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Xiaosu Guo,1– 4,* Huimin Shi,1,2,* Yuteng Sun,1 Yuan Xing,1– 3 Xin Guo,1– 3 Zhiyuan Shen,1– 3 Mengyi Zheng,1 Yaxin Zhang,1 Yicun Jia,1 Ye Li,1 Junqiang Bao,1,2 Shujuan Tian1– 3 1Department of Neurology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Neurology, Hebei Hospital, Xuanwu Hospital, Capital Medical University, Shijiazhuang, Hebei, People’s Republic of China; 3Neuromedical Technology Innovation Center of Hebei Province, Shijiazhuang, Hebei, People’s Republic of China; 4Brain Aging and Cognitive Neuroscience Laboratory of Hebei Province, Shijiazhuang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shujuan Tian; Junqiang Bao, Department of Neurology, The First hospital of Hebei Medical University, Shijiazhuang, Hebei, 050030, People’s Republic of China, Tel +86-0311-87156309, Email 57203005@hebmu.edu.cn; 57903004@hebmu.edu.cnPurpose: To summarize the clinical manifestations, laboratory findings, and magnetic resonance imaging (MRI) characteristics of anti-leucine-rich glioma-inactivated 1 (LGI1) antibody encephalitis (anti-LGI1 antibody encephalitis) and explore the electroencephalogram (EEG) features.Patients and Methods: We retrospectively analyzed the medical history of 16 patients diagnosed with anti-LGI1 antibody encephalitis at the First Hospital of Hebei Medical University from 2021 to 2023. EEGs of patients with anti-LGI1 antibody encephalitis and healthy individuals were analyzed. Based on Video-EEG signal analysis of EEG δ, θ, α, β frequency bands, weighted phase lag index values were calculated to form brain network matrices, studying differences in coherence between brain regions of patients with anti-LGI1 antibody encephalitis and healthy individuals.Results: Patients with anti-LGI1 antibody encephalitis often presented with subacute onset seizures and cognitive decline. Routine test of cerebrospinal fluid was mostly normal. Serum testing revealed hyponatremia in 62.50% of patients, along with positive serum antinuclear antibodies, decreased vitamin B12, and abnormal cytokines such as interleukin-6. Head MRI revealed abnormal lesions related to the disease in seven cases (43.75%), mainly located in the unilateral or bilateral frontal and temporal lobes of the hippocampus. The EEG mainly showed generalized and focal slow waves, sometimes with focal discharges. Brain network functional connectivity analysis found a significant weakening of functional connections in the frontal-temporal lobe in the δ and β frequency bands. Intravenous pulse corticosteroids and intravenous immunoglobulin are first-line immunotherapies for anti-LGI1 antibody-related encephalitis. The disease recovery and cognitive decline improved in most patients.Conclusion: Anti-LGI1 antibody encephalitis is characterized by seizures and cognitive dysfunction. Serum may show abnormalities in immune indicators such as cytokines. Head MRI mainly reveals abnormal signals in the frontal-temporal lobes and the hippocampus. EEG brain network connectivity analysis reveals characteristic weakening of functional connections in the frontal-temporal lobe in the δ and β frequency bands.Keywords: anti-LGI1 antibody encephalitis, epilepsy, electroencephalogram, brain network functional connectivity, immunotherapy

Meng Zheng,1 Chongfang Meng,2 Qi Zhang,3 Xiang Yan,1 Na Li1 1Dermatology Department of the First Affiliated Hospital of Kunming Medical University, Kunming, Yunan, People’s Republic of China; 2Department of Oncology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunan, People’s Republic of China; 3Nursing Department of Zhongshan Hospital Affiliated to Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Na Li, Dermatology Department of the First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Wuhua District, Kunming, Yunnan, People’s Republic of China, Email 4845878@qq.comObjective: This study aims to systematically search, screen, evaluate, and synthesize evidence related to discharge preparation for elderly chemotherapy patients, providing an evidence-based reference for implementing discharge preparation services for this demographic.Methods: Systematic searches were conducted on databases including BMJ Best Clinical Practice, JBI Library, UpToDate Clinical Advisor, Cochrane Library, and relevant guideline websites. The collected literature comprised thematic summaries, clinical practice guidelines, technical reports, expert consensus, and systematic reviews related to discharge preparation for elderly chemotherapy patients. Relevant evaluation tools were selected based on the type of literature to assess methodological quality, and the evidence was extracted, summarized, and organized.Results: Fifteen pieces of evidence were selected according to inclusion and exclusion criteria, including one clinical decision, two expert consensuses, six systematic reviews, two meta-analyses, and four guidelines. Twenty-nine pieces of evidence were summarized across four domains: assessment, planning, implementation, and evaluation.Conclusion: The summarized evidence provides a reliable basis for implementing evidence-based discharge preparation services for elderly chemotherapy patients, laying a foundation for future clinical practice applications. Based on the evidence content and relevant literature, this paper explores the screening and evaluation tools applicable for use in clinical practice.Keywords: elderly, chemotherapy, discharge preparation, evidence-based nursing, evidence synthesis, review

Yali Yuan,1,2,* Hairong Hu,1,* Zhongmei Sun,3,* Wenting Wang,4 Zhibin Wang,1 Mengyu Zheng,5 Yunqi Xing,1 Wenji Zhang,1 Muyuan Wang,1 Xinyu Lu,1 Yitong Li,1 Chengtao Liang,1 Zhengdao Lin,1 Chune Xie,6 Junxiang Li,1 Tangyou Mao1 1Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Hebei North University, Zhangjiakou, Hebei, People’s Republic of China; 3Tianjin Nankai Hospital, Tianjin, People’s Republic of China; 4Beitaipingzhuang Community Health Service Center, Beijing, People’s Republic of China; 5King’s College, London, UK; 6Shenzhen Bao’an Traditional Chinese Medicine Hospital, Shenzhen, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tangyou Mao; Junxiang Li, Email maotangyouqun@126.com; lijunxiang1226@163.comBackground: Inflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disease that lacks effective treatments. Qingchang Wenzhong Decoction (QCWZD) is a clinically effective herbal prescription that has been proven to attenuate intestinal inflammation in IBD. However, its molecular mechanism of action has not been clearly elucidated.Purpose: We aimed to probe the mechanism of QCWZD for the treatment of IBD.Methods: The dextran sulfate sodium (DSS)-induced mouse model of IBD was used to identify the molecular targets involved in the mechanism of action of QCWZD. Metagenomics sequencing was utilized to analyze the differences in gut microbiota and the functional consequences of these changes. Network pharmacology combined with RNA sequencing (RNA-seq) were employed to predict the molecular targets and mechanism of action of QCWZD, and were validated through in vivo experiments.Results: Our results demonstrated that QCWZD treatment alleviated intestinal inflammation and accelerated intestinal mucosal healing that involved restoration of microbial homeostasis. This hypothesis was supported by the results of bacterial metagenomics sequencing that showed attenuation of gut dysbiosis by QCWZD treatment, especially the depletion of the pathogenic bacterial genus Bacteroides, while increasing the beneficial microorganism Akkermansia muciniphila that led to altered bacterial gene functions, such as metabolic regulation. Network pharmacology and RNA-seq analyses showed that Th17 cell differentiation plays an important role in QCWZD-based treatment of IBD. This was confirmed by in vivo experiments showing a marked decrease in the percentage of CD3+CD4+IL-17+ (Th17) cells. Furthermore, our results also showed that the key factors associated with Th17 cell differentiation (IL-17, NF-κB, TNF-α and IL-6) in the colon were significantly reduced in QCWZD-treated colitis mice.Conclusion: QCWZD exerted beneficial effects in the treatment of IBD by modulating microbial homeostasis while inhibiting Th17 cell differentiation and its associated pathways, providing a novel and promising therapeutic strategy for the treatment of IBD. Keywords: intestinal bowel disease, Qingchang Wenzhong Decoction, microbial homeostasis, Th17 cells, mucosal immunity

Dan Ye,1 Ding Ding,1 Ling-Yun Pan,2 Qing Zhao,3 Long Chen,2 Min Zheng,1 Tong Zhang,1 Bing-Liang Ma1 1Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 3Department of Pharmacy, Jing’an District Zhabei Central Hospital, Shanghai, 200070, People’s Republic of ChinaCorrespondence: Bing-Liang Ma; Tong Zhang, Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, No. 1200 Cai Lun Road, Pudong New District, Shanghai, 201203, People’s Republic of China, Tel +86-021-5132 2199 ; +86-021-5132 2318, Fax +86-021-5132 2192, Email bingliang.ma@hotmail.com; zhangtongshutcm@hotmail.comPurpose: Docetaxel (DTX) is a valuable anti-tumor chemotherapy drug with limited oral bioavailability. This study aims to develop an effective oral delivery system for DTX using natural nanoparticles (Nnps) derived from Coptidis Rhizoma extract.Methods: DTX-loaded self-assembled nanoparticles (Nnps-DTX) were created using an optimized heat-induction strategy. Nnps-DTX’s shape, size, Zeta potential, and in vitro stability were all carefully examined. Additionally, the study investigated the encapsulation efficiency, loading capacity, crystal form, and intermolecular interactions of DTX in Nnps-DTX. Subsequently, the solubility, release, cellular uptake, metabolic stability, and preclinical pharmacokinetics of DTX in Nnps-DTX were systematically evaluated. Finally, the cytotoxicity of Nnps-DTX was assessed in three tumor cell lines.Results: Nnps-DTX was spherical in shape, 138.6 ± 8.2 nm in size, with a Zeta potential of − 20.8 ± 0.6 mV, a DTX encapsulation efficiency of 77.6 ± 8.5%, and a DTX loading capacity of 6.8 ± 1.9%. Hydrogen bonds, hydrophobic interactions, and electrostatic interactions were involved in the formation of Nnps-DTX. DTX within Nnps-DTX was in an amorphous form, resulting in enhanced solubility (23.3 times) and release compared to free DTX. Following oral treatment, the mice in the Nnps-DTX group had DTX peak concentrations 8.8, 23.4, 44.6, and 5.7 times higher in their portal vein, systemic circulation, liver, and lungs than the mice in the DTX group. Experiments performed in Caco-2 cells demonstrated a significant increase in DTX uptake by Nnps-DTX compared to free DTX, which was significantly inhibited by indomethacin, an inhibitor of caveolae-mediated endocytosis. Furthermore, compared to DTX, DTX in Nnps-DTX demonstrated better metabolic stability in liver microsomes. Notably, Nnps-DTX significantly reduced the viability of MCF-7, HCT116, and HepG2 cells.Conclusion: The novel self-assembled nanoparticles considerably enhanced the cellular absorption, solubility, release, metabolic stability, and pharmacokinetics of oral DTX and demonstrated strong cytotoxicity against tumor cell lines. Keywords: docetaxel, oral delivery, self-assembly, nanoparticles, pharmacokinetics, coptidis rhizoma

Junjie Cheng,1,* Yuan Yuan,1,* Jinmeng Li,1 Ruoying Zhang,1 Xudong Fan,1 Zhirou Xu,2 Huirong Lin,3 Xinjun Cai,1 Mingfeng Zheng4 1Department of Pharmacy, Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, People’s Republic of China; 2Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, People’s Republic of China; 3Department of Pharmacy, Taizhou Cancer Hospital, Taizhou, People’s Republic of China; 4Department of Orthopaedics, Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mingfeng Zheng; Xinjun Cai, Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, Zhejiang Province, 310003, People’s Republic of China, Email zmfyxz3@163.com; zjtcmcxj@zcmu.edu.cnPurpose: Previous studies have indicated that the development of severe adverse events is associated with linezolid peak concentration (Cmax), but the factors affecting linezolid Cmax and evidences on therapeutic drug monitoring to anticipate toxicity in drug-resistant tuberculosis (DR-TB) patients have not been clarified clearly. This study aimed to explore the factors influencing linezolid Cmax and investigate the association between linezolid concentration and hematological toxicity.Patients and Methods: This study included patients with drug-resistant tuberculosis treated with linezolid from January 2022 to September 2023. We analyzed the factors affecting linezolid Cmax using chi-squared and binary logistic regression. The diagnostic utility of linezolid Cmax in predicting hematological toxicity was evaluated using receiver operating characteristic (ROC) analysis.Results: A total of 76 patients were enrolled in the study. 63.20% met the standard rates for linezolid Cmax. Age (P=0.036), weight (P=0.0016), and creatinine clearance (P=0.0223) significantly correlated with the Cmax. Hematological toxicity was observed in 46.05% (35/76) of patients, characterized by thrombocytopenia (31.58%, 24/76), anemia (6.58%, 5/76), and leukopenia (21.05%, 16/76). ROC curve analysis confirmed the predictive value of linezolid Cmax for thrombocytopenia with an area under curve of 0.728.Conclusion: Suboptimal linezolid Cmax was prevalent among patients with DR-TB, with age, weight, and renal function emerging as influential factors. Elevated linezolid Cmax increases the risk of thrombocytopenia. Meticulous monitoring of linezolid Cmax is imperative during anti-DR-TB therapy to tailor treatment and mitigate hematological toxicity.Keywords: linezolid, therapeutic drug monitoring, influencing factors, hematological toxicity

