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Ling Yang *, Qi Shen *, Chao Hu, Ying Wang, Xiaohong Zhu, Shiqing Shu, Zhu Luo Clinical Trial Center, National Medical Products Administration Key Laboratory for Clinical Research and Evaluation of Innovative Drugs, West China Hospital Sichuan University, Chengdu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhu Luo, Clinical Trial Center, National Medical Products Administration Key Laboratory for Clinical Research and Evaluation of Innovative Drugs, West China Hospital Sichuan University, No. 37 Guoxue Lane, Chengdu, Sichuan, 610044, People’s Republic of China, Tel +86 28 85422707, Email luozhu720@163.comBackground: Imrecoxib is a novel and moderately selective cyclooxygenase-2 inhibitor with properties of anti-inflammation and alleviating pain, which is widely applied in osteoarthritis patients. The pharmacokinetic data supporting imrecoxib’s rational use in elderly population are not available.Purpose: The study aims to investigate the pharmacokinetics of imrecoxib and its main metabolites and explore the safety of imrecoxib in elderly healthy subjects.Methods: A total of 19 healthy subjects including 10 non-elderly and 9 elderly subjects received single dose of 100 mg imrecoxib under fasting condition. Pharmacokinetics, safety and tolerability profiles were assessed.Results: After oral administration of single dose of 100 mg imrecoxib, it was absorbed into plasma with median time to reach peak concentration (Tmax) around 2 hours. The concentration–time curves of imrecoxib (M0) showed higher interindividual variability in elderly subjects compared with non-elderly subjects. Peak concentration (Cmax) of M0, its hydroxyl metabolite M1 and carboxylated metabolite M2 in plasma increased by 39%, 21% and 17%, and area under concentration–time curve from time 0 to time t (AUC0-t) of M0, M1 and M2 in plasma increased by 34%, 13% and 27%, respectively, in elderly subjects compared with non-elderly subjects. The 90% CIs of geometric mean ratios of Cmax, AUC0-t and AUC0-∞ of M0, M1 and M2 between the two groups were not located within 80– 125%, indicating Cmax, AUC0-t and AUC0-∞ were not completely equivalent between non-elderly and elderly healthy subjects. However, comparison of pharmacokinetic data of M0, M1 and M2 between the two groups showed no significant difference (P> 0.05). Imrecoxib was well tolerated in both non-elderly and elderly healthy subjects, especially with favorable gastrointestinal and cardiovascular safety profiles.Conclusion: Pharmacokinetic and safety profiles of imrecoxib in elderly healthy subjects indicated that no dose adjustment should be required for elderly population.Keywords: cyclooxygenase-2 inhibitor, imrecoxib, pharmacokinetics, safety, elderly

Li Yang,1 Zhinan Zhai,2 Jinxiang Zhang3 1Department of Respiratory and Critical Care Medicine, Tianjin Chest Hospital, Tianjin, People’s Republic of China; 2Department of Medical Laboratory Science, Tianjin Chest Hospital, Tianjin, People’s Republic of China; 3Department of Nutrition, Tianjin Chest Hospital, Tianjin, People’s Republic of ChinaCorrespondence: Li Yang, Department of Respiratory and Critical Care Medicine, Tianjin Chest Hospital, No. 261 Taierzhuang South Road, Jinnan District, Tianjin, 300222, People’s Republic of China, Tel +86 22-88185009, Email yangli.409@163.comObjective: Biomarkers for the acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) are urgently needed to provide better patient management. We aimed to investigate whether serum 1,25(OH)2D3 (1,25-dihydroxy vitamin D3) levels predict AE-IPF and whether they could be a potential prognostic biomarker for IPF.Participants and Methods: This prospective study included 72 patients with IPF (31 with stable IPF and 41 with AE-IPF). All participants were recruited during hospitalisation at Tianjin Chest Hospital and were followed up for at least 12 months. Demographics, comorbidities, arterial blood gas, and serum biochemical profile, radiological features, and anti-fibrotic therapy were evaluated. Serum concentrations of 1,25(OH)2D3 and transforming growth factor beta1 (TGFβ 1) were detected using enzyme-linked immunosorbent assay (ELISA). Risk factors for AE-IPF were identified using multivariate analysis. Prognostic factors were assessed using Kaplan-Meier and Cox regression analyses.Results: Baseline values of alveolar-arterial oxygen difference (A-aDO2) (40.85 mmHg vs 29.2 mmHg, p =0.035), white blood cell counts (10.09 ± 4.2× 109/L vs 7.46 ± 7.84× 109/L, p < 0.001), percentage of monocytes (7.36 ± 1.36% vs 6.6 ± 1.2%, p =0.017), C-reactive protein (CRP) (2.1 mg/dL vs 1.12 mg/dL, p =0.015) and procalcitonin (PCT) (36.59% vs 3.23%, p < 0.001) were significantly higher in AE-IPF patients than in stable IPF patients. Instead, the mean concentration of serum calcium and 1,25(OH)2D3 at baseline were higher in IPF patients with stable disease than in those with acute exacerbation (2.17 ± 0.13 nmol/L vs 2.09 ± 0.13 nmol/L, p =0.023 and 16.62 pg/mL vs 11.58 pg/mL, p < 0.001, respectively). In multivariate analysis, a higher proportion of patients with lower serum 1,25(OH)2D3 levels experienced AE-IPF (OR 0.884, 95% CI 0.791– 0.987, p =0.029), and rising serum PCT level (PCT > 0.05 ng/mL) was associated with an increased risk of mortality (HR 3.664, 95% CI 1.010– 12.900, p =0.043).Conclusion: Decreased serum 1,25(OH)2D3 is associated with an increased risk of acute exacerbation for patients with IPF. A high serum PCT level is predictive of worse prognosis in IPF patients. 1,25(OH)2D3 may be a potential biomarker for AE-IPF, while PCT could be a prognostic biomarker for IPF.Keywords: idiopathic pulmonary fibrosis, acute exacerbation, 1,25(OH)2D3, procalcitonin

Wenliang Liu, Gongying Li, Congjie Wang, Mingchao Yu, MengYa Zhu, Lin Yang Department of Psychological, Huai’an No.3 People’s Hospital, Huaian, People’s Republic of ChinaCorrespondence: Gongying Li, Department of Psychological, Huai’an No.3 People’s Hospital, No. 272, Huaihai West Road, Huai an, 223001, People’s Republic of China, Tel +86-517-83285124, Email ligongying2005@126.comObjective: The efficacy of medication and psychotherapy for adolescent depression is controversial, so we conducted a meta-analysis to evaluate the efficacy of combination therapy.Methods: We followed the PRISMA checklist in completing the meta-analysis. Relevant literature was searched in PubMed, Web of Science and Embase, Chinese databases CNKI and WanFang Data. We included the literature on the comparison of the fluoxetine plus psychotherapy or cognitive-behavioral therapy (CBT) and each treatment alone for adolescent depression published in 1980– 2021. All statistical analyses were performed using Stata software.Results: After careful review, a total of 489 relevant articles were retrieved, and 13 studies were finally included. In comparison with the control group (fluoxetine alone), fluoxetine plus CBT achieved higher response rate (RR=1.12, 95% CI: 1.04, 1.21), lower incidence of adverse Reactions (RR=0.62,95% CI:0.40,0.96), lower proportion of suicide or self-injury (RR=0.94,95% CI:0.74,1.20), and lower one-year recurrence rate (RR=0.27, 95% CI: 0.16, 0.45). Before treatment, there were no significant differences in Hamilton Depression Scale score (HAMD), Children’s Depression Rating Scale Revised (CDRS-R) score, and Clinical Global Impression (CGI) Severity score. After treatment, HAMD score (SMD=− 1.01, 95% CI:-1.39,-0.63), CDRS-R score (SMD= − 0.10,95% CI:-0.26,-0.07), and CGI score (SMD = − 0.22, 95% CI: − 0.54, − 0.10) were significantly lower in the combined treatment group than in the control group.Conclusion: Adolescents simultaneously treated with fluoxetine and CBT had significantly reduced incidence of depressive symptoms, suicide or NSSI, adverse reactions, and one-year recurrence of symptoms, than adolescents treated with fluoxetine alone. This indicates fluoxetine plus CBT may be superior to fluoxetine alone for the clinical treatment of adolescent depression.Keywords: adolescent depression, fluoxetine, psychotherapy, cognitive behavioral therapy, CBT, meta-analysis

Yu Luo,1 Jianan Hao,1,2 Xiaoyu He,1,2 Cuiyu Wang,1 Hang Zhao,1 Zhimei Zhang,1 Liqun Yang,1 Luping Ren1 1Endocrinology Department, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 2Graduate School, Hebei Medical University, Shijiazhuang, People’s Republic of ChinaCorrespondence: Luping Ren, Hebei General Hospital, No. 348, Heping West Road, Shijiazhuang, Hebei, 050051, People’s Republic of China, Tel +18633021149, Fax +86 311 85988406, Email renluping1122@163.comPurpose: The triglyceride–glucose index (TyG) is positively correlated with serum uric acid (SUA) in patients with type 2 diabetes mellitus (T2DM). However, whether this relationship exists in non-obese T2DM patients remains unknown. The study investigated the relationship between TyG and SUA in Chinese non-obese T2DM patients and examined the prognostic value of TyG in hyperuricemia (HUA).Patients and Methods: In total, 719 T2DM patients who were not obese were enrolled from among those who visited the Hebei General Hospital. The patients were categorized into groups according to their SUA levels. The relationship between TyG and clinical parameters was examined through correlation analysis. To consider covariates and examine the independent impact of TyG on HUA, logistic regression was performed. The receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of TyG and homeostasis model assessment of insulin resistance (HOMA-IR) for HUA.Results: The HUA prevalence was 12.10%. TyG was statistically different among the four SUA groups, with lower TyG levels in the Q1, Q2, and Q3 groups than that in the Q4 group. TyG was positively correlated with SUA (r = 0.176, P < 0.001). Logistic regression exhibited that TyG and SUA were independently correlated (OR = 2.427, 95% CI = 1.134-5.195, P = 0.022) even after adjustment for confounding factors. The ROC curve showed that the predictive value of TyG for HUA was higher than that of HOMA-IR (AUROC = 0.613, P = 0.001).Conclusion: TyG was positively correlated with SUA in non-obese T2DM patients. TyG may better predict HUA in non-obese T2DM patients than HOMA-IR.Keywords: type 2 diabetes mellitus, insulin resistance, uric acid, hyperuricemia, TyG, HOMA-IR, inflammation

Long Yang,1,&ast; Yue Lin,2,&ast; Xiangqun Zhang,1 Bing Wei,1 Junyu Wang,1 Bo Liu1 1Emergency Medicine Clinical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, & Beijing Key Laboratory of Cardiopulmonary Cerebral Resuscitation, Beijing, 100020, People’s Republic of China; 2Department of Radiology, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China&ast;These authors contributed equally to this work Correspondence: Bo Liu; Junyu Wang, Emergency Medicine Clinical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, & Beijing Key Laboratory of Cardiopulmonary Cerebral Resuscitation, Beijing, 100020, People’s Republic of China, Tel/Fax +86 10-51718171, Email ripplecyyy@126.com; wangjunyu_cyyy@126.comPurpose: Procalcitonin and predisposition, infection, response, and organ dysfunction (PIRO) system have high predictive value for the prognosis of critically ill patients. There are few studies on the predictive value of patients with positive blood cultures. The aim of the study was to evaluate risk stratification and sepsis-related mortality in patients with positive blood cultures via procalcitonin (PCT) combined with the PIRO system in emergency departments (ED).Methods: A total of 1074 patients with positive blood cultures were admitted to Beijing Chao-Yang Hospital ED from December 2017 to October 2020. Their serum PCT was recorded, along with a Sequential Organ Failure Assessment (SOFA) score, Mortality in Emergency Department Sepsis (MEDS) score, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and PIRO score to predict the prognosis of septic patients with positive blood culture in terms of ICU (intensive care unit) admission, multiple organ dysfunction syndrome (MODS) development, and 28-day mortality. Receiver operating characteristic (ROC) curves and logistic regression analysis were used to assess the prognostic value of the scoring systems.Results: A total of 978 patients met the inclusion criteria. PCT, MEDS, APACHE II, and PIRO scores were found to independently predict ICU-admission, MODS development, and 28-day mortality (P< 0.05), whereas SOFA did not. The AUC values of the PCT, MEDS, APACHE II, and PIRO scores for ICU-admission were 0.620, 0.740, 0.780, and 0.751, respectively. In the prediction of 28-day mortality, the AUC values of PCT, MEDS, APACHE II, and PIRO were 0.782, 0.745, 0.805, and 0.831, respectively. The AUC values combined PCT and PIRO system in predicting MODS and 28-day mortality were better than when predicting ICU-admission.Conclusion: This study indicates that PCT combined with the PIRO scoring system has a higher predictive value and is superior in predicting MODS and 28-day mortality in septic patients with positive blood cultures.Keywords: procalcitonin, PIRO scoring system, positive blood culture, 28-day mortality

