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Hongyun Shu,1,&ast; Sisi Han,1,&ast; Weiping Qiu,1 Jianhong Li,1 Xiaoyong Zhang,1 Haicui Su,1 Hongjie Wu,2 Guojun Zhao,1 Qiaowen Li3 1Department of Cardiovascular Medicine, The Affiliated Qingyuan Hospital (Qingyuan People’s Hospital) of Guangzhou Medical University, Qingyuan, Guangdong, People’s Republic of China; 2Department of Urology, The Affiliated Qingyuan Hospital (Qingyuan People’s Hospital) of Guangzhou Medical University, Qingyuan, Guangdong, People’s Republic of China; 3Institute of Gerontology, The Affiliated Guangzhou Geriatric Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiaowen Li, Institute of Gerontology, Guangzhou Geriatric Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China, Email Stevenxzf@sina.com Guojun Zhao, Department of Cardiovascular Medicine, The Affiliated Qingyuan Hospital (Qingyuan People’s Hospital) of Guangzhou Medical University, Qingyuan, Guangdong, People’s Republic of China, Email zhaoguojun@gzhmu.edu.cnBackground: The monocyte to high-density lipoprotein cholesterol (MHR) and neutrophil to high-density lipoprotein cholesterol ratio (NHR) are novel comprehensive indicators reflecting the body’s inflammation and lipid metabolism. Previous studies have found that MHR and NHR are associated with the risk of cardiovascular and cerebrovascular events and death. However, the correlation between MHR, NHR, and the severity of newly diagnosed coronary artery disease (CAD) has not been thoroughly explored.Methods: In this retrospective study, we enrolled 1489 patients who underwent coronary angiography for the first time between January 2022 and December 2023, of which 1143 were diagnosed with CAD. The severity of CAD was gauged by the Gensini score (GS). The relationship between MHR and NHR with CAD was validated through logistic regression analysis, adjusting for traditional cardiovascular risk factors and medication therapy. The nonlinear relationship between MHR and NHR with CAD and GS was assessed by using restricted cubic spline (RCS) models. Their independent and combined predictive effects on CAD were evaluated through receiver operating characteristic (ROC) curve analysis.Results: MHR and NHR were independently associated with CAD (both P< 0.001). In the fully adjusted model, an increase in MHR was significantly associated with an increased odds ratio (OR) for CAD (OR=4.29, 95% CI 2.72– 6.78, P< 0.001). Sensitivity analysis revealed a consistent trend (P for trend< 0.05). RCS curve analysis indicated a nonlinear relationship between the two biomarkers and GS (P< 0.05) and there were clear inflection points. The area under the curve for predicting CAD was 0.68 for MHR and 0.69 for NHR, with optimal cut-off values of 0.42 (Youden index:0.29) and 5.43 (Youden index:0.31) respectively. Combined MHR and NHR has higher predictive value.Conclusion: MHR and NHR are independently associated with CAD, and there is a nonlinear correlation with the GS. Both have some predictive value for the severity of CAD.Keywords: monocyte to high-density lipoprotein cholesterol ratio, neutrophil to high-density lipoprotein cholesterol, coronary artery disease, coronary artery disease severity, Gensini score

Wenjuan Qiu,1 Ruifang Wang,1 Lili Liang,1 Yuning Sun,1 Rong Zhou,2 Xiaoli Wang,2 Wen Sun,3 Xuefan Gu1 1Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research, Shanghai, 200092, People’s Republic of China; 2Medical Affairs, GeneScience Pharmaceuticals Co. Ltd. (Gensci), Shanghai, 200233, People’s Republic of China; 3Beijing Intelligent Decision Medical Technology Co. Ltd., Beijing, 100028, People’s Republic of ChinaCorrespondence: Xuefan Gu, Email gu_xfan@163.comIntroduction: Growth hormone (GH) is crucial for immune system development and regulation, potentially benefiting COVID-19 outcomes. However, there are limited studies on the role of GH treatment in COVID-19 in children with short stature.Methods: We conducted a survey study to evaluate the association between GH treatment and COVID-19 risk in short stature children aged 7 to 18 years. Two groups were defined: GH Treated and GH Untreated. The primary endpoint was the proportion of children with COVID-19 histories. Secondary endpoints included the presence, severity, and duration of COVID-19 symptoms. Exploratory endpoints included the frequency of common colds after GH treatment. We further performed two-sample Mendelian randomization (MR) analyses to explore the causal relationship between GH levels and COVID-19 susceptibility, hospitalization, and severity using genome-wide association study summary-level data.Results: Of the 201 children, 113 (56.2%) reported COVID-19 history, and 149 (74.1%) used GH. The mean age was 11.02 ± 2.10 years. GH treatment was associated with a somewhat lower proportion of COVID-19 history (− 9.77%, 95% confidence interval [CI] − 26.41% to 6.87%; P = 0.289), and the odds ratio (OR) is 0.58 (95% CI 0.29 to 1.14, P = 0.120) after adjusting for confounders. Among the 113 children with COVID-19 histories, the highest body temperature was significantly lower in the GH Treated group (P = 0.040). In the MR analyses, for one unit increase in GH level, the OR was 0.95 (95% CI 0.92 to 0.99, P = 0.022) for COVID-19 susceptibility, 0.86 (95% CI 0.77 to 0.96, P = 0.007) for COVID-19 hospitalization, and 0.95 (95% CI 0.84 to 1.07, P = 0.392) for COVID-19 severity.Conclusion: GH treatment was associated with somewhat decreased COVID-19 susceptibility but was not statistically significant. Higher GH levels were causally associated with a significantly lower rate of COVID-19 susceptibility and hospitalization.Keywords: Mendelian randomization analysis, growth hormone treatment, COVID-19, children with short stature

Shaojie Li,1,&ast; Qiangqiang Feng,1,&ast; Jiayin Wang,1 Baofang Wu,1 Weizhi Qiu,1 Yiming Zhuang,2 Yong Wang,3 Hongzhi Gao1 1Department of Neurosurgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, 362000, People’s Republic of China; 2Internal Medicine, Quanzhou Quangang District Hillside Street Community Health Service Center, Quanzhou, Fujian, 362000, People’s Republic of China; 3Child and Adolescent Psychiatry, The Third Hospital of Quanzhou, Quanzhou, Fujian, 362000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong Wang; Hongzhi Gao, Email 120432246@qq.com; gaohongzhi@fjmu.edu.cnObjective: To develop a validated machine learning (ML) algorithm for predicting the risk of hospital-acquired pneumonia (HAP) in patients with traumatic brain injury (TBI).Materials and Methods: We employed the Least Absolute Shrinkage and Selection Operator (LASSO) to identify critical features related to pneumonia. Five ML models—Logistic Regression (LR), Extreme Gradient Boosting (XGB), Random Forest (RF), Naive Bayes Classifier (NB), and Support Vector Machine (SVC)—were developed and assessed using the training and validation datasets. The optimal model was selected based on its performance metrics and used to create a dynamic web-based nomogram.Results: In a cohort of 858 TBI patients, the HAP incidence was 41.02%. LR was determined to be the optimal model with superior performance metrics including AUC, accuracy, and F1-score. Key predictive factors included Age, Glasgow Coma Score, Rotterdam Score, D-dimer, and the Systemic Immune Response to Inflammation Index (SIRI). The nomogram developed based on these predictors demonstrated high predictive accuracy, with AUCs of 0.818 and 0.819 for the training and validation datasets, respectively. Decision curve analysis (DCA) and calibration curves validated the model’s clinical utility and accuracy.Conclusion: We successfully developed and validated a high-performance ML algorithm to assess the risk of HAP in TBI patients. The dynamic nomogram provides a practical tool for real-time risk assessment, potentially improving clinical outcomes by aiding in early intervention and personalized patient management.Keywords: traumatic brain injury, machine learning, hospital-acquired pneumonia, dynamic nomogram, imaging metrics

