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Xia Zhao,1,* Huimin Guo,2,* Guangxi Shi,3 Bingying Li,1 Ning Wang2 1Department of Radiology, Shandong University of Traditional Chinese Medicine Affiliated Hospital, Jinan, 250014, People’s Republic of China; 2Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, People’s Republic of China; 3Department of Breast and Thyroid Surgery, Shandong University of Traditional Chinese Medicine Affiliated Hospital, Jinan, 250014, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ning Wang, Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 9677 Jingshi Road, Jinan, Shandong, 250021, People’s Republic of China, Email 327242909@qq.comIntroduction: Incidental Enhancement Lesions (IELs) complicate patient management but may be detected through multiparameter MRI including dynamic contrast enhancement magnetic resonance imaging (DCE-MRI) and synthetic magnetic resonance imaging (syMRI). The multiparameter MRI model gave greater objectivity to avoid unnecessary biopsy.Case Presentation: A 60 year-old woman had a history of occasional right breast pain and a mass was identified in the right breast. A thickening in the upper quadrant of the right outer breast was found during physical examination but no mass was palpable. Breast dynamic contrast enhancement MRI and synthetic MRI were performed prior to ultrasound-guided biopsy of the right breast lesion. Resection of the right breast lesion and sentinel lymph node was performed 2 days later. Chronic inflammation, locally invasive ductal carcinoma and high-grade ductal carcinoma in situ were found by pathological examination.Discussion: Differentiation between benign and malignant breast IELs was facilitated by use of a multiparameter MRI model with DCE-MRI and syMRI, giving greater objectivity in differentiating between benign and malignant lesions.Keywords: breast cancer, intraductal carcinoma, magnetic resonance imaging

Xinyu Zhang,1,* Xiaoxuan Tao,2,* Yuxin Zhou,1,* Guangyue Shi,1 Tianjiao Wang1 1Department of Internal Medicine-Oncology, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, People’s Republic of China; 2Department of Radiotherapy, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guangyue Shi; Tianjiao Wang, Email sgy2012@126.com; mm0719@126.comBackground: Bladder carcinoma (BLCA) is characterized by high morbidity, mortality, and treatment costs. Breast cancer gene 1 (BRCA1), a tumor suppressor gene, inhibits the development of malignant tumors. However, research on the significance of BRCA1 in BLCA is limited. This study aims to explore the importance of BRCA1 in BLCA using bioinformatic methods and immunohistochemistry.Methods: Gene expression, clinical, and survival data were collected from the TCGA databases through the UCSC Xena platform (http://xena.ucsc.edu/). The TPM data from the TCGA and GETEx databases were integrated using the GEPIA database (http://GEPIA.cancer-pku.cn). The study then explored the differential expression, survival prognosis, functional enrichment, and immune cell infiltration analyses of BRCA1 in BLCA. A PPI network of BRCA1 was constructed using the STRING database, and a BRCA1-associated gene-gene interaction network was generated using the GeneMANIA database. Immunohistochemistry (IHC) assays were performed to verify the expression levels of BRCA1 in bladder tumour tissues and adjacent normal tissues.Results: BRCA1 is associated with BLCA. Differential analysis indicated that BRCA1 acts as a risk factor for BLCA but does not show significant expression differences across genders, stages, tumor stages, lymph node stages, or metastasis stages. Additionally, staging was based on the eighth edition of the American Joint Committee on Cancer (AJCC) for BLCA. Co-expression network and Gene Set Enrichment Analysis (GESA) confirmed that BRCA1 is involved in various BLCA pathways. Furthermore, BRCA1 expression was also linked to immune cell infiltration. However, survival prognosis analysis revealed no significant correlation between the prognosis of BLCA and BRCA1.Conclusion: We demonstrated that BRCA1 is a prospective predicted and immunological biomarker in BLCA, offering new avenues for potential therapies.Keywords: bladder cancer, BRCA1, expression, immune cell infiltration, prognosis

Mengdi Zhang,1 Dongqing Pu,1 Dandan Feng,1 Guangxi Shi,2 Jingwei Li2 1First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan City, People’s Republic of China; 2Department of Thyroid and Breast Diagnosis and Treatment Center, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan City, People’s Republic of ChinaCorrespondence: Jingwei Li, Department of Thyroid and Breast Surgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan City, People’s Republic of China, Email 71000395@sdutcm.edu.cnPurpose: Granulomatous mastitis (GLM) is a rare and complex chronic inflammatory disease of the breast with an unknown cause and a tendency to recur. As medical science advances, the cause, treatment strategies, and comprehensive management of GLM have increasingly attracted widespread attention. The aim of this study is to assess the development trends and research focal points in the GLM field over the past 24 years using bibliometric analysis.Methods: Using GLM, Granulomatous mastitis (GM), Idiopathic granulomatous lobular mastitis (IGLM), and Idiopathic granulomatous mastitis (IGM) as keywords, we retrieved publications related to GLM from 2000 to 2023 from the Web of Science, excluding articles irrelevant to this study. Citespace and VOSviewer were employed for data analysis and visualization.Results: A total of 347 publications were included in this analysis. Over the past 24 years, the number of publications has steadily increased, with Turkey being the leading contributor in terms of publications and citations. The University of Health Sciences, Istanbul University, and Istanbul University Cerrahpasa were the most influential institutions. The Breast Journal, Breast Care, and Journal of Investigative Surgery were the journals that published the most on this topic. The research primarily focused on the cause, differential diagnosis, treatment, and comprehensive management of GLM. Issues related to recurrence, hyperprolactinemia, and Corynebacterium emerged as current research hotspots.Conclusion: Our bibliometric study outlines the historical development of the GLM field and identifies recent research focuses and trends, which may aid researchers in identifying research hotspots and directions, thereby advancing the study of GLM.Keywords: granulomatous lobular mastitis, bibliometric analysis, visual analysis, knowledge graphs, review

Guanfeng Shi,1,2 Yuying Wu,1 Huiwei Pang,1 Zhaohui Liu1 1Department of Economics and Management, Shihezi University, Shihezi, People’s Republic of China; 2Department of Corporate Governance and Management Innovation Research Center, Shihezi University, Shihezi, People’s Republic of ChinaCorrespondence: Yuying Wu, Email yuying_wu@stu.shzu.edu.cnPurpose: Fear of Missing out (FoMO) is a widely observed phenomenon in the workplace. Previous research has primarily focused on employees’ FoMO, with limited exploration of leaders’ FoMO and its impact on their creativity. This study aims to investigate how leaders’ FoMO affects their creativity, based on the transactional stress theory.Patients and Methods: Using an experience sampling method, we collected 836 observations from 102 leaders across various industries in China for two consecutive weeks (10 working days). Subsequently, hierarchical regression analysis and structural equation modeling were employed to test the hypotheses.Results: This study suggests that both challenge stress and hindrance stress mediate the relationship between leaders’ FoMO and their creativity. Role breadth self-efficacy moderates the relationship between leaders’ FoMO and challenge stress and hindrance stress, and moderates the positive and negative mediating effects of challenge stress and hindrance stress in the relationship between leaders’ FoMO and their creativity.Conclusion: Research has shown that leaders’ FoMO can either enhance creative performance by increasing challenge stress or inhibit it by increasing hindrance stress. Role breadth self-efficacy significantly amplifies the positive relationship between leaders’ FoMO and challenge stress, while moderating the negative effect of leaders’ FoMO on hindrance stress.Innovations: Firstly, this study expands workplace FoMO research by illustrating the double-edged sword effect of leaders’ FoMO on their creativity. Secondly, this study contributes to the academic community’s comprehension of the underlying mechanisms linking leaders’ FoMO and its outcomes by demonstrating the mediating role of challenge stress and hindrance stress. Thirdly, the study shows the boundary conditions for the effects of leaders’ FoMO by validating the moderating role of their role breadth self-efficacy.Keywords: workplace fear of missing out, challenge stress, hindrance stress, leader’s creativity, role breadth self-efficacy