Pengjia Wu, Jiashun Zeng, Lei Yang Department of Rheumatology and Immunology, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550000, People’s Republic of ChinaCorrespondence: Jiashun Zeng, Email zengjiashun@sina.comAbstract: Patients with systemic lupus erythematosus (SLE) are prone to various infections due to autoimmune defects and long-term use of immunosuppressive agents. Mycobacterium tuberculosis (TBC) infection is a common infection in patients with SLE, especially in developing countries such as China. SLE and TBC may overlap and confuse a clinical picture, bringing great difficulties for the diagnosis and treatment. This article reports a case of vesicorectal fistula caused by intestinal TBC complicated with SLE, where the manifestation was recurrent diarrhea, initially treated as lupus-associated intestinal vasculitis without notable response. This case suggests that we should pay attention to close monitoring of tuberculosis-related indicators during the follow-up period of SLE patients, especially in endemic areas, and early diagnosis and treatment of TBC can reduce tuberculosis-related complications and significantly improve the quality of life of patients.Keywords: systemic lupus erythematosus, vesicorectal fistula, intestinal tuberculosis, infect, diarrhea

Shasha Jin,&ast; Yixin Wang,&ast; Chenxin Qie, Lu Yang, Yinhao Wu, Tingting Zhang, Jianwen Di, Jun Liu New Drug Screening Center, Institute of Pharmaceutical Sciences, China Pharmaceutical University, Nanjing, 210009, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Liu, New Drug Screening Center, China Pharmaceutical University, Nanjing, 210009, People’s Republic of China, Tel +86-25-83271043, Fax +86-25-83271142, Email junliu@cpu.edu.cnPurpose: Psoriasis is a chronic systemic inflammatory skin disease with a high recurrence rate. The immune response plays an important role in psoriasis. However, the subsets of immune cells involved in inflammation in psoriatic mice have not been fully studied. This study showed the immune environment characteristics of psoriasis in mice.Methods: We used single-cell RNA sequencing (10× Genomics) as an unbiased analytical strategy to investigate the heterogeneity of skin immune cells in imiquimod-induced psoriasis mice systematically.Results: We identified 10 major clusters and their marker genes among 14,439 cells. The proportions of macrophages, NK/T cells, conventional dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs) were increased in psoriatic mice. Macrophages were the largest group and were further divided into 7 subgroups, and all macrophage clusters were increased in psoriatic mice. Differentially expressed genes in control versus psoriatic mice skin lesions showed that Fcgr4, Saa3 and Acp5 in macrophages, Acp5, Fcgr4 and Ms4a6d in NK/T cells, Saa3 in cDCs, and Ifitm1 in pDCs were upregulated in psoriasis mice. Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis emphasized the role of oxidative phosphorylation signals and antigen processing and presentation signals in murine psoriasis-like models.Conclusion: Our study reveals the immune environment characteristics of the commonly used IMQ induced psoriasis-like models and provides a systematic insight into the immune response of mice with psoriasis, which is conducive to comparing the similarities and differences between the mouse model and human psoriasis.Graphical Abstract: Keywords: single-cell RNA sequencing, psoriasis, imiquimod, immune cells

Lanyao Yang1,2 &ast;, Lanlan Wu3 &ast;, 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&ast;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

Zhili Zhang,1,&ast; Xin Zhang,1,2,&ast; Xue Chen,1,2 Xiao Cui,1 Miaotian Cai,1 Liu Yang,1 Yulin Zhang1,2 1Department of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yulin Zhang, Department of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China, Tel +86 10-83997143, Fax +86 10-63293371, Email yulinzhang@ccmu.edu.cnPurpose: Brucellosis is an ongoing zoonotic disease in China, but there are few data in Beijing. This study was designed to illustrate clinical characteristics of patients with brucellosis in Beijing, China and explore the risk factors for focal brucellosis.Patients and Methods: Data of patients with brucellosis were retrospectively collected from the patients’ electronic medical records in Beijing Youan Hospital during 2010 to 2021, including epidemiological, demographic and clinical features. Risk factors for focal brucellosis were identified by multivariable logistic regression models.Results: A total of 197 patients were included in the study, with 165 (83.8%) cases in acute phase and 32 (16.2%) cases in chronic phase. Patients in acute phase were more likely to have splenomegaly (24.2% vs 3.1%, p=0.007) than those in chronic phase, but had less arthralgia (62.4% vs 81.3%, p=0.040). The median level of alanine aminotransferase (36.9 vs 20.7, p=0.001) was higher in patients at acute stage than those at chronic stage. Of all the patients, 76 (38.6%) were reported with focal complications, including 16 (8.1%) peripheral arthritis, 36 (18.3%) spondylitis, 17 (8.6%) epididymoorchitis, 8 (4.1%) meningitis and 3 (1.3%) endocarditis. Additionally, male (OR 2.76, 95% CI 1.15– 6.64, p = 0.023), arthralgia (OR 6.23, 95% CI 2.36– 16.43, p < 0.001) and higher level of platelets (OR 1.01, 95% CI 1.00– 1.01, p < 0.001) were the independent risk factors for focal brucellosis.Conclusion: The control of human brucellosis still cannot be ignored due to the re-emerging cases in Beijing, which are more likely to present splenomegaly and abnormal liver function in acute phase. Moreover, male, arthralgia and high level of platelets were the independent risk factors for focal brucellosis.Keywords: brucellosis, clinical characteristics, epidemiology, focal complications, risk factors

Yukun Chen,1 Zhenzhi Wang,2 Xiaofan Wang,3 Mingliang Su,1 Fan Xu,1 Lian Yang,1 Lijun Jia,1 Zhanxia Zhang1 1Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China; 2Shaanxi University of Chinese Medicine, Xianyang, 712046, People’s Republic of China; 3Department of Oncology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, 100078, People’s Republic of ChinaCorrespondence: Lijun Jia; Zhanxia Zhang, Email ljjia@shutcm.edu.cn; zhanxiazhang@shutcm.edu.cnAbstract: 10-Hydroxycamptothecin (HCPT) is a natural plant alkaloid from Camptotheca that shows potent antitumor activity by targeting intracellular topoisomerase I. However, factors such as instability of the lactone ring and insolubility in water have limited the clinical application of this drug. In recent years, unprecedented advances in biomedical nanotechnology have facilitated the development of nano drug delivery systems. It has been found that nanomedicine can significantly improve the stability and water solubility of HCPT. NanoMedicines with different diagnostic and therapeutic functions have been developed to significantly improve the anticancer effect of HCPT. In this paper, we collected reports on HCPT nanomedicines against tumors in the past decade. Based on current research advances, we dissected the current status and limitations of HCPT nanomedicines development and looked forward to future research directions.Keywords: 10-hydroxycamptothecin, antitumor, nanomedicine, nano-drug delivery systems

Fang Liu,&ast; Rongfeng Qu,&ast; Limin Yang, Guang Shi, Shuhong Hao, Chunmei Hu Department of Hematology and Oncology, The Second Hospital of Jilin University, Changchun, Jilin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunmei Hu, Department of Hematology and Oncology, The Second Hospital of Jilin University, Ziqiang Street No. 265, Changchun, Jilin, 130041, People’s Republic of China, Tel/Fax +86043181136427, Email guyue_111@163.comAbstract: Circular RNAs (circRNAs) participate in the occurrence and development of various diseases through different mechanisms, such as by acting as a microRNA (miRNA) sponge, interacting with RNA-binding proteins, and regulating gene transcription and protein translation. For example, the abnormal expression of specific circRNAs in tumor cells can alter key regulatory factors and the cell cycle network, resulting in cell cycle disorders and the development and metastasis of tumors. Here, we summarize the mechanisms involved in the circRNA-mediated processes that lead to uncontrolled cell cycle and tumor cell proliferation. Extensive studies investigating the abnormal expression of circRNAs in different cancer types have been conducted. The unique characteristics of circRNAs and their ability to regulate the cell cycle through diverse mechanisms is extremely valuable in tumor diagnosis, treatment, and prognosis. Our review may assist in further understanding the circRNA-mediated regulation of the cell cycle in tumors and provide insights for research on circRNA-based therapeutic strategies and biological diagnosis for cancer.Keywords: circRNA, cancer, cyclins, CDKs, CKIs, p53

Liuying Li,1 Lanying Yang,2 Biao Luo,2 Lvyu Deng,2 Yue Zhong,2 Daohui Gan,2 Xiaohan Wu,2 Peimin Feng,1 Fengya Zhu2 1Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Traditional Chinese Medicine Department, Zigong First People’s Hospital, Zigong, People’s Republic of ChinaCorrespondence: Peimin Feng; Fengya Zhu, Email fpmmed@cdutcm.edu.cn; notfounds@foxmail.comBackground: Post-stroke cognitive impairment (PSCI) is one of the most common complications after stroke. In recent years, as a complementary alternative therapy, many systematic reviews (SRs) and meta-analysis (MAs) have reported the efficacy and safety of acupuncture in improving cognitive function in patients with PSCI, but the quality of evidence is unknown and therefore needs to be evaluated comprehensively.Aim: We aimed to evaluate the SRs of acupuncture for patients with PSCI, to summarize the evidence quality of SRs to provide scientific evidence.Methods: We searched for relevant SRs and MAs in seven databases up to March 22, 2022. Two reviewers independently completed literature retrieval, screening, and data extraction. We used A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) to evaluate the methodological quality; the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool to determine the strength of evidence; and the ROBIS tool to assess RoB.Results: We identified 14 SRs. The methodological quality of all SRs was low (2/14) or very low (12/14). GRADE results showed 13 were moderate quality (26%), 5 were low quality (10%), and 32 were very-low quality (64%). RoB showed that one SR had a low risk and 13 had a high risk. Moderate quality results showed that combined acupuncture therapy was superior to western medicine or cognitive rehabilitation training in improving cognitive function, the total response rate, and the daily living ability of patients with PSCI.Conclusion: Based on the evidence, acupuncture appears to be effective and safe in improving cognitive function for patients with PSCI, but the overall quality of SRs is not high. High-quality randomized controlled trials are needed to confirm the effectiveness and safety of acupuncture on the cognitive function of patients with PSCI.Systematic Review Registration: PROSPERO CRD42022315441.Keywords: acupuncture, PSCI, overview, AMSTAR-2, GRADE

Xu Yang,1 Amin Liu,1 Lin Yang,1 Tiantian Wen,2 Jia Wang,3 Jingmiao Shi,3 Hui Zhou,2 Zhimeng Chen,1 Meng Lei,1 Yongqiang Zhu2 1College of Science, Nanjing Forestry University, Nanjing, People’s Republic of China; 2College of Life Science, Nanjing Normal University, Nanjing, People’s Republic of China; 3Jiangsu Chia Tai Fenghai Pharmaceutical Co. Ltd, Nanjing, People’s Republic of ChinaCorrespondence: Meng Lei; Yongqiang Zhu, Tel +86 25 85427621 ; +86 25 85891591, Email hk-lm@163.com; zhyqscu@hotmail.comIntroduction: FHND6091, a novel N-capped dipeptidyl boronic acid proteasome inhibitor with promising pharmacological properties, entirely converted into active form FHND6081 under physiological conditions. The proteasome, a key component of the ubiquitin-proteasome pathway (UPP), has emerged as a validated target of multiple myeloma (MM) therapeutics. FHND6091 is a selective oral proteasome inhibitor that binds irreversibly to the β 5 submit of the 20S proteasome and exerts anti-cancer roles.Methods: In this study, we investigated the metabolic stability, metabolite production, metabolic pathways and plasma protein binding (PPB) of FHND6081 along with its absorption, tissue distribution, excretion (ADME) and pharmacokinetics (PK) in animals.Results: Ultra-high performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) identified a total of nine new metabolites after co-incubation with FHND6091 in hepatocytes from different species. A hypothetical CYP450-metabolic pathway including dehydrogenation, N-dealkylation plus mono-oxygenation and other was proposed. In addition, FHND6081 was highly bound to plasma proteins (> 99%); nevertheless, it preferred to partition to red blood cells (B/P ratio: 4.91). The results of microsomal metabolic stability corroborated that FHND6081 was a moderate-clearance compound. In Caco-2 cell experiments, the compound displayed modest permeability suggesting that it may show limited bioavailability via oral routes. Furthermore, FHND6081 was extensively distributed in rats and the highest exposure was achieved in the stomach followed by the small intestine and adrenal gland. Pharmacokinetic studies were done by using Sprague-Dawley (SD) rats, oral absorption was fast and plasma exposure was dose-dependent and oral bioavailability were low. At the same dose, FHND6081 exposure was severalfold higher in whole blood than in plasma, which was consistent with blood cell partitioning. Moreover, only a small fraction of the parent compound was excreted via feces and urine and oxidative metabolites were detected in feces and plasma.Conclusion: The overall preclinical pharmacokinetic profile supported the selection and development of FHND6091 as a clinical candidate.Keywords: FHND6091, active form FHND6081, proteasome inhibitor, preclinical pharmacokinetics, tissue distribution, drug-availability