Jing-Jing Huang,1,&ast; Lin Jia,2,3,&ast; Qiao-Jun Zhang,4 Hao-Hong Li,5 Da-Li Zheng,2 Ming Zheng3 1Second Department of Dental Implant, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, 350001, People’s Republic of China; 2Fujian Key Laboratory of Oral Diseases, Fujian Biological Materials Engineering and Technology Center of Stomatology, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian, 350004, People’s Republic of China; 3Department of Prosthodontics, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, 350001, People’s Republic of China; 4Zhongshan Hospital Affiliated to Xiamen University, Xiamen, 361000, People’s Republic of China; 5College of Chemistry, Fuzhou University, Fuzhou, Fujian, 350116, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ming Zheng, Department of Prosthodontics, School and Hospital of Stomatology, Fujian Medical University, 246 Yangqiao Middle Road, Fuzhou, 350001, People’s Republic of China, Tel +86-591-83736431, Email zmdentist@163.com Da-Li Zheng, Fujian Key Laboratory of Oral Diseases, School and Hospital of Stomatology, Fujian Medical University, 88 Jiaotong Road, Fuzhou, 350004, People’s Republic of China, Tel +86-591-83720599, Email dalizheng@fjmu.edu.cnPurpose: To investigate the inhibition of Streptococcus mutans (S.mutans) and its biofilm by AgBr-nanoparticles (NP) @CTMAB (cetyltrimethyl-ammonium bromide) and evaluate the changes in Polymethyl methacrylate (PMMA)’s surface roughness (Ra), microhardness, and flexural strength during prolonged immersion in AgBr-NP@CTMAB for application in the denture cleaning industry.Patients and Methods: The antibacterial activity of AgBr-NP@CTMAB against S.mutans was measured colony formation assay, OD600 and laser confocal microscopy. Changes in the specimens’ values for surface roughness, microhardness, and flexural strength (MPa) were measured after immersion solutions for 180 or 360 days.Results: The AgBr-NP@CTMAB solution exhibited a robust antibacterial effect on planktonic S. mutans, with a minimum bactericidal concentration of 5 μg/mL. The 10 μg/mL AgBr-NP@CTMAB solution efficiently inhibited S. mutans biofilm formation. (2) No significant difference in surface roughness after immersion in AgBr-NP@CTMAB (10 μg/mL and 20 μg/mL) comparing with distilled water (P > 0.05) and Polident had significantly higher than distilled water (P < 0.05). There was a significant decrease in the surface hardness of the PMMA specimens that were immersed in the Polident compared with those in distilled water (P < 0.05). While, no significant differences in surface hardness after immersion in the AgBr-NP@CTMAB (P > 0.05). The result of flexural strength suggested that there was no statistically significant difference (P < 0.05) between AgBr-NP@CTMAB as well as Polident and water.Conclusion: AgBrNP@CTMAB can efficiently inhibit the growth of plankton S.mutans and biofilm formation, without affecting the flexural strength, microhardness, or surface roughness of PMMA. Therefore, AgBrNP@CTMAB holds promise as a new denture cleaning agent.Keywords: AgBr-NP@CTMAB, S.mutans, polymethyl methacrylate, denture cleanser, biofilm

Wenxiu An,1,2 Lijie Bao,1,2 Chenyu Wang,1,2 Mingxin Zheng,3 Yan Zhao1,2 1Cancer Hospital of Dalian University of Technology (Liaoning Cancer Hospital & Institute), Shenyang City, Liaoning Province, People’s Republic of China; 2Liaoning Provincial Key Laboratory of Interdisciplinary Research on Gastrointestinal Tumor Combining Medicine with Engineering, Shenyang City, Liaoning Province, People’s Republic of China; 3Neusoft Research of Intelligent Healthcare Technology, Co. Ltd, Shenyang City, Liaoning Province, People’s Republic of ChinaCorrespondence: Yan Zhao, Liaoning Cancer Hospital & Institute, No. 44 Xiaoheyan Road, Dadong District, Shenyang City, Liaoning Province, 110042, People’s Republic of China, Tel +86-24-81916608, Email zhaoyan@cancerhosp-ln-cmu.comBackground: Gastric cancer (GC) has a poor prognosis, particularly in patients with liver metastasis (LM). This study aims to identify relevant factors associated with the occurrence of LM in GC patients and factors influencing the prognosis of gastric cancer with liver metastasis (GCLM) patients, in addition to developing diagnostic and prognostic nomograms specifically.Patients and Methods: Overall, 6184 training data were from the Surveillance, Epidemiology, and End Results (SEER) database from 2011 to 2015. 1527 validation data were from our hospital between January 2018 and December 2022. Logistic regression was used to identify the risk factors associated with the occurrence of LM in GC patients, Cox regression was used to confirm the prognostic factors of GCLM patients. Two nomogram models were established to predict the risk and overall survival (OS) of patients with GCLM. The performance of the two models was evaluated using the area under the curve (AUC), concordance index (C-index), and calibration curves.Results: A nomogram included five independent factors from multivariate logistic regression: sex, lymph node removal, chemotherapy, T stage and N stage were constructed to calculate the possibility of LM. Internal and external verifications of AUC were 0.786 and 0.885, respectively. The other nomogram included four independent factors from multivariate Cox regression: surgery at primary site, surgery at other site, chemotherapy, and N stage were constructed to predict OS. C-index for internal and external validations were 0.714 and 0.702, respectively, and the calibration curves demonstrated the robust discriminative ability of the models.Conclusion: Based on the SEER database and validation data, we defined effective nomogram models to predict risk and OS in patients with GCLM. They have important value in clinical decision-making and personalized treatment.Keywords: gastric cancer, liver metastasis, nomogram, SEER database, external validation

Jiali Liu,1,&ast; Yuanqiang Zhu,1,&ast; Yingjuan Chang,1,&ast; Ziliang Xu,1 Chen Wang,1 Pengpeng Zhang,1 Shuangxin Li,1 Wenxuan Yang,1 Rui An,1,2 Didi Wen,1 Jian Xu,1,2 Minwen Zheng1 1Department of Radiology, Xijing Hospital, Air Force Medical University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Interventional Surgery Center, Xijing Hospital, Air Force Medical University, Xi’an, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Minwen Zheng, Department of Radiology, Xijing Hospital, Air Force Medical University, 127&num; Changle West Road, Xi’an, Shaanxi, 710032, People’s Republic of China, Tel +86-29-84775421, Fax +86-29-84773732, Email zhengmw2007@163.com Jian Xu, Department of Interventional Surgery Center, Xijing Hospital, Air Force Medical University, 127&num; Changle West Road, Xi’an, Shaanxi, 710032, People’s Republic of China, Tel +86-29-84775299, Fax +86-29-84775299, Email xujian771939@163.comPurpose: While prior research has highlighted a significant association between sleep characteristics and angina pectoris (AP) incidence, the link between sleep efficiency (SE) and angina remains unexplored. This study seeks to elucidate the relationship between AP and objectively quantified SE.Patients and Methods: We examined a cohort of 2990 participants (1320 males and 1670 females; mean age 63.69 ± 13.2 years) from the Sleep Heart Health Study. The main exposure variable was SE, as determined by baseline home polysomnography, while the primary outcome was the first incidence of angina pectoris (AP) during the period between the baseline polysomnography and the end of follow-up. A multivariate Cox regression model was utilized, controlling for factors such as age, gender, BMI, smoking and alcohol consumption habits, diabetes, hypertension, sleep duration, triglycerides, cholesterol, high-density lipoprotein, apnea-hypopnea index, nocturnal oxygen saturation, to analyze the relationship between SE and AP.Results: During an average follow-up of 11 years, 284 patients developed AP. The unadjusted Kaplan-Meier analysis identified the 2nd quartile of SE as having the lowest AP risk. The multivariate Cox proportional hazards model demonstrated a higher risk of AP in quartile 1 (HR, 1.679; 95% CI, 1.109– 2.542; P < 0.014) and quartile 3 (HR, 1.503; 95% CI, 1.037– 2.179; P < 0.031), compared to quartile 2 of SE. Upon stratified analysis, this relationship was particularly pronounced in hypertensive individuals.Conclusion: Our results highlight the critical role of optimal sleep efficiency in mitigating the risk of angina pectoris, especially among hypertensive individuals.Keywords: sleep efficiency, angina pectoris, polysomnography, cardiovascular risk, sleep heart health study, hypertension

Chen Chen,1,2,&ast; Meng Zheng,1,2,&ast; Junli Zhu1,2,&ast; 1School of Public Health, Capital Medical University, Beijing, People’s Republic of China; 2Research Center for Capital Health Management and Policy, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junli Zhu, School of Public Health, Capital Medical University & Research Center for Capital Health Management and Policy, No. 10, Xitoutiao, Youanmen Wai, Fengtai District, Beijing, 100069, People’s Republic of China, Tel +86 18701515093, Fax +86 01083911578, Email smallying@126.comBackground: The impact of fiscal decentralization on health outcomes still has not reached a consensus, and studies conducted in the context of the new round of fiscal and taxation system reform are even less available. China’s fiscal decentralization system has its own special characteristics, so it is necessary to analyze the impact of fiscal decentralization on health outcomes before and after the new round of fiscal and taxation system reform in China.Methods: Panel data from 2007 to 2019 were obtained through China’s Health Statistics Yearbook and China’s Statistical Yearbook. The effects of fiscal decentralization on health outcomes before and after the reform are explored separately by SYS-GMM, which introduce a dynamical model with a lag period of the explained variables. The Hansen test is used to determine excessive identification. The AR(2) is used to determine whether the residual term of the differential equation has a second-order serial correlation.Results: Fiscal decentralization consistently had a negative impact on health outcomes, yet government health expenditures did not mediate the impact of fiscal decentralization on health outcomes. Fiscal decentralization had a positive effect on per capita government health expenditure before the new reforms, yet had a negative effect on the percentage of government health expenditures, both before and after the new reform.Conclusion: China’s fiscal decentralization has caused local governments to pay insufficient attention to the construction of people’s livelihoods, and the problem of insufficient government investment in health has not been improved. The new round of fiscal and taxation system reform has not reversed this situation either. It is recommended to adjust the incentive system for local officials, include medical and health in the evaluation indicators of local governments, optimize the structure of government expenditure, and improve the efficiency of the use of government health expenditure.Keywords: fiscal decentralization, government health expenditure, health outcomes, China’s new round of fiscal and tax reforms

Qiang Wei,1,&ast; Dong Lv,1,2,&ast; Shuna Fu,3,&ast; Dongmei Zhu,1 Minxiao Zheng,1 Si Chen,3 Shihang Zhen4 1Department of Psychology, Jianghan University, WuHan, People’s Republic of China; 2School of Business Administration, Huaqiao University, Quanzhou, People’s Republic of China; 3Department of Applied Psychology & Human Development, University of Toronto, Toronto, Canada; 4College of Economics and Management, Northwest Agriculture and Forestry University, XianYang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiang Wei, Department of Psychology, Jianghan University, WuHan, HuBei, People’s Republic of China, Tel +86-18671454618, Email weiqiang@jhun.edu.cn Dong Lv, School of Business Administration, Huaqiao University, Quanzhou, FuJian, People’s Republic of China, Tel +86-15798002728, Email lvdong@stu.hqu.edu.cnBackground: Tourism consumption is a topic with heated debates in tourism research, and pricing tourism products is a crucial task for tourism managers. Different types of tourist attractions offer different experiences to tourists, which affect their price perceptions and purchase decisions.Methods: This study combined questionnaires and event-related potentials (ERPs) measures to explore the magnitude of psychological conflict and the degree of emotional arousal that consumers experience when faced with different prices of goods in different scenic types.Results: The questionnaire results showed that attraction type influenced consumers’ price perceptions and that consumers were willing to pay higher prices for products in attractions. The ERP results implied that in the early stage of cognition, attraction type did not affect consumers’ perceptual processing, while price information attracted consumers’ cognitive attention. In the late stage of cognition, attraction type, and price information jointly influenced consumers’ decision-making, and consumers tended to accept high prices of products in entertainment attractions and cultural attractions, but consumers were more sensitive to the price of products in cultural attractions and less tolerant to price increases.Conclusion: The study elucidated how price information influenced consumers’ purchase decisions of tourism products at different stages of the dual-process theory, which can assist tourism managers in devising different pricing strategies and positioning strategies based on the attributes of attractions, to enhance product sales and revenues. This would further the vision of the World Tourism Organization (UNWTO) of “tourism fostering economic development”.Keywords: tourist attractions, price perception, neuromarketing, event-related potentials, P2, LPP

