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Nanan Miao,1,* Tao Jiang,1,* Yuanchao Li,1 Sihong Xue,1 Shilei Hao,2 Chunli Zhou,1 Yujie Gu,1 Ran Li,1 Bo Yu,1 Xiaoqu Duan,1 Wenchao Xu,1 Rupeng Wang,1 Lei Ran1 1Department of Rheumatology and Dermatology, The Second Affiliated Hospital of Army Medical University, Chongqing, People’s Republic of China; 2College of Bioengineering, University of Chongqing, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rupeng Wang; Lei Ran, Department of Rheumatology and Dermatology, The Second Affiliated Hospital of Army Medical University, Chongqing, 400037, People’s Republic of China, Tel +86 23 68755739, Email Wrp71@tmmu.edu.cn; ranlei1010@tmmu.edu.cnBackground: Wound healing is a complex physiological process that can be roughly divided into four stages: hemostasis, inflammation, proliferation, and remodeling. Conventional wound dressings often fail to meet the diverse needs of these healing stages due to their limited functionality. Cryogels, however, possess several attractive properties, such as large, interconnected pores, good mechanical strength, and ease of modification, making them suitable for developing advanced dressings with multiple functions. In this study, we developed a multifunctional cryogel dressing, with biocompatible polysaccharides as the main component, designed to provide a breathable, moist, and antibacterial microenvironment for chronic infected wounds, thereby promoting wound healing.Methods: Recombinant keratin 31 (RK31) was combined with chitosan (CS) to produce a CS/RK31 cryogel, referred to as CK. Gallic acid-reduced silver nanoparticles (GA/Ag NPs) were incorporated as the active antibacterial component to create the CS/K31@GA/Ag cryogel, known as CKGA. The cryogel was characterized using scanning electron microscopy (SEM) and a universal testing machine, and its biocompatibility was assessed in vitro. The dynamic hemostatic performance of the cryogel was evaluated with a rat tail amputation bleeding model. Additionally, the antibacterial effects of the cryogel against Staphylococcus aureus and Escherichia coli were tested using agar diffusion assays and turbidimetry. The antioxidant capacity of the CKGA cryogel was also measured in vitro. Finally, the cryogel’s ability to promote wound healing was tested in an SD rat model of infected wounds.Results: Characterization results showed that the CKGA cryogel features an interpenetrating porous network structure and exhibits excellent mechanical properties, with a swelling rate of up to 1800%. Both in vitro and in vivo experiments confirmed that the cryogel has good biocompatibility, effectively absorbs exudates, and rapidly stops bleeding. The addition of GA/Ag NPs provided significant antibacterial effects, achieving an inhibition rate of over 99.9% against both S. aureus and E. coli. Furthermore, CKGA cryogels demonstrated a strong scavenging capacity for ROS in a dose-dependent manner. Studies using the SD rat infected wound model showed that the cryogel effectively inhibited bacterial proliferation on wound surfaces, reduced local tissue inflammation, and promoted the healing of infected wounds.Conclusion: The multifunctional cryogel, with its rapid hemostatic, antibacterial, and antioxidant properties, as well as its ability to promote cell proliferation, could be widely used as a wound dressing for the healing of bacterial infections. Keywords: nanocomposite cryogel, hemostasis, antioxidant, antibacterial, wound healing

Qian Cao,1,* Ruijie Zhou,2,* Songlin Guo,3 Kai Meng,4 Xiaojuan Yang,5 Miao Liu,1 Bin Ma,6 Chunxia Su,5 Xiangguo Duan2 1The First School of Clinical Medicine, Ningxia Medical University, Yinchuan, 750004, People’s Republic of China; 2School of Inspection, Ningxia Medical University, Yinchuan, 750004, People’s Republic of China; 3Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, Yinchuan, 750004, People’s Republic of China; 4Traditional Chinese Medicine Hospital of Ningxia Medical University, Yinchuan, 750003, People’s Republic of China; 5School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, 750004, People’s Republic of China; 6Department of Oncology Surgery, the First People’s Hospital of Yinchuan, Yinchuan, 750004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chunxia Su, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, 750004, People’s Republic of China, Email 1651085195@qq.com Xiangguo Duan, School of Inspection, Ningxia Medical University, Yinchuan, 750004, People’s Republic of China, Email 2455281549@qq.comBackground: Tumor vaccines have achieved remarkable progress in treating patients with various tumors in clinical studies. Nevertheless, extensive research has also revealed that tumor vaccines are not up to expectations for the treatment of solid tumors due to their low immunogenicity. Therefore, there is an urgent need to design a tumor vaccine that can stimulate a broad anti-tumor immune response.Methods: In this work, we developed a nanovaccine (NP-TCL@APS), which includes nanoparticles loaded with colorectal cancer tumor cell lysates (TCL) and Astragalus polysaccharides (APS) into poly (lactic-co-glycolic acid) to induce a robust innate immune response. The NP-TCL@APS was identified by transmission electron microscopy and Malvern laser particle size analyzer. The killing and immune activation effects of NP-TCL@APS were evaluated in vitro. Finally, safety and anti-tumor efficacy were evaluated in the colorectal cancer tumor-bearing mouse model.Results: We found that NP-TCL@APS was preferentially uptaken by DC and further promoted the activation of DC in vitro. Additionally, nanoparticles codelivery of TCL and APS enhanced the antigen-specific CD8+ T cell response and suppressed the growth of tumors in mouse models with good biocompatibility.Conclusion: We successfully prepared a nanovaccine termed NP-TCL@APS, which can promote the maturation of DC and induce strong responses by T lymphocytes to exert anti-tumor effects. The strategy proposed here is promising for generating a tumor vaccine and can be extended to various types of cancers.Keywords: colorectal cancer, nanovaccine, PLGA, Astragalus polysaccharide, tumor cell lysates (TCL)

Xinru Hu,* Meng Chen,* Jahanzeb Nawaz, Xi Duan Department of Dermatovenereology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xi Duan, Department of Dermatovenereology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China, Email dancing913@126.comBackground: The mechanism underlying skin photoaging remains elusive because of the intricate cellular and molecular changes that contribute to this phenomenon, which have yet to be elucidated. In photoaging, the roles of keratinocytes and fibroblasts are vital for maintaining skin structure and elasticity. But these cells can get photo-induced damage during photoaging, causing skin morphological changes. Recently, the function of natural active ingredients in treating and preventing photoaging has drawn more attention, with researches often focusing on keratinocytes and fibroblasts.Methods: We searched for studies published from 2007 to January 2024 in the Web of Science, PubMed, and ScienceDirect databases through the following keywords: natural plant, natural plant products or phytochemicals, traditional Chinese Medicine or Chinese herbal, plant extracts, solar skin aging, skin photoaging, and skin wrinkling. This review conducted the accordance of Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines.Results: In total, 87 researches were included in this review (Figure 1). In keratinocytes, natural compounds may primarily regulate signal pathways such as the NF-κB, MAPK, PI3K/AKT, and Nrf2/ARE pathways, reducing inflammation and cellular damage, thus slowing skin photoaging. Additionally, in fibroblasts, natural active ingredients primarily promote the TGF-β pathway, inhibit MMPs activity, and enhance collagen synthesis while potentially modulating the mTOR pathway, thereby protecting the dermal collagen network and reducing wrinkle formation. Several trials showed that natural compounds that regulate keratinocytes and fibroblasts responses have significant and safe therapeutic effects.Conclusion: The demand for natural product-based ingredients in sunscreen formulations is rising. Natural compounds show promising anti-photoaging effects by targeting cellular pathways in keratinocytes and fibroblasts, providing potential therapeutic strategies. However, comprehensive clinical studies are needed to verify their efficacy and safety in mitigating photoaging, which should use advanced pharmacological methods to uncover the complex anti-photoaging mechanisms of natural compounds.Keywords: photoaging, natural ingredients, natural compounds, keratinocytes, fibroblasts

