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Yitong Cai,1 Ming Liu,2 Weixiang Luo,3 Jingping Zhang,1 Chaoran Qu4 1Xiangya School of Nursing, Central South University, Changsha, Hunan, People’s Republic of China; 2Evidence-Based Medicine Center, Lanzhou University, Lanzhou, Gansu, People’s Republic of China; 3Department of Nursing, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People’s Republic of China; 4Department of Operating Room, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Jingping Zhang, Xiangya School of Nursing, Central South University, No. 172, Tong-Zi-Po Road, Yue Lu District, Changsha, Hunan, People’s Republic of China, Email jpzhang1965@csu.edu.cn Chaoran Qu, Department of Operating Room, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People’s Republic of China, Email qvchaoran@outlook.comBackground: Nurses frequently experience both direct and indirect trauma, leading to significant psychological challenges. While much research has focused on the negative impacts of such trauma, less attention has been given to vicarious post-traumatic growth (VPTG). Given the high levels of indirect trauma that nurses face, understanding VPTG is crucial for mitigating its adverse effects and enhancing mental health and work efficiency.Objective: To map and synthesize the literature on vicarious post-traumatic growth and identify key knowledge gaps in vicarious post-traumatic growth research.Methods: This scoping review follows the approach proposed by Arksey and O’Malley. We conducted this scoping review using the methodology recommended by the Joanna Briggs Institute, supported by the PAGER framework. We searched 7 databases and gray literature on May 19, 2023 to obtain relevant research.Results: Finally, we included 29 studies from 9 countries. There are currently no reliable data on the incidence of vicarious post-traumatic growth among nurses worldwide. There are multiple instruments available to investigate vicarious post-traumatic growth in nurses, and the vicarious post-traumatic growth inventory is more recommended. Factors affecting nurses’ vicarious post-traumatic growth include coping styles, psychological factors, and social support. Indirect trauma exposure and vicarious post-traumatic growth coexist. There are currently three intervention strategies for vicarious post-traumatic growth, but none have been proven in clinical trials.Conclusion: This is the first scoping review on vicarious post-traumatic growth, there are a lot of research deficiencies and gaps in current research on vicarious post-traumatic growth for nurses. In view of the impact of secondary traumatic events on nurses, future research should pay more attention to nurses’ vicarious post-traumatic growth and promote the development of vicarious post-traumatic growth.Plain Language Summary: What is already known about the topic?Nurses are exposed to secondary traumatic events as part of their every-day work.Nurses experiencing these different secondary trauma exposures experience both positive and negative outcomes, but there has been less research on vicarious post-traumatic growth.The influencing factors of nurses’ vicarious post-traumatic growth and its related survey tools are not clear yet.What this paper addsGender, trauma type, and nurses’ core beliefs, self-efficacy, coping styles, and social support are influencing factors of vicarious post-traumatic growth.Currently, vicarious post-traumatic growth -related survey tools are roughly divided into three types, among which secondary posttraumatic growth inventory and vicarious post-traumatic growth inventory tools are specific survey tools.There are various relationships between indirect exposure to trauma and vicarious post-traumatic growth, and there are differences between different types of indirect trauma exposure. However, there is basically a consensus that indirect exposure to trauma and vicarious post-traumatic growth coexist. There are currently no targeted, scalable, and repeatable interventions for vicarious post-traumatic growth.Keywords: nurse, vicarious post-traumatic growth, secondary traumatic, scoping review

Jing Yang,1,&ast; Mei Liu,1,&ast; Lei Yang,1 Shujing Fang,2 Guangling Wang,2 Zejuan Gu1 1Nursing Department, Jiangsu Province Hospital and the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China; 2Orthopedics Department, Jiangsu Province Hospital and the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zejuan Gu, Nursing Department, Jiangsu province hospital and the First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, People’s Republic of China, Tel +8602568305379, Email jassicagu@163.comObjective: To analyze the current utilisation of delirium risk assessment and screening for older patients after hip fracture surgery in tertiary hospitals in Jiangsu Province, China.Methods: This cross-sectional study was conducted from April 1 to April 30, 2023 among nurses working in orthopedics from Level III hospitals in Jiangsu Province, China. Data were collected using a self-designed questionnaire that focused on the utilisation of delirium risk assessment and prevention measures for older patients after hip fracture surgery. The questionnaire was administered through the online platform Questionnaire Star. Differences between data were analyzed using chi-square and rank-sum tests.Results: A total of 616 nurses from 48 hospitals in Jiangsu province responded to the survey. Among them, 50.17% reported having no training in delirium management, 66.88% did not assess patients for delirium risk, and 73.21% did not screen patients for delirium in their clinical practice. It was observed that nurses with longer tenure, nurses specialising in orthopaedics, and nurses with ICU experience were more attentive to delirium risk assessment and delirium screening of patients (P< 0.001).Conclusion: Medical institutions must focus on strengthening nurses’ training in delirium management for older patients after hip fracture surgery, improve their ability to undertake risk assessment and risk screening, unify delirium management norms, and ultimately improve nurses’ delirium management ability.Keywords: risk assessment and screening, delirium, older patients, postoperative Hip fracture

Jing Zhao,&ast; Jiuxiang He,&ast; Xiaoyan Ding, Yuxin Zhou, Minchi Liu, Xiaozhong Chen, Wenxuan Quan, Dong Hua, Jun Tong, Jintao Li College of Basic Medicine, Army Medical University, Chongqing, 400038, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jintao Li, College of Basic Medicine, Army Medical University, Gaotanyan Street, No. 30, Shapingba District, Chongqing, 400038, People’s Republic of China, Tel +1-86-23-68771389, Fax +1-86-23-68771391, Email ljtqms@tmmu.edu.cnBackground: The global prevalence of Dengue virus (DENV) infection poses a significant health risk, urging the need for effective vaccinations. Peptide vaccines, known for their capacity to induce comprehensive immunity against multiple virus serotypes, offer promise due to their stability, safety, and design flexibility. Spherical nucleic acid (SNA), particularly those with gold nanoparticle cores, present an attractive avenue for enhancing peptide vaccine efficacy due to their modularity and immunomodulatory properties.Methods: The spherical nucleic acid-TBB (SNA-TBB), a novel nanovaccine construct, was fabricated through the co-functionalization process of SNA with epitope peptide, targeting all four serotypes of the DENV. This innovative approach aims to enhance immunogenicity and provide broad-spectrum protection against DENV infections. The physicochemical properties of SNA-TBB were characterized using dynamic light scattering, zeta potential measurement, and transmission electron microscopy. In vitro assessments included endocytosis studies, cytotoxicity evaluation, bone marrow-dendritic cells (BMDCs) maturation and activation analysis, cytokine detection, RNA sequencing, and transcript level analysis in BMDCs. In vivo immunization studies in mice involved evaluating IgG antibody titers, serum protection against DENV infection and safety assessment of nanovaccines.Results: SNA-TBB demonstrated successful synthesis, enhanced endocytosis, and favorable physicochemical properties. In vitro assessments revealed no cytotoxicity and promoted BMDCs maturation. Cytokine analyses exhibited heightened IL-12p70, TNF-α, and IL-1β levels. Transcriptomic analysis highlighted genes linked to BMDCs maturation and immune responses. In vivo studies immunization with SNA-TBB resulted in elevated antigen-specific IgG antibody levels and conferred protection against DENV infection in neonatal mice. Evaluation of in vivo safety showed no signs of adverse effects in vital organs.Conclusion: The study demonstrates the successful development of SNA-TBB as a promising nanovaccine platform against DENV infection and highlights the potential of SNA-based peptide vaccines as a strategy for developing safe and effective antiviral immunotherapy.Keywords: nanovaccine, dengue virus, spherical nucleic acid, immunogenicity, peptide antigen

Jinghui Zhang,1 Mowei Liu,2 Qing Zhang,1 Yan Li1 1Shanghai Institute of Early Childhood Education, Shanghai Normal University, Shanghai, People’s Republic of China; 2Department of Psychology, Trent University, Peterborough, ON, CanadaCorrespondence: Yan Li, Email liyan@shnu.edu.cnPurpose: This study investigates the relationship between mother phubbing and preschoolers’ problematic media use, examining the mediating role of the mother-child relationship and the moderating effects of paternal coparenting. Drawing on the Interactive Theory of Childhood Problematic Media Use and family system theory, we aim to identify key family dynamics that influence early childhood media habits. The findings could provide insights into mitigating the negative impacts of parental phubbing on children’s media habits and inform targeted interventions to promote healthier media use among young children.Methods: The study examined 1008 mothers (Mage = 35.58 years, SD = 3.90) with preschool-aged children (Mage = 4.59 years, SD = 0.92) who completed self-report questionnaires. Path analysis with bootstrap sampling was executed to assess the moderated mediation model.Results: Mother phubbing was positively associated with preschoolers’ problematic media use, with this relationship mediated by the mother-child relationship. Paternal coparenting moderated both the direct and indirect pathways in this relationship. Specifically, paternal coparenting directly mitigated the impact of mother phubbing on child problematic media use. Additionally, it alleviated the negative influence of mother phubbing on the mother-child relationship, thereby indirectly reducing its adverse effect on preschoolers’ problematic media use. Overall, paternal coparenting demonstrated a protective function against the negative consequences of mother phubbing.Conclusion: The findings significantly contribute to our understanding of how mother phubbing might increase the risk of problematic media use among preschoolers and underscore the potential importance of reducing mother phubbing and increasing paternal coparenting as integral steps to prevent preschoolers’ problematic media use.Keywords: mother phubbing, mother-child relationship, problematic media use, paternal coparenting, preschoolers

Minjing Liu,1,2,&ast; Jiaojiao Li,2,&ast; Jing Xu,2 Ya Chen,2 Chiafu Chien,3 Hui Zhang,4 Qing Zhang,5 Li Wang2 1Department of Nursing, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2School of Nursing, Suzhou Medical College of Soochow University, Suzhou, People’s Republic of China; 3Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4School of Nursing, Suzhou Vocational Health College, Suzhou, People’s Republic of China; 5Physical Education and Sports School, Soochow University, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Wang, School of Nursing, Suzhou Medical College, Soochow University, No. 1 Shi zi Street, Suzhou, Jiangsu, 215006, People’s Republic of China, Email li-wang-1@suda.edu.cn Qing Zhang, Physical Education and Sports School, Soochow University, Suzhou, People’s Republic of China, Email zhangqing@suda.edu.cnPurpose: This randomized parallel controlled trial aimed to determine the effectiveness of graded progressive home-based resistance combined with aerobic exercise in improving physical fitness in community-dwelling older adults with sarcopenia.Patients and Methods: Community-dwelling older adults (≥ 60 years) with sarcopenia were randomly assigned to the intervention group (IG), receiving 12 weeks of graded progressive home-based resistance and aerobic exercise training, and the control group (CG), maintaining lifestyle unchanged. The primary outcomes were knee extensor muscle strength and the six-minute walk distance (6MWD). Intention-to-treat analysis was applied to the data from all participants in the CG and IG. Post-intervention differences between the intervention and control groups were determined using a generalized estimated equation model with pre-values adjusted.Results: Data from all the participants in the IG (n=41) and CG (n=45) were analyzed. After the intervention, knee extensor muscle strength (95% CI: 0.140– 3.460, P=0.036), 6MWD (95% CI: 35.350– 80.010, P< 0.001), flexor muscle strength and the results of 30s bicep curls, 30s chair stand, the chair sit and reach test and back stretch test in the IG were larger and value of the timed up-and-go test was smaller than those in the CG (P< 0.05). The body composition, quality of life and their changes showed no group differences. The attendance rates were 82.9% and 85.4% for resistance and aerobic exercise, respectively.Conclusion: The 12-week graded progressive home-based resistance and aerobic exercise intervention improved muscle strength, balance, flexibility, and cardiorespiratory fitness in community-dwelling older adults with sarcopenia, whereas body composition and quality of life remained unchanged. The research was approved by the Ethics Committee of Soochow University (ECSU-2019000161) and registered at the Chinese Clinical Trial Registry (ChiCTR1900027960, http://www.chictr.org.cn/showproj.aspx?proj=45968).Keywords: physical function, muscle strength, multicomponent exercise, walking, skeletal muscle disease

Zhou Zhu,1– 3 Mingjuan Liu,1– 3 Hanlin Zhang,1,2 Heyi Zheng,1,2 Jun Li1,2 1Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 3 4+4 Medical Doctor Program, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Jun Li, Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, People’s Republic of China, Email lijun35@hotmail.comBackground: Acral melanoma presents distinct biological characteristics compared to cutaneous melanoma. While adjuvant therapeutic strategies for high-risk resected acral melanoma closely resemble those for cutaneous melanoma, the evidence supporting the clinical application of adjuvant therapy for acral melanoma remains inadequate. Our aim was to systematically analyze the efficacy and safety profile of adjuvant therapy in acral melanoma.Methods: This systematic review adhered to a pre-registered protocol. We comprehensively searched four electronic databases and reference lists of included articles to identify eligible studies. The primary outcome was therapeutic efficacy, and the secondary outcome was adverse events (AEs).Results: This systematic review included 11 studies with 758 acral melanoma patients undergoing adjuvant therapy. High-dose interferon α-2b (IFN) regimens showed no significant difference in recurrence-free survival (RFS), though the longer regimen was linked to increased hepatotoxicity. Adjuvant anti-PD-1 therapy demonstrated varying efficacy, with improved RFS in patients who experienced immune-related AEs. Targeted therapy with dabrafenib plus trametinib achieved high 12-month RFS in patients with BRAF-mutated acral melanoma. Comparative studies suggested that adjuvant anti-PD-1 therapy is similarly effective to IFN in prolonging survival for high-risk acral melanoma patients. Additionally, prior treatment with pegylated IFN enhanced RFS in patients receiving adjuvant pembrolizumab.Conclusion: High-dose IFN was widely used as adjuvant therapy for acral melanoma, but serious AEs prompted the search for alternatives. Adjuvant anti-PD-1 therapy shows promise, though it may be less effective than in non-acral melanoma. Further prospective studies are needed to determine the optimal adjuvant treatment for acral melanoma.Keywords: acral melanoma, adjuvant therapy, anti-PD-1 antibody, high-dose interferon α-2b, systematic review

