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Zhiyun Shen,1,* Yaping Zhang,2,* Chun Yang,3 Jie Liu,3 Chenxu Huang,1 Xian Zhang,1 Yuxia Zhang,1 Ying Lin1 1Department of Nursing, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Emergency, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Network Center, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuxia Zhang; Ying Lin, Department of Nursing, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China, Tel +86 21-64041990, Email zhang.yuxia@zs-hospital.sh.cn; lin.ying@zs-hospital.sh.cnBackground: For a long time, fluid balance monitoring has been one of the most difficult problems in the management of patients with heart failure (HF). There is considerable interest in technology-facilitated fluid balance monitoring. However, little is known about patient acceptance and the use of mobile technology for fluid balance monitoring.Objective: The aim of this study was to develop a mobile app for technology-facilitated fluid balance monitoring and to determine its usability.Methods: A mixed-methods study was conducted in a tertiary hospital in Shanghai, China. A mobile app named I-Self-Care was developed through a best practice implementation project. Patients and nurses both completed the System Usability Scale (SUS, 0– 100) and participated in semistructured interviews.Results: I-Self-Care includes patients’ daily fluid intake and output (I&O), symptoms, hospitalization, and diuretic records. It can automatically calculate food water content and perform real-time analysis of I&O. The average SUS scores were 81.74 (SD 5.44) among 36 patients and 80.80 (SD 13.26) among 28 nurses (scale 0– 100, with 100 being the best usability), which means that I-Self-Care has high usability for both patients and nurses. Semistructured interviews about the usability of the app were conducted with 17 participants. During the interviews, the patients expressed the high ease of use of I-Self-Care, their expectations for a continuously updated database, and improved self-management behaviour. The nurses thought that family support and repeated operation demonstrations were needed for patients to use the app. The nurses also expressed the convenience of this app for nursing work and the information security of patients.Conclusion: With participant feedback, we confirmed the usability of I-Self-Care for fluid balance monitoring in patients with HF. Continuously updated databases, family support, repeated operation demonstrations, and information security are important for HF patients to use I-Self-Care.Keywords: fluid balance monitoring, intake and output, mobile applications, telemedicine, heart failure

Chao Yang, Yin-gen Luo, Hong-cai Yang, Zhi-hang Yao, Xiao Li Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Xiao Li, Department of Interventional Therapy, National Cancer Center/National Clinical Research, Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, People’s Republic of China, Tel/Fax +86 010 8778 8309, Email simonlixiao@263.netPurpose: To investigate the effect of early transarterial chemoembolization (TACE) refractoriness on hepatocellular carcinoma (HCC) patient survival and to explore whether viable lesions > 50% after two consecutive TACE treatments negatively affect the prognosis of HCC patients.Patients and Methods: From January 2014 to August 2017, 323 HCC patients who received TACE as the initial treatment were analyzed. TACE refractoriness was diagnosed according to the Japan Society of Hepatology 2021 version. Propensity score matching (PSM) was used to create a 1:1 matched group (nonrefractoriness vs refractoriness). To determine survival outcomes and prognostic factors, the Kaplan-Meier method and Cox proportional hazards model were used.Results: In total, 51.1% of patients developed early TACE refractoriness (n = 165). After PSM, 120 patients from each group were matched and analyzed. The median overall survival (OS) time of the early TACE refractoriness group was significantly shorter than that of the nonrefractory group [21 months (95% CI: 15.7– 26.3) vs 34 months (95% CI: 27.5– 40.5), p = 0.002]. Thirty-eight patients with viable lesions > 50% after two consecutive TACE procedures were identified and matched with patients of non-refractoriness. No significant difference in median OS was observed [35 months (95% CI: 21.6– 48.5) vs 31 months (95% CI: 25.4– 36.6), p = 0.611]. Multivariate analysis revealed that the BCLC stage, tumor size, tumor capsule, tumor distribution, α-fetoprotein level (AFP), and early TACE refractoriness were independent risk factors for prognosis in HCC patients.Conclusion: Early TACE refractoriness may shorten the OS of HCC patients. However, viable lesions > 50% after two consecutive TACE treatments did not impair the survival of patients. It may be inappropriate to consider these patients as having developed TACE refractoriness.Keywords: hepatocellular carcinoma, transarterial chemoembolization, TACE refractoriness, overall survival, viable lesions

Shoujun Xu,1,&ast; Meng Li,2,&ast; Chunlan Yang,3 Xiangling Fang,4 Miaoting Ye,4 Yunfan Wu,2 Binrang Yang,4 Wenxian Huang,4 Peng Li,1 Xiaofen Ma,2 Shishun Fu,2 Yi Yin,2 Junzhang Tian,2 Yungen Gan,1 Guihua Jiang2 1Department of Radiology, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of China; 2Department of Medical Imaging, Guangdong Second Provincial General Hospital, Guangzhou, People’s Republic of China; 3Department of Hematology and Oncology, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of China; 4Department of Department of Children Healthcare, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of China&ast;These authors have contributed equally to this workCorrespondence: Guihua Jiang; Yungen Gan, Email jianggh@gd2h.org.cn; gdszgyg-1@126.comPurpose: This study used the graph-theory approach, degree centrality (DC) to analyze whole-brain functional networks at the voxel level in children with ASD, and investigated whether DC changes were correlated with any clinical variables in ASD children.Methods: The current study included 86 children with ASD and 54 matched healthy subjects Aged 2– 5.5 years. Next, chloral hydrate induced sleeping-state functional magnetic resonance imaging (ss-fMRI) datasets were acquired from these ASD and healthy subjects. For a given voxel, the DC was calculated by calculating the number of functional connections with significantly positive correlations at the individual level. Group differences were tested using two-sample t-tests (p < 0.01, AlphaSim corrected). Finally, relationships between abnormal DCs and clinical variables were investigated via Pearson’s correlation analysis.Results: Children with ASD exhibited low DC values in the right middle frontal gyrus (MFG) (p

Mingchong Liu,1,&ast; Chensong Yang,1,&ast; Qining Chu,2 Xiao Fu,1 Yue Zhang,1 Guixin Sun1 1Department of Traumatic Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Emergency Trauma Center, Nanyang Second General Hospital, Nanyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guixin Sun, Department of Traumatic Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China, Tel +21-38804518, Fax +21-65983047, Email sunguixin@sina.comBackground: Oxidative stress status may affect bone metabolism and regeneration. However, few studies reported whether oxidative stress could impact the outcomes of hip fractures. This study aimed to explore if superoxide dismutase and glutathione reductase, the critical antioxidant enzymes, correlated with the prognosis of hip fractures.Methods: Patients with hip fractures were extracted from our database, and those who met the inclusion criteria were analyzed. Propensity score matching was used to reduce the influence of confounding factors, and ROC curves based on matched populations were created to determine the optimal cutoff points of SOD and GR. Then, outcomes between SOD or GR and outcomes of hip fractures were compared.Results: Out of 301 patients enrolled in this study, 50 patients died within one year. After a 1:1 PSM, the patients with less than 1-year survival had significantly lower SOD (p = 0.026) and GR (p = 0.021) than those who were still alive at one year. Logistics analysis showed that low SOD and low GR may be independent risk factors for 6-month survival, 1-year survival, 6-month free walking ability, and 1-year free walking ability.Conclusion: SOD and GR may be the independent risk factors for survival and walking abilities of hip fractures.Keywords: hip fractures, oxidative stress, superoxide dismutase, glutathione reductases, prognosis

Fenglin Wang,1,2 Luyao Zhou,1 Di Zhu,2 Caizhe Yang2 1Hebei North University, Zhangjiakou, Hebei, 075000, People’s Republic of China; 2Department of Endocrinology, Air Force Medical Center, Beijing, 100142, People’s Republic of ChinaCorrespondence: Caizhe Yang; Di Zhu, Department of Endocrinology, Air Force Medical Center, Beijing, 100142, People’s Republic of China, Tel +86-1066928242 ; +86-1066926242, Email yangcaizhe2008@163.com; judy3481@163.comBackground: The fat-soluble molecule vitamin D has attracted much attention since its pleiotropism was discovered. Its effectiveness can be attributed to the presence of vitamin D receptors in most of the body’s tissues. Based on the classical role of vitamin D in regulating calcium and phosphorus metabolism and maintaining bone health, the role of vitamin D in immunity, type 2 diabetes mellitus (T2DM), tumor and cardiovascular diseases has been further discovered. Some experiments have shown that vitamin D can restore the production of antimicrobial peptides (AMP) in primary diabetic foot ulcer (DFU) cells, which can improve in vitro wound healing, indicating its potential therapeutic use in DFU therapy. In addition, vitamin D can also inhibit the secretion of T-helper type 1 (Th1) cytokines IFN-Y and IL-2 while stimulating the production of Th2 cytokines, thereby promoting wound healing.Objective: To investigate the relationship between 25-OH-vitamin D level and DFU in diabetes mellitus (DM) patients, and to provide a theoretical basis for the early prevention and treatment of DFU.Methods: The clinical data of 429 hospitalized patients with DM were retrospectively analyzed in this case–control study. The patients were divided into the DFU group (n = 242) and non-DFU group (n = 187). Fasting venous blood was drawn from all subjects to detect serum 25-OH-vitamin D levels and blood biochemical parameters, the difference of parameters between DFU group and non-DFU group were analyzed, and the risk factors of DFU were analyzed by logistic regression.Results: The difference between the two groups in age, DM duration, gender, diastolic blood pressure, serum creatinine, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, albumin, white blood cell count, hemoglobin, hematocrit, 25-OH-vitamin D was statistically significant (p < 0.05). Multivariate logistic regression analysis showed that 25-OH-vitamin D is an independent protective factor for DFU [OR 95%, CI 0.984 (0.969, 0.998), p < 0.05]. 25-OH-vitamin D nutrition status distribution was different between non-DFU group and DFU group (P < 0.05). Vitamin D deficiency (< 50 nmol/L) accounted for 86.78% of all DFU patients, which was only 74.33% in non-DFU patients. The 25-OH-vitamin D levels of DFU patients from Wagner Grades 1 to 5 showed a downward trend (p < 0.01).Conclusion: In conclusion, our study confirms that 25-OH-vitamin D is closely correlated with DFU and that 25-OH-vitamin D is an independent protective factor for DFU. Therefore, vitamin D screening or supplementation might be beneficial to prevent DFU and improve the prognosis of DM patients.Keywords: 25-OH-vitamin D, diabetic foot ulcer, vitamin D, diabetes mellitus

Huajie Yang,1,&ast; Xiang Huang,2,&ast; Chunyu Yang,3 Sufen Zhu,4 Xiaoyi Chen,5 Man Zhang,2 Xiao Yu,3 Harry HX Wang3,6,7 1School of Health Technology, Guangdong Open University (Guangdong Polytechnic Institute), Guangzhou, People’s Republic of China; 2Department of Public Health, Sanxiang Community Health Service Centre of Zhongshan, Zhongshan, People’s Republic of China; 3School of Public Health, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 4Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK; 5School of Nursing, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 6Department of General Practice, The Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 7JC School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region&ast;These authors contributed equally to this workCorrespondence: Harry HX Wang, School of Public Health, Sun Yat-Sen University, Guangzhou, People’s Republic of China, Tel +86 20 87330672, Email wanghx27@mail.sysu.edu.cn; haoxiangwang@cuhk.edu.hk Huajie Yang, School of Health Technology, Guangdong Open University (Guangdong Polytechnic Institute), Guangzhou, 510091, People’s Republic of China, Tel +86 760 89911522, Email hjyang@gdpi.edu.cnIntroduction: Time-to-treatment window is critical for managing acute ischaemic stroke. The community healthcare practitioners (CHPs) who deliver frontline care in the health system play an important role in stroke prevention and treatment.Methods: A multi-stage sampling design was adopted in Guangdong province, China. A total of 997 CHPs who participated in the survey were divided into two groups (the awareness group vs the unawareness group) according to their knowledge on the time window for stroke management. Logistic regression analysis was performed to explore factors associated with the awareness of “time window”.Results: Overall, less than half (49.1%) of CHPs were aware of the time window for stroke management. The proportion of CHPs who were able to recognise stroke symptoms were higher in the awareness group (42.7%) than that in the unawareness group (38.8%). Most CHPs (82.9%) in the awareness group had the knowledge about the effectiveness of intravenous thrombolysis in treating acute cerebral infarction, whereas this was perceived by only less than half (43.6%) of CHPs in the unawareness group. Factors associated with the knowledge of time window for stroke management included participation in cerebrovascular disease management training (adjusted odds ratio [aOR]=4.203, 95% CI: 1.707– 10.348, p=0.002), awareness of the time frame for CT initiation (aOR=5.214, 95% CI: 1.803– 15.078, p=0.002) and for urokinase thrombolysis administration (aOR=11.927, 95% CI: 4.393– 32.382, p< 0.001), accurate perceptions about the target for blood pressure lowering (aOR=4.181, 95% CI: 1.713– 10.207, p=0.002) and blood glucose control (aOR=2.446, 95% CI: 1.019– 5.869, p=0.045), and the familiarity with prehospital stroke management principles (aOR=3.593, 95% CI: 1.383– 9.332, p=0.009).Conclusion: The CHPs need to enhance their ability to address the acute ischaemic stroke onset promptly to provide effective treatment within the beneficial “time window”. This may help improve the stroke chain of survival with better multidisciplinary decision support systems that enable optimal stroke care delivery.Keywords: time window, stroke, cross-sectional study, primary care

