contributing to false-negative results. In the second cohort, we prospectively studied IL-10 expression levels in peripheral blood mononuclear cells (PBMCs) of IGRAs-positive and IGRAs-negative TB cases after antigenic stimulation to correlate IL-10 expression with IGRAs results.Results: Of 1232 culture-confirmed TB cases, 1124 produced true-positive IGRA results and 108 had false-negative IGRA results. Multivariate logistic regression analysis identified glucocorticoid use and extrapulmonary TB as independent risk factors for false-negative IGRA results. Notably, IL-10 expression of the IGRA-negative group was significantly up-regulated as compared to that of the IGRA-positive group. The average cell supernatant IL-10 concentration of the IGRA-negative group was 4.77 pg/mL, a value that was statistically greater than the IGRA-positive group concentration (1.47 pg/mL, P = 0.007). After PBMCs pretreatment with BRD6989 (to enhance IL-10 secretion), average IFN-γ concentrations in cell supernatants from the IGRA-positive group significantly decreased from 59.73 pg/mL to 33.79 pg/mL (P = 0.011). By contrast, addition of AS101 (to inhibit IL-10 secretion) to false-negative group PBMCs led to an increase of average IFN-γ concentration in cell supernatants from 19.01 pg/mL to 45.10 pg/mL (P = 0.030), a result that was inversely correlated with IL-10 concentration.Conclusion: Our data demonstrate that increased IL-10 secretion by PBMCs is inversely correlated with IGRA assay results in culture-confirmed TB patients. Glucocorticoids use and extrapulmonary TB are significantly associated with false-negative IGRA results. Combination testing to measure IL-10 secretion and IFN-γ release is recommended to improve IGRAs specificity.Keywords: tuberculosis, interferon-γ release assay, interleukin 10

Jidong Guo,1,&ast; Rongmei Liu,1,&ast; Jin Shi,1,&ast; Fengmin Huo,2 Yuanyuan Shang,3 Fen Wang,2 Mengqiu Gao,1 Shanshan Li3 1Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, 101149, People’s Republic of China; 2National Clinical Laboratory on Tuberculosis, Beijing Key laboratory on Drug-resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, 101149, People’s Republic of China; 3Department of Bacteriology and Immunology, Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, 101149, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shanshan LiDepartment of Bacteriology and Immunology, Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, No. 9, Beiguan Street, Tongzhou District, Beijing, 101149, People’s Republic of ChinaTel +86-10-8950 9368Fax +86-10-8950 9366Email Lss9011@126.comMengqiu GaoDepartment of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, No. 9, Beiguan Street, Tongzhou District, Beijing, 101149, People’s Republic of ChinaTel +86-10-8950 9322Fax +86-10-8950 9322Email gaomqwdm@aliyun.comBackground: Early and accurate diagnosis of rifampicin (RIF)-resistant Mycobacterium tuberculosis (MTB) is essential for controlling community spread of drug-resistant tuberculosis (TB). In order to discover mutations residing outside the rifampicin resistance-determining region (RRDR) of the MTB rpoB gene, we conducted this retrospective study.Methods: We retrospectively screened patient records to obtain Xpert MTB/RIF assay results for patients who received care at the Beijing Chest Hospital from 2016 to 2019 in order to identify subjects who met study selection criteria. Stored frozen patient isolates were cultured, harvested, and then subjected to drug susceptibility testing. Concurrently, entire rpoB gene DNA of each isolate was amplified and then sequenced to reveal rpoB mutations.Results: Overall, 104 RIF-susceptible tuberculosis patients who were tested using the Xpert MTB/RIF assay also had poor first-line regimen treatment responses. Isolates obtained from these cases included 101 MTB isolates that possessed wild-type rpoB allelic profiles, as demonstrated using Sanger sequencing. However, sequences from the other three isolates confirmed that rpoB of one isolate harbored a mutation encoding the amino acid substitution Ile491Phe and that rpoB genes of two isolates contained a mutation encoding the amino acid substitution Ser450Leu.Conclusion: Our data demonstrated that mutations found outside the RRDR of MTB rpoB are rare in Beijing, China, indicating that World Health Organization-approved molecular diagnostics are generally suitable for diagnosing RIF resistance.Keywords: tuberculosis, rifampicin-resistance, rpoB, diagnosis