Qingwei Li,1 Haiyin Zhang,2 Guozhen Lin,3 Shenxun Shi,4 Yingli Zhang,5 Jianlin Ji,6 Lipeng Yang,7 Jun Yao,1 Wenyuan Wu1 1Department of Psychiatry, Tongji Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Clinical Psychology, Shanghai Mental Health Center, Shanghai, People’s Republic of China; 3Department of Psychiatry, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Psychiatry Department, Fudan University Affiliated Huashan Hospital, Shanghai, People’s Republic of China; 5Department of Depressive Disorders, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, People’s Republic of China; 6Department of Psychological Medicine, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 7Department of Neurology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, People’s Republic of ChinaCorrespondence: Wenyuan Wu, Department of Psychiatry, Tongji Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China, Email wuwy@tongji.edu.cnPurpose: To determine the relative safety and efficacy of different doses of tandospirone in treating generalized anxiety disorder (GAD).Patients and Methods: This parallel randomized controlled trial enrolled patients with GAD from eight centers in China. The patients were randomly assigned to 60 mg/day or 30 mg/day tandospirone groups. The primary endpoint was the overall response rate after receiving 6-week treatment. The secondary endpoints included significant response rate, clinical recovery rate, change in the Hamilton Anxiety Scale (HAMA) total score, HAMA subscale score, Hamilton Depression Scale-17 (HAMD-17), Clinical Global Impression-Severity Scale (CGI-S) score, and Impression-Improvement scale (CGI-I) score.Results: No significant difference was found in the overall response rate between the two groups (65.7% vs 58.4%, p = 0.213). A higher significant response rate and change in the HAMA total score were found in the 60 mg/day group. The reduction in the CGI-S score and percentage of patients with a CGI-I score of ≤ 2 were higher in 60 mg/day group. The reduction in HAMA somatic anxiety factor, cardiovascular symptom factor, gastrointestinal symptom factor, and HAMD-17 score were more significant in the 60 mg/day group. The incidence of total adverse events was higher in the 60 mg/day group than in the 30 mg/day group. No significant difference was found in the proportion of withdrawal due to adverse events.Conclusion: Both 60 mg/day and 30 mg/day tandospirone show good efficacy in treating patients with GAD. High doses of tandospirone may have advantages in relieving the somatic symptoms but also present disadvantages due to their high level.Trial Registration: The trial registration no. was NCT01614041.Keywords: generalized anxiety disorder, tandospirone, randomized controlled trial, safety, efficacy

Lu Yang,1 Shuangxin Zhang,1 Jiaqi Leng,2 Zhiguang Fan,2 Yi Luo1 1Department of Nursing, Changchun University of Chinese Medicine, Changchun City, Jilin Province, People’s Republic of China; 2Department of Education, Jilin International Studies University, Changchun City, Jilin Province, People’s Republic of ChinaCorrespondence: Zhiguang Fan, Department of Education, Jilin International Studies University, Jingyue Street 3658, Changchun City, Jilin Province, People’s Republic of China, Tel +86 1 594-831-4623, Fax +86 431-84924101, Email fanyqm@126.comIntroduction: Occupational stigma toward nurses exerts a negative impact on the physical and mental health and work performance of nurses. However, hitherto, there has been no quantitative instrument designed to assess occupational stigma toward nurses.Objective: The present study aimed to develop the Nurse Occupational Stigma Scale (NOSS) and test its reliability and validity in the Chinese context.Methods: The items of the scale were formed through the open-ended interview and literature review. A questionnaire survey was administered among 765 patients using NOSS and the Caring Behaviors Inventory (CBI-24).Results: In the initial questionnaire, a total of 21 items were developed, and 5 items were dropped for cross-loadings. The formal scale consists of 16 items divided into three dimensions of negative label, nurse-patient relationship, and devaluation and discrimination. The results of confirmatory factor analysis (CFA) indicated that the three-factor model fitted well (χ2/df=2.635, RMSEA=0.064, RFI=0.926, CFI=0.962, NFI=0.941, IFI=0.953). The total scores of the NOSS and the scores of all dimensions were significantly negatively correlated with the scores of the CBI-24. The internal consistency coefficients of the scale and all dimensions were between 0.827– 0.920, and the split-half reliability coefficients were between 0.826– 0.942. The NOSS had the measurement invariance across gender.Conclusion: With its good reliability and validity, the NOSS can be an appropriate instrument for researchers to conduct studies about nurse occupational stigma.Keywords: nurse, occupational stigma, reliability, validity

Yuetian Wang,1,&ast; Chun Liu,2,&ast; Huiling Liu,3 Haoyong Fu,1 Chunde Li,1 Lei Yang,3,4 Haolin Sun1 1Department of Orthopedics, Peking University First Hospital, Beijing, People’s Republic of China; 2Medical Research Centre, Changzhou Second People’s Hospital Affiliated to Nanjing Medical University, Jiangsu, People’s Republic of China; 3Institute of Orthopedics, Department of Orthopedics, Soochow University, Suzhou, People’s Republic of China; 4Center for Health Sciences and Engineering (CHSE), School of Health Sciences and Biomedical Engineering, Hebei University of Technology, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Yang; Haolin Sun, Tel +86 13681146156, Email ylei@hebut.edu.cn; sunhaolin@vip.163.comPurpose: To evaluate the effect of cement augmentation of cortical bone trajectory (CBT) screws using a novel calcium phosphate–based nanocomposite (CPN).Material and Methods: CBT screws were placed into cadaveric lumbar vertebrae. Depending on the material used for augmentation, they were divided into the following three groups: CPN, polymethylmethacrylate (PMMA), and control. Radiological imaging was used to evaluate the cement dispersion. Biomechanical tests were conducted to measure the stability of CBT screws. A rat cranial defect model was used to evaluate biodegradation and osseointegration of the CPN.Results: After cement augmentation, the CPN tended to disperse into the distal part of the screws, whereas PMMA remained limited to the proximal part of the screws (P < 0.05). As for cement morphology, the CPN tended to form a concentrated mass, whereas PMMA arranged itself as a scattered cement cloud, but the difference was not significant (P > 0.05). The axial pullout test showed that the average maximal pullout force (Fmax) of CPN-augmented CBT screws was similar to that of the PMMA group (CPN, 1639.56 ± 358.21 N vs PMMA, 1778.45 ± 399.83 N; P = 0.745) and was significantly greater than that of the control group (1019.01 ± 371.98 N; P < 0.05). The average torque value in the CPN group was higher than that in the control group (CPN, 1.51 ± 0.78 N∙m vs control, 0.97 ± 0.58 N∙m) and lower than that in the PMMA group (1.93 ± 0.81 N∙m), but there were no statistically significant differences (P > 0.05). The CPN could be biodegraded and gradually replaced by newly formed bone tissue after 12 weeks in a rat cranial defect model.Conclusion: The biocompatible CPN could be a valuable augmentation material to enhance CBT screw stability.Keywords: cement augmentation, CBT screws, osteoporotic spine, PMMA, CPN

Lu Yang,1,&ast; Li Sun,1 Yalan Cao,1 Qi Wang,1,2 Anni Song,1 Ru Zhu,1 Wenqi Liu,1 Shengjun Lu1,&ast; 1Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Histology and Embryology, School of Basic Medicine, Guizhou Medical University, Guiyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shengjun Lu; Wenqi Liu, Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China, Tel +86 15307159688 ; +86 13886014791, Fax +86-27-83692608, Email Lushengjun@hust.edu.cn; liu_wq2002cn@hotmail.comPurpose: In schistosomiasis-associated hepatic fibrosis, the role of murine UL16-binding protein-like transcript 1 (MULT1), the strongest ligand of natural killer group 2-member D receptor (NKG2D), remains unclear. Here, Schistosoma japonicum-infected mice administered with MULT1-encoding DNA were used to test MULT1 as a potential therapy for schistosomiasis-associated hepatic fibrosis and explore relevant mechanisms.Materials and Methods: A recombinant plasmid encoding MULT1 (p-rMULT1) was constructed and administered to Schistosoma japonicum-infected BALB/c mice via hydrodynamic tail vein injection. Egg granulomas in liver, hepatic fibrosis biomarkers and levels of cytokines were investigated. Comparisons of CD4+ T, CD8+ T, NK and NKT proportions as well as their phenotype were performed not only between Schistosoma infected, p-rMULT1 treated group and Schistosoma infected, backbone plasmid pEGFP-N1 treated group but also between infected, nontreated group and health control group.Results: Reduced area of granuloma formation and fibrosis around single eggs, downregulated expression of collagen I, α-smooth muscle actin, TGF-β and IL-10, and upregulated expression of IFN-γ, were observed in the livers of p-rMULT1 treated mice. p-rMULT1 treatment improved Schistosoma infection impacted immune microenvironment by modulating proportion of CD4+ T CD8+ T, natural killer (NK) and NKT cells, enhancing expression of NKG2D, in lymphocytes, and augmenting IFN-γ secretion by CD4+ T, CD8+ T, NK and NKT cells, as well as partially reversing some other phenotype changes of lymphocytes.Conclusion: To the best of our knowledge, we provided the first in vivo evidence that MULT1 is a favorable anti-fibrosis factor in the context of schistosomiasis. The inhibitory effect of MULT1 overexpression on schistosomiasis associated with hepatic fibrosis may result from augmenting the proportion and function of NKG2D-expressing immune cells, and from enhancing NK- and T-cell activation, as well as regulating the helper T (Th)1/Th2 balance.Keywords: schistosomiasis, NKG2D, liver fibrosis, IFN-γ, natural killer cells, T lymphocytes

Yun Yan,1,&ast; Lei Yang,2,&ast; Xiaoli Li,3,&ast; Jian Hao,4,&ast; Bijue Wang,4 Dan Wang,5 Junning Wang3 1Department of Orthopedics and Traumatology, Honghui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, 710054, People’s Republic of China; 2Department of Osteoporosis, Honghui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, 710054, People’s Republic of China; 3Department of Respiratory, Honghui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, 710054, People’s Republic of China; 4Xi’an Public Health Center, Xi’an, Shaanxi, 710200, People’s Republic of China; 5Department of Pathology, Honghui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, 710054, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junning Wang, Department of Respiratory, Honghui Hospital, Xi’an Jiaotong University, No. 555, Youyi East Road, Nanshaomen, Xi’an, Shaanxi, 710054, People’s Republic of China, Tel/Fax +86 02962818354, Email wangjunningde@163.comPurpose: At present, it has been found that managing patients with a redetected positive RNA test after recovery from foreign-imported coronavirus disease 2019 (COVID-19) cases in China is challenging. The purpose of the current study was to describe the clinical characteristics of these patients.Methods: This retrospective cohort study included 137 COVID-19 patients who were discharged from the Xi’an Public Health Center from 28 July 2020 to 31 December 2021. We compared the clinical characteristics between positive retest patients and non-positive retest patients.Results: 137 COVID-19 patients entered our study, 27 (19.7%) cases of COVID-19 with a redetected positive RNA test by the end of the follow-up period. Fever [(n = 31 (22.6%)], cough [n = 26 (18.9%)] and sore throat [n = 20 (14.5%)] were the most common initial symptoms among the foreign-imported COVID-19 patients, and there were almost no significant differences in initial symptoms between positive retest patients and non-positive retest patients. The positive retest patients had a higher lymphocyte count (p = 0.031) and lymphocyte percentage (p = 0.007) during readmission. There were generally no significant differences in other routine blood test findings, IgG and IgM antibody responses, between positive retest patients and non-positive retest patients, or in positive retest patients over time (before, during, or after positive patient detection). After readmission, positive retest patients displayed fewer symptoms or no obvious disease progression and more sustained remission by CT imaging.Conclusion: Our findings revealed that the clinical characteristics at the time of initial diagnosis were not closely related to redetected positive RNA tests after recovery from foreign-imported COVID-19 cases. Positive retest patients had virtually no symptoms and displayed no obvious disease progression during readmission. These findings provide important information and clinical evidence for the effective management of foreign-imported COVID-19 patients during their convalescent phase.Keywords: SARS-CoV-2, COVID-19, clinical characteristics, foreign-imported cases, redetected positive RNA test

Shuna Yang, Xuanting Li, Wei Qin, Lei Yang, Wenli Hu Department of Neurology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Wenli Hu, Email wenlihu3366@126.comBackground and Objective: Motor dysfunction is common in the elderly, and is associated with adverse consequences. Enlarged perivascular spaces in basal ganglia (BG-EPVSs) are considered an MRI marker of cerebral small-vessel diseases. However, the consequences of BG-EPVSs are largely unknown. In the present study, we aimed to explore the association between large numbers of BG-EPVSs and motor performance.Methods: We prospectively recruited elderly individuals in the Neurology Department of our hospital from December 1, 2020 to January 31, 2022. Participants with > 20 BG-EPVSs on the unilateral side of the slice containing the most EPVSs were classified as the BG-EPVS group (n=99) and the rest as controls (n=193). Motor performance was assessed by quantitative gait analysis, Tinetti test, timed up-and-go (TUG) test, and the Short Physical Performance Battery (SPPB). Spearman correlation analysis and multivariate linear regression analysis were performed to investigate the association between BG-EPVSs and motor performance.Results: Compared with the control group, the BG-EPVS group had lower gait speed and cadence, shorter stride length, longer TUG duration, and lower Tinetti gait test, Tinetti balance test, and SPPB scores (P< 0.01). Spearman correlation analysis showed that BG-EPVSs were negatively related to gait speed, gait cadence, stride length, and Tinetti gait test, Tinetti balance test, and SPPB scores (ρ= – 0.539 to – 0.223, P< 0.001) and positively related to TUG duration (ρ=0.397, P< 0.001). Regression analysis indicated that BG-EPVSs were an independent risk factor of lower gait speed, shorter stride length, poor balance, and poor general physical performance after adjusting for confounders (β= – 0.313 to – 0.206, P< 0.01).Conclusion: Large numbers of BG-EPVSs were independently related to poor gait, balance, and general physical performance in elderly individuals, which provides information about the consequences of BG-EPVSs and risk factors for motor dysfunction.Keywords: cerebral small-vessel diseases, enlarged perivascular spaces, motor, gait, balance, physical performance

