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Dongyan Duan,1,&ast; Hua Xie,2,&ast; Jiayi Jiang,1 Ping Yang,1 Zhiyuan Guo,2 Xiaoqiang Guo,1 Xingyu Chen,1 Qian Yao1 1Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu, 610106, People’s Republic of China; 2Sichuan Provincial Institute for Drug Control and Research, Chengdu, 610000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qian Yao, School of Pharmacy, Chengdu University, Shiling Town, Longquan District, Chengdu, Sichuan Province, 610106, People’s Republic of China, Email yaoqian@cdu.edu.cnPurpose: Most absorption enhancers boost the oral absorption of drugs via increasing intestinal permeability. However, they often damage intestinal mucosa and induce inflammatory reactions. The aim of this study is to synthesize a new absorption enhancer, punicic acid ethyl ester (PAEE), with excellent absorption-prompting effect and low toxicity.Methods: The structure of PAEE was confirmed by NMR, MS, IR and UV. Setting oleic acid (OA) as the control, the three forms of punicic acid (PA), ie, free PA, PAEE, and pomegranate seed oil, in which PA exists in the form of triglyceride, were formulated into nanoemulsions (NE). The stability, physiochemical properties of the oils and NE were compared. The permeation-enhancing effect was estimated by phenol red intestinal transport experiments. The potential damage on small intestines was assessed by biochemical assay and pathological section.Results: Though the three forms of PA had various strength in enhancing intestinal permeability, the difference was not significant (p > 0.05). Moreover, the effect was notably stronger than that of OA (p < 0.05) and was inversely related to the density and required HLB value of the oils. Compared to the corresponding oils, the NE exhibited much weaker effect in prompting intestinal permeability. Oral administration of OA and OA NE for 10 d impaired intestinal mucosa and villi along with strong inflammatory reactions in the small intestines. In contrast, the oils from PA series and their NE did not induce obvious intestinal inflammation. PAEE and its NE hindered the release of cytokines and increased the ratio of intestinal villus length to crypt depth.Conclusion: PAEE is a promising absorption enhancer with a strong permeability-prompting effect and mucosa-protecting capacity against intestinal inflammation. It provides a practical strategy to enhance the bioavailability of the drugs with poor biological membrane penetration. Keywords: punicic acid, punicic acid ethyl ester, pomegranate seed oil, nanoemulsions, permeability-enhancing effect

Junpeng Chen, Qiuyun Yao, Xirui Wang, Jinpeng Jiang, Huiyong Zhu, Dan Yu Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, People’s Republic of ChinaCorrespondence: Dan Yu, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Shangcheng District, Hangzhou City, Zhejiang Province, 310003, People’s Republic of China, Tel/Fax, Email yudang85@zju.edu.cnObjective: The multidisciplinary team (MDT) approach is increasingly being utilized in the management of complex head and neck diseases. This study analyzed the benefits of MDT for patients with head and neck diseases as primary or secondary conditions and categorized MDT meetings into two types: head and neck surgery initiation (HNI) and head and neck surgery participation (HNP). The study further explored the characteristics of these MDT meetings and the factors influencing patient compliance, aiming to optimize MDT treatment models to maximize patient benefits.Design: Retrospective analysis.Methods: MDT meetings from January 2021 to December 2023 were reviewed. The meetings and patients were classified into the HNI group and the HNP group. Various factors, including general patient conditions, disease characteristics et al were analyzed using chi-square tests and point biserial correlation tests. P-values < 0.05 were considered statistically significant.Results: A total of 292 MDT cases were analyzed, comprising 127 cases in the HNI group and 165 cases in the HNP group. In the HNI group, the initial diagnosis was modified in 11 cases (8.7%), with 92 patients (72.4%) receiving major recommendations for their treatment plans. In the HNP group, the initial diagnosis was modified in 28 cases (17.0%). The head and neck surgeons had a major impact on treatment plans in 47 cases (28.5%). Notably, patients with head and neck tumors received more major recommendations (p

