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Gang Deng, Yuanyuan Yang, Song Lu, Lin Ma, Guohua Wu College of Biotechnology and Sericultural Research Institute, Jiangsu University of Science and Technology, Zhenjiang, 212100, People’s Republic of ChinaCorrespondence: Guohua Wu, Email ghwu@just.edu.cnIntroduction: With the development of technology, personal heat management has become a focus of attention. Phase change fabrics, as intelligent materials, are expected to be widely used in multiple fields, bringing comfortable, intelligent and convenient living experience.Methods: In this study, miniature phase change microcapsules (MPCM) with n-octadecane as core and poly(methyl methacrylate) as shell were successfully prepared. Using the in-situ reduction property of polydopamine, gold nanoparticles were deposited on the surface of the microcapsules, which retained the heat storage function and imparted photothermal and antibacterial properties. The MPCM with photothermal conversion function was modified on the surface of silk fabric using aqueous polyurethane after verified by comprehensive material characterisation techniques.Results: Under the near infrared light of 808 nm wavelength and 0.134 W/cm² irradiation intensity, the MPCM@PDA@Au modified silk fabrics showed excellent photothermal conversion performance, which could be increased from 25°C to 60°C in 50s. After the light source was cut off, the fabrics showed good heat release ability, with melting enthalpy and crystallisation enthalpy reaching 41.58 J/g and 43.3 J/g, respectively, which were not changed after repeated cycles. After the light source is cut off, the fabric has good heat release ability, and the enthalpy of melting and crystallisation reaches 41.58 J/g and 43.3 J/g, respectively, and the photothermal efficiency remains unchanged after many cycles of use, which proves that it has excellent durability and stability. The antimicrobial test shows that the fabric has significant antibacterial effect on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus).Discussion: MPCM@PDA@Au silk fabrics bring new possibilities for the future of personal thermal management and antimicrobial protection in the field of medical health, outdoor sports and other areas of broad application prospects, heralding the birth of a series of innovative applications and solutions.Keywords: photothermal conversion, phase change material, thermal energy storage, functional textile

Jianguo Song,1,* Huanliang Meng,2,* Guoying Deng,1 Haodong Lin1 1Trauma Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, People’s Republic of China; 2Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guoying Deng; Haodong Lin, Trauma Center, Shanghai General Hospital, 650 New Songjiang Road, Shanghai, 201620, People’s Republic of China, Email guoying.deng@shgh.cn; haodong.lin@hotmail.comBackground: Inhibiting ROS overproduction is considered a very effective strategy for the treatment of peripheral nerve injuries, and Se has a remarkable antioxidant effect; however, since the difference between the effective concentration of Se and the toxic dose is not large, we synthesized a nanomaterial that can release Se slowly so that it can be used more effectively.Methods: Se@SiO2 NPs were synthesized using a mixture of Cu2-x Se nanocrystals, and the mechanism of action of Se@SiO2 NPs was initially explored by performing sequencing, immunofluorescence staining and Western blotting of cellular experiments. The mechanism of action of Se@SiO2 NPs was further determined by performing behavioral assays after animal experiments and by sampling the material for histological staining, immunofluorescence staining, and ELISA. The effects, mechanisms and biocompatibility of Se@SiO2 NPs for peripheral nerve regeneration were determined.Results: Porous Se@SiO2 was successfully synthesized, had good particle properties, and could release Se slowly. CCK-8 experiments revealed that the optimal experimental doses were 100 μM H2O2 and 200 μg/mL Se@SiO2, and RNA-seq revealed that porous Se@SiO2 was associated with cell proliferation, apoptosis, and the PI3K/AKT pathway. WB showed that porous Se@SiO2 could increase the expression of cell proliferation antigens (PCNA and S100) and antiapoptotic proteins (Bcl-2), decrease the expression of proapoptotic proteins (Bax), and increase the expression of antioxidative stress proteins (Nrf2, HO-1, and SOD2). EdU cell proliferation and ROS fluorescence assays showed that porous Se@SiO2 promoted cell proliferation and reduced ROS levels. The therapeutic effect of LY294002 (a PI3K/AKT pathway inhibitor) was decreased significantly and its effect was lost when it was added simultaneously with porous Se@SiO2. Animal experiments revealed that the regenerated nerve fiber density, myelin thickness, axon area, gastrocnemius muscle wet-to-weight ratio, myofiber area, sciatic nerve function index (SFI), CMAP, apoptotic cell ratio, and levels of antioxidative stress proteins and anti-inflammatory factors were increased following the administration of porous Se@SiO2. The levels of oxidative stress proteins and anti-inflammatory factors were significantly greater in the Se@SiO2 group than in the PNI group, and the effect of LY294002 was decreased significantly and was lost when it was added simultaneously with porous Se@SiO2.Conclusion: Se@SiO2 NPs are promising, economical and effective Se-releasing nanomaterials that can effectively reduce ROS production, inhibit apoptosis and promote cell proliferation after nerve injury via the PI3K/AKT pathway, ultimately accelerating nerve regeneration. These findings could be used to design new, promising drugs for the treatment of peripheral nerve injury. Keywords: Se@SiO2, PI3K/AKT, PNI, antioxidative stress, apoptosis

Min Yang,1– 3,* Wenfei Wang,3,* Peize Zhang,4 Guizhen Liu,5 Hailin Lu,6 Mingjie He,5 Guofang Deng,2,3 Xiaoyou Chen1,7 1Department of Pharmacology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Second Department of Pulmonary Medicine and Tuberculosis, the Third People’s Hospital of Shenzhen, Southern University of Science and Technology, Shenzhen, Guangdong, People’s Republic of China; 3National Clinical Research Center for Infectious Disease, the Third People’s Hospital of Shenzhen, Southern University of Science and Technology, Shenzhen, Guangdong, People’s Republic of China; 4Fourth Department of Pulmonary Medicine and Tuberculosis, the Third People’s Hospital of Shenzhen, Southern University of Science and Technology, Shenzhen, Guangdong, People’s Republic of China; 5The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, People’s Republic of China; 6Gannan Medical University, Ganzhou, Jiangxi, People’s Republic of China; 7Infectious Diseases Department, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoyou Chen; Guofang Deng, Email chenxy1998@hotmail.com; jxxk1035@yeah.netObjective: We aimed to investigate dysregulated metabolic pathways and identify diagnostic and therapeutic targets in patients with tuberculosis-diabetes (TB-DM).Methods: In our prospective cohort study, plasma samples were collected from healthy individuals, diabetic (DM) patients, untreated TB-only (TB-0)/TB-DM patients (TB-DM-0), and cured TB (TB-6)/TB-DM patients (TB-DM-6) to measure the levels of amino acids, fatty acids, and other metabolites in plasma using high-throughput targeted quantification methods.Results: Significantly different biological processes and biomarkers were identified in DM, TB-DM-0, and TB-DM-6 patients. Moreover, quinolinic acid (QA) showed excellent predictive accuracy for distinguishing between DM patients and TB-DM-0 patients, with an AUC of 1 (95% CI 1– 1). When differentiating between TB-DM-0 patients and TB-DM-6 patients, the AUC was 0.9297 (95% CI 0.8460– 1). Compared to those in DM patients, the QA levels were significantly elevated in TB-DM-0 patients and decreased significantly after antituberculosis treatment. We simultaneously compared healthy controls and untreated tuberculosis patients and detected an increase in the level of QA in the plasma of tuberculosis patients, which decreased following treatment.Conclusion: These findings improve the current understanding of tuberculosis treatment in patients with diabetes. QA may serve as an ideal diagnostic biomarker for TB-DM patients and contribute to the development of more effective treatments.Keywords: pulmonary tuberculosis, diabetes, metabolomics, quinolinic acid, biomarker

Liang Fu,1,2,* Wenfei Wang,2,3,* Juan Xiong,4,* Peize Zhang,2 Hui Li,2 Xilin Zhang,5 Hancheng Liang,6 Qianting Yang,2 Zhaoqin Wang,2 Xinchun Chen,3 Guofang Deng,2 Yi Cai,3 Shenjie Tang1 1Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumour Research Institute, Beijing, People’s Republic of China; 2Shenzhen Third People’s Hospital, National Clinical Research Center for Infectious Disease (Shenzhen), Shenzhen Clinical Research Center for Tuberculosis, Southern University of Science and Technology, Shenzhen, Guangdong, People’s Republic of China; 3Department of Pathogen Biology, Guangdong Key Laboratory of Regional Immunity and Diseases, Shenzhen University School of Medicine, Shenzhen, Guangdong, People’s Republic of China; 4Health Science Center, Shenzhen University, Shenzhen, Guangdong, People’s Republic of China; 5Tuberculosis Prevention and Control Department, the Fourth People’s Hospital of Foshan, Foshan, Guangdong, People’s Republic of China; 6Division Two of Tuberculosis Diseases Department, the Sixth People’s Hospital of Dongguan, Dongguan, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shenjie Tang; Yi Cai, Email tangsj1106@hotmail.com; caiyi0113@szu.edu.cnBackground: The rising prevalence and limited efficacy of treatments for pre-extensively drug-resistant tuberculosis (pre-XDR-TB) underscore an immediate need for innovative therapeutic options. A combination of host-directed therapy (HDT) and anti-TB treatment presents a viable alternative for pre-XDR-TB management. Sulfasalazine (SASP), by targeting the amino acid transport system xc (xCT), potentially reduces the intracellular Mycobacterium tuberculosis load and mitigates lung pathology, positioning it as a promising TB HDT agent. This study aims to assess the efficacy of SASP as a supplementary therapy for pre-XDR-TB.Methods: A pilot study examined the safety and effectiveness of two 9-month short-course, all-oral regimens for pre-XDR-TB treatment: Bdq-regimen (consisting of Bdq, linezolid, cycloserine, clofazimine, and pyrazinamide) and SASP-regimen (comprising SASP, linezolid, cycloserine, clofazimine, and pyrazinamide). The primary endpoint was the incidence of unfavorable outcomes 12 months post-treatment.Results: Of the 44 participants enrolled, 43 were assessable 12 months post-treatment. Culture conversion rates stood at 73.2% by Month 2 and escalated to 95.1% by Month 6. Overall, 88.4% (38/43) of the participants exhibited favorable outcomes, 85.2% (19/23) for the Bdq-regimen and 93.8% (14/15) for the SASP-regimen. The SASP-regimen group recorded no deaths or treatment failures.Conclusion: Both 9-month short-course, all-oral regimens manifested commendable primary efficacy in treating pre-XDR-TB patients. The SASP-regimen emerged as effective, safe, well-tolerated, and cost-effective.Plain language summary: This study explored a new way to treat a hard-to-treat type of tuberculosis (TB) using a medicine called Sulfasalazine, alongside usual TB treatments. Over 9 months, two groups of patients were given different sets of medicines, one including Sulfasalazine. The results, checked 12 months after treatment, showed that most patients improved, especially those given Sulfasalazine. No one in the Sulfasalazine group died or had their treatment fail, suggesting that Sulfasalazine could be a promising addition to current treatments for this tough-to-treat TB.Keywords: Sulfasalazine, host-directed therapy, pre-extensive drug-resistant tuberculosis, short-course, treatment