Lei Sun,1,&ast; Qi Zhao,2,&ast; Yanning Wang,3,&ast; Yongsheng Wang,2 Ming Zheng,2 Xuansheng Ding,4 Liyun Miao2 1School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University Nanjing Drum Tower Hospital, Nanjing, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China; 3Clinical Stem Cell Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China; 4School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liyun Miao, Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, People’s Republic of China, Tel +86 13813920964, Fax +86-25-68183333, Email liyunmiao462@163.comPurpose: Anlotinib is widely used in the clinical treatment of non-small cell lung cancer (NSCLC), alone or in combination with other anticancer drugs. The aim of this study was to investigate the real-world efficacy and safety of anlotinib-containing regimens.Patients and Methods: Confirmed advanced NSCLC patients who had received anlotinib alone or in combination were enrolled. An overall analysis of the efficacy and safety of anlotinib was performed in all patients, and then subgroup analysis was used to further compare the efficacy between anlotinib monotherapy and combination therapy. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were ADR, ORR, and DCR.Results: A total of 240 patients were included. The overall median PFS was 8.5 months (95% confidence interval [CI]: 7.1– 9.9 months). Anlotinib treatment regimens (monotherapy or combination therapy) and whether they received previous antiangiogenesis were associated with PFS. Anlotinib plus immunotherapy achieved longer PFS than anlotinib monotherapy (median PFS: 10.5 vs 6.5 months, p=0.007). Stratification analysis showed the PFS of anlotinib plus immunotherapy was significantly longer in male, adenocarcinoma,

Yan Jin,1,2 Mengmeng Zheng,1 Shiyi He,1 Meiping Chen,1 Chao Cao1 1Department of Respiratory and Critical Care Medicine, Key Laboratory of Respiratory Disease of Ningbo, The First Affiliated Hospital of Ningbo University, Ningbo, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Municipal Hospital Affiliated to Taizhou University, Taizhou, People’s Republic of ChinaCorrespondence: Chao Cao, Email caocdoctor@163.comAbstract: The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), commonly known as COVID-19, poses significant risk to human health worldwide. The primary strategy for controlling the disease is through vaccination. However, there is an urgent need to establish confidence in the safety of global vaccination efforts, particularly among populations with allergies, as evidence on the adverse effects of SARS-CoV-2 vaccines in this group remains limited. To address this gap, our study aimed to evaluate the safety of inactivated SARS-CoV-2 vaccines in individuals with food and/or drug allergies. The study enrolled a total of 150 participants, who were subjected to a series of questionnaires to evaluate local and systemic reactions within 7 days after each dose. The results revealed that the most prevalent adverse reactions were pain at the injection site (30%) and fatigue (16%) following the initial vaccination. Notably, the incidence of both local and systemic adverse reactions decreased after the second vaccination, which was unexpected. The food allergy and drug allergy subgroups exhibited a similar phenomenon. Furthermore, the incidence of adverse events observed in this study was consistent with the range reported in Phase III clinical trials of inactivated SARS-CoV-2 vaccines. Our findings suggest that individuals with pre-existing food and/or drug allergies have a favorable safety profile when receiving inactivated SARS-CoV-2 vaccination.Keywords: inactivated SARS-CoV-2 vaccine, COVID-19, food allergy, drug allergy, vaccination safety

Jiecheng Lin,1,2,&ast; Na Huang,2,&ast; Mingjuan Li,2 Mengyuan Zheng,2 Zhuoxiang Wang,2 Xiaojuan Zhang,2 Huan Gao,2 Yunzhe Lao,2 Jie Zhang,2 Baoyue Ding2 1School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 214122, People’s Republic of China; 2Department of Pharmaceutics, Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics, College of Medicine, Jiaxing University, Jiaxing, 314001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Baoyue Ding; Jie Zhang, Department of Pharmaceutics, Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics, College of Medicine, Jiaxing University, No. 118 Jiahang Road, Jiaxing, Zhejiang Province, 314001, People’s Republic of China, Tel/Fax +86-0573-83643808, Email lena_310@163.com; zhangjiepharm@zjxu.edu.cnPurpose: Malignant melanoma (MM), the most lethal skin cancer, is highly invasive and metastatic. These qualities are related to not only genetic mutations in MM itself but also the interaction of MM cells with the immune system and microenvironment. This study aimed to construct a combined immunotherapy and gene therapy drug delivery system for the effective treatment of MM.Methods: Mature dendritic cell (mDC) exosomes (mDexos) with immune induction functions were used as carriers. BRAF siRNA (siBRAF) with the ability to silence mutated BRAF in MM was encapsulated in mDexos by electroporation to construct a biomimetic nanosystem for the codelivery of immunotherapy and gene therapy drugs (siBRAF-mDexos) to the MM microenvironment. Then, we investigated the nanosystem’s serum stability and biocompatibility, uptake efficiency in mouse melanoma cells (B16-F10 cells), cytotoxicity against B16-F10 cells and inhibitory effect on BRAF expression. Furthermore, we evaluated its antimelanoma activity and safety in vivo.Results: SiBRAF-mDexos were nanosized. Compared to siBRAF, siBRAF-mDexos displayed significantly increased serum stability, biocompatibility, uptake efficiency in B16-F10 cells, and cytotoxicity to B16-F10 melanoma cells; they also had a significantly greater inhibitory effect on BRAF expression and induced T-lymphocyte proliferation. Moreover, compared with siBRAF, siBRAF-mDexos showed significantly enhanced anti-MM activity and a high level of safety in vivo.Conclusion: The study suggests that the siBRAF-mDexo biomimetic drug codelivery system can be used to effectively treat MM, which provides a new strategy for combined gene therapy and immunotherapy for MM.Keywords: malignant melanoma, dendritic cell exosomes, BRAF siRNA, immunotherapy, gene therapy

Guanghao Wu,1,&ast; Guanye Yu,2,&ast; Meiling Zheng,3,&ast; Wenhui Peng,2 Lei Li4 1School of Materials Science and Engineering, Beijing Institute of Technology, Beijing, 100081, People’s Republic of China; 2Department of Cardiology, Shanghai Tenth People’s Hospital, Tongji University, School of Medicine, Shanghai, 200072, People’s Republic of China; 3Dongzhimen Hospital Beijing University of Chinese Medicine, Beijing, 101121, People’s Republic of China; 4National Clinical Research Center for Obstetric & Gynecologic Diseases, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Li, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Shuai Fu Yuan, Eastern District, Beijing, 100730, People’s Republic of China, Tel +8613426328126, Fax +86 10 69158100, Email lilei64@pumch.cn Guanghao Wu, School of Materials Science and Engineering, Beijing Institute of Technology, Beijing, 100081, People’s Republic of China, Email bitwgh@126.comAbstract: Atherosclerosis (AS) is a chronic inflammatory disease, which may lead to high morbidity and mortality. Currently, the clinical treatment strategy for AS is administering drugs and performing surgery. However, advanced therapy strategies are urgently required because of the deficient therapeutic effects of current managements. Increased number of energy conversion-based organic or inorganic materials has been used in cancer and other major disease treatments, bringing hope to patients with the development of nanomedicine and materials. These treatment strategies employ specific nanomaterials with specific own physiochemical properties (external stimuli: light or ultrasound) to promote foam cell apoptosis and cholesterol efflux. Based on the pathological characteristics of vulnerable plaques, energy conversion-based nano-therapy has attracted increasing attention in the field of anti-atherosclerosis. Therefore, this review focuses on recent advances in energy conversion-based treatments. In addition to summarizing the therapeutic effects of various techniques, the regulated pathological processes are highlighted. Finally, the challenges and prospects for further development of dynamic treatment for AS are discussed.Keywords: atherosclerosis, nanomaterial, physiochemical, reactive oxygen species, energy conversion, therapy

Zheng Yuan,1 Lixia Gao,2 Meijie Zheng,3 Xiaobo Ye,4 Sujuan Sun1 1Department of Nursing, Hebei General Hospital, Shijiazhuang, 050000, People’s Republic of China; 2Department of Cardiovascular Medicine for the Elderly, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 3Department of Gastroenterology, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 4Second Department of Thoracic Surgery, Hebei General Hospital, Shijiazhuang, People’s Republic of ChinaCorrespondence: Sujuan Sun, Department of Nursing, Hebei General Hospital, No. 348, Heping West Road, Shijiazhuang, Hebei, People’s Republic of China, Tel +86-311-85988114, Email sunsujuan1818@163.comObjective: To explore the effect of multimodal health education combined with a feedback method in perioperative patients with lung cancer.Methods: A total of 200 lung cancer patients were divided into the observation group and the control group. The observation group adopted the multimodal health education combined with the feedback method, and the control group adopted the conventional health education model. The postoperative extubation time, length of hospital stay, time to first leaving the bed, postoperative exercise compliance, emotional-distress index and patient satisfaction were compared between the two groups.Results: The postoperative extubation time (2.80 ± 1.03 days), the emotional-distress index (8.26 ± 3.01) and the time to first leaving the bed (23.74 ± 11.87 h) were all lower in the observation group than in the control group, with a statistically significant difference (P < 0.05). The postoperative exercise compliance (49.69 ± 3.60) and patient satisfaction (98.32 ± 1.66) values were higher in the observation group than in the control group, with statistically significant differences (P < 0.05).Conclusion: Multimodal health education combined with the feedback method can improve the postoperative exercise compliance of lung cancer patients, reduce their postoperative rehabilitation time and improve their postoperative psychological state and satisfaction, which is in line with the concept of promoting the enhanced recovery of lung cancer patients.Keywords: lung cancer, enhanced recovery after surgery, feedback method, multimodal health education

Li Chen,1,&ast; Qin Chen,2 Xueping Chen,3,4 Pengli Zhu,5 Meinan Chen,6 Wei Wang,7,8 Shandong Ye,7,8 Mao Zheng7,8,&ast; 1Department of Endocrinology, The Third Affiliated Hospital of Anhui Medical University (The First People’s Hospital of Hefei City), Hefei, People’s Republic of China; 2Department of Pharmacy, Taihe County People’s Hospital, Taihe, People’s Republic of China; 3Department of Pharmacy, Hefei Fourth People’s Hospital, Hefei, People’s Republic of China; 4Psychopharmacology Research Laboratory, Anhui Mental Health Center and Department of Pharmacy, Affiliated Psychological Hospital of Anhui Medical University, Hefei, People’s Republic of China; 5Department of Pharmacy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China; 6Ethics Committee on Medical Research, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China; 7Department of Endocrinology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China; 8Laboratory of Diabetes, Department of Endocrinology, The First Affiliated Hospital of USTC, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shandong Ye; Mao Zheng, Department of Endocrinology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, People’s Republic of China, Tel +86 189 6378 9135 ; +86 13215603125, Fax +86 0551-62283524, Email ysd196406@163.com; zhengmao1999@foxmail.comPurpose: Given the importance of metformin, reasonable utilization is essential. We designed a cross-sectional survey on physicians’ attitude and clinical application of metformin in Anhui Province, China.Methods: The survey was distributed via an electronic questionnaire among endocrinologists and general practitioners. Seven representative questions were used to evaluate professional levels.Results: Among the 477 valid responses, 72.75% of the respondents preferred to prescribe metformin extended-release, while only 34.38% of them would prescribe metformin extended-release at the correct frequency. More than half of the respondents thought that estimated glomerular filtration rate ˂ 45 mL/min/1.73 m² should be the contraindication of metformin prescription. Less than 10% of the physicians selected correct responses for two questions regarding metformin usage and contrast agent. Physicians with higher levels of hospital grades, education background and professional titles as well as working in general hospitals and in the Department of Endocrinology achieved high scores (P˂0.05). Logistic regression showed that department was an independent predictor for high scores.Conclusion: Physicians, especially non-endocrinologists, are not at a professional level for prescribing metformin. Physicians should be highly vigilant in terms of standardized prescription for metformin. The guidelines or consensuses about diabetes care for physicians should be promoted.Keywords: metformin, professional knowledge, clinical application, diabetes mellitus, physicians