Minghao Li,1,2,* Hua Liu,1,3,* Mingyang Xu,1,3 Baiyang Yu,3,4 Minwang Guo,1,3 Xiaorong Wang,1,3 Guomei Shi,1,3 Rujuan Zhou1,3 1Stroke Center, Taixing People’s Hospital, Taixing, Jiangsu, People’s Republic of China; 2Department of Vascular Surgery, Taixing People’s Hospital, Taixing, Jiangsu, People’s Republic of China; 3Department of Neurology, Taixing People’s Hospital, Taixing, Jiangsu, People’s Republic of China; 4Department of Neurology, Taixing Clinical College of Bengbu Medical College, Bengbu, Anhui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guomei Shi; Rujuan Zhou, Stroke Center, Taixing People’s Hospital, No. 1 Changzheng Road, Taixing, Jiangsu Province, 225400, People’s Republic of China, Tel +86-15240200702 ; +86-13951158499, Email 15240200702@yzu.edu.cn; zhourujuan123@163.comBackground: The correlation between glial fibrillary acidic protein (GFAP) and symptomatic intracranial hemorrhage (sICH) in acute ischemic stroke (AIS) patients undergoing endovascular thrombectomy (EVT) treatment remains uncertain. We aimed to assess the association between levels of GFAP in the bloodstream and the occurrence of sICH.Methods: Between June 2019 and May 2023, 142 consecutive AIS patients undergoing EVT at Stroke Center and 35 controls from the Physical Examination Center were retrospectively included. The levels of GFAP in the bloodstream were quantified using enzyme-linked immunosorbent assay prior to endovascular treatment (T1) and 24 h after the procedure (T2). The identification of sICH was based on the Heidelberg Bleeding Classification.Results: Serum GFAP levels at T1 in AIS patients were significantly higher than those in the controls (0.249 [0.150– 0.576] versus 0.065 [0.041– 0.110] ng/mL, p = 0.001), and there was a notably elevation in GFAP levels at T2 compared to T1 (3.813 [1.474, 5.876] versus 0.249 [0.150– 0.576] ng/mL, p = 0.001). Of the 142 AIS patients, 18 (14.5%) had sICH after EVT. Serum GFAP levels at T2 showed significant associations with sICH in both the unadjusted model (OR 1.513, 95% CI 1.269– 1.805, p = 0.001) and multivariable adjusted model (OR 1.518, 95% CI 1.153– 2.000, p = 0.003). Furthermore, the addition of GFAP at T2 to conventional model resulted in a significant enhancement of risk reclassification for sICH (integrated discrimination improvement [IDI] 0.183, 95% CI 0.070– 0.295, p = 0.001).Conclusion: Serum GFAP levels were notably increased in AIS patients 24 h after EVT. Elevated GFAP levels were correlated to an elevated risk of sICH. GFAP could potentially serve as a dependable indicator for sICH in AIS individuals who treated with EVT.Keywords: glial fibrillary acidic protein, stroke, symptomatic intracranial hemorrhage, indicator, endovascular thrombectomy

Liao X, Shen M, Li T, et al. Int J Nanomedicine. 2023;18:5925–5942. The authors wish to advise, following publication of the article they identified errors were made during the collection and organization of data for Figures 3 and 4 on pages 5934 and 5935, respectively. The correct Figures 3 and 4 are as follows. Figure 3 Antioxidant properties of POM or hydrogel. (A) DCFH-DA assay showing intracellular ROS of MC3T3-E1 after incubation with POM in the presence of H2O2 (100 μM). (B) Quantification analysis of DCFH-DA staining (*And #Indicate p < 0.05 in comparison with the H2O2 group and GelMA group, respectively.) (C) Cell capacity of migration (scratch test). (D) Quantitative analysis of percent migration in scratch assay. (*And #Indicate p < 0.05 in comparison with the H2O2 group and GelMA group, respectively.) (E) Live/dead staining showing MC3T3-E1 cell viability after culturing on hydrogel in the presence of H2O2. (F) Quantification analysis of live cells. (*And #Indicate p < 0.05 in comparison with the H2O2 group and GelMA group, respectively.) (G) LSCM images showing MC3T3-E1 cultured on different hydrogels following H2O2 treatment. (n = 3, each group). (H2O2, cells cultured on the tissue culture plate with H2O2). Scale bar: 200 μm (A), 200 μm (C), 100 μm (E) and 100 μm (G). Figure 4 The osteogenesis properties of GelMA/POM hydrogel in vitro. In vitro assay of effects of hydrogel on ALP activity and extracellular calcium nodule production during osteogenesis differentiation of MC3T3-E1. (A) Alizarin red S staining. (B) Quantitative analysis of mineralized nodules. (C) Alkaline phosphatase activity. (D) Alkaline phosphatase staining. (*, # And a indicate p < 0.05 in comparison with the Control group, H2O2 group and GelMA group, respectively). (Control, cells cultured without H2O2). (n = 3, each group). Scale bar: 200 μm (A) and 200 μm (D). The authors advise these corrections do not significantly impact the overall findings and conclusions of the article or alter the interpretations or validity of the research. The authors apologize for any confusion these errors may have caused and appreciate the opportunity to rectify them.

Guiqiang Qi,1 Guangyue Shi,1 Shengchao Wang,1 Haifeng Hu,2 Zhichen Zhang,1 Qiangqiang Yin,1 Zhongtao Li,1 Liguo Hao1,3 1Department of Molecular Imaging, School of Medical Technology, Qiqihar Medical University, Qiqihar, Heilongjiang, 161006, People’s Republic of China; 2Medical Imaging Center, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang, 161000, People’s Republic of China; 3Department of Molecular Imaging, The First Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang, 161041, People’s Republic of ChinaCorrespondence: Liguo Hao, Email haoliguo@qmu.edu.cnIntroduction: This study developed a pancreatic cancer targeted drug delivery system that responds to changes in acidity. The system was based on iron oxide core-shell magnetic mesoporous silica nanoparticles (M-MSNs) to treat pancreatic cancer through combined chemotherapy and starvation therapy.Methods: Glucose oxidase (Gox) was coupled to the cancer cell surface to reduce glucose availability for cancer cells, exacerbating the heterogeneity of the tumor microenvironment. Reduced pH accelerated the depolymerization of pH-sensitive polydopamine (PDA), thereby controlling the spatial distribution of Gox and release of doxorubicin (DOX) within tumor cells.Results: Characterization results showed the successful synthesis of DG@M-MSN-PDA-PEG-FA (DG@NPs) with a diameter of 66.02 ± 3.6 nm. In vitro data indicated DG@NPs were highly effective and stable with good cellular uptake shown by confocal laser scanning microscopy (CLSM). DG@NPs exhibited high cytotoxicity and induced apoptosis. Additionally, in vivo experiments confirmed DG@NPs effectively inhibited tumor growth in nude mice with good biosafety. The combination of starvation therapy and chemotherapy facilitated drug release, suggesting DG@NPs as a novel drug delivery system for pancreatic cancer treatment.Conclusion: This study successfully constructed a doxorubicin release system responsive to acidity changes for targeted delivery in pancreatic cancer, providing a new strategy for combination therapy.Keywords: mesoporous silica nanoparticle, drug delivery, multitherapy modality, magnetic resonance imaging, glucose oxidase

Sheng Liu,1,&ast; Guanyun Shi,1 Zhengbo Pan,1 Weisong Cheng,1 Linfei Xu,1 Xingzhang Lin,1 Yongfeng Lin,1 Liming Zhang,1 Guanghua Ji,1 Xin Lv,1 Dongguo Wang2,&ast; 1Department of Urinary Surgery, Taizhou Municipal Hospital Affiliated with Taizhou University, Taizhou, Zhejiang Province, People’s Republic of China; 2Department of Central Laboratory, Taizhou Municipal Hospital Affiliated with Taizhou University, Taizhou, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongguo Wang, Department of Central Laboratory, Taizhou Municipal Hospital Affiliated with Taizhou University, 381-1 Eastern Road of Zhongshan, Taizhou, Zhejiang Province, 318000, People’s Republic of China, Tel +86-13566871738, Email wdgtzs@163.comPurpose: The overall survival of clear cell renal cell carcinoma (ccRCC) is poor. Markers for early detection and progression could improve disease outcomes. This study aims to reveal the potential pathogenesis of ccRCC by integrative bioinformatics analysis and to further develop new therapeutic strategies.Patients and Methods: RNA-seq data of 530 ccRCC cases in TCGA were downloaded, and a comprehensive analysis was carried out using bioinformatics tools. Another 14 tissue samples were included to verify the expression of selected lncRNAs by qRT-PCR. DGIdb database was used to screen out potential drugs, and molecular docking was used to explore the interaction and mechanism between candidate drugs and targets.Results: A total of 58 differentially expressed lncRNAs (DElncRNAs) and 660 differentially expressed mRNAs (DEmRNAs) were identified in ccRCC. LINC02038, FAM242C, LINC01762, and PVT1 were identified as the optimal diagnostic lncRNAs, of which PVT1 was significantly correlated with the survival rate of ccRCC. GO analysis of cell components showed that DEmRNAs co-expressed with 4 DElncRNAs were mainly distributed in the extracellular area and the plasma membrane, involved in the transport of metal ions, the transport of proteins across membranes, and the binding of immunoglobulins. Immune infiltration analysis showed that MDSC was the most correlated immune cells with PVT1 and key mRNA SIGLEC8. Validation analysis showed that GABRD, SIGLEC8 and CDKN2A were significantly overexpressed, while ESRRB, ELF5 and UMOD were significantly down-regulated, which was consistent with the expression in our analysis. Furthermore, 84 potential drugs were screened by 6 key mRNAs, of which ABEMACICLIB and RIBOCICLIB were selected for molecular docking with CDKN2A, with stable binding affinity.Conclusion: In summary, 4 key lncRNAs and key mRNAs of ccRCC were identified by integrative bioinformatics analysis. Potential drugs were screened for the treatment of ccRCC, providing a new perspective for disease diagnosis and treatment.Keywords: clear cell renal cell carcinoma, bioinformatics analysis, lncRNA, mRNA, drugs prediction, molecular docking