Yingxin Chen, Linlin Zhang, Zhiling Liu, Qiming Liu, Minghong Gao Department of Ophthalmology, General Hospital of Northern Theater Command, Shenyang, People’s Republic of ChinaCorrespondence: Minghong GaoDepartment of Ophthalmology, General Hospital of Northern Theater Command, 83 Wenhua Road, Shenhe District, Shenyang, 110840, People’s Republic of ChinaTel +86-133-5245-9433Email gaominghong88@yeah.netBackground: The aim of this study was to investigate the efficacy of acellular porcine corneal stroma (APCS) transplantation in the treatment of infectious central and peripheral corneal ulcers.Methods: A total of 45 patients with infectious corneal ulcers who had undergone lamellar keratoplasty using APCS grafts were included. Among these, 24 had lesions located near the pupil (infectious central corneal ulcer group) and 21 had lesions located in the limbus or around the cornea (infectious peripheral corneal ulcer group). Efficacy was assessed in terms of best-corrected visual acuity, graft transparency, corneal neovascularization, corneal reepithelialization, survival rate, and postoperative complications.Results: Baseline characteristics showed that poor visual acuity and larger-diameter APCS graft in the infectious central corneal ulcer group were comparable with the infectious peripheral corneal ulcer grouper group (P< 0.05). After lamellar keratoplasty using APCS grafts, no obvious differences were observed in aspects of graft transparency, corneal neovascularization, or survival rate (P> 0.05). Postoperative complications, ie, delayed corneal epithelial healing, rejection episode, recurrence of infection, and graft melting, were not significantly different between the two groups (P> 0.05). Visual acuity in bothgroups had improved significantly at 3 months and 6 months postoperation, respectively.Conclusion: APCS transplantation is safe and efficacious for treating infectious central and peripheral corneal ulcers. Despite its good efficacy, APCS-graft size, implant position, patient indications, and postoperative management should be kept in mind in treatment for infectious corneal ulcers in different locations.Keywords: acellular porcine corneal stroma, lamellar keratoplasty, infectious central corneal ulcers, infectious peripheral corneal ulcers

Shijiang Liu,* Peipei Peng,* Youli Hu, Cunming Liu, Xiaofei Cao, Chun Yang, Mei Gao Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mei GaoAnesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Nanjing, People’s Republic of ChinaTel +86-25-68303569Email drgaomei@njmu.edu.cnPurpose: The present study aimed to determine the effectiveness of intravenous dexmedetomidine of different concentrations and to evaluate its maternal and neonatal safety when combined with butorphanol in parturients undergoing cesarean section.Patients and Methods: A total of 114 parturients between 24 and 43 years of age, with singleton pregnancy who underwent elective cesarean section under epidural anesthesia, were randomly allocated to four groups: group C received 0.9% sodium chloride after delivery, followed by butorphanol (3 μg·kg− 1·h− 1); patients in groups D1, D2, and D3 received 0.5 μg·kg− 1·h− 1 dexmedetomidine after delivery, followed by butorphanol (3 μg·kg− 1·h− 1) combined with dexmedetomidine 0.03, 0.05, and 0.08 μg·kg− 1·h− 1, respectively. The primary outcome was the visual analogue scale (VAS) score at 6 h after delivery when patients were at rest. Secondary outcome measures included VAS after delivery when patients were on movement and uterine cramping, Ramsay sedation scale (RSS), relative infant dose (RID) of dexmedetomidine, satisfaction with analgesia after surgery and symptoms of CNS depression in neonates.Results: There were no significant differences in patient characteristics among the groups (P > 0.05). The VAS at all timepoints after delivery in groups D2 and D3 were significantly lower than in groups C and D1 (P < 0.001). RSS scores were clearly higher in group D3 than in the other three groups at 6 h and 12 h (P < 0.0001). RID in groups D1, D2, and D3 was 0.171%, 0.197%, and 0.370%, respectively. Compared with group D1, RID was higher in group D3 (P = 0.0079). Degree of satisfaction with analgesia was higher in groups D2 and D3 (P < 0.005).Conclusion: Continuous intravenous infusion of 0.05 μg·kg− 1·h− 1 dexmedetomidine combined with 3 μg·kg− 1·h− 1 butorphanol could be safely applied in healthy parturients with satisfactory analgesia after cesarean section without changes in sedation.Keywords: cesarean section, dexmedetomidine, analgesia, relative infant dose, anesthesia