Li Chen,1,&ast; Zhangxiang Zhu,1,&ast; Shandong Ye,2,3 Mao Zheng2,3,&ast; 1Department of Endocrinology, the Third Affiliated Hospital of Anhui Medical University (The First People’s Hospital of Hefei), Hefei, People’s Republic of China; 2Department of Endocrinology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China; 3Laboratory of Diabetes, Department of Endocrinology, the First Affiliated Hospital of USTC, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Chen, Department of Endocrinology, the Third Affiliated Hospital of Anhui Medical University (The First People’s Hospital of Hefei), Hefei, Anhui, 230001, People’s Republic of China, Tel +86 13855169122, Fax +86 055162283524, Email daisy1982@foxmail.com Mao Zheng, Department of Endocrinology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, People’s Republic of China, Tel +86 13215603125, Fax +86 0551-62283524, Email zhengmao1999@foxmail.comPurpose: A retrospective study was designed to evaluate whether the serum uric acid to serum creatinine ratio (SUA/SCr) can be used as an indicator of diabetic kidney disease (DKD) and macroangiopathy in patients with type 2 diabetes mellitus (T2DM).Patients and Methods: We screened 2227 patients diagnosed with T2DM, and 450 patients were finally included. They were assigned to three groups based on the tertile of SUA/SCr (Group Tertile 1, Tertile 2, Tertile 3). Demographic information and biochemical parameters were collected from Electronic Patient Record (EPR).Results: The estimated glomerular filtration rate (eGFR) values were lowest in Group Tertile 1 and highest in Group Tertile 3 (P < 0.05). There was no significant difference in urinary albumin creatinine ratio (UACR) among the three groups (P > 0.05). Partial correlation analyses revealed that SUA/SCr levels were significantly and positively correlated with eGFR, SUA, body mass index, gamma-glutamyl transpeptidase, alanine transaminase, triglycerides, C-peptide, high-density lipoprotein cholesterol and fatty liver, while they were negatively correlated with SCr, blood urea nitrogen, cystatin-c, age, male sex, DM duration and hypertension history (P < 0.05). Logistic regression analysis revealed that SUA/SCr was an independent risk factor for eGFR < 60 mL/min/1.73 m² (P < 0.05). The ROC curve showed that the cutoff value of SUA/SCr for the identification of eGFR < 60 mL/min/1.73 m² was 3.434. In patients with normal UACR, SUA/SCr levels of patients with eGFR < 60 mL/min/1.73 m² were lower than those with eGFR ≥ 60 mL/min/1.73 m² (P < 0.05). Regression analysis did not show SUA/SCr associate to macrovascular disease after adjusting for confounding factors.Conclusion: SUA/SCr is an independent risk factor for DKD in patients with T2DM and may be helpful for identifying normoalbuminuric DKD.Keywords: diabetes mellitus, glomerular filtration rate, serum uric acid, creatinine

Tianyu Jin,1,&ast; Danyu Chen,2,&ast; Zhicai Chen,3 Dujin Feng,4 Manqi Zheng,5 Peng Wang,6 Chao Xu6 1Department of Neurology, The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2Department of Neurology, Tongxiang First People’s Hospital, Tongxiang, People’s Republic of China; 3Department of Neurology, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, People’s Republic of China; 4Department of Laboratory, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, People’s Republic of China; 5Department of Psychiatry, The Third Hospital of Quzhou, Quzhou, People’s Republic of China; 6Center for Rehabilitation Medicine, Department of Neurology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chao Xu; Peng Wang, Center for Rehabilitation Medicine, Department of Neurology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College. No.158 Shangtang Road, Hangzhou, People’s Republic of China, 310014, Email raymond1202@126.com; 1979wwww@163.comBackground: We aimed to investigate the association of post-thrombolytic D-dimer elevation with symptomatic intracranial hemorrhage (sICH) and functional outcome in AIS patients receiving intravenous thrombolysis.Methods: We retrospectively reviewed our database for patients with AIS who received intravenous thrombolysis between August 2018 and December 2021. ΔD-dimer was calculated as follow-up D-dimer minus baseline D-dimer. Poor functional outcome was defined as 3 months modified Rankin score (mRS) 3– 6. sICH was defined as cerebral hemorrhagic transformation in combination with clinical deterioration of National Institutes of Health Stroke Scale (NIHSS) score ≥ 4 points at 24 hours. Binary logistic regression analysis was used to investigate the association of post-thrombolytic D-dimer parameters with sICH and poor functional outcome. The receiver operating characteristic (ROC) curve derived optimal cut-off of different D-dimer parameters was determined at the maximal Youden’s Index.Results: A total of 325 patients were finally included. After controlling for clinical variables, follow-up D-dimer level (OR 1.230; 95% CI 1.119 to 1.351; P < 0.001) and ΔD-dimer (OR 1.347; 95% CI 1.165 to 1.559; P < 0.001) were independently associated with poor functional outcome. Additionally, follow-up D-dimer level (OR 1.095; 95% CI 1.009 to 1.188; P = 0.030) was independently related to sICH. The optimal cut-off value of follow-up D-dimer level for predicting sICH was 4185 μg/L (area under the curve 0.760; sensitivity 76.0%; specificity 81.3%); and the optimal cut-off value of follow-up D-dimer level and ΔD-dimer as a predictor for poor functional outcome was projected to be 3838 μg/L and 2190 μg/L, which yielded a sensitivity and a specificity of 62.3%, 84.5% and 73.8%, 85.2%, respectively.Conclusion: Elevated follow-up D-dimer levels are associated with sICH and poor functional outcome in AIS patients following intravenous rt-PA. Moreover, post-thrombolytic D-dimer elevation, measured by ΔD-dimer, was a better predictive biomarker for long-term outcome at 3 months.Keywords: acute ischemic stroke, D-dimer, intravenous thrombolysis, hemorrhagic transformation, outcome

Zike Sheng,1,&ast; Junjie Li,2,&ast; Tingting Chen,3 Yan Zhu,4 Xueping Yu,5 Xiuhua He,5 Yijuan Zheng,5 Cuiping Ma,6 Minghui Zheng,5 Peiyun Wang,1 Ziqiang Li,1 Yumin Xu,7 Qing Xie,1 Zhijun Su,5 Sumei Chen5 1Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Pharmacy, The First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou, People’s Republic of China; 4Clinical Laboratory, The First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou, People’s Republic of China; 5Department of Infectious Diseases, The First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou, People’s Republic of China; 6Department of Infection Control, The First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou, People’s Republic of China; 7Department of Infection Control, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhijun Su; Sumei Chen, Department of Infectious Diseases, The First Hospital of Quanzhou Affiliated to Fujian Medical University, Licheng District, Quanzhou, People’s Republic of China, Tel +86-595-22277011 ; +86-595-22277173, Fax +86-595-222781, Email su2366@sina.com; chensm561119190@sina.comPurpose: Hypervirulent Klebsiella pneumoniae (hvKP) is emerging globally and can cause various infections. This study aimed to investigate the clinical and microbiological characteristics of bloodstream infection (BSI) caused by hvKP.Patients and Methods: The clinical data of hospitalized patients with K. pneumoniae BSI were retrospectively analyzed. The K. pneumoniae strains were collected and re-identified, and antimicrobial susceptibility testing was performed using the broth microdilution method. Capsular serotypes and virulence genes were detected using polymerase chain reaction, and hvKP was defined as aerobactin positive. Molecular typing was done by multilocus sequence typing. The hvKP and classic K. pneumoniae (cKP) subgroups were compared.Results: Of the 66 nonrepetitive BSI K. pneumoniae strains included, 29 (43.9%) were hvKP. In these BSI hvKP strains, salmochelin and yersiniabactin accounted for 86.2% and 72.4%, respectively. The prevalence of rmpA, iroBCD cluster, ybtS, clbA, and allS was 89.7%, 86.2%, 72.4%, 51.7%, and 41.4%, respectively, which were all significantly different between the hvKP and cKP subgroups. Serotypes K1 and K2 were strongly associated with hypervirulence (P < 0.05). Nineteen sequence types were scattered in the 29 hvKP strains, and the most common was ST23 (24.1%). None of the hvKP strains were carbapenem resistant. Compared with cKP, hvKP was more capable of developing a liver abscess. However, the 30-day mortality rate was lower (13.8% vs 21.6%) in the hvKP subgroup than in the cKP subgroup.Conclusion: This study demonstrated a high proportion of hvKP in BSI K. pneumoniae, most of which were RmpA and siderophore producing, and of multiclonal origin.Keywords: capsular serotypes, hypervirulence, infection, mortality, sequence type

Xingyue Zeng,1,&ast; Songsong Lu,1,&ast; Meng Li,1 Mohan Zheng,2 Tianci Liu,1 Rui Kang,1 Lijuan Xu,3 Qinzhu Xu,1 Ying Song,1 Chen Liu1 1Department of Clinical Laboratory, Peking University People’s Hospital, Beijing, People’s Republic of China; 2School of Basic Medical Sciences, Peking University Health Science Centre, Beijing, People’s Republic of China; 3Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Centre, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chen Liu, Department of Clinical Laboratory, Peking University People’s Hospital, 11# Xizhimen South Street, Beijing, 100044, People’s Republic of China, Tel +86 10 88326203, Fax +86 10 88326300, Email liuchen-best@pku.edu.cnBackground: Follicular T helper (TFH) and follicular regulatory T (TFR) cells play important roles in humoral immunity. Nevertheless, their significance in rheumatoid arthritis (RA) pathogenesis has not been fully elucidated. As an important treatment strategy, the effect of inflammatory factor-neutralizing antibodies on TFH and TFR in RA remains unclear.Methods: We used the collagen-induced arthritis (CIA) mouse model to illustrate the quantity and functional changes in TFH and TFR cells. The changes of plasmablast, TFH and TFR cells in the spleen and peripheral blood of CIA mice were analyzed by flow cytometry. The levels of TFH and TFR and their functional subsets in the spleen after anti-inflammatory antibody treatment were analyzed and compared. The functional changes of TFH and TFR in CIA mice before and after treatment were detected by in vitro culture experiments.Results: Plasmablast levels were increased in CIA spleen and peripheral blood and both TFH and TFR cell levels were upregulated. TFH and TFR cells were decreased significantly after the anti-inflammatory antibody treatment. TIGIT+ and TIGIT+CD226− TFH cells in CIA mouse spleen were elevated and PD-1 and ICOS expression on spleen TFH and TFR cells was increased. Both the ability of TFH cells to secrete IL-21 and aid B cells and the ability of TFR cells to secrete IL-10 and inhibit TFH cells were enhanced in the CIA mice. After antibody treatment, the cell subsets and functions were recovered.Conclusion: Germinal center TFH and TFR cells were increased and their functions were enhanced. With inflammatory factor-neutralizing antibody treatment, TFH and TFR subsets and their functions returned to normal. These findings provide important information on the dynamics of humoral immune-related cell subsets in RA and the effects of treatment on them.Keywords: TFH, TFR, collagen-induced arthritis, rheumatoid arthritis, inflammatory cytokines

Jin Cao,&ast; Mingxue Zheng,&ast; Zhenyan Sun, Zhiye Li, Xueyong Qi, Song Shen School of Pharmacy, Jiangsu University, Zhenjiang, 212013, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Song Shen; Xueyong Qi, School of Pharmacy, Jiangsu University, 301 Xuefu Road, 212013, Zhenjiang, Jiangsu, People’s Republic of China, Tel +86-0511-88795939, Email jsda.shensong@163.com; qixyemail@163.comBackground: Sonodynamic therapy (SDT) and its synergistic cancer therapy derivatives, such as combined chemotherapy-SDT (chemo-SDT), are promising approaches for tumor treatment. However, the main drawbacks restricting their applications are hypoxia in tumors and the reducing microenvironment or high glutathione (GSH) levels.Methods: In this study, a hybrid metal MnO2 was deposited onto nanoparticles fabricated using poly(lactic-co-glycolic acid) (PLGA), carrying docetaxel (DTX) and the sonosensitizer hematoporphyrin monomethyl ether (HMME) (PHD@MnO2) via a one-step flash nanoprecipitation (FNP) method. Characterization and in vitro and in vivo experiments were conducted to explore the chemo-SDT effect of PHD@MnO2 and evaluate the synergetic antitumor treatment of this nanosystem.Results: When low-power ultrasound is applied, the acquired PHD@MnO2, whether in solution or in MCF-7 cells, generated ROS more efficiently than other groups without MnO2 or those treated via monotherapy. Specifically, GSH-depletion was observed when MnO2 was introduced into the system. PHD@MnO2 presented good biocompatibility and biosafety in vitro and in vivo. These results indicated that the PHD@MnO2 nanoparticles overcame hypoxia in tumor tissue and suppressed the expression of hypoxia-inducible factor 1 alpha (HIF-1α), achieving enhanced chemo-SDT.Conclusion: This study provides a paradigm that rationally engineered multifunctional metal-hybrid nanoparticles can serve as an effective platform for augmenting the antitumor therapeutic efficiency of chemo-SDT.Keywords: sonodynamic therapy, flash nanoprecipitation, manganese dioxide, PLGA nanoparticle, GSH-depletion, hypoxia