Guomei Shi,1,2,&ast; Dongdong Ke,2,3,&ast; Pengyu Gong,4,5 Peng Yu,2,6 Junshan Zhou,5 Meng Wang,5 Xiaohao Zhang,5 Xiaorong Wang,1,2 Minwang Guo,1,2 Mingyang Xu,1,2 Rujuan Zhou1,2 1Department of Neurology, the Taixing People’s Hospital, Taixing, Jiangsu, People’s Republic of China; 2Stroke Center, the Taixing People’s Hospital, Taixing, Jiangsu, People’s Republic of China; 3Department of Rehabilitation, the Taixing People’s Hospital, Taixing, Jiangsu, People’s Republic of China; 4Department of Neurology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People’s Republic of China; 5Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 6Department of Radiology, the Taixing People’s Hospital, Taixing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rujuan Zhou, Tel +86-13951158499, Email zhourujuan123@163.comBackground: White matter hyperintensity (WMH) is associated with risk of acute ischemic stroke (AIS) and poor outcomes after AIS. The purpose of this prospective study was to evaluate the association between serum YKL-40 levels and WMH burden in patients with AIS.Methods: From February 2020 to March 2021, a total of 672 consecutive AIS patients with magnetic resonance imaging data were prospectively recruited form two centers. Serum YKL-40 levels were quantified using enzyme-linked immunosorbent assay. The burden of WMH was semiquantitatively measured by the Fazekas visual grading scale. According to severity of overall WMH, patients were dichotomized into none–mild WMH group (Fazekas score 0– 2) or moderate–severe WMH group (Fazekas score 3– 6). Besides, based on severity of periventricular WMH (PV-WMH) and deep WMH (D-WMH), patients were categorized as none–mild (Fazekas score 0– 1) or moderate–severe (Fazekas score 2– 3).Results: Among the 672 patients, 335 (49.9%) participants were identified with moderate–severe overall WMH, 326 (48.5%) with moderate–severe PV-WMH and 262 (39.0%) with moderate–severe D-WMH. Compared with the first quartile of serum YKL-40, the adjusted odds ratio (OR) of the fourth quartile for moderate–severe PV-WMH was 2.473 (95% confidence interval [CI] 1.316– 4.646; P=0.005). No significant association was observed between YKL-40 and overall WMH (OR 0.762; 95% CI 0.434– 1.336; P=0.343) or D-WMH (OR 0.695; 95% CI 0.413– 1.171; P=0.172).Conclusion: Our results suggested that higher YKL-40 levels appeared to be associated with PV-WMH, but not with overall WMH or D-WMH in patients with AIS.Keywords: acute ischemic stroke, YKL-40, white matter hyperintensities, biomarkers

Yidan Sun,1– 3,&ast; Xiaozhou Yao,1– 3,&ast; Yingmeng Ni,1– 3 Yibing Peng,4 Guochao Shi1– 3 1Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Institute of Respiratory Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Shanghai Key Laboratory of Emergency Prevention, Diagnosis and Treatment of Respiratory Infectious Diseases, Shanghai, People’s Republic of China; 4Faculty of Medical Laboratory Science, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guochao Shi, Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, People’s Republic of China, Tel +86-13918462035, Fax + 021-64314162, Email shiguochao@hotmail.com Yibing Peng, Faculty of Medical Laboratory Science, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, People’s Republic of China, Tel +86-13795243560, Email pyb9861@sina.comPurpose: To explore the diagnostic efficacy and optimal diagnosis threshold of T-SPOT.TB for active tuberculosis in adults and to evaluate the influential factors for T-SPOT.TB results.Patients and Methods: A retrospective study of 1193 adult inpatients from April 2015 to March 2018 in Ruijin Hospital was conducted. All included patients underwent T-SPOT.TB assay, and were divided into two groups, active tuberculosis (ATB) and non-active tuberculosis (non-ATB) groups. Their demographic data, underlying diseases, personal history and laboratory findings were collected to calculate the diagnostic efficacy at different diagnosis thresholds and analyze the impact factors. Symptoms and imaging features of ATB patients were recorded and analyzed.Results: A total of 114 ATB patients and 1079 non-ATB patients were included in the study, and ATB patients had a higher level of T-SPOT.TB than the non-ATB group. Sensitivity and specificity of T-SPOT.TB for diagnosing ATB are 78.95% and 68.58% as the threshold at 6sfu. In the diagnosis accordance curves, ESAT-6, CFP-10, and max (ESAT-6 or CFP-10) reached the plateau at 40sfu, while sum (ESAT-6 and CFP-10) reached the plateau at 70sfu. Multivariate logistic regression analysis showed that obsolescent tuberculosis (p=0.001), smoking history(p=0.005), diabetes(p=0.035) and advanced age (≥ 65 years old) (p=0.031) were risk factors for false-positive result of T-SPOT.TB. In terms of imaging features, logistic regression analysis suggested that the thin-wall cavitary lesion was the only feature associated with the result of T-SPOT.TB.Conclusion: As for using T-SPOT.TB test to diagnose active tuberculosis, increased threshold could significantly elevate the diagnosis accordance. And we suggest that the threshold of T-SPOT.TB could be increased to 40sfu for diagnosing ATB. Attention should be paid when diagnose ATB in population with obsolescent tuberculosis, smoking history, diabetes and advanced age, for the risk of false-positive.Keywords: T-SPOT.TB, active tuberculosis, diagnosis threshold

Hongxia Lin,1,2,&ast; Yulian Gao,1,2,&ast; Yanli Qiu,3,&ast; Haixing Zhu,1,2 Shengxiong Zhang,1,2 Hanssa Dwarka Summah,4 Guochao Shi,1,2 Tingting Cheng,5,&ast; Zhitao Yang,6 Yun Feng1,2 1Department of Respiratory and Critical Care Medicine, Ruijin Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 2Institute of Respiratory Diseases, School of Medicine, Shanghai Jiao Tong University, Shanghai, 20025, People’s Republic of China; 3Department of Anesthesia, Ruijin Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 4Poudre D’Or Chest Hospital, Rivière du Rempart, Mauritius; 5Department of Respiratory and Critical Care Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 20025, People’s Republic of China; 6Department of Emergency, Ruijin Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhitao Yang; Yun Feng, Email yangzhitao@hotmail.fr; fy01057@163.comIntroduction: Elderly patients with immunosuppressive status may have increased risk of mortality. At present, few studies have explored the clinical characteristics of the elderly immunosuppressed population with bloodstream infection. Our objectives were to evaluate the prognostic factors in immunosuppressed elderly patients with bloodstream infection.Methods: Three hundred and seventy-six elderly patients who were diagnosed with bloodstream infection in immunosuppressive status while receiving treatment in our hospital were selected from 2015 to 2019. The demographic data, underlying diseases, comorbidity, inducement, complications, pathogen sources, etiologies and the antibiotic therapy were analyzed between 90-day survival groups and 90-day mortality groups. The prognostic factors of 90-day mortality were evaluated by univariate logistic regression analysis and multivariate logistic regression analysis.Results: The clinical characteristics of 376 immunosuppressed elderly people diagnosed with bloodstream infection were analyzed, and among those people about 111 were 90-day mortality. By univariate logistic regression analysis and multivariate logistic regression analysis, we found ICU admission (OR: 2.052, 95%CI: 1.088– 3.871, p=0.026), the decrease in BMI (OR: 0.307, 95%CI: 0.130– 0.723, p=0.007), coronary heart disease (OR: 2.028, 95%CI: 1.078– 3.816, p=0.028), biliary infection (OR: 4.406, 95%CI: 1.794– 10.821, p=0.001) and the use of tigecycline (OR: 2.480, 95%CI: 1.195– 5.147, p=0.015) were significantly different between the 90-day survival and 90-day mortality groups.Conclusion: ICU admission, coronary heart disease, biliary infection, and the use of tigecycline were the independent prognostic risk factors of 90-day mortality in immunosuppressed elderly people, and the decrease in BMI was the protective factor, which would have the benefit of discriminating the prognostic factors in immunosuppressed elderly people with bloodstream infection.Keywords: bloodstream infection, elderly people, mortality, immunosuppressive states, prognosis