Yuhua Mai,1,2 Liheng Meng,1 Ganlu Deng,2,3 Yingfen Qin1 1Department of Endocrinology, The First Affiliated Hospital of GuangXi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 2Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer (Guangxi Medical University), Ministry of Education, Nanning, Guangxi, 530021, People’s Republic of China; 3Department of Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of ChinaCorrespondence: Yingfen Qin, Department of Endocrinology, The First Affiliated Hospital of GuangXi Medical University, Nanning, 530021, Guangxi, People’s Republic of China, Tel/Fax +86-13607862619, Email yingfenq@126.com Ganlu Deng, Department of Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China, Tel/Fax +86-15676132389, Email dengganlu@gxmu.edu.cnAbstract: With changes in modern lifestyles, type 2 diabetes mellitus (T2DM) has become a global epidemic metabolic disease, and hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. T2DM is a complex metabolic disorder and has been considered an independent risk factor for HCC. Growing evidence supports that T2DM-related risk factors facilitate hepatocarcinogenesis via abundant mechanisms. With the wide implementation of microbiomics, transcriptomics, and immunotherapy, the understanding of the complex mechanisms of intestinal flora and immune cell subsets have advanced tremendously in T2DM-related HCC, uncovering new findings in T2DM-related HCC patients. In addition, reports have indicated the different effects of anti-DM drugs on the progression of HCC. In this review, we summarize the effects of major T2DM-related risk factors (including hyperglycemia, hyperinsulinemia, insulin, chronic inflammation, obesity, nonalcoholic fatty liver disease, gut microbiota and immunomodulation), and anti-DM drugs on the carcinogensis and progression of HCC, as well as their potential molecular mechanisms. In addition, other factors (miRNAs, genes, and lifestyle) related to T2DM-related HCC are discussed. We propose a refined concept by which T2DM-related risk factors and anti-DM drugs contribute to HCC and discuss research directions prompted by such evidence worth pursuing in the coming years. Finally, we put forward novel therapeutic approaches to improve the prognosis of T2DM-related HCC, including exploiting novel diagnostic biomarkers, combination therapy with immunocheckpoint inhibitors, and enhancement of the standardized management of T2DM patients.Keywords: type 2 diabetes mellitus, hepatocellular carcinoma, NAFLD, gut microbiota, inflammatory, immunotherapy

Jiahan Qiu,1,2 Jiaxun Chen,2 Gaopi Deng,1,* Shuo Yuan1,* 1Department of Gynaecology, the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shuo Yuan, Department of Gynaecology, the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Jichang Road 16#, District Baiyun, Guangzhou, 510405, People’s Republic of China, Tel +86-13632466654, Email twinklingyuan@gzucm.edu.cnBackground: In this study, we conducted an integrated study of the diagnostic value of MiR-223 in ectopic pregnancy (EP).Methods: We used GSE44731 downloaded from GEO and GEO2R to identify differentially expressed miRNA. The hub genes corresponding to the differential miRNA were then identified by using the Xiantao academic tool, GO (Gene Ontology), and KEGG (Kyoto Encyclopedia of Genes and Genomes). Afterward, we used the miEAA database to perform gene set enrichment analysis (GSEA) of differential miRNA, and used Xiantao academic tools again to conduct the ceRNA network based on the target genes. Protein–protein interaction (PPI) network construction and lncRNA of hub miRNA target genes were then predicted by the starbase database. For validation, the villus tissue from intrauterine pregnancy and tubal pregnancy was collected and assayed by qPCR.Results: In total 19 differentially expressed miRNAs were screened out, of which MiR-223 had a relatively clear diagnostic significance. Hub genes were enriched and analyzed by GO, KEGG, and GSEA, and the results showed that regulation of NF-κB and other signaling pathways are primarily enriched in ectopic pregnancy. We also obtained 215 key genes from PPI analysis. Our ceRNA analysis indicated that LRRC75A-AS1 and PITPNA-AS1 were associated with MiR-223, and the expression of MiR-223 in qPCR was significantly high in tubal pregnancy group.Conclusion: We found that MiR-223 can be used in the diagnosis of EP. Our findings provide valuable information and direction for future research into novel targets for EP diagnosis.Keywords: MiRNA-223, tubal pregnancy, disease marker, biomarker, GEO

Zhilin Liang,1,* Weiming Liao,2,* Qifu Chen,3 Hui Li,1 Meiling Ye,1 Jin Zou,4 Guofang Deng,1 Peize Zhang1 1Department of Pulmonary Medicine & Tuberculosis, The Third People’s Hospital of Shenzhen, National Clinical Research Center for Infectious Disease, Southern University of Science and Technology, Shenzhen, People’s Republic of China; 2Department of Thoracic Oncology, Jiangxi Provincial Cancer Hospital, Nanchang, People’s Republic of China; 3Department of Neurosurgery, The Third People’s Hospital of Shenzhen, National Clinical Research Center for Infectious Disease, Southern University of Science and Technology, Shenzhen, People’s Republic of China; 4Department of Clinical Laboratory, The Third People’s Hospital of Shenzhen, National Clinical Research Center for Infectious Disease, Southern University of Science and Technology, Shenzhen, People’s Republic of China*These authors contributed equally to this workCorrespondence: Peize Zhang; Guofang Deng, Tel +8613509650204 ; +8613530027001, Email 82880246@qq.com; jxxk1035@yeah.netAbstract: Drug-resistant tuberculous meningitis (TBM) is the most devastating and critical form of extrapulmonary tuberculosis. Here, we present a case of a 45-year-old male with pre-extensive drug-resistant tuberculosis meningitis (pre-XDR-TBM). He underwent emergency surgery for the long-tunneled external ventricular drainage (LTEVD). Molecular test and phenotypic drug sensitivity test (DST) of Mycobacterium tuberculosis in cerebrospinal fluid (CSF) showed that the isolate was resistant to both rifampin and fluoroquinolones. An anti-tuberculous regimen of isoniazid, pyrazinamide, cycloserine, moxifloxacin, clofazimine, and linezolid was tailored accordingly. We monitored the drug concentration in his plasma and CSF before (at 0-hour) and after anti-TB drugs administration (at 1-hour, 2-hour, 6-hour, and 12-hour) on 10th day after treatment initiation. We hope to provide reference values of drug exposures in plasma and CSF for patients with pre-XDR-TBM.Keywords: pre-extensive drug resistant TB, tuberculous meningitis, pharmacokinetics, long-tunneled external ventricular drain, drug concentration

Lanyao Yang1,2 *, Lanlan Wu3 *, Yao Liu,3 Hengying Chen,4 Yuanhuan Wei,3 Ruifang Sun,3 Siwen Shen,3 Bowen Zhan,1,2 Jianjun Yang,1,2 Guifang Deng3 1Department of Nutrition and Food Hygiene, School of Public Health and Management, Ningxia Medical University, Yinchuan, People’s Republic of China; 2Key Laboratory of Environmental Factors and Chronic Disease Control, School of Public Health and Management, Ningxia Medical University, Yinchuan, People’s Republic of China; 3Department of Clinical Nutrition, Union Shenzhen Hospital of Huazhong University of Science and Technology, Shenzhen, People’s Republic of China; 4Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guifang Deng, Department of Clinical Nutrition, Union Shenzhen Hospital of Huazhong University of Science and Technology, No. 89 Taoyuan Road, Shenzhen, Guangdong, 518052, People’s Republic of China, Email misyfly@163.com Jianjun Yang, Department of Nutrition and Food Hygiene, School of Public Health and Management, Ningxia Medical University, No. 1160 Shengli Road, Yinchuan, Ningxia, 750004, People’s Republic of China, Email yangjj@nxmu.edu.cnObjective: This study evaluated the associations of serum ferritin (SF) concentration during pregnancy with the risk of adverse maternal and fetal pregnancy outcomes.Methods: We conducted a retrospective study of 2327 pregnant women from 2015 to 2020 in Guangdong, China. SF concentrations were measured at 16– 18th and 28– 32th week of gestation. Logistic regression models were applied to estimate the association between SF concentration and the risk of adverse pregnancy outcomes.Results: After multivariable adjustment, the odds ratio (OR) of the highest quartile of SF concentration at 16– 18th week of gestation was 1.43 (95% confidence interval [CI]: 1.09, 1.89) for gestational diabetes mellitus (GDM) and 1.79 (95% CI: 1.15, 2.79) for small for gestational age (SGA) when compared with the lowest quartile. At 28– 32th week of gestation compared with the lowest quartile, women with SF in the highest quartile had an increased risk of SGA (OR: 1.62; 95% CI: 1.01, 2.62). Moreover, the lowest quartile of SF concentration decreased risk of SGA by 90% (95% CI: 0.01, 0.80) when compared with the highest quartile among pregnancy women with GDM.Conclusion: Elevated SF concentrations increased the risk of GDM and SGA during pregnancy. Maintaining an appropriately low level of maternal SF at 28– 32th week of gestation in women with GDM could reduce the risk of SGA.Keywords: ferritin, adverse pregnancy outcomes, gestational diabetes mellitus, small for gestational age

Youli Jiang,1,* Lan Luo,2,3,* Min Gui,1 Linlin Liu,1 Yi Lin,2,3 Guofang Deng,2,3 Jingfang Chen,1,3 Peize Zhang2,3 1Hengyang Medical School, School of Nursing, University of South China, Hengyang, People’s Republic of China; 2Department of Pulmonary Medicine and Tuberculosis, The Third People’s Hospital of Shenzhen, Shenzhen, People’s Republic of China; 3National Clinical Research Center for Infectious Diseases, The Third People’s Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jingfang Chen; Peize Zhang, Email 13823139640@163.com; 82880246@qq.comBackground: Early diagnosis and timely treatment of tuberculosis are critical for disease control and management. However, diagnostic delay remains severe around the world. We aim to evaluate the duration and factors associated with diagnostic delay of tuberculosis in Shenzhen, China.Methods: We conducted a face-to-face interview to collect the whole care-seeking process of patients diagnosed with active TB in Shenzhen, China, from April 1 to September 30, 2021. The duration from symptom onset to confirmed diagnosis was recorded. The risk factors of diagnostic delay were identified by binary stepwise logistic regression analysis.Results: Among 288 confirmed TB cases, 170 (59.0%) were delayed diagnosis. The median diagnostic delay was 39.5 days. Median patient delay was 23 days and health system delay was 7 days. Income ≤ 315USD/month (OR = 2.97 [95% CI: 1.15– 7.69]), cough (OR = 3.00 [95% CI: 1.16– 7.76]), weight loss (OR = 15.59 [95% CI: 1.85– 131.56]), use of traditional Chinese Medicine (OR = 5.03 [95% CI: 1.04– 24.31]) and over-the-counter cough syrup (OR = 2.73 [95% CI: 1.10– 6.76]) were significant risk factors for patient delay. Fever (OR = 0.13[95% CI: 0.04– 0.48]) and hemoptysis (OR = 0.06 [95% CI0.01– 0.30]) were protective factors for patient delay. Cough (OR = 2.85 [95% CI: 1.49– 5.49]) and availability of chest X-ray (OR = 0.21[CI: 0.11– 0.39]) were factors associated with health system delay.Conclusion: Delayed diagnosis of tuberculosis remains an unresolved problem. Patients with low income, self-treatment with over-the-counter medicine and accepting TCM suffered from a higher risk of patient delay. It is important to give more help to the vulnerable people and strengthen tuberculosis knowledge among primary health providers. Keeping all health providers alert to TB symptoms can facilitate earlier TB diagnosis and better disease control.Keywords: tuberculosis, diagnosis, delay, patient delay, health system delay