Lili Yang,1,&ast; Siyi Yu,1,2,&ast; Leixiao Zhang,3 Wei Peng,1 Youping Hu,1 Fen Feng,4 Jie Yang1 1Department of Acupuncture & Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610075, People’s Republic of China; 2Acupuncture and Brain Science Research Center, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, People’s Republic of China; 3Department of Integrated Traditional and Western Medicine, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 4Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fen Feng, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shierqiao Road, Chengdu, Sichuan, 610072, People’s Republic of China, Email fengf01@126.com Jie Yang, Department of Acupuncture & Tuina, Chengdu University of Traditional Chinese Medicine, No. 37 Shierqiao Road, Chengdu, Sichuan, 610075, People’s Republic of China, Email jenny_yang_jie@126.comBackground: Gender differences in hippocampal and parahippocampal gyrus (HIP/PHG) volumes have been reported in sleep disorders. Therefore, this study investigated the moderating effect of gender on the relationship between chronic insomnia disorder (CID) and the HIP/PHG functional connectivity (FC) network.Methods: For this study, 110 patients diagnosed with CID (43 men and 67 women) and 60 matched good sleep control (GSC) (22 men and 38 women) were recruited. These participants underwent resting-state functional magnetic resonance imaging scans, after which a 2 × 2 (diagnosis × gender) analysis of variance was used to detect the main and interactive effect of insomnia and gender on their HIP/PHG FC networks.Results: Although the main effect of insomnia on the HIP FC network was observed in the bilateral cerebellar tonsil, superior frontal gyrus, and the medial orbitofrontal cortex, effects on the PHG FC network were observed in the bilateral HIP and amygdala. In contrast, the main effect of gender on the HIP FC network was observed in the right cerebellum posterior lobe, the dorsolateral prefrontal cortex (DLPFC), and the supplemental motor area. Of note, the interactive effect of both insomnia and gender was observed in FCs between the right HIP and the dorsal anterior cingulate cortex, and then between the right PHG and DLPFC. Moreover, the FC between the right PHG and left DLPFC was positively associated with anxiety scores in the female patients with CID.Conclusion: Our study identified that gender differences in brain connectivity existed between the HIP/PHG and executive control network in patients diagnosed with CID, these results will eventually extend our understanding of the important role that gender plays in the pathophysiology of CID.Keywords: insomnia, gender difference, functional connectivity, hippocampus, parahippocampal gyrus

Changqing Liu,1,2,&ast; Qi Sun,1,2,&ast; Junmei Xu,1,2 Weiyun Shen,1,2 Hui Li,1,2 Lin Yang1,2 1Department of Anesthesiology, Second Xiangya Hospital, Central South University, Changsha, Hunan Province, People’s Republic of China; 2Hunan Province Center for Clinical Anesthesia and Anesthesiology, Research Institute of Central South University, Changsha, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Li, Department of Anesthesiology, Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China, Fax +86 85295970, Email lihui_1166@csu.edu.cn Lin Yang, Department of Anesthesiology, Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China, Fax +86 85295970, Email linyang@csu.edu.cnBackground: Neuropathic pain (NP) is known to be highly correlated with microglial polarization, of which the regulatory mechanism remains to be elucidated. Here, the aim of this study is to further investigate the relationship between bone morphogenetic protein 4 (BMP4) and microglial polarization in the process of NP.Methods: Firstly, normal adult rats received intrathecal BMP4 administration to assess BMP4ʹs effect on microglial polarization. Secondly, a BMP4 antagonist – Noggin – was applied to a rat NP model achieved by L5 spinal nerve ligation (SNL) to investigate whether antagonizing BMP4 signaling could alleviate allodynia by reversing the imbalance of the M1/M2 polarization ratio. In both experiments, Von-Frey filaments were used to test the changes in the paw withdrawal threshold (PWT), and Western blotting, immuno-fluorescence, PCR and flow cytometry were further performed to investigate microglial activity and the expression patterns of M1 and M2 markers, respectively.Results: Firstly, BMP4 administration induced a significant PWT decrease and microglial activation in normal rats; Western blotting, PCR and flow cytometry further revealed that M1 markers including CD16, MHCII, and TNF-α showed a marked elevation after BMP4 application; while M2 markers, such as Arg-1, CD204 and IL-4, peaked at an early stage (P1 or P4) and then fell to the Sham level on P7, leading to a persistent imbalance of the M1/M2 ratio throughout the 1st week. Secondly, Noggin treatment significantly relieved allodynia and microglial activation in SNL rats. Moreover, Noggin persistently downregulated the M1 marker levels and simultaneously induced a late-stage elevation of M2 markers expressions, thereby reversing the imbalance of the M1/M2 polarization ratio.Conclusion: Our results indicate that BMP4 has the ability to induce microglial polarization. Antagonizing BMP4 signaling can relieve pain behavior via mitigating microglial activation and reversing the imbalance of the M1/M2 polarization ratio in the process of NP.Keywords: bone morphogenetic protein-4, Noggin, microglia, polarization, neuropathic pain

Hao Chen,&ast; Qing Jiang,&ast; Yaqi Yang, Wei Zhang, Lin Yang, Rongfei Zhu Department of Allergy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rongfei Zhu, Department of Allergy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China, Tel/Fax +86-27-8366 2912, Email zrf13092@163.comBackground: Cross-reacting carbohydrate determinants (CCD) exist in some pollen and food allergens, but they do not contribute to allergic symptoms. However, CCD can induce specific IgE (sIgE) production and may lead to incorrect allergen diagnosis and treatment. CCD inhibitor is a specific antibody adsorbent which can preclude CCD from binding to sIgE. Currently, the data of CCD inhibition in allergen sIgE test are limited.Methods: The allergic patients with positive skin prick reactions to two or more pollen and/or food allergen extracts were included in our study. Their sera were obtained and sIgE was tested with an allergen panel that included 29 single and mixed allergens (MEDIWISS Analytic GmbH, China) before and after CCD inhibition. The changes of sIgE against these allergens and the correlations of sIgEs to clinical symptoms were analyzed.Results: A total of 44 patients were included and 36 (81.82%) of those were multi-sensitized to house dust mites and pollen allergens based on skin prick tests. The sIgE levels and positive rates against most pollen and food allergens were significantly lower after CCD inhibition. The sIgE levels of pollen were positively correlated to those of food allergens before CCD inhibition. However, these correlations were weakened or no longer existed after CCD inhibition. The sIgE against pollen and food allergens showed significantly higher consistency with clinical symptoms after CCD inhibition.Conclusion: Cross-sensitization caused by CCD is widespread in pollen and food. CCD inhibition test can improve the diagnostic accuracy of pollen and food allergy.Keywords: cross-reacting carbohydrate determinants, inhibition test, pollen, food, IgE

Ye Tian,1,2 Heng Zhang,1,2 Ying Cao,2 Lu Yang,3 Guangheng Luo1 1Department of Urology, Guizhou Provincial People’s Hospital, Guiyang, People’s Republic of China; 2Guizhou University School of Medicine, Guiyang, People’s Republic of China; 3Department of Urology, West China Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Guangheng Luo, Tel +86-173-8501-5539, Fax +86-851-8562 1836, Email luoguangheng1975@163.comPurpose: Transurethral resection of the prostate (TURP) is often indicated for benign prostatic hyperplasia (BPH). Some patients, however, fail to adequately respond to these interventions. Accordingly, a powerful prediction model for TURP efficacy is warranted. This study aimed to create a nomogram with preoperative parameters for the prediction of individual TURP efficacy.Methods: Clinical data from 356 BPH subjects who underwent TURP were retrospectively collected between November 2015 and June 2021 for nomogram development. The prediction model was developed using multivariable logistic regression analysis and presented as a nomogram. Nomogram performance was assessed through calibration curves and the concordance index (C-index). An independent validation cohort containing 177 consecutive patients in the corresponding period was used for external validation. The optimal cutoff value was determined through receiver operating characteristic curve (ROC) analysis by maximizing the Youden index, and its accuracy was assessed through sensitivity, specificity and predictive values.Results: In multivariate analysis of the primary cohort, the independent factors for TURP efficacy were age, International Prostate Symptom Score (IPSS), intravesical prostatic protrusion (IPP), bladder wall thickness (BWT), peripheral zone thickness (PT) and transitional zone thickness (TT), all of which were included in the nomogram. The calibration curve for survival probability showed good agreement between the nomogram predictions and actual observations. The C-index for predicting TURP efficacy was 0.860 (95% confidence interval [CI], 0.808– 0.911). The optimal cutoff total nomogram score was 177, with a maximum Youden index of 0.643. The sensitivity, specificity, positive predictive value, and negative predictive value for predicting TURP efficacy were 70.6%, 75.6%, 90.6%, and 43.7% in the validation cohort, respectively. Logistic regression analysis in the validation cohort demonstrated that the area under the curve (AUC) was 0.806 (95% CI, 0.733– 0.879).Conclusion: The P.R.OS.T.A.T.E nomogram objectively and accurately predicted TURP efficacy, thereby facilitating the clinical decision-making process.Keywords: nomogram, benign prostatic hyperplasia, lower urinary tract symptoms, transurethral resection of prostate, efficacy

Wangxia Tong,1 Lilan Yang,1 Li Liu,1 Xudong Liu,1 Ning Luo2 1The Medical Department of Hepatology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, 530011, People’s Republic of China; 2RuiKang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, 530011, People’s Republic of ChinaCorrespondence: Ning Luo, RuiKang Hospital Affiliated to Guangxi University of Chinese Medicine, 10 Huadong Road, Nanning, People’s Republic of China, 530011, Tel +86 0771-2183191, Fax +86 0771-4733943, Email ln760320@163.comPurpose: As a novel genetic biomarker, little information is available about the possible role of SPINDOC in different malignant tumors and in hepatocellular carcinoma (HCC).Methods: Based on The Cancer Genome Atlas (TCGA) database, the expression level of SPINDOC in pan-cancer and hepatocellular carcinoma samples was first determined using bioinformatics analysis. The potential relationship between the expression level as well as the clinical characteristics and the molecular mechanisms through which SPINDOC can promote the proliferation, invasion and migration of HCC cells was evaluated. In addition, cell-based studies and in vivo experiments were used to verify the bioinformatics analysis results.Results: Bioinformatics analysis showed that SPINDOC expression was significantly increased in 18 human malignancies and the gene expression level was positively correlated with poor clinical prognosis in kidney renal papillary cell carcinoma (KIRP), pheochromocytoma and paraganglioma (PCPG) and liver hepatocellular carcinoma (LIHC). The main type of genetic variation of SPINDOC was amplification, and the increase of SPINDOC mRNA expression level was directly related to the amplification of this gene. The expression level of SPINDOC in patients with primary HCC was positively correlated with poor clinical prognosis, as well as the clinical grade and stage of carcinoma. Gene set enrichment analysis (GSEA) analysis showed that high expression of SPINDOC could activate Wnt/β-catenin signaling pathway. Moreover, in vitro and in vivo experiments showed that SPINDOC gene silencing significantly inhibited the proliferation, migration and invasion of Huh7 and SK-HEP-1 cells and decreased the expression of SPIN1, Wnt1, β-catenin and cyclin D1 but increased the expression of AXIN2.Conclusion: SPINDOC is highly expressed in pan-cancer and HCC samples. This factor can effectively promote the invasion and migration of hepatocellular carcinoma (HCC) cells by activating Wnt/β-catenin signaling pathway, and thus can serve as a potential therapeutic target for HCC management.Keywords: SPINDOC, SPIN1, Wnt/ß-catenin, pan-cancer, hepatocellular carcinoma

Lijuan Yang, Huihui Deng, Wei Pan, Xiaoyan Huang, Ke Xu, Xingxing Zhang, Xiang Hu, Xuejiang Gu Department of Endocrine and Metabolic Diseases, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of ChinaCorrespondence: Xiang Hu; Xuejiang Gu, Department of Endocrine and Metabolic Diseases, the First Affiliated Hospital of Wenzhou Medical University, Ouhai District, Wenzhou, 325000, People’s Republic of China, Tel/Fax +86-577-55579381, Email huxiang@wmu.edu.cn; guxuejiang@wmu.edu.cnPurpose: Recent studies revealed that high levels of thigh fat were independently associated with better glucose and lipid metabolism, as well as lower risk of hypertension and cardiometabolic disease. Therefore, the purpose of this study was to evaluate the association between leg fat mass (FM) and osteoporosis (OP) in individuals with type 2 diabetes (T2DM).Patients and Methods: In this cross-sectional study, a total of 1,259 individuals aged 50 years or older with T2DM (female 536, male 723) were included. A bioelectrical impedance analyser was used to assess the segment body composition containing FM and lean mass (LM) of arms, legs, and trunk. Bone mineral density (BMD) was determined by dual-energy X-ray absorptiometry.Results: Leg FM was positively correlated with BMD of all sites in females and BMD of femoral neck and total hip in males after adjusting age, diabetes duration, glucose and lipid metabolism indexes, and lifestyle (all P< 0.05). LM was positively associated with BMD at almost sites (P< 0.001), while leg FM/LM ratio had no relationship with BMD at any skeleton sites (P> 0.05). Compared with the bottom tertile group of leg FM, the risk of OP was significantly lower in the top tertile group both in females (T3 vs T1: OR=0.206, 95% CI=0.098– 0.433, P< 0.001) and males (T3 vs T1: OR=0.385, 95% CI=0.182– 0.815, P< 0.05), even after adjusting for LM.Conclusion: In the present study, higher leg FM was correlated with the lower risk of OP in both men and postmenopausal women with T2DM independently of total LM.Keywords: leg fat mass, bone mineral density, osteoporosis, type 2 diabetes mellitus