Renlun Huang,1,* Lang Guo,1,* Menghan Gao,2 Jing Li,1 Songtao Xiang1 1Department of Urology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 2Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden*These authors contributed equally to this workCorrespondence: Songtao XiangDepartment of Urology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of ChinaTel/Fax +86-13711515862Email tonyxst@gzucm.edu.cnAbstract: Prostate cancer (PCa) is considered as the most common cancer of urologic neoplasms, and its development and prognosis are associated with many factors. Chemokine receptor signaling combine with advances in advanced clinicopathological characteristics have provided new insights into the molecular landscape of prostate cancer. Chemokine (C-C motif) ligand 5 (CCL5) is an important member of the CC subfamily of chemokines. The expression of chemokine CCL5 is positively correlated with poor prognostic features in patients with PCa. Current study suggested that CCL5/CCR5 axis plays a significant role in the proliferation, metastasis, angiogenesis, drug resistance of prostate cancer cells and promotes self-renewal of prostate cancer stem cells (PCSCs). Due to the major domination in CCL5 by prostate cancer and the high cancer-specific mortality with prostate cancer, research on the CCL5/CCR5 axis effective antagonists is widespread application. However, challenges for precision oncology of CCL5/CCR5 axis and effective antagonists in CRPC remain. Herein, we summarized the crucial role of CCL5 in promoting the development of PCa and discussed the antitumor application of the antagonists of CCL5/CCR5 axis.Keywords: chemokine, tumor development, CCR5, antagonists

Yanhua Song,1,* Yifeng Ma,2,* Rongmei Liu,1,* Yuanyuan Shang,3,* Liping Ma,1 Fengmin Huo,3 Yunxu Li,3 Wei Shu,4 Yufeng Wang,5 Mengqiu Gao,1 Yu Pang3 1Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, People’s Republic of China; 2Clinical Laboratory, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, People’s Republic of China; 3Department of Bacteriology and Immunology, Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, People’s Republic of China; 4Clinical Center on TB, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, People’s Republic of China; 5Department of Laboratory Quality Control, Innovation Alliance on Tuberculosis Diagnosis and Treatment (Beijing), Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mengqiu GaoDepartment of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, No. 9, Beiguan Street, Tongzhou District, Beijing 101149, People’s Republic of ChinaTel/Fax +86-10-8950 9322Email gaomqwdm@aliyun.comYu PangDepartment of Bacteriology and Immunology, Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, No. 9, Beiguan Street, Tongzhou District, Beijing 101149, People’s Republic of ChinaTel/Fax +86-10-8950 9359Email pangyupound@163.comObjective: A prospective study was conducted to ascertain the accuracy of oral swab specimens collected in the early morning, spot and at night for detecting pulmonary tuberculosis (TB).Methods: We prospectively enrolled patients with symptoms suggestive of pulmonary TB in Beijing Chest Hospital. An early morning sputum specimen was collected from each patient for GeneXpert MTB/RIF (Xpert) and mycobacterial culture. In addition, three oral swabs were collected for TB-LAMP testing.Results: With the combined results of three oral swab specimens, the proportion of Mycobacterium tuberculosis (MTB)-positive cases achieved 40.6%, which was comparable to results for Xpert and MGIT (P=0.603). Using Xpert plus MGIT as reference, the sensitivity of OS-LAMP on a single specimen ranged from 32.6% on the night oral swab to 50.0% on the morning swab. The combination of three oral swab specimens correctly identified 38 MTB-positive cases, indicating an overall sensitivity of 82.6%, which was significantly higher than that of a single oral swab specimen (P< 0.001, P=0.001).Conclusion: Oral swab can be used as an alternative specimen for diagnosis of pulmonary TB using TB-LAMP. Morning oral swab exhibits the highest sensitivity, and the inclusion of more specimens at different time points provides compensation in diagnostic sensitivity with single oral swab.Keywords: diagnosis, oral swab, TB-LAMP, pulmonary tuberculosis, China