Ziliang Xu,1,&ast; Yuanqiang Zhu,1,&ast; Hongliang Zhao,1,&ast; Fan Guo,1 Huaning Wang,2 Minwen Zheng1 1Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China; 2Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Minwen Zheng, Department of Radiology, Xijing Hospital, Fourth Military Medical University, 127# Changle West Road, Xi’an 710032, People’s Republic of China, Email zhengmw2007@163.com Huaning Wang, Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, 127# Changle West Road, Xi’an 710032, People’s Republic of China, Email xskzhu@fmmu.edu.cnPurpose: To investigate the general sleep stage classification performance of deep learning networks, three datasets, across different age groups, mental health conditions, and acquisition devices, comprising adults (SHHS) and children without mental health conditions (CCSHS), and subjects with mental health conditions (XJ), were included in this study.Methods: A long short-term memory (LSTM) network was used to evaluate the effect of different ages, mental health conditions, and acquisition devices on the sleep stage classification performance and the general performance.Results: Results showed that the age and different mental health conditions may affect the sleep stage classification performance of the network. The same acquisition device using different parameters may not have an obvious effect on the classification performance. When using a single dataset and two datasets for training, the network performed better only on the training dataset. When training was conducted with three datasets, the network performed well for all datasets with a Cohen’s Kappa of 0.8192 and 0.8472 for the SHHS and CCSHS, respectively, but performed relatively worse (0.6491) for the XJ, which indicated the complexity effect of different mental health conditions on the sleep stage classification task. Moreover, the performance of the network trained using three datasets was similar for each dataset to that of the network trained using a single dataset and tested on the same dataset.Conclusion: These results suggested that when more datasets across different age groups, mental health conditions, and acquisition devices (ie, more datasets with different feature distributions for each sleep stage) are used for training, the general performance of a deep learning network will be superior for sleep stage classification tasks with varied conditions.Keywords: sleep stage classification, deep learning network, electroencephalogram, time-frequency spectrum

Chen Wang,1,&ast; Peng Fang,2,&ast; Ya Li,1,&ast; Lin Wu,2,&ast; Tian Hu,3 Qi Yang,4 Aiping Han,5 Yingjuan Chang,1 Xing Tang,1 Xiuhua Lv,1 Ziliang Xu,1 Yongqiang Xu,1 Leilei Li,1 Minwen Zheng,1 Yuanqiang Zhu1 1Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of China; 2Department of Military Medical Psychology, Air Force Medical University, Xi’an, People’s Republic of China; 3Department of Radiology, Yan’an University Affiliated Hospital, Yan’an, People’s Republic of China; 4Department of Radiology, Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine, Xianyang, People’s Republic of China; 5Imaging Diagnosis and Treatment Center, Xi’an International Medical Center Hospital, Xi’an, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanqiang Zhu, Department of Radiology, Xijing Hospital, Fourth Military Medical University, No. 127 West Changle Road, Xi’an, 710032, People’s Republic of China, Tel/Fax +86-29-84775415, Email Zhu_YQ_fmmu@163.com Minwen Zheng, Department of Radiology, Xijing Hospital, Fourth Military Medical University, No. 127 West Changle Road, Xi’an, 710032, People’s Republic of China, Tel/Fax +86-29-84771938, Email zhengmw2007@163.comBackground: Large individual differences exist in sleep deprivation (SD) induced sustained attention deterioration. Several brain imaging studies have suggested that the activities within frontal-parietal network, cortico-thalamic connections, and inter-hemispheric connectivity might underlie the neural correlates of vulnerability/resistance to SD. However, those traditional approaches are based on average estimates of differences at the group level. Currently, a neuroimaging marker that can reliably predict this vulnerability at the individual level is lacking.Methods: Efficient transfer of information relies on the integrity of white matter (WM) tracts in the human brain, we therefore applied machine learning approach to investigate whether the WM diffusion metrics can predict vulnerability to SD. Forty-nine participants completed the psychomotor vigilance task (PVT) both after resting wakefulness (RW) and after 24 h of sleep deprivation (SD). The number of PVT lapse (reaction time > 500 ms) was calculated for both RW condition and SD condition and participants were categorized as vulnerable (24 participants) or resistant (25 participants) to SD according to the change in the number of PVT lapses between the two conditions. Diffusion tensor imaging were acquired to extract four multitype WM features at a regional level: fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. A linear support vector machine (LSVM) learning approach using leave-one-out cross-validation (LOOCV) was performed to assess the discriminative power of WM features in SD-vulnerable and SD-resistant participants.Results: LSVM analysis achieved a correct classification rate of 83.67% (sensitivity: 87.50%; specificity: 80.00%; and area under the receiver operating characteristic curve: 0.85) for differentiating SD-vulnerable from SD-resistant participants. WM fiber tracts that contributed most to the classification model were primarily commissural pathways (superior longitudinal fasciculus), projection pathways (posterior corona radiata, anterior limb of internal capsule) and association pathways (body and genu of corpus callosum). Furthermore, we found a significantly negative correlation between changes in PVT lapses and the LSVM decision value.Conclusion: These findings suggest that WM fibers connecting (1) regions within frontal-parietal attention network, (2) the thalamus to the prefrontal cortex, and (3) the left and right hemispheres contributed the most to classification accuracy.Keywords: sleep deprivation, vulnerability, diffusion tensor imaging, machine learning, psychomotor vigilance task

Wei Huang,1,2,&ast; Jinyong Zhang,3,&ast; Shiyi Liu,1 Chunxia Hu,1 Min Zhang,1 Shumin Cheng,1 Huijuan Yu,1,2 Manling Zheng,1 Jinsong Wu,2 Yuemei Lu,2 Quanming Zou,3 Ruiqin Cui1 1Bacteriology & Antibacterial Resistance Surveillance Laboratory, Shenzhen Institute of Respiratory Diseases, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, People’s Republic of China; 2Department of Clinical Microbiology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, People’s Republic of China; 3National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Quanming Zou; Ruiqin Cui, Email qmzou2007@163.com; screening_sz@163.comBackground: The use of antibiotic adjuvants is a complementary strategy to the development of new antibiotics. The essential role of the ArnA dehydrogenase domain (ArnA_DH) in the addition of 4-amino-L-arabinose (L-Ara4N) to lipid A makes it a potential target in polymyxin adjuvant design.Purpose: This study aimed to identify a dehydrogenase inhibitor that enhances the antibacterial effect of polymyxin B (PB) and to further understand the mechanism of this drug combination.Methods: A susceptible K. pneumoniae strain, ATCC13883, was used to screen a dehydrogenase inhibitor library based on 3-(4,5)-dimethylthiazol(-z-y1)-2,5-diphenyltetrazolium bromide (MTT) and chequerboard assays. The protein- and cell-based effects of disulfiram (DSF) on ArnA activity were assessed, and the transcription levels of genes in the arn operon were evaluated by quantitative real-time polymerase chain reaction (qRT–PCR). Lipid A was isolated, and a structural analysis was performed. The cell wall function was evaluated through membrane integrity and bacterial viability assays. The in vivo antibacterial activity was evaluated using a mouse pulmonary infection model.Results: We screened a dehydrogenase inhibitor library and found that the anti-alcoholism drug DSF significantly enhanced the antibacterial activity of PB in vitro and in vivo. The protein-based enzyme activity assay showed that DSF exerted no direct effect on the dehydrogenase activity of ArnA. Treatment with the combination of DSF and PB but not with PB alone decreased both the transcription level of genes in the arn operon and the modification level of lipid A. DSF also strengthened the disruption of the cell membrane integrity of PB. Moreover, the enhanced PB antibacterial activity was effective against clinical PB-resistant strains.Conclusion: We identified a new drug combination that can be used to reduce the necessary dosage of PB and overcome PB resistance, and this drug combination has good prospects for clinical application.Keywords: polymyxins, antibiotic adjuvants, antibacterial, cell membrane

Xuan Chen,1,&ast; Mingrui Duan,1,2,&ast; Rui Hou,1,2,&ast; Manqi Zheng,1,2 Haibin Li,3 Manjot Singh,4,5 Changwei Li,6 Kuo Liu,1,2 Feng Zhang,1,2 Xinghua Yang,1,2 Yanxia Luo,1,2 Yan He,1,2 Lijuan Wu,1,2 Deqiang Zheng1,2,7 1Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Municipal Key Laboratory of Clinical Epidemiology, Capital Medical University, Beijing, People’s Republic of China; 3Heart Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands and Centre for Medical Research, University of Western Australia, Crawley, WA, Australia; 5School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia; 6Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA; 7Center for Primary Health Care Research, Lund University/Region Skåne, Malmö, Sweden&ast;These authors contributed equally to this workCorrespondence: Deqiang ZhengDepartment of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, 10 Xitoutiao, Youanmen, Fengtai District, Beijing, 100069, People’s Republic of ChinaTel/Fax +86 10 8391 1497Email dqzheng@ccmu.edu.cnLijuan WuDepartment of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, 10 Xitoutiao, Youanmen, Fengtai District, Beijing, 100069, People’s Republic of ChinaTel +86 10 8391 1497Email xiaowu@ccmu.edu.cnBackground: Few studies have focused on the prevalence of abdominal obesity in Chinese middle-aged and older adults with a normal body mass index (BMI). Furthermore, it is still unclear whether abdominal obesity is an independent risk factor for type 2 diabetes mellitus (T2DM). Participants with a normal BMI are usually neglected during assessments of abdominal obesity-associated T2DM risk since the current recommendations for medical interventions are mainly focused on overall body mass index rather than fat deposition patterns.Methods: In this study, 7942 normal-BMI participants aged over 45 years from the China Health and Retirement Longitudinal Study were included to assess the prevalence of abdominal obesity defined by waist circumference (WC) or waist-to-height ratio (WHtR). In addition, 4348 normal-BMI individuals with no diabetes at baseline were included to evaluate the association between abdominal obesity and the risk of T2DM with the Cox proportional hazards model.Results: The prevalence (95% confidence interval, CI) of increased WC and substantially increased WC among adults with a normal BMI was 22.0% (21.1%-22.9%) and 18.1% (17.3%-19.0%), respectively. The adjusted hazard ratios and 95% CIs for T2DM incidence were 1.39 (1.05– 1.85) and 1.89 (1.42– 2.53) for those with increased WC and substantially increased WC, respectively, compared to the individuals with a normal WC. Similar HRs were obtained for the association between WHtR and the risk of T2DM. In prediabetic patients, the HRs (95% CIs) for new-onset T2DM for those with increased WC and substantially increased WC were 1.85 (1.27– 2.69) and 2.46 (1.67– 3.61), respectively, when compared with individuals with normal WC. This positive association was observed in women but not in men or adults with normal glucose tolerance (NGT).Conclusion: Abdominal obesity is highly prevalent among middle-aged and older Chinese adults with a normal BMI, and maintaining a normal waist circumference may be beneficial in the prevention of T2DM.Keywords: abdominal obesity, normal body mass index, prevalence, type 2 diabetes mellitus, hazard ratio

Vertical axis wind turbine (VAWT) is one of the main windmills for wind energy conversion, which can be further divided into lift type and drag type. The term rotor solidity is defined by product of blade number and chord length divided by the rotor diameter for Lift Type VAWT, which has been identified as a key parameter on the performance of a lift type VAWT. Computational fluid dynamics (CFD) simulation indicated that there exists a maximum power coefficient when the solidity value varies between 0.2 and 0.5 for lift type VAWT. However, the solidity has not been well defined for Drag Type VAWT till now. In this article, the solidity is defined by product of blade number and blade radius divided by the effective diameter of rotor for Modified Savonius VAWT analogically, which is a typical drag type VAWT. CFD simulation indicated that there exists a maximum power coefficient when the value of solidity stands about 0.609 for each Modified Savonius VAWT with varying blades averagely, which is a new Golden Ratio Section appeared in Optimal Design of Modified Savonius VAWT and close to the universal Golden Ratio Section number, 0.618.