Xiangzhen Nan, Yean Zhang, Nana Su, Lei Yang, Guoquan Pan Department of Pediatric Intensive Care Unit, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Guoquan Pan, Department of Pediatric Intensive Care Unit, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China, Email gq_pan@163.comPurpose: This study aimed to analyze the application value of metagenomic next-generation sequencing (mNGS) as a basis for the proper adjustment of the clinical treatment of bloodstream infections (BSIs) in pediatric patients under intensive care.Methods: We retrospectively enrolled 46 pediatric patients with clinically diagnosed BSIs who were hospitalized in the pediatric intensive care unit of the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University from June 2018 to July 2021. Blood samples were collected for cultivation and for mNGS detection of pathogens.Results: Among the 46 children, the average turnaround time for blood culture tests was 3.2 days, and the results revealed pathogens in three children (6.5%). The average turnaround time for mNGS was 2.2 days, and pathogens were found in 30 children (65.2%). The difference in positivity rates between blood culture and mNGS was significant (p< 0.05). Blood culture tests found three pathogens, while mNGS identified 28 pathogens, indicating that mNGS detected significantly more types of pathogens than the traditional diagnostic method for pathogenic microorganisms. In some children, more than one pathogen was detected.Conclusion: mNGS can help identify pathogenic microorganisms associated with BSI in some pediatric patients under intensive care.Keywords: pediatric intensive care unit, bloodstream infection, next-generation sequencing, metagenomics

Yehua Wang,1,&ast; Chuyao Deng,1,&ast; Lili Yang2 1Department of International Healthcare Center, Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 2Nursing Education Department, Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lili Yang, Nursing Education Department, Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine, No.3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, People’s Republic of China, Tel +86-139-581-31637, Email 3200006@zju.edu.cnBackground: Due to globalization, an increasing number of international visitors comes to China. The needs of their medical care are understudied, which can cause low patient satisfaction and lead to poor clinical outcomes for the clients. To meet those international clients’ medical care needs, hospitals in China are seeking strategies to improve services.Purpose: The aim of this study was to explore international clients’ medical care experiences in China, and their perceptions of the quality of these international healthcare services.Patients and Methods: In May 2020, focus group interviews with 24 clients and four healthcare professionals were conducted in the international clinic at Sir Run Run Shaw Hospital (SRRSH). In the client group, 24 representatives of international clients from nine countries were invited and divided into three groups to discuss healthcare needs of international clients who seek healthcare in China. Four healthcare providers, including two nurses and two physicians who usually serve in the international clinic, were also interviewed. Data were analyzed using hybrid inductive/deductive thematic analysis.Results: Six major healthcare needs of international clients were identified, namely: needs for privacy and confidentiality; effective communication; multicultural sensitive care; pleasant environments; qualified care and procedures; and respect. International healthcare is a complex process for both international clients and healthcare professionals.Conclusion: The government and institutional administrators around the world should construct the policies and protocols and integrate cultural competence, communication skills, and privacy and confidentiality protection into health professionals training program to ensure the quality services in the international clinics.Keywords: assessment of healthcare needs, international aspects, qualitative research, focus groups

Xiaowei Sun,1 Fenqin Xue,2 Jialin Wen,1 Limin Gao,1 Yang Li,1 Lijun Yang,1 Hong Cui1 1Department of Pediatrics, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Core Facility Center, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Lijun Yang; Hong Cui, Beijing Friendship Hospital, Capital Medical University, No. 95 Yongan Road, Xicheng District, Beijing, 100050 People’s Republic of China, Email yanglijun1979@ccmu.edu.cn; cuihong100@ccmu.edu.cnObjective: Sleep is necessary for brain maturation in infants. Perinatal hypoxic-ischemic encephalopathy (HIE) is a major cause of chronic neurological disease in infants. Although the developmental changes of electroencephalogram (EEG) in human newborns have been described, little is known about the EEG normal maturation characteristics in rodents and the changes in sleep-awake states caused by hypoxia-ischemia (HI). This study aimed to investigate the pathological response of sleep-wake states in neonatal rats with HIE.Methods: We constructed HIE and sham models on postnatal day (P) 3 rats and continuously monitored them using electroencephalography and electromyography for up to P12. The distribution of sleep-wake states was analyzed to estimate the effects of HIE.Results: Compared with the sham group, the HI group showed lower rapid eye movement (REM) sleep percentage, but wake percentage and frequency was higher during P4-P12. The frequency of REM and non-rapid eye movement (NREM) sleep increased and the duration of REM and NREM sleep decreased after HI induction. However, it gradually returned to the normal level with an increase in daytime.Conclusion: HI damage alters the sleep-wake patterns during early neural development. The findings provide a comprehensive assessment of serial sleep-wake state recordings in neonatal rats from P4-P12.Keywords: electroencephalography, EEG, hypoxia-ischemia, rapid eye movement, premature

Jun Wang,1– 3 Linlin Yang,4 Linquan Yang,4 Fei Zhou,1 Hang Zhao,2 Jing Liu,2 Huijuan Ma,1,2,4,&ast; Guangyao Song1,2,&ast; 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Endocrinology and Metabolic Diseases, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of China; 3Department of Emergency, Baoding First Central Hospital, Baoding, Hebei, People’s Republic of China; 4Hebei Key Laboratory of Metabolic Diseases, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huijuan Ma, Hebei Key Laboratory of Metabolic Diseases, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, 050051, Hebei, People’s Republic of China, Email huijuanma76@163.com Guangyao Song, Department of Endocrinology and Metabolic Diseases, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, 050051, Hebei, People’s Republic of China, Email sguangyao2@163.comPurpose: To investigate changes in the protein expression profile of white adipose tissue in low-birth weight (LBW) mice with high-fat diets using tandem mass tag (TMT) and liquid chromatography-mass spectrometry (LC-MS/MS) and parallel reaction monitoring (PRM).Methods: Institute of Cancer Research (ICR) mice were used to establish an LBW model using malnutrition during pregnancy. Male pups were randomly selected from LBW and normal-birth weight (NBW) offspring, then all given a high-fat diet. Blood glucose, serum insulin, total cholesterol (TC) and triglyceride (TG) levels were measured. The weight ratio of liver, muscle, and adiposity index were calculated. Hematoxylin and eosin staining was used to visualize adipose tissue morphology. Oil red O staining of liver and TG content of muscle were used to determine ectopic lipid deposition. TMT combined with LC-MS/MS was used to analyze protein expression in white adipose tissue. PRM and Western blot were used to verify the expression of CD36, SCD1, PCK1 and PPARγ.Results: Compared with NBW mice, fasting blood glucose, insulin and HOMA-IR significantly increased in LBW mice, indicating insulin resistance and impaired glucose regulation; TC, TG, adipocyte size, and adiposity index were increased in LBW mice, suggesting obesity and disorder of lipid metabolism. We observed ectopic lipid deposition in liver and muscle. There were 996 differentially expressed proteins (DEPs) in the LBW/NBW groups. Peroxisome proliferator-activated receptor (PPAR) was a relatively important signaling pathway regulating metabolic process in functional enrichment analysis of DEPs. Up-regulated expression of CD36, SCD1, and PCK1 in the adipose tissue of LBW mice was observed through PPAR pathways cluster analysis. And PRM and Western blot assay validated the proteomics findings.Conclusion: When exposed to high-fat diets, LBW mice exhibited insulin resistance and disorder of lipid metabolism compared with NBW mice. The expression of PPARγ was elevated, as well as upstream CD36, downstream SCD1 and PCK1 of the PPARγ in the adipose tissue of LBW mice. It was suggested that the activation in CD36/PPARγ/SCD1 and CD36/PPARγ/PCK1 pathways may induce adipose dysfunction, thereby increasing susceptibility to insulin resistance.Keywords: low birth weight, adipose tissue, insulin resistance, lipid metabolism

Yanwu Nie,1,&ast; Chenchen Wang,2,&ast; Lei Yang,3 Zhen Yang,4 Yahong Sun,4 Maozai Tian,5,6 Yuhua Ma,7,8 Yuxia Zhang,9 Yimu Yuan,10 Liping Zhang6 1State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, School of Public Health, Xinjiang Medical University, Urumqi, 830017, People’s Republic of China; 2Center for Disease Control and prevention of Xinjiang Uygur Autonomous Region, Urumqi, 830017, People’s Republic of China; 3School of Nursing, Xinjiang Medical University, Urumqi, 830017, People’s Republic of China; 4School of Public Health, Xinjiang Medical University, Urumqi, 830017, People’s Republic of China; 5Center for Applied Statistics, School of Statistics, Renmin University of China, Beijing, 100872, People’s Republic of China; 6College of Medical Engineering and Technology, Xinjiang Medical University, Urumqi, 830017, People’s Republic of China; 7Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, People’s Republic of China; 8Department of Pathology, Karamay Central Hospital of XinJiang Karamay, Karamay, Xinjiang Uygur Autonomous Region, 834000, People’s Republic of China; 9Department of Clinical Nutrition, Urumqi Maternal and Child Health Institute, Urumqi, 830001, People’s Republic of China; 10Department of General Practice Medicine, Xinjiang Corps Hospital, Urumqi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liping Zhang, Email zhanglp1219@163.comPurpose: The role of inorganic arsenic (iAs) in the risk of metabolic syndrome (MetS) remains unclear. This investigation focused on the effect of iAs exposure on MetS and whether the results are consistent in different subgroups.Patients and Methods: The present study was conducted on 629 men and 616 women aged 35– 70 years and living in Xinjiang Uygur Autonomous Region, China. The 1:1 propensity score matching (PSM) was adopted to regulate the confounding factors, and the multivariate logistic regression was performed to assess the relationship between urinary iAs and MetS.Results: The median content of urinary iAs was examined as 2.20 μg/dL (interquartile range: 1.30– 3.20 μg/dL), and the MetS prevalence reached 23.69% (295 cases/950 participants). After the confounding factors were adjusted, the ORs (95% CIs) for MetS from the minimal to the maximum urinary iAs quartiles reached 1.171 (0.736,1.863), 1.568 (1.008, 2.440) and 2.011 (1.296, 3.120), respectively (referencing 1.00) (P for trend=0.001). After the PSM, the urinary iAs content still plays a potential prediction role in MetS (P for trend=0.011). In addition, as revealed from the subgroup analysis, the urinary iAs content was a predictor of MetS in the female patients, whereas it did not serve as a significant predictor of MetS in the male patients (P for interaction< 0.05).Conclusion: The increased urinary iAs content was associated with the increased prevalence of MetS in Chinese population. More attention should be paid to female urinary iAs content to avoid the high prevalence of MetS.Keywords: metabolic syndrome, urinary inorganic arsenic, propensity score matching, subgroup analysis

Luting Yang, Yaping Yan Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi’an, People’s Republic of ChinaCorrespondence: Luting Yang; Yaping Yan, Email yangluting@snnu.edu.cn; yaping.yan@snnu.edu.cnAbstract: Post-translational modifications (PTMs) of proteins represent as a key step in regulating their biological functions and dynamic interaction with other players. This process is fine-tuned by a myriad of enzymes named “writers, readers and erasers” whose actions are precisely controlled. Either the mutation, aberration in the expression of the aforementioned enzymes or their substrates have shown to participate in the pathogenesis of various skin diseases such as melanoma, vitiligo, psoriasis, eczema, atopic dermatitis and inherited dermatological diseases. It is becoming increasingly clear that key transcriptional factors, inflammation-related molecules are prone to PTMs. Despite their importance in regulating key processes including inflammation, keratinocyte apoptosis, proliferation and differentiation, PTMs have received less attention due to the challenges involved. Here in this review we summarize the role of the most common types and the newly discovered PTMs, including acetylation, glycosylation, citrullination, PARylation and sumoylation in dermatoses and surveys the recent progress in PTM-based therapeutic approaches in skin diseases.Keywords: post-translational modification, skin diseases, molecular mechanism, therapeutics