Jiacheng Wu,1,2,* Haifei Xu,1,* Hao Ji,1 Baoqian Zhai,2 Jinfeng Zhu,1 Mingde Gao,3 Haixia Zhu,2 Xiaolin Wang1 1Department of Urology, Tumor Hospital Affiliated to Nantong University, Nantong University, Nantong 226361, People’s Republic of China; 2Cancer Research Center Nantong, Tumor Hospital Affiliated to Nantong University, Nantong University, Nantong 226361, People’s Republic of China; 3Department of Urology, Medical College of Nantong University, Nantong 226019, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haixia ZhuCancer Research Center Nantong, Tumor Hospital Affiliated to Nantong University, Nantong University, No. 30 Tongyang Bei Road, Tongzhou District, Nantong 226361, People’s Republic of ChinaTel +86 138 6290 6771Fax +86 513 8671 2287Email zhx19891027@163.comXiaolin WangDepartment of Urology, Tumor Hospital Affiliated to Nantong University, Nantong University, No. 30 Tongyang Bei Road, Tongzhou District, Nantong 226361, People’s Republic of ChinaTel +86 159 5086 8500Fax +86 513 8672 9043Email cxhwyc2010@163.comObjective: To investigate the association between KRT17 and the prognosis in bladder cancer patients.Methods: The clinical data of 101 patients with bladder cancer from May 2013 to May 2015 were retrospectively analyzed. At the same time, the expression of KRT17 and its correlation with clinicopathological factors were examined by immunohistochemistry. We search the prognostic value of KRT17 in bladder cancer from the cancer genome map (TCGA) online database. To explore the possible cellular mechanism, gene set enrichment analysis (GSEA) was used. The patients were divided into two groups: high expression of KRT17 and low expression of KRT17. The patients were followed up for 5 years to observe the survival. Kaplan–Meier method and Log rank test were used for univariate survival analysis, and Cox regression analysis was used for multivariate analysis. Finally, a nomogram was constructed on this basis for internal verification.Results: Among the 101 patients, 46 (45.5%) were in the KRT17 low expression group and 55 (54.5%) in the high KRT17 expression group. After 5 years of follow-up, 79 patients survived with a survival rate of 78.2% and 22 patients died with a mortality rate of 21.8%. Kaplan–Meier survival analysis showed that OS and PFS of patients with high expression of KRT17 were significantly higher than those of patients with low expression of KRT17 (p< 0.001, p=0.005). Cox multivariate analysis showed that KRT17 expression was an independent risk factor for tumor progression (p=0.019). And tumor size, vascular tumor thrombus, and T stage also affected tumor progression (p< 0.05). In the internal validation, the c-index of nomogram was 0.898 (95% CI: 0.854– 0.941).Conclusion: The decreased expression of KRT17 is associated with poor prognosis in patients with bladder cancer. KRT17 can be used as a novel predictive biomarker to provide a new therapeutic target for bladder cancer patients.Keywords: keratin17, bladder cancer, overall survival, prognosis, progression-free survival, risk factors, nomograph

Yanhua Song,1 Guirong Wang,2 Qiang Li,1 Rongmei Liu,1 Liping Ma,1 Qi Li,3 Mengqiu Gao1 1Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing 101149, People’s Republic of China; 2National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing 101149, People’s Republic of China; 3Clinical Center on Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing 101149, People’s Republic of ChinaCorrespondence: Qi LiClinical Center on Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing 101149, People’s Republic of ChinaTel +86 10 89509322Fax +86 1069546790Email liqi88_dr@163.comMengqiu GaoDepartment of Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing 101149, People’s Republic of ChinaTel +86 10 89509322Fax +86 1069546790Email gaomengqi55_dr@163.comObjective: This study aims to analyze the correlation between gene inhA mutations by melting curve technology and phenotypic drug susceptibility (DST) results of ethionamide (ETH), and evaluate whether gene inhA mutations detection can serve as a molecular marker in predicting ETH resistance.Methods: A retrospective analysis was conducted on 382 strains of Mycobacterium tuberculosis (MTB) with the anti-tuberculosis drugs isoniazid (INH), rifampicin (RIF), ETH, and others. Phenotypic drug susceptibility and the results of inhA and katG genotypes (mutation and no mutation) were obtained using the melting curve technology MeltPro TB assay.Results: Of the 382 clinical strains of MTB tested, 118 (30.9%) were resistant to INH, and 28 (7.3%) were resistant to ETH. Among the 28 phenotypically ETH-resistant strains, inhA mutations accounted for 42.9% (12/28). These ETH-resistant strains comprise 35.3% (12/34) of the 34 inhA mutant strains. Of 8 single inhA mutation strains (without katG or rpoB mutation), 4(50%) were resistant to INH; however, all of these 8 strains were sensitive to ETH.Conclusion: The inhA mutation test may not be a reliable predictor of ETH resistance. Mutant inhA strains are not necessarily resistant to ETH. The strains with single inhA mutation (without katG or rpoB mutation) may be effective for ETH treatment. The use of ETH in clinical medicine should be guided by gene (other than inhA alone) detection and phenotypic drug susceptibility testing.Keywords: melting curve technique, Mycobacterium tuberculosis, drug resistance, inhA, gene mutation, prothionamide, ethionamide