Yuling Lai,1,2 Fuling Zeng,1 Zhenyue Chen,1 Min Feng,1 Yanxi Huang,3 Pin Qiu,3 Lihua Zeng,1 Yan Ke,4 Gaopi Deng,3,* Jie Gao3,* 1First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Department of Sports Medicine, Guangzhou Sport University, Guangzhou, People’s Republic of China; 3Department of Gynaecology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 4Department of Gynaecology, Shenzhen Chinese and Western Medicine Hospital, Shenzhen, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jie Gao; Gaopi Deng, Email gaojie1769@gzucm.edu.cn; denggaopi@126.comBackground: Albeit oxidative stress has been implied in the pathogenesis of tubal pregnancy (TP), there are scant data to suggest that ferroptosis occurs in TP. Shikonin plays a pivotal role in redox status, but whether it can regulate ferroptosis to treat TP remains unknown.Methods: We collected and analyzed ferroptosis-related indices from the villous tissue (VT) of women suffering from TP and from women with a normal pregnancy. In vitro, we used shikonin and/or RAS-selective lethal 3 (RSL3) to intervene HTR-8/SVneo cells and further detected ferroptosis indices and cell functions. Finally, the expression of the nuclear factor erythroid 2-related factor 2 (Nrf2) is pharmacologically activated to explore the effect of Nrf2 on shikonin regulating ferroptosis.Results: Increased malondialdehyde content, reduced levels of glutathione and glutathione peroxidase (GPx), and upregulated protein expression which promoted ferroptosis were observed in the VT of TP patients, suggesting that ferroptosis occurred during TP. In vitro, shikonin enhanced ferroptosis sensitivity in HTR-8/SVneo cells induced by RSL3 via amplifying lipid peroxidation, which mainly included increasing cellular reactive oxygen species (ROS), lipid ROS and Fe2+ level. RSL3 and/or shikonin inhibited Nrf2 and downregulated protein expression of SLC7A11 and GPx4 caused by RSL3 + shikonin co-treatment, which could be reversed under activation of Nrf2. Hence, shikonin facilitated lipid peroxidation by inhibiting Nrf2 signaling. Additionally, shikonin and/or RSL3 potently inhibited the invasion and migration of HTR-8/SVneo cells.Conclusion: This study firstly showed that ferroptosis may be involved in TP pathogenesis and shikonin potentially targeted ferroptosis to treat TP.Keywords: ectopic pregnancy, shikonin, lipid peroxidation, iron dependent

Senlin Zhan,1,&ast; Xiong Juan,2,&ast; Tantan Ren,1 Yuxiang Wang,1 Liang Fu,1 Guofang Deng,1 Peize Zhang1 1Department of Pulmonary Medicine and Tuberculosis, The Third People’s Hospital of Shenzhen, Shenzhen, Guangdong, People’s Republic of China; 2School of Public Health, Health Science Center, Shenzhen University, Shenzhen, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guofang Deng; Peize Zhang, Email jxxk1035@yeah.net; 82880246@qq.comBackground: Diabetes mellitus (DM) is believed to affect tuberculosis (TB) at multiple levels in disease control and treatment efficacy, but clinical and radiological presentation resulting from interaction of the two diseases is not known.Methods: A cross-sectional study was conducted on data obtained from medical records of 438 patients confirmed with TB-DM comorbidity at the Third people’s hospital of Shenzhen from May 01, 2014, to April 30, 2019. Their CT images were reviewed, and patients were divided into subgroups according to lung cavitation: with and without cavities, and number of segments showing pulmonary infiltration: < 4 segment, 4– 8 segment, > 8 segment infiltrates. We then compared clinical parameters between these groups.Results: The median age of the patients was 50.0 years (IQR 43.3– 56.0) and 86% (n=375) of them were male. Pulmonary cavities were found in 80.8% patients. About 42.7% and 27.2% patients were seen to have infiltration involving 4– 8 and > 8 lung segments, respectively. Patients presented with cavitation and infiltration involving a greater number of lung segments had significantly higher values of WBC, MONO%, GRA%, CRP, lower LYN% level and higher bacterial burden in sputum (P< 0.001). Higher HbA1c and FBG were only observed in patients with lung cavities (P< 0.001). There was no difference in positive ELISPOT.TB and PCT level between the groups regardless of presence or absence of lung cavity (P> 0.9 and P=0.1 respectively). Lower HGB, ALB and higher PCT were observed in patients with infiltration involving more lung segments.Conclusion: Hyper-inflammation in peripheral blood was significantly associated with cavity and the number of lung lesions. Hyperglycemia was significantly associated with the development of lung cavity. Glycemic control and inflammation influenced radiographic manifestations in patients with TB-DM.Keywords: diabetes mellitus, tuberculosis, lung cavity, lung infiltration, radiography

Peize Zhang,1,2 Wei Li,3 Miaona Liu,3 Senlin Zhan,2 Hailin Zhang,2 Guofang Deng,2 Xiaoyou Chen1 1Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, People’s Republic of China; 2Department of Pulmonary Medicine and Tuberculosis, The Third People’s Hospital of Shenzhen, Shenzhen, Guangdong, People’s Republic of China; 3Department of Pharmacy, The Third People’s Hospital of Shenzhen, Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Guofang Deng; Xiaoyou Chen, Email jxxk1035@yeah.net; chenxy1998@hotmail.comObjective: Linezolid is one of the key drugs for the treatment of multidrug-resistant/extensively drug-resistant tuberculosis (MDR/XDR-TB). We aimed to describe the incorporation of the Michigan Neuropathy Screening Instrument (MNSI) and serum trough concentration as screening tools for neurotoxicity in the management of MDR/XDR-TB patients receiving a linezolid-based treatment regimen in Shenzhen, China.Methods: A total of 73 patients on a linezolid-containing anti–MDR/XDR-TB regimen were prospectively enrolled. The MNSI was used for peripheral neuropathy screening. Optic neuropathy was diagnosed by ophthalmologists. Serum trough concentration was recorded and its relationship with neuropathy analyzed.Results: Of all patients, neuropathy was observed in 40% (29) during anti-TB treatment. Of these, 20 (69%) had peripheral neuritis, seven (24%) optic neuritis, and two (7%) both. Serum trough concentration > 2 mg/L was observed in 17 (59%) patients with neuropathy and 13 (30%) patients without neuropathy. There was a significant statistical difference between the two groups (P=0.013). Time to onset of neuropathy from initiation of the linezolid-containing regimen was within 2 months for eight (28%) patients, 2– 6 months for 18 (62%) patients, and > 6 months for three (10%) patients. Sixteen (55%) patients were adjusted to a lower dose of 300 mg linezolid daily. Four (14%) patients had linezolid permanently removed from their regimen.Conclusion: Neuropathy is a commonly reported adverse event associated with long-term use of linezolid. MNSI and serum trough–concentration monitoring can be adopted as simple screening tools for early detection of neuropathy to balance linezolid efficacy and tolerability.Keywords: linezolid, MDR/XDR-TB, neuropathy, MNSI, serum trough concentration

Yi Zhong,1,2,* Guoyong Du,1,2,* Jie Liu,1,2,* Shaohua Li,1 Junhua Lin,1 Guoxiong Deng,1,2 Jinru Wei,1,2 Jun Huang1,2 1Department of Cardiology, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530022, People’s Republic of China; 2Department of Cardiology, The First People’s Hospital of Nanning, Nanning, Guangxi, 530022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jinru Wei; Jun Huang, Tel +867712636193, Email weijinru@stu.gxmu.edu.cn; huangjijun1981@163.comBackground: Cardiovascular complications are a major cause of death and disability in patients with diabetes mellitus, but how such complications arise is unclear.Methods: Weighted gene correlation network analysis (WGCNA) was performed on gene expression profiles from healthy controls, individuals with diabetes mellitus, and individuals with diabetes mellitus-associated coronary artery disease (DMCAD). Phenotypically related module genes were analyzed for enrichment in Gene Ontology (GO) terms and Kyoto Gene and Genome Encyclopedia (KEGG) pathways. Predicted biological functions were validated using gene set enrichment analysis (GSEA) and ClueGo analysis. Based on the TRRUST v2 database and hypergeometric tests, a global network was built to identify transcription factors (TFs) and downstream target genes potentially involved in DMCAD.Results: WGCNA identified three modules associated with progression from diabetes mellitus to DMCAD. The module genes were significantly involved in biological processes related to interferon and viral infection, while GSEA of DMCAD samples suggested involvement in viral myocarditis, chemokine signaling and phagosomes. RUNX1 was identified as a potential TF regulating these module genes. Analysis of the global regulatory network of TFs and their targets suggested that CCL3 may be a key regulator in DMCAD.Conclusion: We found bioinformatic evidence that CCL3 may be a key regulator and RUNX1 a key TF in DMCAD.Keywords: diabetes mellitus, coronary artery disease, transcription factors

Jie Liu,1,2,&ast; Xiaodong Wang,1,2,&ast; Junhua Lin,1,&ast; Shaohua Li,1 Guoxiong Deng,1,2 Jinru Wei1,2 1Department of Cardiology, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530022, People’s Republic of China; 2Department of Cardiology, The First People’s Hospital of Nanning, Nanning, Guangxi, 530022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guoxiong DengThe Fifth Affiliated Hospital of Guangxi Medical University, 89 Qixing Road, Nanning, Guangxi, 530022, People’s Republic of ChinaEmail dengguoxiong@stu.gxmu.edu.cnJinru WeiThe Fifth Affiliated Hospital of Guangxi Medical University, 89 Qixing Road, Nanning, Guangxi, 530022, People’s Republic of ChinaTel +86 77 12636193Email weijinru@stu.gxmu.edu.cnObjective: Coronary artery disease (CAD) is a serious global health concern. Current diagnostic methods for CAD involve risk to the patient and are costly, so better diagnostic tools are needed. We defined four classifiers based on gene expression profiles in peripheral blood mononuclear cells and determined their potential for CAD detection.Methods: We downloaded a CAD-related data set (GSE113079) from the Gene Expression Omnibus (GEO) database. We identified differentially expressed genes (DEGs) in peripheral blood mononuclear cells between CAD samples and healthy controls. DEGs were analyzed for functional enrichment. To create a robust CAD classifier, DEGs were identified by feature selection using the principal component analysis. Then, least absolute shrinkage and selection operator (LASSO) logistic regression, random forest, and support vector machine (SVM) models were created. Gene set variation analysis (GSVA) score and gene set enrichment analysis (GSEA) were also conducted. The performance of the models was evaluated in terms of the area under receiver operating characteristic curves (AUC).Results: In the training set, we found 135 up-regulated genes and 104 down-regulated genes in CAD patients compared with controls. The DEGs were involved in some pathways associated with CAD, such as pathways involving calcium and interleukin-17 signaling. Twenty genes were identified as optimal features and used to generate the logistic classifier based on LASSO. The AUC for the classifier was 1.00 in the training set and 0.997 in the test set. Using the 20 DEGs, SVM and random forest classifiers were also generated and showed high diagnostic efficacy, with respective AUCs of 0.997 and 1.00 against the training set. A GSVA score was also established using the top 20 significant DEGs, which showed an AUC of 0.971 in the training set and 0.989 in the test set. Furthermore, GSEA showed autophagy and the proteasome to be major pathways involving the DEGs.Conclusion: We identified a set of genes specific for CAD whose expression can be measured non-invasively. Using these genes, we defined four diagnostic classifiers using multiple methods.Keywords: coronary artery disease, diagnosis, gene expression, classifier