Mingtao Liu,1,&ast; Zhangkai J Cheng,1,&ast; Jiaxi Chen,2,&ast; Haiyang Li,1,3 Mingshan Xue,4,5 Xing Fu,1 Yanjun Li,2 Jiaxin Wang,2 Chenwei You,2 Haisheng Hu,1 Haojie Wu,1 Huimin Huang,1 Baoqing Sun1,4 1Department of Clinical Laboratory of the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, 510120, People’s Republic of China; 2KingMed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, 511495, People’s Republic of China; 3MRC Biostatistics Unit, University of Cambridge, Cambridge, CB2 0SR, UK; 4Guangzhou Laboratory, Guangzhou, 510005, People’s Republic of China; 5Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, 510440, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Baoqing Sun; Huimin Huang, Department of Clinical Laboratory of the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, 510120, People’s Republic of China, Tel +86 13824124015 ; +86 13631496651, Email sunbaoqing@vip.163.com; huanghuimin311@126.comBackground: While serum periostin and Krebs von den Lungen-6 (KL-6) have been acknowledged as independent markers in idiopathic pulmonary fibrosis (IPF) diagnosis, the clinical combinatory potential of these biomarkers combined with high-resolution computed tomography (HRCT) has yet to be fully explored.Methods: This retrospective study involved 78 participants, comprising 51 UIP-IPF patients and 27 healthy controls. All subjects underwent clinical and laboratory examinations, particularly the detection of periostin and KL-6 using ELISA with innovative HRCT fibrosis score evaluations at admission and discharge during hospitalization in UIP-IPF patients.Results: In our cohort of patients with IPF, predominantly male, over an average follow-up period of 195.27 days. Serum levels of periostin and KL-6 were significantly elevated in IPF patients compared to healthy controls (&ast;p < 0.05). Post-treatment, KL-6 levels decreased significantly, while periostin levels increased. Notably, periostin exhibited superior prognostic accuracy over KL-6, with a higher AUC of 0.875 than 0.639 in ROC analysis. An increase in periostin levels correlated with disease progression, as evidenced by worsened HRCT fibrotic scores and decreased survival probability. These findings underscore periostin’s potential as a reliable biomarker for assessing IPF severity and therapeutic response.Conclusion: Our findings underscore the preeminence of serum periostin over KL-6 in UIP-IPF diagnosis, particularly when conjoined with HRCT fibrosis score.Keywords: periostin, Krebs von den Lungen-6, idiopathic pulmonary fibrosis, HRCT fibrosis score, diagnostic hematology

Yi Zhou,1 Weina Gao,2 Zhijiao Cao,3 Shumin Gao,2 Xutong Guo,2 Meng Liu,2 Congjie Cao4 1School of Nursing, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Orthopedics, Baoding No.1 Central Hospital, Baoding, Hebei, People’s Republic of China; 3Department of Nursing, Baoding No.1 Central Hospital, Baoding, Hebei, People’s Republic of China; 4Nursing Department, Langfang Health Vocational College, Langfang, Hebei, People’s Republic of ChinaCorrespondence: Weina Gao, Department of Orthopedics, Baoding No.1 Central Hospital, No. 320, Changcheng North Street, Lianchi District, Baoding, Hebei, 071000, People’s Republic of China, Tel +86 0312-5975023, Email gaoweina984926@163.comBackground: Kinesiophobia is common in patients after total knee arthroplasty and is an important risk factor for post-operative recovery outcomes. Little is known about the complex intercorrelations between different components of pain catastrophizing, self-efficacy, and kinesiophobia. This study aimed to identify the central components of kinesiophobia and to explore the interconnectedness between components of pain catastrophizing, self-efficacy, and kinesiophobia.Methods: A total of 216 patients after total knee arthroplasty were recruited in this study. Pain Catastrophizing Scale, Self-efficacy of Rehabilitation Outcome Scale and Tampa Scale for Kinesiophobia were used to assess pain catastrophizing, self-efficacy and kinesiophobia. R software was used to visualize the networks and analyze the centrality of the networks. The index “strength” and “bridge expected influence” were employed to identify the central components and the bridge components of the networks.Results: In the item network of kinesiophobia, three items (“Simply being careful that I do not make any unnecessary movements is the safest thing I can do to prevent my pain from worsening”, “My accident has put my body at risk for the rest of my life”, and “My body is telling me I have something dangerously wrong”) had the highest strength centrality. In the pain catastrophizing/self-efficacy–kinesiophobia network, rumination had the highest positive bridge expected influence, while coping self-efficacy had the highest negative value.Conclusion: The three central components of kinesiophobia identified in this study, as well as two bridge variables (rumination and coping self-efficacy), could be promising and effective targets for prevention and intervention of kinesiophobia.Keywords: pain catastrophizing, self-efficacy, kinesiophobia, total knee arthroplasty, network analysis

Zixu Zhang,1,2 Muhan Chen,1,2 Jiahua Wang,1,2 Mo Liu,1,2 Ruibo Guo,1,2 Lu Zhang,1,2 Liang Kong,1,2 Yang Liu,1,2 Yang Yu,1– 3 Xuetao Li1,2 1School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, 116600, People’s Republic of China; 2Shenyang Key Laboratory of Chinese Medicine targeted Delivery Key laboratory, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, People’s Republic of China; 3Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang, 110032, People’s Republic of ChinaCorrespondence: Xuetao Li; Yang Yu, School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, 116600, People’s Republic of China, Tel +86411 8589 0170, Fax +86411 8589 0128, Email lixuetao1979@163.com; yuqn0702@163.comIntroduction: Resistance of intracellular pathogens is a challenge in microbial therapy. Methicillin-resistant Staphylococcus aureus (MRSA), which is able to persist inside the cells of infected tissues, is protected from attack by the immune system and many antimicrobial agents. To overcome these limitations, nano-delivery systems can be used for targeted therapy of intracellular MRSA.Methods: Hyaluronic acid-modified azithromycin/quercetin micelles (HA-AZI/Qe-M) were synthesized by thin film hydration. The micelles were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and Fourier transform infrared spectroscopy (FTIR), and the drug loading (DL) and encapsulation efficiency (EE) were detected by high performance liquid chromatography (HPLC). The uptake ability of RAW264.7 cells was investigated, and its distribution in mice was evaluated by in vivo imaging. The inhibitory effect of the micelles against MRSA in vitro and its ability to eliminate intracellular bacteria were evaluated. Bacterial muscle-infected mice were constructed to evaluate the therapeutic effect of the micelles on bacterial infections in vivo and the biocompatibility of the micelles was investigated.Results: HA-AZI/Qe-M had suitable physical and chemical properties and characterization. In vitro antibacterial experiments showed that HA-AZI/Qe-M could effectively inhibit the growth of MRSA, inhibit and eliminate the biofilm formed by MRSA, and have an excellent therapeutic effect on intracellular bacterial infection. The results of RAW264.7 cells uptake and in vivo imaging showed that HA-AZI/Qe-M could increase the cellular uptake, target the infection site, and prolong the treatment time. The results of in vivo antibacterial infection experiments showed that HA-AZI/Qe-M was able to ameliorate the extent of thigh muscle infections in mice and reduce the expression of inflammatory factors.Conclusion: HA-AZI/Qe-M is a novel and effective nano-drug delivery system that can target intracellular bacterial infection, and it is expected to be safely used for the treatment of MRSA infection.Keywords: MRSA, hyaluronic acid, antibiotics, micelles, azithromycin, quercetin

Qian Cao,1,&ast; Ruijie Zhou,2,&ast; 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&ast;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)

Honglin Wang,1,2,&ast; Na Li,1,3,4,&ast; Ying Ye,5 Nan Zhao,6 Meizi Liu,1 Min Xu,3 Qiuhong Zhou3,4 1Xiangya School of Nursing, Central South University, Changsha, People’s Republic of China; 2School of Health and Nursing, Guangzhou Huali College, Jiangmen, People’s Republic of China; 3Teaching and Research Section of Clinical Nursing, Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 4National Clinical Research Center for Geriatric Disorders, Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 5Department of Nursing, First People’s Hospital of Yunnan, Kunming, People’s Republic of China; 6School of Nursing, Zhengzhou Shuqing Medical College, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiuhong Zhou, Teaching and Research Section of Clinical Nursing, Xiangya Hospital of Central South University, Changsha, 410008, People’s Republic of China, Tel +8613786136512, Email 928555448@qq.comObjective: Timely screening and intervention can prevent the development of the diabetic foot. However, delayed visits to the clinic are common among diabetic foot patients. The study aimed to develop and validate a questionnaire to assess healthcare-seeking behavior among patients with diabetic high-risk foot.Methods: The questionnaire of healthcare-seeking intention for patients with diabetic high-risk foot was developed in two phases: (1) Developing the questionnaire: 1) questionnaire items were formulated after literature review, group discussion and semi-qualitative interview; 2) a two-round modified Delphi method was to examine the content validity and the degree of consistency in questionnaire items; 3) conducting pre-survey to revise the questionnaire items. (2) Assessing the internal reliability and construct validity.Results: The final questionnaire consisted of five main themes and 28 items with a five-point rating. Cronbach’s alpha coefficients for the five dimensions were respectively 0.937 (relevant knowledge of diabetic foot), 0.669 (attitudes toward seeking care), 0.896 (social support for seeking care), 0.621 (efficacy in coping with foot symptoms), 0.871 (intention to seek care). The Scale-level Content Validity Index of the five parts was 1.00, 0.80, 1.00, 1.00, and 1.00, respectively. The Kaiser-Meyer-Olkin values for each dimension was greater than 0.7, and the p-value for Bartlett’s test of sphericity was less than 0.05.Conclusion: This questionnaire showed good validity, internal consistency, and reliability. It provided a potentially useful instrument to evaluate healthcare-seeking intention among patients with diabetic high-risk foot.Keywords: healthcare-seeking intention, questionnaire development, high-risk foot, patients

Murong Wang,1,&ast; Qunfang Zhou,2,&ast; Hui Li,1 Mingyu Liu,3 Ruixia Li,4 Wei Wang,5 Xiaohui Wang,6 Jinhua Huang,1 Feng Duan2 1Department of Minimally Invasive Interventional Radiology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong province, People’s Republic of China; 2Department of Interventional Radiology, 5th Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong province, People’s Republic of China; 4Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong province, People’s Republic of China; 5Department of General Surgery, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning Province, People’s Republic of China; 6Department of Hepatobiliary Surgery, Hunan Provincial People’s Hospital, Changsha, Hunan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinhua Huang, Department of Minimally Invasive Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong province, People’s Republic of China, Tel/Fax +86-020-87343272, Email huangjh@sysucc.org.cn Feng Duan, Department of Interventional Radiology, 5th Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China, Tel/Fax +8610-66939123, Email duanfeng@vip.sina.comPurpose: The outcome between Lenvatinib plus programmed cell death protein-1 (PD-1) inhibitor and Lenvatinib in HCC beyond oligometastasis was unclear. In this multicenter, we compared the prognosis of Lenvatinib plus PD-1 inhibitor with Lenvatinib in HCC beyond oligometastasis.Patients and Methods: A total of 296 patients from six institutions were included. The patients were divided into two groups: (a) concurrent Lenvatinib plus PD-1 inhibitor treatment (Len+PD-1 group) and (b) Lenvatinib monotherapy (Len group). The primary endpoint was overall survival (OS), the second endpoint was progression-free survival (PFS) and efficacy.Results: The median OS was 20.1 ± 1.2 (17.7– 22.5) months and 15.7 ± 1.5 (12.8– 18.6) months in the Len+PD-1 and Len groups, respectively. The 12-, 24-, and 36-month OS rates were 79.1%, 39.4%, and 10.7% in the Len+PD-1 group, and 76.3%, 29.7%, and 0% in the Len group, respectively. The OS and PFS rates of the Len+PD-1 group were significantly longer compared with the Len group (hazard ratio [HR], 0.88; 95% confidence index [CI], 0.49– 0.94; P = 0.021) and (HR, 0.66; 95% CI, 0.50– 0.87; P = 0.003). A subgroup analysis revealed that OS (HR, 0.57; 95% CI, 0.36– 0.90; P = 0.016) was improved between the Len+PD-1 and Len groups with hepatic artery infusion chemotherapy (HAIC) treatment, whereas OS (HR, 1.11; 95% CI, 0.68– 1.80; P = 0.689) was similar between the Len and Len+PD-1 groups without HAIC.Conclusion: Lenvatinib combined with PD-1 inhibitor significantly improves the survival of HCC beyond oligometastasis. For patients with HAIC, there was obviously significance between Len and Len+PD-1 groups.Plain Language Summary: Lenvatinib as one of system therapy, is recommended treatment for HCC with multimetastases. The LEAP-002 trial, which evaluated Lenvatinib combined with Pembrolizumab exhibited improved progression-free survival (PFS) and overall survival (OS) compared with Lenvatinib alone. However, the combination efficacy on HCC beyond oligometastasis is unknown. In this multicenter study, we found that Lenvatinib combined with PD-1 inhibitor significantly improved both the OS and PFS and this combination could be recommended for HCC beyond oligometastases. OS and PFS were improved in the Len+PD-1 versus the Len group with hepatic artery infusion chemotherapy (HAIC) treatment, whereas the OS and PFS were similar between the Len and Len+PD-1 groups without HAIC. We provided clinical value that HAIC could be recommended as an effective local therapy to improve the prognosis for advanced HCC.Keywords: advanced hepatocellular carcinoma, Lenvatinib, beyond oligometastasis, prognosis, programmed death receptor-1 inhibitor