Yantao Yu,1– 3,&ast; Chenkai Zhang,2,3,&ast; Qiannan Sun,2– 4 Shantanu Baral,2,3 Jianyue Ding,2,3 Fanyu Zhao,2,3 Qing Yao,2,3 Shuyang Gao,2,3 Bin Liu,2– 4 Daorong Wang1– 4 1The Yangzhou School of Clinical Medicine of Dalian Medical University, Yangzhou, 225001, People’s Republic of China; 2General Surgery Institute of Yangzhou, Yangzhou University, Yangzhou, 225001, People’s Republic of China; 3Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases, Yangzhou, 225001, People’s Republic of China; 4Northern Jiangsu People’s Hospital, Yangzhou, 225001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Daorong Wang; Bin Liu, Email 18051062590@yzu.edu.cn; liubin2006cool@126.comBackground: Gastric cancer (GC) is a highly phenotypically heterogeneous disease and is caused by a combination of factors. Retinol binding protein 4 (RBP4) is a member of a family of lipid transport proteins that are involved in the transport of substances between cells and play a crucial role in a variety of cancers. However, the expression and role of RBP4 in GC remain unknown.Methods: In this study, we explored the expression, prognostic significance, immune microenvironment, drug responsiveness and function of associated signaling pathways of RBP4 in GC using web-based bioinformatics tools. Immunohistochemistry and real-time quantitative PCR were utilized to analyze the tissue and cell expression levels of RBP4. CCK-8, colony formation, EDU incorporation, wound healing and transwell assays were applied to demonstrate the effect of RBP4 on GC cell function. Flow cytometric detection of apoptosis after RBP4 knockdown. Nude mice xenograft model elucidates the role of RBP4 for GC in vivo. Related proteins of the RAS signaling pathway were analyzed by employing Western blot assays.Results: RBP4 is highly expressed in GC. RBP4 is closely associated with patient survival and sensitivity to a wide range of antitumor agents. Knockdown of RBP4 promoted apoptosis and inhibited cell proliferation, invasion and migration. RBP4 promotes GC tumorigenesis in vivo. Finally, RBP4 modulates the RAS/RAF/ERK axis.Conclusion: RBP4 may promote gastric carcinogenesis and development through the RAS/RAF/ERK axis and is expected to be a novel target for GC treatment.Keywords: RBP4, gastric cancer, invasion, migration, RAS/RAF/ERK axis

Qingyuan Huang,1– 3,&ast; Hang Cao,1– 3,&ast; Qianlan Yao,3– 5,&ast; Xiaoyan Zhou,3– 5 Hang Li,1– 3 Qianming Bai,3– 5 Hong Hu1– 3 1Departments of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, People’s Republic of China; 2Institute of Thoracic Oncology, Fudan University, Shanghai, 200032, People’s Republic of China; 3Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of China; 4Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, People’s Republic of China; 5Institute of Pathology, Fudan University, Shanghai, 200032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Hu; Qianming Bai, Email huhong0997@163.com; baiqianming@163.comBackground: NOTCH1 is frequently mutated in non-small cell lung cancer (NSCLC), and also is a poor therapeutic target. It is of clinical importance to investigate the effects of NOTCH1 mutations on anti-tumor immunity and response to immune checkpoint blockade (ICB).Methods: An observational study with targeted sequencing in 963 NSCLC patients at our center were performed (FUSCC cohort). Data of the Cancer Genome Atlas Pan-Lung Cancer study (TCGA cohort) were analyzed, and gene set enrichment analysis (GSEA) was performed. The Samstein et al cohort included 350 patients with advanced NSCLC undergoing genomic profiling with the MSK-IMPACT assay, and receiving at least one dose of ICB therapy.Results: NOTCH1 mutations were more common in smokers and patients with squamous-cell carcinoma (SCC) (all P value < 0.05). For patients who did not receive ICB therapy (TCGA cohort), the overall survival (OS) of NOTCH1-mutant and -WT patients were comparable (log-rank P = 0.72), while for patients who received ICB therapy in the Samstein et al cohort, NOTCH1-mutant patients had significantly superior OS than WT patients (log-rank P = 0.041). On multivariate Cox analysis, the predictive value of NOTCH1 mutations reached marginal statistical