Peize Zhang,1,&ast; HouMing Liu,2,&ast; Hui Wang,3,&ast; Yanbo Wu,4 Liqin Sun,3 Man Rao,3 Xinyun Jia,3 Ying Song,3 Guofang Deng,1 Tianpin Li,2 Feidi Ye,2 Yang Zhou,3 Yi Liao5 1Department of Lung Disease, The Third People’s Hospital of Shenzhen, Shenzhen City, Guangdong Province, People’s Republic of China; 2Department of Clinical Laboratory, The Third People’s Hospital of Shenzhen, Shenzhen City, Guangdong Province, People’s Republic of China; 3Department of Infectious Disease No.1, The Third People’s Hospital of Shenzhen, Shenzhen City, Guangdong Province, People’s Republic of China; 4Department of Infectious Disease, Shenzhen Longhua New District Central Hospital, Shenzhen City, Guangdong Province, People’s Republic of China; 5Department of Primary Health Promotion, Shenzhen Center for Disease Control and Prevention, Shenzhen City, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Zhou; Yi Liao Email yangzhou@szsy.sustech.edu.cn; ly_jht@126.comBackground: Sputum is commonly used for the diagnostic testing of pulmonary tuberculosis (PTB), but people living with HIV/AIDS (PLWHA) usually have little sputum. Moreover, the automated molecular test, Xpert MTB/RIF assay (Xpert), has a low sensitivity in PLWHA. We aimed to estimate the performance of Xpert Ultra on the detection of Mycobacterium tuberculosis (MTB) using bronchoalveolar lavage (BAL).Methods: From February 5, 2018 to March 30, 2019, a total of 99 PLWHA with suspected PTB at the Third People’s Hospital of Shenzhen, China, were recruited. The information on demographics and medical history, blood MTB antigen-specific interferon gamma enzyme-linked immunospot assay (T-SPOT.TB), T lymphocyte subsets, and plasma HIV RNA load were collected. Computed tomography (CT) and flexible bronchoscopy were performed, and BAL and blood samples were collected. Testing of acid-fast bacilli (AFB), tuberculosis real-time fluorescence quantitative PCR (TBDNA), Ultra, Xpert, and MTB culture were conducted.Results: Compared to BAL MTB culture for tuberculosis diagnosis, Ultra, Xpert, T-SPOT.TB, TBDNA and AFB smear had the sensitivity of 0.96 (24/25), 0.80 (20/25), 0.84 (21/25), 0.44 (11/25), and 0.12 (3/25), respectively; and the specificity of 0.92 (68/74), 0.96 (71/74), 0.93 (69/74), 0.96 (71/74), and 0.99 (73/74), respectively. Our study found that the sensitivity of Ultra was higher than that of culture and Xpert (AUC 0.92, 0.86 and 0.84, respectively). The results also indicated that PLWHA with CD4 < 200 cells/mm3 had reduced both sensitivity (from 1.00 and 0.86 to 0.94 and 0.78, respectively) and specificity (from 0.96 and 1.00 to 0.90 and 0.41, respectively) of Ultra and Xpert for the diagnosis of PTB.Discussion: Our data supported an increased sensitivity of Ultra compared to that of Xpert on BAL samples of PLWHA, regardless of the CD4 counts and reference diagnosis standards.Keywords: diagnosis of pulmonary tuberculosis, Xpert MTB/RIF Ultra, HIV-TB co-infection

Xiaonan Zhang,1,&ast; Huimin Fang,1,&ast; Zhigang Zeng,1 Kaijun Zhang,1 Zhanyi Lin,1,2 Gang Deng,1 Weiping Deng,1 Lichang Guan,1 Xuebiao Wei,1 Xinyi Li,2 Lei Jiang,1– 3 Lishu Xu1– 3 1Guangdong Provincial Geriatrics Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 2School of Medicine, South China University of Technology, Guangzhou, 510641, People’s Republic of China; 3The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Jiang; Lishu Xu Tel +86-20-83827812; +86-20-13660032429Email jianglei@smu.edu.cn; xulishu70@163.comPurpose: Gastric cancer is a common tumor type associated with nutritional and immune status. The aim of the current study was to investigate the prognostic value of a preoperative prognostic nutritional index (PNI), composed of nutritional factors and immune factors in elderly patients undergoing gastric cancer surgery.Patients and Methods: A total of 454 patients undergoing gastric cancer surgery were divided into two groups based on preoperative PNI scores: ≤ 45.1 (n = 307) and > 45.1 (n = 147). Survival analysis was performed using the Kaplan–Meier method and Log rank tests. Univariate and multivariate analyses were conducted to identify independent prognostic factors using a Cox proportional hazards model.Results: According to the X-tile program, the optimal cutoff value for predicting overall survival (OS) with the PNI was 45.1. The receiver operating characteristic analysis revealed that PNI exhibited 70.6% sensitivity and 56.5% speci&filig;city for predicting death during long-term follow-up. The cumulative incidence of postoperative 4-year mortality indicated that the risk of death increased significantly for PNI ≤ 45.1. In multivariate analysis, preoperative PNI was a significant independent predictor of mortality. In the age-stratified subgroup analysis, preoperative PNI was more sensitive for the old elderly subgroup than for the young elderly subgroup.Conclusion: Preoperative PNI is a sensitive and specific prognostic predictor among elderly patients undergoing gastric cancer surgery.Keywords: elderly patients, gastric cancer, prognostic nutritional index, radical gastrectomy

Yong Yang,1,* Guoying Deng,2,* Peng Wang,1 Guangzhao Lv,1 Rui Mao,1 Yuhao Sun,3 Baofeng Wang,3 Xijian Liu,4 Liuguan Bian,3 Dong Zhou1 1Department of Neurosurgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 2Trauma Center, Shanghai General Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 201620, People’s Republic of China; 3Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200025, People’s Republic of China; 4College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai, 201620, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liuguan BianDepartment of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, 197 Rui Jin Er Road, Shanghai, 200025, People’s Republic of ChinaTel +86 21 64370045 Ext 666091Fax +86 21 64333548Email blg11118@rjh.com.cnDong ZhouDepartment of Neurosurgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, No. 106 Zhongshan Er Road, Yuexiu District, Guangzhou, 510080, People’s Republic of ChinaTel +86 20 83827812 Ext 61521Email zhoudong5413@163.comBackground: Intracerebral hemorrhage (ICH) is a common neurological crisis leading to high mortality and morbidity. Oxidative stress-induced secondary injury plays a critical role in neurological deterioration. Previously, we synthesized a porous Se@SiO2 nanocomposite and identified their therapeutic role in osteonecrosis of the femoral head. Whether this nanocomposite is neuroprotective remains to be elucidated.Methods: A porous Se@SiO2 nanocomposite was synthesized, and its biosafety was determined using a CCK-8 assay. The neuroprotective effect was evaluated by TUNEL staining, and intracellular ROS were detected with a DCFH-DA probe in SH-SY5Y cells exposed to hemin. Furthermore, the effect of the nanocomposite on cell apoptosis, brain edema and blood–brain barrier permeability were evaluated in a collagenase-induced ICH mouse model. The potential mechanism was also explored.Results: The results demonstrated that Se@SiO2 treatment significantly improved neurological function, increased glutathione peroxidase activity and downregulated malonaldehyde levels. The proportion of apoptotic cells, brain edema and blood–brain barrier permeability were reduced significantly in ICH mice treated with Se@SiO2 compared to vehicle-treated mice. In vitro, Se@SiO2 protected SH-SY5Y cells from hemin-induced apoptosis by preventing intracellular reactive oxygen species accumulation.Conclusion: These results suggested that the porous Se@SiO2 nanocomposite exerted neuroprotection by suppressing oxidative stress. Se@SiO2 may be a potential candidate for the clinical treatment of ICH and oxidative stress-related brain injuries.Keywords: selenium nanocomposites, oxidative stress, blood–brain barrier, brain edema, apoptosis

Peize Zhang,1,* Juan Xiong,2,* Jianfeng Zeng,1,* Senlin Zhan,1 Tao Chen,1 Yuxiang Wang,1 Guofang Deng1 1Department of Pulmonary Medicine and Tuberculosis, The Third People’s Hospital of Shenzhen, Shenzhen, Guangdong, People’s Republic of China; 2School of Public Health, Health Science Center, Shenzhen University, Shenzhen, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guofang DengDepartment of Pulmonary Medicine and Tuberculosis, The Third People’s Hospital of Shenzhen, No. 29, Bulan Road, Longgang District, Shenzhen, Guangdong 518112, People’s Republic of ChinaTel +86 135 300 27001Fax +86 0755 6123 8928Email jxxk1035@yeah.netObjective: The aim of this study was to assess active tuberculosis-related deaths in Shenzhen city of China to identify major causes of mortality in different age groups.Patients and Methods: Medical records of mortality cases of patients with active TB diagnosed during 2013– 2018 were reviewed. All TB deaths were classified into two broad age groups (the young group: 18– 65 years old and the elderly group: > 65 years old). Causes of death were analyzed based on medical records.Results: A total of 279 mortality cases of active TB were reviewed during the study period. Among them, mean age was 54.0± 20.5 years old; 80.6% (225/279) were male. There were 5.7% and 4.6% MDR/XDRTB patients in the young and elderly group. Newly treated TB accounted for 89.6% in the young group and 85.1% in the elderly group. Pulmonary TB was a major infection type in both groups (65.1% vs 77.0%). Advanced TB (23.4%) and HIV co-infection (20.8%) were the leading causes of deaths in the young group, but deaths in the elderly group were mostly associated with underlying diseases, including cardiovascular disease (52.9%), diabetes (33.3%), COPD (16.1%) and cancer (11.5%). Malnutrition was a significant condition in both groups (43.2% vs 35.6%). In terms of respiratory complications, bacterial infection was the leading comorbidity in both groups (27.1% vs 18.4%), followed by septic shock (18.2% vs 12.6%) and respiratory failure (12.0% vs 11.5%). There were no significant statistical differences between the two groups.Conclusion: Our findings suggest that screening for HIV co-infection and early diagnosis of TB is vital in lowering TB-related deaths in young patients. Most deaths in elderly TB patients were caused by underlying health conditions or complications other than TB.Keywords: active tuberculosis, TB-related death, tuberculosis complication, tuberculosis comorbidity, young death