Kaiyu Wang,1,* Yan Gao,1,* Shan Wu,1,* Jin Zhang,1 Manfang Zhu,2 Xiayu Chen,1 Xizi Fu,1 Xingmei Duan,2 Ke Men1 1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xingmei Duan, Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of China, Email duanxingmei2003@163.com Ke Men, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, 610041, People’s Republic of China, Email mendingbob@hotmail.comBackground: Messenger RNA (mRNA)-based immunogene therapy holds significant promise as an emerging tumor therapy approach. However, the delivery efficiency of existing mRNA methods and their effectiveness in stimulating anti-tumor immune responses require further enhancement. Tumor cell lysates containing tumor-specific antigens and biomarkers can trigger a stronger immune response to tumors. In addition, strategies involving multiple gene therapies offer potential optimization paths for tumor gene treatments.Methods: Based on the previously developed ideal mRNA delivery system called DOTAP-mPEG-PCL (DMP), which was formed through the self-assembly of 1.2-dioleoyl-3-trimethylammonium-propane (DOTAP) and methoxypoly (ethylene glycol)-b-poly (ϵ-caprolactone) (mPEG-PCL), we introduced a fused cell-penetrating peptide (fCPP) into the framework and encapsulated tumor cell lysates to form a novel nanovector, termed CLSV system (CLS: CT26 tumor cell lysate, V: nanovector). This system served a dual purpose of facilitating the delivery of two mRNAs and enhancing tumor immunogene therapy through tumor cell lysates.Results: The synthesized CLSV system had an average size of 241.17 nm and a potential of 39.53 mV. The CLSV system could not only encapsulate tumor cell lysates, but also deliver two mRNAs to tumor cells simultaneously, with a transfection efficiency of up to 60%. The CLSV system effectively activated the immune system such as dendritic cells to mature and activate, leading to an anti-tumor immune response. By loading Bim-encoded mRNA and IL-23A-encoded mRNA, CLSV/Bim and CLSV/IL-23A complexes were formed, respectively, to further induce apoptosis and anti-tumor immunity. The prepared CLSV/dual-mRNA complex showed significant anti-cancer effects in multiple CT26 mouse models.Conclusion: Our results suggest that the prepared CLSV system is an ideal delivery system for dual-mRNA immunogene therapy.Keywords: mRNA gene therapy, dual-mRNA delivery, tumor cell lysates, Bim and IL-23A mRNAs, immune response

Jing Huang,1,* Kaiyu Wang,1,* Xizi Fu,1,* Manfang Zhu,2 Xiaohua Chen,1 Yan Gao,1 Pingchuan Ma,3 Xingmei Duan,2 Ke Men1 1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of China; 3State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ke Men, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China, Email mendingbob@hotmail.com Xingmei Duan, Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of China, Email duanxingmei2003@163.comBackground: Messenger ribonucleic acid (mRNA)-based gene therapy has great potential in cancer treatment. However, the application of mRNA-based cancer treatment could be further developed. Elevated delivery ability and enhanced immune response are advantages for expanding the application of mRNA-based cancer therapy. It is crucial that the prepared carrier can cause an immune reaction based on the efficient delivery of mRNA.Methods: We reported DMP nanoparticle previously, which was obtained by the self-assembly of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) and (ethylene glycol)-b-poly (ϵ-caprolactone) (mPEG-PCL). Research demonstrated that DMP can deliver mRNA, siRNA, and plasmid. And it is applied to various tumor types. In our work, the tumor cell lysate was introduced to the internal DMP chain, fusing cell-penetrating peptides (CPPs) modification on the surface forming the CLSV system. And then mixed encoded IL-22BP (interleukin-22 binding protein) mRNA and CLSV to form CLSV/IL-22BP complex.Results: The size of the CLSV system was 213.2 nm, and the potential was 45.7 mV. The transfection efficiency of the CLSV system is up to 76.45% in C26 cells via the micropinocytosis pathway. The CLSV system also could induce an immune response and significantly elevate the expression of CD80, CD86, and MHC-II in vivo. Then, by binding with IL-22BP (Interleukin-22 binding protein) mRNA, the CLSV/IL-22BP complex inhibited tumor cell growth, with an inhibition rate of up to 82.3% in vitro. The CLSV/IL-22BP complex also inhibited tumor growth in vivo, the tumor cell growth inhibition up to 75.0% in the subcutaneous tumor model, and 84.9% in the abdominal cavity metastasis tumor model.Conclusion: Our work demonstrates that the CLSV system represents a potent potential for mRNA delivery.Keywords: mRNA, cell-penetrating peptide, gene therapy, tumor cell lysate, immune response

Hanxiao Liu,1– 3 Hui Lv,2,3 Xuehui Duan,3 Yan Du,3 Yixuan Tang,3 Wei Xu1– 3 1School of Pharmacy, Weifang Medical University, Weifang, Shandong, 261053, People’s Republic of China; 2Department of Pharmacy, the First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, 250014, People’s Republic of China; 3School of Pharmaceutical Sciences & Institute of Materia Medica, National Key Laboratory of Advanced Drug Delivery System, Medical Science and Technology Innovation Center, Key Laboratory for Biotechnology Drugs of National Health Commission, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, People’s Republic of ChinaCorrespondence: Yixuan Tang; Wei Xu, Email tangyixuan@sdfmu.edu; xuwei6420@126.comAbstract: Macrophages play a crucial role in tissue homeostasis and the innate immune system. They perform essential functions such as presenting antigens, regulating cytokines, and responding to inflammation. However, in diseases like cancer, cardiovascular disorders, and autoimmune conditions, macrophages undergo aberrant polarization, which disrupts tissue regulation and impairs their normal behavior. To address these challenges, there has been growing interest in developing customized targeted drug delivery systems specifically designed for macrophage-related functions in different anatomical locations. Nanomedicine, utilizing nanoscale drug systems, offers numerous advantages including improved stability, enhanced pharmacokinetics, controlled release kinetics, and precise temporal drug delivery. These advantages hold significant promise in achieving heightened therapeutic efficacy, specificity, and reduced side effects in drug delivery and treatment approaches. This review aims to explore the roles of macrophages in major diseases and present an overview of current strategies employed in targeted drug delivery to macrophages. Additionally, this article critically evaluates the design of macrophage-targeted delivery systems, highlighting limitations and discussing prospects in this rapidly evolving field. By assessing the strengths and weaknesses of existing approaches, we can identify areas for improvement and refinement in macrophage-targeted drug delivery.Keywords: macrophages, nanomedicine, drug delivery, tumors, autoimmune disease

Jingmei Li,1,* Jin Zhang,1,* Yan Gao,1 Sibei Lei,1 Jieping Wu,1 Xiaohua Chen,1 Kaiyu Wang,1 Xingmei Duan,2 Ke Men1 1Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ke Men, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, 610041, People’s Republic of China, Email mendingbob@hotmail.com Xingmei Duan, Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of China, Email duanxingmei2003@163.comIntroduction: Cell-membrane nanocarriers are usually constructed by modifying the nanoparticle surface with cell membrane extracts, which has a direct benefit in endowing targeting capacity to nanocarriers based on their original cell types. However, delivering nucleic acid cargos by cell membrane–based nanoparticles is difficult owing to the strong negative charge of the cell membrane fraction. In this study, we developed a cancer cell membrane–based drug delivery system, the cMDS, for efficient siRNA delivery. Meanwhile, the cancer-specific immune response stimulated by the gene vector itself could offer synergistic anti-cancer ability.Methods: The cMDS was prepared by ultrasound, and its transfection efficiency and anti-cancer ability were examined using cultures of CT26 cells. MTT and red blood cell hemolysis tests were performed to assess the safety of cMDS, while its targeted gene delivery and strong immune stimulation were investigated in a subcutaneous tumor model. Moreover, the detailed anti-cancer immune stimulation mechanisms of cMDS are uncovered by protein chip analysis.Results: The cMDS was spherical core-shell structure. It showed high transfection efficiency and anti-cancer ability in vitro. In animal experiments, intravenously administered cMDS/siStat3 complex efficiently suppress the growth of colon cancer. Moreover, the result of protein chip analysis suggested that cMDS affect the migration and chemotaxis of immune cells.Conclusion: The cMDS shows obvious tumor tissue-specific accumulation properties and strong immune stimulation ability. It is an advanced targeted gene delivery system with potent immunotherapeutic properties.Keywords: bioinspired material, cancer cell membrane, targeted siRNA delivery, immunotherapeutic, colon cancer

Lanzhi Li,1,&ast; Keshuai Liu,1,&ast; Xingwu Duan,1 Limei Xu,2 Qingqi Yang,2 Fang Liu2 1Department of Dermatology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Department of Dermatology, Air Force Medical Center of PLA, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xingwu Duan, Email xwduan@sina.comBackground: Psoriasis is a chronic, inflammatory skin disease that is often accompanied by multiple comorbidities. Obesity is considered an independent risk factor for the development of psoriasis. However, most of the related data are derived from epidemiological studies conducted in the United States of America and Europe. This study aimed to compare the clinical characteristics of patients with psoriasis who are overweight/obese and patients with psoriasis with normal weight in China.Methods: We reviewed the medical records of 208 patients with psoriasis. Based on their body mass index (BMI), the patients were divided into two groups: patients with psoriasis who were overweight/obese and patients with psoriasis with normal weight.Results: The most patients enrolled in this study were men (77.40%). Patients with psoriasis who were overweight/obese had a higher mean age, longer disease duration, and significantly higher Psoriasis Area and Severity Index (PASI) values (P=0.032). Additionally, the incidence of fatty liver, hyperlipidemia, hyperuricemia, and abnormal liver function was higher among patients with psoriasis who were overweight/obese (P< 0.05). Linear regression analysis revealed a linear relationship between PASI values and BMI (P=0.016). Moreover, patients with psoriasis who were overweight/obese had significantly higher levels of serum alanine transaminase (ALT), aspartate transaminase (AST), uric acid (UC), total cholesterol (TC), low-density lipoprotein (LDL), and fasting plasma glucose (FPG) (P< 0.05) and lower serum high-density lipoprotein (HDL) levels and absolute lymphocyte count (ALC) (P< 0.05).Conclusion: Patients with psoriasis who are overweight/obese have more severe psoriatic lesions and metabolic comorbidities. Detailed assessment of the BMI of patients with psoriasis revealed that weight loss may be necessary for patients who are overweight/obese to reduce the risk of metabolic disorders.Keywords: psoriasis, obesity, metabolic disorders