Xinyi Chen,1 Jingyao Tu,1 Li Ma,1 Yongbiao Huang,1 Chunguang Yang,2 Xianglin Yuan1 1Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Xianglin Yuan, Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jie Fang Road 1095, Wuhan, Hubei Province, People’s Republic of China, Tel/Fax +8602783662683, Email yuanxianglin@hust.edu.cnBackground: Clear cell renal cell carcinoma (ccRCC) is the most aggressive subtype of renal cell carcinoma. Ferroptosis is an iron-dependent programmed cell death. Long non-coding RNAs (lncRNAs) emerge as a critical role in regulating cancer progression.Objective: This study aimed to identify molecular regulation of ferroptosis-related lncRNAs (FRLs) in ccRCC.Methods: The prognostic value of FRLs was investigated in ccRCC samples downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset. The FRLs were screened out by Pearson correlation test. The 465 FRLs confirmed as potential prognostic factors through univariate Cox regression analysis were entered into Lasso and multivariate Cox regression to build a FRLs prognostic signature. A risk score based on the prognostic model divided ccRCC patients into low- and high-risk groups. A prognostic nomogram, derived from the prognostic signature and integrating clinical characteristics, was constructed. Gene set enrichment analysis (GSEA) revealed the immune- and tumor-associated pathways. Two distinct clusters were identified with different immune signatures through consensus clustering analysis. The prognostic value of some hub FRLs was externally validated via three GEO datasets (GSE46699, GSE53757 and GSE66272) and online databases. Finally, the three FRLs (LINC00460, LINC00941 and LINC02027) were verified through in vitro experiments.Results: The FRLs prognostic signature, including 7 independent prognostic lncRNAs, exhibited good accuracy in predicting overall survival (OS) of ccRCC patients. This signature was correlated with immune infiltration and immune checkpoint blockade (ICB). We correlated two distinct clusters with immune infiltration signature of ccRCC. The worse prognosis of cluster 2 was probably mediated by immune evasion. We also found that the expression levels of LINC00460 and LINC00941 in ccRCC cell lines were higher than those in HK-2 cells, but LINC02027 showed the inverse trend.Conclusion: Collectively, our study demonstrated a FRLs prognostic signature which had great clinical value in prognosis assessment.Keywords: clear cell renal cell carcinoma, ferroptosis, long non-coding RNA, immune microenvironment, prognostic signature

Huasheng Huang,&ast; Xiwen Liao,&ast; Guangzhi Zhu, Chuangye Han, Xiangkun Wang, Chengkun Yang, Xin Zhou, Tianyi Liang, Ketuan Huang, Tao Peng Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao Peng; Xiwen Liao, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Shuang Yong Road 6, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China, Tel +86-771-5356528, Fax +86-771-5350031, Email pengtaogmu@163.com; LXWen1991@hotmail.comBackground: The aim of our study was to evaluate the potential of expression and single nucleotide polymorphism of Acyl-CoA binding domain containing 4 (ACBD4) gene as prognosis biomarkers in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after hepatectomy.Methods: HBV-related HCC patients from the First Affiliated Hospital of Guangxi Medical University and GSE14520 were included in the current study, as well as The Cancer Genome Atlas (TCGA) HCC verification cohort. Prognostic analysis and multiple functional enrichment analysis methods were used to evaluate the prognostic value and potential biological functions of the ACBD4 gene in HBV-related HCC.Results: We found that ACBD4 gene is highly expressed in normal liver tissues and markedly down-regulated in HBV-related HCC tissues. ACBD4 gene was significantly related to overall survival (OS) of HCC in TCGA and GSE14520 cohorts, and patients with low ACBD4 expression were markedly related to poor OS. Rs4986172 was observed as an OS biomarker after hepatectomy in the Guangxi HBV-related HCC cohort. The OS of rs4986172 GG genotype was worse than that of HCC patients with A allele (AA and AG genotypes). Multifunctional enrichment analysis suggested that ACBD4 gene is closely related to the metabolic, peroxisome proliferator-activated receptor and cytochrome P450 pathway. Through connectivity map, we also identified eight compounds that may be used as targeted therapeutic agents for ACBD4 gene in HBV-related HCC; these compounds were scopoletin, alfaxalone, bephenium hydroxynaphthoate, apramycin, 4,5-dianilinophthalimide, DL-thiorphan, aminohippuric acid and quinidine. Immune microenvironment analysis revealed that there were significant differences in immune scores of HBV-related HCC tumor tissues with different ACBD4 expression levels.Conclusion: Our study reveals that ACBD4 expression and rs4986172 can be serve as biomarkers of OS in HBV-related HCC patients after hepatectomy.Keywords: rs4986172, ACBD4, HBV-related HCC, overall survival, hepatectomy

Tongqiang Li,1,2,&ast; Qin Shi,1,2,&ast; Jiacheng Liu,1,2,&ast; Yingliang Wang,1,2 Chen Zhou,1,2 Chaoyang Wang,1,2 Shuguang Ju,1,2 Songjiang Huang,1,2 Chongtu Yang,1,2 Yang Chen,1,2 Yaowei Bai,1,2 Bin Xiong1,2 1Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin XiongDepartment of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022, People’s Republic of ChinaEmail herr_xiong@126.comObjective: To investigate the efficiency and safety of callispheres beads loaded with donafenib (DCBs) for embolization in a VX2 liver tumor, as well as the improvement of tumor angiogenesis following embolization.Methods: Forty New Zealand white rabbit VX2 liver tumors were treated with four different drugs via the hepatic artery: NS (normal saline), CB (blank callispheres beads), ACB (adriamycin-loaded callispheres beads) and DCB (DCBs). Hematoxylin-eosin staining was performed to assess tumor necrosis, while MRI was employed to detect the changes in tumor size. The safety was evaluated by the liver and kidney function parameters, and the immunofluorescence and immunohistochemical staining were performed to reflect the tumor hypoxia and tumor angiogenesis following embolization.Results: The DCB group had the smallest tumor growth rate, but the tumor necrosis rate was the highest of the four groups. Compared to the CB and ACB groups, the DCB group did not aggravate the liver damage and had no influence on kidney function. The staining results showed that, although the tumor hypoxia deteriorated after DCBs embolization, the expression of VEGF (vascular endothelial growth factor) reduced, thus inhibiting tumor angiogenesis.Conclusion: DCB administration via hepatic artery is an effective and safe treatment for a preclinical liver cancer model, with the unique benefit of suppressing tumor angiogenesis following embolization.Keywords: hepatocellular carcinoma, donafenib, transcatheter arterial chemoembolization, tumor angiogenesis, efficacy, safety

Zhiquan Hu,1,&ast; Jingjing Li,2,&ast; Chunguang Yang,1 Fen Chen,3 Zhihua Wang,1 Ping Lei,4 Guanxin Shen4 1Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunguang YangDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095, Jiefang Road, Wuhan, 430030, People’s Republic of ChinaTel +86-13871084024Fax +86-27-83663460Email cgyang-hust@hotmail.comFen ChenDepartment of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaEmail 54113447@qq.comBackground: COVID-19 outbreak began in Wuhan and pandemics occur. Although SARS-CoV-2-specific immunoglobulins have been detected in serum of COVID-19 patients, their dynamics and association with outcomes have not been fully characterized.Methods: This retrospective cohort study investigated the association between SARS-CoV-2-specific immunoglobulins and clinical outcomes of COVID-19 patients. We recruited 137 participants who were diagnosed with COVID-19 in four wards of the Tongji Hospital in Wuhan, China. Among the 137 participants, 81 patients were recovered, 23 patients died, and 33 patients remained hospitalized by the end of the study. SARS-CoV-2-specific immunoglobulins were analyzed by chemiluminescence assays. Laboratory and radiological characteristics, and clinical outcomes were compared between the recovered group and the deceased group. Furthermore, a matched cohort study was conducted in which each non-survivor was matched to two recovered patients of similar age.Results: SARS-CoV-2-specific IgM levels peaked in the fourth week after the onset of COVID-19, while serum IgG levels rose earlier and remained high up to the eighth week. In the age-matched cohort study, the serum IgM, but not IgG levels, were higher among the non-survivors than in the recovered group (P = 0.006). The area under the ROC curve for the IgM and IgG levels was 0.702 (95% CI: 0.560– 0.845, P = 0.006) and 0.596 (95% confidence interval: 0.449– 0.744, P = 0.194), respectively. We also showed that patients with COVID-19 who had high IgM or IgG levels (stratified according to best cut-off) exhibited significantly lower overall survival (Kaplan–Meier survival curves, P < 0.05).Discussion: These results indicate the association between immunoglobulins and outcome in patients with COVID-19 and demonstrated that elevated serum IgM levels could indicate poor outcomes in patients with COVID-19. Further, the information about the profile of SARS-CoV-2-specific IgGs may be useful for the future epidemiological investigations of COVID-19 therapies.Keywords: SARS-CoV-2, COVID-19, immunoglobulin, prognosis, antibodies, IgM, IgG, diagnosis

Cong Yang,1,&ast; Mengmeng Han,1,2,&ast; Ruoyu Li,1,&ast; Ligui Zhou,1,3 Ying Zhang,1,2 Lining Duan,1,4 Shiyu Su,1,4 Min Li,1,4 Qi Wang,1 Tongkai Chen,1,&ast; Yousheng Mo5,&ast; 1Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, People’s Republic of China; 2The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, People’s Republic of China; 3Laboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, People’s Republic of China; 4Clinical Medical College of Acupuncture Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, 510405, People’s Republic of China; 5The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tongkai Chen; Yousheng Mo Email chentongkai@gzucm.edu.cn; 378480308@qq.comBackground: Intracerebral hemorrhage (ICH) is a form of severe stroke, the pathology of which is tied closely to a recently discovered form of programmed cell death known as ferroptosis. Curcumin (Cur) is a common phenolic compound extracted from the rhizome of Curcuma longa capable of hematoma volume and associated neurological damage in the context of ICH. Despite exhibiting therapeutic promise, the efficacy of Cur is challenged by its poor water solubility, limited oral bioavailability and inability to efficiently transit across the physiological barriers. Polymer-based nanoparticles (NPs) have widely been employed to aid in drug delivery efforts owing to their ideal biocompatibility and their ability to improve the bioavailability and pharmacokinetics of specific drugs of interest.Methods: In this study, we encapsulated Cur in NPs (Cur-NPs) and explored the effect of these Cur-NPs to enhance Cur delivery both in vitro and in vivo. Furthermore, we evaluated the anti-ferroptosis effect of Cur-NPs in ICH model mice and erastin-treated HT22 murine hippocampal cells.Results: The resultant Cur-NPs were spherical and exhibited a particle size of 127.31± 2.73 nm, a PDI of 0.21± 0.01 and a zeta potential of − 0.25± 0.02 mV. When applied to Madin Darby canine kidney (MDCK) cells in vitro, these Cur-NPs were nonspecifically internalized via multiple endocytic pathways, with plasma membrane microcapsules and clathrin-mediated uptake being the dominant mechanisms. Within cells, these NPs accumulated in lysosomes, endoplasmic reticulum and mitochondria. Cur-NPs were capable of passing through physiological barriers in a zebrafish model system. When administrated to C57BL/6 mice, they significantly improved Cur delivery to the brain. Most notably, when administered to ICH model mice, Cur-NPs achieved superior therapeutic outcomes relative to other treatments. In a final series of experiments, these Cur-NPs were shown to suppress erastin-induced ferroptosis in HT22 murine hippocampal cells.Conclusion: These Cur-NPs represent a promising means of improving Cur delivery to the brain and thereby better treating ICH.Keywords: Intracerebral hemorrhage, nanoparticles, curcumin, brain delivery, blood-brain barrier, ferroptosis