Wei Sun,1 Meng Gao,2 Guangyuan Hu,1 Xun Yuan1 1Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430020, Hubei, People’s Republic of China; 2Department of Medical Ultrasound, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430020, Hubei, People’s Republic of ChinaCorrespondence: Xun YuanDepartment of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, Hubei, People’s Republic of ChinaTel +86-027-8366-3406Fax +86-027-8366-3630Email yuanxun@tjh.tjmu.edu.cnBackground: Inflammation is involved in the progression of oral squamous cell carcinoma. We therefore postulate that a blood-based inflammatory marker, the neutrophil-to-lymphocyte ratio, could help to predict the prognosis in patients with oral squamous cell carcinoma receiving chemo-radiotherapy, and build a prognostic nomogram.Methods: In 111 cases of oral squamous cell carcinoma, several baseline variables, including inflammatory markers and lactate dehydrogenase, were measured within the week of chemo-radiotherapy initiation as predictors of mortality and separate risk scores were developed.Results: Dichotomized neutrophil-to-lymphocyte ratio was found to be associated with AJCC stage (p< 0.001). Patients with oral squamous cell carcinoma with a low neutrophil-to-lymphocyte ratio survived longer than those with a high neutrophil-to-lymphocyte ratio (overall survival HR=2.39, 95% CI 1.24– 4.61, p=0.009). The Harrell’s concordance (C)-statistic of the nomogram was 0.74 and the calibration curve demonstrated the goodness of fit.Conclusion: The inflammatory marker neutrophil-to-lymphocyte ratio, obtained before chemo-radiotherapy, was an independent factor of survival prediction for oral squamous cell carcinoma. The nomogram incorporating immunological markers could more accurately predict individualized survival probability than the existing models. These findings are significant for the creation of personalized treatment strategies in the clinical setting.Keywords: nomogram, oral squamous cell carcinoma, LDH, platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio

Yudan Yang,1 Ming Gao,1 Yunpeng Li,2 Mengyi Li,1 Qingqing Ma1 1Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, People’s Republic of China; 2Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, People’s Republic of ChinaCorrespondence: Yudan Yang Email yudan62@126.comBackground: This study aimed at probing into the effect of long non-coding RNA (lncRNA) C-terminal binding protein 1 antisense RNA 2 (CTBP1-AS2) on gastric cancer (GC) cell proliferation and apoptosis, and its regulatory function on miR-139-3p and MMP11.Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to examine the expressions of CTBP1-AS2, miR-139-3p and MMP11 mRNA in GC cell lines and clinical specimens. Cell counting kit-8 (CCK-8) assay, flow cytometry and EdU assay were conducted to examine the effects of CTBP1-AS2 and miR-139-3p on GC cell proliferation and apoptosis. Western blot was applied for detecting the expressions of Bax, Bcl-2 and MMP11. A lung metastasis mouse model was used to evaluate metastasis of GC cells in vivo. Bioinformatics, dual-luciferase report assay, RIP and RNA pull-down assays were utilized to validate the targeted relationship between CTBP1-AS2 and miR-139-3p as well as the targeting relationship between miR-139-3p and MMP11.Results: CTBP1-AS2 was highly expressed in GC, and its high expression was strongly associated with increased TNM stage, increased tumor size and low degree of differentiation of the tumor tissues. Meanwhile, CTBP1-AS2 promoted GC cell proliferation, metastasis and suppressed apoptosis, while miR-139-3p could weaken these effects. In addition, CTBP1-AS2 was identified as a molecular sponge for miR-139-3p, and MMP11 was verified as a target gene of CTBP1-AS2. CTBP1-AS2 could increase the expression of MMP11 via repressing miR-139-3p.Conclusion: CTBP1-AS2 promotes GC cells and inhibits apoptosis by regulating the miR-139-3p/MMP11 molecular axis.Keywords: CTBP1-AS2, GC, proliferation, apoptosis

Xiuyong Wang, Yuan Chang, Ming Gao, Fan Zhang Department of Dermatology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan 471000, People’s Republic of ChinaCorrespondence: Xiuyong Wang Department of DermatologyLuoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan 471000, People’s Republic of ChinaEmail wangxiuyo@sina.comPurpose: Cutaneous squamous cell carcinoma (cSCC) is the most common second basal cell carcinoma in our population. Wogonoside, the main in vivo metabolite of wogonin, possesses anti-inflammatory, anti-angiogenesis and anti-cancer activities. Nevertheless, the effectiveness of wogonoside therapy on cSCC has not been clarified.Methods: In this study, we investigated the effects of wogonoside on cell proliferation, invasion, epithelial–mesenchymal transition (EMT) and cancer stem-like cell (CSC) properties of SCL-1 and SCC12 cell lines, and the effects on tumor formation in vivo. In vitro, cells were treated with 0, 25, 50 and 100 μM wogonoside for 48 h. In vivo, SCL-1 cells were subcutaneously injected into the right thigh of mice to form xenograft tumors. Animals were randomly divided into two groups (n=10): the control group and the 80 mg/kg wogonoside group.Results: The results showed that wogonoside attenuated proliferation, invasion and EMT of SCL-1 and SCC12 cell lines, and enhanced the rate of apoptosis. Meanwhile, wogonoside efficiently abolished the CSC traits of cSCC; the expression of CSC markers (ALDH1, SOX-2, Oct4 and CD44) and the percentage of CD133+ cells were remarkably downregulated. In addition, we found that wogonoside repressed the activation of both PI3K/AKT and Wnt/β-catenin pathways. In vivo, wogonoside significantly inhibited tumor formation.Conclusion: The results indicated that wogonoside could attenuate cSCC by reducing EMT, invasion and CSC properties. The efficacy of intervention may be related to inhibition of the PI3K/Akt and Wnt/β-catenin pathways. These novel findings could furnish new ideas on the potential therapeutic application of wogonoside in cSCC cancellation and cancer intervention.Keywords: cSCC, ALDH1, Wnt/β-catenin pathway, PI3K/AKT pathway, EMT