Linxin Xu,1,2,&ast; Junfang Cui,3,&ast; Mina Li,2 Qianqian Wu,2 Ming Liu,2 Minggang Xu,4 Guoliang Shi,4 Jianhong Yin,2 Jing Yang1,2 1First Clinical Medical College, Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of Endocrinology, First Hospital of Shanxi Medical University, Shanxi Medical University, Taiyuan, Shanxi, 030001, People’s Republic of China; 3Department of Geratology, First Hospital of Shanxi Medical University, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China; 4Department of Endocrinology, Changzhi Second People’s Hospital, Changzhi, 046000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Yang; Jianhong Yin, Tel +86-351-4639756, Email yangjlm@126.com; yinjianhong0351@163.comObjective: To explore the association between serum asprosin and diabetic nephropathy (DN) in patients with type 2 diabetes mellitus (T2DM) in the community.Methods: In this cross-sectional study, we retrospectively collected the clinical data of T2DM patients from a community health service center in southeastern Shanxi Province between November 2019 and July 2021. Logistic regression analysis was used to calculate the odds ratio (OR) and the 95% confidence interval (95% CI) of asprosin levels on the risk of DN.Results: Among 498 T2DM patients included in this study, 221 had microalbuminuria, 105 had massive albuminuria, and 172 did not have any signs of nephropathy. Serum asprosin level was positively correlated with diastolic blood pressure, body mass index, triglycerides, aspartate aminotransferase, alanine aminotransferase, creatinine, ACR and albumin-to-creatinine ratio (all P < 0.05) and negatively correlated with low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting plasma glucose, HbA1c and estimated glomerular filtration rate (all P < 0.05). After adjusting for covariates, increased asprosin was associated with diabetic nephropathy (all OR = 2.560, 95% CI: 1.1592– 4.116; P < 0.001).Conclusion: The risk of DN significantly increases with serum asprosin levels, especially among female patients.Keywords: asprosin, type 2 diabetes mellitus, diabetic nephropathies, creatinine, albuminuria, logistic models, community health services

Shigeto Maekawa,1 Kota Sato,1,2 Taiki Kokubun,1 Noriko Himori,1,3 Takeshi Yabana,1 Michiko Ohno-Oishi,1 Ge Shi,1 Kazuko Omodaka,1,4 Toru Nakazawa1,2,4– 6 1Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan; 2Department of Advanced Ophthalmic Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan; 3Department of Aging Vision Healthcare, Tohoku University Graduate School of Biomedical Engineering, Sendai, Miyagi, Japan; 4Department of Ophthalmic Imaging and Information Analytics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan; 5Collaborative Program for Ophthalmic Drug Discovery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan; 6Department of Retinal Disease Control, Tohoku University Graduate School of Medicine, Sendai, Miyagi, JapanCorrespondence: Toru Nakazawa, Department of Ophthalmology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aoba, Sendai, Miyagi, 980-8574, Japan, Tel +81-22-717-7294, Fax +81-22-717-7298, Email ntoru@oph.med.tohoku.ac.jpPurpose: To investigate the effect of plant-derived antioxidant compounds, identified with primary culture screening, on retinal ganglion cell (RGC) survival in mice under excitotoxic conditions. Additionally, to determine the effect of these compounds on the involvement of calpain inactivation.Materials and Methods: Plant-derived antioxidant compounds including hesperidin, crocetin, and Tamarindus indica were administrated orally to C57BL/6J mice. The levels of lipid oxidation and calpain activation were assessed with a TBARS assay and western blotting. RGC survival was evaluated with a TUNEL assay and RBPMS immunostaining after intravitreal injection of NMDA.Results: Plant-derived antioxidant compounds significantly ameliorated the increase in the level of MDA in the retinas after NMDA injury. Cleaved α-fodrin fragments were detected in the NMDA-injured retinas, and these fragments were significantly lower in mice that received the plant-derived antioxidant compounds. The plant-derived antioxidants also ameliorated increases in TUNEL-positive cells and RGC death after NMDA injection.Conclusion: These results indicate that oral administration of plant-derived antioxidant compounds such as hesperidin, crocetin, and Tamarindus indica suppressed RGC death. This oral supplementation decreased lipid oxidation and excessive calpain activation in NMDA-injured retinas. Thus, our newly developed antioxidant supplement has a potential role in neuroprotective treatment for retinal diseases, such as glaucoma.Keywords: plant-derived antioxidant compounds, oxidative stress, retinal ganglion cells, glaucoma

Guoshuai Shi,1 Ni Zhu,2 Lin Qiu,3 Hong Yan,1,4 Lingxia Zeng,1 Duolao Wang,5 Shaonong Dang,1 Zhaoqing Li,1 Yijun Kang,1 Tao Chen,6 Chao Li1 1Department of Epidemiology and Biostatistics, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi, People’s Republic of China; 2Department of Communicable Disease Control and Prevention, Shaanxi Provincial Center for Disease Control and Prevention, Xi’an, Shaanxi, People’s Republic of China; 3Department of Chronic and Noncommunicable Disease Control and Prevention, Shaanxi Provincial Center for Disease Control and Prevention, Xi’an, Shaanxi, People’s Republic of China; 4Nutrition and Food Safety Engineering Research Center of Shaanxi Province, Xi’an, Shaanxi, People’s Republic of China; 5Department of Clinical Sciences, Liverpool School of Tropical Medicine Pembroke Place, Liverpool, Merseyside, L3 5QA, UK; 6Department of Public Health, Policy & Systems, Institute of Population Health, The University of Liverpool, Liverpool, L69 3GB, UKCorrespondence: Chao LiDepartment of Epidemiology and Biostatistics, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi, People’s Republic of ChinaEmail lcxjtu@xjtu.edu.cnTao ChenDepartment of Public Health, Policy & Systems, Institute of Population Health, The University of Liverpool, Whelan Building, Quadrangle, Liverpool, L 69 3GB, UKEmail Tao.chen@liverpool.ac.ukPurpose: This study aimed to estimate the impact of the 2020 China Diabetes Society’s (CDS) guideline on the prevalence of diabetes mellitus and eligibility for antidiabetic treatment in China.Material and Methods: Baseline data from the China Health and Retirement Longitudinal Study (CHARLS, 2011– 2012) were used to estimate the prevalence of diabetes mellitus and compare the recommendations for antidiabetic medication and intensification of therapy between the 2017 and 2020 CDS guidelines.Results: According to the 2017 CDS guideline, the prevalence of diabetes mellitus was 12.56% among Chinese adults who were ≥ 45 years of age. However, according to the 2020 CDS guideline, 0.65% (0.35%, 1.20%), or 3.54 (2.50, 4.57) million Chinese adults who were ≥ 45 years would additionally be diagnosed with diabetes mellitus. Among Chinese adults not taking antidiabetic medications, 1.06% (0.87%, 1.28%), or 5.37 (4.36, 6.38) million Chinese adults with diabetes mellitus were recommended to start antidiabetic medication according to the 2017 CDS guideline, while 1.27% (1.01%, 1.58%), or 6.44 (5.29, 7.60) million Chinese adults with diabetes would be recommended to initiate antidiabetic medication according to the 2020 CDS guideline. Among Chinese adults taking antidiabetic medication, 51.59% (44.19%, 58.93%), or 18.35 (15.58, 21.12) million Chinese adults with diabetes received antidiabetic treatment but had a hemoglobin A1c (HbA1c) level higher than that mentioned in the 2017 and 2020 CDS guidelines.Conclusion: The addition of HbA1c in the 2020 CDS guideline will result in a modest increase in the number of Chinese adults who are diagnosed with diabetes and diabetes patients recommended for antidiabetic medication; however, the 2020 CDS guideline does not affect the number of diabetes patients eligible for intensification of treatment.Keywords: China Diabetes Society, diabetes, glycated hemoglobin A1c

Guomei Shi,1,2,&ast; Wenxiu Chen,3,&ast; Pengyu Gong,4 Meng Wang,4 Junshan Zhou,4 Xiaorong Wang,1 Minwang Guo,1 Jingye Lu,1 Yan Li,1 Hongxuan Feng,2,5 Xuetao Fu,2,6 Rujuan Zhou,1 Shouru Xue2 1Department of Neurology, The Taixing People’s Hospital, Taixing, Jiangsu, People’s Republic of China; 2Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 3Department of Critical Care Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 4Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 5Department of Neurology, The Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), Suzhou, Jiangsu, People’s Republic of China; 6Department of Neurology, Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rujuan Zhou; Shouru Xue Tel +86-13951158499; +86-18962133036Email zhourujuan123@163.com; xueshouru@suda.edu.cnBackground: Stroke-associated pneumonia (SAP) is a standout complication after acute ischemic stroke (AIS), with a prevalence of 7– 38%. The aim of this prospective study was to investigate the relationship between serum YKL-40 levels at admission and SAP.Methods: Between August 2020 and February 2021, consecutive AIS patients from two centers were enrolled prospectively. Serum YKL-40 concentrations were measured via enzyme-linked immunosorbent assay. We performed logistic regression analyses to explore the relationship between YKL-40 and SAP. Receiver operating characteristic curve was also used to assess the predictive ability of YKL-40 in predicting SAP.Results: Ultimately, a total of 511 AIS patients were recruited. Multivariate logistic regression analysis showed that YKL-40 was independently related to SAP, whether as a continuous variable or as quartiles (P=0.001). The area under curve of YKL-40 to predict SAP was 0.765. The optimal cutoff value of YKL-40 as a predictor of SAP was determined to be 206.4 ng/mL, where the sensitivity was 63.1% and the specificity was 82.0%.Conclusion: Our study demonstrated that YKL-40 might be considered as a useful biomarker to predict SAP in AIS patients.Keywords: acute ischemic stroke, YKL-40, stroke-associated pneumonia