Xiaowu Ma,1,2,&ast; Hongkai Zhuang,1,2,&ast; Qingbin Wang,1,2 Lei Yang,1,2 Zhiqin Xie,1,2 Ziyu Zhang,1,2 Wenliang Tan,1,2 Chenwei Tang,1,2 Yajin Chen,1,2 Changzhen Shang1,2 1Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yajin Chen; Changzhen Shang, Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China, Tel +86-2034070701, Email cyj0509@126.com; shangcz_sysu@163.comBackground: Solute carrier family 39 member 1 (SLC39A1) has been identified as a zinc ion transport protein that possesses oncogenic properties in various types of cancers. However, its potential function in hepatocellular carcinoma (HCC) remains unknown. This study aimed to investigate the expression profile and potential mechanisms of SLC39A1 in HCC.Methods: SLC39A1 expression was analyzed using multiple databases. The clinical significance and associated biological pathways of SLC39A1 were investigated using bioinformatics analysis. Potential correlations between SLC39A1 expression and tumor immunity in HCC were also evaluated using single-sample gene set enrichment analysis (GSEA). Sixty paired HCC samples were used to verify the expression pattern of SLC39A1. In vitro studies were performed to investigate the oncogenic effects of SLC39A1 in HCC. Western blot analysis was conducted to further investigate the possible involved signaling pathways.Results: The overexpression of SLC39A1 in HCC was determined by bioinformatics analysis and was confirmed in tissues from our center. SLC39A1 overexpression was also significantly correlated with worse prognosis, advanced TNM stage, and histological grade. GSEA analysis demonstrated that SLC39A1 overexpression was involved in various tumor-related pathways, such as the cell cycle and Wnt signaling pathway. SLC39A1 knockdown repressed the proliferation, invasion, and migration abilities of HCC cells. Furthermore, SLC39A1 knockdown decreased the expression of the tumor progression-related proteins (eg, cyclin D1 and MMP2) and Wnt signaling pathway-related proteins (eg, Wnt3A and β-catenin). In addition, SLC39A1 overexpression may be associated with impaired tumor immunity in HCC, as evidenced by the increased infiltration of Th2 cells and reduced infiltration of cytotoxic cells.Conclusion: These findings preliminarily suggested the crucial effect of SLC39A1 overexpression on HCC tumor progression and immunosuppression, suggesting its potential as a novel prognostic and therapeutic target in HCC.Keywords: SLC39A1, hepatocellular carcinoma, prognosis, Wnt signaling pathway, immune infiltration

Chi Zhou,1,&ast; Fang Tan,1,&ast; Sihong Lai,1 Jingchun Chen,1 Qi Cai,1 Xiaoyu Yin,1 Shuli Guo,1 Shuang Wu,2 Lei Yang1 1School of Public Health, Hangzhou Normal University, Hangzhou, 311121, People’s Republic of China; 2The Second Affiliated Hospital of Zunyi Medical University, Zunyi, 563100, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Yang, School of Public Health, Hangzhou Normal University, No. 2318, Yuhangtang Road, Cangqian, Yuhang District, Hangzhou, 311121, People’s Republic of China, Tel/Fax +86-0571-28865510, Email yanglei62@hznu.edu.cnBackground: This study evaluated the current health promotion capacity level of Chinese healthcare professionals and explored the association between health promotion capacity and preventive health service practices.Methods: A total of 124 doctors and 72 nurses were recruited from 6 county hospitals and 12 community health centers from June to August 2019 in Zhejiang Province, China. Health promotion capacity was measured using the revised Chinese version of the Health Promotion Professionals Core Competency Scale.Results: The mean total score on the health promotion capacity scale was 45.04 (SD = 7.30). Total health promotion capacity score was negatively associated with county hospitals (β = − 0.32, p < 0.001; Ref: community health center) and positively associated with a monthly income of more than 5001 RMB ($786.39) (β = 0.25, p = 0.004; Ref: less than 5000 RMB ($786.24)). All domain scores of the health promotion capacity scale were positively related to preventive health service practices.Conclusion: Health promotion capacity is one of the most important capacities among healthcare professionals, and there is a particular need to improve nurses’ capacity. A higher level of health promotion capacity is beneficial for implementing preventive health services.Keywords: healthcare professionals, health promotion, primary care, capacity

As a refractory industrial solid waste, high-alumina fly ash is discharged into nature in large quantities, causing serious environmental harm. The extraction of valuable components, such as aluminum, from high-alumina fly ash has become a research hotspot at home and abroad. The shortcomings of traditional alumina extraction from high-alumina fly ash include long technological processes, large amounts of waste acid and alkali, and serious equipment corrosion. A novel method for alumina preparation by electrotransformation AlCl3 solution(EAS) under NH4Cl catalysis with injected CO2 has been proposed by Northeastern University. The process has advantages, such as short flow and no waste acid discharge. In this study, the influence of initial NH4Cl concentration in the cathodic chamber on solution pH, phase and morphology of electrotransformation products, phase, D(50) and D(90) of roasting products, and Al recovery rate were examined. Simultaneously, EAS was examined and compared with and without injected CO2, as well as EAS under NH4Cl catalysis with and without injected CO2. The results showed that, when the solution in the cathodic chamber was NH4Cl with CO2 injection, with electrotransformation time extension, pH increased slowly and the morphology of electrotransformation products were all rough and fluffy block structures. Increasing initial NH4Cl concentration effectively improved the product crystallization states, roasting products D(50) and D(90), and Al recovery rate.

Yuan-Yuan Liu,1,2 Ren-Feng Zhao,2 Chao Liu,2 Jie Zhou,2 Liu Yang,2 Li Li1 1Department of Gynecologic Oncology, Guangxi Medical University Cancer Hospital, Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Ministry of Education, Nanning, Guangxi, People’s Republic of China; 2The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, People’s Republic of ChinaCorrespondence: Yuan-Yuan Liu; Li Li Tel +86-13877152206; +86-13878113406Email 43322045@qq.com; yuanyuan_liu2021@163.comObjective: Nomograms are statistics-based predictive tools that integrate predictive factors. Herein, a nomogram was developed and validated to predict the overall survival (OS) in serous ovarian cancer (SOC).Methods: Primary SOC patients with satisfactory cytoreductive surgery, chemotherapy, and OS ≥ 1 month were included in this study. A total of 6957 patients from the Surveillance, Epidemiology, and End Results (SEER) database comprised the training group and 1244 patients comprised the external validation group. The nomogram was structured on Cox models and evaluated in both the training and validation groups using consistency index, area under the receiver operating characteristics curve, calibration plots, and risk subgroup classification. Kaplan–Meier curves were plotted to compare the survival outcomes between subgroups. A decision-curve analysis was used to test the clinical value of the nomogram.Results: Independent factors, including age, tumor grade, and Federation of Gynecology and Obstetrics (FIGO) stage, identified by multivariate analysis in the training cohort, were selected for the nomogram. The consistency indexes for OS were 0.689 in the training cohort and 0.639 in the validation cohort. The calibration curves showed good consistency between predicted and actual 3- and 5-year OS. Significant differences were observed in the survival curves of different risk subgroups. The decision-curve analysis indicated that our nomogram was superior to the American Joint Committee on Cancer (AJCC) staging system.Conclusion: A nomogram was constructed to predict the long-term OS in SOC and verified in Asians. The accurate predictions facilitated personalized treatments and follow-up strategies.Keywords: nomograms, serous ovarian cancer, overall survival, SEER, external verification

Lei Yang,1,&ast; Dingxiu He,2,&ast; Dong Huang,1,&ast; Zhongwei Zhang,3 Zongan Liang1 1Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Emergency Medicine, The People’s Hospital of Deyang, Deyang, Sichuan, People’s Republic of China; 3Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zongan Liang Tel +8618980601259Email liangza@scu.edu.cnPurpose: Risk factors and prognostic model of fatal outcomes need to be investigated for the increasing number of immunocompromised hosts (ICHs) who are hospitalized for severe pneumonia with high hospital mortality.Patients and Methods: In this single-center, retrospective study, we recruited 1,933 ICHs with severe pneumonia who were admitted to the intensive care unit (ICU) in West China hospital, Sichuan university, China between January, 2012 and December, 2018. Clinical features, laboratory findings, and fatal outcomes were collected from electronic medical records. Patients were randomly separated into a 70% training set (n=1,353) and a 30% testing set (n=580) for the development and validation of a prediction model. All data within 24 hours of ICU admission were compared between survivors and non-survivors. The risk factors were identified through LASSO and multivariate logistic regression analysis, and then used to develop a predicting nomogram. The nomogram for predicting hospital mortality of ICHs with severe pneumonia in the ICU was validated by C-index, AUC (area under the curve), calibration curve, and Decision Curve Analysis (DCA).Results: Eight risk factors, including age, fever, dyspnea, chronic renal disease, platelet counts, neutrophil counts, PaO2/FiO2 ratio, and the requirement for vasopressors, were adopted in a nomogram for predicting hospital mortality. The nomogram had great predicting accuracy with a C-index of 0.819 (95% CI=0.795– 0.842) in the training set, and a C-index of 0.819 (95% CI=0.783– 0.855) in the testing set for hospital mortality. Additionally, the nomogram had well-fitted calibration curves. DCA demonstrated that the nomogram was clinically beneficial.Conclusion: This study developed a novel nomogram for predicting hospital mortality of ICHs with severe pneumonia in the ICU. Validation showed good discriminatory ability and calibration, indicating that the nomogram was expected to be a superior predictive tool for doctors to identify risk factors and predict mortality, and might be generally applied in clinical practice after more external validations.Keywords: immunocompromised, severe pneumonia, ICU, risk factors, nomogram

Longbing Yang,1 Zhuqing Tian,1 Luoxiong Zhou,1,2 Lijuan Zhu,1 Chaoqin Sun,1 Mingjiao Huang,1 Jian Peng,1,3 Guo Guo1,3,4 1School of Basic Medical Sciences, The Key and Characteristic Laboratory of Modern Pathogen Biology, Guizhou Medical University, Guiyang, 550025, People’s Republic of China; 2School of Public Health, Guizhou Medical University, Guiyang, 550025, People’s Republic of China; 3Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, 550025, People’s Republic of China; 4Translational Medicine Research Center, Guizhou Medical University, Guiyang, 550025, People’s Republic of ChinaCorrespondence: Guo GuoBuilding Wuben, School of Basic Medical Sciences, Guizhou Medical University, College Town, Gui’an New District, Guiyang, 550025, People’s Republic of China, Tel/fax +86 851 882 59268, Email guoguojsc@163.comBackground: Cryptococcus neoformans is a common human fungal pathogen in immunocompromised people, as well as a prevalent cause of meningitis in HIV-infected individuals. With the emergence of clinical fungal resistance and the shortage of antifungal drugs, it is urgent to discover novel antifungal agents. AMP-17, a novel antimicrobial peptide from Musca domestica, has antifungal activity against C. neoformans. However, its antifungal and anti-biofilm activities remain unclear. Thus, this study aimed to evaluate the antifungal activity of AMP-17 against planktonic cells and biofilms of C. neoformans.Methods: The minimum inhibitory concentration (MIC), the biofilm inhibitory and eradicating concentration (BIC and BEC) were determined by the broth microdilution assay or the 2, 3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction assay, respectively. The inhibitory and killing activities of AMP-17 against C. neoformans were investigated through the time-inhibition/killing kinetic curves. The potential antifungal mechanism of AMP-17 was detected by flow cytometry, scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). The efficiency of AMP-17 against biofilm formation or preformed biofilm was evaluated by crystal violet staining and XTT reduction assays. The morphology of pre-biofilms was tested by optical microscopy (OM) and CLSM.Results: AMP-17 exhibited in vitro antifungal activity against C. neoformans planktonic cells and biofilms, with MICs of 4∼ 16 μg/ml, BIC80 and BEC80 of 16∼ 32 μg/ml, 64∼ 128 μg/ml, respectively. In addition, the 2× and 4× MIC of AMP-17 exhibited similar inhibition levels compared to the 2× and 4× MIC of the clinical drugs FLC and AMB in C. neoformans growth. Moreover, the time-kill results showed that AMP-17 (8× MIC) did not significantly eliminate colony forming units (CFU) after 6 h of treatment; however, there was 2.9-log reduction in CFU of C. neoformans. Furthermore, increasing of the permeability of the fungal cell membrane was observed with the treatment of AMP-17, since the vast change as fungal leakage and cell membrane disruption. However, the DNA binding assay of AMP-17 indicated that the peptide did not target DNA. Besides, AMP-17 was superior in inhibiting and eradicating biofilms of C. neoformans compared with FLC.Conclusion: AMP-17 exhibited potential in vitro antifungal activity against the planktonic cells and biofilms of C. neoformans, and it may disrupt fungal cell membranes through multi-target interactions, which provides a promising therapeutic strategy and experimental basis for Cryptococcus-associated infections.Keywords: antimicrobial peptides, AMP-17, Cryptococcus neoformans, antifungal mechanism, anti-biofilm

No thermodynamic description was performed for the Co-Mg binary system according to literature review. Consequently, this binary system has been investigated by means of CALPHAD (CALculation of PHAse Diagrams) approach in the present work. The experimental phase diagram and thermodynamic data available in the literature were critically assessed. Based on the reliable literature data, a new set of self-consistent thermodynamic parameters for the Co-Mg system is obtained. The calculated results agree well with the experimental data from the literature, indicating the reasonability of the present thermodynamic optimization.