Wenbin Wang,1 Lin Liu,2 Weida Qiu,1 Chaolei Chen,1 Yuqing Huang,1 Anping Cai,1 Zhiqiang Nie,1 Yanqiu Ou,1 Yicheng Zhu,1 Yingqing Feng1 1Department of Cardiology, Hypertension Research Laboratory, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Medicine, The University of Hong Kong, Hong Kong, ChinaCorrespondence: Yingqing Feng; Yicheng Zhu, Department of Cardiology, Hypertension Research Laboratory, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, No. 106, Zhongshan 2nd Road, Yuexiu District, Guangzhou, 510080, People’s Republic of China, Email fengyingqing@gdph.org.cn; zhuyicheng@gdph.org.cnIntroduction: Traditional clinical risk factors are insufficient to estimate the residual risk of large-vessel ischemic stroke. Non-targeted lipidomic techniques provide an opportunity to evaluate these risks.Methods: Plasma samples were collected from 113 hypertensive individuals, including 55 individuals at high risk of ischemic stroke and 58 matched individuals, in a prospective nested case-control cohort. To identify dysregulated lipid metabolites, we conducted multivariate and univariate analyses. A classifier based on a cross-validated procedure was employed to select the optimal combination of lipid species and their ratios.Results: We identified 23 dysregulated lipid species in patients with and without ischemic stroke, including 16 (69.6%) up-regulated and 7 (30.4%) down-regulated lipid species. Through internal cross-validation, the optimal combination of two lipid features (phosphatidylcholine 34:2 and triglyceride 18:1/18:1/22:1 / phosphatidylcholine 34:2, referred to as ischemic stroke-related 2 lipid features - IS2LP) was selected, leading to a more precise prediction probability for ischemic stroke within 3.9 years. In the comparison of different risk factors, the traditional risk score, the IS2LP risk score, and the combination of the traditional risk score with IS2LP yield AUC values of 0.613(95% CI:0.509– 0.717), 0.833(95% CI:0.755– 0.911), and 0.843(95% CI:0.777– 0.916), respectively. The combination of the traditional risk score and IS2LP exhibited significantly improved discriminative performance, with an integrated discrimination improvement (IDI) of 0.31 (p< 0.001) and a continuous net reclassification improvement (NRI) of 1.06 (p < 0.001) compared to the traditional risk score.Conclusion: We identified new lipidomic biomarkers associated with the futural event of large-vessel ischemic stroke. These lipid species could serve as potential blood biomarkers for assessing the residual risk of ischemic stroke in hypertensive individuals.Keywords: hypertension, lipidomics, ischemic stroke, risk factors

Qingqing Luo,1,&ast; Yibo Quan,1,&ast; Wei Liu,1 Zixin Wu,1 Wenjing Qiu,1 Wenlong Liang,1 Ping Yang,1 Qing Huang,1 Guanwei Li,1 Jianchang Wei,1 Qiang Wang,1 Fei Shen,2 Wanglin Li,1 Feng He,3 Jie Cao1 1Department of Gastrointestinal Surgery, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510180, People’s Republic of China; 2Department of Thyroid Surgery, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510180, People’s Republic of China; 3Department of Nephrology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510180, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Cao, Department of Gastrointestinal Surgery, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510180, People’s Republic of China, Email eycaojie@scut.edu.cn Feng He, Department of Nephrology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510180, People’s Republic of China, Email eyhefeng@scut.edu.cnPurpose: Consensus molecular subtypes (CMS) are mainly used for biological interpretability and clinical stratification of colorectal cancer (CRC) in primary tumors (PT) but few in metastases. The heterogeneity of CMS distribution in metastases and the concordance of CMS between PT and metastases still lack sufficient study. We used CMS to classify CRC metastases and combine it with histopathological analysis to explore differences between PT and distant metastases.Patients and Methods: We obtained gene expression profiles for 942 PT samples from TCGA database (n=376) and GEO database (n=566), as well as 442 metastasis samples from GEO database. Among these, 765 PT samples and 442 metastasis samples were confidently identified with CMS using the “CMS classifier” and enrolled for analysis. Clinicopathological manifestation and CMS classification of CRC metastases were assessed with data from GEO, TCGA, and cBioPortal. Overall, 105 PT-metastasis pairs were extracted from 10 GEO datasets to assess CMS concordance. Tumor microenvironment (TME) features between PT and metastases were analyzed by immune-stromal infiltration with ESTIMATE and xCell algorithms. Finally, TME features were validated with multiplex immunohistochemistry in 27 PT-metastasis pairs we retrospectively collected.Results: Up to 64% of CRC metastases exhibited concordant CMS groups with matched PT, and the TME of metastases was similar to that of PT. For most common distant metastases, liver metastases were predominantly CMS2 and lung and peritoneal metastases were mainly CMS4, highlighting “seed” of tumor cells of different CMS groups had a preference for metastasis to “soil” of specific organs. Compared with PT, cancer-associated fibroblasts (CAF) reduced in liver metastases, CD4+T cells and M2-like macrophages increased in lung metastases, and M2-like macrophages and CAF increased in peritoneal metastases.Conclusion: Our findings underscore the importance of CMS-guided specific organ monitoring and treatment post-primary tumor surgery for patients. Differences in immune-stromal infiltration among different metastases provide targeted therapeutic opportunities for metastatic CRC.Keywords: colorectal cancer, primary tumors, metastases, consensus molecular subtypes, tumor microenvironment