Mei Liu,1,&ast; Sili Guo,1,&ast; Xiaohan Li,1,&ast; Yang Tian,1 Yanjie Yu,2 Lili Tang,1 Qimei Sun,1 Ting Zhang,1 Mingwei Fan,3 Lili Zhang,1 Yingjiang Xu,4 Jiajia An,5 Xiangqian Gao,6 Lei Han,7 Lei Zhang1 1Department of Endocrinology and Metabolism, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China; 2Department of Ultrasound Medicine, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China; 3Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China; 4Department of Interventional Vascular Surgery, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China; 5Department of Clinical Laboratory, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China; 6Department of Pathology, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China; 7Department of Reproductive Medicine, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Zhang, Department of Endocrinology and Metabolism, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China, Email binzhouzhanglei@outlook.comBackground: GLP-1 receptor agonists (GLP-1 RA) have been proven to treat several metabolic diseases; however, the effects of GLP-1 RA on polycystic ovary syndrome (PCOS) remain unclear. Here, we aimed to investigate whether semaglutide, a novel GLP-1 RA, could alleviate ovarian inflammation in PCOS mice.Methods: Female C57BL/6J mice were subcutaneously injected with dehydroepiandrosterone for 21 days to establish the PCOS model. Then the mice were randomly divided into three groups: PCOS group (n = 6), S-0.42 group (semaglutide 0.42 mg/kg/w, n = 6), and S-0.84 group (semaglutide 0.84 mg/kg/w, n = 6). The remaining six mice were used as controls (NC). After 28 days of intervention, serum sex hormones and inflammatory cytokine levels were measured. Hematoxylin and eosin staining was used to observe the ovarian morphology. Immunohistochemical staining was used to detect the relative expression of CYP19A1, TNF-α, IL-6, IL-1β, and NF-κB in ovaries. CYP17A1 and StAR were detected using immunofluorescence staining. Finally, the relative expressions of AMPK, pAMPK, SIRT1, NF-κB, IκBα, pIκBα, TNF-α, IL-6, and IL-1β were measured using Western blotting.Results: First, after intervention with semaglutide, the weight of the mice decreased, insulin resistance improved, and the estrous cycle returned to normal. Serum testosterone and IL-1β levels decreased significantly, whereas estradiol and progestin levels increased significantly. Follicular cystic dilation significantly improved. The expression of TNF-α, IL-6, IL-1β, NF-κB, CYP17A1, and StAR in the ovary was significantly downregulated, whereas CYP19A1 expression was upregulated after the intervention. Finally, we confirmed that semaglutide alleviates ovarian tissue inflammation and improves PCOS through the AMPK/SIRT1/NF-κB signaling pathway.Conclusion: Semaglutide alleviates ovarian inflammation via the AMPK/SIRT1/NF‑κB signaling pathway in PCOS mice.Keywords: GLP-1 receptor agonist, polycystic ovary syndrome, semaglutide, inflammation

Deying Xiao,1,2,&ast; Long Xie,1,&ast; Wenhong Lin,1 Jinhua Fu,1 Lin Deng,1 Qian Zhuang,2,3 Maobai Liu2,3 1Longyan First Affiliated Hospital of Fujian Medical University, Longyan, 364000, People’s Republic of China; 2The School of Pharmacy, Fujian Medical University, Fuzhou, 350004, People’s Republic of China; 3Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, 350001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Maobai Liu; Qian Zhuang, Department of Pharmacy, Fujian Medical University Union Hospital, No. 29, Xinquan Road, Antai Street, Gulou District, Fuzhou, 350001, People’s Republic of China, Tel +86-591-83357896, Email liumaobai10@163.com; ZhuangQ0591@163.comBackground: This evaluation aims to provide a reference for clinical decision-making regarding the use of SPN in intensive care unit (ICU) patients. The objective of this study is to evaluate the quality of clinical practice guidelines for the use of supplementary parenteral nutrition (SPN) in ICU patients, both domestically and internationally.Patients and Methods: The quality of clinical practice recommendations for SPN use in ICU patients was assessed using a systematic approach.Results: Five nutrition recommendations in total were included for analysis. The average standardized scores for the recommendations across the six domains of the Appraisal of Guidelines for Research and Evaluation II (AGREE II) are as follows: Scope and purpose scored 87.96%, stakeholder Involvement scored 68.52%, rigour of development scored 73.40%, clarity of presentation scored 84.80%, applicability scored 64.72%, and editorial independence scored 91.10%. In the comprehensive evaluation, two guidelines were rated as grade A recommendations, and three were rated as grade B recommendations. Most guidelines recommended against early use of SPN when energy and protein requirements could not be met solely through enteral nutrition (EN) in ICU patients. The guidelines emphasized achieving target energy levels and discontinuing parenteral nutrition (PN) as soon as the energy requirements were met to prevent overfeeding.Conclusion: This study utilized the AGREE II scale to assess the quality of five nutrition guidelines. All 5 guidelines were deemed acceptable Recommendations include focusing on participants, rigour, and applicability to enhance guideline quality. Clinicians should exercise professional judgment when applying guidelines as they complement training and judgment, rather than replacing them.Keywords: ICU, patients, supplementary parenteral nutrition, clinical practice guidelines, guideline evaluation

Qinying Zhao,&ast; Ziyue Zhang,&ast; Shuo Li, Ming Liu Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ming Liu, Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, 300052, People’s Republic of China, Email mingliu@tmu.edu.cnAim: Although the interplay of insulin resistance (IR) and low muscle mass is increasingly recognized, it remains unknown whether the triglyceride-glucose (TyG) index, as an indicator of IR, is associated with low muscle mass in patients with type 2 diabetes (T2D). Our study aimed to investigate the association between TyG index and low muscle mass in hospitalized T2D patients.Methods: This cross-sectional study involved 2687 hospitalized participants with T2D. The TyG index was calculated by fasting plasma glucose (FPG) and triglyceride levels. The outcome variables were defined as appendicular skeletal muscle mass index (ASMI) and low muscle mass. To explore the relationship between TyG index and low muscle mass, we conducted the multivariate linear regression, multivariate logistic regression, and subgroup analysis.Results: In the fully adjusted multivariate linear regression, there was a negative correlation between TyG index (β=− 0.10, 95% CI: − 0.14, − 0.06) and ASMI. TyG index (OR = 1.34, 95% CI: 1.08, 1.65) had a more significant association with low muscle mass compared to FPG (OR = 1.05, 95% CI: 1.01, 1.09) and glycated hemoglobin A1c (OR = 1.07, 95% CI: 0.99, 1.15). The statistical significance of the trend persisted among the TyG index quartile groups. Subgroup analysis revealed stronger positive associations between TyG index and low muscle mass in females, individuals aged 60 years or older, those with a body mass index of 28kg/m2 or higher, and HbA1c levels of 6.5% or higher, as well as those with hypertension and dyslipidemia.Conclusion: A higher TyG index level is positively associated with a higher risk of low muscle mass, suggesting that TyG index could be a potential biomarker of low muscle mass in hospitalized T2D patients.Keywords: triglyceride-glucose index, low muscle mass, type 2 diabetes, insulin resistance, cross-sectional study

Jinfeng Ai,1 Yihan Sun,2 Minrong Yan,1 Maolin Liu,1 Dongjun Zhong,1 Wei He,2 Xu Kang,2 Xinsheng Chen2 1The Second Clinical Medical College, Guangzhou University of Traditional Chinese Medicine, Guangzhou, People’s Republic of China; 2Dermatology, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, People’s Republic of ChinaCorrespondence: Xu Kang; Xinsheng Chen, Email Kangxuwf@163.com; xinshengchen@souhu.comAbstract: Follicular atresia triad, also known as paradoxical acne (FOT), is a rare and serious clinical syndrome in dermatology, mainly manifested by coalescing acne, purulent perifolliculitis of the head, and suppurative sweating inflammation, and FOT combined with necrotising fasciitis of the lower limbs and squamous cell carcinoma is rare both at home and abroad. In this article, we share the clinical data and treatment of a patient with follicular atresia triad and necrotising fasciitis and squamous cell carcinoma of the left lower limb for your reference.Keywords: follicular atresia triad, necrotising fasciitis, squamous cell carcinoma

Zhi-Jun Shen, Miao Liu, Jun-Xia Zhang, Yu Huang, Ying Kong, Shi-Guo Liu Department of Clinical Laboratory, Hubei Third People´s Hospital Affiliated to Jianghan University, Wuhan, 430033, People’s Republic of ChinaCorrespondence: Shi-Guo Liu, Department of Clinical Laboratory, Hubei Third People´s Hospital Affiliated to Jianghan University, No. 26, Zhongshan Road, Wuhan, Qiaokou District, People’s Republic of China, Email llsgg518@163.comBackground: Although observational studies have reported a correlation between vitamin D deficiency and type 2 diabetes mellitus (T2DM), epidemiological evidence on the risk of obese subjects suffering T2DM due to a vitamin D deficiency is limited. Therefore, we investigated the correlation between T2DM and serum vitamin D, lipids, blood pressure, insulin indexes in an obese population.Methods: A total of 1440 participants including 450 healthy controls and 990 obese subjects, 470 without T2DM and 520 with T2DM. Serum vitamin D levels were measured, and the association between low levels and T2DM in obese subjects was examined using multinomial and linear regression analyses.Results: Of the participants, 35% had deficient or insufficient vitamin D levels (ie, < 20 ng/mL). Compared with healthy controls, obese subjects, particularly those with T2DM had lower vitamin D levels. Multinomial logistic regression analysis showed that obese subjects with T2DM had a gradually increasing risk for desirable (RO = 1.41, 95% CI 1.06– 1.93, P = 0.027), insufficient (RO = 1.83, 95% CI 1.27– 2.84, P < 0.001), or deficient ((RO = 2.14, 95% CI 1.15– 3.75, P = 0.014) vitamin D levels. In obese subjects with T2DM, vitamin D levels correlated inversely with the risk indicators for diabetes, such as the levels of HbA1c (β = − 0.16, P = 0.002), fasting insulin (Fins; β = − 0.31, P = 0.008), and HOMA-IR (β = − 0.19, P < 0.001). In obese subjects without T2DM, vitamin D was associated negatively with the risk of having T2DM at five-year follow-up (relative risk = 0.93, 95% CI 0.79– 0.97, P = 0.037).Conclusion: This study demonstrates that low vitamin D levels correlate with the presence of T2DM in the obese population. This finding indicates that hypovitaminosis D may be a potential biological vulnerability factor for the development of T2DM in obese subjects.Keywords: vitamins, T2DM, obesity, biomarker

Xiaoyun Li,1,&ast; Yuke Fu,2,&ast; Wanjuan Weng,1 Mowei Liu,2 Yan Li1 1Shanghai Institute of Early Childhood Education, Shanghai Normal University, Shanghai, People’s Republic of China; 2Department of Psychology, Trent University, Peterborough, Ontario, Canada&ast;These authors contributed equally to this workCorrespondence: Mowei Liu, Department of Psychology, Trent University, Peterborough, Ontario, K9L 0G2, Canada, Email moweiliu@trentu.ca Yan Li, Shanghai Institute of Early Childhood Education, Shanghai Normal University, No. 100 Guilin Road, Shanghai, 200234, People’s Republic of China, Email liyan@shnu.edu.cnPurpose: Given that mother plays the main nurturing role in a family unit and their unique influence on children’s development, the current study aimed to examine the influence of maternal phubbing on children’s problematic media use and the independent and interactive moderating role of children’s negative affectivity and effortful control.Methods: Participants were 1986 children aged 3 to 6 years in Shanghai, China. Their mothers were asked to complete a series of questionnaires including parental phubbing scale, problematic media use measure, and child behavior questionnaire. To investigate the moderating influence of children’s negative affectivity and effortful control, hierarchical linear regression analyses were conducted using SPSS 24.0. Simple slopes analyses and the Johnson–Neyman technique were further used to depict moderation effects.Results: Maternal phubbing was associated with higher levels of problematic media use in preschool children (β = 0.18, p < .001, [0.14, 0.22]). Children’s negative affectivity acts as a risk factor, exacerbating the adverse effects of maternal phubbing on children’s problematic media use (β = 0.05, t = 2.69, p < 0.05), whereas children’s effortful control acts as a protective factor, buffering the link between maternal phubbing and children’s problematic media use (β = − 0.10, t = − 5.00, p < 0.001).Conclusion: These results suggest that interventions seeking to promote appropriate digital development in preschoolers should take the child’s temperament into account and be complemented by active parental mediation and involvement.Keywords: maternal phubbing, problematic media use, negative affectivity, effortful control, preschoolers

Kang He,1,&ast; Jie Zang,2,&ast; Tingting Ren,1,&ast; Shaojie Feng,3 Mohan Liu,1 Xude Zhang,3 Wenchang Sun,2 Jinjin Chu,2 Donghua Xu,2 Fengxia Liu3 1Department of Clinical Medicine of Shandong Second Medical University, Weifang, People’s Republic of China; 2Central Laboratory, Weifang People’s Hospital, Shandong Second Medical University/Weifang People’s Hospital, Weifang, People’s Republic of China; 3Department of Allergy, Weifang People’s Hospital, Shandong Second Medical University, Weifang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Donghua Xu; Fengxia Liu, Email flower322@163.com; wf_lfx@163.comAbstract: Atopic dermatitis (AD) is a chronic and inflammatory skin disease with intense itchiness that is highly prevalent worldwide.The pathogenesis of AD is complex and closely related to genetic factors, immunopathogenic factors, environmental factors, and skin infections. Mesenchymal stem cells (MSCs) are non-hematopoietic progenitor cells derived from the mesenchymal stroma. They have anti-inflammatory, anti-apoptotic, and regenerative properties. Numerous studies demonstrate that MSCs can play a therapeutic role in AD by regulating various immune cells, maintaining immune homeostasis, and promoting the repair of damaged tissues. The key mediators for their biological functions are extracellular vesicles (MSC-Evs) and soluble cytokines derived from MSCs. The safety and efficacy of MSCs have been demonstrated in clinical Phase I / IIa trials for AD. This paper provides a comprehensive review of the pathogenesis of AD and the currently published studies on the function of MSCs and MSC-Evs in AD, primarily including the pathogenesis and the immunomodulatory impacts of MSCs and MSC-Evs, along with advancements in clinical studies. It provides insights for comprehending AD pathogenesis and investigating treatments based on MSCs.Keywords: atopic dermatitis, mesenchymal stem cells, Th2-associated immunity, extracellular vesicle

Mingtang Zeng,1,&ast; Maozhu Liu,2,&ast; Xuelin Tao,1,&ast; Xi Yin,1 Chao Shen,1 Xueyan Wang1 1Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xueyan Wang, Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China, Email wxy1226@126.comAbstract: Inflammation involves complex immune responses where cytokines such as TNF-α, IL-1, and IL-6 promote vasodilation and increased vascular permeability to facilitate immune cell migration to inflammation sites. Persistent inflammation is linked to diseases like cancer, arthritis, and neurodegenerative disorders. Although oral anti-inflammatory drugs are favored for their non-invasiveness and cost-effectiveness, their efficacy is often compromised due to gastrointestinal degradation and limited bioavailability. Recent advancements highlight the potential of extracellular vesicles (EVs) as nanocarriers that enhance drug delivery by encapsulating therapeutic agents, ensuring targeted release and reduced toxicity. These EVs, derived from dietary sources and cell cultures, exhibit excellent biocompatibility and stability, presenting a novel approach in anti-inflammatory therapies. This review discusses the classification and advantages of orally administered EVs (O-EVs), their mechanism of action, and their emerging role in treating inflammatory conditions, positioning them as promising vectors in the development of innovative anti-inflammatory drug delivery systems.Keywords: extracellular vesicles, anti-inflammatory, drug delivery systems, food, oral administration