Yan Liu,1,2,* Meng Gao,3,* Juan An,2,* Xin Wang,4 Yan Jia,4 Junfeng Xu,4 Jihai Zhu,5 Jiantao Cui,1 Wenmei Li,1 Rui Xing,1 Li Song,6 Kejia Liu,6 Yuqi He,4 Jianqiu Sheng,4 Shengmei Qi,3 Yuanming Pan,1,4 Youyong Lu1 1Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Beijing Cancer Hospital/Institute, School of Oncology, Peking University, Beijing, Haidian District 100142, People’s Republic of China; 2Department of Basic Medical Sciences, Medical College of Qinghai University, Xining City, Qinghai 810001, People’s Republic of China; 3OnkoRx Ltd. Beijing, Beijing, Haidian District 100085, People’s Republic of China; 4Department of Gastroenterology, The 7th Medical Center of Chinese PLA General Hospital, Beijing, Dongcheng District 100700, People’s Republic of China; 5Department of Cardiothoracic Surgery, The Affiliated Hospital of Qinghai University, Xining City, Qinghai 810001, People’s Republic of China; 6Yidu Cloud (Beijing) Technology Co., Ltd. 8F, Health Work, Beijing, Haidian District 100083, People’s Republic of China*These authors contributed equally to this workCorrespondence: Youyong Lu, MD, Ph.D.Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Beijing Cancer Hospital/Institute, School of Oncology, Peking University, Beijing 100142, People’s Republic of ChinaTel +86-10-88196765Fax +86-10-88122437Email youyonglu@hsc.pku.edu.cnBackground: Gastrin (GAST) is a well-known hormone regulating gastric biofunctions in the secretion of acid and maintaining its structural integrity. Furthermore, the dysregulation of GAST is also involved in the development of various forms of cancer. However, there are some limitations for illustrating the cellular regulation of GAST and its regulatory mechanisms in gastric malignant transformation and the potential epigenetic regulators systematically.Methods: We explored the role of GAST expression in gastric cancer (GC) and normal tissues with the clinical features and investigated the potential relationship between GAST and STAT3/MMP11 pathway by gain or loss of function analyses. Besides, based on our microRNA/mRNA expression profiles, miR-30a-3p was the potential epigenetic regulator and additional experiments were performed to identify the hypothesis.Results: Elevated GAST expression was frequently detected in GC and was associated with worse outcomes (p< 0.001). And we firstly demonstrated that GAST was negatively regulated by miR-30a-3p. Moreover, GAST induced GC cell proliferation, migration and invasion mediating STAT3/MMP11 pathway in this study.Conclusion: MiR-30a-3p was the promising suppressor gene through negatively regulating the expression of GAST, and dysregulation of GAST was a prognostic signature associated cell proliferation and metastasis through STAT3/MMP11 pathway in GC.Keywords: gastrin, proliferation, invasion, miR-30a-3p, STAT3/MMP11 pathway, gastric cancer