significance (HR, 0.42; 95% CI, 0.17– 1.04; P = 0.059). The median of TMB for NOTCH1-mutant tumors was significantly higher than that for NOTCH1-WT tumors, and GSEA revealed that NOTCH1 mutations manifested various defects in the repair of DNA damage. NOTCH1-mutant tumors displayed an inflamed tumor microenvironment (TME), manifesting as increased PD-L1 expression and tumor-infiltrating CD8+ T cells.Conclusion: NOTCH1 mutations define a molecular subtype of NSCLC, which are more common in smokers and patients with SCC, are characterized with higher TMB, inflamed TME, and display improved survival of ICB therapy for NSCLC patients.Keywords: NOTCH1, non-small cell lung cancer, immunotherapy, survival, tumor mutational burden, tumor microenvironment

Qianqian Yao,1,&ast; Kexin Jiang,1,&ast; Fei Lin,2 Tao Zhu,3 Nazeer Hussain Khan,1,4 Enshe Jiang1,4 1Institute of Nursing and Health, Henan University, Kaifeng, People’s Republic of China; 2School of Medicine, Shangqiu Institute of Technology, Shangqiu, People’s Republic of China; 3Department of Geriatrics, Kaifeng Traditional Chinese Medicine Hospital, Kaifeng, People’s Republic of China; 4Henan International Joint Laboratory for Nuclear Protein Regulation, Henan University, Kaifeng, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Enshe Jiang, Email esjiang@gmail.comAbstract: Alzheimer’s disease (AD), the most common cause of dementia and the fifth leading cause of death in the adult population has a complex pathophysiological link with hypertension (HTN). A growing volume of published literature on a parallel elevation of blood pressure (BP), amyloid plaques, and neurofibrillary tangles formation in post-middle of human brain cells has developed new, widely accepting foundations on this association. In particular, HTN in elderly life mediates cerebral blood flow dysfunction, neuronal dysfunction, and significant decline in cognitive impairment, primarily in the late-life populace, governing the onset of AD. Thus, HTN is an established risk factor for AD. Considering the impact of AD, 1.89 million deaths annually, and the failure of palliative therapies to cure AD, the scientific research community is looking to adopt integrated approaches to target early modified risk factors like HTN to reduce AD burden. The current review highlights the significance and impact of HTN-based prevention in lowering the AD burden in the elderly by providing a comprehensive overview of the physiological relationship between AD and HTN with an in-detail explanation of the role and applications of pathological biomarkers in this clinical association. The review will gain worth in presenting new insights and providing inclusive discussion on the correlation between HTN and cognitive impairment. It will increase across a wider scientific audience to expand understanding of this pathophysiological association.Keywords: Alzheimer’s disease, hypertension, elderly population, clinical biomarkers

Yingli Wu,1– 3,&ast; Yu Yang,1– 3,&ast; Xiaolin Lv,1– 3 Menghan Gao,1 Xujin Gong,1– 3 Qingqiang Yao,1– 4 Yanna Liu1– 3 1School of Pharmacy and Pharmaceutical Sciences & Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, People’s Republic of China; 2NHC Key Laboratory of Biotechnology Drugs (Shandong Academy of Medical Sciences), Jinan, Shandong, 250117, People’s Republic of China; 3Key Laboratory for Rare & Uncommon Diseases of Shandong Province, Jinan, Shandong, 250117, People’s Republic of China; 4Jining Medical University, Jining, Shandong, 272067, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingqiang Yao, Jining Medical University, No. 133 HeHua Road, Jinan, Shandong, 272067, People’s Republic of China, Email qqyao@sdfmu.edu.cn Yanna Liu, Shandong First Medical University, No. 6699 Qingdao Road, HuaiYin District, Jinan, Shandong, 250117, People’s Republic of China, Email liuyanna@sdfmu.edu.cnAbstract: Ovarian cancer is one of the most common malignant tumors in gynecology with a high incidence. Combination therapy, eg, administration of paclitaxel followed by a platinum anticancer drug is recommended to treat ovarian cancer due to its advantages in, eg, reducing side effects and reversing (multi)drug-resistance compared to single treatment. However, the benefits of combination therapy are often compromised. In chemo and chemo/gene