Zhou X, Liu Z, Huang B, et al. Drug Des Devel Ther. 2019;13:2703–2713. The Editor and Publisher of Drug Design, Development and Therapy wish to retract the published article. Concerns were raised regarding the alleged duplication of Oil Red O images in Figures 4 and Figure 6. Specifically, Figure 4C, Oil Red O, Ctrl, appears to have been duplicated with the same image for Figure 6D, Oil Red O, OG+ICG-001. The authors cooperated with the investigation and provided data associated with the study. However, despite the authors’ assistance, it was still not clear how the images came to be duplicated, and, as we cannot verify the validity of the published work, we are therefore retracting the article and the authors agree with this decision. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Hui Yang,1– 3 Shaoxing Sun,1– 3 Zijie Mei,1– 3 Qingming Xiang,1– 3 Chunxu Yang,1– 3 Min Chen,1– 3 Conghua Xie,1– 3 Yunfeng Zhou,1– 3 Hui Qiu1– 3 1Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 3Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of ChinaCorrespondence: Hui Yang; Hui QiuDepartment of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, 430071, People’s Republic of ChinaEmail huiyangwhu@whu.edu.cn; qiuhuiznyy@whu.edu.cnBackground: Anlotinib is an oral anti-angiogenesis inhibitor targeting vascular endothelial growth factor receptors (VEGFRs), platelet-derived growth factor receptors, fibroblast growth factor receptors, etc., and its clinical value in cervical cancer is rarely reported. We designed a retrospective study to evaluate the efficacy and safety of anlotinib in patients with persistent, metastatic, or recurrent cervical cancer who have failed first-line therapy, and compare the efficacy of anlotinib with that of apatinib which targets only VEGFR2 and has shown efficacy in recent studies.Methods: Fifty-two patients with persistent, metastatic, or recurrent cervical cancer who failed first-line therapy and administrated anlotinib or apatinib as monotherapy or combination with chemo-, radio- or immunotherapy were included in this study. Among the 52 patients, 20 patients who received anlotinib from January 2019 to August 2020 were defined as anlotinib group, whereas 32 patients who received apatinib from our previous study were selected as apatinib group. The safety, objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were reviewed and recorded.Results: The ORR and DCR in patients receiving anlotinib were 25% and 80%, respectively. The median PFS and OS in anlotinib group were significantly longer than those in apatinib group, respectively (PFS: 5 months vs 3 months, p=0.015; OS: 10 months vs 5 months, p=0.008). Moreover, the patients treated with anlotinib had better survival with a significantly lower cumulative incidence of cancer-related death than those treated with apatinib (HR=0.31, 95% CI: 0.13– 0.77, p=0.012). The most common adverse effects in the patients treated with anlotinib were hypertension (20%), fatigue (20%), and nausea (15%). No drug-related death occurred.Conclusion: Anlotinib showed beneficial efficacy and safety and can be a treatment option for patients with persistent, metastatic, or recurrent cervical cancer who have failed the first-line therapy.Keywords: angiogenesis, anlotinib, cervical cancer, efficacy, safety, retrospective study

Weixuan Wang,1,&ast; Changmei Yang,2,&ast; Haiteng Deng2 1Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 2MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haiteng DengMOE Key Laboratory of Bioinformatics, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing, People’s Republic of ChinaTel +86-10-62790498Email dht@mail.tsinghua.edu.cnPurpose: Lung cancer is one of the most commonly diagnosed cancer as well as the leading cause of cancer-related mortality worldwide, among which lung adenocarcinoma (LUAD) is the most frequent form of lung cancer. Previous studies have shown that 15-hydroxyprostaglandin dehydrogenase (15-PGDH) catalyzes the oxidation of prostaglandins to reduce their biological activities and behaves as a tumor suppressor in various cancers. Thus, we aimed to systematically examine the effects of 15-PGDH overexpression on cellular processes in lung adenocarcinoma cells.Methods: The stable 15-PGDH-overexpressing A549 cell line was constructed using lentivirus particles. CCK-8 assay was used to determine the cell proliferation rate and sensitivity to cisplatin. Tandem mass tag (TMT)-based quantitative proteomic analysis was used to identify differentially expressed proteins between control and 15-PGDH-overexpression cells. The cell cycle was determined by a flow cytometer. The expression levels of mesenchymal and epithelial markers were measured using Western blotting. Wound healing and transwell assays were used to detect the cell migration and cell invasion ability, respectively.Results: Analysis of datasets in The Cancer Genome Atlas revealed that the PGDH gene expression level in the lung adenocarcinoma tissues was significantly lower than that in the pericarcinous tissues. 15-PGDH overexpression in A549 cells reduced cell proliferation rate. Quantitative proteomics revealed that 15-PGDH overexpression inhibited PI3K/AKT/mTOR signaling pathway, which is a signaling pathway driving tumor cell growth and epithelial-mesenchymal transition (EMT) process. In addition, both cell cycle and DNA repair-related proteins were down-regulated in 15-PGDH overexpressed cells. 15-PGDH overexpression induced G1/S cell cycle arrest and increased susceptibility to DNA damaging reagent cisplatin. Importantly, overexpression of 15-PGDH inhibited EMT process with the downregulation of β-catenin and Snail-1 as well as upregulation of E-cadherin and ZO-1.Conclusion: 15-PGDH is a tumor suppressor in lung cancer and may serve as a potential therapeutic target to prevent lung adenocarcinoma.Keywords: 15-PGDH, proteomics, lung adenocarcinoma, cell proliferation, cell cycle arrest, epithelial-mesenchymal transition

Li Bao,1,2 Chunjing Yang,1,2 Zhengyuan Shi,1,2 Zhanrong Wang,3 Dechun Jiang1,2 1Department of Pharmacy, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Key Laboratory of Biocharacteristic Profiling for Evaluation of Rational Drug Use, Beijing, People’s Republic of China; 3Department of Traditional Chinese Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Zhanrong WangDepartment of Traditional Chinese Medicine, Beijing Shijitan Hospital, Capital Medical University, 10 Tieyi Road, Haidian District, Beijing 100038, People’s Republic of China, Tel +86-10-6392-6405Email dor_j@163.comDechun JiangDepartment of Pharmacy, Beijing Shijitan Hospital, Capital Medical University, 10 Tieyi Road, Haidian District, Beijing 100038, People’s Republic of China, Tel +86-10-6392-6723Email jiangdechun@sina.comBackground: Obesity is a public health problem all over the world, and dietary habits are considered one of the important reasons.Methods: In this study, serum metabolites of mice fed a normal or high-fat diet (HFD) were analyzed using UPLC-QTOF-MS.Results: A significant increase in body weight was noted in HFD mice. The HFD and control groups were significantly different from each other on OPLS-DA scores. The major metabolites contributing to obesity were lipid metabolites (phosphatidylcholines, phosphatidylethanolamine, and lysophosphatidylcholines). In addition, this study revealed that glycerophospholipid metabolism, α-linolenic acid metabolism, and linoleic acid metabolism were related to obesity and obesity-associated diseases.Conclusion: These results can be used to better understand obesity and assess its risk, which will provide new ideas for treatment.Keywords: obesity, serum metabolomics, high-fat diet, UPLC-QTOF-MS technique

Zhiwei Zheng,1,&ast; Cui Yang,2,&ast; Chun Cai,1 Huide Zhu1 1Department of Pharmacy, Cancer Hospital of Shantou University Medical College, Shantou, 515041, People’s Republic of China; 2Department of Obstetrics and Gynecology Shantou Central Hospital, Shantou, 515000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huide ZhuDepartment of Pharmacy, Cancer Hospital of Shantou University Medical College, Shantou, 515041, People’s Republic of ChinaTel +86 075488555844-1140Fax +86 0754 88555844Email zhuhuide_2009@163.comBackground: Recent studies have revealed that the presence of systemic inflammation is associated with poor survival for esophageal squamous cell carcinoma. We aimed to investigate prognostic values of preoperative neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) in resectable esophageal squamous cell carcinoma.Methods: A cohort of 167 resectable ESCC patients was retrospectively reviewed between January 2017 and September 2020. The best cut-off value of NLR and PLR was selected by plotting the receiver operating characteristic curve. All reviewed patients were divided into high NLR/PLR or low NLR/PLR group to evaluate prognostic factors.Results: Among the 167 patients, 34 (20.36%) were women and 133 (79.64%) were men. The mean age was 62.64 ± 7.91 years, with an age range from 44 to 85 years. All patients were divided into low NLR (< 2.20) or high NLR (≥ 2.20) group (AUC=62.5% with the sensitivity of 61.8% and specificity 60.9%, P=0.025), low PLR (< 110) or high PLR (≥ 110) group (AUC=59.6% with the sensitivity of 82.4% and specificity 35.3%, P=0.083). High NLR and PLR were associated with a larger tumor diameter (P< 0.05), while high NLR was also associated with poor tumor classification (P=0.022). There was a positive correlation between NLR and PLR (r = 0.614, P < 0.001). High NLR and PLR were significantly associated with poor disease-free survival. Multivariate analyses identified NLR as a prognostic factor in resectable ESCC.Conclusion: The NLR and PLR predict disease-free survival in resectable esophageal squamous cell carcinoma.Keywords: neutrophil lymphocyte ratio, platelet lymphocyte ratio, disease-free survival, resectable esophageal squamous cell carcinoma

Wenmin Zeng,1 Guojing Liu,1 Qingxian Luan,1 Chunyu Yang,1 Shiyi Li,1 Xiaoqian Yu,1 Li Su2 1Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing, People’s Republic of China; 2Center of Medical and Health Analysis, Peking University, Beijing, People’s Republic of ChinaCorrespondence: Xiaoqian YuDepartment of Periodontology, Peking University School and Hospital of Stomatology, Beijing, 100081, People’s Republic of ChinaEmail Y_PK@163.comLi SuCenter of Medical and Health Analysis, Peking University, Beijing, 100191, People’s Republic of ChinaEmail lisu76@bjmu.edu.cnObjective: Periodontitis, one of the most prevalent chronic oral infectious diseases in humans, is induced by the breakdown in the balance between the biofilm and host immune system. Previous studies have shown the presence of large numbers of B cells in periodontitis lesions, implicating that B lymphocytes play a predominant role during the pathogenesis of periodontitis. This study aimed to investigate the role of all B cells in the initiation of periodontitis.Methods: Experimental periodontitis was induced in B cell-deficient (CD19Cre) mice and wild-type (WT) control mice by 5-0 silk ligation around the maxillary second molar. Four weeks after ligation, alveolar bone loss was determined by micro-computed tomography. The levels of inflammatory cytokines and receptor activator of NF-κB ligand (RANKL)/osteoprotegerin in periodontal lesions were analyzed using real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemistry. Lymphocyte populations in the cervical lymph nodes and spleen and among the peripheral blood mononuclear cells were detected by flow cytometry.Results: B-cell deficiency resulted in increased severity of alveolar bone loss in mouse experimental periodontitis, which was associated with increased osteoclast activity and upregulated RANKL expression in the periodontal lesions. In addition, gingiva cytokine expression profiles were shifted to T helper type 1 (Th1) and Th17 in the CD19Cre mice with ligature-induced periodontitis compared with WT mice. In addition, a reduced CD4+/CD8+ T cell ratio was observed in the CD19Cre mice.Conclusion: B-cell deficiency exacerbates the inflammation and alveolar bone loss in ligature-induced experimental periodontitis in mice, implicating that B cells may overall play a protective role in the initiation of periodontitis.Keywords: periodontitis, experimental periodontitis, alveolar bone loss, B lymphocytes