Li-juan Wu,1,* Yan Luo,2,* Guo-lu Shi,3,* Zhong-yue Li1 1Department of Gastroenterology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing Key Laboratory of Pediatrics, Chongqing, People’s Republic of China; 2Department of Pediatrics, Wushan County People’s Hospital of Chongqing, Chongqing, People’s Republic of China; 3Department of Pediatrics, Suining Central Hospital, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhong-yue LiDepartment of Gastroenterology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing Key Laboratory of Pediatrics, No. 136, 2nd Zhongshan Road, Yuzhong District, Chongqing, People’s Republic of ChinaTel +86-18225022855Fax +86-68370225Email lizhongyue1001@hotmail.comPurpose: Nontyphoidal Salmonella (NTS) is a leading bacterial cause for acute gastroenteritis in children. With the increasing use of antibiotics worldwide, antibiotic resistance has become a global problem. However, data on NTS infections and changes in antibiotic resistance among children remain limited in China. We aimed to characterize the prevalence, clinical feature, serotype and the changes of antibiotic resistance of NTS in children in Chongqing.Methods: 501 hospitalized children with NTS infections (confirmed by positive NTS culture) in Children’s Hospital of Chongqing Medical University from January 2009 to December 2018 were included. The clinical data and drug sensitivity test results were retrospectively reviewed and analyzed. Antibiotic resistance in NTS infections was compared between 2009– 2013 and 2014– 2018.Results: A total of 501 isolates were detected. Most NTS infections occurred in children under three years old, which mainly occurred between July and October. The numbers of patients with diarrhea, fever, and vomiting were 472 (94.2%), 422 (84.2%) and 146 (29.1%), respectively. Serogroup B (67.5%) was the predominant serogroup isolates. And Salmonella Typhimurium was the most common serotype (79.2%). The study compared the drug resistance of NTS from 2009 to 2013 with that from 2014 to 2018. We found the drug resistance rates of NTS to cefazolin, cefotaxime, ciprofloxacin, levofloxacin and imipenem showed an upward trend. The drug resistance rates of NTS to chloramphenicol, ampicillin, ceftriaxone, cefepime and compound sulfamethoxazole decreased slightly, but still showed high drug resistance rates. And drug resistance rates of NTS to piperacillin/tazobactam and ceftazidime decreased significantly in the last ten years. Multi-drug resistance (MDR) isolates, were detected among 69 cases (13.7%) of 501 children with NTS infections.Conclusion: The overall antibiotic resistance rates remained at a high level in Chongqing. Continuous surveillance of antibiotic resistance in NTS and control measures such as avoiding unnecessary antibiotic therapy in general NTS gastroenteritis are important. For severe or invasive infections caused by NTS infection in Southwest China, the use of ceftazidime is recommended until antibiotic sensitivity test results are available. And the choice of antibiotics should be based on the curative effect and the antibiotics sensitivity results.Keywords: nontyphoidal Salmonella, pediatric, prevalence, antibiotic resistance

Hong Liu,1,* Quan Wang,1,* Ge Shi,1 Wenqiang Yang,2 Yanmin Zhang,1 Weidong Chen,1 Sheng Wan,1 Fei Xiong,1 Zengsi Wang1 1Department of Nephrology, Wuhan No. 1 Hospital, Wuhan, Hubei, 430022, People’s Republic of China; 2Department of Central Laboratory, Wuhan No. 1 Hospital, Wuhan, Hubei, 430022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fei Xiong; Zengsi WangDepartment of Nephrology, Wuhan No. 1 Hospital, No. 215 Zhongshan Avenue, Wuhan, Hubei, 430022, People’s Republic of ChinaTel +86-27-85332356; +86-27-85332346Email xiongf23@sina.com; wangzengsi@hotmail.comPurpose: The activation of autophagy has potential protective effect on diabetic nephropathy (DN) podocyte injury, and the AMPK/mTOR signaling pathway is an important regulatory pathway of autophagy. Emodin has been reported to effectively delay DN progression; however, the therapeutic mechanisms involved in vivo remain ambiguous. The present study aimed to elucidate the mechanism of emodin in improving renal tissue and podocyte injury in DN by regulating the AMPK/mTOR-autophagy signaling pathway.Methods: All rats were divided into 4 groups: a Sham group, a Vehicle group, a low-dose emodin (LD-Emo) group (20 mg/kg/day) and a high-dose emodin (HD-Emo) group (40 mg/kg/day). The different doses of Emo and distilled water were daily administrated for 8 weeks after the induction of DN by the unilateral nephrectomy combined with intraperitoneal injections of streptozotocin (STZ). The rats’ general status, blood glucose, biochemical parameters, urinary protein excretion, renal histological changes and cell apoptosis in renal tissue, as well as the key protein expressions in the AMPK/mTOR signaling pathway and apoptosis-related proteins were examined, respectively.Results: Emodin ameliorated the general condition, kidney weight and urinary protein excretion of the rats, but has little influence on serum biochemical parameters and did not lower blood glucose; emodin attenuated renal fibrosis including the cell numbers, extracellular matrix rate and collagen area in glomerulus, simultaneously relieved podocyte foot process fusion, up-regulated the expression of nephrin protein and suppressed glomerular and tubular epithelial cell apoptosis. In addition, emodin can induce and enhance autophagy in podocytes including increased expression of LC3-II/I, Beclin-1, p-AMPK protein and decreased expression of p62, p-mTOR protein, as well as increased autophagosomes in podocytes.Conclusion: We have demonstrated that emodin, as a natural regulator in vivo, reduced proteinuria and alleviated renal fibrosis without affecting hyperglycemia in DN rats. The potential mechanisms by which emodin exerts its renoprotective effects in vivo are through suppressing cell apoptosis and enhancing autophagy of podocytes via the AMPK/mTOR signaling pathway in the kidney.Keywords: emodin, diabetic nephropathy, autophagy, cell apoptosis, AMPK/mTOR signaling pathway

Shulan Lv,1,* Qing Wang,1,* Yan Li,1,2,* Lanbo Zhao,3 Yiran Wang,1 Xue Feng,1 Lu Han,1 Kailu Zhang,1 Panyue Yin,1 Huilian Hou,4 Guizhi Shi,5 Qiling Li1 1Department of Obstetrics and Gynecology, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China; 2Department of Obstetrics and Gynecology, Yan’an People’s Hospital, Yan’an, Shaanxi, China; 3Health Science Center, Xi’an Jiaotong University, Xi’an, Shaanxi, China; 4Department of Pathology, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China; 5Aviation General Hospital of Beijing, Medical, Pathology Department of Aviation General Hospital of Beijing, Beijing, China*These authors contributed equally to this workCorrespondence: Qiling LiDepartment of Obstetrics and Gynecology, First Affiliated Hospital of Xi’an Jiaotong University, 277 West Yanta Road, Xi’an, Shaanxi, ChinaTel +86-29-85323849Fax +86-29-88214667Email liqiling@mail.xjtu.edu.cnPurpose: Cytopathology detecting for endometrial cancer is becoming accepted, and Tao Brush is the most widely used sampler for endometrial cells. This study aims to compare the effectiveness between Li brushes and Tao brushes for the diagnosis of endometrial lesions and to evaluate the diagnostic accuracy of endometrial cytology compared with histology.Methods: There were 109 patients needing dilation and curettage (D&C) and 21 patients needing hysterectomies included from November 2017 to April 2018. Every patient was sampled by Tao brush and Li brush before D&C or hysterectomy performed. The cytological results were compared based on the gold standard histological results of D&C or hysterectomy.Results: The sensitivity of Li brush cytology for detecting endometrial cancer and atypical hyperplasia was estimated at 83.33%, specificity at 100%, positive predictive value (PPV) at 100%, and negative predictive value (NPV) at 98.02%, respectively. While for the Tao brush, it was 91.67% of sensitivity, 96.04% of specificity, 73.33% of PPV, and 98.98% of NPV, respectively. The kappa value was 0.767, which indicated a substantial agreement. Cytology by both two brushes had a lower insufficient sample rate (2.75% of Tao brush, 4.59% of Li brush) than did D&C (11.93%).Discussion: Endometrial cytology is a reliable approach for evaluating endometrium with a lower insufficient sample rate. Cytology sampled by both Li brushes and Tao brushes has a high accuracy with histological diagnosis in detecting endometrial cancer and atypical hyperplasia. Combining social and economic benefits, the Li brush may be a better endometrial cell collector.Keywords: Li brush, Tao brush, cytology, dilation and curettage, endometrial cancer