combinations, co-deposition of the combined therapeutics in the tumor cells is required, which is difficult to achieve due to dramatic pharmacokinetic differences between combinational agents in free forms. Moreover, some undesired properties such as the low-water solubility of chemodrugs and the difficulty of cellular internalization of gene therapeutics also hinder the therapeutic potential. Delivery of dual or multiple agents by nanoparticles provides opportunities to tackle these limits. Nanoparticles encapsulate hydrophobic drug(s) to yield aqueous dispersions facilitating its administration and/or to accommodate hydrophilic genes facilitating its access to cells. Moreover, nanoparticle-based therapeutics can not only improve drug properties (eg, in vivo stability) and ensure the same drug disposition behavior with controlled drug ratios but also can minimize drug exposure of the normal tissues and increase drug co-accumulation at targeted tissues via passive and/or active targeting strategies. Herein, this work summarizes nanoparticle-based combination therapies, mainly including anticancer drug-based combinations and chemo/gene combinations, and emphasizes the advantageous outcomes of nanocarriers in the combination treatment of ovarian cancer. In addition, we also review mechanisms of synergetic effects resulting from different combinations.Keywords: ovarian cancer, nanoparticles, combination therapy, chemotherapy, gene therapy

Ying Shi1– 3&ast;, Wenming Kong1 &ast;, Haiqin Jiang,2,3 Wenyue Zhang,2,3 Chen Wang,2– 4 Limei Wu,1 Yunliang Shen,1 Qiang Yao,1 Hongsheng Wang1– 3,5 1Department of Leprosy Control, Zhejiang Provincial Institute of Dermatology, Huzhou, People’s Republic of China; 2Hospital of Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, People’s Republic of China; 3National Centre for STD and Leprosy Control, China CDC, Nanjing, People’s Republic of China; 4Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China; 5Centre for Global health, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China&ast; These authors contributed equally to this workCorrespondence: Qiang Yao, Department of Leprosy Control, Zhejiang Provincial Institute of Dermatology, St 61, Zhejiang, People’s Republic of China, Email 7793908@qq.com Hongsheng Wang, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 12 Jiangwangmiao Street, Nanjing, People’s Republic of China, Tel: +86 025 8547 8953, Email whs33@vip.sina.comPurpose: Reports on antimicrobial resistance (AMR) of Mycobacterium leprae (M. leprae) in Zhejiang Province are limited. Thus, this study aimed to investigate the drug resistance of new leprosy cases within several years and analyse the emergence of AMR mutations from Zhejiang Province.Methods: This study enrolled 34 leprosy cases in Zhejiang Province, China, from 2018 to 2021. Gene mutation of WHO-recommended DRDRs (folP1, rpoB and gyrA) and genes of compensatory AMR-associated DRDRs, including nth, rpoA, rpoC, gyrB and 23S rRNA, were detected by amplification. Clinical data analysis was performed to investigate the epidemiological association of leprosy.Results: Of the 34 samples, 2 (5.9%) strains showed drug resistance, which were mutated to dapsone and ofloxacin, separately. Two single mutations in gyrB were detected in different strains (5.9%), whereas one of the rpoC mutation was also detected in one strain each (2.9%), which were proved to be polymorphs. No correlation of drug resistance proportion was identified in male vs female, nerve vs no nerve involvement, deformity vs no deformity and reaction vs non-reaction cases.Conclusion: Results showed well control of leprosy patients in Zhejiang Province. Gene mutations of WHO-recommended DRDRs folP1 and gyrA confirmed the resistance to dapsone and ofloxacin. Compensatory AMR-associated mutations confirmed to be polymorphs still require further study to determine their phenotypic outcomes in M. leprae. The results demonstrated that drug-resistant strains are not epidemic in this area. Given the few cases of leprosy, analysing the AMR of M. leprae in Zhejiang Province more comprehensively is difficult. However, regular MDT treatment and population management in the early stage may contribute to the low prevalence of leprosy.Keywords: M. leprae, antimicrobial resistance, gene mutation