Yunhao Yang,1,2 Fang Pang,1– 3 Min Zhou,1,2 Xiao Guo,1,2 Yan Yang,1,2 Wei Qiu,1,2 Cai Liao,1,2 Yang Chen,1,2 Chenglin Tang1,2 1College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, Chongqing, People’s Republic of China; 3Institute of Sports Biology, Shaanxi Normal University, Xi’an, Shaanxi, People’s Republic of ChinaCorrespondence: Chenglin Tang, Email tangchenglin@cqmu.edu.cnBackground: Electroacupuncture (EA) is used to treat inflammatory bowel disease (IBD). Nevertheless, the precise mechanisms by which this approach safeguards against obesity-induced intestinal barrier damage has not been fully understood.Objective: This study aimed to assess whether EA could ameliorate intestinal barrier damage that had been reversed in a mouse model of obesity induced by a high-fat diet (HFD) and whether this repair is correlated with ferroptosis and gut microbiota enhancement.Methods: To assess the potential of EA to prevent obesity and restore the intestinal barrier, we divided in C57BL/6J mice into two groups; one was fed with HFD and another one with a normal diet. Samples of stool, blood, fat, and intestinal epithelium were then evaluated, along with body weight.Results: Following EA, we observed a significant reduction in body weight, fat accumulation, and serum triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels; an increase was seen in high-density lipoprotein cholesterol (HDL-C) levels. EA also activated the Nrf2 signaling pathway; upregulated the expression of GPX4, FTH1, and SLC7A11; and downregulated the expression of TFR1. In addition, the administration of EA resulted in a notable modification of the gut microbiota composition, characterized by a decrease in the Firmicutes to Bacteroidetes ratio.Conclusion: EA had beneficial effects on weight loss and showed potential ability to repair the intestinal barrier by activating the Nrf2 signaling pathway, inhibiting intestinal inflammation and ferroptosis, and regulating the intestinal microbiota to treat IBD caused by HFD-induced obesity. Keywords: ferroptosis, electrostimulation, acupuncture, Chinese medicine, obesity, intestinal epithelium

Yixin Ding,1,&ast; Kongjia Wang,2,&ast; Shufen Zhao,1 Yu Li,3 Wensheng Qiu,1 Chunyang Zhu,1 Yan Wang,1 Chen Dong,1 Jiani Liu,1 Yangyang Lu,1 Weiwei Qi1 1Department of Oncology, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 2Department of Urology, Qingdao Municipal Hospital, Qingdao University, Qingdao, People’s Republic of China; 3Department of Gastrointestinal Surgery, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weiwei Qi, Email qwwqdfy@126.comPurpose: Kinetochore scaffold 1 (KNL1), a crucial protein during cell mitosis participating in cell division, was widely expressed in multiple kinds of cancers. However, the expression profile, the effect on cell biological function, tumor immune microenvironment, and predictive value of clinical prognosis in pan-cancer of KNL1 still require a comprehensive inquiry.Methods: The mRNA and protein expression profile of KNL1 was validated in pan-cancer using different databases. Six algorithms were used to explore the correlation between KNL1 and immune infiltration and the relationship between KNL1 and tumor mutation burden (TMB), microsatellite instability (MSI), and TIDE score were calculated. The diagnostic and clinical prognostic predictive ability of KNL1 was assessed. Differentially expressed genes (DEGs) of KNL1 were screened out and function enrichment analyses were performed in pancreatic adenocarcinoma (PAAD), stomach adenocarcinoma (STAD), and bladder urothelial carcinoma (BLCA). Finally, 8 cases of pancreatic adenocarcinoma tissues and paired adjacent tissues were collected for immunohistochemical (IHC) staining and the histological score (H-score) was calculated. Real-time PCR was performed in gastric cancer and bladder cancer cell lines.Results: KNL1 was abnormally upregulated in more than half of cancers across different databases. IHC and real-time PCR verified the up-regulated expression in cancer tissues in PAAD, gastric cancer, and BLCA. The satisfactory diagnostic value of KNL1 was indicated in 30 cancers and high KNL1 expression was associated with poorer overall survival (OS) in 12 cancers. The prognostic role of KNL1 as a predictive biomarker of PAAD was clarified. KNL1 played an active part in the cell cycle and cell proliferation. Moreover, KNL1 was likely to mold the Th2-dominant suppressive tumor immune microenvironment and was associated with TMB, MSI, and immune checkpoint-related genes in pan-cancer.Conclusion: Our study elucidated the anomalous expression of KNL1 and revealed that KNL1 was a promising prognostic biomarker in pan-cancer.Keywords: KNL1, bioinformatics, pan-cancer, immune infiltration, prognosis, clinical prognostic model

Jieying Wang,&ast; Chunchun Yu,&ast; Yuni Xu,&ast; Zhuolin Chen, Wenhua Qiu, Shaowen Chen, Hua Pei, Yeteng Zhong Department of Clinical Laboratory, The Second Affiliated Hospital of Hainan Medical University, Haikou, 570216, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yeteng Zhong, Department of Clinical Laboratory, The Second Affiliated Hospital of Hainan Medical University, Haikou, 570216, People’s Republic of China, Email zhongyeteng@163.comPurpose: Given the high burden of Tuberculosis (TB) in China, the prevalence of multidrug-resistant tuberculosis (MDR-TB) is significant. Whole-genome sequencing (WGS) of Mycobacterium tuberculosis (MTB) enables the identification of lineages, drug-resistant mutations, and transmission patterns, offering valuable insights for TB control, clinical diagnosis, and treatment.Methods: We collected 202 MDR-MTB strains from 3519 suspected pulmonary TB patients treated at The Second Affiliated Hospital of Hainan Medical University between July 2019 and June 2021. Proportional drug-susceptibility testing was performed using 8 common anti-tuberculosis drugs. Subsequently, the genotypic drug resistance and genetic characteristics were analyzed by the WGS.Results: Lineages are identified by TB-profiler revealed 202 MDR-MTB strains, showcasing three predominant lineages, with lineage 2 being the most prevalent. Close genomic relatedness analysis and evidence of MTB transmission led to the formation of 15 clusters comprising 42 isolates, resulting in a clustering rate of 20.8%. Novelty, lineage 2.1 (non-Beijing) accounted for 27.2% of the MDR-MTB strains, which is rare in China and Neighboring countries. Regarding first-line anti-TB drugs, genes associated with rifampicin resistance, primarily the rpoB gene, were detected in 200 strains (99.0%). Genes conferring resistance to isoniazid, ethambutol, and streptomycin were identified in 191 (94.5%), 125 (61.9%), and 100 (49.5%) strains, respectively. Among the second-line drugs, 97 (48.0%) strains exhibited genes encoding resistance to fluoroquinolones. Comparing the results to phenotypic drug susceptibility-based testing, the sensitivity of WGS for detecting resistance to each of the six drugs (rifampicin, isoniazid, ethambutol, ofloxacin, kanamycin, capreomycin) was 90% or higher. With the exception of ethambutol, the specificity of WGS prediction for the remaining drugs exceeded 88%.Conclusion: Our study provides crucial insights into genetic mutation types, genetic diversity, and transmission of MDR-MTB on Hainan Island, serving as a significant reference for MDR-MTB surveillance and clinical decision-making.Keywords: tuberculosis, MDR-TB, whole-genome sequencing, WGS, genetic diversity, Hainan Island, China