Zhaoxia Xu,1,&ast; Lei Zhang,2,&ast; Ran Han,1 Chengwei Ding,1 Haochang Shou,1 Xueguang Duan,1 Shengwei Zhang1 1Department of Clinical Laboratory, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xueguang Duan; Shengwei Zhang, Department of Clinical Laboratory, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China, Tel +86 13911179092 ; +86 13124780206, Email duanxg714@163.com; zswo6@aliyun.comBackground: Candida auris is a pathogen first found in external ear canal, becoming a major threat to global health. Here, we describe a candidemia case caused by a novel drug-resistant Candida auris strain.Case Presentation: An 80-year-old patient, with multiple serious medical conditions, was suffered from candidemia caused by Candida auris, died 9 days after admission in our hospital. Phylogenetic analysis indicates that this C. auris isolate (designated BJCA003) belongs to the South Asian clade, carries the Y132F mutation in the protein Erg11. And antibiotic susceptibility test indicated that BJCA003 is resistant to fluconazole and amphotericin B, not susceptible to caspofungin. In addition, this strain has multiple colony and cellular morphologies under different culture conditions.Conclusion: Strain BJCA003 is a novel drug resistant C. auris strain in mainland China, the Y132F mutation in Erg11 may attribute to fluconazole-resistance, alarming that we still face more challenges about C. auris.Keywords: Candida auris, candidemia, drug-resistant, mutation, morphologies

Linhao Jian,1,2,&ast; Zhixiang Zhang,2,&ast; Quan Zhou,3 Xiangjie Duan,4 Liangqing Ge2 1Department of the First Clinical College, Jinan University, Guangzhou, 510632, People’s Republic of China; 2Department of Cardiology, The First People’s Hospital of Changde, Changde City, 415003, People’s Republic of China; 3Department of Science and Education, The First People’s Hospital of Changde, Changde City, 415003, People’s Republic of China; 4Department of Infectious Diseases, The First People’s Hospital of Changde, Changde City, 415003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liangqing Ge, Department of Cardiology, the First People’s Hospital of Changde, Changde City, Hunan Province, 415003, People’s Republic of China, Tel +86-0736-7788467, Email geliangqing@163.comPurpose: Red cell distribution width (RDW) and albumin level are linked to adverse outcomes in patients with acute myocardial infarction (AMI). Nonetheless, it remains unknown whether the RDW/albumin ratio (RAR) is associated with the short-term prognosis of AMI. Using a large cohort, we aimed to explore the association between RAR and in-hospital all-cause mortality in intensive care unit (ICU) patients with AMI.Patients and Methods: The patients’ data analyzed in this retrospective cohort investigation were obtained from the eICU Collaborative Research Data Resource. RAR was calculated based on the serum albumin level and RDW. The primary outcome was in-hospital all-cause mortality. Receiver operating characteristic curve, multiple logistic regression model, and Kaplan–Meier survival analysis were performed to explore the prognostic value of RAR.Results: We enrolled 2594 patients in this study. After correcting for confounding factors, the RAR was an independent predictor for in-hospital mortality in our model (odds ratio [OR] 1.27, 95% confidence interval [CI] 1.12, 1.43). A similar relationship was observed with mechanical ventilation use. RAR showed a better predictive value with an area under the curve (AUC) of 0.738 (cutoff, 4.776) for in-hospital all-cause mortality compared to RDW or albumin alone. Kaplan–Meier estimator curve analyses for RAR demonstrated that the group with RAR ≥ 4.776%/g/dL had poorer survival than the group with RAR < 4.776%/g/dL (p< 0.0001). The subgroup analysis revealed no significant interaction between RAR and in-hospital all-cause mortality in all strata.Conclusion: RAR was an independent risk factor for in-hospital all-cause mortality in ICU patients with AMI. Higher RAR values corresponded to higher mortality rates. RAR is a more accurate predictor of in-hospital all-cause mortality in patients with AMI in the ICU than albumin or RDW. Thus, RAR may be a potential biomarker of AMI.Keywords: red blood cell distribution width, albumin, in-hospital all-cause mortality, eICU-CRD, acute myocardial infarction

Fayin Mo,1,2 Minjun Zhang,1 Xuewei Duan,1 Chuyan Lin,1 Duanping Sun,2,3 Tianhui You1 1School of Nursing, Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 2Center for Drug Research and Development, Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 3Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, People’s Republic of ChinaCorrespondence: Duanping Sun; Tianhui You, Email sundp@gdpu.edu.cn; youth888cn@aliyun.comAbstract: Bacterial-infected wounds are a serious threat to public health. Bacterial invasion can easily delay the wound healing process and even cause more serious damage. Therefore, effective new methods or drugs are needed to treat wounds. Nanozyme is an artificial enzyme that mimics the activity of a natural enzyme, and a substitute for natural enzymes by mimicking the coordination environment of the catalytic site. Due to the numerous excellent properties of nanozymes, the generation of drug-resistant bacteria can be avoided while treating bacterial infection wounds by catalyzing the sterilization mechanism of generating reactive oxygen species (ROS). Notably, there are still some defects in the nanozyme antibacterial agents, and the design direction is to realize the multifunctionalization and intelligence of a single system. In this review, we first discuss the pathophysiology of bacteria infected wound healing, the formation of bacterial infection wounds, and the strategies for treating bacterially infected wounds. In addition, the antibacterial advantages and mechanism of nanozymes for bacteria-infected wounds are also described. Importantly, a series of nanomaterials based on nanozyme synthesis for the treatment of infected wounds are emphasized. Finally, the challenges and prospects of nanozymes for treating bacterial infection wounds are proposed for future research in this field.Graphical Abstract: Keywords: nanozyme, wound healing, bacterial infections, antibacterial, antibiofilms

Xuhua Duan,&ast; Wenze Xu,&ast; Hao Li, Manzhou Wang, Wenhui Wang, Huibin Lu, Yancang Zhang, Xinwei Han Department of Interventional Radiology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yancang Zhang; Xinwei Han, Department of Interventional Radiology, The First Affiliated Hospital, Zhengzhou University, No. 1, East Jian She Road, People’s Republic of China, 450052, Tel +86-371-66278081, Email zhangyancang2016@126.com; zzudxh@yeah.netPurpose: Chemoresistance is a major factor contributing to the failure of cancer treatment. The conventional chemotherapy agent 5-fluorouracil (5-FU) has been used for cancer treatment for decades. However, its use is limited in the treatment of hepatocellular carcinoma (HCC) due to acquired resistance. Nrf2 (NF-E2-related factor 2) is known to be associated with drug resistance across a wide range of cancer types. Also, since arsenic trioxide (As2O3) showed antitumor effects on HCC, the purpose of this study was to determine whether As2O3 and Nrf2-siRNA could inhibit HCC synergistically.Methods: We generated two separate 5-FU-resistant HCC cell lines (SNU-387/5-FU and Hep3B/5-FU). Western blotting was used to determine protein levels. An efficient lentiviral delivery system was used to establish stable knockdown or overexpression of Nrf2 and HIF-1α. In vitro and in vivo analyses of the effects of Nrf2 gene knockdown and As2O3 on 5-FU-resistant HCC cells were conducted.Results: The expression of Nrf2 was higher in the 5-FU-resistant HCC cell lines than in the parental cell lines. When coupled with Nrf2 knockdown, As2O3 treatment significantly decreased 5-FU-resistant SNU-387 and Hep3B cell viability, migration, and invasion, inactivated HIF-1α/HSP70 signaling, inhibited anti-apoptotic B-cell lymphoma (Bcl-2) activity, and increased the expression of pro-apoptotic Bcl-2-associated X protein (BAX) along with caspase-3. The synergistic effect was also confirmed using a 5-FU-resistant Hep3B mouse xenograft model in vivo.Conclusion: Nrf2 knockdown could improve the effect of As2O3 on reversing drug resistance in 5-FU-resistant HCC cells.Keywords: arsenic trioxide, 5-fluorouracil, chemoresistance, hepatocellular carcinoma, Nrf2, HIF-1&#x03B1