Yunxiao Liu, Hao Zhang, Mingyu Zheng, Chunlin Wang, Zhiqiao Hu, Yang Wang, Huan Xiong, BoYang Fan, Yuliuming Wang, Hanqing Hu, Qingchao Tang, Guiyu Wang Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of ChinaCorrespondence: Guiyu WangDepartment of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of ChinaTel +86-451-86296599Email guiywang@163.comPurpose: Distant metastasis (DM) is relatively rare in T1 colon cancer (CC) patients, especially in those with negative lymph node metastasis. The aim of this study was to explore the main clinical factors and build nomogram for predicting the occurrence and prognosis of DM in T1N0 colon cancer patients.Methods: Patients with T1N0 stage CC were collected from the Surveillance, Epidemiology, and End Result (SEER) database. All patients were divided into development and validation cohorts with the 3:1 ratio. Logistic regressions were performed to analyze the clinical risk factors for DM. Cox regression model was used to identify potential prognostic factors for patients with DM. The performance of nomogram was evaluated by concordance index (C-index), calibration curves, receiver operating characteristic (ROC) curves and decision curve analyses (DCAs). Based on cancer-specific survival (CSS), Kaplan–Meier curves were generated and analyzed using Log rank tests.Results: A total of 6770 patients were enrolled in this study, including 428 patients (6.3%) with DM. Age, size, grade, CEA were independent risk factors associated with DM. Age, grade, CEA, surgery and chemotherapy were independent prognostic factors for CSS. Nomograms were applied and C-index, calibration curves, ROC curves and DCA curves proved good discrimination, calibration and clinical practicability of the nomogram in predicting the occurrence and prognosis of DM in T1N0 CC patients. In the DM nomogram, the AUCs for development and validation cohort were 0.901 (95% CI = 0.879– 0.922) and 0.899 (95% CI=0.865– 0.940), respectively. The calibration curves (development cohort: S: p = 0.712; validation cohort: S: p = 0.681) showed the relatively satisfactory prediction accuracy. Similarly, the AUCs of the nomogram at 1-, 2-, and 3-year were 0.763 (95% CI=0.744– 0.782), 0.794 (95% CI=0.775– 0.813), and 0.822 (95% CI=0.803– 0.841) for the development cohort, and 0.785 (95% CI=0.754– 0.816), 0.748 (95% CI=0.717– 0.779) and 0.896 (95% CI=0.865– 0.927) for the validation cohort in the CSS nomogram. The C-indices of the development and validation cohort were 0.718 (95% CI=0.639– 0.737) and 0.712 (95% CI=0.681– 0.743).Conclusion: The population-based nomogram could help clinicians predict the occurrence and prognosis of DM in T1N0 CC patients and provide a reference to perform appropriate metastatic screening plans and rational therapeutic options for the special population.Keywords: T1N0 colon cancer, distant metastasis, nomogram, SEER

Yan Du,1,&ast; Xueru Duan,1,&ast; Murui Zheng,2,&ast; Wenjing Zhao,3,&ast; Jun Huang,4 Lixian Lao,5 Fan Weng,6 Dan-Er Lin,7 Zhenxiao Yang,1 Haiyi Li,1 Xudong Liu,1 Hai Deng5 1Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Guangzhou Center for Disease Control and Prevention, Guangzhou, People’s Republic of China; 3Department of Public Health, Faculty of Medicine, Hokkaido University, Sapporo, Japan; 4Department of Geriatrics, Institute of Geriatrics, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Science, Guangzhou, People’s Republic of China; 5Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Science, Guangzhou, People’s Republic of China; 6Guangzhou Yuexiu District Center for Disease Control and Prevention, Guangzhou, People’s Republic of China; 7Guangzhou Baiyun District Center for Disease Control and Prevention, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xudong Liu; Hai Deng Tel +86-20-87330619; +86-20-83827812-10263Email liuxudong@mail.sysu.edu.cn; doctordh@hotmail.comObjective: The effect of dietary factors on OSA remains unclear. This study was to investigate the association of obstructive sleep apnea (OSA) with individual and overall effects of eating habits among adult Chinese.Methods: A total of 9733 participants were selected from the baseline survey of the Guangzhou Heart Study. OSA was ascertained by Berlin Questionnaire. Food consumption was collected using a food frequency questionnaire, and eating patterns were extracted by principal component analysis. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated by the logistic regression model.Results: After adjustment for confounders, fried food intake with ≥ 1/week was associated with an increased risk of OSA (OR: 1.77, 95% CI: 1.37– 2.27), while fruit consumption of ≥ 1/day was associated with a 26% reduced risk of OSA (OR: 0.74, 95% CI: 0.62– 0.88). Three eating patterns were defined and labeled as pattern I, II, and III. Eating pattern III which had higher factor loadings of animal innards, fried food, salted food, carbonate, and non-carbonated beverages was associated with an increased risk of OSA (OR: 1.30, 95% CI: 1.09– 1.55) when comparing the highest with the lowest tertile of pattern score, after adjusting for confounders; every 1-unit increment of pattern III score was associated with an increased risk of OSA (OR: 1.09, 95% CI: 1.04– 1.14). Neither pattern I nor pattern II was observed to be associated with OSA risk.Conclusion: A higher frequency intake of fruits was associated with a reduced OSA risk and a diet with higher levels of consumption of animal innards, fried food, salted food, carbonated beverages, and non-carbonated beverages may increase the risk of OSA.Keywords: obstructive sleep apnea, eating habits, diet, fruits, fried food

Aftab Ullah,1 Gang Chen,2 Abid Hussain,3,4 Hanif Khan,1 Azar Abbas,5 Zhanwei Zhou,5 Muhammad Shafiq,6 Saleem Ahmad,7 Usman Ali,8 Muhammad Usman,6 Faisal Raza,8 Abrar Ahmed,8 Zijie Qiu,5 Maochao Zheng,1 Daojun Liu1 1Department of Pharmacy, Shantou University Medical College, Shantou, 515041, Guangdong, People’s Republic of China; 2Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, People’s Republic of China; 3School of Life Science, Key Laboratory of Molecular Medicine and Biotherapy, Beijing Institute of Technology, Beijing, 100081, People’s Republic of China; 4Chinese Academy of Sciences (CAS) Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing, 100190, People’s Republic of China; 5School of Pharmacy, China Pharmaceutical University, Nanjing, 210028, Jiangsu, People’s Republic of China; 6Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, 515041, people’s Republic of China; 7Department of Medicine, Shantou University Medical College Cancer Hospital, Shantou, People’s Republic of China; 8School of Pharmacy, Shanghai Jiaotong University, Shanghai, 200240, Shanghai, People’s Republic of ChinaCorrespondence: Aftab Ullah; Daojun Liu Email aftab@stu.edu.cn; liudj@stu.edu.cnBackground: Liver fibrosis is a chronic liver disease with excessive production of extracellular matrix proteins, leading to cirrhosis, hepatocellular carcinoma, and death.Purpose: This study aimed at the development of a novel derivative of polyethyleneimine (PEI) that can effectively deliver transforming growth factor β (TGFβ) siRNA and inhibit chemokine receptor 4 (CXCR4) for TGFβ silencing and CXCR4 Inhibition, respectively, to treat CCl4-induced liver fibrosis in a mouse model.Methods: Cyclam-modified PEI (PEI-Cyclam) was synthesized by incorporating cyclam moiety into PEI by nucleophilic substitution reaction. Gel electrophoresis confirmed the PEI-Cyclam polyplex formation and stability against RNAase and serum degradation. Transmission electron microscopy and zeta sizer were employed for the morphology, particle size, and zeta potential, respectively. The gene silencing and CXCR4 targeting abilities of PEI-Cyclam polyplex were evaluated by luciferase and CXCR4 redistribution assays, respectively. The histological and immunohistochemical staining determined the anti-fibrotic activity of PEI-Cyclam polyplex. The TGFβ silencing of PEI-Cyclam polyplex was authenticated by Western blotting.Results: The 1H NMR of PEI-Cyclam exhibited successful incorporation of cyclam content onto PEI. The PEI-Cyclam polyplex displayed spherical morphology, positive surface charge, and stability against RNAse and serum degradation. Cyclam modification decreased the cytotoxicity and demonstrated CXCR4 antagonistic and luciferase gene silencing efficiency. PEI-Cyclam/siTGFβ polyplexes decreased inflammation, collagen deposition, apoptosis, and cell proliferation, thus ameliorating liver fibrosis. Also, PEI-Cyclam/siTGFβ polyplex significantly downregulated α-smooth muscle actin, TGFβ, and collagen type III.Conclusion: Our findings validate the feasibility of using PEI-Cyclam as a siRNA delivery vector for simultaneous TGFβ siRNA delivery and CXCR4 inhibition for the combined anti-fibrotic effects in a setting of CCl4-induced liver fibrosis.Keywords: polyethyleneimine, cyclam, gene delivery, liver fibrosis, CXCR4

Meng Zheng,1,2 Junli Zhu1,2 1School of Public Health, Capital Medical University, Beijing, People’s Republic of China; 2Research Center for Capital Health Management and Policy, Beijing, People’s Republic of ChinaCorrespondence: Junli ZhuDepartment of Health Management and Policy, School of Public Health, Capital Medical University, No. 10, Xitou Road, Youanmen Wai, Beijing, 100069, People’s Republic of ChinaTel +86 18701515093Fax +86 01083911578Email smallying@126.comBackground: During the transformation of economy to a high-quality level in China, industrial restructuring and upgrading have played an important role. The upgrading of the industrial structure has affected not only the development in society and economy but also other fields, thereby having great impact on social security. In recent years, with the aging of the population and economic development, the social medical insurance fund is undertaking more payment pressure. However, the existing research rarely focuses on the impact of industrial structure upgrading on medical insurance.Objective: The main aim of this study was to analyze the impact of the upgrading of industrial structure on the income and expenditure of the urban employee basic medical insurance fund.Methods: China’s provincial panel data from 2007 to 2018, collected by the National Bureau of Statistics of China, were used to establish a panel regression model in order to investigate the impact of the upgrading of the industrial structure on the income and expenditure of the urban employee basic medical insurance fund.Results: The research showed that the upgrading of the industrial structure, in combination with the internal upgrading in the tertiary industry, had a positive impact on the income and expenditure of the urban employee basic medical insurance fund and that there were regional differences. The simple upgrading of the three major industries had no effect on the income or expenditure of the urban employee basic medical insurance fund. In addition to the upgrading of industrial structure, other factors such as the average salary of employed persons in urban units, the proportion of retirees among all insured persons in urban employee basic medical insurance and the expenditure of urban employee basic medical insurance were also found to have impact on the income of urban employee basic medical insurance. Moreover, the expenditure of urban employee basic medical insurance was associated with the proportion of retirees among all insured persons in urban employee basic medical insurance, GDP and an aging population.Conclusion: In the context of the upgrading of the industrial structure, measures such as strengthening employment and income security, delaying retirement, adjusting birth policy, strengthening the scientific management of personal accounts and accurately positioning the regional industrial structure were suggested to be adopted in order to minimize the payment pressures on the urban employee basic medical insurance fund.Keywords: industrial structure upgrading, urban employee basic medical insurance, panel regression model, employment structure

Qiao-Jun Zhang,1,2,* Yue Liu,3,* Wen-Ting Zhang,3 Jing-Jing Huang,2 Hao-Hong Li,3 You-Guang Lu,1 Ming Zheng,2 Da-Li Zheng1 1Fujian Key Laboratory of Oral Diseases, Fujian Biological Materials Engineering and Technology Center of Stomatology, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian, 350004, People’s Republic of China; 2Department of Prosthodontics, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, 350001, People’s Republic of China; 3College of Chemistry, Fuzhou University, Fuzhou, Fujian, 350116, People’s Republic of China*These authors contributed equally to this workCorrespondence: Da-Li ZhengFujian Key Laboratory of Oral Diseases, School and Hospital of Stomatology, Fujian Medical University, 88 Jiaotong Road, Fuzhou, 350004, People’s Republic of ChinaTel +86-591-83720599Email dalizheng@fjmu.edu.cnMing ZhengDepartment of Prosthodontics, School and Hospital of Stomatology, Fujian Medical University, 246 Yangqiao Middle Road, Fuzhou, 350001, People’s Republic of ChinaTel +86-591-83736431Email zmdentist@163.comObjective: To synthesize and determine the antifungal activity of AgBr-nanoparticles (NP) @CTMAB (cetyltrimethyl-ammonium bromide) against Candida albicans (C. albicans) for use in the field of denture cleaning.Methods: The morphology and structure of AgBr-NP@CTMAB were characterized by IR, UV-Vis, XRD and SEM. The antifungal potential of AgBr-NP@CTMAB against C. albicans was determined by colony formation assay and growth curve analysis. PMMA containing AgBr-NP@CTMAB was prepared, and the long-term antifungal efficacy was analyzed. The effect against C. albicans biofilm was analyzed by SEM and OD600 , and the color changes of the specimens were observed by stereomicroscopy after 1 week of incubation. Cytotoxicity to human oral gingival fibroblasts and oral mucosal epithelial cells was detected by Cell Counting Kit-8 (CCK-8) in vitro.Results: The compound showed a good crystalline phase, the presence of AgBr nanoparticles and the hybridization of CTMAB+ with AgBr-NPs. AgBr-NP@CTMAB showed significant antifungal activity against C. albicans at concentrations of 10 μg/mL and 20 μg/mL. PMMA specimens containing AgBr-NP@CTMAB showed no long-term antifungal effect against C. albicans biofilm. The clearance rate of C. albicans attached to PMMA was 44.73% after soaking in 10 μg/mL AgBr-NP@CTMAB solution for 30 min and 91.35% for 8 h. There was no significant residual cytotoxicity or visual color change after soaking.Significance: AgBr-NP@CTMAB showed promising potential treatment for denture cleaners.Keywords: C. albicans, AgBr-NP@CTMAB, polymethyl methacrylate, cytotoxicity, biofilm