Xiaoming Li,1,2,&ast; Qiandong Yao,3,&ast; Chen Liu,1,&ast; Jian Wang,1 Huarong Zhang,4 Shiguang Li,2,5 Ping Cai1 1Department of Radiology, Southwest Hospital, Third Military Medical University (Army Military Medical University), Chongqing, People’s Republic of China; 2Department of Radiology, The First People’s Hospital of Zunyi, The Third Affiliated Hospital of Zunyi Medical University, Zunyi, People’s Republic of China; 3Department of Radiology, Sichuan Science City Hospital, Mianyang, People’s Republic of China; 4Institute of Pathology and Southwest Cancer Center, Third Military Medical University (Army Military Medical University), Chongqing, People’s Republic of China; 5The Second People’s Hospital of Guiyang (Jinyang Hospital), Guiyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shiguang Li; Ping Cai, Email imaging_sgli@163.com; 530305942@qq.comAbstract: Hepatocellular carcinoma is one of the most common malignancies globally. Recently, a newly identified histological subtype, designated as “macrotrabecular-massive hepatocellular carcinoma” (MTM-HCC), has been associated with an aggressive phenotype and has received extensive attention. MTM-HCC was a strong independent prognostic predictor of early and overall recurrence because it is closely related to tumor molecular subclass, gene mutation, carcinogenesis pathways, and immunohistochemical markers. In addition, preoperative imaging examination can potentially provide an essential clue for diagnosing MTM-HCC, intratumor necrosis or ischemia is an independent predictor for MTM-HCC on Gd-EOB-DTPA enhanced MRI or CT. Early diagnosis and appropriate treatment of MTM-HCC could prove beneficial for preventing early recurrence and could improve outcomes.Keywords: hepatocellular carcinoma, macrotrabecular-massive, molecular subclass, gene mutation, magnetic resonance imaging

Changqing Zhang,1 Changqi Cui,1 Qi Yao2 1School of Economics and Business Administration, Chongqing University, Chongqing, 400030, People’s Republic of China; 2School of Economics and Management, Chongqing Jiaotong University, Chongqing, 400074, People’s Republic of ChinaCorrespondence: Changqi CuiSchool of Economics and Business Administration, Chongqing University, Shazheng Street, No. 174, Shapingba District, Chongqing, 400030, People’s Republic of ChinaTel +86 13752905059Email cuichangqi@cqu.edu.cnPurpose: In the big data era, many institutions (ie, hospitals) and firms use various methods to encourage people to disclose more personal information to gain competitive advantages in many businesses, such as healthcare and the Internet of Things (IoT) devices. Discussions on antecedents of individuals’ willingness to reveal private data from individual differences perspective are limited. Drawing on information boundary theory, we examine how self-construal prompts a different regulatory focus (promotion focus versus prevention focus), thus, affects individuals’ willingness to disclose private data.Methods: A mixed-method approach was used to examine our hypothesis. Study 1 (N = 93, participants in China) manipulated self-construal in lab experiments and examined participants’ actual disclosure behavior in the emerging IoT context of connected cars. Study 2 (an online survey, N = 200, participants in US) measured chronic self-construal in another disclosure context (healthcare app), replicating the preliminary effect and examined the mediating effect of the regulatory focus. Study 3 (an online experiment, N = 284, participants in US) tested the moderating effect of message framing.Results: Study 1 showed that participants primed an independent self-construal were more willing to share private information, whether it is real driving data or private identity information. Study 2 showed that independent (interdependent) self-construal individuals tend to have promotion focus (prevention focus), thus leading to higher (lower) willingness to disclose personal health information. Study 3 demonstrated that independent (interdependent) self-construal individuals are more willing to share information when presented with gain-framing (loss-framing) information.Conclusion: Independent (interdependent) self-construal positively (negatively) affects individuals’ willingness to disclose and these effects will be mediated by regulatory focus and moderated by message farming. Our study provides a theoretical paradigm that is new to the willingness to disclose literature, and offers an effective, actionable strategy on how institutions and firms can facilitate individuals’ personal information disclosure.Keywords: self-construal, willingness to disclose, regulatory focus, information boundary theory, message framing, privacy