Wenju Sun,1,&ast; Yuqing Cui,1,&ast; Xiaojuan Zhang,1,&ast; Yuze Wang,1 Zihao Zhang,2 Xianfei Ding,1 Huoyan Liang,1 Dong Wang,1 Yali Sun,1 Shaohua Liu,1 Xiaoguang Duan,1 Yibin Lu,3 Tongwen Sun1 1General ICU, The First Affiliated Hospital of Zhengzhou University, Henan Key Laboratory of Critical Care Medicine, Zhengzhou Key Laboratory of Sepsis, Henan Engineering Research Center for Critical Care Medicine, Zhengzhou, 450052, People’s Republic of China; 2Department of Clinical Medicine, Sanquan College of Xinxiang Medical University, Xinxiang, 453003, People’s Republic of China; 3Department of Critical Care Medicine, Xinyang Hospital Affiliated to Zhengzhou University, Xinyang, 464000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tongwen Sun, General ICU, The First Affiliated Hospital of Zhengzhou University, Henan Key Laboratory of Critical Care Medicine, Zhengzhou Key Laboratory of Sepsis, Henan Engineering Research Center for Critical Care Medicine, Zhengzhou, Henan Province, 450052, People’s Republic of China, Email suntongwen@163.comBackground: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. However, there is still no single drug that could reduce septic mortality. Previous studies have reported gabexate mesylate (GM) significantly reduced serum inflammatory factors, alleviated sepsis-induced lung injury and improved clinical outcomes. This study aimed to combine with microbiome sequencing and metabolomics analysis to explore the effects of GM administration in septic rats.Methods: Sixty SD rats were randomly divided into the sham control (SC), cecal ligation and puncture (CLP), and GM injection (GM) groups. The mortality was measured and colonic feces were collected to examine the gut microbiota and metabolism 24 h after the procedure. The lung tissues were collected for hematoxylin-eosin staining.Results: We observed the relative abundance of Pygmaiobacter, which contributed to short-chain fatty acids (SCFAs) promotion, Lactobacillus and Erysipelotrichaceae UCG-003 increased in the GM-treated rats, while Escherichia–Shigella and Akkermansia decreased compared to the sepsis-induced lung injury group. Furthermore, these 3 metabolites including Palmitoylethanolamide, Deoxycholic acid and Chenodeoxycholic acid correlated significantly to CLP- and GM-rich genus (P < 0.05). Besides, the lung tissues of CLP group showed more severe inflammatory infiltration and edema, and the mortality rate in the CLP group (10/20) was significantly higher than in the SC group (0/20) (P < 0.001) and GM group (4/20) (P < 0.05).Conclusion: Our findings showed that GM attenuated sepsis-induced lung injury rats and regulated metabolites related to gut microbiota, which may provide an effective treatment for sepsis patients.Keywords: sepsis, gabexate mesylate, gut microbiota, metabolomics, rats

Hai Feng,1,&ast; Yunhui Zhuo,2,&ast; Xuemei Zhang,2 Yuyao Li,1 Yue Li,1 Xiangjuan Duan,2 Jia Shi,1 Chengbin Xu,3 Yueqiu Gao,1,2 Zhuo Yu2 1Institute of Infectious Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Department of Informatics, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yueqiu Gao, Institute of Infectious Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China, Tel +86 21 20256507, Fax +86 21 20256699, Email gaoyueqiu@shutcm.edu.cn Zhuo Yu, Department of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China, Tel +86 21 20256507, Fax +86 21 20256699, Email zhuoyu@shutcm.edu.cnAbstract: Hepatocellular carcinoma (HCC) remains a serious medical therapeutic challenge as conventional curative avenues such as surgery and chemotherapy only benefit for few patients with limited tumor burden. Immunotherapy achieves clinical progress in the treatment of this prevalent malignant disease by virtue of the development of tumor immunology; however, most patients have experienced minimal or no clinical benefit in terms of overall survival. The complexity and diversity of tumor microenvironment (TME) built by immune and stromal cell subsets has been considered to be responsible for the insufficiency of immunotherapy. The advance of bioanalytical technology boosts the exploration of the composition and differentiation of these infiltrated cells, which reflect the immune state of the TME and impact the efficacy of the antitumor immune response. Targeting these cells to remodel the TME is one of the important immunotherapeutic approaches to improve HCC treatment. In this review, we focused on the role of these non-cancerous cells in the tumor progression, and elaborated their function on cancer immunotherapy when manipulating them as potential targets.Keywords: immune cells, stromal cells, tumor microenvironment, hepatocellular carcinoma, immunotherapy

Meixue Yao,1,&ast; Mengda Liu,2,&ast; Xia Chen,3 Jianjun Li,4 Yan Li,5 Yu Run Wei,2 Yong Liu,3 Kang Long Yang,3 Xiaoxiao Duan,5 Weixing Shao,2 Xiangxiang Sun,2 Xiaoxu Fan,2 Shufang Sun,2 Lili Tian,2 Dehui Yin,1 Mingjun Sun2 1Key Laboratory of Human Genetics and Environmental Medicine, School of Public Health, Xuzhou Medical University, Xuzhou, 221004, People’s Republic of China; 2Laboratory of Zoonoses, China Animal Health and Epidemiology Center, Qingdao, 266032, People’s Republic of China; 3Yubei Animal Husbandry and Aquatic Products Station, Chongqing, 401120, People’s Republic of China; 4School of Animal Science and Veterinary Medicine, Tianjin Agriculture College, Tianjin, 300384, People’s Republic of China; 5Qingdao Animal Disease Prevention and Control Center, Qingdao, 266000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingjun Sun, Laboratory of Zoonoses, China Animal Health and Epidemiology Center, No. 369 Nanjing Road, Qingdao, 266032, People’s Republic of China, Email sunmingjun@cahec.cn Dehui Yin, Key Laboratory of Human Genetics and Environmental Medicine, School of Public Health, Xuzhou Medical University, Xuzhou, 221004, People’s Republic of China, Email yindh16@xzhmu.edu.cnBackground: Brucellosis is one of the most important zoonotic diseases in the world. Canine brucellosis, caused mainly by Brucella canis, is seriously neglected, and there is a lack of accurate diagnostic tools.Methods: In this study, to compare BP26, Omp25, Omp31 and a multiepitope-based fusion protein in the serological detection of canine brucellosis, using 34 brucellosis-positive dog sera and 62 negative control sera, the Brucella outer membrane proteins Omp31, BP26, Omp25 and a multiepitope-based fusion protein were evaluated by iELISA for their potential use as antigens in the serological diagnosis of canine brucellosis.Results: The results showed that the multiepitope-based fusion protein performed best in distinguishing brucellosis-positive and brucellosis-negative dog sera, with a positive predictive value (PPV) of 100% and a negative predictive value (NPV) of 98.41%. BP26 and Omp31 showed excellent sensitivity in detecting brucellosis-positive dog sera, but their cross reaction to sera infected with Vibrio parahaemolyticus and Listeria monocytogenes may hinder their application as diagnostic reagents. Omp25 lacked sufficient sensitivity and showed limited ability in distinguishing positive and negative dog sera.Conclusion: The multiepitope-based fusion protein can be used as an ideal antigen for serologically diagnosing canine brucellosis currently prevalent worldwide.Keywords: Brucella, outer membrane protein, multiepitope, canine brucellosis

Lei Zhang,1 Yixiong Li,2 Hao Yang,1 Yunzhu Mu,1 Jingjing Jiang,1 Xi Duan1 1Department of Dermatology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan Province, People’s Republic of China; 2Department of Anorectal, The First Affiliated Hospital of Chengdu Medical College, Chengdu, People’s Republic of ChinaCorrespondence: Xi Duan, Department of Dermatology, Affiliated Hospital of North Sichuan Medical College, 1 Maoyuan South Road, Shunqing District, Nanchong City, Sichuan Province, 637000, People’s Republic of China, Tel +8618783983097, Email dancing@126.comAbstract: We describe a 62-year-old woman with a 1-month-old unhealed cat bite wound caused by Mycobacterium chelonae presenting with persistent infection despite treatment with cefazolin and amoxicillin. This is the first reported case of M. chelonae infection caused by a cat bite. Cat bites are affected by the cat’s food microbiome, so clinicians should consider the cat’s diet if wounds are not responding as expected to first-line therapy.Keywords: cat bite, Mycobacterium chelonae, wound infection