Ya Li, Meng Gao, Kuo Zeng, Jia-xin Xing, Feng-ling Xu, Jin-feng Xuan, Xi Xia, Yong-ping Liu, Jun Yao, Bao-jie Wang School of Forensic Medicine, China Medical University, Shenyang 110122, People’s Republic of ChinaCorrespondence: Bao-jie Wang; Jun Yao Email wangbj77@163.com; yaojun198717@163.comBackground: Epidemiological studies have shown that genetic factors are among the causes of schizophrenia. Galanin receptor 1 is an inhibitory receptor of galanin that is widely distributed in the central nervous system. This study mainly explored the relationship between polymorphisms of the 5′ region of the GALR1 gene and schizophrenia in the northern Chinese Han population.Methods: A 1545 bp fragment of the 5′ regulatory region of the GALR1 gene was amplified and sequenced in 289 schizophrenia patients and 347 healthy controls.Results: Among the haplotypes composed of the 16 detected SNPs, the haplotype H3 was identified as conferring a risk of schizophrenia (p=0.011, OR=1.430, 95% CI=1.084– 1.886). In addition, the haplotypes H4 and H7 were both protective against schizophrenia (p=0.024, OR=0.526, 95% CI=0.298– 0.927; p=0.037, OR=0.197, 95% CI=0.044– 0.885, respectively). In the subgroup analysis by sex, it was found that seven SNP alleles (rs72978691, rs11662010, rs11151014, rs11151015, rs13306374, rs5373, rs13306375) conferred a risk of schizophrenia in females (p< 0.05), while allele G of rs7242919 (p=0.007) was protective against schizophrenia in females. Moreover, the rs72978691 AA+AC genotype (p=0.006, OR=1.874, 95% CI=1.196– 2.937, power=0.780), rs7242919 CC+CG genotype (p=0.002, OR=2.027, 95% CI=1.292– 3.180, power=0.861), rs11151014 GG+GT genotype (p=0.008, OR=1.834, 95% CI=1.168– 2.879, power=0.735), rs11151015 GG+AG genotype (p=0.002, OR=2.013, 95% CI =1.291– 3.137, power=0.843), rs13306374 CC+AC genotype (p=0.006, OR=1.881, 95% CI=1.198– 2.953, power=0.788), and rs13306375 GG+AG genotype (p=0.006, OR=1.868, 95% CI=1.194– 2.921, power=0.770) increased the risk of schizophrenia in females. The haplotype FH2 consisting of rs72978691, rs11662010, rs7242919, rs11151014, rs11151015, rs13306374, rs5373, and rs13306375 may also be associated with the risk of schizophrenia in females (p=0.024).Conclusion: This study identified an association between polymorphisms in the 5′ region of the GALR1 gene and schizophrenia, especially in females.Keywords: galanin receptor 1, schizophrenia, single-nucleotide variant, genetic polymorphism, northern Chinese Han population

Ziguang Xu,1,* Hongxia Li,2,* Yujie Dong,3,* Peng Cheng,4 Fang Luo,4 Shijun Fu,5 Min Gao,5 Lingfei Kong,1 Nanying Che3 1Department of Pathology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Pathology, Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Novogene Co., Ltd, Beijing, People’s Republic of China; 5Medical Affairs Department, Pfizer Oncology, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Nanying CheDepartment of Pathology, Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, No. 97 Ma Chang, Tongzhou District, Beijing 101149, People’s Republic of ChinaEmail nany_che@126.comLingfei KongDepartment of Pathology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, No. 7, Weiwu Road, Zhengzhou, Henan 450003, People’s Republic of ChinaEmail lfkong9@163.comBackground: Mesenchymal–epithelial transition (MET) exon14 skipping mutations represent a clinically unique molecular subtype of NSCLC. The prevalence rates of MET exon 14 skipping in lung adenocarcinoma (ADC) range from 0.9% to 4.0% in Asian populations. Since some somatic variants that do not encompass the MET exon 14 splice sites might also induce MET exon 14 skipping, the RNA-based sequencing is speculated as the most accurate method for detecting exon 14 skipping.Patients and Methods: A total of 951 NSCLC patients from two hospitals were enrolled in this study. MET exon14 skipping was detected using RNA-based next-generation sequencing (NGS). Also, immunohistochemistry (IHC) was performed in 405 samples simultaneously.Results: The overall estimated prevalence of MET exon 14 skipping was approximately 1.8% in ADCs and 1.7% in NSCLCs. The detection rate of MET exon 14 skipping from surgical resection specimen was 2.3% in NSCLCs and 2.0% in ADCs. The MET exon 14 skipping was identified in 6.6% of EGFR/KRAS/ALK/ROS1/RET-negative ADCs. Additionally, PD-L1 was found to be highly expressed in NSCLC patients harboring MET exon 14 skipping (P< 0.01).Conclusion: The prevalence of MET exon14 skipping in lung ADCs in the East Asian population was similar to that of the Western population as assessed by RNA-based NGS. The NSCLC patients with MET exon 14 skipping were older than those with other oncogenic driver mutations, such as EGFR, ALK, and ROS1. In addition, PD-L1 was highly expressed in NSCLC patients with MET exon 14 skipping.Keywords: non-small cell lung cancer, MET exon14 skipping, next-generation sequencing, PD-L1