Junwang Gu,&ast; Qi Wang,&ast; Xuanhui Wu, Han Zhang, Chunmei Wu, Wei Qiu School of Public Health and Health Management, Gannan Medical University, Ganzhou, Jiangxi Province, 341000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Qiu; Chunmei Wu, Tel/Fax +86-7978169236, Email qw21046@163.com; wuchunmei82@qq.comBackground: Comorbidity is a common problem among elderly people, significantly damaging individuals’ health and healthcare systems. However, observational studies may be susceptible to residual confounding factors and bias. The present study aimed to assess the causal effect of common chronic disease comorbidity using the Mendelian randomization (MR) approach.Methods: Data for the present study were obtained from a community survey conducted between 2018 and 2020 in four counties in Ganzhou City, southern China. A cross-sectional survey was conducted using a multi-stage stratified random sampling method. A total of 1756 valid questionnaires were collected to analyze common chronic disease comorbidities. Genetic variants associated with hypertension, diabetes, stroke, and hyperlipidemia-related factors were selected as instrumental variables for univariate and multivariate MR analyses.Results: The self-reported prevalence of chronic disease in the older adult population in Southern China was 68.1%, with hypertension (46.1%), diabetes (10.5%), and hyperlipidemia (8.5%) being the three most common conditions. The prevalence of chronic disease comorbidity was 20.7% among the 12 chronic diseases studied. Hypertension was identified as a predictor of diabetes (OR [95% CI]: 1.114 [1.049, 1.184], p < 0.001), and diabetes mellitus was equally identified as a risk factor for hypertension (OR [95% CI]: 1.118 [1.069, 1.187], p < 0.001). Furthermore, high triglyceride levels were identified as a risk factor for hypertension (OR [95% CI]: 1.262 [1.129, 1.411], p < 0.001). In contrast to intracranial hemorrhages, hypertension had a significant impact on ischemic stroke (OR [95% CI]: 1.299 [1.161, 1.454], p < 0.001).Conclusion: The causal association between multiple cardiovascular and metabolism-related diseases is mediated by hypertension, with a bidirectional cause-and-effect relationship between hypertension and diabetes. Hypertension is a risk factor for ischemic stroke, and the hyperlipidemia-related factor triglycerides (TG) influence hypertension. Therefore, prioritizing hypertension prevention and control in the elderly is critical for effective chronic disease management.Keywords: hypertension, diabetes, hyperlipidemia, stroke, causal, mendelian randomization

Jieying Wang,&ast; Zhuoling Chen,&ast; Yuni Xu, Wenhua Qiu, Shaowen Chen, Hua Pei, Yeteng Zhong Department of Clinical Laboratory, The Second Affiliated Hospital Hainan Medical University, Haikou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yeteng Zhong; Hua Pei, Department of Clinical Laboratory, The Second Affiliated Hospital Hainan Medical University, Haikou, People’s Republic of China, Email zhongyeteng@163.com; phzmh61@aliyun.comBackground: China has seen a drastic increase in the incidence of non-tuberculous mycobacteria (NTM) infection, which is a notable public health issue. Due to a lack of reliable epidemiological surveillance information, there is a need to gather accurate epidemiological and surveillance data, which can help clinicians effectively treat NTM patients. Moreover, drug susceptibility testing for NTM is not frequently performed in China. This retrospective study, therefore, determined the prevalence and resistance characteristics of NTM to provide a reference to control the NTM epidemic.Methods: Sputum, alveolar lavage fluid, and other respiratory specimens were collected from 3025 patients with suspected pulmonary tuberculosis attending The Second Affiliated Hospital of Hainan Medical University from January 2014 to December 2021. Strain identification and species distribution of NTM were performed by DNA chip technology and gene sequencing, and the drug resistance of NTM isolates was evaluated by calculating the minimum inhibitory concentration through antimicrobial susceptibility testing for NTM.Results: From 2014 to 2021, 373 strains of NTM were isolated and identified from respiratory specimens of 3025 suspected tuberculosis patients. Except in 2014, NTM-infected patients accounted for more than 10% of suspected tuberculosis patients in other years. The median age of patients with NTM infection was 62.0 years (53.0, 71.0), and the male-to-female ratio among these patients was 0.79:1. Among culture-positive strains, 12.3% (373/3040; 95% CI 11.1– 13.4%) were identified as NTM comprising forty species of NTM. The forty species of NTM included 23 slow-growing mycobacteria (SGM) and 17 rapidly-growing mycobacteria (RGM). Among the NTM isolates, 58.7% (219/373; 95% CI 53.7– 63.7%) were SGM and 41.3% (154/373; 95% CI 36.3– 46.3%) were RGM. M.avium complex(MAC)(41.3%; 95% CI 36.3– 46.3%) and M.abscessus complex (MABC)(33.2%; 95% CI 28.4– 38.0%) were the most frequently detected species, followed by M.simiae Complex (11.8%; 95% CI 8.5– 15.1%), M.fortuitum group (5.1%; 95% CI 2.9– 7.3%), and others. Drug sensitivity test results showed that most of the NTM isolates were susceptible to amikacin and clarithromycin with a drug resistance rate of less than 10%. However, clarithromycin could induce drug resistance, followed by linezolid and moxifloxacin, and their drug resistance rate was less than 50%.Conclusion: During 2014– 2021, the number of NTM isolates detected in the respiratory specimens of the study patients in The Second Affiliated Hospital of Hainan Medical University increased year by year. M. intracellulare is the most common pathogenic NTM species, and there is a high incidence of NTM infection on Hainan Island. Our findings might be of great importance for diagnosing and treating this patient population in Hainan.Keywords: Mycobacterium, non-tuberculous mycobacteria, pulmonary disease, drug resistance

Weiling Qiu, Chen Zheng, Shumin Huang, Yuanyuan Zhang, Zhimin Chen Department of Pulmonology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Zhimin Chen, Department of Pulmonology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, No. 3333, Binsheng Road, Binjiang District, Hangzhou, Zhejiang, 310052, People’s Republic of China, Tel +86-571-88873731, Fax +86-571-86658672, Email zmchen@zju.edu.cnObjective: This study aimed to explore the epidemiological trend and clinical characteristics of respiratory syncytial virus (RSV) infection among inpatient children with lower respiratory tract infection (LRTI) before and during the coronavirus disease 2019 (COVID-19) pandemic.Methods: A retrospective study of inpatients with LRTI was conducted at the Department of Pulmonology, The Children’s Hospital, Zhejiang University School of Medicine (Hangzhou, China) from January 2019 to December 2021. All respiratory specimens were tested for common respiratory pathogens. The clinical data in children with RSV-induced LRTI in the past three years were collected and analyzed.Results: A total of 11,290 patients were enrolled, and RSV positive cases were 402 (7.6%), 288 (9.6%), 415 (13.8%) in 2019, 2020, 2021, respectively, with a significant statistical difference of the RSV positive rate among the three groups (p < 0.001). Most patients were under 2-year old, especially under 1-year old, and the median age of patients was 4 months, 5 months, 6 months in 2019, 2020, 2021, respectively, with a tendency to increase in age. In terms of the seasonal distribution, most patients of LRTI with RSV infection were admitted in winter, while in 2021 compared with in 2019, the cases significantly reduced in winter and increased in autumn. From 2019 to 2021, there was an increase in autumn trend year by year.Conclusion: RSV infection was still an important cause of hospitalization in children with LRTI after the outbreak of COVID-19, and its proportion increased gradually. LRTI caused by RSV is still more common in infants under 1-year old, but there is a trend of increasing in older children. What deserves the attention of pediatricians and Center for Disease Control is that the incidence of RSV infection continues to rise in autumn, and the difference in seasonal distribution is narrowed.Keywords: respiratory syncytial virus, RSV, COVID-19, lower respiratory tract infection, non-pharmaceutical interventions