Linlin Yang,1,2 Xin Chen,3 Zhiqi Liu,3 Wei Sun,3 Dexin Yu,3 Haiqin Tang,1,2,&ast; Zhiqiang Zhang3,&ast; 1Department of Geriatrics Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Department of General Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 3Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haiqin TangDepartment of Geriatrics Cardiology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, Anhui, 230022, People’s Republic of ChinaEmail tanghq_card@126.comZhiqiang ZhangDepartment of Urology, The Second Affiliated Hospital of Anhui Medical University, No. 678 Furong Road, Hefei, Anhui, 230032, People’s Republic of ChinaEmail zhangzq_urology@126.comObjective: This study aimed at exploring whether illness perceptions may mediate the relationship between depressive symptoms and lower urinary tract symptoms (LUTS) among benign prostatic hyperplasia (BPH) patients.Methods: The Patient Health Questionnaire (PHQ-9) for depression, the International Prostate Symptom Score (IPSS) for the severity of LUTS and the brief Illness Perception Questionnaire (B-IPQ) for illness perceptions (IPs) were used among the 157 BPH patients with LUTS. Pearson’s correlation test and hierarchical regression analyses were used to assess the correlations between LUTS, depressive symptoms and IPs.Results: Our study found that the severity of LUTS was associated with depressive symptoms and subscales of illness perception; meanwhile, IPs were associated with the level of education. A positive relationship was found between the scores of PHQ9 and the B-IPQ subscales of illness consequences, identity, timeline, concern and emotion; thus, a negative correlation was found between scores of PHQ9 and the B-IPQ subscales of illness coherence, personal control and treatment control. The hierarchical regression analysis showed IPSS and the B-IPQ subscales of illness consequences, concern and emotion were significantly associated with depression, and explained 85.1% of the variance in depressive symptoms (R2 = 0.851, p < 0.05).Conclusion: The relationship between LUTS and depressive symptoms may be mediated by the negative IPs, including consequences, concern and emotions. Clinicians should not only focus on the LUTS but also on the IPs to improve depressive symptoms among BPH patients.Keywords: lower urinary tract symptom, illness perceptions, benign prostatic hyperplasia, depression

Ailing Luo,1,&ast; Lihua Yang,2,&ast; Ming Li,3 Mansi Cai,1 Amin Huang,4 Xiaodan Liu,5 Xu Yang,1 Yaping Yan,1 Xueliang Wang,1 Xuedong Wu,6 Ke Huang,7 Libin Huang,8 Shanshan Liu,1 Ling Xu,1 Xiaoping Liu1 1Department of Hematology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Pediatric Center of Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 3The Emergency Department of Zhuzhou Central Hospital, Zhuzhou, Hunan, People’s Republic of China; 4Department of Medical Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 5Division of Birth Cohort Study, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 6Department of Pediatrics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 7Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 8Pediatrics Department, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoping Liu; Ling XuDepartment of Hematology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, No. 9, Jinsui Road, Tianhe District, Guangzhou, 510623, Guangdong, People’s Republic of ChinaTel +86-13822283646; +86-13798111250Fax +86-2038076069; +86-2038076557Email liu_xiaoping@gwcmc.org; xuling@gwcmc.orgBackground/Aim: Acute lymphoblastic leukemia (ALL) is the most common form of pediatric cancer. METTL14, an N6-methyladenosine (m6A) modification protein, plays several roles in cancer development and is involved in the pathogenesis of various types of cancers. However, the role of METTL14 gene single nucleotide polymorphisms (SNPs) in pediatric ALL susceptibility remains to be investigated.Methods: A case-control design and multinomial logistic regression were used to develop models to estimate the overall risk for pediatric ALL and three METTL14 gene SNPs (rs298982 G/A, rs298981 A/G and rs1064034 T/A) in 808 cases and 1340 controls, which were genotyped using a TaqMan assay. The associations were estimated by odds ratios (ORs) with their 95% confidence intervals (CIs). Furthermore, stratified analysis was performed to explore associations of rs298982 and rs1064034 with pediatric ALL susceptibility in terms of age, sex, immunophenotype, minimal residual disease (MRD), and other clinical characteristics.Results: Among the three analyzed SNPs, rs298982 G/A and rs1064034 T/A exhibited a significant association with decreased childhood ALL risk, while rs298981 A/G exhibited no difference. In stratified analysis, rs298982 GA/AA and rs1064034 TA/AA had a protective effect in children < 120 months of age and males, common B ALL, TEL-AML, non gene fusion, normal diploid, and high WBC. However, the rs1064034 TA/AA genotype was associated with an increased risk of mixed immunophenotyping. Compared with the reference haplotype GAT, haplotypes CAA, CGT and CGA were significantly associated with elevated ALL risk, while haplotype GGT was significantly associated decreased ALL risk. Moreover, subjects carrying rs298982 A or rs1064034 A exhibited less minimal MRD after induced chemotherapy. Functional annotations revealed that METTL14 gene SNPs rs298982 G/A and rs1064034 T/A could be potential functional variants.Conclusion: In conclusion, METTL14 gene polymorphisms influence the risk of ALL in southern Chinese children and might be potential biomarkers for pediatric ALL susceptibility and chemotherapeutics.Keywords: ALL, METTL14, SNP, susceptibility, Chinese children

Ke Huang,1,2 Kewu Huang,3 Jianying Xu,4 Lan Yang,5 Jianping Zhao,6 Xiangyan Zhang,7 Chunxue Bai,8 Jian Kang,9 Pixin Ran,10 Huahao Shen,11 Fuqiang Wen,12 Yahong Chen,13 Tieying Sun,14 Guangliang Shan,15 Yingxiang Lin,3 Sinan Wu,2,16 Ting Yang,1,2,17 Chen Wang1,2,17,18 1Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, National Clinical Research Center for Respiratory Diseases, Beijing, People’s Republic of China; 3Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Department of Pulmonary and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, Shanxi Dayi Hospital, Taiyuan, People’s Republic of China; 5Department of Pulmonary and Critical Care Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 6Department of Pulmonary and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 7Department of Pulmonary and Critical Care Medicine, Guizhou Provincial People’s Hospital, Guiyang, People’s Republic of China; 8Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 9Department of Pulmonary and Critical Care Medicine, First Hospital of China Medical University, Shenyang, People’s Republic of China; 10State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Diseases, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China; 11Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, People’s Republic of China; 12State Key Laboratory of Biotherapy of China and Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, People’s Republic of China; 13Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, People’s Republic of China; 14Department of Respiratory and Critical Care Medicine, Beijing Hospital, Beijing, People’s Republic of China; 15Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, People’s Republic of China; 16Institute of Clinical Medical Sciences, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 17Department of Respiratory Medicine, Capital Medical University, Beijing, People’s Republic of China; 18Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Chen Wang; Ting YangDepartment of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Chaoyang District, Beijing, 100029, People’s Republic of ChinaTel +86 10 65105565; +86 10 84206276Email cyh-birm@263.net; dryangting@qq.comPurpose: Anxiety and depression are often underdiagnosed and affect the prognosis of patients with chronic obstructive pulmonary disease (COPD). We analyzed data from the China Pulmonary Health (CPH) study to assess the prevalence of anxiety and depression in COPD patients and their relationship with disease severity.Patients and Methods: A total of 57,779 subjects aged 20 years or older were recruited in the CPH study. All participants were assessed using a standard questionnaire and underwent pulmonary function tests before and after the use of a bronchodilator in local health centers. The Hospital Anxiety and Depression Scale (HADS) questionnaire with a cutoff score of 8 was used to define anxiety and depression. The prevalence of anxiety and depression in patients of COPD were investigated. Multivariate logistic regression was used to investigate the effects of COPD and lung function on anxiety and depression.Results: A total of 49,053 participants (20,661 men and 28,392 women) completed the questionnaire with reliable post-bronchodilator pulmonary function test results and were included in the final analysis, of which 4686 (9.55%) were diagnosed with COPD. Of the patients with COPD, 10.79% had anxiety, 13.65% had depression, and 7.08% had anxiety and depression concomitantly. In the multivariate logistic regression analysis, COPD was not significantly associated with anxiety, depression, or both. After adjusting for confounders in model 1, patients in the GOLD III–IV group had a significantly higher risk of anxiety, depression, and their coincidence. After further adjusting for respiratory symptoms in model 2, lung function impairment in the GOLD III–IV group was only significantly associated with a higher risk of depression or at least one of anxiety and depression.Conclusion: Anxiety and depression are prevalent in patients with COPD in China. More severe lung function impairment is significantly associated with a higher risk of depression.Keywords: anxiety, COPD, depression, Hospital Anxiety and Depression Scale, HADS

Jie Tang,1 Liqun Zhu,1 Yuejiao Huang,2,3 Lixiang Yang,4 Dangen Ge,5 Zhengyu Hu,6 Chun Wang1 1Department of Oncology, Liyang People’s Hospital, Liyang, 213300, People’s Republic of China; 2Medical School, Nantong University, Nantong, 226019, People’s Republic of China; 3Department of Medical Oncology, Affiliated Tumor Hospital of Nantong University, Nantong, 226399, People’s Republic of China; 4Department of Neurosurgery, Affiliated Zhongda Hospital of Southeast University, Nanjing, 210009, People’s Republic of China; 5Department of Pharmacy, Liyang People’s Hospital, Liyang, 213300, People’s Republic of China; 6Department of General Surgery, Shanghai Tenth People’s Hospital, Affiliated to Tongji University School of Medicine, Shanghai, 200072, People’s Republic of ChinaCorrespondence: Chun WangDepartment of Oncology, Liyang People’s Hospital, 70 Jianshe Road, Liyang, Jiangsu, 213300, People’s Republic of ChinaEmail zlkwangchun@163.comObjective: Anal canal cancer is a rare malignancy with increasing incidence in recent times. This study aimed to develop two nomograms to predict the overall survival (OS) and cancer-specific survival (CSS) of patients with anal canal cancer.Methods: Information of patients with anal canal cancer from 2004 to 2015 was extracted from the surveillance, epidemiology, and end results (SEER) database. Cox analysis was used to select the risk factors for prognosis, and nomograms were constructed using the R software. The C-index, area under the curve (AUC) of time-dependent receiver operating characteristic (ROC) curves, calibration plot and decision curve analysis (DCA) were used to assess the clinical utility of the nomograms.Results: A total of 2458 patients with malignant tumours of the anal canal were screened out. Sex, age, marital status, histological type, grade, tumour size, AJCC stage, SEER stage and chemotherapy were independent prognostic factors for OS, whereas sex, age, race, histological type, grade, tumour size, AJCC stage, SEER stage and radiotherapy were independent prognostic factors for CSS. In the training cohort, the C-index value for OS nomogram was 0.73 (95% CI, 0.69– 0.77), and the AUC values that predicted the 1-, 3- and 5-year survival rates were 0.764, 0.758 and 0.760, respectively, whereas the C-index value for CSS nomogram model was 0.74 (95% CI, 0.69– 0.79), and the AUC values were 0.763, 0.769 and 0.763, respectively. The calibration plot and DCA curves demonstrated good prediction performance of the model in both the training and validation cohorts.Conclusion: The established nomogram is a visualisation tool that can effectively predict the OS and CSS of patients with anal canal cancer.Keywords: anal canal cancer, cancer specific survival, nomogram, overall survival, prognosis

Keyu Guo,&ast; Qi Tian,&ast; Lin Yang, Zhiguang Zhou National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lin Yang; Zhiguang Zhou Email yanglin_nfm@csu.edu.cn; zhouzhiguang@csu.edu.cnAbstract: Type 1 diabetes mellitus (T1DM) is a progressive disease as a result of the severe destruction of islet β-cell function, which leads to high glucose variability in patients. However, α-cell function is also compromised in patients with T1DM, characterized by aberrant fasting and postprandial glucagon secretion. According to recent studies, this aberrant glucagon secretion plays an increasing role in hyperglycemia, insulin-induced hypoglycemia and exercise-associated hypoglycemia in patients with T1DM. With application of continuous glucose monitoring system, dozens of metrics enable the assessment of glycemic variability, which is an integral component of glycemic control for patients with T1DM. There is growing evidences to illustrate the contribution of glucagon secretion to the glycemic variability in patients with T1DM, which may promote the development of new treatment strategies aiming to mitigate glycemic variability associated with aberrant glucagon secretion.Keywords: type 1 diabetes, glucagon secretion, continuous glucose monitoring, hyperglycemia, hypoglycemia, glycemic variability

Yanlong Yang,1,&ast; Zaoxiu Hu,2,&ast; Hongwen Sun,1 Qinghe Yu,1 Linzhu Yang,1 Fang Yin,1 Yongmen Sun,1 Lisha Pu,3 Xingming Zhu,1 Shen Li,4 Xiaobo Chen,1 Yunping Zhao1 1Department of Thoracic Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, People’s Republic of China; 2Department of Pathology, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital, Yunnan Cancer Center), Kunming, 650118, People’s Republic of China; 3Department of Nephrology, Kunming Yanan Hospital, Kunming, 650051, People’s Republic of China; 4Department of Thoracic Surgery, Baoshan People’s Hospital, Baoshan, 678000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaobo Chen; Yunping ZhaoDepartment of Thoracic Surgery, The First Affiliated Hospital of Kunming Medical University, No. 295 Xichang Road, Wuhua District, Kunming, 650032, Yunnan Province, People’s Republic of ChinaTel/Fax +86 87165324888Email chenxb@ydyy.cn; zhaoypcq@126.comBackground: Lung adenocarcinoma (LUAD) is a major type of NSCLC and has high morbidity and mortality. The identification of useful prognostic biomarkers for LUAD is important. CBX7 has been reported in various cancers yet its expression level and potential roles have not been fully understood.Methods: GEPIA, Oncomine, TCGA, KM plotter and OSluca databases were used to explore the expression profile and prognostic effects of CBX7 mRNA expression in patients with LUAD. TIMER was used to explore the relationship between CBX7 and immune infiltrating cells. GSEA was used to further explore the potential biological process and pathways regulated by CBX7 in LUAD. Lastly, IHC detection of CBX7 in 95 samples was used to validate the result.Results: We found CBX7 was downregulated in LUAD in GEPIA, Oncomine and TCGA databases. TCGA, KM plotter and OSluca databases suggested that CBX7 was associated with poor clinical outcomes and low survival rate. Using TIMER, we found that CBX7 might be associated with immune infiltration. Via gene set enrichment analysis, we found that tumor-associated biological processes and signaling pathways were enriched in the CBX7 downregulated group. Using clinical samples, we found that CBX7 protein has low expression in LUAD and was associated with poor survival.Conclusion: CBX7 might serve as a promising biomarker and potential molecular target in LUAD.Keywords: CBX7, LUAD, prognosis, biomarker, immune infiltration