Ming Gao,1,* Liying Liu,2,* Dianbao Zhang,3 Yudan Yang,1 Zhiwei Chang1 1Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People’s Republic of China; 2Department of Medical Record, The First People’s Hospital of Zhengzhou, Zhengzhou 450004, People’s Republic of China; 3Department of Oncology, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang 471003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ming GaoDepartment of Oncology, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou 450052, People’s Republic of ChinaEmail gaoming_zz@163.comIntroduction: Long non-coding RNA (lncRNA) was reported to be a crucial regulator in cancer. In this work, our purpose is to explore the biological roles of nuclear paraspeckle assembly transcript 1 (NEAT1) in gastric cancer (GC).Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect NEAT1 expression in GC cells and normal cells. GC cell behaviors after NEAT1 overexpression or downregulation were analyzed by Cell Counting Kit-8 assay, colony formation assay, wound-healing assay, and flow cytometry assay. Bioinformatic tools were used to analyze the significance of NEAT1 in GC. The involvement of microRNA-365a-3p (miR-365a-3p) and ATP-binding cassette subfamily C member 4 (ABCC4) in the biological roles of NEAT1 in GC progression was validated by luciferase activity reporter assay and rescue experiments.Results: We found NEAT1 increased expression in both GC tissues and cells and correlated with poorer overall survival of cancer patients. We found NEAT1 overexpression promotes, while its knockdown inhibits GC cell proliferation, colony formation, invasion, and cell cycle progression in vitro. Mechanism analyses showed that NEAT1 serves as a ceRNA to upregulate ABCC4 expression via sponging miR-365a-3p.Conclusion: In this study, we revealed a NEAT1/miR-365a-3p/ABCC4 triplet in GC progression, which may provide novel targeted therapy markers for GC.Keywords: long non-coding RNA, NEAT1, miR-365a-3p, ABCC4, gastric cancer

Huikang Yang,1,* Yufang He,1,* Yan Wang,2,* Ruimeng Yang,1 Nianhua Wang,1 Li-Ming Zhang,3,* Meng Gao,4 Xinqing Jiang1 1Department of Radiology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province 510640, People’s Republic of China; 2Department of Urology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province 510640, People’s Republic of China; 3School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou, Guangdong Province 510275, People’s Republic of China; 4National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, Guangdong Province 510006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinqing JiangDepartment of Radiology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Yuexiu District, Guangzhou, Guangdong Province 510640, People’s Republic of ChinaTel/Fax +86 13802961338Email eyjiangxq@scut.edu.cnMeng GaoNational Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Tianhe District, Guangzhou, Guangdong Province 510006, People’s Republic of ChinaTel/Fax +86 15521393090Email msmgao@scut.edu.cnIntroduction: Advanced tumor-targeted theranostic nanoparticles play a key role in tumor diagnosis and treatment research. In this study, we developed a multifunctional theranostic platform based on an amphiphilic hyaluronan/poly-(N-ϵ-carbobenzyloxy-L-lysine) derivative (HA-g-PZLL), superparamagnetic iron oxide (SPIO) and aggregation-induced emission (AIE) nanoparticles for tumor-targeted magnetic resonance (MR) and fluorescence (FL) dual-modal image-guided photodynamic therapy (PDT).Materials and Methods: The amphiphilic hyaluronan acid (HA) derivative HA-g-PZLL was synthesized by grafting hydrophobic poly-(N-ϵ-carbobenzyloxy-L-lysine) (PZLL) blocks onto hyaluronic acid by a click conjugation reaction. The obtained HA-g-PZLLs self-assembled into nanoparticles in the presence of AIE molecules and SPIO nanoparticles to produce tumor-targeted theranostic nanoparticles (SPIO/AIE@HA-g-PZLLs) with MR/FL dual-modal imaging ability. Cellular uptake of the theranostic nanoparticles was traced by confocal laser scanning microscopy (CLSM), flow cytometry and Prussian blue staining. The intracellular reactive oxygen species (ROS) generation characteristics of the theranostic nanoparticles were evaluated with CLSM and flow cytometry. The effect of PDT was evaluated by cytotoxicity assay. The dual-mode imaging ability of the nanoparticles was evaluated by a real-time near-infrared fluorescence imaging system and magnetic resonance imaging scanning.Results: The resulting theranostic nanoparticles not only emit red fluorescence for high-quality intracellular tracing but also effectively produce singlet oxygen for photodynamic tumor therapy. In vitro cytotoxicity experiments showed that these theranostic nanoparticles can be efficiently taken up and are mainly present in the cytoplasm of HepG2 cells. After internalization, these theranostic nanoparticles showed serious cytotoxicity to the growth of HepG2 cells after white light irradiation.Discussion: This work provides a simple method for the preparation of theranostic nanoparticles with AIE characteristics and MR contrast enhancement, and serves as a dual-modal imaging platform for image-guided tumor PDT.Keywords: aggregation-induced emission, MR imaging, dual-modal imaging, photodynamic therapy