Qingquan Wei,1,&ast; Wei Qiu,1,&ast; Qing Liu,1,2 Yanyun Jiang1 1Department of Ophthalmology, Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200336, People’s Republic of China; 2Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, 200080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qing Liu; Yanyun Jiang, Department of Ophthalmology, Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200335, People’s Republic of China, Tel +8618121226956, Email LQ1098@shtrhospital.com; JYY3378@shtrhospital.comPurpose: The purpose of this study was to explore the changes in macular thickness (MT) in normal people, patients without obvious diabetic retinopathy (NDR) and patients with nonproliferative diabetic retinopathy (NPDR) and to study the possible risk factors for early diabetic retinopathy (DR).Methods: Thirty-one healthy individuals, 40 people with no sign of DR and 60 people with mild NPDR were included in this cross-sectional study. All patients underwent a complete ophthalmological examination. Optical coherence tomography (OCT) was used to measure the MT of each participant. The potential relationship between MT and systemic risk factors for DR, including diabetes duration, body mass index (BMI), hemoglobin A1c (HbA1c), serum lipids, and blood pressure, was analyzed.Results: The MT of the right and left eyes in the central and inner ring regions of the NPDR group and NDR group were significantly different from that in the control group. The MTs of the right and left eyes in the central region and inner ring region were also significantly different between the NPDR group and NDR group, but the MTs of the right and left eyes in the outer ring region were not significantly different among the three groups. Diabetic duration, total cholesterol (TC), triglycerides (TGs), systolic pressure, and diastolic pressure were positively correlated with the MT of the right and left eyes in the central region.Conclusion: MT increases, especially in the central region and inner ring, may be the first structural retinal change in diabetic patients and is related to the duration of diabetes, TC, TG, systolic pressure and diastolic pressure.Keywords: diabetic retinopathy, macular thickness, optical coherence tomography, risk factors

Liya Fu,1,2,&ast; Wanlong Zhu,1,2,&ast; Dongmei Tian,1,2 Yong Tang,2,3 Yun Ye,1 Qiming Wei,1 Chengbin Zhang,1 Wenqiao Qiu,2 Dalian Qin,2 Xuping Yang,1,2 Yilan Huang1,2 1Department of Pharmacy, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 2School of Pharmacy, Southwest Medical University, Luzhou, People’s Republic of China; 3State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, 999078, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuping Yang; Yilan Huang, Department of Pharmacy, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China, Email yangxuping6552@163.com; lzyxyyxp123@163.comPurpose: Anoectochilus roxburghii (Wall.) Lindl. polysaccharides (ARPs) have been reported to exhibit multiple pharmacological activities including anti-inflammatory and anti-hyperglycemia. This study aims to investigate the effect of ARPs on cognitive dysfunction induced by high fat diet (HFD).Methods: Six-week-old male mice were treated with ARPs by dietary supplementation for 14 weeks. The effect of ARPs on cognitive function was determined by assessing the changes in spatial learning and memory ability, neurotrophic factors in hippocampus, inflammatory parameters, intestinal barrier integrity, and gut microbiota.Results: ARPs supplementation can effectively ameliorate cognitive dysfunction, decrease the phosphorylation levels of Tau protein in hippocampus. Meanwhile, the increased body weight, plasma glucose, total cholesterol, inflammatory factors induced by HFD were abolished by ARPs treatment. Furthermore, ARPs treatment restored the intestinal epithelial barrier as evidenced by upregulation of intestinal tight junction proteins. Additionally, ARPs supplementation significantly decreased the relative abundance of several bacteria genus such as Parabacteroides, which may play regulatory roles in cognitive function.Conclusion: These results suggest that ARPs might be a promising strategy for the treatment of cognitive dysfunction induced by HFD. Mechanistically, alleviation of cognitive dysfunction by ARPs might be associated with the “gut-brain” axis.Graphical Abstract: Keywords: Anoectochilus roxburghii (Wall.) Lindl. polysaccharides, diet-induced-obesity, cognitive dysfunction, gut microbiota, “gut-brain” axis

Wenli Qiu,1 Haibin Chen,2 Jian Zhang,3 Ren Shuai,1 Huifeng Zhang,1 Kai Guo,1 Li Zhu,1 Zhongqiu Wang1 1Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 2Science and Technology Department, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 3Department of Radiology, Liyang Traditional Chinese Medicine Hospital, Changzhou, Jiangsu, People’s Republic of ChinaCorrespondence: Zhongqiu WangDepartment of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong Road, Nanjing, 210029, Jiangsu Province, People’s Republic of ChinaTel +86 25 8861 8472Fax +86 25 8661 8139Email zhq200105@sina.comPurpose: To assess the performance of high-resolution computed tomography (HRCT) in discriminating the consolidation pattern of pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma from lobar pneumonia.Patients and Methods: This retrospective study comprised 26 patients with pathologically confirmed consolidation pattern of pulmonary MALT lymphoma (12 men and 14 women; mean age, 59.4± 12.1 years) and 36 patients with lobar pneumonia confirmed by body fluids or respiratory secretion culture (16 men and 20 women; mean age, 41.8± 26.3 years). Two radiologists independently evaluated the CT images. The effectiveness of these variables in distinguishing lobar pneumonia from MALT lymphoma was analyzed using logistic regression analysis.Results: The average age of lobar pneumonia patients was younger than that of MALT lymphoma patients (p=0.002). The respiratory symptom was more common in lobar pneumonia than MALT lymphoma (p=0.002). Signs of bronchiectasis within the consolidation and bulging of interlobar fissure occurred significantly more often in MALT lymphoma than pneumonia (69.2% vs 11.1%, p< 0.0001; 46.2% vs 19.4%, p=0.024). We used the predictors with p< 0.05 (age, respiratory symptoms, bronchiectasis, and bulging of interlobar fissure) to construct a logistic regression model. The area under curve (AUC), negative predictive value (NPV), positive predictive value (PPV), sensitivity, specificity, and accuracy were 0.891, 84.21%, 83.33%, 88.89%, 76.92%, and 83.87% for discriminating lobar pneumonia from MALT lymphoma.Conclusion: Middle-aged, presence of mild clinical symptoms, bronchiectasis and bulging of the interlobar fissure on chest CT images are potential markers to distinguish pulmonary MALT lymphoma from lobar pneumonia.Keywords: high-resolution computed tomography, pulmonary mucosa-associated lymphoid tissue lymphoma, lobar pneumonia, diagnosis