Gaofeng Shi,1,* Xue Han,1,* Qi Wang,1 Yan Ding,1 Hui Liu,1 Yunfei Zhang,2 Yongming Dai2 1Department of Radiology, Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, People’s Republic of China; 2Department of Research Collaboration Hospital (MRI), Central Research Institute, United Imaging Healthcare, Shanghai 201800, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hui Liu; Yunfei Zhang Tel +86-311-86095716; Tel +86-311-86095716Fax +86-311-8609-5692Email liuhui_lh111@163.com yunfei.zhang@united-imaging.comPurpose: To predict multiple prognostic factors of HCC including histopathologic grade, the expression of Ki67 as well as capsule formation with intravoxel incoherent motions imaging by extracting the histogram metrics.Patients and Methods: A total of 52 patients with HCC were recruited with the MR examinations undertaken at a 3T scanner. Histogram metrics were extracted from IVIM-derived parametric maps. Independent student t-test was performed to explore the differences in metrics across different subtypes of prognostic factors. Spearman correlation test was utilized to evaluate the correlations between the IVIM metrics and prognostic factors. ROC analysis was applied to evaluate the diagnostic performance.Results: According to the independent student t-test, there were 18, 4, and 8 IVIM-derived histogram metrics showing the capability for differentiating the subtypes of histopathologic grade, Ki67, and capsule formation, respectively, with P-values of less than 0.05. Besides, there existed a lot of significant correlations between IVIM metrics and prognostic factors. Finally, by integrating different histogram metrics showing significant differences between various subgroups together via establishing logistic regression based diagnostic models, greatest diagnostic power was obtained for grading HCC (AUC=0.917), diagnosing patients with highly expressed Ki67 (AUC=0.861) and diagnosing patients with capsule formation (AUC=0.839).Conclusion: Multiple prognostic factors including histopathologic grade, Ki67 expression status, and capsule formation can be accurately predicted with assistance of histogram metrics sourced from a single IVIM scan.Keywords: diffusion magnetic resonance imaging, intravoxel incoherent motions, hepatocellular carcinoma, prognostic factors, histogram analysis

Xu Jing,1 Yingjie Chen,2 Ye Chen,1 Guangyan Shi,1 Shuanghao Lv,1 Nana Cheng,1 Chaolin Feng,1 Zhen Xin,1 Liping Zhang,3 Jing Wu1 1Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, People’s Republic of China; 2Department of Physiology and Pathophysiology, School of Basic Medicine, Shandong University, Jinan, People’s Republic of China; 3Department of Clinical Laboratory, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, People’s Republic of ChinaCorrespondence: Jing WuDepartment of Clinical Laboratory, The Second Hospital of Shandong University, No. 247 Beiyuan West Road, Jinan 250033, People’s Republic of ChinaEmail wujing19830603@126.comLiping ZhangDepartment of Clinical Laboratory, The First Affiliated Hospital of Henan University of Chinese Medicine, No. 19 Renmin Road, Zhengzhou 450000, People’s Republic of ChinaEmail weier_528@163.comObjective: Cholangiocarcinoma is the second most common primary hepatobiliary malignancy with high incidence and recurrence rate. Ubiquitin-specific protease 8 (USP8) is recently reported to be involved in tumor progression. Herein, we aimed to investigate the effects of USP8 on the growth and metastasis abilities of cholangiocarcinoma cells.Methods: The siRNA interference was used to knock down USP8 in cholangiocarcinoma cell lines QBC939 and RBE; Hucct-1 cells were transfected with pcDNA3.1-USP8 to up-regulate its expression. The effects of USP8 on cholangiocarcinoma were detected by cell function assays. We analyzed the expressions of USP8, Bcl2, Bax, cleaved caspase-3, cleaved caspase-9, Akt, p-Akt, Cyclin D1 and P70S6K by Western blot analysis.Results: We demonstrated that knockdown of USP8 significantly inhibited the proliferation, migration and invasion of QBC939 and RBE cells in vitro, while USP8 overexpression showed significant promoting effects on Hucct-1 cells. Moreover, silencing of USP8 also promoted apoptosis in cholangiocarcinoma cells by regulating the Bcl-2/Bax axis and Caspase cascade; up-regulation of USP8 decreased apoptosis in Hucct-1 cells. Importantly, knockdown of USP8 inhibited activation of the Akt signaling pathway by decreasing the phosphorylation level of Akt and up-regulated p53 expression, while USP8 overexpression increased activation of the Akt signaling pathway in Hucct-1 cells. Further, IGF-1 could reverse the inhibitory effects of USP8 knockdown on the Akt signaling pathway and the proliferation of QBC939 and RBE cells.Conclusion: Taken together, our findings suggest that USP8 exerts an oncogenic role in the progression of cholangiocarcinoma and may be a potential therapeutic target for cholangiocarcinoma treatment.Keywords: cholangiocarcinoma, ubiquitin-specific protease 8, Akt signaling pathway

Rongfeng Qu,* Chunmei Hu,* Yan Tang, Qiong Yu, Guang Shi Department of Hematology and Oncology, The Second Hospital of Jilin University, Changchun 130041, Jilin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guang ShiDepartment of Hematology and Oncology, The Second Hospital of Jilin University, No. 218 Ziqiang Street, Changchun 130041, Jilin, People’s Republic of ChinaEmail drshiguang_shju@163.comIntroduction: At present, drug resistance remains a major obstacle for breast cancer (BCa) patients who receive tamoxifen (TAM) chemotherapy. In this study, we aimed to investigate the functional role of long non-coding RNA BLACAT1 in the acquisition of TAM resistance in BCa.Methods: TAM-resistant BCa cells were derived by exposure to 1 μM of TAM for 6 months. The expression levels of BLACAT1 and miR-503 were detected by RT-qPCR analysis. Chemosensitivity of BCa cells to TAM was measured by MTT assay. Apoptosis of BCa cells was detected by flow cytometric analysis, and the expression levels of apoptosis-related proteins were detected by Western blot analysis. The direct binding relation between BLACAT1 and miR-503 was predicted by bioinformatics analysis and verified by dual-luciferase reporter assay.Results: Our findings showed that BLACAT1 was significantly upregulated in TAM-resistant BCa cells (MCF-7/TR and T47D/TR), and BLACAT1 knockdown markedly reduced the TAM resistance in these cells. Importantly, we observed that BLACAT1 might function as a competing endogenous RNA of miR-503 in MCF-7/TR and T47D/TR cells, thereby increasing the expression of oncogenic Bcl-2 protein. Rescue experiments showed that miR-503 inhibition partly blocked the inhibitory effect of BLACAT1 knockdown on TAM resistance of MCF-7/TR and T47D/TR cells.Conclusion: To conclude, this study revealed that overexpressed BLACAT1 induces TAM resistance in human BCa partly by regulating miR-503/Bcl-2 axis, potentially benefiting BCa treatment in the future.Keywords: breast cancer, tamoxifen resistance, long non-coding RNA BLACAT1, miR-503, Bcl-2

Yutong He,1 Jin Shi,1 Bernd Schmidt,2 Qingyi Liu,3 Gaofeng Shi,4 Xiaoli Xu,5 Congmin Liu,1 Zhaoyu Gao,1 Tiantian Guo,1 Baoen Shan1 1Cancer Institute, The Fourth Hospital of Hebei Medical University/The Tumor Hospital of Hebei Province, Shijiazhuang, Hebei 050011, People’s Republic of China; 2Department of Internal Medicine - Pneumology and Sleep Medicine, Central Emergency Room, Palliative Medicine, DRK Kliniken Berlin, Berlin 13359, Germany; 3Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University/The Tumor Hospital of Hebei Province, Shijiazhuang, Hebei 050011, People’s Republic of China; 4Department of Radiology, The Fourth Hospital of Hebei Medical University/The Tumor Hospital of Hebei Province, Shijiazhuang, Hebei 050011, People’s Republic of China; 5Follow-Up Centre, The Fourth Hospital of Hebei Medical University/The Tumor Hospital of Hebei Province, Shijiazhuang, Hebei 050011, People’s Republic of ChinaCorrespondence: Baoen ShanCancer Institute, The Fourth Hospital of Hebei Medical University/The Tumor Hospital of Hebei Province, Shijiazhuang, Hebei 050011, People’s Republic of ChinaTel/Fax +86 311 86095613Email baoenshan62@sina.comBackground and Objective: Compared with tissue biopsy, liquid biopsy is the most preferable non-invasive promising method in personalized medicine, although it has many limitations in isolating circulating tumor cells (CTC). Lung cancer associated mortality is drastically increased due to a shortfall of early-stage detection, which remains a challenge. Herein, we aimed to detect lung cancer at an early-stage using CellCollector device.Methods: 39,627 volunteers underwent low-dose computed tomography; 2508 cases with pulmonary nodules and 7080 with no pulmonary nodules were chosen. After follow-up, 24 patients were diagnosed with early-stage non-small cell lung cancer (NSCLC), and subjected to CTC detection using CellCollector, along with 72 healthy volunteers. Immunofluorescence staining for EpCAM/CKs and CD45 were performed for CTC validation.Results: Fifteen out of twenty-four (stage I, n = 18; stage II, n = 6) early-stage lung cancer patients were found to be CTC-positive, whereas no CTC was found in the control group. Genetic mutation of TP53, ERBB2, PDGFRA, CFS1R and FGFR1 in the CTC revealed 71.6% of the mutation sites similar to the tumor tissues of 13 patients. Molecular characterization revealed higher expression of protein PD-LI in CTC (40%) as compared to tumor tissue (26.7%). Moreover, CTC clusters were detected in 40% of patients.Conclusion: CTC detection using the CellCollector in early-stage NSCLC had a relative high capture rate. Moreover, CTC analysis is a prospective setting for molecular diagnostic in cases when tumor tissue biopsy is not desirable.Keywords: CellCollector, in vivo detection, PD-L1, gene mutation, next generation sequencing