Yuanna Zhou,&ast; Lin Han,&ast; Wuxing Zhang, Yujun Fan, Wenjian Liu, Muzi Liu, Yishan Fan, Xiaoyuan Qu&ast; School of Nursing and Health, Henan University, Kaifeng, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoyuan Qu, School of Nursing and Health, Henan University, Jinming Avenue, Kaifeng City, Henan Province, People’s Republic of China, Email quxiaoyuan@henu.edu.cnPurpose: China has made considerable efforts to promote the development of maternal and child health (MCH) care since the new health system reform in 2009. This study aims to evaluate the trend and equity of MCH resources allocation in China from 2008 to 2020 and provide a reference for rational distribution of MCH resources.Methods: Data were collected from the China Health Statistics Yearbook and China Statistics Yearbook. The number of MCH hospitals, licensed (assistant) physicians, registered nurses and beds were selected for the measurement of the equity of MCH resources allocation. The Health Resource Agglomeration Degree and Theil index were used in evaluating MCH resource allocation equity and to compare differences among regions.Results: From 2008 to 2020, the average annual growth rates for MCH hospitals, beds, licensed (assistant) physicians, and registered nurses were 0.72%, 6.95%, 5.04%, and 9.57%, respectively. However, regional disparities in the equity of MCH resource allocation have been identified. Although the western region has shown growth in MCH resource allocation by geography, the agglomeration degree of the four indicators remains less than 1, significantly lower than the average value of greater than 2 in the eastern region. Additionally, the equity of human resource allocation in the western region is lower than the equity in the allocation of institutions. In the densely populated eastern region, the equity of MCH resource allocation by population is decreasing, with the agglomeration degree of all four indicators below 1 in 2020. The disparity in healthcare resource allocation within regions is the main cause of inequitable MCH resource allocation in China.Conclusion: The allocation of MCH resources in China has improved since 2009, however, geographic equity needs further improvement, particularly in densely populated regions. Population and geographic balances should be considered in the development and implementation of MCH resource allocation policies, and improving intraregional equity should be the focus.Keywords: maternal and child health, resources allocation, equity, health resource agglomeration degree, theil index

Peigang Zhang,1,2,&ast; Lingling Zheng,1,3,4,&ast; Xiaorui Zhang,1,3 Miao Liu,1,3 Mingli Li,2 Mengting Zhang,1 Jian-Lin Wu,4 Martin MF Choi,5 Wei Bian1– 3 1Department of Medical Chemistry, School of Basic Medical Science, Shanxi Medical University, Taiyuan, Shanxi, 030000, People’s Republic of China; 2Department of Cardiothoracic Surgery, People’s Hospital of Lvliang, Lvliang, Shanxi, 033099, People’s Republic of China; 3Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Taiyuan, Shanxi, 030000, People’s Republic of China; 4State Key Laboratory for Quality Research of Chinese Medicine, Macau University of Science and Technology, Taipa, Macao, People’s Republic of China; 5Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Bian, Department of Medical Chemistry, School of Basic Medical Science, Shanxi Medical University, Taiyuan, Shanxi, 030000, People’s Republic of China, Email weibian@sxmu.edu.cnIntroduction: Lung cancer is the most common cancer worldwide, among which non-small cell lung cancer (NSCLC) accounts for about 80% of all lung cancers. Chemotherapy, a mainstay modality for NSCLC, has demonstrated restricted effectiveness due to the emergence of chemo-resistance and systemic side effects. Studies have indicated that combining chemotherapy with phototherapy, such as photodynamic therapy (PDT) and photothermal therapy (PTT), can enhance efficacy of therapy. In this work, an aminated mesoporous graphene oxide (rPGO)-protoporphyrin IX (PPIX)-hyaluronic acid (HA)@Osimertinib (AZD) nanodrug delivery system (rPPH@AZD) was successfully developed for combined chemotherapy/phototherapy for NSCLC.Methods: A pH/hyaluronidase-responsive nanodrug delivery system (rPPH@AZD) was prepared using mesoporous graphene oxide. Its morphology, elemental composition, surface functional groups, optical properties, in vitro drug release ability, photothermal properties, reactive oxygen species production, cellular uptake and cell viability were evaluated. In addition, the in vivo therapeutic effect, biocompatibility, and imaging capabilities of rPPH@AZD were verified by a tumor-bearing mouse model.Results: Aminated mesoporous graphene oxide (rPGO) plays a role as a drug delivery vehicle owing to its large specific surface area and ease of surface functionalization. rPGO exhibits excellent photothermal conversion properties under laser irradiation, while PPIX acts as a photosensitizer to generate singlet oxygen. AZD acts as a small molecule targeted drug in chemotherapy. In essence, rPPH@AZD shows excellent photothermal and fluorescence imaging effects in tumor-bearing mice. More importantly, in vitro and in vivo results indicate that rPPH@AZD can achieve hyaluronidase/pH dual response as well as combined chemotherapy/PTT/PDT anti-NSCLC treatment.Conclusion: The newly prepared rPPH@AZD can serve as a promising pH/hyaluronidase-responsive nanodrug delivery system that integrates photothermal/fluorescence imaging and chemo/photo combined therapy for efficient therapy against NSCLC. Keywords: NSCLC, mesoporous graphene oxide, combination therapy, hyaluronidase/pH dual-response, nanodrug delivery system

Yuan Li,1 Tong Wu,1 Hongye Li,2 Mingming Liu,2 Haiyan Xu1 1School of Basic Medicine, Xuzhou Medical University, Xuzhou, 221004, People’s Republic of China; 2Lianyungang Clinical School of Xuzhou Medical University, Lianyungang, 222006, People’s Republic of ChinaCorrespondence: Haiyan Xu, School of Basic Medicine, Xuzhou Medical University, Xuzhou, 221004, People’s Republic of China, Email xhy_8@163.comPurpose: Tanshinone IIA (Tan-IIA) is widely used in patients with diabetic nephropathy (DN), but its protective effect on podocytes in DN has not been well studied. In this study, the effects of Tan-IIA on autophagy and inflammation of glomerular podocytes in DN were observed in vivo and in vitro, and the underlying mechanisms were investigated. Irbesartan, an angiotensin II receptor blocker, is a representative medication for the clinical treatment of DN. So irbesartan was chosen as a positive control drug.Methods: Eight-week-old male db/db mice were randomly divided into a DN group, an irbesartan group, and three groups receiving different doses of Tan-IIA. The control group consisted of the db/m littermate mice. Blood, urine, and kidney samples were taken from the mice after 12 weeks of continuous administration. Renal protection of Tan-IIA was evaluated using enzyme-linked immunosorbent assay kits, haematoxylin and eosin staining, transmission electron microscopy, Western blotting, and immunohistochemistry. In vitro, the protective effect of Tan-IIA on podocytes was explored using MPC5 cells cultured with high glucose.Results: Tan-IIA significantly improved renal pathological injury and relieved the renal dysfunction in DN. Compared with the DN group, Tan-IIA could up-regulate the expression of Synaptopodin, Podocin, LC3II/I and Beclin-1 (p < 0.05), and down-regulate the expression of p62, F4/80, NF-κB p65, IL-1β, TNF-α and IL-6 (p < 0.05) both in vivo and in vitro, suggesting that Tan-IIA treatment alleviated podocyte injury by promoting autophagy and inhibiting inflammation during DN. The levels of p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR in Tan-IIA group were lower than those in DN group (p < 0.05), indicating that Tan-IIA inhibited the PI3K/Akt/mTOR signalling pathway in podocytes, which was a key pathway in regulating both autophagy and inflammation.Conclusion: Tan-IIA prevented podocyte injury in DN by fostering autophagy and inhibiting inflammation, at least in part via inhibition of the PI3K/Akt/mTOR signalling pathway.Keywords: tanshinone IIA, podocyte, diabetic nephropathy, autophagy, inflammation, PI3K/Akt/mTOR signalling pathway

Jun Zhang,1 Shengjun Zhang,2 Minli Liu,1 Zhe Yang,1 Rong Huang1 1Department of Medical College of Yan’an University, Yan ‘an, People’s Republic of China; 2Department of General Surgery, Affiliated Hospital of Yan ‘an University, Yan ‘an, People’s Republic of ChinaCorrespondence: Shengjun Zhang; Minli Liu, Email zsj@yau.edu.cn; lml@yau.edu.cnAbstract: In recent years, more and more researches on cell death mode in breast cancer, including apoptosis, ferroptosis, etc. Ferroptosisis a regulated form of cell death characterized by iron-dependent accumulation of lipid peroxidation to lethal levels, and numerous studies have shown that ferroptosis is closely associated with tumor cells. Breast cancer is one of the malignant tumors with the highest incidence in women, and TNBC accounts for about 15– 20% of all types of breast cancer. Due to the poor prognosis, strong aggressiveness, high drug resistance and lack of molecular targeting characteristics of TNBC, the treatment of TNBC faces many difficulties and great challenges. A large number of studies have shown that ferroptosis plays an important role in the occurrence and development of TNBC, tumor diagnosis, treatment and prognosis, among which the main mechanisms inducing ferroptosis include oxidative stress pathway, iron metabolism pathway and lipid metabolism pathway. Since TNBC is highly sensitive to oxidative stress pathways, intracellular GSH reduces reactive oxygen species under the action of GSH peroxidase (GPX), and when intracellular lipid peroxidase (LPO) accumulates to a certain level, ferroptosis will be induced, thus achieving the purpose of killing TNBC cells. In addition, lipid metabolism is highly consistent with the high lipid level of TNBC tumor cells. As a new therapeutic method, nanotechnology has added security to the treatment of cancer with its high safety and excellent biocompatibility. Therefore, the combination of nanotechnology with iron-based radiotherapy, chemotherapy, targeting and immunization has great research value for the treatment of TNBC In addition, the novel idea of treating TNBC with ethnopharmacology combined with ferroptosis is also involved. This article reviews the mechanism of ferroptosis and the recent research on the treatment prospects of TNBC based on ferroptosis and nanotechnology, hoping to provide references for the treatment of diseases based on ferroptosis.Keywords: triple-negative breast cancer, ferroptosis, nanotechnology, treatment

Na Qu,1 Ke Song,2 Yating Ji,1 Mingxia Liu,1 Lijiang Chen,1 Robert J Lee,3,4 Lesheng Teng3,5 1School of Pharmacy, Liaoning University, Shenyang, 110036, People’s Republic of China; 2MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, 6229 ER, the Netherlands; 3School of Life Sciences, Jilin University, Changchun, 130023, People’s Republic of China; 4College of Pharmacy, The Ohio State University, Columbus, OH, 43210, USA; 5State Key Laboratory of Long-Acting and Targeting Drug Delivery System, Yantai, 264000, People’s Republic of ChinaCorrespondence: Lesheng Teng, Email tenglesheng@jlu.edu.cnAbstract: Nanoparticle-based systems are extensively investigated for drug delivery. Among others, with superior biocompatibility and enhanced targeting capacity, albumin appears to be a promising carrier for drug delivery. Albumin nanoparticles are highly favored in many disease therapies, as they have the proper chemical groups for modification, cell-binding sites for cell adhesion, and affinity to protein drugs for nanocomplex generation. Herein, this review summarizes the recent fabrication techniques, modification strategies, and application of albumin nanoparticles. We first discuss various albumin nanoparticle fabrication methods, from both pros and cons. Then, we provide a comprehensive introduction to the modification section, including organic albumin nanoparticles, metal albumin nanoparticles, inorganic albumin nanoparticles, and albumin nanoparticle-based hybrids. We finally bring further perspectives on albumin nanoparticles used for various critical diseases.Plain Language Summary: Albumin appears to be a promising carrier for drug delivery with superior biocompatibility and enhanced targeting capacity. This review focuses on the importance of albumin nanoparticles in drug delivery and concludes the recent fabrication techniques to prepare albumin nanoparticles, the modification strategies to require functional albumin nanoparticles, and critical applications of albumin nanoparticles in various diseases. The aim of this review is to help readers understand the significant potential of albumin nanoparticles in drug delivery. Keywords: albumin nanoparticle, drug delivery, fabrication, modification, application

Zhaoting Wu,1,2 Lihua Tang,1 Yaozhen Lai,1 Muyuan Liu,3 Li Zhou1 1Department of Gynecologic Oncology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, People’s Republic of China; 2Department of Gynecology, the First People’s Hospital of Chenzhou, Chenzhou, Hunan, People’s Republic of China; 3Head and Neck Surgery Department, Cancer Hospital of Shantou University, Medical College, Shantou, Guangdong, People’s Republic of ChinaCorrespondence: Li Zhou, Email zlyyzl@126.com Muyuan Liu, Email muyuan-1981@163.comPurpose: Struma ovarii is a highly specialized teratoma consisting primarily of mature thyroid tissue. However, malignant struma ovarii coexisting with thyroid carcinoma, not to mention autoimmune disease, is uncommon. Malignant struma ovarii complicated with papillary thyroid carcinoma, Hashimoto’s thyroiditis and polycystic ovarian syndrome has never been reported in literature.Patients and Methods: A 32-year-old female was admitted to our hospital due to a history of abdominal distension and menolipsis over the past half a year. Physical examination touched a 6 × 6 cm mass with a clear boundary, normal movement, and no pressing pain in the right adnexal area, Imaging revealed a cystic solid mass of 6 × 7 cm in the right ovary and the level of tumor markers including CA125, CA199, CA153, CEA, AFP were normal, but with low TSH and increased TPOAb, TGAb, TRAb. Laparoscopic right ovary tumor resection was performed, followed by comprehensive staging surgery, as well as thyroidectomy after pathologic diagnosis. The patient was diagnosed with a combination of follicular thyroid cancer from struma ovarii, papillary thyroid carcinoma and Hashimoto’s thyroiditis, along with polycystic ovarian syndrome. Immunohistochemical staining showed positivity for Ag, CK-pan, CK7, PAX8 and TTF-1 in the right ovarian mass, and the left thyroid was positive for the BRAF V600E mutation.Results: The patient underwent thyroxine suppression therapy and radioactive iodine 131I therapy after operation. Serum thyroglobulin was undetectable, and no signs of recurrence or metastasis were detected in the imaging examination at the 2-year follow-up.Conclusion: Malignant struma ovarii coexisting with thyroid carcinoma is rare. No report has been identified in literature review on the rare malignant struma ovarii coexisting with thyroid carcinoma, Hashimoto’s thyroiditis and polycystic ovarian syndrome. Our case can offer experience of diagnosis and treatment to some extent for such rare case. Therefore, it is essential to consider the association between ovarian tumors and the endocrine system. This case is valuable in understanding the diagnosis and management of such an unusual complicated disease.Keywords: struma ovarii, follicular thyroid carcinoma, case report, gynaecological tumor