Jia He, Xi Duan, Ting Liu, Hao Yang, Jingjing Jiang, Yunzhu Mu Department of Dermatology, Affiliated Hospital of North Sichuan Medical College, Nanchong, People’s Republic of ChinaCorrespondence: Yunzhu Mu, Department of Dermatology, Affiliated Hospital of North Sichuan Medical College, No. 1 Maoyuan South Road, Shunqing District, Nanchong City, Sichuan Province, 637000, People’s Republic of China, Tel +8615983785601, Email hymyz@126.comAbstract: Immune-related adverse events have been reported in relation to programmed cell death protein-1 (PD-1). However, there are few reports on PD-1 inhibitor-induced bullous pemphigoid. We report the case of a patient who developed bullous pemphigoid following long-term administration of sintilimab for renal cell carcinoma. He developed scattered erythema, blisters, and generalized pruritus for 1 week before admission. Histopathology showed subepidermal blisters and direct immunofluorescence showed linear deposition of immunoglobulin G and complement 3 on the basement membrane; the level of BP180 was 146.93U/mL. A regimen containing methylprednisolone, minocycline, and niacinamide was administered and the patient was discharged following resolution of symptoms.Keywords: bullous pemphigoid, PD-1, PD-L1, sintilimab

Platinum-based nanocatalysts play a crucial role in various electrocatalytic systems that are important for renewable, clean energy conversion, storage and utilization. However, the scarcity and high cost of Pt seriously limit the practical application of these catalysts. Decorating Pt catalysts with other transition metals offers an effective pathway to tailor their catalytic properties, but often at the sacrifice of the electrochemical active surface area (ECSA). Here we report a single-atom tailoring strategy to boost the activity of Pt nanocatalysts with minimal loss in surface active sites. By starting with PtNi alloy nanowires and using a partial electrochemical dealloying approach, we create single-nickel-atom-modified Pt nanowires with an optimum combination of specific activity and ECSA for the hydrogen evolution, methanol oxidation and ethanol oxidation reactions. The single-atom tailoring approach offers an effective strategy to optimize the activity of surface Pt atoms and enhance the mass activity for diverse reactions, opening a general pathway to the design of highly efficient and durable precious metal-based catalysts.

Pingchuan Ma,1 Jingmei Li,2 Yan Gao,2 Jieping Wu,2 Ke Men,2 Chunjie Li,1 Yi Men,1 Xingmei Duan3 1State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan Province, 610041, People’s Republic of China; 2State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, 610041, People’s Republic of China; 3Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan Province, 610072, People’s Republic of ChinaCorrespondence: Yi Men, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan Province, People’s Republic of China, Email yurimen@163.com Xingmei Duan, Department of Pharmacy Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of China, Email duanxingmei2003@163.comPurpose: Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, with more than 300,000 new cases annually. Despite advances in existing treatments, including surgery, radiation, chemotherapy, and immunotherapy, the overall survival and prognosis have remained poor. However, gene therapy based on non-viral vectors provides new ideas for the treatment of OSCC. Here, we aimed to prepare and describe the synthesis, biosafety, and preclinical efficacy of DOTAP-mPEG-PCL (DMP) in OSCC gene therapy.Methods: We prepared a nano-sized hybrid cationic micelle DMP. DMP micelles were prepared by self-assembling cationic lipid DOTAP and mPEG-PCL polymer. We evaluated the characteristics of this cationic micelle in vitro. Combined with encoding the apoptosis-inducing BimS gene, we established the DMP/phBimS complex and evaluated its anti-tumor effect in vitro. We also established a mouse tongue xenograft model to evaluate the antitumor effect of the DMP/phBimS complex in vivo through local and systemic administration prospectively.Results: The DMP cationic micelle is spherical in shape, with an average diameter of 28.32 ± 3.56 nm and an average zeta potential of 43.43 ± 0.82 mV. By activation of lipid raft-mediated endocytosis caveolin-mediated endocytosis, DMP could efficiently deliver plasmid into SCC15 cells (efficiency: 52.07% ± 1.63%), with an ideal biosecurity. When loaded by plasmid encoding the apoptosis-inducing BimS gene, the DMP/phBimS complex exhibited an obvious anti-proliferation effect of SCC15 in vitro through the apoptosis pathway (33.9% ± 2.62% apoptosis rate). By local administration, the DMP/phBimS complex showed ideal anti-tumor properties in the nude mouse tongue xenograft model, with an average tumor inhibition rate of 65.66%. Furthermore, through systematic administration, the DMP/phBimS complex obviously inhibited OSCC growth, with an average inhibition rate of 45.63% (DMP/phBimS) and an appropriate biocompatibility.Conclusion: The DMP/phBimS complex is an optional effective option for suicide gene therapy for OSCC.Keywords: gene therapy, Bim, micelle, oral squamous cell carcinoma, non-viral delivery

Xinxin Li,1– 3 Yibao Chen,1– 3 Shuang Wang,1– 3 Xiaochao Duan,1– 3 Fenqiang Zhang,1– 3 Aizhen Guo,1– 3 Pan Tao,1– 3 Huanchun Chen,1– 3 Xiangmin Li,1– 3 Ping Qian1– 3 1State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, 430070, People’s Republic of China; 2College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, People’s Republic of China; 3Key Laboratory of Preventive Veterinary Medicine in Hubei Province, the Cooperative Innovation Center for Sustainable Pig Production, Wuhan, Hubei, 430070, People’s Republic of ChinaCorrespondence: Ping Qian, Tel +86-27-87282608, Fax +86-27-87282608, Email qianp@mail.hzau.edu.cnBackground: Methicillin-resistant Staphylococcus aureus (MRSA) is an important zoonotic pathogen worldwide. Infections due to MRSA are associated with higher mortality rates compared with methicillin-susceptible S. aureus. Meanwhile, bacteriophages have been shown to overcome the emergence of MRSA.Methods: Phage PHB22a, PHB25a, PHB38a, and PHB40a were isolated. Here, we evaluated the ability of a phage cocktail containing phages PHB22a, PHB25a, PHB38a, and PHB40a against MRSA S-18 strain in vivo and in vitro. Phage whole-genome sequencing, host-range determination, lytic activity, and biofilm clearance experiments were performed in vitro. Galleria mellonella larvae and a mouse systemic infection model to evaluate the efficacy of phage therapy in vivo.Results: The phage cocktail exhibited enhanced antibacterial and anti-biofilm effects compared to the single phage. Phage cocktail contained with Ca2+/Zn2+ significantly reduced the number of viable bacteria (24-h or 48-h biofilm) by more than 0.81-log compared to the phage cocktail alone. Furthermore, we demonstrated that the addition of Ca2+ and Zn2+ phage cocktail could increase the survival rate of G. mellonella larvae infected with S. aureus by 10% compared with phage cocktail alone. This was further confirmed in the mouse model, which showed a 2.64-log reduction of host bacteria S-18, when Ca2+ and Zn2+ were included in the cocktail compared with the phage cocktail alone.Conclusion: Our results indicated that phage cocktail supplemented with Ca2+/Zn2+ could effectively remove bacteria in biofilms and mice tissues infected with S. aureus.Keywords: methicillin-resistant Staphylococcus aureus, phage cocktail, metal ions, biofilm, phage therapy

Yan Yang,1,&ast; Xi Zheng,1,&ast; Lu Chen,1 Xuefeng Gong,2 Hao Yang,2 Xingmei Duan,1 Yuxuan Zhu1 1Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Science & Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of China; 2POWERCHINA Chengdu Engineering Corporation Limited, Chengdu, 611130, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuxuan Zhu, Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Science & Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of China, Email zhuyuxuan6688@163.comAbstract: Cancer is the second leading cause of death in the world, behind only cardiovascular diseases, and is one of the most serious diseases threatening human health nowadays. Cancer patients’ lives are being extended by the use of contemporary medical technologies, such as surgery, radiotherapy, and chemotherapy. However, these treatments are not always effective in extending cancer patients’ lives. Simultaneously, these approaches are often accompanied with a series of negative consequences, such as the occurrence of adverse effects and an increased risk of relapse. As a result, the development of a novel cancer-eradication strategy is still required. The emergence of nanomedicine as a promising technology brings a new avenue for the circumvention of limitations of conventional cancer therapies. Gold nanoparticles (AuNPs), in particular, have garnered extensive attention due to their many specific advantages, including customizable size and shape, multiple and useful physicochemical properties, and ease of functionalization. Based on these characteristics, many therapeutic and diagnostic applications of AuNPs have been exploited, particularly for malignant tumors, such as drug and nucleic acid delivery, photodynamic therapy, photothermal therapy, and X-ray-based computed tomography imaging. To leverage the potential of AuNPs, these applications demand a comprehensive and in-depth overview. As a result, we discussed current achievements in AuNPs in anticancer applications in a more methodical manner in this review. Also addressed in depth are the present status of clinical trials, as well as the difficulties that may be encountered when translating some basic findings into the clinic, in order to serve as a reference for future studies.Keywords: gold nanoparticles, cancer, drug delivery, photothermal therapy, photodynamic therapy