Yi Zhao,1 Gang Wang,2 Wenqiong Ni,3 Zhiqiang Song,4 Kun Chen,5 Chunlei Zhang,6 Shoumin Zhang,7 Yangfeng Ding,8 Min Zheng,9 Yulin Shi,10 Zhimiao Lin,11 Xiaomin Liu,12 Xiaofei Zhang,13 Qintian Zhou,14 Kazi Deluwar Ahmed14 1Department of Dermatology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, People’s Republic of China; 2Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of China; 3Department of Dermatology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, People’s Republic of China; 4Department of Dermatology, Southwest Hospital, The Third Military Medical University, Chongqing, People’s Republic of China; 5Institute of Dermatology, Chinese Academy of Medical Science and Peking Union Medical College, Nanjing, People’s Republic of China; 6Department of Dermatology, Peking University Third Hospital, Beijing, People’s Republic of China; 7Department of Dermatology, Henan Provincial People’s Hospital, Zhengzhou 450003, People’s Republic of China; 8Department of Dermatology, Shanghai Skin Disease Hospital, Shanghai, People’s Republic of China; 9Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 10Department of Dermatology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine; Institute of Psoriasis, Tongji University School of Medicine, Shanghai, People’s Republic of China; 11Department of Dermatology and Venereology, Peking University First Hospital, Beijing, People’s Republic of China; 12Department of Dermatology, The University of Hong Kong–Shenzhen Hospital, Shenzhen, People’s Republic of China; 13Department of Clinical Epidemiology and Biostatistics, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, People’s Republic of China; 14Scientific Affairs and MSL Department, LEOPharma China, Shanghai, People’s Republic of ChinaCorrespondence: Yi ZhaoDepartment of Dermatology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, No. 168 Litang Road, Beijing 102218, People’s Republic of ChinaEmail zhaoyimd@tsinghua.edu.cnGang WangDepartment of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, People’s Republic of ChinaEmail xjwgang@fmmu.edu.cnObjective: We aimed to prospectively evaluate the visit adherence in mild to moderate psoriasis patients.Methods: Plaque psoriasis patients aged 18 or above who were prescribed with a two-component formula ointment were eligible for the study. The patients were randomly assigned to group A or B, and received management with or without planned patient-doctor communication via a mobile platform. The outpatient visit was scheduled at week 2, 8, 16, 28, 48, and 52. Visit adherence was evaluated as the visit rate of the patients.Results: Two hundred twenty-one patients were included. Generally, the visit adherence dropped over time during follow-up. The visit rates in group A were 5.2– 15.7% through the 52 weeks, and similar rates were found in group B (7.5– 17.0%, vs group A, P > 0.05). A negative binomial regression model showed that older age and higher BSA were correlated with more frequent visits.Conclusion: The visit adherence of mild to moderate psoriasis patients was very low in China. Proactive inquiries of the doctors via the mobile platform failed to improve the visit adherence of the patients.Keywords: psoriasis, visit adherence, topical treatment

Wenjun Hu,1,2,* Shuchun Li,1,2,* Sen Zhang,1,2 Bowen Xie,1 Minhua Zheng,1,2 Jing Sun,1,2 Xiao Yang,1,2 Lu Zang1,2 1Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lu Zang; Xiao Yang Email zanglu@163.com yangxiao19890125@163.comPurpose: Previous studies found that gap junction alpha-1 protein (GJA1) was a potent tumor suppressor in colorectal cancer (CRC). We designed the present study to evaluate the clinical importance and molecular mechanisms of GJA1 in CRC.Methods: Clinical and transcriptomic data from TCGA and GEO datasets were retrospectively collected. CRC patients were divided into two subgroups according to the expression level of GJA1 mRNA. Difference between survival time and response to neoadjuvant chemotherapy was then evaluated. Functional assays including wound-healing assay, transwell invasion assay and flow cytometry assay were performed to investigate the effects of GJA1 on invasive ability and response to chemotherapy drugs of CRC cells. Moreover, we explored the mechanisms of GJA1 by which it regulates CRC malignant phenotypes.Results: The expression level of GJA1 was significantly higher in normal tissue than cancer tissue, indicating a tumor suppressive role of GJA1 in CRC. Patients with higher expression of GJA1 showed better prognosis than those with low GJA1 expression level. Consistently, overexpression of GJA1 suppressed the invasive ability of CRC cells while enhancing the sensitivity of CRC cells to oxaliplatin-induced apoptosis. Mechanically, we found that GJA1 suppressed the epithelial mesenchymal transition process. Moreover, GJA1 could modulating infiltrating levels of several immune cells in the tumor microenvironment.Conclusion: These findings suggested that GJA1 was correlated with prognosis and immune infiltrating levels of CD8+ T cells, macrophages, neutrophils, and DCs in CRC. In addition, GJA1 expression contributes to regulation of tumor-associated macrophages (TAMs) and tumor infiltrating neutrophils (TINs) in CRC. These findings suggest that GJA1 is a promising biomarker for determining prognosis and immune infiltration in colorectal cancer.Keywords: colorectal cancer, the gap junction channel protein, metastasis, chemotherapy, immune infiltrates

Ruoyao Zou,1,2 Mingjun Zheng,3 Mingzi Tan,4 Haoya Xu,1,2 Nannan Luan,1 Liancheng Zhu1,2 1Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, People’s Republic of China; 2Key Laboratory of Maternal-Fetal Medicine of Liaoning Province, Key Laboratory of Obstetrics and Gynecology of Higher Education of Liaoning Province, Shenyang, Liaoning, People’s Republic of China; 3Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Munich, Germany; 4Department of Gynecology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning 110042, People’s Republic of ChinaCorrespondence: Liancheng ZhuDepartment of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, People’s Republic of ChinaEmail medecin@126.comPurpose: To identify key pathogenic genes and reveal the potential molecular mechanisms of endometrial cancer (EC) using bioinformatics analysis and immunohistochemistry validation.Materials and Methods: Through weighted gene co-expression network analysis (WGCNA), a co-expression network was constructed based on the top 25% variant genes in the GSE50830 dataset downloaded from gene expression omnibus (GEO). GO and KEGG pathway enrichment analyses were performed using the DAVID online tool. Candidate genes were selected using the cytoHubba plug-in of Cytoscape, mRNA expression levels and prognostic values in EC were analyzed by Oncomine, GEPIA, and Kaplan–Meier Plotter database to determine hub genes. One hub gene was validated by immunohistochemical (IHC) staining of 116 paraffin-embedded endometrial tissues and TCGA-UCEC cohort. Genes co-expressed with this hub gene were identified by LinkedOmics. Finally, its correlation with immune infiltration was evaluated by TIMER.Results: Three co-expression modules and five candidate genes in each module were obtained by WGCNA; four hub genes were identified (LGR5, SST, ZNF558, and PTGDS). The mRNA levels of LGR5 and SST were significantly upregulated in EC, whereas those of ZNF558 and PTGDS were significantly downregulated; the expression of all four genes was associated with EC prognosis. Further validation demonstrated that PTGDS was significantly downregulated in the EC group compared with the atypical hyperplasia and normal endometrial groups, and its low expression was an independent risk factor for worse prognosis of EC. Biological function analysis indicated that PTGDS might be involved in the adaptive immune response, leukocyte migration, as well as in the regulation of cell adhesion molecules and chemokine signaling. Additionally, PTGDS expression was positively correlated with immune infiltration status of B cells, CD4+ T cells and macrophages.Conclusion: LGR5, SST, ZNF558, and PTGDS may participate in the development, progression, and prognosis of EC, in which PTGDS may be a novel biomarker and therapeutic target for EC.Keywords: endometrial cancer, bioinformatics analysis, WGCNA, immunohistochemistry, PTGDS

Leqi Zhou,*,1,2 Sen Zhang,*,1,2 Xia Zou,3 Jishun Lu,3 Xiao Yang,1,2 Zhijue Xu,3 Aidong Shan,3 Wenjuan Jia,3 Feng Liu,3 Xialin Yan,1,2 Hao Su,1,2 Tao Liang,3 Minhua Zheng,1,2 Yan Zhang,3 Bo Feng1,21Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine (SCSB), Shanghai Jiao Tong University, Shanghai, People’s Republic of China*These authors contributed equally to this workBackground: Colorectal cancer (CRC) is one of the most frequent malignancies of the digestive system. Elevated expression of β-galactoside α2,6-sialyltranferase 1 (ST6GAL1) has been observed in multiple cancers. But the mechanism of how ST6GAL1 might affect cancer cells remains to be clarified. Our previous study recognized intercellular adhesion molecule-1(ICAM-1) as a probable substrate of ST6GAL1 through mass spectrometry (MS) analysis. ICAM-1 is related to tumor metastasis in various cancers.Methods: First, ST6GAL1 was overexpressed and knocked down to perform transwell and wound healing assays, and the results were further confirmed in vivo. Based on the results of MS, GO and KEGG analysis were applied to reveal the connection between ST6GAL1 and ICAM-1. Immunoblot and tissue microarrays were administered to investigate the expression of ICAM-1 in different stages of CRC. Next, PCR, lectin precipitation and cycloheximide (CHX) were used to demonstrate the mechanism of ST6GAL1 on ICAM-1. Moreover, we investigated the sialylation on soluble ICAM in serum and its connection to tumor staging.Results: Overexpression of ST6GAL1 inhibited the migratory ability, while knockdown of ST6GAL1 cells had the reverse effect. Moreover, nude mice injected with ST6GAL1-knockdown cells harvested more liver metastases. Based on the GO and KEGG analysis, data from TCGA database showed a positive correlation between ST6GAL1 and ICAM-1. ICAM-1 also demonstrated a significant decrease in stage III/IV compared with stage I/II tumors. Our results revealed that ST6GAL1 could increase the stability of ICAM-1 through sialylation but had little influence on transcriptional level. Additionally, results of serum lectin precipitation revealed a correlation between the level of sialylation on soluble ICAM and CRC staging.Conclusion: This study illustrated that ST6GAL1 inhibited the metastatic ability of CRC by stabilizing ICAM-1 via sialylation and demonstrated a correlation between CRC staging and the sialylation on soluble ICAM-1 in serum.Keywords: colorectal cancer, β-galactoside α2, 6-sialyltranferase 1, ST6GAL1, intercellular adhesion molecule-1, ICAM-1, sialylation, metastasis

Guang-Fen Zhang,1 Jie Guo,2 Li-Li Qiu,1 Shu-Ming Li,1 Man Zheng,2 Jiang-Yan Xia,1 Jian-Jun Yang1,31Department of Anesthesiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Anesthesiology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 3Department of Anesthesiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaPurpose: To evaluate the effects of dezocine on the prevention of postoperative catheter-related bladder discomfort (CRBD).Patients and methods: Ninety-six adult patients undergoing abdominal surgery with urinary catheterization under general anesthesia were randomized into dezocine and control (flurbiprofen) groups. The postoperative CRBD, pain score, sedation score and adverse effects were evaluated at 0, 1, 2 and 6 hrs after tracheal extubation.Results: The primary outcome showed a lower incidence of CRBD at 1 hr post-extubation in the dezocine group (29.17%) than the control group (58.33%, P0.05); however, the overall severity of CRBD was decreased in the dezocine group compared with the control group (P

Xin Nie,1,2 Cong Liu,3 Qian Guo,1,2 Ming-jun Zheng,1,2 Ling-ling Gao,1,2 Xiao Li,1,2 Da-wo Liu,1,2 Lian-cheng Zhu,1,2 Juan-juan Liu,1,2 Bei Lin1,2 1Department of Obstetrics and Gynaecology, Shengjing Hospital Affiliated to China Medical University, Liaoning, China; 2Key Laboratory of Maternal-Fetal Medicine of Liaoning Province, Key Laboratory of Obstetrics and Gynecology of Higher Education of Liaoning Province, Liaoning, China; 3Department of Obstetrics and Gynaecology, Wuxi Materal and Child Health Hospital, Jiangsu, China Background: Transmembrane protein with epidermal growth factor-like and two follistatin-like domains 1 (TMEFF1) has an anticarcinogenic effect in brain tumors. However, little is known about the role of TMEFF1 in epithelial ovarian cancer (EOC).Materials and methods: TMEFF1 expression in EOC was detected by immunohistochemistry; its relationship with clinical pathological parameters and its influence on prognosis were analyzed. The MTT, scratch, Transwell assays, and flow cytometry were used to assess the malignant behavior of ovarian cancer cell. Changes in node proteins in MAPK and PI3K/AKT signaling pathways and the expression of epithelial–mesenchymal transformation markers were measured by Western blot. The regulatory effect of p53 on TMEFF1 was verified by chromatin immunoprecipitation (ChIP) assay and Western blot.Results: TMEFF1 expression was higher in the EOC group than in the borderline and benign tumor groups and normal ovary group; its high expression was significantly related to International Federation of Gynecology and Obstetrics stage (P=0.024) and independently predicted shorter overall survival (P