Zhou Zhu,1– 3,&ast; Huizi Gong,4,&ast; Mingjuan Liu,1– 3 Hanlin Zhang,1,2 Leyan Yang,1,2 Xinyi Zhang,5 Heyi Zheng,1,2 Yanfeng Li,6 Mingli Li,7 Jun Li1,2 1Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 3 4+4 Medical Doctor Program, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 4Department of Dermatology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 5Departments of Internal Medicine and Cellular & Molecular Physiology, Yale School of Medicine, New Haven, CT, USA; 6Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 7Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingli Li, Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, People’s Republic of China, Email limingli@pumch.cn Jun Li, Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, People’s Republic of China, Email lijun35@hotmail.comBackground: Tabes dorsalis is a late manifestation of neurosyphilis, characterized by progressive ataxia, lightning pains, loss of proprioception, and urinary incontinence. The absence of a definitive diagnostic standard and the non-specific clinical manifestations have led to a significant rate of misdiagnoses.Methods: Hospitalized patients with tabes dorsalis at Peking Union Medical College Hospital between January 2010 and December 2023 were reviewed.Results: A total of 13 patients were included, with 10 males and 3 females. The median age was 50 years (range, 34– 64). The most frequent initial symptoms were limb numbness (30.8%) and lightning pains (30.8%). Eleven patients (84.6%) received misdiagnoses prior to the final diagnosis. The most frequently observed physical sign was positive Romberg’s sign (84.6%). Notably, Argyll Robertson pupil was presented in 7 subjects (53.8%). Serological tests revealed positive rapid plasma regain (RPR) and Treponema pallidum particle agglutination (TPPA) for all patients. All CSF samples were TPPA-reactive. Intramedullary hyperintensity on T2-weighted imaging of spinal MRI was found in 5 patients (38.5%). All patients received anti-syphilitic treatment, with effective treatment recorded in five cases.Conclusion: This study underscores the importance of neurological symptoms and signs in diagnosing tabes dorsalis. Individuals with progressive ataxia and positive Romberg’s sign should be closely monitored for potential neurosyphilis. Integrating clinical features, laboratory tests, and neuroimaging could reduce misdiagnosis and expedite the initiation of anti-syphilitic therapy.Keywords: tabes dorsalis, neurosyphilis, ataxia, cerebrospinal fluid

Boyu Li,1,&ast; Meishan Liu,2,&ast; Ying Wang,2 Hong Zhang,2 Lingling Xuan,1 Kewu Huang,2 Zhuoling An1 1Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kewu Huang; Zhuoling An, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongtinan Road, Beijing, People’s Republic of China, Tel/Fax +86 010 85231167 ; Tel/Fax +86 010 85231362, Email kewuhuang@126.com; anzhuoling@163.comPurpose: Vitamin D deficiency (VDD, 25-hydroxyvitamin D < 20 ng/mL) has been reported associated with exacerbation of chronic obstructive pulmonary disease (COPD) but sometimes controversial. Research on severe vitamin D deficiency (SVDD, 25-hydroxyvitamin D < 10 ng/mL) in exacerbation of COPD is limited.Patients and Methods: We performed a retrospective observational study in 134 hospitalized exacerbated COPD patients. 25-hydroxyvitamin D was modeled as a continuous or dichotomized (cutoff value: 10 or 20 ng/mL) variable to evaluate the association of SVDD with hospitalization in the previous year. Receiver operator characteristic (ROC) analysis was performed to find the optimal cut-off value of 25-hydroxyvitamin D.Results: In total 23% of the patients had SVDD. SVDD was more prevalent in women, and SVDD group tended to have lower blood eosinophils counts. 25-hydroxyvitamin D level was significantly lower in patients who were hospitalized in the previous year (13.6 vs 16.7 ng/mL, P = 0.044), and the prevalence of SVDD was higher (38.0% vs 14.3%, P = 0.002). SVDD was independently associated with hospitalization in the previous year [odds ratio (OR) 4.34, 95% CI 1.61– 11.72, P = 0.004] in hospitalized exacerbated COPD patients, whereas continuous 25-hydroxyvitamin D and VDD were not (P = 0.1, P = 0.9, separately). The ROC curve yielded an area under the curve of 0.60 (95% CI 0.50– 0.71) with an optimal 25-hydroxyvitamin D cutoff of 10.4 ng/mL.Conclusion: SVDD probably showed a more stable association with hospitalization in the previous year in hospitalized exacerbated COPD patients. Reasons for lower eosinophil counts in SVDD group needed further exploration.Keywords: association, vitamin D, severe deficiency, hospitalization for exacerbation, COPD

Keke Li,1,&ast; Yaozhou Wu,1,2,&ast; Meng Liu,1 Junwen Yan,1 Lianhua Wei1 1Department of Clinical Laboratory, Gansu Provincial Hospital, Lanzhou, 730000, People’s Republic of China; 2First School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lianhua Wei; Junwen Yan, Department of Clinical Laboratory, Gansu Provincial Hospital, No. 204 Donggang West Road, Chengguan District, Lanzhou, 730000, People’s Republic of China, Email 3752131518@qq.com; 249380017@qq.comPurpose: Accurate detection and identification of pathogens and their associated resistance mechanisms are essential prerequisites for implementing precision medicine in the management of Carbapenem-resistant Enterobacterales (CRE). Among the various resistance mechanisms, the production of KPC carbapenemase is the most prevalent worldwide. Consequently, this study aims to develop a convenient and precise nucleic acid detection platform specifically for the blaKPC gene.Methods: The initial phase of our research methodology involved developing a CRISPR/Cas12a detection framework, which was achieved by designing highly specific single-guide RNAs (sgRNAs) targeting the blaKPC gene. To enhance the sensitivity of this system, we incorporated three distinct amplification techniques—polymerase chain reaction (PCR), loop-mediated isothermal amplification (LAMP), and recombinase polymerase amplification (RPA)—into the CRISPR/Cas12a framework. Subsequently, we conducted a comparative analysis of the sensitivity and specificity of these three amplification methods when used in combination with the CRISPR/Cas12a system. Additionally, we assessed the clinical applicability of the methodologies by evaluating fluorescence readouts from 80 different clinical isolates. Furthermore, we employed lateral flow assay technology to provide a visual representation of the results, facilitating point-of-care testing.Results: Following a comparative analysis of the sensitivity and specificity of the three methods, we identified the RPA-Cas12a approach as the optimal detection technique. Our findings demonstrated that the limit of detection (LoD) of the RPA-Cas12a platform was 1 aM (~1 copy/μL) for plasmid DNA and 5 × 10³ fg/μL for genomic DNA. Furthermore, both the sensitivity and specificity of the platform achieved 100% upon validation with 80 clinical isolates.Conclusion: These findings suggest that the developed RPA-Cas12a platform represents a promising tool for the cost-effective, convenient, and accurate detection of the blaKPC gene.Keywords: Klebsiella pneumoniae carbapenemase, CRISPR-Cas12a, isothermal amplification, polymerase chain reaction, loop-mediated isothermal amplification, recombinase polymerase amplification, lateral flow strips

Min Liu,1,2 Bo Liu,2 Ziyang Liu,3 Zhen Yang,2 Thomas J Webster,4 Huan Zhou,2 Lei Yang2 1School of Materials Science and Engineering, Hebei University of Technology, Tianjin, People’s Republic of China; 2Center for Health Science and Engineering, Hebei Key Laboratory of Biomaterials and Smart Theranostics, School of Health Sciences and Biomedical Engineering, Hebei University of Technology, Tianjin, 300131, People’s Republic of China; 3Department of Orthopedics, Tianjin Hospital, Tianjin, People’s Republic of China; 4School of Engineering, Saveetha University, Chennai, IndiaCorrespondence: Huan Zhou; Lei Yang, Center for Health Science and Engineering, School of Health Sciences and Biomedical Engineering, Hebei University of Technology, Tianjin, 300131, People’s Republic of China, Email zhouhuan@hebut.edu.cn; ylei@hebut.edu.cnIntroduction: Lumbar interbody fusion is widely employed for both acute and chronic spinal diseases interventions. However, large incision created during interbody cage implantation may adversely impair spinal tissue and influence postoperative recovery. The aim of this study was to design a shape memory interbody fusion device suitable for small incision implantation.Methods: In this study, we designed and fabricated an intervertebral fusion cage that utilizes near-infrared (NIR) light-responsive shape memory characteristics. This cage was composed of bisphenol A diglycidyl ether, polyether amine D-230, decylamine and iron oxide nanoparticles. A self-hardening calcium phosphate-starch cement (CSC) was injected internally through the injection channel of the cage for healing outcome improvement.Results: The size of the interbody cage is reduced from 22 mm to 8.8 mm to minimize the incision size. Subsequent NIR light irradiation prompted a swift recovery of the cage shape within 5 min at the lesion site. The biocompatibility of the shape memory composite was validated through in vitro MC3T3-E1 cell (osteoblast-like cells) adhesion and proliferation assays and subcutaneous implantation experiments in rats. CSC was injected into the cage, and the relevant results revealed that CSC is uniformly dispersed within the internal space, along with the cage compressive strength increasing from 12 to 20 MPa.Conclusion: The results from this study thus demonstrated that this integrated approach of using a minimally invasive NIR shape memory spinal fusion cage with CSC has potential for lumbar interbody fusion.Keywords: shape memory, interbody fusion cage, NIR responsive, calcium phosphate cement, minimally invasive

Kaiyang Xue,1 Xianzhu Wang,1 Caihong Xiao,2 Ning Zhang,1 Minghui Liu,3 Jing Fu,1 Jin Cui1 1College of Acupuncture and Massage, Guizhou University of Traditional Chinese Medicine, Guiyang, 550002, People’s Republic of China; 2Department of Acupuncture and Moxibustion, No.1 Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, 550001, People’s Republic of China; 3Department of Acupuncture and Moxibustion, No.2 Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, 550001, People’s Republic of ChinaCorrespondence: Jin Cui, College of Acupuncture and Massage, Guizhou University of Traditional Chinese Medicine, No. 50 Shidong Road, Nanming District, Guiyang, 550002, People’s Republic of China, Email 516260179@qq.comObjective: Our pilot study shows that a modified moxibustion therapy called Ma’s bamboo-based medicinal moxibustion can alleviate the symptoms of low back pain in lumbar disc herniation (LDH), and has the potential to treat LDH. The aim of this study is to evaluate the efficacy and safety of Ma’s bamboo-based medicinal moxibustion for low back pain in LDH.Methods: A total of 312 LDH patients with low back pain were randomized to receive Ma’s bamboo-based medicinal moxibustion (MBMM) or acupuncture (AT). The primary efficacy measure was the change of Visual Analogue Scale (VAS) on the 14th day compared with that at baseline. The secondary efficacy measures included VAS score, Oswestry disability index (ODI), modified Japanese Orthopaedic Association (M-JOA) score, and the content of β-endorphin (β-EP) and substance-P (SP). The safety measures included the occurrence of adverse events and the changes in laboratory indicators.Results: In total, 304 patients were incorporated for the analysis of efficacy, including 96 males and 208 females, aged 21– 65 years. There was no statistically significant difference in the change of VAS score between the two groups on the 14th day [mean difference (95% CI) = − 2.31 (− 2.48, − 2.13) and − 2.28 (− 2.45, − 2.11), respectively; p = 0.819]. The VAS, ODI, and M-JOA scores changed after the intervention in both groups (p < 0.001), with increased β-EP content (p = 0.014, p = 0.032) and decreased SP content (p < 0.001, p = 0.048). The ODI score (p = 0.039) and M-JOA score (p = 0.032) of the MBMM group on the 28th day were lower than those of the AT group.Conclusion: The efficacy of Ma’s bamboo-based medicinal moxibustion therapy in relieving low back pain of LDH patients is comparable to that of acupuncture, and it has post-effect advantages in improving lumbar dysfunction and daily living ability, which can be used as a safe and effective alternative method for LDH treatment.Keywords: LDH, low back pain, Ma’s bamboo-based medicinal moxibustion, acupuncture, randomized controlled trial

Qian Zhang,1 Xiaomei Wang,1 Mingzhe Liu,1 Bin Li,1 Kun Zhang,1 Yaqi Han,1 Jiali Li,2 Yan Xin,3 Yan Huo,1 Zhenjie Hu1 1Department of Intensive Care Unit, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050000, People’s Republic of China; 2Department of Intensive Care Unit, The Sixth People’s Hospital of Hengshui, Hengshui, Hebei Province, 053000, People’s Republic of China; 3Department of Intensive Care Unit, The Third Hospital of Shijiazhuang, Shijiazhuang, Hebei Province, 050000, People’s Republic of ChinaCorrespondence: Yan Huo; Zhenjie Hu, Department of Intensive Care Unit, The Fourth Hospital of Hebei Medical University, No. 12 of Jiankang Road, Changan District, Shijiazhuang, 050011, People’s Republic of China, Tel +86 311 86095367, Email huoyan523@hebmu.edu.cn; 46400533.hebmu.edu.cnObjective: The aim of this study is to examine the diagnostic significance of using handgrip dynamometry and diaphragmatic ultrasound in intensive care unit-acquired weakness (ICU-AW).Methods: This study included patients who received mechanical ventilation in the ICU at the Fourth Hospital of Hebei Medical University from July to December 2020. We collected comprehensive demographic data and selected conscious patients for muscle strength and ICU-AW assessments. The evaluation comprised grip strength measurement and bedside ultrasound for diaphragmatic excursion (DE) and thickening fraction (DTF). Results were documented for comparative analysis between patient groups, focusing on the diagnostic efficacy of grip strength, DE, DTF, and their combined application in diagnosing ICU-AW.Results: A total of 95 patients were initially considered for inclusion in this study. Following the exclusion of 20 patients, a final cohort of 75 patients were enrolled, comprising of 32 patients (42.6%) diagnosed with ICU-AW and 43 patients (57.4%) classified as non-ICU-AW. Comparative analysis revealed that grip strength, DE, and DTF were significantly lower in the ICU-AW group (P < 0.05). Subgroup analysis specific to male patients demonstrated a noteworthy decrease in grip strength, DE, and DTF within the ICU-AW group (P < 0.05). Receiver operating characteristic curve analysis indicated statistically significant diagnostic value for ICU-AW with grip strength, DE, DTF, and grip strength and diaphragmatic ultrasound (P < 0.01). Furthermore, it was observed that the amalgamation of grip strength and diaphragmatic ultrasound significantly enhanced the diagnostic accuracy of ICU-AW in patients who are critically ill.Conclusion: Grip strength, DE, DTF, and the combined use of grip strength with diaphragm ultrasound demonstrated diagnostic efficacy in ICU-AW. Notably, the integration of grip strength with diaphragm ultrasound exhibited a heightened capacity to enhance the diagnostic value specifically in patients diagnosed who are critically ill with ICU-AW.Keywords: diaphragmatic excursion, diaphragm thickening fraction, handgrip dynamometer, ICU acquired weakness