Xiaoye Duan,1,2 Qi Pan,1 Lixin Guo1,2 1Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Lixin Guo, Email glx1218@163.comBackground: This study aimed to assess the effects of chronic sleep deprivation (CSD) on bone metabolism in growing rats and the likely underlying mechanism.Methods: Twenty 5-week-old male Wistar rats and randomly divided into the CSD and normal control (NC) groups after one-week acclimatization. After a 6-week intervention of sleep deprivation, the distal femurs of both groups were harvested for micro-computed tomography scans and histological analysis. Meanwhile, the femur tissues were measured the mRNA and protein expression via RNA sequencing and immunohistochemical analysis. Serum bone turnover markers were evaluated at 0, 2, 4, and 6 weeks.Results: CSD impaired the bone growth, showing an imbalance of bone turnover status, dysphasia in the metaphysis growth plate, and deterioration of bone microarchitecture. Further, CSD suppressed bone formation, showing that the expression of osteogenesis-related proteins (col1α 1 and osteocalcin) and mRNA (igf1, bglap, runx2, col1α 1, pth1r) are down-regulated. Differentially expressed genes were detected, and functional enrichment analyses revealed that the PI3K/AKT pathway was significantly down-regulated in the CSD group.Conclusion: These results suggest that CSD can significantly impaire bone health, and it may exert these effects in part by suppressing bone formation and osteoblast differentiation, and inactivating the PI3K/AKT signaling pathway.Keywords: chronic sleep deprivation, sleep loss, growth, bone formation, RNA sequencing, PI3K/AKT pathway

Xiaoyan Jiang,1,&ast; Fang Deng,1,2,&ast; Shunli Rui,1 Yu Ma,1 Min Wang,1 Bo Deng,1 Hongyan Wang,1 Chenzhen Du,1 Bing Chen,2 Xiuhua Yang,3 Johnson Boey,4 David G Armstrong,5 Wuquan Deng,1 Xiaodong Duan6 1Department of Endocrinology, Chongqing University Central Hospital, School of Medicine Chongqing University, Chongqing, 400014, People’s Republic of China; 2Department of Endocrinology, Chongqing Southwest Hospital, Chongqing, 400038, People’s Republic of China; 3Department of Lower Extremity Surgery, NO.1 Orthopedics Hospital of Chengdu, Chengdu City, 610000, Sichuan, People’s Republic of China; 4Department of Podiatry, National University Hospital, 169608, Singapore; 5Department of Surgery, Keck School of Medicine of University of Southern California, Los Angeles, CA, 90033, USA; 6Department of Rehabilitation, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wuquan Deng, Department of Endocrinology, Chongqing University Central Hospital, School of Medicine Chongqing University, No. 1 Jiankang Road, Yuzhong District, Chongqing, 400014, People’s Republic of China, Tel +86 23 63692185, Email wuquandeng@cqu.edu.cn Xiaodong Duan, Department of Rehabilitation, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China, Email duanxiaodong2032@sina.comObjective: Falls often occur in patients with diabetic neuropathy due to biomechanical alternation. The implication of diabetic peripheral neuropathy (DPN) on gait and balance remains poorly understood.Methods: A total of 11 dynamic gait, balance and electrophysiological parameters were evaluated in 176 participants. The biomechanical parameters were compared between groups.Results: Stride length and stride velocity were significantly lower in all subgroups of DPN compared with healthy subjects (p< 0.05). Stance phase and double support phase were significantly higher, but swing phase were significantly lower across all subgroups of DPN than healthy subjects (p< 0.05). Under eyes-open standing, the ML and AP range parameters of CoM sway, ankle sway and hip sway, CoM sway index, ankle swing index in both subclinical and confirmed DPN patients were all significantly higher compared to healthy subjects (p< 0.05). Under eyes-closed standing, AP range parameters of CoM sway in subclinical DPN and confirmed DPN patients were significantly higher than healthy subjects (p< 0.05). The hip sway areas in diabetics were significantly higher compared to healthy subjects (p< 0.05).Conclusion: The abnormal biomechanical parameters existed in the early stages of patients with DPN. The static balance under eyes-open and eye-closed condition is maintained by ankle joint compensation strategy and hip joint protection strategy. An early evaluation and better risk management is essential for diabetic patients with a history of more than 5 years even without DPN clinical symptoms and signs.Clinical Trial Registration Number: No. ChiCTR1800019179, www.chictr.org.cn.Keywords: gait, balance, diabetic peripheral neuropathy, risk assessment, wearable biomechanical system

Zuoan Qin,1,2 Nuohan Liao,3 Xuelin Lu,4 Xiangjie Duan,5 Quan Zhou,6 Liangqing Ge1,2 1Jinan University, Guangzhou, 510632, People’s Republic of China; 2Department of Cardiology, The First People’s Hospital of Changde City, Changde, 415003, People’s Republic of China; 3University of South China, Hengyang, Hunan, 421002, People’s Republic of China; 4Department of Pathology, The First People’s Hospital of Changde City, Changde, 415003, People’s Republic of China; 5Department of Infectious Diseases, The First People’s Hospital of Changde City, Changde, 415003, People’s Republic of China; 6Department of Science and Education, The First People’s Hospital of Changde City, Changde, 415003, People’s Republic of ChinaCorrespondence: Liangqing Ge, Email geliangqing@163.comAim: To investigate the association between the hemoglobin-to-red cell distribution width (RDW) ratio (HRR) and all-cause mortality in ischemic stroke patients with atrial fibrillation (AF).Design: This study was a retrospective cohort analysis. In total, 1018 ischemic stroke patients with AF were enrolled using the Medical Information Mart for Intensive Care database, (MIMIC)-IV. The patients were divided into four groups according to the HRR values. The primary outcome was 180-day all-cause mortality.Methods: Multivariate Cox proportional risk regression models were used to examine the association between HRR and all-cause mortality. The non-linear relationship between HRR and all-cause mortality was confirmed using a Cox proportional risk regression model fitted by cubic spline function and smooth curve fitting.Results: A total of 246/1018 patients (24.17%) died. The serum HRR values were negatively associated with 180-day all-cause mortality (hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.68– 0.94). A two-piecewise regression model was used to obtain a threshold inflection point value of 9.74. The HR and the 95% CI on the left inflection point were 0.73 and 0.61– 0.87 (p = 0.0005); on the right inflection point they were 1.06 and 0.82– 1.38 (p = 0.6383).Conclusion: The relationship between all-cause mortality and the HRR values was non-linear in ischemic stroke patients with AF. All-cause mortality and HRR values were negatively correlated when the HRR value was ≤ 9.74.Keywords: ischemic stroke, atrial fibrillation, all-cause mortality, MIMIC-IV

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

Xiaoyan Duan,1 Yiri Du,1 Chunmei Wang,1,2 Zhenfeng Zhao,1,2 Chao Li,1 Jianbo Li1,2 1Inner Mongolia Medical University Affiliated Hospital, Hohhot, 010050, People’s Republic of China; 2Inner Mongolia Key Laboratory of Molecular Imaging, Hohhot, 010050, People’s Republic of ChinaCorrespondence: Jianbo LiInner Mongolia Medical University Affiliated Hospital, No. 1 Tongdao North Street, Hohhot, 010050, People’s Republic of ChinaTel/ Fax +86 471 345 1574Email lijianbo_1235@msn.cnPurpose: DNA nanostructures, with the advantages of structural designability and spatial addressability, have shown a great potential in the field of drug delivery and bio-medicine. Herein, we aimed to prepare technetium-99m radiolabeled DNA cube nanoparticles (99mTc-DCN) and expect to build a DCN-based drug carrier and nuclear medicine imaging platform.Methods: DCN could be readily assembled with 6 designed DNA oligonucleotides at an equal mole ratio in a single annealing procedure. 99mTc-MAG3-ssDNA (A20) was obtained by labeling MAG3-ssDNA (A20) with technetium-99m by using a stannous chloride reduction method. 99mTc-DCN was prepared by hybridize DCN with side chains (T20-DCN) with 99mTc-MAG3-ssDNA (A20). The biodistribution study and SPECT/CT imaging were conducted on KM mice.Results: DCN was successfully assembled, and as-prepared DCN was characterized by native polyacrylamide gel electrophoresis, atomic force microscope and fluorescence resonance energy transfer. The size of DCN was about 5 nm. The radiolabeling yield of 99mTc-MAG3-ssDNA (A20) was approximately 90% by radio thin-layer chromatography. T20-DCN mixed with 99mTc-MAG3-ssDNA (A20) in PBS could generate 99mTc-DCN upon hybridization. The retention time (RT) of 99mTc-MAG3-ssDNA (A20) was at ∼ 22 min, and the RT of as-prepared 99mTc-DCN was at ∼ 12 min by radio-HPLC. The results from biodistribution study and SPECT/CT imaging showed that a significant proportion of DCNs were metabolized through the liver and kidney. Intestine exhibited a relatively indicative signal as well, which might be explained by the enterohepatic circulation of DCN via the liver and gallbladder.Conclusion: We have successfully prepared 99mTc-DCN as a SPECT/CT imaging probe via the side-chain hybridization strategy. The probe was metabolized mainly by the liver and excreted primarily to the bladder. Due to the superior properties of DNA cube nanoparticles, we believe DCN may potentially be translated into a preclinical setting for diagnosis and treatment of cancer-related diseases.Keywords: DNA cube nanoparticles, Tc-99m labeling, biodistribution, SPECT/CT imaging