Yan Li,1,* Tingwei Yu,2,* Zengyou Liu,2 Hengying Chen,3 Yao Liu,4 Yuanhuan Wei,4 Ruifang Sun,4 Hongmei Zhang,2 Wei Wang,2 Yihua Lu,2 Yingyu Zhou,1 Guifang Deng,4 Zheqing Zhang1 1Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Obstetrics, Union Shenzhen Hospital of Huazhong University of Science and Technology, Shenzhen, People’s Republic of China; 3Injury Prevention Research Center, Shantou University Medical College, Shantou, People’s Republic of China; 4Department of Clinical Nutrition, Union Shenzhen Hospital of Huazhong University of Science and Technology, Shenzhen, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zheqing ZhangDepartment of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, No. 1023-1063, Shatai South Road, Baiyun District, Guangzhou, Guangdong 510515, People’s Republic of ChinaEmail zzqaa501@smu.edu.cnGuifang DengDepartment of Clinical Nutrition, Union Shenzhen Hospital of Huazhong University of Science and Technology, No. 89 Taoyuan Road, Shenzhen, Guangdong 518052, People’s Republic of ChinaEmail misyfly@163.comObjective: To evaluate the associations of serum uric acid (UA), urea nitrogen (UN), and urine specific gravity (USG) levels in the first trimester of pregnancy with the risk of gestational diabetes mellitus (GDM).Patients and Methods: A retrospective cohort study was conducted in 1,769 pregnant women aged 31.55 ± 3.91 years. UA, UN, and USG levels were measured during the 16– 18th week of gestation. GDM was diagnosed by an oral 75 g glucose tolerance test during the 24– 28th week of gestation.Results: A multivariate adjusted logistic regression analysis showed that UA levels in the highest quartile increased the risk of GDM by 55.7% (odds ratio [OR]: 1.557, 95% confidence interval [CI]: 1.055– 2.298; p = 0.026) compared to those in the lowest quartile. USG levels in the second, third, and fourth quartiles increased the risk of GDM by 67.6% (95% CI: 1.090– 2.421), 112.4% (95% CI: 1.446– 3.119), and 94.5% (95% CI: 1.314– 2.880), respectively, compared to those in the first quartile (p trend = 0.001). No significant association between UN levels and the GDM risk was observed. When the extreme composite biomarker score quartiles were compared, the adjusted OR (95% CI) for GDM was 1.909 (95% CI: 1.332– 2.736). Age-stratified analyses revealed similar results in women aged ≤ 35 years only, but not in those aged > 35 years.Conclusion: Higher levels of UA and USG and a higher composite kidney function biomarker score during the 16– 18th week of gestation were positively and independently associated with an increased risk of GDM.Keywords: uric acid, urea nitrogen, urine specific gravity, gestational diabetes mellitus, retrospective cohort study

Yeyang Chen,1,2,* Junfu Wang,1,* Siyu Liu,1 Weikun Lai,1 Jinlu Liu,1 Zhen Wang,1 Bopei Li,1 Yuantian Mao,1 Ye Wang,1 Guofei Deng,1 Junqiang Chen1 1Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China; 2Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital of Guangxi Medical University, Yulin, Guangxi Zhuang Autonomous Region, People’s Republic of China*These authors contributed equally to this workCorrespondence: Junqiang Chen Department of Gastrointestinal SurgeryThe First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi 530021, People’s Republic of ChinaTel +86 771-5356552Email gxhans@163.comPurpose: The present study aimed to develop the official Chinese version of the QoR-40 (QoR-40C) and to test its reliability, validity, and responsiveness.Patients and Methods: A systematic translation procedure was established and performed to develop the QoR-40C from the original English QoR-40 version. After the pilot study, 223 surgical patients were administered the QoR-40C at four time points. The validity, reliability, and responsiveness were assessed to validate the QoR-40C.Results: The test–retest reliability of the QoR-40C in the morning and afternoon of the third day after surgery was 0.917 (P < 0.001). The split-half reliability for all domains was 0.938 in the morning of the third day after surgery. The median item-to-own dimension and total score of Cronbach’s α for internal consistency of the QoR-40C at different assessment time points were more than 0.70. All the correlation coefficients between each subscale and the QoR-40 total score showed good correlation and were greater than those for other subscales in the morning of the third day after surgery. Furthermore, in the morning of the third day after surgery, the QoR-40C total score was moderately positively correlated with the SF-36 score (ρ = 0.575, P < 0.001), while the QoR-40C score was negatively correlated with the visual analogue scale (VAS) score (ρ = − 0.299, P < 0.001). The factor loadings of each item were within the required range. A statistically significant difference was observed in the QoR-40C total scores before and after the surgery (P < 0.001) with the standardized responsive mean (SRM) of 0.51.Conclusion: The QoR-40C showed good reliability, validity, and responsiveness and was appropriate to be used as a quality of life measurement questionnaire for patients after surgery in China.Keywords: China, quality of life, questionnaire, validity, reliability, responsiveness

Peize Zhang,1,* Guanghui Xu,2,* Yanhua Song,3,* Jie Tan,1 Tao Chen,1 Guofang Deng1 1Department of Pulmonary Medicine & Tuberculosis, The Third People’s Hospital of Shenzhen, Shenzhen, People’s Republic of China; 2Jiangmen Institute of Tuberculosis Prevention and Control, Guangdong, People’s Republic of China; 3Department of Tuberculosis, Chest Hospital of Peking, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guofang Deng Email jxxk1035@yeah.netPurpose: The aim of this study was to analyze socioeconomic burdens and other difficulties that multidrug-resistant tuberculosis (MDR-TB) patients in cities are facing, to identify major obstacles and which groups of patients are most affected.Methods: Face-to-face and phone-call interviews were conducted in early 2018 to follow-up with patients newly diagnosed with MDR-TB in 2017 in three tuberculosis hospitals in three financially affluent Chinese cities. Demographic data and information on their medical care, insurance coverage, and medical expenses were collected and analyzed.Results: A total of 144 newly diagnosed MDR-TB cases were reviewed during the study period, excluding 38 who were lost to follow-up and 29 patients who refused to participate, 77 patients were enrolled in this study. A total of 61 (79%) of these patients were hospitalized after MDR-TB diagnosis with an average hospital stay of 14 days, of them 57 (74%) were sputum positive on diagnosis. The proportion of patients who failed community care were 48% married, 56% in white collar employment and 43% in temp jobs/unemployed. In terms of insurance coverage, the proportion of patients who failed community care were 23% with no insurance and/or New Rural Co-operative Medical Care Scheme (NRCMS) and 45% with Urban Employee Basic Medical Insurance (UEBMI)/Urban Residents Basic Medical Insurance (URBMI) and commercial insurance. Difficulties patients encountered were, financial pressure (33%), psychological stress (26%), adverse drug reactions (23%), repulsive reaction to injections (17%). Fourty-eight percent of the patients spent over ¥ 2000 (USD300) per month on TB treatment.Conclusion: Despite insurance coverage, financial hardship remains the number one difficulty MDR-TB patients encountered in relatively financially affluent cities. Among them, the married working class were found to be the most financially sensitive group and have the highest tendency to fail community care. It is of utmost urgency to enhance the current medical policy to improve treatment adherence.Keywords: socioeconomic burden, MDR-TB, patient care, financial support, catastrophic cost, treatment adherence

Guo-chao Deng,1,2 Huan Yan,2 Zhi-peng Guo,2 Guanghai Dai1,2 1School of Medicine, Nankai University, Tianjin 300071, People’s Republic of China; 2Department of Medical Oncology, The First Medical Center of Chinese People’s Liberation Army (PLA) General Hospital, Beijing, 100853, People’s Republic of ChinaCorrespondence: Guanghai DaiDepartment of Medical Oncology, The First Medical Center of Chinese People’s Liberation Army (PLA) General Hospital, Beijing 100853, People’s Republic of ChinaTel +86-13801232381Email daigh301@vip.sina.comPurpose: In pancreatic cancer (PC), CA 19– 9, CEA and CA 125 are the most widely used tumor markers. The aim of this study was to explore the prognostic significance of baseline levels of serum CA 19– 9, CEA, and CA 125, and to evaluate the clinical significance of these markers in PC patients.Patients and Methods: A total of 278 patients with advanced PC that had received first-line chemotherapy treatments were examined. Correlation analysis between the tumor markers and clinical characteristics was performed using a Pearson’s Chi-squared test or Fisher’s exact test. A Pearson’s correlation test was utilized to investigate the relationship between tumor markers and peripheral blood parameters. Univariate analysis was estimated using a Kaplan–Meier analysis and compared using a Log rank test. Multivariate analysis was performed using a Cox proportional hazards regression model.Results: Both individually and collectively, the baseline CA 19– 9, CEA and CA 125 levels were positively associated with the primary tumor site (p < 0.01), liver metastasis (p < 0.05), and number of organ metastases (p < 0.05). Furthermore, CA 19– 9, CEA and CA 125 were correlated to baseline WBC (p < 0.001) and LDH (p < 0.01) levels. Additionally, CA 19– 9 was correlated with years of smoking (p = 0.024); diabetes and years of diabetes (p = 0.012); baseline glycemic levels (p = 0.004); and neutrophil counts (p < 0.001). Moreover, CA 125 levels were associated with the baseline neutrophil counts (p < 0.001) and peritoneal metastasis (p = 0.008). When examining neutrophil, LDH, CA 19– 9 and CA 125 levels were found to be associated with overall survival (OS) and shown to be independent prognostic factors.Conclusion: CA 19– 9, CEA and CA 125 are correlated with multiple clinical factors. Baseline neutrophil, LDH, CA 19– 9 and CA 125 levels are associated with OS and may potentially serve as prognostic factors.Keywords: pancreatic cancer, CA 19-9, CEA, CA 125, correlation analysis, prognosis

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

Yihong Chen,1 Ganlu Deng,2 Yaojie Fu,1,3 Ying Han,1,3 Cao Guo,1,3 Ling Yin,1 Changjing Cai,1,3 Hong Shen,1,3 Shaobin Wu,4 Shan Zeng1,5 1Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People’s Republic of China; 2Department of Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of China; 3Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People’s Republic of China; 4Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People’s Republic of China; 5National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People’s Republic of ChinaCorrespondence: Shan ZengDepartment of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People’s Republic of ChinaTel +86 731-8975-3034Email zengshan2000@csu.edu.cn Shaobin WuDepartment of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People’s Republic of ChinaTel +86 731-8975-3007Email shaobinwu@csu.edu.cnBackground: Chemoresistance is a major obstacle to improving the survival rate of colorectal cancer (CRC) patients. Forkhead box protein C2 (FOXC2), a member of the forkhead box (Fox) transcription factor family, is reported to be an important regulator of epithelial-to-mesenchymal transition (EMT) and plays a key role in tumor progression. However, little is known about the effects of FOXC2 on oxaliplatin (OXA) resistance in CRC.Methods: OXA-resistant cells were generated from HCT116 cells. CCK-8, colony formation, flow cytometry and Transwell assays were used to compare the characteristics of OXA-resistant HCT116/OXA cells and the corresponding parental HCT116 cells. The expression of FOXC2 was confirmed by qRT-PCR and Western blotting in HCT116/OXA and HCT116 cells. Gain- and loss-of-function assays were performed to evaluate the effects of FOXC2 on OXA sensitivity and EMT in HCT116/OXA and HCT116 cells both in vitro and in vivo, and the possible molecular mechanisms were investigated.Results: The relative expression of FOXC2 was significantly increased in HCT116/OXA cells compared with the parental HCT116 cells. Upregulation of FOXC2 in HCT116 cells reduced OXA sensitivity and promoted EMT. However, knockdown of FOXC2 in HCT116/OXA cells markedly increased the in vitro and in vivo sensitivity of HCT116/OXA cells to OXA by regulating EMT progression. Furthermore, FOXC2 activated MAPK/ERK signaling, and blockade of ERK attenuated FOXC2-induced EMT and FOXC2-enhanced OXA resistance.Conclusion: FOXC2 induced EMT to promote oxaliplatin resistance by activating the MAPK/ERK signaling pathway. FOXC2 may be a potential therapeutic target for overcoming OXA resistance in human CRC.Keywords: forkhead box protein C2, epithelial-mesenchymal transition, colorectal cancer, oxaliplatin resistance, MAPK/ERK