Yongxiong Huang,1,2,&ast; Xianshuai Qiu,3,&ast; Jinlian Liu,4 Jiangtao Wan,5 Cheng Yu,1 Chun Liu,1 Yang Duan,1 Chong Chen,2 Jingxing Dai,6 Jun Ouyang,6 Ming Liu,3 Shaoxiong Min,1,5 Sujun Qiu1 1Department of Spine Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, People’s Republic of China; 2Department of Spine Surgery, Guangdong Provincial People’s Hospital, Southern Medical University, Guangzhou, 510000, People’s Republic of China; 3Department of Orthopedics and Sports Medicine Center, Heyou Hospital, Foshan, 528333, People’s Republic of China; 4Department of Pathophysiology, Guangdong Provincial Key Laboratory of Shock and Microcirculation, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 5Shenzhen Key Laboratory of Spine Surgery, Department of Spine Surgery, Peking University Shenzhen Hospital, Shenzhen, 518036, People’s Republic of China; 6Guangdong Provincial Key Laboratory of Medical Biomechanics & National Key Discipline of Human Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Sujun Qiu, Department of Spine Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, People’s Republic of China, Email qiusjspine@126.com Shaoxiong Min, Shenzhen Key Laboratory of Spine Surgery, Department of Spine Surgery, Peking University Shenzhen Hospital, Shenzhen, 518036, People’s Republic of China, Email msxbear24@163.comBackground: Intervertebral disc degeneration (IDD) is the leading cause of low back pain (LBP). The mechanism of IDD development and progression is not fully understood. Peripheral biomarkers are increasingly vital non-radioactive methods in early detection and diagnosis for IDD. Nevertheless, less attention has been paid to the role of mitophagy genes in the progress of IDD. This study aimed to identify the mitophagy disease-causing genes in the process of IDD and mitophagy diagnostic biomarkers for IDD.Methods: Mitophagy-related differentially expressed genes (MRDEGs) related to IDD were investigated by analyzing the microarray datasets of IDD cases from GEO, PathCards and Molecular Signatures Databases. We used R software, WGCNA, PPI, mRNA-miRNA, mRNA-TF, GO, KEGG, GSEA, GSVA and Cytoscape to analyze and visualize the data. We further used ssGSEA for immunoinfiltration analysis to obtain different immune cell infiltration. LASSO model was developed to screen for genes that met the diagnostic gene model requirements. Finally, qRT-PCR, Western blotting and HE were used to verify hub genes and their expression from clinical IDD samples.Results: We identified 14 MRDEGs and 12 hub genes. GO, KEGG, GSEA and GSVA analyses demonstrated that hub genes were critical for the development of IDD. LASSO diagnostic model consisted of six hub genes, among which SQSTM1, ATG7 and OPTN were significantly different between the two IDD disease subtypes. At the same time, SQSTM1 also had a high correlation with immune characteristic subtypes. The results of qRT-PCR and Western blotting also indicated that these genes were significantly differentially expressed in nucleus pulposus cells (NPCs) of the IDD group.Conclusion: We explored an association between MRDEGs-associated signature in IDD and validated that hub genes like SQSTM1 might serve as biomarkers for diagnostic and therapeutic targets for IDD. Meanwhile, this study can provide new insights into the functional characteristics and mechanism of mitophagy in the development of IDD. Keywords: intervertebral disc degeneration, mitophagy-related differentially expressed genes, immune infiltration, diagnostic model, SQSTM1, nucleus pulposus cells

Yueda Jihu,1,2,&ast; Ruobing Leng,1,&ast; Mengchang Liu,1,2 Hongjing Ren,1,2 Defu Xie,1,2 Chong Yao,1,2 Hong Yan1,2 1Clinical College of Medicine, Southwest Medical University, Lu zhou, People’s Republic of China; 2Department of Plastic and Burn Surgery, the Affiliated Hospital of Southwest Medical University, Lu zhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Yan, Email zxsswk@163.comIntroduction: Angiotensin (1– 7) (Ang-(1-7)) is an emerging component of the renin-angiotensin system (RAS) with effective anti-fibrosis properties and has been shown to interfere with epithelial-mesenchymal transition (EMT) by numerous studies. In recent years, EMT has been proposed as a new therapeutic target for skin fibrotic diseases such as keloids. However, the effect of Ang-(1-7) on EMT in skin is still unclear. Hence, the purpose of this study was to explore the effect of Ang-(1-7) on Transforming growth factor-β 1(TGF-β 1)–induced EMT of human immortalized keratinocytes HaCaT in vitro.Methods: The study involved the use of the human immortalized keratinocyte cell line (HaCaT). The cells were cultured in high-glucose DMEM medium with 10% fetal bovine serum and 1% penicillin-streptomycin. Four groups were created for experimentation: control group (Group C), TGF-β 1-treated group (Group T), Ang-(1-7)-treated group (Group A), and a group treated with both TGF-β 1 and Ang-(1-7) (Group A + T). Various assays were conducted, including a cell proliferation assay using CCK-8 solution, a scratch wound healing assay to evaluate cell migration, and Western blotting to detect protein expressions related to cell characteristics. Additionally, quantitative real-time polymerase chain reaction (PCR) was performed to analyze epithelial-mesenchymal transition (EMT) related gene expression levels. The study aimed to investigate the effects of TGF-β 1 and Ang-(1-7) on HaCaT cells.Results: We found that Ang-(1-7) not only reduced the migration of HaCaT cells induced by TGF-β 1 in vitro but also reduced the expression of α-SMA and vimentin, and restored the protein expression of E-cadherin and claudin-1. Mechanistically, Ang-(1-7) inhibits the phosphorylation levels of Smad2 and Smad3 in the TGF-β 1 canonical pathway, and suppresses the expression of EMT-related transcription factors (EMT-TFs) such as SNAI2, TWIST1, and ZEB1.Discussion: Taken together, our findings suggest that Ang-(1-7) inhibits TGF-β 1–induced EMT in HaCaT cells in vitro by disrupting the TGF-β 1-Smad canonical signaling pathway. These results may be helpful in the treatment of EMT in skin fibrotic diseases such as keloids.Keywords: angiotensin (1-7), epithelial-mesenchymal transition, transforming growth factor-β, keratinocytes

Yan Ma,1,2,&ast; Qian Cui,3,&ast; Wenjing Zhu,1,4,&ast; Mei Wang,1,2 Li Zhai,5 Wenmin Hu,1,2 Dongdong Liu,6 Min Liu,5 Yongchun Li,2 Meng Li,2 Wei Han1,2 1Qingdao Key Laboratory of Common Diseases, Qingdao Municipal Hospital, School of Medicine and Pharmacy, Ocean University of China, Qingdao, Shandong, 260071, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Qingdao Municipal Hospital, University of Health and Rehabilitation Sciences, Qingdao, 266071, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Shenzhen Luohu People’s Hospital, Shenzhen, 518000, People’s Republic of China; 4NMPA Key Laboratory for Quality Research and Evaluation of Traditional Marine Chinese Medicine, Qingdao, 266071, People’s Republic of China; 5Department of Pharmacy, Qingdao Municipal Hospital, University of Health and Rehabilitation Sciences, Qingdao, 266071, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Shanting District People’s Hospital, Zaozhuang, 277200, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Han; Meng Li, Department of Respiratory and Critical Care Medicine, Qingdao Municipal Hospital, University of Health and Rehabilitation Sciences, Qingdao, 266071, People’s Republic of China, Email hanw@uor.edu.cn; cqdpd@126.comPurpose: Lung adenocarcinoma currently ranks the leading causes of cancer-related mortality worldwide. Many anti-inflammation herbs, like tetramethylpyrazine, have shown their anti-tumor potentials. Here, we evaluated the role of a novel chalcone derivative of tetramethylpyrazine ((E) -1- (E) -1- (2-hydroxy-5-chlorophenyl) -3- (3,5,6-trimethylpyrazin-2-yl) -2-propen-1, HCTMPPK) in lung adenocarcinoma.Methods: The effects of HCTMPPK on cell proliferation, apoptosis, and invasion were investigated by in-vitro assays, including CCK-8, colony formation assay, flow cytometry, transwell assay, and wound-healing assay. The therapeutic potential of HCTMPPK in vivo was evaluated in xenograft mice. To figure out the target molecules of HCTMPPK, a network pharmacology approach and molecular docking studies were employed, and subsequent experiments were conducted to confirm these candidate molecules.Results: HCTMPPK effectively suppressed the proliferative activity and migration, as well as enhanced the apoptosis of A549 cells in a concentration-dependent manner. Consistent with this, tumor growth was inhibited by HCTMPPK significantly in vivo. Regarding the mechanisms, HCTMPPK down-regulated Bcl-2 and MMP-9 and up-regulating Bax and cleaved-caspase-3. Subsequently, we identified 601 overlapping DEGs from LUAD patients in TCGA and GEO database. Then, 15 hub genes were identified by PPI network and CytoHubba. Finally, MELK was verified to be the HCTMPPK targeted site, through the molecular docking studies and validation experiments.Conclusion: Overall, our study indicates HCTMPPK as a potential MELK inhibitor and may be a promising candidate for the therapy of lung cancer.Keywords: HCTMPPK((E) -1- (E) -1- (2-hydroxy-5-chlorophenyl) -3- (3,5,6-trimethylpyrazin-2-yl) -2-propen-1), chalcone, TMP, lung adenocarcinoma, network pharmacology, AutoDock

Menglin Liu,1 Mingyang Gao,1 Yufei Hu,1 Xiaoqin Ren,1 Yanan Li,1 Fang Gao,1 Jianglong Dong,1 Jiangtao Dong,2 Qiujun Wang1 1Department of Anesthesiology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, People’s Republic of China; 2Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, People’s Republic of ChinaCorrespondence: Qiujun Wang, Third Hospital of Hebei Medical University, No. 139, Ziqiang Road, Shijiazhuang City, Hebei, People’s Republic of China, Tel/Fax +86-311-8860-2072, Email wangqiujunsy@163.comPurpose: Patients undergoing arthroscopic hip surgery (AHS) require good analgesia and early rehabilitation after surgery, and there is no consensus on the optimal nerve block. We aimed to compare the efficacy of the pericapsular nerve group (PENG) block with lateral femoral cutaneous nerve (LFCN) block compared to fascia iliaca compartment block (FICB) in patients with AHS.Patients and Methods: A total of 80 patients receiving AHS under general anesthesia were randomized to receive either FICB (group F) or PENG block in combination with LFCN block (group P). The primary outcomes were the rate of quadriceps weakness after block on the afflicted side, as well as muscle strength grading and pain score after block, and the quality of recovery on the second postoperative day.Results: Compared with group F, group P had a lower incidence of quadriceps weakness 48 h after block (76.9% vs 28.2%, P < 0.001), and had less impact on muscle strength grade and lower static pain score at 6, 12, 18, 24, 36, and 48 h after block (P < 0.001), and a lower dynamic pain score at 6 and 12 h after block in group P (p < 0.05). The quality of recovery on the second postoperative day improved (p < 0.05).Conclusion: In comparison to FICB, PENG block in combination with LFCN block can affect less quadriceps muscle strength and reduce the use of postoperative analgesics, which is beneficial for the postoperative recovery of AHS patients.Keywords: analgesia, fascia iliaca compartment block, hip arthroscopy, nerve group block, pericapsular, postoperative pain

Juan-Min Zha,1,&ast; Mei Zhang,1,&ast; Tao Wang,2,&ast; Hua-Shan Li,1,2,&ast; Quan-Yao Ban,1,&ast; Mei Liu,1 Xue-Xue Jiang,1 Shi-Ying Guo,2 Jing Wang,2 Ya-Ru Zhou,2 Yu-Hong Liu,2 Wei-Qi He,1,2 Hong Xu1 1Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, People’s Republic of China; 2Jiangsu Key Laboratory of Neuropsychiatric Diseases and Cambridge-Suda (CAM-SU) Genomic Resource Center, Medical College of Soochow University, Suzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei-Qi He; Hong Xu, Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, People’s Republic of China, Tel +86-512-6588-3545, Email whe@suda.edu.cn; hongxusuda@outlook.comObjective: This cross-sectional study aimed to explore the association of overweight and inflammatory indicators with breast cancer risk in Chinese patients.Methods: Weight, height, and peripheral blood inflammatory indicators, including white blood cell count (WBC), neutrophil count (NE), lymphocyte count (LY), platelet count (PLT) and the concentration of hypersensitivity C-reactive protein (hsCRP), were collected in 383 patients with benign breast lumps (non-cancer) and 358 patients with malignant breast tumors (cancer) at the First Affiliated Hospital of Soochow University, China, from March 2018 to July 2020. Body mass index (BMI), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) were determined according to the ratio equation. The correlations among overweight, inflammatory indicators, and the proportion of non-cancer or cancer cases were analyzed.Results: BMI is associated with an increased breast cancer risk. Compared with non-cancer patients, the average WBC count, NE count, NLR, and level of hsCRP were significantly higher in cancer patients. The level of hsCRP was closely associated with the size of malignant breast tumors.Conclusion: We conclude that overweight and high levels of hsCRP may serve as putative risk factors for malignant breast tumors in Chinese women.Keywords: breast cancer, body mass index, overweight, chronic inflammation, inflammatory indicator