Yan Gao,1,&ast; Ke Men,1,&ast; Congbin Pan,1 Jingmei Li,1 Jieping Wu,1 Xiaohua Chen,2 Sibei Lei,1 Xiang Gao,1 Xingmei Duan2 1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ke MenState Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, 610041, People’s Republic of ChinaEmail mendingbob@hotmail.comXingmei DuanDepartment of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of ChinaEmail duanxingmei2003@163.comBackground: Gene therapy has emerged as a new strategy for cancer therapy. As an alternative nucleic acid material, messenger ribonucleic acid (mRNA) is being increasingly utilized in cancer gene therapy. However, unfulfilled requirements and a lack of ideal mRNA delivery vectors persist.Methods: We developed an advanced mRNA delivery system, DMP-039, by fusing a cell-penetrating peptide, cRGD-R9, and a cationic nano-sized DMP backbone together. The DMP gene vector backbone was synthesized by the self-assembly of DOTAP lipid and mPEG-PCL polymer. Introduction of the cRGD-R9 peptide onto the DMP backbone was performed to elevate the mRNA delivery capacity, which resulted in a peptide-functionalized hybrid delivery system.Results: The average size of the synthesized DMP-039 was 268.9 ± 12.4 nm (PDI = 0.382), with a potential of 17.4 ± 0.5 mV. The synthesized DMP-039 hybrid nanoparticles exhibited high mRNA delivery efficiency through multiple mechanisms during transmembrane transportation. By loading the encoding mRNA from the suicide gene Bim, a locally administered mBim/DMP-039 complex strongly inhibited growth in two colon cancer models. Moreover, intravenous administration of the mBim/DMP-039 complex efficiently suppressed C26 pulmonary metastatic tumor progression with high safety. The in vivo distribution, degradation, and excretion were also investigated in detail.Conclusion: Our results suggest that the DMP-039 peptide-functionalized hybrid nanoparticle is an advanced candidate for mRNA-based suicide gene therapy.Keywords: mRNA, Bim, cell-penetrating peptide, gene therapy

Duan X, Lu L, Wang Y, et al. Int J Nanomedicine. 2017;12:6705–6719. The authors have advised that Figures 6, 8 and 9 on pages 6713, 6715 and 6716, respectively, of the published paper are incorrect. The errors were introduced by the Editorial staff during the publication process. The correct figures are shown in Download Article. Read the original article

Bo Deng,1,* Yi Yuan,1,* Miao Zhong,1,* Rui Ren,1 Wuquan Deng,1 Xiaodong Duan2 1Department of Endocrinology, Chongqing University Central Hospital, Chongqing Emergency Medical Center, Chongqing, 400014, People’s Republic of China; 2Department of Rehabilitation, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaodong Duan Email duanxiaodong2032@sina.comAim: The relationship between thyroid status and metabolic factors was investigated as well as iodine nutrition in the general population and among the elderly population.Methods: We performed a cross-sectional survey of 2483 subjects to assess the status of national iodine nutrition and incidence of thyroid disease. The general and elderly populations were divided into normal thyroid function (NTF) and subclinical hypothyroidism (SCH) groups. The anthropometric parameters and biochemical indicators were then analyzed.Results: Overall, 327 participants were diagnosed with thyroid diseases, 73 (22.32%) of whom were 65 years or older. For the general population, compared with the NTF group, individuals in the SCH group were older, presented with higher systolic blood pressure, fasting blood glucose, serum cholesterol, and urinary iodine concentration (all p< 0.05) but lower blood uric acid (UA) (p< 0.05). Linear regression analysis further revealed that age and triglyceride (TG) serum levels positively correlated with serum thyroid-stimulating hormone (TSH) levels. Multiple regression analyses revealed that age, TG, waist circumference (WC), and body mass index were independent predictors for abnormal TSH serum levels. For the elderly population, compared with NTF group, individuals in the SCH group were substantially older (p< 0.05) but presented with lower UA (p< 0.05). Pearson linear regression analysis revealed a positive correlation between age (p=0.003) as well as TG levels (p< 0.001) and serum TSH levels. In contrast, WC (p=0.003) was negatively related to TSH serum levels. Further multiple regression analysis revealed that age, TG, WC and heart rate were independent predictors of blood TSH.Conclusion: The large-scale national study of iodine nutrition, thyroid disease has shown a vital relationship between metabolic indicators and serum TSH levels. Age and metabolic diseases increase the likelihood of developing thyroid diseases, both the general population and among the elderly.Keywords: thyroid function, metabolic status, aging

Shasha Liu,1 Jinxue Wei,2,3 Rongjun Ni,2,3 Tianhao Gao,1 Peiyan Ni,2,3 Liansheng Zhao,2,3 Xiyu Duan,2,3 Xiaohong Ma,2,3 Pak C Sham,4,5 Tao Li1– 3,6 1Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, People’s Republic of China; 2Psychiatric Laboratory and Mental Health Center, West China Hospital of Sichuan University, Chengdu, People’s Republic of China; 3Huaxi Brain Research Center, West China Hospital of Sichuan University, Chengdu, People’s Republic of China; 4Department of Psychiatry, The University of Hong Kong, Pokfulam, Hong Kong, People’s Republic of China; 5State Key Laboratory for Cognitive and Brain Sciences, The University of Hong Kong, Pokfulam, Hong Kong, People’s Republic of China; 6Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangzhou, People’s Republic of ChinaCorrespondence: Tao LiPsychiatric Laboratory of West China Hospital, Sichuan University, 1 Keyuan Si Road, Chengdu, Sichuan, 610041, People’s Republic of ChinaEmail litaohx@scu.edu.cnBackground: Mice with a deletion at exon 19 of the circadian locomotor output cycles Kaput gene (Clockdelta19) exhibit mania-like behavior and have been one of the most common animal models for bipolar disorder (BD). The predictive validity of the Clockdelta19 was investigated via studies using lithium previously. Determination of effects of other mood stabilizers on Clockdelta19 mouse would be helpful for better understanding of the mechanism underlined.Methods: Wildtype (WT) and Clockdelta19 mice were treated with saline (n = 10 for WT and n=10 for Clockdelta19) or valproate (VPA) (n = 10 for WT and n=10 for Clockdelta19) for 10 days. The hyperactivity, anxiety-like behaviors and depression-like behaviors were tested. The concentration of monoamine neurotransmitters and their metabolites in the hippocampus of saline or VPA treated WT and Clockdelta19 mouse (n = 8 for each) were also determined.Results: VPA can reverse hyperactivity, lower level of anxiety-like and depression-like behaviors of the Clockdelta19 mouse. Clockdelta19 mouse exhibited lower levels of serotonin (5-HT) and dopamine (DA) in right hippocampus compared to WT mouse. Chronic VPA treatment did not affect the levels of 5-HT and DA, but can reduce the level of levodopa (L-DOPA) in the right hippocampus of Clockdelta19 mouse.Conclusion: Our results indicated that chronic VPA treatment can reverse the mania-like behaviors of the Clockdelta19 mouse and further consolidate the validity of the Clockdelta19 mouse as a model of BD. Monoamine neurotransmitters and their metabolites in the hippocampus are partly regulated by mutation of the Clock gene or VPA treatment.Keywords: bipolar disorder, Clockdelta19 mouse, valproate, mania-like behavior, neurotransmitter