Juan Zhao,1 Wenjuan Wang,1 Suhua Wei,1 Lihong Yang,2 Yanhua Wu,2 Bin Yan2,3 1Department of Haematology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Department of Clinical Research Center, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 3Department of Psychiatry, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of ChinaCorrespondence: Bin YanDepartment of Clinical Research Center, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of ChinaTel +86 02985323614Email yanbin.1987@hotmail.comObjective: We aimed to investigate the association between fragmented sleep and the prevalence of hypertension in middle-aged and older individuals.Methods: This study included 5804 participants with an average age of 63.1± 11.2 years from the Sleep Heart Health Study. Fragmented sleep parameters including arousal index in total sleep (ArI-Total), rapid eye movement sleep (ArI-REM), non-rapid eye movement sleep (ArI-NREM), fragmented sleep index (SFI), sleep efficiency (SE) and wake after sleep onset (WASO) were monitored using polysomnography. The information on hypertension, defined as systolic blood pressure (SBP) ≥ 140 mmHg and/or diastolic blood pressure (DBP) ≥ 90 mmHg or under antihypertensive treatment, was collected at baseline. We conducted multivariable logistic regression to explore the cross-sectional association between fragmented sleep and the prevalence of hypertension.Results: After adjusting for potential confounders, fragmented sleep parameters (per 5-unit change) including SE (odds ratio [OR] 0.904; 95% confidence interval [CI] 0.877– 0.932; P < 0.001), WASO (OR 1.019; 95% CI 1.012– 1.027; P < 0.001), ArI-Total (OR, 1.036; 95% CI, 1.005– 1.068; P = 0.024), and ArI-NREM (OR 1.032; 95% CI 1.004– 1.062; P = 0.027) were significantly associated with the prevalence of hypertension. In addition, ArI-Total, ArI-NREM, and ArI-REM were positively correlated with both systolic blood pressure and diastolic blood pressure.Conclusion: We found a high prevalence of hypertension among middle-aged and older individuals with fragmented sleep. The causal association between fragmented sleep and hypertension warrants further investigation.Keywords: blood pressure, polysomnography, fragmented sleep, Sleep Heart Health Study, cross-sectional study

Kangqi Ren,1,&ast; Guanggui Ding,1,&ast; Shuying Xie,2 Lin Yang1 1Department of Thoracic Surgery, Shenzhen People’s Hospital & The Second Clinical Medical College of Jinan University, Shenzhen, People’s Republic of China; 2Department of Medicine, Burning Rock Biotech, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lin YangDepartment of Thoracic Surgery, Shenzhen People’s Hospital & The Second Clinical Medical College of Jinan University, 1017 North Dongmen Road, Shenzhen, People’s Republic of ChinaTel +86-13798314779Email szrmyyxwk10@163.comAbstract: Targeted therapy for patients with advanced non-small cell lung cancer (NSCLC) is often challenged by the arising of drug resistance. After progression to targeted therapy, treatment options include continued targeted therapy, definitive local therapy, and the combination of both. While there is evidence that local ablative radiotherapy may prolong the disease control by targeted therapy, little is known regarding the relevance of salvage thoracic surgery in this setting. Herein, we presented a case of stage IV lung adenocarcinoma with concurrent EML4-ALK and TAC1-ALK fusion who had long-term survival after salvage thoracic surgery. The patient underwent a multidisciplinary treatment scheme that consisted of radiotherapy, ALK inhibitor crizotinib, and surgery, with blood-based genomic profiling for monitoring disease progression. Notably, salvage thoracic surgery was performed after progression on the crizotinib therapy and acquired ALK F1174C mutation was identified, which has been shown to be resistant to crizotinib and possibly sensitive to ceritinib. The patient benefited from salvage thoracic surgery with a remarkable progression-free survival of 31 months at last follow-up, and the patient maintained high-performance status throughout the course of management. To the best of our knowledge, this is the first case reporting on the long-term survival outcome from salvage thoracic surgery after crizotinib treatment in an NSCLC patient carrying double ALK fusion.Keywords: advanced non-small cell lung cancer, multidisciplinary treatment, salvage thoracic surgery, crizotinib, ALK F1174C mutation

Zhicong Wang,&ast; Xi Chen,&ast; Yuxuan Wu,&ast; Wei Jiang, Ling Yang, Hong Wang, Shuping Liu, Yuehong Liu Orthopaedic Center of Deyang City, Department of Orthopedics, Deyang People’s Hospital, Deyang, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shuping Liu; Yuehong LiuOrthopaedic Center of Deyang City, Department of Orthopedics, Deyang People’s Hospital, No. 173 Taishan North Road, Jingyang District, Deyang, 618000, People’s Republic of ChinaTel +86 838 241 8102Fax +86 838 241 8102Email doctorliushuping@126.com; doctorliuyuehong@163.comPurpose: To investigate the relationship between admission resting heart rate (RHR) and all-cause mortality in elderly patients with hip fracture.Methods: A retrospective cohort study with 837 patients based on the established hip fracture database was conducted. Admission RHR was measured via electrocardiogram, and patients were grouped by the median RHR value (beats per minute, bpm). The main outcomes were 1-year and total all-cause mortality. Cox proportional hazard models and restricted cubic spline were used to assess the relationship between RHR and mortality. Sensitivity analyses were further performed to determine whether the results were stable.Results: The mean and median RHR were 82.3 and 80.0 bpm, respectively. After a median follow-up of 31.8 months, the 1-year and total all-cause mortality were 17.6% and 31.2%. Multivariable Cox analyses showed that high RHR was an independent risk factor for 1-year mortality (HR = 1.51; 95% CI: 1.08– 2.13; p = 0.016), and total mortality (HR = 1.44; 95% CI: 1.12– 1.85; p = 0.005). For each 10 bpm increase in RHR, the risk of 1-year death increased by 23.0% (HR = 1.23; 95% CI: 1.09– 1.39; p = 0.001), and total death increased by 21.0% (HR = 1.21; 95% CI: 1.09– 1.34; p < 0.001). A typical J-shaped curve was observed in the restricted cubic spline for the association between RHR and 1-year mortality, with the lowest mortality risk at 70 bpm. Sensitivity analyses yielded similar findings.Conclusion: An increase in RHR was independently associated with all-cause mortality, and may be a useful prognostic predictor for elderly patients with hip fracture.Keywords: elderly, hip fracture, resting heart rate, prognosis, mortality

Lu Yang,1 Zhen’an He,2 Xuan Gu,3 Hao Cheng,4 Lin Li5 1Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital City, Hangzhou, Zhejiang Province, People’s Republic of China; 2Shaanxi Institute of Medical Device Quality Supervision and Inspection, Xi’an City, Shaanxi Province, People’s Republic of China; 3Xi’an Hospital of Civil Aviation, Xi’an City, Shaanxi Province, People’s Republic of China; 4Department of Ultrasonography, Shaanxi Cancer Hospital Affiliated to Xi’an Jiaotong University, Xi’an City, Shaanxi Province, People’s Republic of China; 5Shaanxi Cancer Hospital Affiliated to Xi’an Jiaotong University, Xi’an City, Shaanxi Province, People’s Republic of ChinaCorrespondence: Hao Cheng; Lin Li Email uschenghao@163.com; lloyd_115599@sina.comObjective: The purpose of the current study is to explore the demographic characteristics of hyperuricemia in China.Study Design: The cross-sectional study was conducted, and the CHARLS dataset in 2011 was used.Methods: Logistic regression model was used to assess the association between BMI and hyperuricemia. We also used restricted cubic spline with three knots to assess the dose–response relationship. To investigate the differences in dose–response relationships in various groups, stratification analysis was conducted.Results: Of the 9408 middle and older participants, those who were overweight or obese had higher risk for hyperuricemia (OR=1.26, 95% CI=1.01– 1.57; OR=1.90, 95% CI=1.46– 2.47). In the subgroup, the effect of obesity on hyperuricemia was robust in varying gender and age. However, among overweight group, those with being male and aged over 60 years had higher risk for hyperuricemia (male: OR=1.42, 95% CI=1.07– 1.90; over 60 years: OR=1.28, 95% CI=1.03– 1.60). A dose-response relationship was examined between BMI and the risk of hyperuricemia. The result showed that the odds ratio of hyperuricemia and BMI displayed U-shaped nonlinear relationship (Ptrend< 0.001, non-linear P< 0.001).Conclusion: The association between BMI and hyperuricemia showed positive relationship. Specifically, the group with male and age over 60 years had higher risk of hyperuricemia along with increased weight.Keywords: body mass index, hyperuricemia, CHARLS, middle and older people

Yuanxiang Li,&ast; Yang Hu,&ast; Bin Yang, Caibao Jin, Hui Ren, Jingyi Wu, Zhijun Wang, Youying Wei, Ling Yang, Yanping Hu Department of Oncology, Hubei Cancer Hospital, TongJi Medical College, Huazhong University of Science and Technology, Wuhan, 430079, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanping HuDepartment of Oncology, Hubei Cancer Hospital, TongJi Medical College, Huazhong University of Science and Technology, Wuhan, 430079, Hubei, People’s Republic of ChinaEmail h-y-p@126.comAbstract: PD-1/PD-L1 inhibitors activate immunological response and have become one of the main modalities of cancer treatment. However, they may result in the immune-related adverse events (irAEs). Immune-related cardiotoxicity is relatively rare but may become fatal. We will present a case of a male patient who experienced immunotherapy-related cardiotoxicity one year after received pembrolizumab treatment. The patient had atypical symptom presentation initially, but his condition deteriorated worsened rapidly and he developed severe cardiac disease. The patient experienced significant relief after corticosteroid treatment. Unfortunately, he experienced a reoccurence of the severe adverse event when discontinuing the use of corticosteroids. Ultimately, larger doses and longer courses of corticosteroid treatment cured the heart damage. Fortunately, we observed that lesions were stable and maintained for a long time after cessation of using pembrolizumab for eight months.Keywords: PD-1/PD-L1 inhibitors, immune-related cardiotoxicity, non-small cell lung cancer

Dechao Feng,&ast; Facai Zhang,&ast; Ling Liu,&ast; Qiao Xiong, Hang Xu, Wuran Wei, Zhenghua Liu, Lu Yang Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhenghua Liu; Lu YangDepartment of Urology, Institute of Urology, West China Hospital, Sichuan University, 37 Guoxue Xiang, Chengdu, 610041, Sichuan, People’s Republic of ChinaTel +86 28-8542-2444Fax +86 28-85422451Email zhliu@scu.edu.cn; wycleflue@163.comBackground: There is a surprising paucity of studies investigating the potential mechanism of SKA3 in the progression and prognosis of kidney renal papillary cell carcinoma (KIRP).Methods: We used TCGA and other databases to analyze the expression, clinical value, and potential mechanisms of SKA3 in KIRP patients. We also explored therapeutic agents for KIRP through GSCALite.Results: SKA3 mRNA expression was significantly upregulated and the area under the curve was 0.792 (95% CI 0.727– 0.856). Increased SKA3 expression was related to shorter overall survival, disease-specific survival and progression-free survival. Hub genes in protein–protein interactions were CDK1, CDC20, CCNB1, CCNA2, BUB1, AURKB, BUB1B, PLK1, CCNB2, and MAD2L1, which were differentially expressed and also associated with KIRP prognosis. Gene-set enrichment analysis indicated that E2F targets, epithelial–mesenchymal transition, glycolysis, the WNT signaling pathway, and other pathways were highly enriched upon SKA3 upregulation. Gene-set variation analysis of SKA3 and its ten hub genes showed that the significant correlation of cancer-related pathways included the cell cycle, DNA damage, hormone androgen receptor, hormone estrogen receptor, PI3K/Akt, and Ras/MAPK. In addition, we found that MEK inhibitors, ie, trametinib, selumetinib, PD0325901, and RDEA119, may be feasible targeting agents for KIRP patients.Conclusion: SKA3 might contribute to poor prognosis of KIRP through cell cycle, DNA damage, hormone androgen receptor, hormone estrogen receptor, PI3K/Akt, and RAS/MAPK. SKA3 potentially serves as a prognostic biomarker and target for KIRP.Keywords: spindle and kinetochore–associated complex subunit 3, kidney renal papillary cell carcinoma, biomarker, enrichment analysis, targeted therapy