Guangtong Deng,1 Lei Yao,1 Furong Zeng,2 Liang Xiao,1,* Zhiming Wang1,* 1General Surgery Department, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Xiangya School of Medicine, Central South University, Changsha, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhiming Wang; Liang XiaoGeneral Surgery Department, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, People’s Republic of ChinaTel +8618773132682Email a846957007@163.com; xiaoliangrick@csu.edu.cnObjective: To preoperatively predict the microvascular invasion (MVI) risk in hepatocellular carcinoma (HCC) using nomogram.Methods: A retrospective cohort of 513 patients with HCC hospitalized at Xiangya Hospital between January 2014 and December 2018 was included in the study. Univariate and multivariate analysis was performed to identify the independent risk factors for MVI. Based on the independent risk factors, nomogram was established to preoperatively predict the MVI risk in HCC. The accuracy of nomogram was evaluated by using receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA).Results: Tumor size (OR=1.17, 95% CI: 1.11–1.23, p

Xiaoduan Zhuang,1 Zhenyu Chen,1 Jianqi Wang,2 Junsheng Chen,1 Xiaosheng Wu,1 Yadong Wang,1 Chudi Chen,1 Guoming Deng,1 Kai Qian,1 Yang Bai1 1Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People’s Republic of China; 2Department of Otolaryngology, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510515, People’s Republic of ChinaCorrespondence: Yang BaiDepartment of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People’s Republic of ChinaTel +86 1 392 500 1665Fax +86 0 206 164 1571Email docbaiyang@sohu.comPurpose: Basal layer type squamous cell carcinoma (BLSCC) is a unique type of squamous cell carcinoma (SCC), characterized by high-grade dysplastic cells occupying the lower half of the epithelium. So far, such special lesions do not seem to attract much attention. The aim of this study was to investigate the clinicopathological features and prognosis of esophageal squamous carcinoma lesions with a BLSCC component.Materials and methods: Between January 2011 and January 2018, 96 patients with esophageal squamous cell carcinoma underwent endoscopic submucosal resection in our hospital were retrospectively analyzed. Patients were divided into BLSCC or typical SCC groups according to the presence or absence of a BLSCC component. The endoscopic findings were compared between the two groups. Furthermore, patients were followed up until October 2018 to compare recurrence rates.Results: BLSCC components were detected in 32 (33.3%, 32/96) lesions. Among them, 13 (40.62%, 13/32) were BLSCC predominant. The intraepithelial papillary capillary loops of 7 pure BLSCC showed type B1 under narrow-band imaging. Single-factor and multivariate analyses indicated that five or more independently scattered, deep-stained spots in iodine-unstained areas were significantly predictive of the presence of BLSCC components (OR=4.837, P=0.015). All patients of typical SCC group survived, but one of BLSCC group died for distant metastases during the follow-up period. The 1-year cumulative recurrence rate (CRR) of BLSCC group were 3.4%, lower than that of typical SCC group (7.1%). Although no significant difference of CRR was seen between the two groups (P>0.05), the 2-year CRR of BLSCC group increased to 11.9%, being higher than that of typical SCC group (7.1%).Conclusion: The presence of multiple, scattered stained spots in iodine-unstained areas was predictive of BLSCC components. Such lesion should be treated actively and subject to a more rigorous follow-up protocol due to a higher likelihood of late recurrence.Keywords: esophagus, basal layer type squamous cell carcinoma, clinicopathology, recurrence

Chunlin Li,1,* Qi Wang,1,2,* Xiaohua Gu,3 Yingjie Kang,4 Yongxing Zhang,1 Yangyang Hu,5 Taixi Li,1 Hansong Jin,1 Guoying Deng,1 Qiugen Wang11Trauma Center, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201620, People’s Republic of China; 2Trauma Center, Shanghai General Hospital of Nanjing Medical University, Shanghai 200080, People’s Republic of China; 3Department of Orthopedics, Shanghai Seventh People’s Hospital, Shanghai, 200137, People’s Republic of China; 4Department of Radiology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, People’s Republic of China; 5Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201620, People’s Republic of China*These authors contributed equally to this workBackground: Delay or failure of bone union is a significant clinical challenge all over the world, and it has been reported that bone marrow mesenchymal stem cells (BMSCs) offer a promising approach to accelerate bone fracture healing. Se can modulate the proliferation and differentiation of BMSCs. Se-treatment enhances the osteoblastic differentiation of BMSCs and inhibiting the differentiation and formation of mature osteoclasts. The purpose of this study was to assess the effects of porous Se@SiO2 nanocomposite on bone regeneration and the underlying biological mechanisms.Methods: We oxidized Se2-, to develop Se quantum dots, then we used the Se quantum dots to form a solid Se@SiO2 nanocomposite which was then coated with polyvinylpyrrolidone (PVP) and etched in hot water to synthesize porous Se@SiO2 nanocomposite. We used XRD pattern to assess the phase structure of the solid Se@SiO2 nanocomposite. The morphology of porous Se@SiO2 nanocomposite were evaluated by scanning electron microscope (SEM) and the biocompatibility of porous Se@SiO2 nanocomposite were investigated by cell counting kit-8 (CCK-8) assays. Then, a release assay was also performed. We used a Transwell assay to determine cell mobility in response to the porous Se@SiO2 nanocomposite. For in vitro experiments, BMSCs were divided into four groups to detect reactive oxygen species (ROS) generation, cell apoptosis, alkaline phosphatase activity, calcium deposition, gene activation and protein expression. For in vivo experiments, femur fracture model of rats was constructed to assess the osteogenic effects of porous Se@SiO2 nanocomposite.Results: In vitro, intervention with porous Se@SiO2 nanocomposite can promote migration and osteogenic differentiation of BMSCs, and protect BMSCs against H2O2-induced inhibition of osteogenic differentiation. In vivo, we demonstrated that the porous Se@SiO2 nanocomposite accelerated bone fracture healing using a rat femur fracture model.Conclusion: Porous Se@SiO2 nanocomposite promotes migration and osteogenesis differentiation of rat BMSCs and accelerates bone fracture healing, and porous Se@SiO2 nanocomposite may provide clinic benefit for bone tissue engineering.Keywords: bone marrow mesenchymal stem cells, porous Se@SiO2 nanocomposite, antioxidant, migration, osteogenic differentiation

Peng Wu,1 Haitian Zhao,2 Xingchun Gou,3 Xingwang Wu,4 Shenqi Zhang,1 Gang Deng,1 Qianxue Chen11Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, People’s Republic of China; 2School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, 150001, People’s Republic of China; 3Shaanxi Key Laboratory of Brain Disorders & Institute of Basic and Translational Medicine, Xi’an Medical University, Xi’an 710021, People’s Republic of China; 4Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230020, People’s Republic of ChinaBackground and purpose: Traumatic brain injury (TBI) is a major disease without effective treatment. Recently, Tat-NR2B9c peptide emerged as a promising neuroprotective agent, but limited in clinical translation by it low brain penetrability. We synthesized Tat-NR2B9c loaded self-assembled activatable protein nanoparticles, termed TN-APNPs, and demonstrated that TN-APNPs enhanced the delivery of Tat-NR2B9c to the brain lesion in stroke. Herein we developed a novel approach to further engineering TN-APNPs for targeted delivery of Tat-NR2B9c to the injured brain with enhanced efficiency through conjugation of CAQK or CCAQK, a short peptide.Methods: Short peptide-conjugated TN-APNPs were synthesized by conjugated with CAQK or CCAQK via a click condensation reaction with CBT, then analyzed by dynamic light scattering, transmission electron microscopy and thrombin responsive assay. Characterization of short peptide-conjugated TN-APNPs were investigated by using cell excitotoxicity assay and transwell blood-brain-barrier model in vitro, and pharmacokinetics, IVIS imaging system and confocal analysis in TBI-bearing mice. Evaluation of therapeutic effects were analyzed by H&E staining, Elevated Plus Maze analysis and Rotarod test.Results: CAQK-conjugated TN-APNPs (C-TN-APNPs) and CCAQK-conjugated TN-APNPs (CC-TN-APNPs) were spherical in morphology and 30 nm in diameter. In vitro studies revealed that TN-APNPs, C-TN-APNPs and CC-TN-APNPs were responsive to thrombin cleavage, reduced the cytotoxicity of Tat-NR2B9c, and increased BBB permeability of Tat-NR2B9c. CC-TN-APNPs demonstrated the better circulation time, better targeting ability and penetrating efficiency to the injured brain, and better therapeutic benefits in vivo studies.Conclusion: This study demonstrated CC-TN-APNPs as a promising therapeutic for clinical management of TBI.Keywords: traumatic brain injury, Nanoparticle, Tat-NR2B9c, CAQK, CCAQK

Zhihuang Zheng,1,* Guoying Deng,2,* Chenyang Qi,3 Yuyin Xu,3 Xijian Liu,4 Zhonghua Zhao,3 Zhigang Zhang,3 Yuening Chu,1 Huijuan Wu,3 Jun Liu1 1Department of Nephrology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; 2Trauma Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; 3Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China; 4Department of Chemical Engineering and Technology, College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai, China *These authors contributed equally to this work Objectives: Acute kidney injury (AKI) is a growing global health concern, and is associated with high rates of mortality and morbidity in intensive care units. Se is a trace element with antioxidant properties. This study aimed to determine whether porous Se@SiO2 nanospheres could relieve oxidative stress and inflammation in ischemia/reperfusion (I/R)-induced AKI. Methods: Male 6- to 8-week-old C57bl/6 mice were divided into four groups: sham + saline, sham + Se@SiO2, I/R + saline, and I/R + Se@SiO2. Mice in the I/R groups experienced 30 minutes of bilateral renal I/R to induce an AKI. Porous Se@SiO2 nanospheres (1 mg/kg) were intraperitoneally injected into mice in the I/R + Se@SiO2 group 2 hours before I/R, and the same dose was injected every 12 hours thereafter. Hypoxia/reoxygenation (H/R) was used to mimic I/R in vitro. PBS was used as a control treatment. Human kidney 2 cells were seeded into 12-well plates (5×105 cells/well) and divided into four groups: control + PBS group, control + Se@SiO2 group, H/R + PBS group, and H/R + Se@SiO2 group (n=3 wells). We then determined the expression levels of ROS, glutathione, inflammatory cytokines and proteins, fibrosis proteins, and carried out histological analysis upon kidney tissues.Results: In vitro, intervention with porous Se@SiO2 nanospheres significantly reduced levels of ROS (P