Wenli Qiu,1 Zhongqiu Wang,1 Rong Chen,2 Haibo Shi,3 Yanxia Ma,4 Hongli Zhou,5 Muhan Li,4 Wenting Li,4 Haibin Chen,6 Hongguang Zhou7 1Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, Republic of China; 2Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA; 3Department of Oncology, Wuxi Xishan Hospital of Traditional Chinese Medicine, Wuxi, Jiangsu, Republic of China; 4Institute of Oncology, The First Clinical Medical College, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, Republic of China; 5The First Clinical Medical College, Liaoning University of Chinese Medicine, Shenyang, Liaoning, Republic of China; 6Science and Technology Department, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, Republic of China; 7Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, Republic of ChinaCorrespondence: Hongguang ZhouDepartment of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong Road, Nanjing 210029, Jiangsu Province, Mainland ChinaTel +86 25 8861 8472Fax +86 25 8661 8139Email zhouhongguang2002@163.comPurpose: Xiaoai Jiedu recipe (XJR), a formula long used by Chinese National Medical Professor Zhou Zhongying, has potent antitumor properties, but the molecular mechanism is still unclear. The aim of the study was to investigate the antitumor mechanism of XJR on hepatocellular carcinoma (HCC) by focusing on miRNA.Methods: Three concentrations of XJR (low, middle, and high) were used to treat tumor xenograft mice models. Microarray technology was used to identify the differential expressed genes after XJR treatment, and bioinformatic tools and luciferase reporter assay to predict the potential pathways. HepG2 cells were transfected with inhibitor of miR-200b-3p to detect the effect of miR-200b-3p and Notch1 on tumor growth.Results: XJR effectively exerted anti-HCC effect both in vitro and in vivo. MiRNA chip analysis results showed that the expression of 75 miRNAs was upregulated and 158 miRNAs was downregulated in blood from XJR-treated mice. Further validation by using real-time polymerase chain reaction (RT-PCR) assay showed that the expression of five miRNAs (miR-453, miR-200b-3p, miR-135a-1-3p, miR-1960, miR-378a-5p, and miR-466f) was consistent with the results of miRNA chip analysis. Among them, miR-200b-3p was selected as candidate for further research. Results of the MTT, migration, and wound healing assays showed that down-expression of miR-200b-3p abrogated the effect of XJR on cell growth and metastasis. Luciferase reporter assay confirmed that Notch1 was the direct target of miR-200b-3p. XJR significantly decreased Notch1 expression in HepG2 cells, whereas miR-200B-3p inhibitor abrogated the XJR-induced decrease in Notch1 expression.Conclusion: This study indicated that XJR could effectively inhibit HCC and might exert its antitumor effect through the miR‐200b-3p/Notch1 axis. These findings provided new avenues for the use of XJR for prevention and treatment of HCC.Keywords: Xiaoai Jiedu recipe, hepatocellular carcinoma, miR‐200b-3p, Notch1

Qinghua Du,1,* Jin Liu,1,* Da Tian,1 Xuelei Zhang,1 Jinwei Zhu,1 Weiwen Qiu,2 Jun Wu3 1Neurosurgery Department, Lishui City People’s Hospital, Lishui 323000, People’s Republic of China; 2Neurology Department, Lishui City People’s Hospital, Lishui 323000, People’s Republic of China; 3Pathology Department, Lishui City People’s Hospital, Lishui 323000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun Wu; Weiwen Qiu Email wwwwjjjj924@163.com; weiwenq@hotmail.comBackground: Glioma is one of the leading causes of cancer-related deaths. This study aimed to investigate the function and mechanism of long noncoding RNA (lncRNA) LINC00173 in the regulation of glioma progression.Methods: LINC00173 expression was measured using qRT-PCR. Survival rate was analyzed through Kaplan–Meier method. CCK8, colony formation and EdU assays were performed to measure cell proliferation while transwell was used to determine cell migration and invasion. Luciferase reporter assay was conducted to test RNA interaction.Results: LINC00173 expression was elevated in glioma tissues and cells. LINC00173 high expression predicted poor prognosis. Loss of LINC00173 inhibited proliferation, migration and invasion. LINC00173 interacted with miR-765 to enhance NUTF2 expression. MiR-765 expression was negatively correlated with LINC00173 and NUTF2 in glioma tissues. NUTF2 level was increased in glioma tissues. NUTF2 overexpression rescued the potential of proliferation, migration and invasion in LINC00173-silenced cells.Conclusion: Our research demonstrated that LINC00173 promotes glioma progression through targeting miR-765/NUTF2 axis.Keywords: LINC00173, miR-765, NUTF2, glioma

Tao Xu,1,2 Bin Wang,1,2 Limin Cao,1,2 Weihong Qiu,1,2 Zhuang Zhang,1,2 Ailian Chen,1,2 Weihong Chen1,2 1Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, People’s Republic of China; 2Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, People’s Republic of ChinaCorrespondence: Weihong ChenDepartment of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, People’s Republic of ChinaTel +86 27 83691677Email wchen@mails.tjmu.edu.cnBackground: Obesity is reported to be associated with oxidative stress which can cause lipid peroxidation. However, the effects of gain in various weight-related anthropometric indices on lipid peroxidation remain unclear. We aimed to examine the cross-sectional and longitudinal associations between altered weight-related anthropometric indices and a marker of lipid peroxidation among urban adults in China.Methods: A total of 3762 participants from the Wuhan-Zhuhai cohort were included in the present study, with a follow-up of 3 years. Six weight-related anthropometric indicators were measured and calculated, including waist circumference (WC), body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), a body shape index (ABSI), and body adiposity index (BAI). Individual urinary 8-iso-prostaglandin-F2α (8-iso-PGF2α) was determined via enzyme-linked immunosorbent assay to evaluate lipid peroxidation. We used generalized linear models to analyze the cross-sectional and longitudinal associations of weight-related anthropometric indices with a marker of lipid peroxidation and stratified analyses to estimate effect modification.Results: We found significant relationships between WHR, WHtR, ABSI, and urinary 8-iso-PGF2α at baseline. Each 1% increase in WHR, WHtR, and ABSI was significantly associated with a 0.007, 0.004, and 0.104 increase in log-transformed 8-iso-PGF2α concentration, respectively (P< 0.05). In longitudinal analysis, positive dose–response relationships were observed between gains in BMI, BAI, and increased 8-iso-PGF2α after adjusting for potential confounders (Ptrend< 0.05). We also found that gender and smoking status modified the association of BMI gain and 8-iso-PGF2α increment, and such an association was more obvious in female and non-smokers.Conclusion: Our research implied that gain in anthropometric indices may result in a higher level of lipid peroxidation.Keywords: weight-related anthropometric indices, lipid peroxidation, obesity, cohort study