Jinrui Zhang,1 Huaicheng Wang,1 Weilong Suo,2 Zhizhou Li,1 Chunxu Yang3 1Department of Orthopedics, China-Japan Union Hospital of Jilin University, Changchun, 130033, People’s Republic of China; 2Key Laboratory of Applied Chemistry and Nanotechnology at Universities of Jilin Province, Changchun University of Science and Technology, Changchun, 130022, People’s Republic of China; 3Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People’s Republic of ChinaCorrespondence: Zhizhou Li; Chunxu Yang Email zhizhou@jlu.edu.cn; youer9youer@163.comPurpose: Radiotherapy (RT) is recommended as an extensive therapeutic regimen for cancer patients; however, cancer radio-resistance results from reduced oxygen levels (hypoxia) in the tumor microenvironment. Herein, we report a therapeutic strategy that greatly enhances the treatment effects of RT.Methods: Specifically, papaverine (ppv), an FDA-approved smooth muscle relaxant, was applied in the strategy. Ppv improved blood flow via vasodilation to deliver sufficient oxygen to the hypoxic solid tumor and further resulted in increased tumor penetration of the radiosensitizer, significantly enhancing the radiosensitization compared with no ppv treatment. Additionally, tantalum oxide nanospheres were cloaked in red blood cell membranes (TaOx@M) to achieve greater biocompatibility, non-immunogenicity, and a longer circulation time.Results: As a high-Z element, tantalum provides localized dose enhancement and thereby boosts the efficacy of RT. Vasodilation, the oxygenation of cancer cells, and the improved accumulation and retention of TaOx@M in the tumor region were verified in vivo. Furthermore, compared with RT alone, the combined vasodilation and nanosphere camouflaging strategy more efficiently suppressed the growth of K7M2 tumors in mice.Conclusion: The results of this study suggest that the integration of TaOx@M and ppv has excellent potential for improving RT efficacy.Keywords: radiotherapy, hypoxia, tantalum oxide, papaverine, vessel vasodilation

Yujin Choi,1 Ae-Ran Kim,2 Ji-Yoon Lee,3 Hae Sook Kim,3 Changsop Yang,1 Jae Kwang Kim,4 Younghoon Go,4 In Chul Jung3 1KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea; 2R&D Strategy Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea; 3Department of Neuropsychiatry, College of Korean Medicine, Daejeon University, Daejeon, Republic of Korea; 4KM Application Center, Korea Institute of Oriental Medicine, Daegu, Republic of KoreaCorrespondence: In Chul JungDepartment of Neuropsychiatry, College of Korean Medicine, Daejeon University, 75 Daedeok-daero 176beon-gil, Seo-gu, Daejeon, Republic of KoreaTel +82-42-470-9129Fax +82-42-470-9005Email npjeong@dju.krPurpose: The potential effects of herbal medicine for patients with cognitive disorders have been reported in various human and animal studies. This study aimed to explore the effect of herbal medicine treatment according to the Korean Medicine (KM) pattern identification for patients with mild cognitive impairment and early dementia.Patients and Methods: Twenty patients with mild cognitive impairment or mild dementia who planned to receive herbal medicine treatment were enrolled. Herbal formulae were prescribed based on the KM pattern for 12– 24 weeks. Seoul Neuropsychological Screening Battery II (SNSB-II) and Montreal Cognitive Assessment (MoCA) were assessed at the baseline, after 12 weeks, and after 24 weeks (Trial registration: cris.nih.go.kr, KCT0004799).Results: Herbal medicine products, including Yukmijihwang-tang, Samhwangsasim-tang, Palmul-tang, Banhasasim-tang, and Yukgunja-tang, were prescribed to the patients. Among the SNSB-II five cognitive function domains, the T scores for language, visuospatial function, memory, and frontal/executive function increased over time. The MoCA score also improved following the treatment (mean difference 4.23 [95% CI: 2.60, 5.86], p < 0.0001 at 12-week follow-up compared to the baseline). Considering the KM pattern scores, phlegm-dampness and fire-heat scores tended to improve after the treatment. No serious adverse events related to the intervention were reported.Conclusion: The potential effect of herbal medicine formulae products on improving cognitive functions in patients with cognitive impairment was observed. Further research is needed to objectify the KM pattern identification process and evaluate the KM pattern-related signs and symptoms.Keywords: mild cognitive impairment, mild dementia, herbal medicine, Korean medicine, traditional east Asian medicine, observational study

Yu He,1 Lina Guo,1 Yanjin Liu,2 Miao Wei,1 Yuanli Guo,1 Xiaofang Dong,1 Caixia Yang,1 Qing Zhou,3 Xiaoyu Lei,4 Gege Zhang,1 Mengyu Zhang4 1Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Nursing, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 3Department of Rehabilitation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 4College of Nursing, Zhengzhou University, Zhengzhou, People’s Republic of ChinaCorrespondence: Yanjin LiuDepartment of Nursing, The First Affiliated Hospital of Zhengzhou University, No. 1, Jianshe East Road, Erqi District, Zhengzhou, People’s Republic of ChinaTel +86 183 9206 1307Email lyjhlb@126.comPurpose: To examine the effectiveness of goal-based health management on health knowledge, health belief and health behavior in people at high risk of stroke.Patients and Methods: This is a two-armed and non-randomized controlled trial from May 31, 2020 to December 31, 2020. Participants were arranged to receive regular health care (n=126) or goal-based health management (n=126). The generalized estimation equation was used to analyze the changes in the participants’ health knowledge, health belief and health behavior at baseline (T0), 1-month (T1), 3-month (T3), and 6-month (T6).Results: A total of 243 participants completed the 6-month study, of which 123 were in the control group and 120 were in the intervention group. After receiving goal-based health management, participants’ health behavior (β= 27.154, p< 0.001), health knowledge (β= 10.504, p< 0.001) and health belief (β= 49.057, p< 0.001) scores increased significantly.Conclusion: Goal-based health management can effectively improve the health knowledge, health belief and health behavior of people at high risk of stroke. We recommend that nurses can provide goal-based health management for people at high risk of stroke with support from hospitals and family members of people at high risk of stroke.Keywords: stroke, prevention, goal setting theory, ecology of health

Chuandong Wang,1,2 Shengtao Lin,1,2 Xiaojuan Zhang,3,4 Changshun Yang,1,2 Weihua Li1 1Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, People’s Republic of China; 2Department of Surgical Oncology, Fujian Provincial Hospital, Fuzhou, 350001, People’s Republic of China; 3Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, 350001, People’s Republic of China; 4Department of Radiology, 900th Hospital Logistic Support Forces of PLA, Fuzhou, 350001, People’s Republic of ChinaCorrespondence: Weihua LiShengli Clinical Medical College of Fujian Medical University, No. 134, East Street, Fuzhou, 350001, People’s Republic of ChinaTel +86-181-06061193Fax +86-591-88217150Email liwh@fjmu.edu.cnPurpose: The benefits of laparoscopic gastrojejunostomy (LGJ) combined with conversion therapy for malignant gastric outlet obstruction (GOO) caused by incurable advanced gastric cancer (AGC) are unclear. This study aimed to examine the feasibility and efficacy of LGJ followed by enteral nutrition and conversion therapy in malignant GOO.Patients and Methods: The clinical outcomes for 66 patients with GOO due to incurable AGC were retrospectively evaluated. The patients were classified into multimodal therapy (LGJ, enteral nutrition, and chemotherapy, n = 35) and chemotherapy alone (n = 31) groups. Conversion surgery was defined as surgery aimed at R0 resection in initially incurable tumours.Results: Compared to the chemotherapy group, multimodal therapy patients had improved oral intake, more chemotherapy cycles, better nutritional indices, less sarcopenia, and improved quality of life (QOL) post-treatment. Conversion surgery was performed in 17 multimodal therapy patients, with no perioperative mortality, and R0 resection achieved in 15 patients (88.2%). The median survival time of multimodal therapy patients was 16.7 months, compared to 4.5 months for chemotherapy patients. Multimodal therapy patients with conversion surgery had significantly longer overall survival than those without surgery (44.2 vs 8.5 months, respectively, P< 0.001). Multivariate analysis identified multimodal therapy and improved or stable QOL as independent prognostic factors.Conclusion: Multimodal therapy was associated with better nutritional and metabolic status, a safely induced high conversion surgery rate with a high R0 resection rate, and a good prognosis. LGJ with enteral nutrition and conversion therapy may improve long-term survival in obstructive incurable AGC.Keywords: gastric cancer, gastrojejunostomy, conversion therapy, metabolism, enteral nutrition

Yingliang Wang,1,2,&ast; Chen Zhou,1,2,&ast; Jiacheng Liu,1,2 Qin Shi,1,2 Songjiang Huang,1,2 Chongtu Yang,1,2 Tongqiang Li,1,2 Yang Chen,1,2 Bin Xiong1,2 1Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Hubei Key Laboratory of Molecular Imaging, Wuhan, 430022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Xiong Email herr_xiong@126.comPurpose: In clinical practice, we found some of the patients who received transarterial chemoembolization (TACE) with molecular targeted agents (MTGs) plus immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC) had obvious liquefactive necrosis formation within the tumor and some even progressed to a liver abscess, which seems more frequent than patients who received other treatments. Thus, we aim to identify this condition and analyze the potential risk factors.Patients and Methods: Medical records of 72 consecutive patients with intermediate (BCLC B) and advanced (BCLC C) HCC who received TACE plus MTGs combined with (n=30) or without (n=42) ICIs were reviewed. Liquefactive necrosis formation was defined as the presence of obvious liquefactive necrosis within the tumor that required intervention.Results: The liquefactive necrosis rate was higher in the TACE+MTGs+ICIs group than in the TACE+MTGs group (30% vs 4.8%, P=0.006). Moreover, 18.2% (2/11) of the patients with liquefactive necrosis within the tumor had a bacterial infection. We then take the binary logistic regression analysis model to identify the predictors of liquefactive necrosis formation, and which showed the tumor size (P=0.006, OR=1.355, 95% CI: 1.090– 1.684), alpha-fetoprotein level (P=0.036, OR=6.745, 95% CI: 1.130– 40.262) and treatment modality (P=0.015, OR=11.717, 95% CI: 1.617– 84.887) were the independent risk factor for liquefactive necrosis formation within the tumor.Conclusion: Patients with HCC who received TACE combined with MTGs plus ICIs have increased liquefactive necrosis formation, and the larger tumor size and higher alpha-fetoprotein level were associated with more liquefactive necrosis formation within the tumor.Keywords: liver cancer, transarterial chemoembolization, molecular targeted agents, immune checkpoint inhibitors, liquefactive necrosis