Lina Chang,&ast; Xiaohui Ma,&ast; Menghua Yuan,&ast; Li Ding, Yian Gu, Lili Liu, Yan Li, Hua Shu, Ming Liu, Qing He Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qing He; Ming Liu, Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, 300052, People’s Republic of China, Email heqing202301@tmu.edu.cn; mingliu@tmu.edu.cnPurpose: Understanding factors that influence blood glucose levels in patients with type 2 diabetes mellitus (T2DM) is crucial for managing hyperglycemia. Currently, there is no standardized interpretation method for glucagon levels in oral glucose tolerance test (OGTT). This study aims to assess the relationship between the lowest glucagon/highest C-peptide ratio (Lglc/Hcp) in OGTT and glucose control levels in T2DM.Patients and Methods: Clinical data from 120 patients with T2DM were examined to compare the correlations of Lglc/Hcp and other pancreatic islet function-associated indices with fasting blood glucose (G0), glucose at 120 minutes in OGTT (G120), hemoglobin A1c (HbA1c), and the area under the glucose curve in OGTT (AUCglu). Additionally, the study investigated difference in Lglc/Hcp between patient groups based on the highest blood glucose levels (Hglu) in OGTT (Hglu ≥ 16.7 mmol/L vs Hglu < 16.7 mmol/L).Results: The generalized linear model suggested that Lglc/Hcp significantly correlated with G0 (B = 0.85, P < 0.001), G120(B = 1.46, P < 0.001), HbA1c (B = 0.67, P < 0.001), and AUCglu (B = 3.46, P < 0.001). This correlation surpassed C-peptide and glucagon-related parameters, even after adjusting for confounding factors. Furthermore, Lglc/Hcp was notably higher in patients with Hglu ≥ 16.7 mmol/L compared to those with Hglu < 16.7 mmol/L (Z = − 3.71, p < 0.001).Conclusion: Lglc/Hcp in OGTT closely relates to blood glucose control in patients with T2DM, potentially reflecting the overall pancreatic islet function in regulating glucose levels. Moreover, inhibiting glucagon secretion may be a crucial consideration for patients requiring insulin treatment. Keywords: C-peptide, glucose control, glucagon, type 2 diabetes mellitus

Han Wu,1,&ast; Hui Wang,2,&ast; Lixia Sun,3,&ast; Mengchen Liu,1 Haoran Wang,1 Xianchang Sun,4 Wenjuan Zhang1 1Center for Reproductive Medicine, The Second Affiliated Hospital of Shandong First Medical University, Taian, 271000, People’s Republic of China; 2Gynecological Minimally Invasive Surgery Center, The Affiliated Taian City Central Hospital of Qingdao University, Taian, 271000, People’s Republic of China; 3Department of Hematology, The Affiliated Taian City Central Hospital of Qingdao University, Taian, 271000, People’s Republic of China; 4Department of Physiology, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenjuan Zhang, Center for Reproductive Medicine, The Second Affiliated Hospital of Shandong First Medical University, 366 Taishan Street, Taian, 271000, People’s Republic of China, Email wenjuanzhang1119@163.com Xianchang Sun, Department of Physiology, Shandong First Medical University & Shandong Academy of Medical Sciences, 6699 Qingdao Road, Jinan, 250117, People’s Republic of China, Email hotsss@163.comPurpose: To study the relationship between the single nucleotide polymorphism (SNP) rs2278426 in the angiopoietin-like protein 8 gene (ANGPTL8) and polycystic ovary syndrome (PCOS).Patients and methods: A total of 122 patients with PCOS and 108 controls were recruited for comparison of glucose, lipid, insulin, sex hormone, and ANGPTL8 levels. Polymerase chain reaction (PCR) and gene sequencing were performed for comparison of the frequency of the CC, CT, and TT rs2278426 genotypes and the rs2278426 allele distributions between the PCOS and control groups and between the obese and non-obese subgroups of the PCOS and control groups.Results: The frequency of the T allele was significantly higher in the PCOS group than that in the controls (P = 0.037). In the dominant genetic model, the proportion of the CT+TT genotype in the PCOS group was significantly higher than that in the controls (P = 0.047). Subgroup analysis demonstrated that the T allele proportion was significantly higher in obese PCOS group than obese control group (P = 0.027). PCOS with the CT+TT genotype had significantly higher body mass index (BMI; P = 0.001), triglyceride (TG; P = 0.005), homeostasis model assessment of insulin resistance (HOMA-IR; P = 0.035), testosterone (P = 0.041), and ANGPTL8 (P = 0.037) levels and significantly lower high-density lipoprotein (HDL) levels (P = 0.025) than PCOS with the CC genotype. Obese PCOS group with the CT+TT genotype had significantly higher TG (P = 0.015), luteinizing hormone (LH; P = 0.030), fasting insulin (FINS; P = 0.039), HOMA-IR (P = 0.018), and ANGPTL8 (P = 0.049) levels than obese PCOS group with the CC genotype.Conclusion: Polymorphisms of rs2278426 may induce glycolipid metabolic disorders by affecting ANGPTL8 levels and functions in Han Chinese females with obesity from the Shandong region, increasing the risk of PCOS in this population.Keywords: angiopoietin-like protein 8, insulin resistance, metabolic disorder, obesity, polycystic ovary syndrome, single nucleotide polymorphism

Jing Zhang,1,2 Ke Ma,3 Jun Yan,4 Pingsheng Pan,5 Jiangshan Yin,6 Fuqing Lin,7 Hui Chen,8 Weiwei Zhao,1,2 Menglei Chen,1,2 Zhe Zhang,1,2 Minghui Liu,1,2 Xiaoli Gu,1,2 Xinghe Liao,1,2 Chenyue Zhang,1,2 Wenwu Cheng1,2 1Department of Integrated Therapy, Shanghai Cancer Center, Fudan University, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 3Department of Pain Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Oncology, Jiading District Central Hospital Affiliated Shanghai University of Medicine and Health Sciences, Shanghai, People’s Republic of China; 5Department of Oncology, Fangta Hospital of Traditional Chinese Medicine in Songjiang District, Shanghai, People’s Republic of China; 6Department of Oncology, Fudan University Shanghai Cancer Center, Minhang Branch, Shanghai, People’s Republic of China; 7Department of Anaesthesiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 8Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People’s Hospital Affiliated to Tongji University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Wenwu Cheng, Email cwwxxm@sina.comPurpose: This study aimed to assess the current status of clinical practice of refractory cancer pain (RCP) among a sample of physicians specializing in cancer pain management in Shanghai.Methods: From 2019 to 2021, a questionnaire survey was conducted among physicians engaged in diagnosis and treatment of cancer pain through the questionnaire WJX network platform in Shanghai, China.Results: A total of 238 responses participated in the survey. This survey reports physicians’ understanding and incidence rate of breakthrough cancer pain (BTCP). The choice of analgesics and satisfaction of analgesic effect were investigated. We also investigated doctors’ knowledge of the diagnostic criteria for RCP and their tendency to choose analgesics. Oral immediate-release morphine and intravenous or subcutaneous morphine injection have been the common treatment approach for transient cancer pain exacerbations. The main barriers to pain management are lack of standardized treatment methods for RCP, lack of knowledge related to RCP, and single drug dosage form. Doctors believe the most necessary measures to improve the current situation of poor cancer pain control include improving medical staff’s understanding and treatment techniques for RCP, updating treatment techniques and methods, and improving the configuration of drug types in medical institutions. Clinicians expect to improve understanding and treatment techniques through systematic training.Conclusion: Despite multiple available analgesic measures, the treatment of RCP remains challenging. Improving the understanding of medical staff towards RCP, improving treatment techniques, and increasing the accessibility of multiple drug types are important ways to improve the satisfaction of cancer pain management in the future.Keywords: refractory cancer pain, breakthrough cancer pain, pain management, opioid drugs

Meihua He,1– 5,&ast; Mingqiang Liu,1– 5,&ast; Xiaohua Tao1– 5,&ast; 1Dermatology Hospital of Jiangxi Province, Nanchang, Jiangxi, People’s Republic of China; 2Jiangxi Provincial Clinical Research Center For Skin Diseases, Nanchang, Jiangxi, People’s Republic of China; 3Candidate Branch of National Clinical Research Center for Skin Diseases, Nanchang, Jiangxi, People’s Republic of China; 4Dermatology Institute of Jiangxi Province, Nanchang, Jiangxi, People’s Republic of China; 5The Affiliated Dermatology Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaohua Tao, Department of Dermatology, Dermatology Hospital of Jiangxi Province, Nanchang, Jiangxi, 330001, People’s Republic of China, Tel +86 15979086756, Fax +86-0791-85207512, Email taoxiaohua@126.comPurpose: Verruciform xanthoma (VX) is a rare, chronic, and benign lesion affecting the skin and mucous membranes. We reported a case of VX in the vulva of a female child.Patients and Methods: A 12-year-old female had vulvar lesions for over 10 years without any discomfort. Physical examination revealed red lobulated patches on the left labia majora with a few scales attached to the surface. Histopathological examination indicated excessive and incomplete keratinization, hypertrophic spinous layer hyperplasia, neutrophil infiltration in the epidermis, and foam-like tissue could be seen in the dermal papilla. Lymphocyte-dominated inflammatory cell infiltration was scattered around the blood vessels. Immunohistochemical results showed positive CD68.Results: The final diagnosis confirmed the presence of VX.Conclusion: Surgical intervention proved successful in achieving favorable outcomes for the patient.Plain Language Summary: Verruciform xanthoma (VX) is a rare and non-cancerous skin condition that usually appears in the mouth but can occur on the genitals. In this case, a 12-year-old girl had red, warty lesions on her left labia majora for over 10 years. The cause of VX is not well understood but may be linked to inflammation, trauma, or immune disorders rather than lipid metabolism. The girl’s condition was confirmed through a biopsy, and she underwent surgical removal with no recurrence after a year. VX in the genital area is known as Vegas xanthomas. Though VX can look like other skin issues, a detailed examination of tissue samples is crucial for an accurate diagnosis. Treatment options include surgery, laser therapy, or topical creams. While VX is generally benign, seeking medical attention is important to rule out other concerns.Keywords: verruciform xanthoma, labia, child, diagnose, treatment

Yixian Wang,1,&ast; Xin Li,2,&ast; Yinde Huang,3,&ast; Qingwei Gang,1 Mingyu Liu,1 Han Zhang,1 Shikai Shen,1 Yao Qi,1 Jian Zhang1 1Department of Vascular and Thyroid Surgery, The First Hospital, China Medical University, Shenyang, Liaoning, 110001, People’s Republic of China; 2Department of Head and Neck Surgery, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning, 110042, People’s Republic of China; 3Department of Breast and Thyroid Surgery, Chongqing General Hospital, Chongqing, 401147, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Zhang, Email jianzhang@cmu.edu.cnBackground: Long non-coding RNAs (lncRNAs) associated with immunogenic cell death (ICD) play a pivotal role in tumorigenesis and offer prognostic insights for papillary thyroid carcinoma (PTC) patients. This study delves into the impact of ICD-related lncRNAs on the prognosis of PTC.Methods: PTC samples were accessed from The Cancer Genome Atlas-Thyroid carcinoma database (TCGA-THCA) and consensus cluster analysis to elucidate the influence of ICD-related lncRNA expression. To gauge the prognostic significance of these lncRNAs, we developed a prognostic model. Additionally, we conducted GO and KEGG enrichment analyses, assessed immune cell infiltration (ICI) using CIBERSORT and ssGSEA, examined immune checkpoint expression, tumor mutation burden (TMB), tumor microenvironment (TME), T-cell dysfunction and exclusion (TIDE), TCIA, and drug sensitivity across various groups. A comprehensive suite of in vitro experiments, encompassing EdU labeling, wound scratch assays, Transwell assays, and flow cytometry, were conducted to elucidate the regulatory role of LINC00924 in two PTC cell lines, BCPAP and TPC1, transfected with LINC00924 overexpression plasmids.Results: Two distinct clusters demonstrated varying TME, BRAF, NRAS, and ICI characteristics, suggesting potential immune mechanisms in PTC. Our prognostic model identified seven lncRNAs: SRRM2-AS1, AC008556.1, BHLHE40-AS1, EGOT, AL39066.1, LINC00924, and PICART1. The expression of ICD-related lncRNAs correlated with progression-free interval (PFI) in PTC patients. Overexpression of LINC00924 significantly reduced cell proliferation, migration, and invasion, while augmenting apoptosis in PTC cells.Conclusion: Our findings highlight the potential of ICD-related lncRNAs as prognostic biomarkers for PFI in PTC. In vitro experiments suggest a protective role of LINC00924 in PTC progression.Keywords: immunogenic cell death, LncRNA, papillary thyroid carcinoma, prognosis

Haitang Qiu,1,&ast; Shajidan Abudureyimu,1,&ast; Mengjia Liu,1 Fen Liu,2 Ying Gao1 1Department of Comprehensive Internal Medicine, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 2State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Clinical Medical Research, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Gao, Department of Comprehensive Internal Medicine, The First Affiliated Hospital of Xinjiang Medical University, 137 Liyushan South Road, Urumqi, Xinjiang, 830054, People’s Republic of China, Tel +86-991-4362625, Email gaoydct@163.comObjective: This study was conducted to investigate the combined effect of genetic variation in the C3 gene and environmental factors on the risk of type 2 diabetes mellitus(T2DM) and coronary artery disease(CAD) in a population from Xinjiang, China.Methods: We conducted a hospital-based case-control study with 896 participants (217 with T2DM+CAD and 679 healthy controls). A polymerase chain reaction-ligase detection reaction was used to identify and genotype TagSNPs in the C3 gene, and the influence of the interaction of two SNP loci (rs1047286 and rs11569562) with the environment on T2DM combined with CAD was evaluated through clinical data, statistical analysis of gene frequencies, and the formation of a gene-environment interaction model.Results: We find that rs11569562 GG is an independent protective factor for T2DM and CAD (OR=0.353, p=0.012), and the variants at its locus may be closely associated with Activated Partial Thromboplastin Time (APTT), lipoprotein a (Lp(a)), Apolipoprotein A (APOA), Aspartate Aminotransferase (AST), Aspartate Aminotransferase (ALT) and AST/ALT levels (all P < 0.05); its GG genotype has significantly lower Gensini score and number of stenoses than the GA and AA genotypes. Multifactorial dimensionality reduction (MDR) finds a strong correlation between rs11569562 and AST (antagonistic effect) (4.44%); the role of rs11569562’s influence remains strong in terms of the independent effects of each attribute (1.72%).Conclusions: In this study, we find that variants in the C3 gene loci rs11569562 are associated with the incidence of type 2 diabetes mellitus combined with coronary heart disease in a Chinese population. It is expected to be an independent predictor of type 2 diabetes mellitus combined with coronary heart disease in the Chinese population. Rs11569562 may be associated with lipid levels and coagulation molecules.Clinical Trial Registration: This trial registered on in 2014 at the China Clinical Trials Registry (ChiCTR-TRC-14005114).Keywords: coronary heart disease, Type 2 diabetes mellitus, complement C3