Background There are currently three strategies for the duration of low molecular weight heparin (LMWH) lead-in before direct oral anticoagulants (DOACs) in patients with acute pulmonary embolism (PE): one is at least 5 days, the other is at least 3 days and the last one is less than 3 days. Which one is the best is yet unknown. Aim To explore optimal initial duration of LMWH lead-in before DOACs for short-term outcomes of hospitalized patients with non-high-risk acute PE. Design Retrospective observational cohort study using propensity score matching. Methods We divided non-high-risk PE patients into short-LMWH (LMWH <3 days), intermediate-LMWH (LMWH 3-5 days) and long-LMWH (LMWH >5 days) groups, in a 1:1:2 ratio by using propensity score matching. Primary outcomes were a composite of mortality including all-cause and PE-related mortality, VTE recurrence and major bleeding, as well as each one of them, at 3-month after PE diagnosis. Results The short-LMWH group (N  = 504) had higher 3-month composite primary outcome (129 [25.6%] vs. 67 [13.3%], P  < 0.001), all-cause mortality (112 [22.2%] vs. 39 [7.7%], P  < 0.001) and PE-related mortality (48 [9.5%] vs. 17 [3.4%], P  < 0.001), than the intermediate-LMWH group (N  = 504). The short-LMWH group also had higher 3-month composite primary outcome (129 [25.6%] vs. 151 [15.0%], P  < 0.001), all-cause mortality (112 [22.2%] vs. 90 [8.9%], P  < 0.001) and PE-related mortality (48 [9.5%] vs. 41 [4.1%], P  < 0.001) than the long-LMWH group (N  = 1008). The VTE recurrence and major bleeding rates were similar between the short-LMWH and intermediate-LMWH groups, and between the short-LMWH and long-LMWH groups. The intermediate-LMWH and long-LMWH groups had similar 3-month primary outcomes rates in whole or in part with each other. Conclusions For patients with non-high-risk acute PE, the optimal duration of initial LMWH lead-in before switching to DOACs could be 3–5 days. [ABSTRACT FROM AUTHOR]

A dual-jet collecting device is highly efficient at picking up small-sized polymetallic nodules; however, its performance is not as effective for large nodules in deep-sea mining. To address this problem, numerical simulations have been conducted to thoroughly investigate the flow characteristics and particle motions during the collection of larger nodules. The collection performance of the enhanced device is analyzed across varying front jet velocities (Vf), suction pressures (Pout), and nozzle heights (h/d). The results reveal that increasing Vf improves the drag force and particle velocity in the jet impingement and upwelling zones, facilitating nodule lifting movement and transport. However, increasing Pout reduces the drag forces in these zones while increasing the particle velocity in the upwelling zone. A large Pout is not conducive to nodule initiation but has benefits for transport. Increasing h/d reduces the drag force in the anti-gravity direction in the jet impingement zone. The improved collecting device attains a pick-up efficiency that exceeds 80% for large-sized nodules when h/d < 1.3. The pick-up efficiency with suction pressure, which remains 40%, is higher than that without suction pressure when h/d > 1.3. The research findings may shed light on the design of more efficient dual-jet collection systems. [ABSTRACT FROM AUTHOR]

Qicen Yao,1,* Qingchao Wu,2,* Xiayu Xu,1 Yixi Xing,1 Jin Liang,1 Qianqi Lin,1 Meiqiong Huang,1 Yiling Chen,1 Bo Lin,3 Weifei Chen1 1Department of Rheumatology and Immunology, The Second Affiliated Hospital of Hainan Medical University, Haikou, People’s Republic of China; 2Department of Rheumatology and Immunology, Minda Hospital of Hubei Minzu University, Enshi, Hubei Province, People’s Republic of China; 3Department of Pharmacy, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weifei ChenDepartment of Rheumatology and Immunology, The Second Affiliated Hospital of Hainan Medical University, 368 Yehai Boulevard, Haikou City, Hainan Province, People’s