Xiao-Xiao Yang,1,2 Chao Yang,2 Li Wang,2 Ying-Bo Zhou,2 Xiang Yuan,2 Nan Xiang,2 Yi-Ping Wang,3 Xiao-Mei Li1,2 1School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China; 2The First Affiliated Hospital of USTC, Department of Rheumatology and Immunology, University of Science and Technology of China, Hefei, People’s Republic of China; 3Westmead Institute for Medical Research, University of Sydney, Sdyney, NSW, 2145, AustraliaCorrespondence: Xiao-Mei Li Email lixiaomei@ustc.edu.cnObjective: Although extensive research has been carried out on CD4+T cells infiltrating the labial glands in patients with primary Sjögren’s Syndrome (pSS), it is still unclear how CD4+T cells remain in the labial gland tissue and develop into tissue resident cells. The aim of this study was to investigate the molecular mechanism by which CD4+T reside in labial glandular tissue of pSS patients.Methods: Lymphocyte infiltration in labial salivary glands (LSG) of pSS patients was detected by H&E staining. Expression of sphingosine-1-phosphate receptor 1 (S1PR1) in LSG was examined by Immunohistochemistry. Immunofluorescence analyses were utilized to detect the co-expression of CD4, CD69 and S1PR1 in T cells of LSG of pSS patients. Expression of gene S1pr1 in peripheral blood CD4+T cells of healthy controls and pSS patients was detected by quantitative real-time PCR (QPCR). QPCR was used to examine the expression of gene S1pr1, Klf2, and Cd69 in the CD4+T cells that were co-cultured in vitro with cytokines TNF-α, TGF-β, and IL-33.Results: S1PR1 was expressed in the infiltrating monocytes in LSG of pSS patients, and S1PR1 was weakly or even not expressed in cytoplasm of CD4+CD69+TRM cells of LSG in patients with pSS. Expression of gene S1pr1 in peripheral blood CD4+T cells of pSS patients was about three-fifths of that of healthy controls (P < 0.05). Expression of genes S1pr1 (P < 0.001) and Klf-2 (P < 0.001) was significantly decreased, and the expression of gene Cd69 (P < 0.05) was significantly increased in peripheral blood CD4+T cells of pSS patients co-cultured in vitro with cytokines TNF-α, TGF-β, and IL-33.Conclusion: Our study suggests that the decrease of S1pr1 gene expression may provide a molecular basis for promoting the tissue retention and development of CD4+CD69+TRM cells.Keywords: primary Sjogren’s syndrome, S1PR1, CD4+TRM

Yulan Yan,1,&ast; Chunmei Yang,1,&ast; Guidong Dai,1 Yu Zhang,1 Guojian Tu,1 Yuwei Li,2 Lu Yang,1 Jian Shu1 1Department of Radiology, The Affiliated Hospital of Southwest Medical University, and Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, Sichuan Province, People’s Republic of China; 2Department of Interventional Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lu Yang; Jian ShuDepartment of Radiology, The Affiliated Hospital of Southwest Medical University, and Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, Sichuan Province, People’s Republic of ChinaTel +86 830-2504762; +86 18980253083Email yangluchem@qq.com; shujiannc@163.comBackground: Development of new long-circulating contrast agents for computed tomography (CT) and magnetic resonance imaging (MRI) of different biological systems still remains a great challenge. Here, we report the synthesis of folic acid (FA)-targeted CuFeSe2 nano-contrast agent for CT and MRI imaging in vitro and in vivo.Methods and Results: In our study, CuFeSe2 was fabricated through a facile and green aqueous reaction and then further aminated through silanization. The amine-functionalized CuFeSe2-NH2 nanoparticles enable the covalent conjugation of folate-conjugated polyethylene glycol (FA-PEG-COOH) as a targeting ligand onto their surface, which could improve the dispersion and endue the targetability of nanoparticles, respectively. The formed multifunctional CuFeSe2-PEG-FA nanoparticles were characterized via different techniques, which exhibited outstanding dispersion, good biocompatibility and excellent FA-targeted capability. Meanwhile, the nanoparticles were quite safe in the given concentration range as confirmed by in vitro and in vivo toxicity assay. Importantly, CuFeSe2-PEG-FA nanoparticles were successfully applied in CT/MRI dual-modality imaging in vitro and in vivo, which showed a better imaging performance and targeted capability.Conclusion: Therefore, the constructed CuFeSe2-PEG-FA nanoparticles have a great potential as an efficient contrast agent for dual-modality imaging of different biological systems.Keywords: CuFeSe2 nanoparticles, magnetic resonance imaging, computed tomography imaging, dual-modality imaging, folic acid

Among kidney cancers, clear cell renal cell carcinoma (ccRCC) has the highest incidence rate in adults. The survival rate of patients diagnosed as having metastatic ccRCC drastically declines even with intensive treatment. We examined the efficacy of simvastatin, a lipid-lowering drug with reduced mevalonate synthesis, in ccRCC treatment. Simvastatin was found to reduce cell viability and increase autophagy induction and apoptosis. In addition, it reduced cell metastasis and lipid accumulation, the target proteins of which can be reversed through mevalonate supplementation. Moreover, simvastatin suppressed cholesterol synthesis and protein prenylation that is essential for RhoA activation. Simvastatin might also reduce cancer metastasis by suppressing the RhoA pathway. A gene set enrichment analysis (GSEA) of the human ccRCC GSE53757 data set revealed that the RhoA and lipogenesis pathways are activated. In simvastatin-treated ccRCC cells, although RhoA was upregulated, it was mainly restrained in the cytosolic fraction and concomitantly reduced Rho-associated protein kinase activity. RhoA upregulation might be a negative feedback effect owing to the loss of RhoA activity caused by simvastatin, which can be restored by mevalonate. RhoA inactivation by simvastatin was correlated with decreased cell metastasis in the transwell assay, which was mimicked in dominantly negative RhoA-overexpressing cells. Thus, owing to the increased RhoA activation and cell metastasis in the human ccRCC dataset analysis, simvastatin-mediated Rho inactivation might serve as a therapeutic target for ccRCC patients. Altogether, simvastatin suppressed the cell viability and metastasis of ccRCC cells; thus, it is a potentially effective ccRCC adjunct therapy after clinical validation for ccRCC treatment.

Yi Wang,1,&ast; Na Li,1,&ast; Di Tian,1,&ast; Chang-Wu Zhou,1 You-Hua Wang,2 Chun Yang,1 Meng-Su Zeng1 1Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, Shanghai, 200032, People’s Republic of China; 2Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Meng-Su Zeng; Chun YangDepartment of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, Xuhui District, Shanghai, 200032, People’s Republic of ChinaTel +86 13501922963; Tel +86 18702135336Email zhudahuaidan@yeah.net; dryangchun@hotmail.comIntroduction: N6-methyladenosine (m6A) modification and long non-coding RNAs (lncRNAs) play pivotal roles in the progression of hepatocellular carcinoma (HCC). However, how their interaction is involved in the prognostic value of HCC and immune checkpoint inhibitors (ICIs) therapy remains unclear.Methods: The RNA sequencing and clinical data of HCC patients were collected from TCGA database. The prognostic m6A-related lncRNAs were screened out with Pearson correlation test, univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) Cox regression. Patients with HCC were classified into 2 subtypes by consensus clustering. Survival analyses were performed to assess the prognostic value of different clusters and risk models. Potential tumor correlated biological pathways correlated with different clusters were explored through gene set enrichment analysis. We also identified the relationship of the risk model and clusters with response to immune checkpoint inhibitors (ICIs) therapy and tumor microenvironment (TME). Furthermore, the prognostic value of the 9 m6A-related lncRNAs was validated in the external cohort. Finally, the role of SNHG4 was explored by silencing and overexpression of SNHG4 through conducting proliferation, migration and invasion experiments.Results: Patients from 2 clusters and different risk groups based on m6A-related lncRNAs had significantly different clinicopathological characteristics and overall survival outcomes. Tumor-correlated biological pathways were found to be correlated with Cluster 2 through GSEA. Moreover, we found that patients from different clusters and risk groups expressed higher levels of immune checkpoint genes and had distinct TME and different responses for ICIs therapy. Prognostic value of this risk model was further confirmed in the external cohort. Finally, consistent with the discovery, SNHG4 played an oncogenic role in vitro.Conclusion: Our study demonstrated that the 9 m6A-related lncRNA signature may serve as a novel predictor in the prognosis of HCC and optimize (ICIs) therapy. SNHG4 plays an oncogenic role in HCC.Keywords: N6-methyladenosine, long non-coding RNAs, prognosis, immune checkpoints inhibitors therapy, hepatocellular carcinoma

Changwu Zhou,1,2,&ast; Xiaoyan Ni,2,&ast; Xin Lu,2 Yi Wang,2 Xianling Qian,2 Chun Yang,2 Mengsu Zeng1,2 1Shanghai Institute of Medical Imaging, Shanghai, People’s Republic of China; 2Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chun YangDepartment of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of ChinaTel +86 18702135336Email dryangchun@hotmail.comMengsu ZengShanghai Institute of Medical Imaging, Shanghai, People’s Republic of ChinaTel +86 13501922963Email zeng.mengsu@zs-hospital.sh.cnPurpose: To investigate the significance of MR features based on the Liver Imaging Reporting and Data System (LI-RADS ver. 2018) for identifying the expression of cytokeratin 19 (CK-19) in patients with combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) before surgery.Patients and Methods: The study enrolled 174 patients pathologically confirmed to have cHCC-CCA according to the 2019 WHO classification. The preoperative MR imaging features and clinicopathological findings were retrospectively evaluated and compared between the CK-19-positive and CK-19-negative cHCC-CCA groups.Results: One hundred seventy-four patients (mean age, males vs females: 56.6 ± 10.0 years vs 54.7 ± 14.2 years) were evaluated. The presence of mosaic architecture, targetoid appearance, cholangiectasis, hepatic capsule retraction, and corona enhancement was significantly higher in the CK-19-positive group (all p < 0.05), while nonrim arterial phase hyperenhancement (APHE) was more common in the CK-19-negative group (p = 0.04). The univariate analysis showed that hepatitis B virus infection, CEA > 5 ng/mL, tumor size, nonrim APHE, mosaic architecture, targetoid appearance, cholangiectasis, hepatic capsule retraction, and corona enhancement were significant risk factors for CK-19-positive cHCC-CCA (all p < 0.05). Unfortunately, the multivariate analysis revealed that only corona enhancement (OR = 2.359, p = 0.03) was an independent risk factor associated with CK-19-positive cHCC-CCA.Conclusion: Corona enhancement is significantly correlated with CK-19 positivity in patients with cHCC-CCA.Keywords: liver neoplasms, magnetic resonance imaging, cytokeratin 19

Xiaotong Song,1,2 Ning Sun,1– 3 Aixia Zhang,1– 3 Lei Lei,1 Xinrong Li,1 Zhifen Liu,1– 3 Yanfang Wang,1 Chunxia Yang,1– 3 Kerang Zhang1 1Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Laboratory of Artificial Intelligence Assisted Diagnosis and Treatment for Mental Disorder, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 3Department of Mental Health, Shanxi Medical University, Taiyuan, People’s Republic of ChinaCorrespondence: Chunxia Yang; Kerang ZhangDepartment of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of ChinaEmail ychunxia2000@163.com; atomsxmu@vip.163.comObjective: Although the pathogenesis of major depressive disorder (MDD) is still unclear, studies have shown that the dopaminergic system of depressed patients is defective, and that NR4A2 is an important transcription factor affecting the development and maintenance of dopaminergic neurons. As such, NR4A2 levels affected by NR4A2 single nucleotide polymorphisms (SNPs) may be associated with MDD. This study examined whether NR4A2 SNPs are associated with depressive symptoms and antidepressant efficacy.Methods: A total of 441 patients with first-episode depression were enrolled in this study. We analysed three SNPs of NR4A2, using the 17-item Hamilton Depression Rating Scale (HAM-D) and its four factors to obtain scores at baseline and at the end of 6 weeks. UNPHASED software was employed for quantitative character analysis, and SPSS software was adopted for antidepressant efficacy analysis.Results: Patients with rs12803-A exhibited higher scores of retardation symptoms. Patients with the rs834834-C allele and rs834834-CC genotype had higher retardation symptom scores. Patients with rs3769340 exhibited greater antidepressant efficacy.Conclusion: NR4A2 gene polymorphisms are associated with retardation symptoms, somatic symptoms (gastro-intestinal), anxiety-based somatic symptoms, insight, and weight loss in patients with MDD. Additionally, rs3769340 may be a predictor of antidepressant efficacy in patients with major depressive disorder.Keywords: major depressive disorder, NR4A2, single nucleotide polymorphism, antidepressant treatment