Ting Cheng,1,2,* Yong Li,1,2,* Shuai Pang,1,2 HuanYing Wan,1,2 GuoChao Shi,2,3 QiJian Cheng,1,2 QingYun Li,2,3 ZiLai Pan,4 ShaoGuang Huang2,31Department of Respiratory Medicine, Ruijin Hospital North, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Institute of Respiratory Diseases, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Respiratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Radiology, Ruijin Hospital North, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workBackgroud and objectives: Although lung attenuation distribution and lung volume on computed tomography (CT) have been widely used in evaluating COPD and interstitial lung disease, there are only a few studies regarding the normal range of these indices, especially in Chinese subjects. We aimed to describe the normal range of lung attenuation distribution and lung volume based on CT.Methods: Subjects with normal lung function and basically normal chest CT findings (derivation group) at Ruijin Hospital, Shanghai (from January 2010 to June 2014) were included according to inclusion and exclusion criteria. The range of the percentage of lung volume occupied by low attenuation areas (LAA%), percentile of the histogram of attenuation values (Perc n), and total lung volume were analyzed. Relationships of these measures with demographic variables were evaluated. Participants who underwent chest CT examination for disease screening and had basically normal CT findings served as an external validation group.Results: The number of subjects in the derivation group and external validation groups were 564 and 1,787, respectively. Mean total lung volumes were 4,468±1,271 mL and 4,668±1,192 mL, and median LAA%(-950 HU) was 0.19 (0.03–0.43) and 0.17 (0.01–0.41), in the derivation and external validation groups, respectively. Reference equations for lung volume and attenuation distribution (LAA% using -1,000–210 HU, Perc 1 to Perc 98) were generated: Lung volume (mL) = -1.015 *10^4+605.3*Sex (1= male, 0= female)+92.61*Height (cm) –12.99*Weight (kg) ±1766; LAA% (-950 HU)=[0.2027+0.05926*Sex (1= male, 0= female) –4.111*10^-3*Weight (kg) +4.924*10^-3*Height (cm) +8.504*10^-4*Age]^7.341–0.05; Upper limit of normal range: [0.2027+0.05926*Sex-4.111*10^-3*Weight+4.924*10^-3*Height+8.504*10^-4*Age+0.1993]^7.341–0.05.Conclusion: This large population-based retrospective study demonstrated the normal range of LAA%, Perc n, and total lung volume measured on CT scans among subjects with normal lung function and CT findings. Reference equations are provided.Keywords: lung attenuation, emphysema, lung volumes, quantitative computed tomography, reference equations, normal range, densitometry

Hong Chen,1,2 Yongjie Ding,1,2 Wei Chen,1,2 Yun Feng,1,2 Guochao Shi1,21Department of Respiration and Critical Care Disease, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 20025, People’s Republic of China; 2Institute of Respiratory Diseases, School of Medicine, Shanghai Jiaotong University, Shanghai 20025, People’s Republic of ChinaBackground: Pulmonary fat embolism (PFE) is one of the important causes of acute lung injury (ALI), but its pathogenesis is unclear. In recent years, it has been found that the NLRP3 inflammasome is closely related to inflammatory response. However, there are no reports about the involvement of NLRP3 in PFE- associated ALI. Glibenclamide is a kind of hypoglycaemic drug with anti-inflammatory effect. It has been reported to have the anti-inflammatory effect related to inhibiting NLRP3.Objective: To determine whether NLRP3 inflammasome was involved in ALI induced by PFE or whether glibenclamide had therapeutic effects on such lung injury, we designed this experiment.Materials and methods: The rat model of intravenous injection of oleic acid (OA) was used to simulate PFE. Rats were divided into three groups: control, OA and glibenclamide treatment group. Blood free fatty acid (FFA) concentration was determined by ACS-ACOD. Histopathological examinations were taken to assess the severity of lung injury. The expression of NLRP3 pathway and its downstream products were analyzed by IHC, WB, qPCR and ELISA.Results: Four hours after intravenous OA injection, the typical pathological manifestations of ALI accompanied by elevated levels of plasma FFAs were found. The activity of NLRP3 inflammasomes increased in OA group, too. Pretreatment with glibenclamide partly inhibited the increase in NLRP3, caspase-1 and IL-1β expression induced by OA, simultaneously attenuated the lung injury. But it has little effect on the expression of Toll-like receptor 4 (TLR4) expression in this experiment.Conclusion: NLRP3 inflammasome, one of the main components of innate immune response, involved in ALI induced by OA. Glibenclamide can alleviate this kind of ALI by inhibiting rather the NLRP3/caspase-1/IL-1β signaling pathway than the levels of FFAs or TLR4 pathway.Keywords: glibenclamide, oleic acid, acute lung injury, oxidative stress, NLRP3 inflammasome

The aim of this paper was exploring the effective utilization of nickel converter slag by means of the methodology of pressure oxidative leaching. The central composite design of response surface methodology was employed to optimize controlling conditions for the leaching of more valuable metals such as nickel, cobalt, and copper, while dissolution of iron was curbed. XRD, SEM-EDS were performed for characterizing the structure of leach residues for analyzing the mechanism of selective leaching. Experimental results demonstrate that the effects of temperature and sulfuric acid concentration on the metals extraction and filtration rate are significant, followed by liquid/solid (L/S) ratio. The optimized conditions for the leaching of converter slag are: temperature 208 °C, sulfuric acid concentration 0.35 mol/L, and L/S ratio 5.4 mL/g. Under these conditions, 99.60% Co, 99.20% Ni, and 96.80% Cu were extracted into solution together with only 0.21% Fe, and the filtration rate of leach slurry reached 576.86 L∙m‒2∙h‒1. The mechanism for achieving selective leaching of nickel, cobalt, and copper against iron dissolution and good filtration performance of the leach slurry was enabled by iron that dissolved in the solution, decomposed, and hydrolyzed mainly to form hematite (α-Fe2O3 and γ-Fe2O3), and letting silicic acid form precipitated SiO2 in the leach residue.

Xiaohong Yang, Gongming Shi, Jian Guo, Chenhui Wang, Yun He Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, People’s Republic of China Background: Staphylococcus aureus survival inside phagocytes is considered to provide a reservoir of bacteria that are relatively protected from antibiotics, thus enabling long-term colonization of the host and explaining clinical failures and relapses after antibiotic therapy. Purpose: The objective of this study was to develop a nanovesicle using exosomes loaded with linezolid to overcome intracellular infections by pathogenic bacteria. Methods: Exosomes were collected from the culture supernatants of RAW 264.7 cells. Their size distribution and zeta potential were characterized by dynamic light scattering, their morphology was characterized by transmission electron microscopy, and their protein content (CD63 and Flotillin 1) was assessed by Western blotting. Linezolid was incorporated into exosomes by co-incubation at 37°C and it’s accumulation in RAW264.7 cells and release in vitro were determined by high performance liquid chromatography. The intracellular bactericidal effect was evaluated in methicillin-resistant S. aureus (MRSA)-infected macrophages in vitro and MRSA peritonitis model in vivo. Results: We prepared a nanoformulation of the antibiotic linezolid using exosomes harvested from mouse RAW264.7 macrophages. The exosomal formulation of linezolid was more effective against intracellular MRSA infections in vitro and in vivo than the free linezolid. Our data also showed no signs of cytotoxicity in macrophages. Conclusion: Exosomes provide an effective alternative for intracellular antibiotic delivery of antibiotic that is efficacious, cost-effective, and safe. This regimen can be viewed as a potential antimicrobial agent for use against intracellular infections. Keywords: exosomes, antibiotic, delivery, intracellular infection, MRSA