Lin Yan,1 Min Zheng,1 Hua Wang2 1Department of Breast Surgery, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, China; 2Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China Background: Although the number of circular RNAs (circRNAs) that has been identified in multiple cancer tissues continues to increase, the relationship between circRNA expression and carcinogenesis remains unknown. The role of hsa_circ_0072309 in breast cancer has remained undefined until now. In this study, we aimed to investigate the role of hsa_circ_0072309 in breast cancer progression. Methods: hsa_circ_0072309 expression in breast cancer tissues was analyzed using qRT-PCR. A series of functional experiments were carried out to investigate hsa_circ_0072309 function in breast cancer development and its underlying molecular mechanisms. Results: hsa_circ_0072309 expression in breast cancer tissues was upregulated relative to that in adjacent normal tissues. hsa_circ_0072309 could serve as a prognostic biomarker of breast cancer. hsa_circ_0072309 overexpression dramatically inhibited the proliferation, migration, and invasion of breast cancer cells in vitro. In vivo assays revealed that the ectopic expression of hsa_circ_0072309 repressed breast cancer growth. The results of our mechanistic studies indicated that hsa_circ_0072309 could act as the sponge of miR-492, which exhibited increased expression in breast cancer tissues. Hsa_circ_0072309 suppressed breast cancer cell proliferation, migration, and invasion by inhibiting miR-492. Conclusion: Our findings revealed for the first time that the hsa_circ_0072309-miR-492 axis plays an essential role in breast cancer progression. Keywords: circular RNA, hsa_circ_0072309, miR-492, breast cancer, progression

Zhu Y, Ren F, Zhu Y, et al. Nat Sci Sleep. 2020;12:1067–1074. The authors have advised that the name of last author on page 1067 is incorrect. Mingwen Zheng should be Minwen Zheng. The authors apologize for this error. Read the original article

In this article, it aims to propose effective approaches for hydro-forming process of bi-metallic composite pipe by assuming plane strain and elastic-perfectly plastic material model. It derives expressions for predicting hydro-forming pressure and residual stress of the forming process of bi-metallic composite pipe. Test data from available experiments is employed to check the model and formulas. It shows the reliability of the proposed model and formulas impersonally.

Yanhong Huang,1 Shaoxiong Zheng,1 Chongtao Xu,1 Kun Lin,2 Kusheng Wu,2 Maochun Zheng,1 Jie Zhang,1 Haiyun Xu1 1Mental Health Center, 2Department of Preventive Medicine, Shantou University Medical College, Shantou, China Abstract: Attention-deficit hyperactivity disorder (ADHD) is a frequent childhood-onset psychiatric condition and categorized into three subtypes of predominantly inattentive (ADHD-I), hyperactive impulsive (ADHD-H), and combined (ADHD-C). The prevalence and subtypes of ADHD vary considerably. The primary aim of this study was to provide a prevalence estimate of ADHD in elementary school students living in Shantou, a district of China, and in addition to examine the influence of informants, age, and gender on the prevalence. A total of 3,497 students aged 7–12 years were enrolled by random and stratified sampling. In stage I, teachers and parents of all participating students in randomly selected schools were asked to complete Chinese versions of the Conners’ 10-item scale. In stage II, students with high scores (.15) were interviewed by a psychiatrist for a diagnosis with or without ADHD. Parents rated many more students with high scores than teachers did in stage I. The prevalence of ADHD determined by Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) was 5.91% (5.27%–6.55%), which is comparable to the rates reported in previous studies with Chinese children. This hits the low border of the ADHD prevalence range from 5.9 to 7.1% worldwide, and is lower than that of Chinese children living in Hong Kong, suggesting an important influence of Chinese culture on the diagnosis of ADHD. The constituent ratios of ADHD-I, ADHD-C, and ADHD-H subtypes were 67.43, 24.57, and 8.00%, respectively. The rate of ADHD-H decreased with age, whereas that of ADHD-I remained at the highest levels in all age groups, suggesting that symptoms in the inattention domain are the most persistent and refractory. Keywords: adolescents, ADHD, prevalence, Chinese culture, informants

Hongtao Sun,1,* Maohua Zheng,2,* Yanmin Wang,1 Yunfeng Diao,1 Wanyong Zhao,1 Zhengjun Wei1 1Sixth Department of Neurosurgery, Affiliated Hospital of Logistics University of People’s Armed Police Force, Tianjin, 2Department of Neurosurgery, The First Hospital of Lanzhou University, Lanzhou, People’s Republic of China *These authors contributed equally to this work Objective: The aim of this study was to investigate the clinical significance and changes of brain tissue partial pressure of oxygen (PbtO2) in the course of mild hypothermia treatment (MHT) for treating severe traumatic brain injury (sTBI). Methods: There were 68 cases with sTBI undergoing MHT. PbtO2, intracranial pressure (ICP), jugular venous oxygen saturation (SjvO2), and cerebral perfusion pressure (CPP) were continuously monitored, and clinical outcomes were evaluated using the Glasgow Outcome Scale score. Results: Of 68 patients with sTBI, PbtO2, SjvO2, and CPP were obviously increased, but decreased ICP level was observed throughout the MHT. PbtO2 and ICP were negatively linearly correlated, while there was a positive linear correlation between PbtO2 and SjvO2. Monitoring CPP and SjvO2 was performed under normal circumstances, and a large proportion of patients were detected with low PbtO2. Decreased PbtO2 was also found after MHT. Conclusion: Continuous PbtO2 monitoring could be introduced to evaluate the condition of regional cerebral oxygen metabolism, thereby guiding the clinical treatment and predicting the outcome. Keywords: severe traumatic brain injury, hypothermia, brain tissue partial pressure of oxygen, therapy

Le Wang,1 Gang Liu,1 Jun Liu,1 Mingqi Zheng,1 Liang Li2 1Department of Cardiology, The First Hospital of Hebei Medical University, 2Department of Cardiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China Objectives: The aim of this study was to investigate the effect of no-reflow phenomenon on ventricular systolic synchrony via myocardial blush grades (MBGs) in patients with acute anterior myocardial infarction after percutaneous coronary intervention (PCI). Patients and methods: All patients were divided into two groups and assessed by MBGs. To observe the parameters of the left ventricular function and left ventricular systolic synchrony, equilibrium radionuclide angiography was performed 1 week after PCI and repeated 6 months after acute myocardial infarction (AMI). Measurement data were compared and analyzed by the Student’s t-test, and the count data were evaluated by the χ2 test. A multivariate regression analysis was performed to assess the contribution of confounding factors.Results: A total of 100 patients were enrolled in this study: 26 in the no-reflow and 74 in the reflow group. There was no significant difference in terms of age, sex, hypertension history, diabetes history, hyperlipidemia history, and smoking history between the two groups. However, the incidence rate of heart failure with Killip’s grade ≥2 in the no-reflow group was significantly higher than that in the reflow group (38.46% vs 18.92%, P

Hong-tao Sun,1,* Maohua Zheng,2,* Yanmin Wang,1 Yunfeng Diao,1 Wanyong Zhao,1 Zhengjun Wei1 1Sixth Department of Neurosurgery, Affiliated Hospital of Logistics University of People’s Armed Police Force, Tianjin, 2Department of Neurosurgery, The First Hospital of Lanzhou University, Lanzhou, People’s Republic of China *These authors contributed equally to this work Abstract: The aim of the study was to evaluate the clinical value of multiple brain parameters on monitoring intracranial pressure (ICP) procedures in the therapy of severe traumatic brain injury (sTBI) utilizing mild hypothermia treatment (MHT) alone or a combination strategy with other therapeutic techniques. A total of 62 patients with sTBI (Glasgow Coma Scale score

Mengliang Zheng, Yanru Guo, Shiqiang Shan, Sen Yang Department of Anesthesiology, Cangzhou Central Hospital, Hebei, People’s Republic of China Background: The purpose of this study was to evaluate the efficacy of dezocine with regard to analgesic and stress reduction outcomes in women undergoing induced abortion.Methods: A total of 126 women in early pregnancy (up to 14 weeks’ gestation) who underwent induced abortion at Cangzhou Central Hospital from May 2012 to May 2013 were randomly assigned to a control (propofol) group (n=63) or an intervention (propofol + dezocine) group (n=63). Wake-up time, orientation force recovery time, incidence of adverse reactions, postoperative visual analog scale (VAS) score, analgesic effect, and respiratory and circulatory monitoring before the operation, 5 minutes into the operation, and 5 minutes after the operation were compared between the two groups.Results: The surgical procedure and anesthesia were performed successfully in all patients. Systolic and diastolic blood pressure and oxyhemoglobin saturation in the intervention group were significantly higher than in the control group; however, heart rate was significantly lower in the intervention group than in the control group 5 minutes into the operation (all P

Linjie Yao,1 Xingqiao Xu,2 Zhenyu Ni,3 Minling Zheng,3 Feiou Lin3 1Department of Pedodontics, 2Department of Oral and Maxillofacial Surgery, 3Department of Orthodontics, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, People’s Republic of China Background: Orthodontic treatment may cause functional restrictions, discomfort, and pain, which may lead to dental anxiety and noncooperation among patients. This study aimed to assess the concerns of adult female patients with respect to such treatment.Patients and methods: We conducted an explorative study using Q methodology among 40 adult female patients with different educational and social backgrounds in Wenzhou, People’s Republic of China. We asked participants to rank a set of 41 statements about seeking orthodontic treatment on an 11-point scale from “agree most” to “disagree most”. The collected data were analyzed using the PQ Method 2.35 program. We extracted significant viewpoints using centroid factor extraction and varimax rotation.Results: We identified major factors based on how the patients ranked statements. Patients in group 1 worried about lack of information about orthodontic treatment, and may have suffered from dental phobia; patients in group 2 were all single women, and they were worried that the braces might lower their chances of finding a partner; patients in group 3 worried about appearance and speech with braces; and patients in group 4 worried about cost, pain, and dental hygiene. The remaining participants who had other viewpoints did not load to any of these four groups.Conclusion: The concerns of adult female individuals seeking orthodontic treatment are complex. A significant feature of this study was using Q methodology to analyze the psychological characteristics of the patients. This study identified four typical characterizations that are associated with each group, and our findings may aid orthodontists in improving doctor–patient relationships. Keywords: orthodontic treatment, Q methodology, adult female patient

Jingmou Yu,1 Xin Xie,1 Meirong Zheng,1 Ling Yu,2 Lei Zhang,1 Jianguo Zhao,1 Dengzhao Jiang,1 Xiangxin Che11Key Laboratory of Systems Biology Medicine of Jiangxi Province, College of Basic Medical Science, Jiujiang University, Jiujiang, 2Division of Nursing, 2nd Affiliated Hospital, Yichun University, Yichun, People's Republic of ChinaBackground: Supramolecular micelles as drug-delivery vehicles are generally unable to enter the nucleus of nondividing cells. In the work reported here, nuclear localization signal (NLS)-modified polymeric micelles were studied with the aim of improving nuclear drug delivery.Methods: In this research, cholesterol-modified glycol chitosan (CHGC) was synthesized. NLS-conjugated CHGC (NCHGC) was synthesized and characterized using proton nuclear magnetic resonance spectroscopy, dynamic light scattering, and fluorescence spectroscopy. Doxorubicin (DOX), an anticancer drug with an intracellular site of action in the nucleus, was chosen as a model drug. DOX-loaded micelles were prepared by an emulsion/solvent evaporation method. The cellular uptake of different DOX formulations was analyzed by flow cytometry and confocal laser scanning microscopy. The cytotoxicity of blank micelles, free DOX, and DOX-loaded micelles in vitro was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in HeLa and HepG2 cells.Results: The degree of substitution was 5.9 cholesterol and 3.8 NLS groups per 100 sugar residues of the NCHGC conjugate. The critical aggregation concentration of the NCHGC micelles in aqueous solution was 0.0209 mg/mL. The DOX-loaded NCHGC (DNCHGC) micelles were observed as being almost spherical in shape under transmission electron microscopy, and the size was determined as 248 nm by dynamic light scattering. The DOX-loading content of the DNCHGC micelles was 10.1%. The DOX-loaded micelles showed slow drug-release behavior within 72 hours in vitro. The DNCHGC micelles exhibited greater cellular uptake and higher amounts of DOX in the nuclei of HeLa cells than free DOX and DOX-loaded CHGC (DCHGC) micelles. The half maximal inhibitory concentration (IC50) values of free DOX, DCHGC, and DNCHGC micelles against HepG2 cells were 4.063, 0.591, and 0.171 µg/mL, respectively. Moreover, the IC50 values of free DOX (3.210 µg/mL) and the DCHGC micelles (1.413 µg/mL) against HeLa cells were nearly 6.96- and 3.07-fold (P < 0.01), respectively, higher than the IC50 value of the DNCHGC micelles (0.461 µg/mL).Conclusion: The results of this study suggest that novel NCHGC micelles could be a potential carrier for nucleus-targeting delivery.Keywords: polymeric micelles, drug delivery, nucleus-targeting delivery