Guoying Deng1,*, Chenyun Dai2,*, Jinyuan Chen1, Anqi Ji1, Jingpeng Zhao1, Yue Zhai1, Yingjie Kang3, Xijian Liu4, Yin Wang5, Qiugen Wang1 1Trauma Center, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; 2Institute of Translation Medicine, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; 3Department of Radiology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China; 4College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai, China; 5Ultrasound Department of Shanghai Pulmonary Hospital, Tongji University, Shanghai, China *These authors contributed equally to this work Background: Methylprednisolone (MPS) is an important drug used in therapy of many diseases. However, osteonecrosis of the femoral head is a serious damage in the MPS treatment. Thus, it is imperative to develop new drugs to prevent the serious side effect of MPS. Methods: The potential interferences Se@SiO2 nanocomposites may have to the therapeutic effect of methylprednisolone (MPS) were evaluated by classical therapeutic effect index of acute respiratory distress syndrome (ARDS), such as wet-to-dry weight ratio, inflammatory factors IL-1β and TNF-α. And oxidative stress species (ROS) index like superoxide dismutase (SOD) and glutathione (GSH) were tested. Then, the protection effects of Se@SiO2 have in osteonecrosis of the femoral head (ONFH) were evaluated by micro CT, histologic analysis and Western-blot analysis. Results: In the present study, we found that in the rat model of ARDS, Se@SiO2 nanocomposites induced SOD and GSH indirectly to reduce ROS damage. The wet-to-dry weight ratio of lung was significantly decreased after MPS treatment compared with the control group, whereas the Se@SiO2 did not affect the reduced wet-to-dry weight ratio of MPS. Se@SiO2 also did not impair the effect of MPS on the reduction of inflammatory factors IL-1β and TNF-α, and on the alleviation of structural destruction. Furthermore, micro CT and histologic analysis confirmed that Se@SiO2 significantly alleviate MPS-induced destruction of femoral head. Moreover, compared with MPS group, Se@SiO2 could increase collagen II and aggrecan, and reduce the IL-1β level in the cartilage of femoral head. In addition, the biosafety of Se@SiO2 in vitro and in vivo were supported by cell proliferation assay and histologic analysis of main organs from rat models. Conclusion: Se@SiO2 nanocomposites have a protective effect in MPS-induced ONFH without influence on the therapeutic activity of MPS, suggesting the potential as effective drugs to avoid ONFH in MPS therapy. Keywords: porous Se@SiO2 nanocomposites, methylprednisolone, osteonecrosis of femoral head, ROS damage, ARDS

Zhenchong Xiong,1–3,* Guangzheng Deng,1–3,* Xinjian Huang,1–3,* Xing Li,1–3 Xinhua Xie,1–3 Jin Wang,1–3 Zeyu Shuang,1–3 Xi Wang1–3 1Department of Breast Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China; 2State Key Laboratory of Oncology in Southern China, Guangzhou, China; 3Collaborative Innovation Center for Cancer Medicine, Guangzhou, China *These authors contributed equally to this work Purpose: Bone is one of the most common sites of breast cancer metastasis, and population-based studies of patients with bone metastasis in initial metastatic breast cancer (MBC) are lacking. Materials and methods: From 2010 to 2013, 245,707 breast cancer patients and 8901 patients diagnosed with initial bone metastasis were identified by Surveillance, Epidemiology, and End Results database of the National Cancer Institute. Multivariate logistic and Cox regression were used to identify predictive factors for the presence of bone metastasis and prognosis factors. Kaplan–Meier method and log-rank test were used for survival analysis. Results: Eight thousand nine hundred one patients with initial MBC had bone involvement, accounting for 3.6% of the entire cohort and 62.5% of the patients with initial MBC. Also, 70.5% of patients with bone metastasis were hormone receptor (HR) positive (HR+/human epidermal growth factor receptor 2 [HER2]−: 57.6%; HR+/HER2+: 12.9%). Patients with initial bone metastasis had a better 5-year survival rate compared to those with initial brain, liver, or lung metastasis. HR+/HER2− and HR+/HER2+ breast cancer had a propensity of bone metastasis in the entire cohort and were correlated with better prognosis in patients with initial bone metastasis. Local surgery had significantly improved overall survival in initial MBC patients with bone metastasis. Conclusion: Our study has provided population-based estimates of epidemiologic characteristics and prognosis in patients with bone metastasis at the time of breast cancer diagnosis. These findings would lend support to optimal surveillance and treatment of bone metastasis in breast cancer. Keywords: initial metastatic breast cancer, bone, molecular subtype, survival

Guoying Deng,1,* Feng Zhou,1,* Zizheng Wu,2–4 Fei Zhang,1 Kerun Niu,2,3 Yingjie Kang,5 Xijian Liu,6 Qiugen Wang,1 Yin Wang,7 Qian Wang1 1Trauma Center, 2Department of Orthopaedics, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 3Department of Orthopaedics, Shanghai General Hospital of Nanjing Medical University, 4Department of Orthopaedics, Baoshan Branch of Shanghai General Hospital of Shanghai Jiaotong University, 5Department of Radiology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 6College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, 7Ultrasound Department of Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: The metastasis of cancer cells is a vital aspect of disease progression and therapy. Although a few nanoparticles (NPs) aimed at controlling metastasis in cancer therapy have been reported, the NPs are normally combined with drugs, yet the direct therapeutic effects of the NPs are not reported. To study the direct influence of NPs on cancer metastasis, the potential suppression capacity of CuS@mSiO2-PEG NPs to tumor cell migration, a kind of typical photothermal NPs, was systemically evaluated in this study. Using CuS@mSiO2-PEG NP stimulation and a trans­well migration assay, we found that the migration of HeLa cells was significantly decreased. This phenomenon may be associated with two classical proteins in metastasis: matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9). In addition, the mechanism may closely associate with non-receptor tyrosine kinase protein (SRC)/focal adhesion kinase (FAK) signaling pathway which varies in vivo and in vitro. To confirm the differences in the expression of SRC and FAK, related inhibitors were studied for additional comparison. Also, the results indicated that even though the migration inhibition was closely related to SRC and FAK signaling pathway, there may be another unknown regulation mechanism existing and its metastasis inhibition was significant. Confirmed by long-term survival curve study, CuS@mSiO2-PEG NPs significantly reduced the metastasis of cancer cells and improved the survival rates of metastasis in a mouse model. Thus, we believe that the direct influence of NPs on cancer cell metastasis is a promising study topic. Keywords: metastasis inhibition, photothermal nanoparticles, SRC/FAK signaling pathway, survival curves, MMPs

Yong Zhu,1,* Guoying Deng,2,* Anqi Ji,2 Jiayi Yao,1 Xiaoxiao Meng,1 Jinfeng Wang,1 Qian Wang,2 Qiugen Wang,2 Ruilan Wang1 1Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, 2Trauma Center, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China *These authors contributed equally to this work Abstract: Acute paraquat (PQ) poisoning is one of the most common forms of pesticide poisoning. Oxidative stress and inflammation are thought to be important mechanisms in PQ-induced acute lung injury (ALI). Selenium (Se) can scavenge intracellular free radicals directly or indirectly. In this study, we investigated whether porous Se@SiO2 nanospheres could alleviate oxidative stress and inflammation in PQ-induced ALI. Male Sprague Dawley rats and RLE-6TN cells were used in this study. Rats were categorized into 3 groups: control (n=6), PQ (n=18), and PQ + Se@SiO2 (n=18). The PQ and PQ + Se@SiO2 groups were randomly and evenly divided into 3 sub-groups according to different time points (24, 48 and 72 h) after PQ treatment. Porous Se@SiO2 nanospheres 1 mg/kg (in the PQ + Se@SiO2 group) were administered via intraperitoneal injection every 24 h. Expression levels of reduced glutathione, malondialdehyde, superoxide dismutase, reactive oxygen species (ROS), nuclear factor-κB (NF-κB), phosphorylated NF-κB (p-NF-κB), tumor necrosis factor-α and interleukin-1β were detected, and a histological analysis of rat lung tissues was performed. The results showed that the levels of ROS, malondialdehyde, NF-κB, p-NF-κB, tumor necrosis factor-α and interleukin-1β were markedly increased after PQ treatment. Glutathione and superoxide dismutase levels were reduced. However, treatment with porous Se@SiO2 nanospheres markedly alleviated PQ-induced oxidative stress and inflammation. Additionally, the results from histological examinations and wet-to-dry weight ratios of rat lung tissues showed that lung damage was reduced after porous Se@SiO2 nanosphere treatment. These data indicate that porous Se@SiO2 nanospheres may reduce NF-κB, p-NF-κB and inflammatory cytokine levels by inhibiting ROS in PQ-induced ALI. This study demonstrates that porous Se@SiO2 nanospheres may be a therapeutic method for use in the future for PQ poisoning. Keywords: porous Se@SiO2 nanospheres, acute lung injury, paraquat poisoning, oxidative stress, inflammatory cytokines, ROS, NF-kappa B

Jingxin Zhang,1,* Guoxia Zhang,2,* Pingping Hu,3 Guodong Deng,4 Qiqi Liu,4 Lili Qiao,4 Hui Luo,1 Jiandong Zhang3 1Department of Oncology, Weifang Medical College, Weifang, 2Department of Pathology, 3Department of Radiation Oncology, Qianfoshan Hospital Affiliated to Shandong University, 4Department of Oncology, Shandong University School of Medicine, Jinan, China *These authors contributed equally to this work Purpose: Vasculogenic mimicry (VM) is known to be a mechanism to nourish the tumor, but little is known about its prognostic significance in esophageal squamous cell carcinoma (ESCC). We characterized the predictive relevance of VM expression and tumor-infiltrating neutrophil (TIN) density in patients with resectable ESCC.Methods: We retrospectively collected clinicopathologic characteristics of 117 esophageal cancer (EC) patients undergoing complete resection and without preoperative therapy. Immunohistochemistry was used to detect the expression of E-cadherin and CD66b. CD34/periodic acid-schiff (PAS) double staining was used to detect the expression of VM.Results: VM expression was observed in 56 (47.9%) patients. VM was negatively correlated with E-cadherin (correlation coefficient =–0.364, P

Jingxin Zhang,1,* Qiqi Liu,2,* Lili Qiao,3 Pingping Hu,2 Guodong Deng,2 Ning Liang,2 Jian Xie,2 Hui Luo,4 Jiandong Zhang2 1Division of Oncology, Department of Graduate, Weifang Medical College, Weifang, 2Department of Radiation Oncology, Qianfoshan Hospital Affiliated to Shandong University, Shandong University, 3Department of Oncology, The Fifth Peoples’ Hospital of Jinan, Jinan, 4Department of Radiation Oncology, Henan Cancer Hospital Affiliated to Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China *These authors contributed equally to this work Purpose: Recent studies demonstrate the possible antitumor effects of granulocyte-macrophage colony-stimulating factor (GM-CSF); however, the exact mechanism is still unclear. The aim of our study was to analyze the effects of GM-CSF on multiple biological functions of human esophageal cancer (EC) cell lines and to explore the potential mechanism of its antitumor effects. Materials and methods: Eca109/9706 human EC cells were examined. Cell proliferation, apoptosis, and migration were analyzed using cell proliferation assay, flow cytometry, and transwell assay, respectively. The expression of signaling molecules were examined by reverse transcription polymerase chain reaction and Western blot. Results: Our results provide experimental evidence that GM-CSF inhibits growth and migration, as well as induction of apoptosis in EC cells. In addition, EC cells stimulated with GM-CSF were more likely to have suppressed epithelial-to-mesenchymal transition (EMT), accompanied by increased E-cadherin and decreased vimentin expression. Conclusion: Our data demonstrate that GM-CSF inhibits cancer cell proliferation and migration, as well as induction of apoptosis. Moreover, our findings indicate that GM-CSF may regulate EMT through JAK2-PRMT5 signaling, and thereby exhibit its antitumor effects on EC cells. Keywords: granulocyte-macrophage colony-stimulating factor, cancer, antitumor, epithelial-to-mesenchymal transition, esophageal cancer