Gehang Ju,1 Keyu Yan,1 Youwei Xu,2 Shilin Chen,3 Zhonghui Zheng,2 Wen Qiu4 1School of Pharmacy Lanzhou University, Lanzhou University, Lanzhou, People’s Republic of China; 2Research Institute, Shandong Xinhua Pharmaceutical Company Limited, Shandong, People’s Republic of China; 3The Department of Analysis, Chengdu Fanweixi Pharmaceutical Technology Company, Limited, Chengdu, People’s Republic of China; 4Phase I Clinical Unit, Lanzhou University Second Hospital, Lanzhou, People’s Republic of ChinaCorrespondence: Wen Qiu Tel/ Fax +86-931-8487117Email qiuwenmm@sina.comPurpose: Glimepiride, an FDA-approved oral hypoglycemic drug, is a long-acting sulfonylurea (SU), used for treating type 2 diabetes. The study aimed to evaluate the bioequivalence and safety profiles of two different formulations of glimepiride 1 mg from two different manufactures in healthy Chinese subjects in the fasting and fed state in order to acquire adequate pharmacokinetic evidence for registration approval of the test formulation.Patients and Methods: This study is an open-label, two-period, two-sequence, randomized, two-way crossover pharmacokinetic study in healthy Chinese subjects in the fasting and fed state. Seventy-two subjects were randomly assigned to the fasting group and the fed group (n=36 each). We collected blood samples, 24-h post drug administration. The plasma concentration of glimepiride was assessed using HPLC coupled with mass spectrometry. The following parameters were evaluated: AUC0-inf, AUC0-last, Cmax, t1⁄ 2, Tmax, and λz. Safety was determined based on the occurrence of adverse events (AEs) and laboratory examinations (biochemistry, hematology, and urinalysis) throughout the entire study period.Results: The geometric mean ratios (GMR) amongst the two glimepiride formulations for the primary pharmacokinetic parameters, ie, AUC0-inf, AUC0-last, and Cmax as well as the corresponding 90% CIs, were all within the range of 80.00– 125.00% in the fasting and fed state. The safety profile for both treatments was comparable.Conclusion: PK analysis revealed that the test and reference formulations of glimepiride were bioequivalent and well tolerated in healthy Chinese subjects. Chinese Clinical Trials Registry identifier: CTR20171121.Clinical Trial Registration Number: CTR20171121.Keywords: glimepiride, bioequivalence, pharmacokinetics, HPLC-MS/MS, adverse event

Jianlu Song,* Ting Yan,* Wangwang Qiu, Youben Fan, Zhili Yang Center of Thyroid and Parathyroid, Department of Thyroid, Parathyroid, Breast and Hernia Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhili Yang; Youben FanCenter of Thyroid and Parathyroid, Department of Thyroid, Parathyroid, Breast and Hernia Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, People’s Republic of ChinaTel +86 21 24058412Fax +86 21 24058933Email yangzhililaoshi@126.com; fanyouben2006@163.comPurpose: To investigate the risk factors for cervical lymph node metastasis (LNM) in papillary thyroid microcarcinoma (PTMC).Patients and Methods: In total, 3686 patients with PTMC who underwent initial surgery in Shanghai Jiao Tong University affiliated Sixth People’s Hospital from January 2010 to December 2019 were retrospectively analyzed. Univariate and multivariate analyses were conducted to identify risk factors associated with cervical LNM.Results: Male gender [odds ratio (OR) =1.420, P < 0.001], age < 55 years (OR =2.128, P < 0.001), tumor size > 6.5 mm (OR =2.112, P < 0.001), lymphovascular invasion (LVI) (OR =2.110, P =0.016), multifocality (OR =1.358, P =0.022), extrathyroidal extension (ETE) (OR =1.598, P < 0.001), and lateral LNM (LLNM) (OR =6.383, P < 0.001) served as independent risk factors for central LNM (CLNM). Moreover, male gender (OR =1.668, P =0.001), tumor size > 6.5 mm (OR =2.223, P < 0.001), chronic lymphocytic thyroiditis (OR =1.402, P =0.021), LVI (OR =4.582, P < 0.001), ETE (OR =1.393, P=0.023), and CLNM (OR =6.212, P < 0.001) served as independent risk factors for LLNM. Furthermore, solitary PTMC with lesions in the upper third of the thyroid gland were more associated with LLNM than lesions in the other regions.Conclusion: This study suggests that meticulous evaluation of risk factors associated with LNM is required in order to guide the surgical treatment of PTMC patients in clinical practice.Keywords: papillary thyroid microcarcinoma, predictors, central lymph node metastasis, lateral lymph node metastasis, extrathyroidal extension

Heng He, 1, 2 Bin Wang, 1, 2 Min Zhou, 1, 2 Limin Cao, 1, 2 Weihong Qiu, 1, 2 Ge Mu, 1, 2 Ailian Chen, 1, 2 Shijie Yang, 1, 2 Weihong Chen 1, 2 1Department of Occupational & Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, People’s Republic of China; 2Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, People’s Republic of ChinaCorrespondence: Weihong ChenDepartment of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, People’s Republic of ChinaTel +86 27 83691677 Email wchen@mails.tjmu.edu.cnBackground: Previous studies reported that obesity indices were inversely associated with lung function. However, the underlying mechanisms remain unclear. We aimed to assess the potential mediating effect of systemic inflammation in the associations between obesity indices and lung function decline among a general population.Methods: We conducted a cross-sectional study among 3442 participants from the Wuhan-Zhuhai cohort. Plasma C-reactive protein (CRP) was assayed as a marker of systemic inflammation. The relationships among several obesity indices (body mass index, BMI; waist circumference, WC; waist-to-hip ratio, WHR; waist-to-height ratio, WHtR), plasma CRP and lung function were assessed by generalized linear models. The role of CRP in the associations between obesity indices and lung function was analyzed using mediation analysis.Results: We observed inverse associations between abdominal obesity indices (WC, WHR and WHtR) and lung function parameters, including forced expiratory volume in 1 s (FEV 1) and forced vital capacity (FVC) (all P< 0.05). Each 1-unit increase in WC was associated with a 3.39 mL decrease in FEV 1 and a 3.96 mL decrease in FVC (all P< 0.05). Each 1% increase in WHR and WHtR was associated with a 5.42 mL and a 14.23 mL decrease in FEV 1, and a 5.70 mL and a 16.92 mL decrease in FVC (all P< 0.05). Mediation analysis indicated that plasma CRP partly mediated the associations between abdominal obesity and lung function. The mediated proportions of CRP in associations of WC, WHR and WHtR with FEV 1 were 7.96%, 9.59% and 5.76%, respectively. The mediated proportions of CRP in associations of WC and WHR with FVC were 8.33% and 11.40%, respectively.Conclusion: Abdominal obesity indices were negatively associated with lung function, and the associations may be partly mediated by systemic inflammation.Keywords: abdominal obesity, systemic inflammation, lung function, mediation analysis