Liangchen Wang &ast;, Chenrui Wang &ast;, Hongmei Chen, Ying Chen, Juan Li, Li Xiao, Di Zhu, Caizhe Yang Department of Endocrinology, Air Force Medical Center, PLA, Beijing, 100142, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Caizhe YangDepartment of Endocrinology, Air Force Medical Center, PLA, Beijing, 100142, People’s Republic of ChinaTel/Fax +86 1066928242Email caizheyang06@outlook.comObjective: The present study explored the effectiveness of using a non-invasive skin-stretching device (NSSD) combined with negative-pressure wound therapy (NPWT) for the postoperative wound repair of diabetic foot (DF) gangrene.Methods: The treatment group in this study involved 42 patients with Wagner grade 3– 4 DF and undergone concomitant toe amputation or debridement, who were given NPWT combined with the use of a NSSD. The control group comprised 42 patients with similar trauma areas (± 20%) that were matched at a ratio of 1:1. Following surgery, these patients received NPWT combined with the use of conventional dressings. A comparison was made of the postoperative wound healing rates and wound healing times of the two groups, with Kaplan–Meier survival analysis being used to compare the healing rate over time.Results: The three-month wound healing rate was higher in the treatment group than in the control group (38 of 42 [90.5%] vs 25 of 42 [59.5%], p = 0.002), and the wound healing time was shorter in the treatment group (44 days [95% CI 40.0– 48.0]) than that in the control group (76 days [95% CI 63.0– 89.0], p = 0.000). Taking the end of the final NPWT as the starting point, the comparison of wound healing time revealed that this period was shorter in the treatment group than that in the control group and the difference was statistically significant (11 days [95% CI 9.0– 13.0] vs 42 days [95% CI 23.0–ND], p = 0.000).Conclusion: The use of the NPWT technique combined with a NSSD can shorten the wound healing time and improve the wound healing rate of DF gangrene patients during the postoperative wound repair period.Keywords: diabetic foot, negative-pressure wound therapy, wound healing, skin-stretching device

Lifen Zhu,1,&ast; Shufang Xie,1,2,&ast; Chen Yang,1,3,&ast; Nanni Hua,1,2 Yi Wu,4 Lei Wang,1 Wanmao Ni,1 Xiangmin Tong,1 Min Fei,5 Shibing Wang1 1Molecular diagnosis laboratory, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 2The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Clinical Medicine, Qingdao University, Qingdao, Shandong, People’s Republic of China; 4Phase I clinical research center, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 5Center of Health Management, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min FeiCenter of Health Management, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of ChinaEmail fammy2001@163.comShibing WangMolecular diagnosis laboratory, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of ChinaEmail wangshibing@hmc.edu.cnAbstract: Despite efforts to abrogate the severe threat to life posed by the profound malignancy of mature natural killer/T-cell lymphoma (NKTCL), therapeutic advances still require further investigation of its inherent regulatory biochemical processes. Next-generation sequencing (NGS) is an increasingly developing gene detection technique, which has been widely used in lymphoma genetic research in recent years. Targeted therapy based on the above studies has also generated a series of advances, making genetic mutation a new research hotspot in lymphoma. Advances in NKTCL-related gene mutations are reviewed in this paper.Keywords: mature T-and NK-cell lymphoma, gene mutation, next generation sequencing

Jing Han,&ast; Ruofei Jia,&ast; Chengzhi Yang,&ast; Zening Jin Department of Cardiology and Macrovascular Disease, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zening JinDepartment of Cardiology and Macrovascular Disease, Beijing Tiantan Hospital, No. 119 South Fourth Ring West Road, Beijing, 100070, People’s Republic of ChinaEmail jin_zening@ccmu.edu.cnAim: The coronavirus (COVID-19) outbreak in 2019 has negatively impacted the care of patients with other life-threatening diseases, including acute myocardial infarction (AMI). However, there is little published information concerning the depth of the impact on the clinical management and outcome following AMI.Methods: We enrolled patients with AMI who received urgent primary percutaneous coronary intervention at the Beijing Tiantan Hospital (Beijing, China) between December 1, 2019 and April 10, 2020. Patients were divided into 2 cohorts, the pre-COVID-19 group (from December 1, 2019 to January 31, 2020) and during-COVID-19 group (from February 1, 2020 to April 10, 2020) for analysis. The door-to-balloon (D to B) time, total hospitalization stay (days) and coronary care unit (CCU) hospitalization days were calculated. New York Heart Association heart functional class (NYHA class), re-hospitalization and death ratio in patients were assessed between the two cohorts.Results: A total of 148 AMI patients were enrolled in this study comprising 53 patients pre-COVID-19 group and 95 patients during-COVID-19 group. Patients with AMI during-COVID-19 group had longer symptom onset to hospital time (4.5 [2.0– 9.3] vs 3.0 [2.0– 5.0] hours, p = 0.013) and D to B time (96 [74– 119] vs 67 [52– 81] minutes, p < 0.001); the D to B time shortened during the study period. The two cohorts did not have significantly different number of hospitalization days, re-hospitalization rates, peak cTnI, BNP or death rates. For the one-year follow-up, the patients in the during-COVID-19 group were classified as NYHA class III–IV more frequently (9 [9.7%] vs 0 [0%], p=0.004).Conclusion: The COVID-19 pandemic significantly affected one measure of critical care of patients with AMI, NYHA classification, which may have resulted in increased medical expenses.Keywords: acute myocardial infarction, COVID-19 pandemic, in-hospital outcome, New York Heart Association heart functional class

Jieling Zhou,1 Keheng Xiang,2,3 Qian Cheng,1 Cao Yang4 1School of Tourism and Urban-Rural Planning, ZheJiang Gongshang University, Hangzhou, 310018, People’s Republic of China; 2School of Hotel and Tourism Management, The Hong Kong Polytechnic University, Kowloon, 999077, Hong Kong, Special Administrative Region of China; 3Zhejiang Technical Institute of Economics, Hangzhou, 310018, People’s Republic of China; 4China Tourism Academy, Beijing, 100008, People’s Republic of ChinaCorrespondence: Keheng Xiang Email keheng.xiang@connect.polyu.hkIntroduction: This study proposed a model based on Izard’s theory of differential emotions to examine the effects of heritage nostalgia on perceived authenticity towards tourist satisfaction and the moderation of self-congruity in Chinese niche tourism.Methods: We examined descriptive statistics to obtain an overview of the sample by using computer program SPSS 22. Then, for evaluation, partial least squares structural equation modelling (PLS-SEM) was employed as the appropriate statistical tool, and the statistical approach was implemented using the Smart PLS 3.0 computer program.Results: The results of partial least squares structural equation modelling showed that heritage nostalgia positively affects existential and object-based authenticity. Existential and object-based authenticity positively influences tourist satisfaction. Self-congruity positively moderates the relationship between existential or object-based authenticity and heritage nostalgia.Conclusion: The linkage mechanism of tourists’ psychology and behavior in heritage tourism has been explored, the internal mechanisms such as heritage nostalgia, tourists’ authenticity and tourists’ satisfaction have been discovered, and the internal mechanism of tourists’ consistency of psychology and behavior has also been explained.Keywords: heritage nostalgia, perceived authenticity, tourist satisfaction, self-congruity, niche tourism

Haijun Li,1,&ast; Dongbei Li,2,&ast; Fangman Chen,3 Chao Yang,3 Xiaogai Li,1 Yuan Zhang,1 Chunlan Hua,1 Xiaoxu Ma,1 Xin Zhao,1 Dan Shao,3 Yingshuai Wang,4 Liang Ming1 1Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China; 2Department of Hematology, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, 450000, People’s Republic of China; 3Institutes for Life Sciences, School of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou, 510630, People’s Republic of China; 4School of Life Science and Technology, Weifang Medical University, Weifang, Shandong, 261053, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingshuai WangSchool of Life Science and Technology, Weifang Medical University, Weifang, Shandong, 261053, People’s Republic of ChinaEmail yingshuaiwang1987@163.comLiang MingDepartment of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of ChinaEmail mingliang3072@163.comPurpose: Antibiotic-resistant bacteria are pathogens that have emerged as a serious public health risk. Thus, there is an urgent need to develop a new generation of anti-bacterial materials to kill antibiotic-resistant bacteria.Methods: Nanosilver-decorated mesoporous organosilica nanoparticles (Ag-MONs) were fabricated for co-delivery of gentamicin (GEN) and nanosilver. After investigating the glutathione (GSH)-responsive matrix degradation and controlled release of both GEN and silver ions, the anti-bacterial activities of Ag-MONs@GEN were systematically determined against several antibiotic-susceptible and antibiotic-resistant bacteria including Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis. Furthermore, the cytotoxic profiles of Ag-MONs@GEN were evaluated.Results: The GEN-loaded nanoplatform (Ag-MONs@GEN) showed glutathione-responsive matrix degradation, resulting in the simultaneous controlled release of GEN and silver ions. Ag-MONs@GEN exhibited excellent anti-bacterial activities than Ag-MONs and GEN alone via inducing ROS generation, especially enhancing synergetic effects against four antibiotic-resistant bacteria including Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis. Moreover, the IC50 values of Ag-MONs@GEN in L929 and HUVECs cells were 313.6 ± 15.9 and 295.7 ± 12.3 μg/mL, respectively, which were much higher than their corresponding minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values.Conclusion: Our study advanced the development of Ag-MONs@GEN for the synergistic and safe treatment of antibiotic-resistant bacteria.Keywords: mesoporous organosilica nanoparticles, nanosilver, gentamicin, GSH-responsive release, antibiotics-resistant bacteria

Huanhuan Chong,1,2 Yuda Gong,3 Xianpan Pan,4 Aie Liu,4 Lei Chen,4 Chun Yang,1 Mengsu Zeng1,2,5 1Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 2Shanghai Institute of Medical Imaging, Shanghai, 200032, People’s Republic of China; 3Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 4Shanghai United Imaging Intelligence Co., Ltd, Shanghai, 200232, People’s Republic of China; 5Department of Medical Imaging, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of ChinaCorrespondence: Mengsu Zeng; Chun YangDepartment of Radiology, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai, 200032, People’s Republic of ChinaTel +86-21-13501922963; +86-21-18702135336Email mengsu_zeng@163.com; dryangchun@hotmail.comBackground: Whether peritumoral dilation radiomics can excellently predict early recrudescence (≤ 2 years) in hepatocellular carcinoma (HCC) remains unclear.Methods: Between March 2012 and June 2018, 323 pathologically confirmed HCC patients without macrovascular invasion, who underwent liver resection and preoperative gadoxetate disodium (Gd-EOB-DTPA) MRI, were consecutively recruited into this study. Multivariate logistic regression identified independent clinicoradiologic predictors of 2-year recrudescence. Peritumoral dilation (tumor and peritumoral zones within 1cm) radiomics extracted features from 7-sequence images for modeling and achieved average but robust predictive performance through 5-fold cross validation. Independent clinicoradiologic predictors were then incorporated with the radiomics model for constructing a comprehensive nomogram. The predictive discrimination was quantified with the area under the receiver operating characteristic curve (AUC) and net reclassification improvement (NRI).Results: With the median recurrence-free survival (RFS) reaching 60.43 months, 28.2% (91/323) and 16.4% (53/323) patients suffered from early and delay relapse, respectively. Microvascular invasion, tumor size > 5 cm, alanine aminotransferase > 50 U/L, γ-glutamyltransferase > 60 U/L, prealbumin ≤ 250 mg/L, and peritumoral enhancement independently impaired 2-year RFS in the clinicoradiologic model with AUC of 0.694 (95% CI 0.628– 0.760). Nevertheless, these indexes were paucity of robustness (P > 0.05) when integrating with 38 most recurrence-related radiomics signatures for developing the comprehensive nomogram. The peritumoral dilation radiomics—the ultimate prediction model yielded satisfactory mean AUCs (training cohort: 0.939, 95% CI 0.908– 0.973; validation cohort: 0.842, 95% CI 0.736– 0.951) after 5-fold cross validation and fitted well with the actual relapse status in the calibration curve. Besides, our radiomics model obtained the best clinical net benefits, with significant improvements of NRI (35.9%-66.1%, P < 0.001) versus five clinical algorithms: the clinicoradiologic model, the tumor-node-metastasis classification, the Barcelona Clinic Liver Cancer stage, the preoperative and postoperative risks of Early Recurrence After Surgery for Liver tumor.Conclusion: Gd-EOB-DTPA MRI-based peritumoral dilation radiomics is a potential preoperative biomarker for early recurrence of HCC patients without macrovascular invasion.Keywords: gadoxetate disodium, hepatocellular carcinoma, radiomics, magnetic resonance imaging, neoplasm recurrence