Republic of ChinaEmail chenwf130@163.comBo LinDepartment of Pharmacy, The Second Affiliated Hospital of Hainan Medical University, 368 Yehai Boulevard, Haikou City, Hainan Province, People’s Republic of ChinaEmail linbo13518072160@163.comPurpose: Resveratrol (Res) is a natural polyphenolic compound found in several plants and reported as a promising biological molecule with effective anti-fibrosis and anti-inflammatory activities. However, the underlying mechanism of Res on systemic sclerosis (SSc) remains unclear. In the study, we identified the key cellular signaling pathways involved in the Res regulatory process on SSc.Methods: Res-targeted genes interaction network was constructed using the STITCH database, and the shared Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways involved in both SSc and Res-targeted genes were then identified. The top five enriched KEGG pathways were visualized by GOplot. KEGG pathways associated with Res-targeted genes were established by Pathway Builder Tool 2.0. Quantitative real-time PCR (qRT-PCR) was used to assess the expression of sirtuin 1 (SIRT1), mammalian targeted of rapamycin (mTOR), and cytokines.Results: Enrichment analysis of Res-targeted genes showed 79 associated pathways, 27 of which were also involved in SSc. Particularly, SIRT1/mTOR signaling was found as one of the crucial regulatory pathways. In vitro results suggested that SIRT1-mediated mTOR degradation ameliorated bleomycin (BLM)-induced fibrosis and inflammation. Res was capable of elevating the SIRT1 level in fibroblasts and partially reversing mTOR-dependent induction of fibrosis and inflammation.Conclusion: These results indicated that Res is a feasible and effective choice for SSc and therapeutic target of mTOR could be a potential alternative for treatment of SSc.Keywords: resveratrol, systemic sclerosis, SIRT1, mTOR, signaling

Yun-Liang Shen,1,* Si-Yu Long,2,* Wen-Ming Kong,1 Li-Mei Wu,1 Li-Juan Fei,1 Qiang Yao,1 Hong-Sheng Wang2 1Department of Leprosy Control, Zhejiang Provincial Institute of Dermatology, Huzhou, People’s Republic of China; 2Laboratory of Leprosy and Other Mycobacterial Infections, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong-Sheng WangLaboratory of Leprosy and Other Mycobacterial Infections, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, St 12 Jiangwangmiao, Nanjing, Jiangsu 210042, People’s Republic of ChinaEmail whs33@vip.sina.comQiang YaoDepartment of Leprosy Control, Zhejiang Provincial Institute of Dermatology, St 61, Wuyuan, Huzhou, Zhejiang 313200, People’s Republic of ChinaEmail 7793908@qq.comPurpose: Genome-wide association studies (GWAS) have identified multiple genetic variants associated with leprosy. To investigate the single and combined associations between single-nucleotide polymorphisms (SNPs) and the development of leprosy, we therefore performed generalized multi-analytical (GMDR) analysis in Chinese leprosy household contacts and constructed a risk prediction model.Patients and Methods: This case–control study included 229 leprosy cases and 233 healthy household contacts in Zhejiang province, China. Participants were genotyped for 17 polymorphisms selected from GWAS. The Pearson χ2 test, logistic regression and GMDR analysis were performed to investigate gene–gene interactions and construct a risk prediction model for leprosy.Results: The genotype and the allele distributions of rs142179458, rs2275606, rs663743 and rs73058713 were significantly different between patients and controls. rs2275606, rs6478108, rs663743 and rs73058713 showed an association after adjusting for sex and age in the logistic regression. A five-way interaction model consisting of rs2058660, rs2275606, rs4720118, rs6478108 and rs780668 was chosen as the optimal model for determining leprosy susceptibility. The model classified 237 (51.3%) into the low-risk group and 225 (48.7%) individuals into the high-risk group. The area under the curve (AUC) of this model was 0.757 (95% CI: 0.712– 0.803), and the odds ratio for leprosy between the high- and low-risk groups was 9.733 (95% CI: 6.384– 14.960; P< 0.001). The sensitivity and specificity of the model were observed to be 74.7% and 76.8%, respectively.Conclusion: Our results suggest that rs2058660, rs2275606, rs4720118, rs6478108 and rs780668, five SNPs with a significant sole effect on leprosy, interact to confer a higher risk for the disease in leprosy household contacts (HHCs).Keywords: leprosy, gene–gene interactions, generalized multi-analytical, risk stratification