XianHu Zhou,1,2* GuiDong Shi,1,2* BaoYou Fan,1,2 Xin Cheng,1,2 XiaoLei Zhang,1,2 Xu Wang,1,2 Shen Liu,1,2 Yan Hao,1,2 ZhiJian Wei,1,2 LianYong Wang,3 ShiQing Feng1,2 1International Science and Technology Cooperation Base of Spinal Cord Injury, Department of Orthopedic Surgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, People’s Republic of China; 3Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin, People’s Republic of China *These authors contributed equally to this work Background: Spinal cord injury (SCI) is a traumatic disease of the central nervous system, accompanied with high incidence and high disability rate. Tissue engineering scaffold can be used as therapeutic systems to provide effective repair for SCI. Purpose: In this study, a novel tissue engineering scaffold has been synthesized in order to explore the effect of nerve repair on SCI. Patients and methods: Polycaprolactone (PCL) scaffolds loaded with actived Schwann cells (ASCs) and induced pluripotent stem cells -derived neural stem cells (iPSC-NSCs), a combined cell transplantation strategy, were prepared and characterized. The cell-loaded PCL scaffolds were further utilized for the treatment of SCI in vivo. Histological observation, behavioral evaluation, Western-blot and qRT-PCR were used to investigate the nerve repair of Wistar rats after scaffold transplantation. Results: The iPSCs displayed similar characteristics to embryonic stem cells and were efficiently differentiated into neural stem cells in vitro. The obtained PCL scaffolds were ~0.5 mm in thickness with biocompatibility and biodegradability. SEM results indicated that the ASCs and (or) iPS-NSCs grew well on PCL scaffolds. Moreover, transplantation reduced the volume of lesion cavity and improved locomotor recovery of rats. In addition, the degree of spinal cord recovery and remodeling maybe closely related to nerve growth factor and glial cell-derived neurotrophic factor. In summary, our results demonstrated that tissue engineering scaffold treatment could increase tissue remodeling and could promote motor function recovery in a transection SCI model. Conclusion: This study provides preliminary evidence for using tissue engineering scaffold as a clinically viable treatment for SCI in the future. Keywords: induced pluripotent stem cells, polycaprolactone, spinal cord injury

Teng Ma,1–3,* Jian Cai,4,* Yin-Sheng Zhu,5 Xue-Feng Chu,5 Yong Wang,5 Guo-Ping Shi,5 Zheng-Dong Wang,5 Shun Yao,1–3 Xiao-Feng Wang,1–3 Xiao-Yan Jiang6–8 1Unit of Epidemiology, Ministry of Education Key Laboratory of Contemporary Anthropology, Fudan University, Shanghai, People’s Republic of China; 2State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, People’s Republic of China; 3National Clinical Research Center for Aging and Medicine (Huashan), Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 4Department of Neurology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 5Rugao People’s Hospital, Rugao, Jiangsu, People’s Republic of China; 6Key Laboratory of Arrhythmias of the Ministry of Education of China, Tongji University School of Medicine, Shanghai, People’s Republic of China; 7Department of Pathology and Pathophysiology, Tongji University School of Medicine, Shanghai, People’s Republic of China; 8Institute of Medical Genetics, Tongji University, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: Risk factors for heart rate-corrected QT interval (QTc) proglongation should be explored to stratify high-risk individuals to aid the prevention of incident cardiovascular events and mortality. The diversity of risk factors for QTc prolongation suggests that use of the frailty index (FI), indicating general health deficits, may be an effective approach, especially in the elderly, to identify the risk of QTc prolongation. Methods: We used the data of 1,780 individuals aged 70–87 years from the Rugao Longevity and Ageing Study (RuLAS), a community-based longitudinal study. The FI was constructed using 20 routine laboratory tests, plus the body mass index and measures of systolic and diastolic blood pressures (FI-Lab). Results: The mean FI-Lab value was 0.24±0.09. The mean heart rate-corrected QT interval (QTc) was 407±38 ms. The prevalence of QTc prolongation was 5.2% in elderly community populations aged 70–87 years. A higher FI-Lab value was associated with a higher risk for QTc prolongation. Each 10% increase in the FI-Lab value increased the odds ratio (OR) by 33% (OR: 1.33; 95% CI: 1.07–1.64). Compared with the lowest quartile, the top quartile FI-Lab score was associated with a 2.50-fold QTc prolongation risk in elderly individuals (95% CI: 1.21–5.19). Conclusion: An FI based on routine laboratory data can identify older adults at increased risk for QTc prolongation. The FI approach may therefore be useful for the risk stratification of QTc prolongation. Keywords: QTc prolongation, frailty, frailty index, Chinese elderly

Zhou X, Shi G, Fan B, et al. Int J Nanomedicine. 2018;13:6265–6277. Following a review of our data post-publication, we found the incorrect original image was supplied for Figure 4C. The correct image is shown in this corrigendum. This correction of the image has no impact to the findings of the study. The authors apologize for this error.Read the original article

Yingmeng Ni, Guochao Shi, Youchao Yu, Jimin Hao, Tiantian Chen, Huihui Song Department of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China Background: In the 2014 Global initiative for chronic Obstructive Lung Disease guidelines, bronchiectasis was for the first time defined as a comorbidity of chronic obstructive pulmonary disease (COPD), and this change has been retained in the 2015 update, which emphasizes the influence of bronchiectasis in the natural history of COPD. The present meta-analysis was aimed at summarizing the impact of bronchiectasis on patients with COPD. Methods: Databases including Embase, PubMed, and the Cochrane Central Register of Controlled Trials were searched comprehensively to identify all relevant human clinical studies published until August 2014. Bronchiectasis was confirmed either by computed tomography or high-resolution computed tomography. One or more clinicopathological or demographical characteristics, including age, sex, smoking history, daily sputum production, exacerbations, inflammatory biomarkers, lung function, and colonization by potentially pathogenic microorganisms (PPMs), were compared between COPD patients with and without bronchiectasis. Results: Six observational studies with 881 patients were included in the meta-analysis. The mean prevalence of bronchiectasis in patients with COPD was 54.3%, ranging from 25.6% to 69%. Coexistence of bronchiectasis and COPD occurred more often in male patients with longer smoking history. Patients with COPD and comorbid bronchiectasis had greater daily sputum production, more frequent exacerbation, poorer lung function, higher level of inflammatory biomarkers, more chronic colonization by PPMs, and higher rate of Pseudomonas aeruginosa isolation. Conclusion: In spite of the heterogeneity between included studies and detectable publication bias, this meta-analysis demonstrated the impact of bronchiectasis in patients with COPD in all directions, indicating that coexistence of bronchiectasis should be considered a pathological phenotype of COPD, which may have a predictive value. Keywords: bronchiectasis, chronic obstructive pulmonary disease, phenotype, meta-analysis

Zhidong Wang,1 Bin Wang,1 Huanchen Guo,2 Guoyu Shi,2 Xiuqin Hong3 1Oncology Department, Eighth Hospital of Changsha, Changsha, People’s Republic of China; 2Department of Respiratory Medicine, Shouguang Hospital of Traditional Chinese Medicine, Shouguang, People’s Republic of China; 3Institute of Gerontology, Hunan Geriatric Hospital, Changsha, People’s Republic of China Background: Previous studies demonstrate that T-cadherin is a candidate tumor suppressor in several types of human tumors, including non-small cell lung cancer (NSCLC). Lack of protein expression of T-cadherin by hypermethylation has been found to play an important role in lung alveolar differentiation regulation and epithelial tumorigenesis. However, the correlation between T-cadherin hypermethylation and clinicopathological characteristics of NSCLC remains unclear. Here we conducted a systematic review and meta-analysis to quantitatively evaluate the effects of T-cadherin hypermethylation on the incidence of NSCLC and clinicopathological characteristics.Methods: A detailed literature search was carried out for related research publications. Analyses of pooled data were performed. Odds ratio (OR) and hazard ratio (HR) were calculated and summarized, respectively.Results: Final analysis of 1,172 NSCLC patients from 15 eligible studies was performed. T-cadherin hypermethylation was observed to be significantly higher in NSCLC than in normal lung tissue, based on the pooled OR from nine studies including 532 NSCLC and 372 normal lung tissue samples (OR=8.19, 95% confidence interval [CI]=5.41–12.39, P

Patients undergoing radical prostatectomy (RP) are at high risk for erectile dysfunction (ED) due to potential cavernous nerve (CN) damage during surgery. Penile hypoxia after RP is thought to significantly contribute to ED pathogenesis.We previously showed that corpora cavernosum smooth muscle cells (CCSMCs) undergo phenotypic modulation under hypoxic conditions in vitro. Here, we studied such changes in an in vivo post-RP ED model by investigating CCSMCs in bilateral cavernous neurectomy (BCN) rats.Sprague-Dawley rats underwent sham (n = 12) or BCN (n = 12) surgery. After 12 weeks, they were injected with apomorphine to determine erectile function. The penile tissues were harvested and assessed for fibrosis using Masson trichrome staining and for molecular markers of phenotypic modulation using immunohistochemistry and western blotting. CCSMC morphological structure was evaluated by hematoxylin-eosin (H&E) staining and transmission electron microscopy (TEM).Erectile function was significantly lower in BCN rats than in sham rats. BCN increased hypoxia-inducible factor-1α and collagen protein expression in corpora cavernous tissue. H&E staining and TEM showed that CCSMCs in BCN rats underwent hypertrophy and showed rough endoplasmic reticulum formation. The expression of CCSMC phenotypic markers, such as smooth muscle α-actin, smooth muscle myosin heavy chain, and desmin, was markedly lower, whereas vimentin protein expression was significantly higher in BCN rats than in control rats.CCSMCs undergo phenotype modulation in rats with cavernous neurectomy. The results have unveiled physiological transformations that occur at the cellular and molecular levels and have helped characterize CN injury-induced ED.