Qiqi Liu,1,* Pingping Hu,1,* Guodong Deng,1 Jingxin Zhang,2 Ning Liang,1 Jian Xie,1 Lili Qiao,3 Hui Luo,4 Jiandong Zhang1 1Department of Radiation Oncology, Qianfoshan Hospital Affiliated to Shandong University, Shandong University, Jinan, 2Division of Oncology, Department of Graduate, Weifang Medical College, Weifang, 3Department of Oncology, The Fifth People’s Hospital of Jinan, Jinan, 4Department of Radiation Oncology, Henan Cancer Hospital Affiliated to Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China *These authors contributed equally to this work Purpose: Soluble cytotoxic T-lymphocyte antigen 4 (sCTLA-4), one of the isoforms of CTLA-4, was discovered to be critical in downregulating the negative signal of CTLA-4 in T-cell responses. Contrary to the classical immunosuppressive effect of CTLA-4, its immunoregulatory function might be complicated. However, the clinical significance of sCTLA-4 to immune regulation and the variation in cancer therapy have not been elucidated. We postulated that the level of sCTLA-4 might affect the outcome of cancer prognosis.Patients and methods: Serum concentrations of sCTLA-4 before and after therapy in 141 locally advanced and advanced cancer patients were measured and survival analyses was performed. Hazard ratio and 95% confidence interval for overall survival (OS) were calculated. Cutoffs were determined by median across the sCTLA-4 level of entire patients.Results: High expression of sCTLA-4 after therapy indicated significant longer OS and progression-free survival (PFS) (all P

Qiang Cai,1,* Gang Xu,2,* Junhui Liu,1 Long Wang,1 Gang Deng,1 Jun Liu,3 Zhibiao Chen1 1Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, 2Department of Neurosurgery, Xiantao First People’s Hospital, Xiantao, 3Department of Emergency, The Central Hospital of Wuhan, Wuhan, Hubei, People’s Republic of China *These authors contributed equally to this work Abstract: Stroke is one of the common causes of death and disability in the world. The intraluminal middle cerebral artery occlusion/reperfusion (MCAO/R) model is a “gold standard” in surgical ischemic stroke models. Here, we optimized the procedure of this model by ligating on external carotid artery (ECA) stump and two ligatures prepared on internal carotid artery, which could improve the success and survival rate in mice. The results show that ECA approach was superior to common carotid artery approach. Meanwhile, we found that the exposure of pterygopalatine artery was not an essential step for MCAO/R model in mice. Keywords: middle cerebral artery occlusion, ischemia stroke, animal model, mice

Liyong Xing, Zhifei Liu, Gang Deng, Huan Wang, Yanfeng Zhu, Peng Shi, Bingyue Huo, Yindong Li Department of Urology, Tangshan People’s Hospital, Tangshan, People’s Republic of China Purpose: Xanthogranulomatous prostatitis (XP) is a rare form of nonspecific granulomatous prostatitis that can clinically mimic high-grade prostatic carcinoma. It is difficult to diagnose it definitely in clinical settings. Methods: We report a case of XP with prostate-rectal fistula and review the relevant literatures. Result: A 75-year-old man presented with rectal bleeding when he urinated. A locally advanced carcinoma of prostate was suspected initially following the physical, imaging, and hematologic examinations. Subsequently on histopathological and immunohistochemical staining after needle biopsy of the prostate, a diagnosis of XP was made definitely. The patient was catheterized temporarily and treated with tamsulosin and estrogen. The patient underwent uneventful recovery after this conservative therapy. Conclusion: Histologic and immunohistochemical analyses are valuable in differentially diagnosing XP from high-grade prostate carcinoma. Treatment strategy of XP in principle is recommended to be the conservative method. Long-term follow-up earns are highly regarded considering the possibility of coexisting prostate cancer. Keywords: xanthogranulomatous prostatitis, prostate-rectal fistula

Lei Zhu, Feizhou Huang, Gang Deng, Wanpin Nie, Wei Huang, Hongbo Xu, Shaopeng Zheng, Zhongjie Yi, Tao Wan Department of Hepatobiliary and Pancreatic Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China Abstract: In spite of improvements in surgical technology, the resectability and curability of intrahepatic cholangiocarcinoma (ICC) are still low. Our previous study showed that the strong Sal-like protein 4 (Sall4)-positive cases had shorter overall survival compared to Sall4-negative cases, indicating an oncogenic role of Sall4 in ICC. In this study, we aimed to explore the precise mechanism of Sall4 on ICC cell invasion and metastasis. We evaluated the expression of Sall4, PTEN, and Bmi-1 in 28 cases of adjacent tissues and 175 cases of ICC tissues by using immunohistochemical staining. We found that the expression of Sall4 and Bmi-1 was significantly increased in ICC tissues compared with the adjacent tissues, while PTEN expression was reduced in ICC tissues compared with the adjacent tissues, and there was a reverse relationship between Sall4 and PTEN in ICC, whereas there was a positive correlation in Sall4 and Bmi-1 expression in ICC. In addition, overall survival analysis showed that ICC patients with low PTEN exhibited a worse prognosis than ICC patients with high PTEN, and lower Bmi-1 expression showed a better prognosis than ICC patients with high Bmi-1. By a battery of experiments in vitro, we demonstrated that Sall4 promotes ICC cell proliferation, and progression of ICC might be through PTEN/PI3K/Akt and Bmi-1/Wnt/β-catenin signaling and enhancing epithelial–mesenchymal transition process. Thus, Sall4 may be a potential target for the treatment of ICC metastasis. Keywords: intrahepatic cholangiocarcinoma, Sal-like protein 4, PTEN, Bmi-1, metastasis, EMT

Claudia M Witt,1–3 Marion Pérard,2 Brian Berman,3,4 Susan Berman,4 Timothy C Birdsall,5 Horst Defren,6 Sherko Kümmel,7 Gary Deng,8 Gustav Dobos,9 Atje Drexler,10 Christine Holmberg,2 Markus Horneber,11 Robert Jütte,9 Lori Knutson,12 Christopher Kummer,13 Susanne Volpers,14 David Schweiger15 1University Hospital Zurich, Institute for Complementary and Integrative Medicine, Zurich, Switzerland; 2Institute for Social Medicine, Epidemiology and Health Economics, Charité-Universitätsmedizin, Berlin, Germany; 3University of Maryland School of Medicine, Center for Integrative Medicine, Baltimore, Maryland, USA; 4The Institute for Integrative Health, Baltimore, USA; 5Cancer Treatment Centers of America, Goodyear, Arizona, USA, 6Kliniken Essen Mitte, Evang, Huyssen-Stiftung/Knappschaft GmbH Patientenmanagement, Essen, Germany; 7Department of Senology, Breast Center, Kliniken Essen-Mitte, Evang. Huyssens Stiftung, Knappschaft GmbH, Essen, Germany; 8Memorial Sloan-Kettering Cancer Center, New York, USA; 9Department of Internal and Integrative Medicine, Kliniken Essen-Mitte, Academic Teaching Hospital of the University of Duisburg-Essen, Germany; 10Robert Bosch Foundation GmbH, Stuttgart, Germany; 11Department of Internal Medicine, Division of Oncology and Hematology, Paracelsus Medical University, Klinikum Nürnberg, Germany; 12Integrative Healthcare Solutions, Minneapolis, Minnesota, USA; 13Institute of Mergers, Acquisitions and Alliances (IMAA), Zurich, Switzerland; 14Frauenselbsthilfe nach Krebs, Bonn, Germany; 15Schweiger, Schweiger & Associates, Hilton Head Island, South Carolina, USA Background: An increasing number of clinics offer complementary or integrative medicine services; however, clear guidance about how complementary medicine could be successfully and efficiently integrated into conventional health care settings is still lacking. Combining conventional and complementary medicine into integrative medicine can be regarded as a kind of merger. In a merger, two or more organizations - usually companies - are combined into one in order to strengthen the companies financially and strategically. The corporate culture of both merger partners has an important influence on the integration.Purpose: The aim of this project was to transfer the concept of corporate culture in mergers to the merging of two medical systems.Methods: A two-step approach (literature analyses and expert consensus procedure) was used to develop practical guidance for the development of a cultural basis for integrative medicine, based on the framework of corporate culture in “mergers,” which could be used to build an integrative medicine department or integrative medicine service.Results: Results include recommendations for general strategic dimensions (definition of the medical model, motivation for integration, clarification of the available resources, development of the integration team, and development of a communication strategy), and recommendations to overcome cultural differences (the clinic environment, the professional language, the professional image, and the implementation of evidence-based medicine).Conclusion: The framework of mergers in corporate culture provides an understanding of the difficulties involved in integrative medicine projects. The specific recommendations provide a good basis for more efficient implementation. Keywords: integrative medicine, mergers, corporate culture

The DESCANT array (Deuterated Scintillator Array for Neutron Tagging) consists of up to 70 detectors, each filled with approximately 2 liters of deuterated benzene. This scintillator material o_ers pulse-shape discrimination (PSD) capabilities to distinguish between neutrons and γ-rays interacting with the scintillator material. In addition, the anisotropic nature of n – d scattering allows for the determination of the neutron energy spectrum directly from the pulse height spectrum, complementing the traditional time-of-flight (ToF) information. DESCANT can be coupled either to the TIGRESS (TRIUMF-ISAC Gamma-Ray Escape Suppressed Spectrometer) γ-ray spectrometer [1] located in the ISAC-II [2] hall of TRIUMF for in-beam experiments, or to the GRIFFIN (Gamma-Ray Infrastructure For Fundamental Investigations of Nuclei) γ-ray spectrometer [3] located in the ISAC-I hall of TRIUMF for decay spectroscopy experiments.

A neutron tagging array based upon liquid deuterated scintillators is being developed for the study of neutron-rich systems. The DEuterated SCintillator Array for Neutron Tagging, or DESCANT, will serve as an auxiliary detector for both the TIGRESS and GRIFFIN γ-ray spectrometers located at TRIUMF’s ISAC radioactive ion beam facility. DESCANT is comprised of 70 pseudohexaconical detectors of five varieties. The array is fully close-packed, subtends a downstream angle of θ = 65° and covers 92.6% of this solid angle or 1.08π sr. Each detector is 150 mm thick and filled with Bicron BC-537 liquid deuterated scintillator. The white, red and blue detectors are viewed by 127 mm diameter Hamamatsu R4155 photomultiplier tubes while the yellow and green detectors are viewed by 78 mm diameter ET Enterprises 9822B photomultiplier tubes. The aim of this work is to report on the mechanical design of DESCANT and the performance of a prototype detector measured using mono-energetic neutrons.