Hongjia Zhang,1,* Ke Men,1,* Congbin Pan,1 Yan Gao,1 Jingmei Li,1 Sibei Lei,1 Guonian Zhu,1 Rui Li,1 Yuquan Wei,1 Xingmei Duan2 1State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ke Men StateKey Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu 610041, People’s Republic of ChinaEmail mendingbob@hotmail.comXingmei DuanDepartment of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, People’s Republic of ChinaEmail duanxingmei2003@163.comBackground: Drugs that work based on the mechanism of RNA interference have shown strong potential in cancer gene therapy. Although significant progress has been made in small interfering RNA (siRNA) design and manufacturing, ideal delivery system remains a limitation for the development of siRNA-based drugs. Particularly, it is necessary to focus on parameters including delivery efficiency, stability, and safety when developing siRNA formulations for cancer therapy.Methods: In this work, a novel degradable siRNA delivery system cRGD-R9-PEG-PEI-Cholesterol (rrPPC) was synthesized based on low molecular weight polyethyleneimine (PEI). Functional groups including cholesterol, cell penetrating peptides (CPPs), and poly(ethylene oxide) were introduced to PEI backbone to attain enhanced transfection efficiency and biocompatibility.Results: The synthesized rrPPC was dispersed as nanoparticles in water with an average size of 195 nm and 41.9 mV in potential. rrPPC nanoparticles could efficiently deliver siRNA into C26 clone cancer cells and trigger caveolae-mediated pathway during transmembrane transportation. By loading the signal transducer and activator of transcription 3 (STAT3) targeting siRNA, rrPPC/STAT3 siRNA (rrPPC/siSTAT3) complex demonstrated strong anti-cancer effects in multiple colon cancer models following local delivery. In addition, intravenous (IV) injection of rrPPC/siSTAT3 complex efficiently suppressed lung metastasis tumor progression with ideal in vivo safety.Conclusion: Our results provide evidence that rrPPC nanoparticles constitute a potential candidate vector for siRNA-based colon cancer gene therapy.Keywords: RNA interfering, nanoparticle, STAT3, colon cancer

Li Chen,1,2,* Jiaxin Liu,1,* Ming Guan,2,3 Tongqing Zhou,2 Xin Duan,1 Zhou Xiang1 1Department of Orthopedics, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People’s Republic of China; 2School of Dentistry, University of Michigan, Ann Arbor, MI, 48109, USA; 3Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xin Duan Tel +86-28-85422426Email dxbaal@hotmail.comZhou Xiang Tel +86-28-85422605Email xiangzhou15@hotmail.comAbstract: The development of biomaterials, stem cells and bioactive factors has led to cartilage tissue engineering becoming a promising tactic to repair cartilage defects. Various polymer three-dimensional scaffolds that provide an extracellular matrix (ECM) mimicking environment play an important role in promoting cartilage regeneration. In addition, numerous growth factors have been found in the regenerative process. However, it has been elucidated that the uncontrolled delivery of these factors cannot fully exert regenerative potential and can also elicit undesired side effects. Considering the complexity of the ECM, neither scaffolds nor growth factors can independently obtain successful outcomes in cartilage tissue engineering. Therefore, collectively, an appropriate combination of growth factors and scaffolds have great potential to promote cartilage repair effectively; this approach has become an area of considerable interest in recent investigations. Of late, an increasing trend was observed in cartilage tissue engineering towards this combination to develop a controlled delivery system that provides adequate physical support for neo-cartilage formation and also enables spatiotemporally delivery of growth factors to precisely and fully exert their chondrogenic potential. This review will discuss the role of polymer scaffolds and various growth factors involved in cartilage tissue engineering. Several growth factor delivery strategies based on the polymer scaffolds will also be discussed, with examples from recent studies highlighting the importance of spatiotemporal strategies for the controlled delivery of single or multiple growth factors in cartilage tissue engineering applications.Keywords: polymer scaffold, growth factor, delivery, cartilage repair

Nan Jiang,1,* Pingting Yang,2,* Shengyun Liu,3,* Hongbin Li,4 Lijun Wu,5 Xiaofei Shi,6 Yongfei Fang,7 Yi Zhao,8 Jian Xu,9 Zhenyu Jiang,10 Zhenbiao Wu,11 Xinwang Duan,12 Qian Wang,1 Xinping Tian,1 Mengtao Li,1 Xiaofeng Zeng1 1Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, People’s Republic of China; 2Department of Rheumatology and Immunology, First Affiliated Hospital, China Medical University, Shenyang, People’s Republic of China; 3Department of Rheumatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 4Department of Rheumatology, Affiliated Hospital of Inner Mongolia Medical College, Hohhot, Inner Mongolia, People’s Republic of China; 5Department of Rheumatology and Immunology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang Uygur Autonomous Region, People’s Republic of China; 6Department of Rheumatology and Immunology, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan, People’s Republic of China; 7Department of Rheumatology, Southwest Hospital, Third Military Medical University, Chongqing, People’s Republic of China; 8Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 9Department of Rheumatology and Immunology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 10Department of Rheumatology, The First Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 11Department of Clinical Immunology and Rheumatology, Xijing Hospital Affiliated to the Fourth Military Medical University, Shanxi, People’s Republic of China; 12Department of Rheumatology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaofeng Zeng; Mengtao LiDepartment of Rheumatology, Peking Union Medical College Hospital, No. 1 Shuaifuyuan, Wangfujing Ave, Beijing 100730, People’s Republic of ChinaTel/ Fax + 86-10-69158793Email zengxfpumc@163.com; mengtao.li@cstar.org.cnPurpose: Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by chronic destructive synovitis and possible multisystem involvement. This study aimed to survey the treatment satisfaction of physicians and patients with RA, and to explore the potential factors.Patients and Methods: This cross-sectional study was conducted in 12 centers across China between March 2018 and April 2018. The Treatment Satisfaction Questionnaire for Medication version II was used to assess the treatment satisfaction of patients and physicians. Multivariable regression analysis was used to determine the factors independently associated with treatment satisfaction of patients.Results: The patients’ satisfaction (n=335) with biological disease-modifying antirheumatic drugs (bDMARDs) was higher than physicians’ satisfaction (n=146) regarding the side effects (95.0± 14.3 vs 84.6± 15.7, P< 0.001) and convenience (74.6± 21.2 vs 69.1± 16.5, P=0.002). Among physicians, global satisfaction with bDMARDs was higher than that with conventional synthetic DMARDs (csDMARDs). The multivariable regression analysis showed that age was positively associated with satisfaction of patients, while college or above education and self-assessment of disease severity were inversely associated with satisfaction. Treatment satisfaction was associated positively with the quality of communication with the physician and inversely with treatment costs.Conclusion: For bDMARDs, the treatment satisfaction of patients with RA is generally higher than that of physicians’. Physicians’ satisfaction with bDMARDs is higher than with csDMARDs. Age, education, disease severity, communication with the physician, and treatment costs are independently associated with the treatment satisfaction among patients. Physician–patient communication should be improved in clinical practice. Treatment costs should be taken into account when physicians make decisions.Keywords: patient, physician, rheumatoid arthritis, treatment satisfaction, TSQM-II

Yuxuan Zhu,* Ting Yuan,* Yuan Zhang, Jianyou Shi, Lan Bai, Xingmei Duan, Rongsheng Tong, Lei Zhong Personalized Drug Therapy Key Laboratory of Sichuan Province, Department of Pharmacy, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lei Zhong; Rongsheng TongPersonalized Drug Therapy Key Laboratory of Sichuan Province, Department of Pharmacy, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, No. 32 West Second Section First Ring Road, Chengdu, Sichuan 610072, People’s Republic of ChinaTel +86 13458580284; +86 28-87393405Email zhl7235301@163.com; 1505855365@qq.comPurpose: Esophageal squamous cell carcinoma (ESCC) is a refractory malignancy with high morbidity and mortality. Thus, there is an urgent need to find effective targets and agents for ESCC treatment. The purpose of this study was to assess the anti-ESCC effects of a pan-histone deacetylase (HDAC) inhibitor AR-42 and its mechanisms of action.Methods: Immunohistochemical staining was performed to detect HDAC1 expression in ESCC and adjacent tissue samples. MTT assay, Edu cell proliferation test, flow cytometry, and subcutaneous xenograft were used to assess the anti-ESCC effects of AR-42; furthermore, the antiangiogenic activity of AR-42 was evaluated using endothelial cell migration, invasion, and tube formation assays as well as zebrafish angiogenesis assay. Western blot analysis was performed to explore the underlying mechanism of the anti-ESCC activity of AR-42.Results: HDAC1-positive expression was much higher in ESCC cells than in paracancerous tissues, and the elevated HDAC1 expression was a strong indicator of lymph node metastasis and a more advanced TNM stage of ESCC. Moreover, AR-42 potently suppressed ESCC cell growth through cellular proliferation inhibition and apoptosis induction. Moreover, AR-42 displayed a moderate antiangiogenic activity, and it could significantly inhibit the migration, invasion and tubulogenesis of human umbilical vein endothelial cells as well as intersegmental vessel formation in zebrafish at micromolar concentrations. More importantly, the inhibitory activity of AR-42 on ESCC cells and angiogenesis could also be observed in the TE-1 xenograft model. Further studies showed that AR-42 exerts its anti-ESCC effects mainly by upregulating the expression of p21 and blocking the transduction of multiple signaling cascades related to tumor growth, especially Stat3-mediated signaling.Conclusion: Overall, AR-42 has significant potency for inhibiting ESCC cell growth and shows moderate effect in suppressing angiogenesis, displaying strong anti-ESCC effects in vitro and in vivo. Thus, AR-42 deserves further evaluation as a potential candidate for ESCC therapy.Keywords: esophageal squamous cell cancer, AR-42, histone deacetylase, angiogenesis