Changlin Han,1,&ast; Xueling Wang,1,&ast; Wenjia Zhang,2,&ast; Mingyue Liu,1,&ast; Yuhuan Xia3,&ast; 1School of Business, Qingdao University, Qingdao, Shandong, People’s Republic of China; 2School of Economics and Management, Beijing Jiaotong University, Beijing, People’s Republic of China; 3School of Innovation and Entrepreneurship, Shandong University, Qingdao, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuhuan Xia, School of Innovation and Entrepreneurship, Shandong University, No. 72 Binhai Road, Jimo District, Qingdao, Shandong, 266237, People’s Republic of China, Email xiayuhuan@sdu.edu.cnPurpose: In recent years, due to the increasingly prominent role of voice behavior in leader decision-making and organizational performance, such behavior has become a central topic for scholars. A majority of studies explore the “uphold” effects of multiple leader behavior toward the voice behavior; nonetheless, our study revealed the “undo” effect --- leader hypocrisy on voice behavior. Drawing on social cognitive theory, we investigated the relationship between leader hypocrisy and voice behavior, examined the mediating effects of cognition-based trust and affect-based trust, and the moderating effect of moral identity.Patients and Methods: We conducted a three-wave survey in a large Chinese corporation to test the hypothesized model. We collected 562 employees to participate in this survey.Results: The results show that leader hypocrisy negatively impacts employees’ cognition-based and affect-based trust, and both types of trust mediate the relationship between leader hypocrisy and voice behavior, respectively. In the meantime, moral identity manifested the negative effect of leader hypocrisy on cognition-based and affect-based trust.Conclusion: Our research not only enriches the related research on leader hypocrisy and voice behavior but also uncovers the underlying mechanism through which leader hypocrisy affects voice behavior and the boundary conditions of this effect. Meanwhile, our research provides a theoretical reference for increasing employees’ voice behavior and promoting the healthy development of enterprises.Keywords: leader hypocrisy, cognition-based trust, affect-based trust, voice behavior, moral identity, social cognitive theory

Yue Zhang,&ast; Yafan Bai,&ast; Yi Zhang, Yingjie Du, Min Liu, Jiayu Zhu, Guyan Wang Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guyan Wang, Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, No. 1 Dongjiaomingxiang, Beijing, 100730, People’s Republic of China, Tel +86-13910985139, Fax +86-10-58268017, Email guyanwang2006@163.comPurpose: Despite the implementation of various insulation measures, the incidence of hypothermia during thyroid surgery remains high. This randomized controlled study aimed to evaluate the effects of aggressive thermal management combined with resistive heating mattresses to prevent perioperative hypothermia in patients undergoing thyroid surgery.Patients and Methods: 142 consecutive patients scheduled for elective thyroid surgery were enrolled in the study. They were randomly and equally allocated to the aggressive warming or routine care groups (n = 71). The patients’ body temperature was monitored before the induction of anesthesia until they returned to the ward. The primary outcome was the incidence of perioperative hypothermia. Secondary outcomes included postoperative complications, such as mortality, cardiovascular complications, wound infection, shivering, postoperative nausea and vomiting (PONV), visual analog scale (VAS) pain scores, fever, headache and hospital length of stay (LOS).Results: In our study, the results showed that a significantly higher rate of hypothermia was observed in the routine care group compared with the aggressive warming group. The incidence of perioperative hypothermia was 19.72% (14/71) in the aggressive warming group and 35.21% (25/71) in the routine care group (P < 0.05). The incidence of shivering in the aggressive warming group (1.41%) was significantly lower than that in the routine care group (11.27%) (P < 0.05), and a one-day reduction in hospital length of stay was observed in the aggressive warming group (P < 0.05). There was no significant difference in mortality or other postoperative complications, such as cardiovascular complications, wound infection, PONV, pain, fever or headache, between the two groups (P > 0.05).Conclusion: Our results suggest that aggressive thermal management combined with resistive heating mattresses provided improved perioperative body temperature and reduced the incidence of perioperative hypothermia and shivering compared to routine thermal management.Plain Language Summary: ●The incidence of perioperative hypothermia during thyroid surgery was high.●The use of resistive heating mattresses during thyroid surgery can effectively reduce the occurrence of perioperative hypothermia.●It is recommended to take aggressive thermal protection during the operation of minor and medium surgeries, and to continuously monitor the temperature.Keywords: hypothermia, thyroid surgery, resistive heating mattresses, perioperative period

Min Liu, Yun-Jiao Duan, Ye Zhang, Jun Yang, Bing Wei, Junyu Wang Emergency Medicine Clinical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, & Beijing Key Laboratory of Cardiopulmonary Cerebral Resuscitation, Clinical Center for Medicine in Acute Infection, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Bing Wei; Junyu Wang, Email dr_weibing@126.com; wangjunyu_cyyy@126.comObjective: This study examines the effectiveness of MIP-3alpha and severity scores in determining the prognosis of elderly sepsis patients.Methods: From October 2020 to April 2021, a total of 171 elderly sepsis patients were admitted to the Emergency Department of the Shijingshan Branch of Beijing Chaoyang Hospital, Capital Medical University. According to the 28-day mortality rate, they were divided into two groups: survivors (48 cases) and deaths (123 cases). At admission, severity scores which are the Sequential Organ Failure Assessment (SOFA) and the Acute Physiology and Chronic Health Evaluation II (APACHE II) were calculated. The logistic regression was used to analyze the independent risk factors associated with 28-day mortality in elderly sepsis patients. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the value of MIP-3alpha, SOFA, and APACHE II in the evaluation of 28-day mortality in elderly sepsis patients.Results: MIP-3alpha, SOFA and APACHE II of the death group were significantly higher than those of the survival group (P < 0.05). Multivariate logistic regression analysis showed that MIP-3alpha, SOFA, APACHE II, and systolic blood pressure (SBP) were independent risk factors for 28-day mortality of senile sepsis (P < 0.05). Analysis of the ROC curve revealed that MIP-3alpha, SOFA, APACHE II had predictive value for the 28-day prognosis of senile sepsis (all P < 0.01). Combing with MIP-3alpha and SOFA showed better predictive ability (Z1 = 3.733, Z2 = 2.996, both P < 0.01), compared to detecting MIP-3alpha and SOFA alone.Conclusion: In senile sepsis, MIP-3alpha, SOFA, APACHE II and SBP are independent risk factors for 28-day mortality. The combination of MIP-3alpha and SOFA can further enhance the predictive value of 28-day mortality in patients with senile sepsis and provide some reference value for the evaluation and treatment of senile sepsis.Keywords: sepsis, the elderly, MIP-3alpha, prognosis

Di-Fei Duan,1,2,&ast; Min Liu,1,2,&ast; Deng-Yan Ma,1,2 Lin-Jia Yan,3 Yue-Yang Huang,1,2 Yi Chen,1,2 Wei Jiang,1,2 Xi Tang,2 An-Qi Xiong,4,5 Yun-Ying Shi2 1West China School of Nursing, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2Department of Nephrology, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 3The Nethersole School of Nursing Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China; 4Department of Nursing, West China Second University Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 5Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, Sichuan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Deng-Yan Ma, Email mdy5104@163.comPurpose: The research on symptom management in patients with diabetic kidney disease (DKD) has shifted from separate symptoms to symptom clusters and networks recently. This study aimed to evaluate the unpleasant symptoms of DKD patients, and to investigate how these symptom clusters could affect patients.Methods: 408 DKD patients were recruited in this cross-sectional study. The symptoms of DKD patients were measured using the modified Dialysis Symptom Index. Network analysis was employed to evaluate the symptom network and the characteristics of individual nodes, while factor analysis was utilized to identify symptom clusters.Results: Blurred vision was the most prevalent symptom among DKD patients. The symptoms identified as the most distressing, severe, and frequent were light headache or dizziness, arteriovenous fistula/catheterization pain, and diarrhea, respectively. Five symptom clusters were obtained from factor analysis, and the most central symptom cluster in the entire symptom network was sexual dysfunction.Conclusion: This study identified five symptom clusters in Chinese DKD patients, with sexual dysfunction emerging as the most central cluster. These findings carry significant clinical implications, underscoring the necessity of assessing symptom clusters and their associations to enhance symptom management in DKD patients. Further research is essential to elucidate the underlying mechanisms of symptoms and to clarify the associations among symptoms in DKD patients across different disease trajectories or treatment modalities.Keywords: diabetic kidney disease, network analysis, symptom cluster, symptom management

Yu Wang,1,2 Yitong Jia,3 Zheng Wang,4 Guang Feng,3 Yanhui Ma,3 Zhen Fan,3 Miao Liu,3 Kunpeng Feng,3 Tianlong Wang3 1Department of Neurosurgery, Beijing Boai Hospital, China Rehabilitation Research Center, Beijing, People’s Republic of China; 2College of Rehabilitation, Capital Medical University, Beijing, People’s Republic of China; 3Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Tianlong Wang, Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China, Email w_tl5595@hotmail.comBackground: Neuropathic pain (NP) is recognized as one of the most difficult pain syndromes which lacks a safe, well-tolerated and effective treatment. Pulsed radiofrequency (PRF), a novel and minimally invasive interventions, has been introduced to alleviate various types of NP. Previous studies reported PRF with higher voltage could further improve the treatment efficacy. Therefore, we conducted this systematic review and meta-analysis to determine whether high-voltage PRF is superior to standard-voltage PRF for the treatment of NP patients.Methods: Databases published from the date of inception until 15 March 2022 on PubMed/MEDLINE, EMBASE, Web of Science and the Cochrane Library were searched for RCTs comparing high-voltage PRF and standard-voltage PRF in NP patients. The primary outcome measures were the efficiency rates of NP patients with high-voltage PRF or standard-voltage PRF treatment. Data analysis was conducted using the Review Manager software (RevMan V.5.3).Results: Six RCTs involving 423 patients were included in our meta-analysis. Compared with standard-voltage PRF group, the high-voltage PRF group attained a higher efficiency rate at 1 month (P = 0.04; I2 = 0%), 3 months (P = 0.04; I2 = 0%), 6 months (P = 0.002; I2 = 0%) post-procedure respectively. There was no significant difference in the complications between the two groups.Conclusion: Our study supported that high-voltage PRF attained more satisfactory efficacy than standard-voltage PRF without increased side effects. High-voltage PRF could be a promising, effective, minimally invasive technology for NP patients.Keywords: trigeminal neuralgia, pulsed radiofrequency, high-voltage, standard-voltage, efficacy

Fei Shu,&ast; Hong Chen,&ast; Zhihao Zhang, Zhiyue Dun, Weijin Lv, Wangxinyue Sun, Mei Liu Department of Prosthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Jiangsu Province Key Laboratory of Oral Diseases, Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mei Liu, Department of Prosthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Jiangsu Province Key Laboratory of Oral Diseases, Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, People’s Republic of China, Tel +86-25-69593081, Fax +86-25-69593186, Email liumei2017@njmu.edu.cnIntroduction: Poor interfacial bonding between the fibers and resin matrix in fiber-reinforced composites (FRCs) is a significant drawback of the composites. To enhance the mechanical properties of FRC, fibers were modified by depositing SiO2 nanofilms via the atomic layer deposition (ALD) technique. This study aims to evaluate the effect of ALD treatment of the fibers on the mechanical properties of the FRCs.Methods: The quartz fibers were modified by depositing different cycles (50, 100, 200, and 400) of SiO2 nanofilms via the ALD technique and FRCs were proposed from the modified fibers. The morphologies, surface characterizations of nanofilms, mechanical properties, and cytocompatibility of FRCs were systematically investigated. Moreover, the shear bond strength (SBS) of FRCs to human enamel was also evaluated.Results: The SEM and SE results showed that the ALD-deposited SiO2 nanofilms have good conformality and homogeneity. According to the results of FTIR and TGA, SiO2 nanofilms and quartz fiber surfaces had good chemical combinations. Three-point bending tests with FRCs showed that the deposited SiO2 nanofilms effectively improved FRCs’ strength and Group D underwent 100 deposition cycles and had the highest flexural strength before and after aging. Furthermore, the strength of the FRCs demonstrated a crescendo-decrescendo tendency with SiO2 nanofilm thickness increasing. The SBS results also showed that Group D had outstanding performance. Moreover, the results of cytotoxicity experiments such as cck8, LDH and Elisa, etc., showed that the FRCs have good cytocompatibility.Conclusion: Changing the number of ALD reaction cycles affects the mechanical properties of FRCs, which may be related to the stress relaxation and fracture between SiO2 nanofilm layers and the built-up internal stresses in the nanofilms. Eventually, the SiO2 nanofilms could enhance the FRCs’ mechanical properties and performance to enamel by improving the interfacial bonding strength, and have good cytocompatibility. Keywords: atomic layer deposition, SiO2 nanofilms, surface modification, interfacial bonding

Mei Liu,1,&ast; Xiangqian Gao,2,&ast; Yang Tian,1 Huiwei Li,3 Ziqi Yin,1 Lei Han,4 Lei Zhang1 1Department of Endocrinology and Metabolism, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China; 2Department of Pathology, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China; 3Department of Intensive Care Unit, the Fifth People’s Hospital of Jinan, Jinan, Shandong, People’s Republic of China; 4Department of Reproductive Medicine, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Zhang, Department of Endocrinology and Metabolism, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China, Email binzhouzhanglei@outlook.com Lei Han, Department of Reproductive Medicine, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China, Email hanleimm@126.comContext: Metrnl is a novel adipokine mainly produced by white adipose tissue, which plays important roles in insulin sensitization, and energy homeostasis. However, information about the function of Metrnl in Metabolic dysfunction-associated fatty liver disease (MAFLD) remains unclear.Methods: This is a control study, which enrolled 176 adults with MAFLD and 176 normal controls. They were matched in body mass index (BMI), age, and sex. Serum Metrnl was determined by ELISA. Other biochemical data were also collected.Results: Compared to the controls, circulating Metrnl was prominently decreased in the MAFLD adults (P< 0.001). Next, binary logistic regression model indicated that sex, waist circumference (WC), triglyceride, γ-gamma glutamyl transferase(γ-GGT), and Metrnl was independently associated with MAFLD. Further, as Metrnl levels elevated across its tertiles, the rate of MAFLD decreased (67.52, 66.95, and 15.38%; P value for trend< 0.001). Data from multivariate logistic regression models evidenced that compared with the lowest tertile of Metrnl, the odds ratio of MAFLD was 0.023(95% CI 0.006– 0.086, P< 0.001) for the highest tertile after adjusting for potential confounders. Besides, area under ROC curve of Metrnl for diagnosis MAFLD was 0.755(95% CI 0.705– 0.805). Metrnl was positively correlated with diastolic blood pressure, WC, BMI, systolic blood pressure, γ-GGT, and Creatinine in MAFLD. Finally, we found systolic blood pressure and Creatinine were independently related to serum Metrnl in MAFLD.Conclusion: Serum Metrnl is reduced in adult with MAFLD. The results suggest that Metrnl may be a protective factor associated with the pathogenesis of MAFLD.Keywords: metabolic dysfunction-associated fatty liver disease, metrnl, adipokine, adipose tissue