Xuefeng Kan,*,1,2 Yong Wang,*,1–3 Ping Han,1,2 Qi Yao,1,2 Kun Qian,1,2 Bin Xiong,*,1,2 Chuansheng Zheng*,1,21Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; 2Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China; 3Department of Vascular and Interventional Radiology, The Second Affiliated Hospital of Hainan Medical University, Haikou 570311, China*These authors contributed equally to this workPurpose: To assess the value of the combined ultrasound (US)/computed tomography (CT) guidance (US guidance was firstly used for puncture with the electrode needle to the site close to the tumor, and subsequently, CT guidance was used for precise positioning of the electrode tips) in percutaneous radiofrequency ablation (RFA) after transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) in the hepatic dome.Methods: From January 1, 2013 to June 30, 2017, medical records of 65 patients with HCCs in the hepatic dome who received TACE treatment before RFA procedure were retrospectively analyzed. Among them, 34 patients with 35 liver tumors underwent percutaneous RFA under combined US/CT guidance, and 31 patients with 35 liver tumors received percutaneous RFA under CT guidance alone. The efficacy of combined US/CT-guided RFA was analyzed, and the procedure time and safety between the two groups were compared.Results: In the combined US/CT-guided RFA group, the 1-, 3-, and 5-year local recurrence rates were 3%, 6%, 9%, respectively, and the 1-, 3-, and 5-year overall survival rates were 100%, 97%, 94%, respectively. The mean procedure time in the CT-guided RFA group was significantly longer than that of the combined US/CT-guided RFA group (P

Yucheng Lin,1-3,* Lu Zhang,4,* Nancy Q Liu,5 Qingqiang Yao,1,2 Ben Van Handel,5 Yan Xu,1,2 Chen Wang,3 Denis Evseenko,5 Liming Wang1,21Department of Orthopaedic Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Digital Medicine Institute, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 3Department of Orthopaedic Surgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China; 4Department of Anesthesiology, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu, People’s Republic of China; 5Department of Orthopaedic Surgery, University of Southern California (USC), Los Angeles, CA, USA*These authors contributed equally to this workPurpose: In order to accelerate the tendon-bone healing processes and achieve the efficient osteointegration between the tendon graft and bone tunnel, we aim to design bioactive electrospun nanofiber membranes combined with tendon stem/progenitor cells (TSPCs) to promote osteogenic regeneration of the tendon and bone interface.Methods: In this study, nanofiber membranes of polycaprolactone (PCL), PCL/collagen I (COL-1) hybrid nanofiber membranes, poly(dopamine) (PDA)-coated PCL nanofiber membranes and PDA-coated PCL/COL-1 hybrid nanofiber membranes were successfully fabricated by electrospinning. The biochemical characteristics and nanofibrous morphology of the membranes, as well as the characterization of rat TSPCs, were defined in vitro. After co-culture with different types of electrospun nanofiber membranes in vitro, cell proliferation, viability, adhesion and osteogenic differentiation of TSPCs were evaluated at different time points.Results: Among all the membranes, the performance of the PCL/COL-1 (volume ratio: 2:1 v/v) group was superior in terms of its ability to support the adhesion, proliferation, and osteogenic differentiation of TSPCs. No benefit was found in this study to include PDA coating on cell adhesion, proliferation and osteogenic differentiation of TSPCs.Conclusion: The PCL/COL-1 hybrid electrospun nanofiber membranes are biocompatible, biomimetic, easily fabricated, and are capable of supporting cell adhesion, proliferation, and osteogenic differentiation of TSPCs. These bioactive electrospun nanofiber membranes may act as a suitable functional biomimetic scaffold in tendon-bone tissue engineering applications to enhance tendon-bone healing abilities.Keywords: electrospinning, TSPCs, nanomaterial, biomimetic scaffold, osteogenic differentiation, tendon-bone healing