Hao Zhang,1,* Linling Ju,2,* Peipei Hu,3,* Jun Ye,4 Canlin Yang,1 Junxing Huang1 1Department of Oncology, Taizhou People’s Hospital Affiliated to Nanjing University of Chinese Medicine, Taizhou, 225300, Jiangsu, People’s Republic of China; 2Nantong Institute of Liver Diseases, Nantong Third People’s Hospital, Nantong University, Nantong, 226000, Jiangsu, People’s Republic of China; 3Department of Pain Medicine, Nantong Hospital of Traditional Chinese Medicine, Nantong Hospital Affiliated to Nanjing University of Chinese Medicine, Nantong, 226000, Jiangsu, People’s Republic of China; 4Institute of Clinical Medicine, Taizhou People’s Hospital Affiliated to Nanjing University of Chinese Medicine, Taizhou, 225300, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Junxing HuangDepartment of Oncology, Taizhou People’s Hospital Affiliated to Nanjing University of Chinese Medicine, 366 Taihu Road, Taizhou, 225300, Jiangsu, People’s Republic of ChinaEmail hjxtz@sina.cnBackground: Circular RNAs (circRNAs) have recently been verified to have multiple biological functions and participate in diverse biological processes in different malignant tumors, including esophageal squamous cell carcinoma (ESCC). Nonetheless, the function of circular RNA 0014715 (hsa_circ_0014715, circ_0014715) in ESCC has not been described.Materials and Methods: We investigated clinical data from sixty-seven patients undergoing surgery for esophageal cancer. The clinical data were collected. And we analyzed the correlation between the clinical characteristics of these patients and the expression of circ_0014715. Besides, we explored the expression of circ_0014715 in ESCC cell lines. We used cell counting kit-8, colony formation, transwell assay, and flow cytometry to detect changes in cell proliferation, migration, apoptosis, and cell cycle progression.Results: We found that circ_0014715 was highly expressed in esophageal squamous cell carcinoma tissues and cell lines. The correlation analysis of clinicopathological features and gene expression revealed that high expression of circ_0014715 was related to nerve invasion, vascular invasion, more advanced tumor-node-metastasis (TNM) stage and poor differentiation grade. Receiver operating characteristic (ROC) curves revealed that circ_0014715 might have diagnostic value for ESCC. Experiments with cultured cells showed that knockdown of circ_0014715 significantly restrained cell proliferation, migration, invasion, wound healing and accelerated cell apoptosis. And cell cycle arrest at G2 phase was observed via flow cytometry. Overexpression of circ_0014715 caused the opposite effects. Collectively, these studies show that circ_0014715 is closely connected with the pathogenesis and development of ESCC. The excess expression of circ_0014715 may have promoting effects on the progression of esophageal cell carcinoma.Conclusion: Our finding revealed that circ_0014715 promoted tumor growth and cell proliferation. All of these suggest that targeting circ_0014715 has potential therapeutic value in the treatment of ESCC.Keywords: circular RNA 0014715, circular RNAs, esophageal squamous cell carcinoma, biological characteristics, cell proliferation

Di Niu,1,2,* Liang Li,3,* Hexi Du,1,2 Haoqiang Shi,1,2 Jun Zhou,1,2 Sheng Tai,1,2 Hanjiang Xu,1,2 Wei Chen,1,2 Cheng Yang,1,2 Chaozhao Liang1,2 1Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Institute of Urology and Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 3Department of Ultrasound, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Cheng Yang; Chaozhao LiangDepartment of Urology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, 230022, ChinaTel +86-18010865815; +86-13505604595Email chengyang_md@163.com; liang_chaozhao@ahmu.edu.cnPurpose: To investigate feasibility, repeatability and usefulness of contrast-enhanced ultrasonography (CEUS) in the assessment of kidney wound recovery after laparoscopic nephron-sparing surgery (LNSS) or robot-assisted nephron-sparing surgery (RANSS) and preliminarily research the clinical factors associated with the length of extravasation (LOE).Patients and Methods: From April 2019 to January 2020, 130 patients that underwent LNSS or RANSS in our hospital were included, and 90 patients (90/130) received CEUS examinations each one day from the postoperative day 1. The discovery of the cessation of contrast medium extravasation from the renal wound was the primary endpoint named “ultrasonic healing”, and LOE ranged from the day of surgery to “ultrasonic healing”. Patient, tumor, perioperative factors and LOE were collected. Univariate analysis and multivariate linear regression analysis were applied for the determination of factors associated with LOE.Results: The average postoperative LOE was 1.76 days (standard deviation, 1.115; 95% confidence interval: 1.52– 1.99). Ultrasonic healing within three days was observed in 95.6% patients (86/90). Univariable and multivariable analyses showed that R and A components in R.E.N.A.L. nephrometry score were associated with LOE. Anterior location and R component score of 2 (tumor size> 4cm) were related to longer LOE than posterior location and R score of 1 (tumor size< 4cm). The incidence of complications in patients with LOE over one day was higher than those with LOE of one day.Conclusion: CEUS was feasible, repeatable and useful in the assessment of kidney wound recovery. Tumor size and location were related to LOE after minimally invasive nephron-sparing surgery (MINSS). Length of stay after MINSS within three days might be relatively safe.Keywords: nephron-sparing surgery, minimally invasive, CEUS, wound healing

Cheng Yang,1 Han-Hua Zeng,1 Yan-Jia Du,1 Juan Huang,1 Qian-Yun Zhang,1 Kun Lin2 1Department of Pulmonary and Critical Care Medicine, Meizhou People’s Hospital, Meizhou, 5143031, Guangdong, People’s Republic of China; 2Department of Preventive Medicine, Shantou University Medical College, Shantou, 515041, Guangdong, People’s Republic of ChinaCorrespondence: Qian-Yun ZhangDepartment of Pulmonary and Critical Care Medicine, Meizhou People’s Hospital, No. 63 Huangtang Road, Meijiang District, Meizhou, 514031, People’s Republic of ChinaTel +86 07532202723Fax +86 07532204840Email zhqianyun@163.comKun LinDepartment of Preventive Medicine, Shantou University Medical College, No. 22 Xinling Road, Jinping District, Shantou, 515041, People’s Republic of ChinaTel +86 075488900445Fax +86 075482903637Email klin@stu.edu.cnBackground and Objective: Luminal mucus plugging in small airways is associated with lung function decline and death of patients with chronic obstructive pulmonary disease (COPD). However, little attention has been paid to the possible role of mucus in large airways in acute exacerbation of COPD (AECOPD). Therefore, this study aimed to explore the relationship between the luminal mucus score of large airways and other physiological parameters of severe AECOPD.Subjects and Methods: A total of 74 AECOPD inpatients were enrolled in this cross-sectional study. All patients underwent lung function tests and bronchoscopy, and their luminal mucus was observed and scored through bronchoscopy. Four questionnaires, including the St. George Respiratory Questionnaire (SGRQ), modified Medical Research Council dyspnea scale (mMRC), COPD Assessment Test (CAT) and Exacerbation of Chronic pulmonary disease Tool (EXACT), were used to assess health-related quality of life (HRQoL).Results: The luminal mucus score of large airways was significantly correlated with spirometry parameters and HRQoL score. Both mMRC grade and SGRQ score were significantly positively correlated with luminal mucus score (ρ=0.527, P< 0.001; ρ=0.441, P< 0.001, respectively). Forced expiratory flow at 25% to 75% of the FVC (FEF25%-75%) and FEV1% predicted, as functional measures reflecting small airway disease, were significantly negatively correlated with luminal mucus score (ρ=− 0.518, P< 0.001; ρ=− 0.498, P< 0.001, respectively). The stepwise multiple linear regression model suggested that mMRC grade and FEV1% predicted could predict luminal mucus score (R2=0.348, F=18.960, P< 0.001).Conclusion: For severe acute exacerbation of COPD, bronchoscopy-identified luminal mucus in large airways is associated with reduced lung function and worse health-related quality of life.Keywords: chronic obstructive pulmonary disease, acute exacerbation, luminal, mucus, bronchoscopy

Yiyun Weng,1,* Tian Zeng,2,3,* Honghao Huang,2,3,* Junli Ren,2,3 Jianing Wang,2,3 Chenguang Yang,2,3 Wenjing Pan,2,3 Jingyu Hu,2,3 Fangyue Sun,2,3 Xinbo Zhou,2,3 Haojie Qiu,2,3 Yufan Gao,2,3 Beibei Gao,4 Lifen Chi,3 Guangyong Chen3 1Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Department of Neurology, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 4Department of Internal Medicine, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guangyong ChenDepartment of Neurology, The Third Affiliated Hospital of Wenzhou Medical University, No. 108 Wansong Road, Wenzhou, 325000, Zhejiang, People’s Republic of ChinaTel +86-13777770788Fax +86-577-65623263Email gychen6@126.comLifen ChiDepartment of Neurology, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of ChinaEmail chilifenry@126.comBackground and Purpose: Systemic immune-inflammation index (SII), a novel inflammation index derived from counts of circulating platelets, neutrophils and lymphocytes, has been studied in developing incident cancer. However, the clinical value of SII in acute ischemic stroke (AIS) patients had not been further investigated. Therefore, we aimed to explore the association between SII and severity of stroke as well as 3-month outcome of AIS patients.Methods: A total of 216 AIS patients receiving intravenous thrombolysis (IVT) and 875 healthy controls (HCs) were retrospectively recruited. Blood samples were collected within 24h after admission. Severity of stroke was assessed by the National Institute of Health stroke scale (NIHSS) scores on admission and poor 3-month functional outcome was defined as Modified Rankin Scale (mRS) > 2.Results: SII levels in AIS patients were higher than in HCs. The cut-off value of SII is 545.14× 109/L. Patients with SII > 545.14× 109/L had higher NIHSS scores (median: 5 vs 9, p < 0.001), a positive correlation between SII and NIHSS was observed (rs = 0.305, p < 0.001). Multivariate logistic regression analyses showed that high SII was one of the independent risk factors for poor prognosis at 3 months of AIS patients (OR = 3.953, 95% CI = 1.702– 9.179, p = 0.001). The addition of SII to the conventional prognostic model improved the reclassification (but not discrimination) of the functional outcome (net reclassification index 39.3%, p = 0.007).Conclusion: SII is correlated with stroke severity at admission and can be a novel prognostic biomarker for AIS patients treated with IVT.Keywords: systemic immune-inflammation index, ischemic stroke, inflammation, prognosis