© 2014 Bunyavanich et al.; licensee BioMed Central Ltd.Background: Allergic rhinitis is a common disease whose genetic basis is incompletely explained. We report an integrated genomic analysis of allergic rhinitis. Methods. We performed genome wide associa

Wenli Qiu,1 Na Duan,1 Xiao Chen,1 Shuai Ren,1 Yifen Zhang,2 Zhongqiu Wang,1 Rong Chen3 1Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2Department of Pathology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 3Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USACorrespondence: Zhongqiu WangDepartment of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong Road, Nanjing 210029, Jiangsu Province, People’s Republic of ChinaTel +86 25 8661 8472Fax +86 25 8661 8139Email zhq200105@sina.comPurpose: To assess the performance of combining computed tomography (CT) texture analysis with machine learning for discriminating different histopathological grades of pancreatic ductal adenocarcinoma (PDAC).Methods: From July 2012 to August 2017, this retrospective study comprised 56 patients with confirmed histopathological PDAC (32 men, 24 women, mean age 64.04±7.82 years) who had undergone preoperative contrast-enhanced CT imaging within 1 month before surgery. Two radiologists blinded to the histopathological outcome independently segmented lesions for quantitative texture analysis. Histogram features, co-occurrence, and run-length texture were calculated. A support-vector machine was constructed to predict the pathological grade of PDAC based on preoperative texture features.Results: Pathological analysis confirmed 37 low-grade PDAC (five well-differentiated/grade I and 32 moderately differentiated/grade II) and 19 high-grade PDAC (19 poorly differentiated/grade III) tumors. There were no significant differences in clinical or biological characteristics between patients with high-grade and low-grade tumors (P>0.05). There were significant differences between low-grade PDAC and high-grade PDAC on nine histogram features, seven run-length features, and two co-occurrence features. Cluster shade was the most important predictor (sensitivity 0.315). Using these texture features, the support-vector machine achieved 86% accuracy, 78% sensitivity, 95% and specificity.Conclusion: Machine learning–based CT texture analysis accurately predicted histopathological differentiation grade of PDAC based on preoperative texture features, leading to maximization patient survival and achievement of personalized precision treatment.Keywords: computed tomography, texture analysis, machine learning, pancreatic ductal adenocarcinoma, histopathological grade

Jiarui Yang,1,* Yushi Liu,1,* Yanhui Xu,1,* Xiaodan Li,1,* Jiayu Fu,1 Xiaodan Jiang,1 Yilin Chou,1 Jiahui Ma,1 Ran Hao,1 Rong Zhang,2 Weiqiang Qiu,1 Xuemin Li11Department of Ophthalmology, Peking University Third Hospital, Beijing, People’s Republic of China; 2Department of Neurobiology, Health Science Center, School of Basic Medical Sciences, Peking University, Beijing, People’s Republic of China*These authors contributed equally to this workPurpose: To present a new ocular nebulization therapy for the treatment of dry eye disease (DED) and investigate the efficacy of vitamin B12 (VB12) and oxytocin (OXT) nebulization with clinical parameters and in vivo confocal microscopy (IVCM).Patients and methods: Thirty-eight patients with DED were enrolled, with 19 receiving VB12 nebulization and 19 receiving OXT nebulization twice weekly for 3 months. Clinical signs and symptoms including Ocular Surface Disease Index, self-assessment of light sensitivity and dryness, tear meniscus height, tear break-up time (BUT), and corneal staining, along with IVCM data of basal epithelial cell density, sub-basal dendritic cell (DC) density, nerve density, and nerve tortuosity were acquired at baseline, 1 month, and 3 months after starting treatment.Results: Patients treated with VB12 improved significantly in all signs and symptoms except for nerve tortuosity during the three-month treatment, while OXT demonstrated similar effects apart from BUT and nerve tortuosity. VB12 group revealed a higher BUT at 1 month and 3 months with a higher basal epithelial cell density at 3 months compared with OXT group, and a lower DC density was observed in OXT group at 1 month. Change of basal epithelial cell density was more significant at 3 months in VB12 group, with OXT group showing a significantly higher DC reduction at 1 month.Conclusion: The nebulization therapy delivering VB12 and OXT appears to be effective in improving the symptoms and signs of dry eye, with a relatively stronger effect of BUT elevation and epithelial repair in VB12 and anti-inflammation in OXT nebulization.Keywords: dry eye, in vivo confocal microscopy, nebulization, oxytocin, vitamin B12

Hui Tong,1,* Xiaohui Liu,2,* Tao Li,1 Weihua Qiu,1 Chenghong Peng,1 Baiyong Shen,1 Zhecheng Zhu1 1Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; 2France National Research Center International Joint Laboratory (CNRS-LIAI), Sino-French Research Center for Life Sciences and Genomics, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China *These authors contributed equally to this work Background: Hepatocellular carcinoma (HCC) is the third leading cause of death by malignancy worldwide. HCC has a poor prognosis due to tumor invasiveness and metastasis. There is substantial evidence that the epithelial-to-mesenchymal transition (EMT) plays a central role in cancer metastasis. In a previous study, a possible association between integrator complex 8 (INTS8) and the progression and development of HCC was discovered. However, its role and the molecular mechanisms in HCC are poorly understood. Methods: The PROGgeneV2 platform database and Kaplan–Meier plotter analysis were used to analyze the potential effects of INTS8 in HCC. Moreover, we performed migration, transwell, and metastasis assays to investigate the effects of INTS8 on HCC cells. In addition, relevant signaling pathways were examined by western blot and RT-qPCR assays.Results: We used the PROGgeneV2 platform database and Kaplan–Meier plotter analysis, which indicated that increased expression of INTS8 is associated with poor overall survival of HCC. Moreover, INTS8 expression was higher in HCC tissues than in adjacent noncancerous tissues. INTS8 depletion reduced the invasion and migration of HCC cell lines. Downregulation of INTS8 in vivo resulted in fewer observed metastatic nodules in lungs. Moreover, INTS8 knockdown also increased the expression of epithelial markers (E-cadherin) and decreased the expression of mesenchymal markers (N-cadherin and vimentin) following the downregulation of SMAD4. In addition, pretreatment with TGF-β1 could partly prevent the decrease in the expression of SMAD4 and EMT markers induced by INTS8 knockdown. Conclusion: Overall, these findings suggest that INTS8 accelerates the EMT in HCC by upregulating the TGF-β signaling pathway. Keywords: INTS8, epithelial-to-mesenchymal transition, hepatocellular carcinoma