Wei-Dong Bao,1,* Qi Jia,2,* Tao Wang,2,3,* Yan Lou,2 Dong-Jie Jiang,2 Cheng Yang,2 Xinghai Yang,2 Quan Huang,2 Hai-Feng Wei,2 Jian-Ru Xiao1,2 1Department of Orthopedics, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China; 2Department of Orthopedic Oncology, Spinal Tumor Center, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, 200003, People’s Republic of China; 3Department of Orthopeadics, Second Affiliated Hospital of Anhui Medical University, Hefei, 230000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hai-Feng Wei; Jian-Ru XiaoDepartment of Orthopedic Oncology, Spine Tumor Center, Changzheng Hospital, Second Military Medical University, #415 Fengyang Road, Shanghai, 200003, People’s Republic of ChinaTel +86-21-81886843Email gkxjl999@163.com; spine925@126.comPurpose: To investigate risk factors for instrumentation failure (IF) in titanium (Ti) mesh reconstruction for thoracic and lumbar tumors.Patients and Methods: The clinical data of patients with thoracic or lumbar tumors who received Ti mesh reconstruction via the posterior approach in our hospital from 2013 to 2018 were analyzed retrospectively. The observation indexes included sex, age, BMI, the vertebra resection mode, the number of resected vertebral segments, application of bone cement, radiotherapy, chemotherapy, revision or primary surgery, and primary tumor metastasis. Correlations between these factors and IF were analyzed by Kaplan–Meier survival and logistics regression analyses.Results: The 178 patients included 108 males and 70 females with a mean age of 48.09± 16.21 (6– 78) years and a mean follow-up period of 51.18 (24– 90) months. The data showed that 17 patients (9.55%) were inflicted with IF, involving the thoracic vertebra in 11 cases, thoracolumbar vertebrae (T12–L1) in 2 cases, and lumbar vertebrae in 4 cases. The mean interval between surgery to IF was 35.18± 14.17 (14– 59) months. Univariate analysis showed that total vertebral body resection, the number of resected vertebral segments, radiotherapy and multiple tumor resection were potential factors for IF, while multivariate analysis showed that only total vertebral body resection, the number of resected vertebral segments and radiotherapy were independent factors.Conclusion: Total vertebra resection, the number of resected vertebral segments (≥ 2) and radiotherapy before and after operation were significant risk factors related to IF.Keywords: instrumentation failure, titanium mesh, thoracic and lumbar tumors

Yue Liu,1,* Chenguang Yang,2,* Wenyuan Qi,1 Zuowei Pei,2 Wei Xue,1 Huolan Zhu,2 Min Dong,2 Ying Guo,2 Duanduan Cong,1 Fang Wang2 1Clinical Trial Center, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Science, Beijing Key Laboratory of Drug Clinical Risk and Personalized Medication Evaluation, Beijing Hospital, Beijing, People’s Republic of China; 2Internal Medicine-Cardiovascular Department, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Science, Beijing Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fang Wang Email bjh_wangfang@163.comAbstract: Dabigatran is a novel direct oral anticoagulant agent, whose plasma concentration is closely related to bleeding risk. Genetic polymorphisms can affect the level of plasma dabigatran. The purpose of this study was to understand the relationship between dabigatran-related genes and the plasma level of dabigatran in healthy Chinese subjects after taking a single oral dose. This study was performed with a single-center, single-dose, randomized, open-label, and four-period crossover trial design under both fasting and fed conditions. A total of 106 eligible healthy subjects were enrolled in the study and 104 were genotyped. One-way analysis of variance (ANOVA) was used to compare pharmacokinetic parameters among different genotypes and linear regression was applied to explore the multiplicative interaction between variables. In this study, we found that the genotype frequencies of CES1 rs2244613 and CES1 rs8192935 were significantly different between Chinese and Caucasians, but the genotype frequencies of ABCB1 rs1045642 and ABCB1 rs4148738 were similar in both populations. CES1 rs8192935 were associated with the peak concentration of dabigatran. There was no significant gender difference in the exposure level of dabigatran. Furthermore, food significantly delayed the absorption of dabigatran but had little effect on Cmax and AUC0-∞.Keywords: anticoagulants, dabigatran, genetics, pharmacogenetics, CES1, ABCB1

Weisong Zhang,* Chaogang Yang,* Shuyi Wang, Zhenxian Xiang, Rongzhang Dou, Zaihuan Lin, Jinsen Zheng, Bin Xiong Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center, Wuhan, 430071, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bin Xiong Email binxiong1961@whu.edu.cnBackground: Detection of aberrant methylated DNA in the stool is an effective early screening method for colorectal cancer (CRC). Previously, reporters identified that syndecan-2 (SDC2) and tissue factor pathway inhibitor 2 (TFPI2) were aberrantly methylated in most CRC tissues. However, the combined diagnostic role of them remains undefined. Our research aimed at probing the role and efficiency of the methylation status of SDC2 and TFPI2 in CRC early screening by using bioinformatics analysis and clinical stool sample validation.Methods: The promoter and CpG site methylation levels of SDC2 and TFPI2 and their correlation with clinicopathological characteristics of CRC were analyzed using UALCAN, Methsurv, and Wanderer. UCSC Xena was used to perform survival analyses. LinkedOmics was used to do functional network analysis. DNA was isolated and purified from stool, and quantitative methylation-specific PCR (qMSP) was applied to detect methylatedSDC2 and TFPI2.Results: The results showed that promoter and most CpG site methylation levels of SDC2 and TFPI2 were significantly higher in CRC than in normal tissues. Moreover, SDC2 and TFPI2 methylation showed a positive correlation. Functional network analysis suggested that both methylated SDC2 and TFPI2 were involved in tumor cells’ metabolic programs. Besides, there was a higher positive integrated detection rate in CRC (n=61) with a sensitivity of 93.4% and in adenoma (Ade) (n=16) with a sensitivity of 81.3% than normal with a specificity of 94.3% in stool samples. What is more, integration of methylated SDC2 and TFPI2 showed a higher sensitivity and Youden index than a single gene in detecting Adeor CRC.Conclusion: Our data indicate that SDC2 and TFPI2 were hypermethylated in CRC, and integrated detection of methylated SDC2 and TFPI2 in stool has the potential to be an effective and noninvasive tool of CRC early screening.Keywords: DNA methylation, colorectal cancer, early detection, SDC2, TFPI2, stool

Zhongbo Han, Chunxia Yang, Qingfeng Wang, Meng Wang, Xi Li, Chao Zhang Department of Gastrointestinal Surgery, Zibo Central Hospital, Shandong University, Zibo, Shandong, People’s Republic of ChinaCorrespondence: Chao ZhangDepartment of Gastrointestinal Surgery, Zibo Central Hospital, Shandong University, 54 West Gongqingtuan Road, Zibo, Shandong, 255000, People’s Republic of ChinaTel +86 05333570671Fax +86 05333570672Email zhangchao20202021@163.comPurpose: High rate of perineal surgical site infection (SSI) is the most common complication following abdominoperineal resection (APR), especially for extralevator abdominoperineal excision (ELAPE). The purpose of this study was to investigate the effect of continuous negative pressure drainage combined with intermittent irrigation (CNPDCII) in the presacral space on the perineal SSI following laparoscopic ELAPE for low rectal cancer.Patients and Methods: The clinical data of 99 patients with low rectal cancer who underwent laparoscopic ELAPE surgery were retrospectively analyzed. Among the 99 patients, 46 patients received CNPDCII and 53 patients received conventional drainage in the presacral space after ELAPE. Self-made irrigation drainage tube: took a silicone drainage tube, cut 3 side holes at every 2cm intervals at the front end, and fixed a flexible tube of an intravenous needle at the front end of the silicone drainage tube. The conventional drainage tube or self-made irrigation drainage tube was placed in the presacral space and poked out from the inside of the ischial tuberosity. The incidence of SSI and other perioperative indicators between the two groups was compared within 30 days after surgery.Results: There was no statistical difference in clinicopathological features between the two groups of patients (p> 0.05). A statistically lower rate of SSI was found in CNPDCII group (17.4%, 8/46) than the conventional drainage group (35.8%, 19/53). The drainage tube retention time (7.8± 1.2 d VS 9.4± 1.6 d) and the postoperative hospital stay (9.7± 1.4 d VS 11.9± 2.3 d) in CNPDCII group were significantly shortened than the conventional drainage group. There was no statistical difference in operating theatre time and intraoperative blood loss between the two groups. Multivariate analysis confirmed that CNPDCII was an independent protective factor for SSI after ELAPE.Conclusion: CNPDCII can effectively reduce the incidence of SSI following laparoscopic ELAPE, which is simple, safe and effective.Keywords: low rectal cancer, extralevator abdominoperineal excision, negative pressure drainage, surgical site infection

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

Gang Zhu,1,* Shirong Yang,2,* Ronglin Wang,3,* Jie Lei,4 Peigang Ji,1 Jiancai Wang,1 Kai Tao,1 Chen Yang,1 Shunnan Ge,1 Liang Wang1 1Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China; 2Department of General Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China; 3Department of Oncology, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China; 4Department of Neurosurgery, Wuhan General Hospital of PLA, Wuhan, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liang Wang; Shunnan GeDepartment of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xinsi Road, Xi’an, 710038, People’s Republic of ChinaTel +86-29-84717851; Tel +86-29-84717824Email drwangliang@126.com; gesn8561@163.comPurpose: Glioblastoma multiforme (GBM) is an aggressive brain tumor with a rather short survival time. Mutation of p53 has been observed and reported to play critical roles in the progression of GBM. However, the pathological mechanisms are still unclear. This study was designed to identify the role of miR-154 in mediating the biological functions of p53 in glioblastoma multiforme.Methods: In the current study, the expression of miR-154 in GBM tissue samples and cell lines with wt-p53 or mutant p53 was evaluated. The functions of miR-154 in tumor migration, invasion and epithelial-mesenchymal transition were analyzed in vitro. A luciferase reporter assay was used to identify the target of miR-154.Results: We found that expression of miR-154 was much lower in patient tissues with mutant p53. Further study revealed that p53 was a transcription factor of miR-154 and that the R273H mutation led to its inactivation. In addition, overexpression of miR-154 remarkably suppressed cell migration, invasion and EMT in vitro and tumor growth in vivo. Moreover, TCF12 was proven to be a direct target of miR-154, and the tumor suppressive effect of miR-154 was reversed by TCF12.Conclusion: Overall, miR-154, which was regulated by wt-p53, inhibited migration, invasion and EMT of GBM cells by targeting TCF12, indicating that miR-154 may act as a biomarker and that the p53/miR-154/TCF12 pathway could be a potential therapeutic target for GBM.Keywords: glioblastoma, p53, microRNA, EMT, TCF12

Yaru Zou,1,2,* Dong Mei,1,* Jinjie Yuan,1,2 Jiaqi Han,1 Jiamin Xu,1 Ning Sun,1 Huan He,1 Changqing Yang,2 Libo Zhao1 1Clinical Research Center, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, People’s Republic of China; 2School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 211198, People’s Republic of China*These authors contributed equally to this workCorrespondence: Libo ZhaoClinical Research Center, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of ChinaTel +86-010-59617018Email libozhao2011@163.comBackground: Acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy in children. It requires a long and rigorous course of chemotherapy treatments. 6-Mercaptopurine (6-MP) is one of the primary drugs used in chemotherapy. Unfortunately, its efficacy has been limited due to its insolubility, poor bioavailability and serious adverse effects. To overcome these drawbacks, we constructed 6-mercaptopurine (6-MP)-loaded nanomedicines (6-MPNs) with biodegradable poly(lactide-co-glycolide) (PLGA) to enhance the anticancer efficacy of 6-MP.Methods: We prepared the 6-MPNs using a double-emulsion solvent evaporation method, characterizing them for the physicochemical properties. We then investigated the plasma, intestinal region and other organs in Sprague Dawley (SD) rats for pharmacokinetics. Additionally, we evaluated its anticancer efficacy in vitro on the human T leukemia cell line Jurkat and in vivo on the ALL model mice.Results: The 6-MPNs were spherical in shape with uniform particle size and high encapsulation efficiency. The in vitro release profile showed that 6-MPNs exhibited a burst release that a sustained release phase then followed. The apoptosis assay demonstrated that 6-MPNs could improve the in vitro cytotoxicity in Jurkat cells. Pharmacokinetics profiles revealed that 6-MPNs had improved oral bioavailability. Tissue distribution experiments indicated that 6-MPNs increased the duodenum absorption of 6-MP, at the same time having a low accumulation of the toxic metabolites of 6-MP. The in vivo pharmacodynamics study revealed that 6-MPNs could prolong the survival time of the ALL model mice. The prepared 6-MPNs, therefore, have superior properties in terms of anticancer efficacy against ALL with reduced systemic toxicity.Conclusion: Our nanomedicines provide a promising delivery strategy for 6-MP; they offer a simple preparation method and high significance for clinical translation.Keywords: 6-mercaptopurine, nanomedicines, Jurkat cells, acute lymphoblastic leukemia, ALL, bioavailability