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Ning Lou,1,* Xiangui Meng,2,* Tiexi Yu,2,* Weiquan Li,2,* Xin Lv,3,* Weiwei Han,1 Wen Xiao,2 Ying Shi2 1Department of Urology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 3Department of Urology, Central Hospital of Hefeng County, Enshi, 445800, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wen Xiao; Ying Shi, Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei Province, 430022, People’s Republic of China, Tel +86-17088353610, Fax +85776343, Email xiaowenx11@163.com; yingshi_whxh@hust.edu.cnBackground: Studies have found that RNA-binding proteins (RBPs) are participated in the occurrence or development of tumours. However, the role of processing of precursor family (POP family) in clear cell renal cell carcinoma (ccRCC) has not been studied yet. Here, we analyzed the expression and prognostic value of POP family in ccRCC analyzed and subsequently revealed the relationship between POP7 and immune infiltration in ccRCC patients.Methods: POP family expression in cancer and normal tissues was analyzed in Cancer Genome Atlas pan-cancer (TCGA-pan-cancer). Kaplan–Meier (KM) survival analysis, univariable and multivariable analysis demonstrated the survival of ccRCC with POP family in Kidney Clear Cell Carcinoma (TCGA-KIRC). POP7 mRNA and protein expression were verified by Gene Expression Omnibus (GEO) data, the quantitative real-time polymerase chain reaction (qRT-PCR), and Office of Cancer Clinical Proteomics Research (CPTAC). The diagnostic ability of POP7 mRNA and protein expression was achieved with ROC curves. Gene Set Enrichment Analysis (GSEA) and TiMER2 evaluated pathogenesis role and immune infiltration of POP7in ccRCC.Results: There is a significant difference in expression of POP family in TCGA-pan-cancer, especially in ccRCC. KM survival analysis, univariable and multivariable analysis demonstrated low expression of POP7 and was associated with poor OS and poor DFS. GEO data, the qRT-PCR, and CPTAC verified the high expression of POP7 mRNA and protein in ccRCC. ROC curves verified a valuable diagnostic ability of POP7 in mRNA and protein expression. GSEA demonstrated POP7 was associated with CD8+cells, CD4+cells, natural killer (NK) cells, and helper T (TH1) cells. TiMER2 results indicated POP7 had a positive correlation with T cell regulatory (Tregs) and myeloid-derived suppressor cells (MDSC) in ccRCC and was an immunosuppressor for ccRCC.Conclusion: POP7 was a reliable immunosuppressor, predictor and biomarker for ccRCC.Keywords: POP7, ccRCC, immunotherapy, prognostic indicator

Shuang Wang,1– 4,* Xuexia Liu,5 Xinhua Lin,1– 4,* Xiaojing Lv,2– 4 Hua Zhang2– 4 1School of Clinical Medicine, Shandong Second Medical University, Weifang, People’s Republic of China; 2Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China; 3Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China; 4Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China; 5Shandong Stem Cell Engineering Technology Research Center, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xuexia Liu; Hua Zhang, Department of Otorhinolaryngology & Head and Neck Surgery, Yuhuangding Hospital Affiliated to Qingdao University, No. 20 East, Yuhuangding Road, Yantai, Shandong, 264000, People’s Republic of China, Tel +86-15154502782, Email xue6er6@163.com; zhang0hua@163.comAbstract: Allergic rhinitis (AR), which presents symptoms like sneezing and a runny nose, is categorized as an upper respiratory condition of type 2. Recent progress in comprehending AR has revealed the significant role played by type 2 cytokines, specifically interleukin (IL)-13, IL-4, and IL-5. These cytokines are released by helper T cells 2 (Th2) and innate lymphoid cells (ILC2s). ILC2s have the ability to interact with various immune cells and are essential in promoting both type 2 immune response and tissue repair, contributing to normal homeostatic functions within the body. This article presents a summary of the latest advancements in comprehending the activity of ILC2s, with particular emphasis on their potential role involvement in AR. It explores how they collaborate with Th2 cells to exacerbate nasal inflammation and interact with regulatory T cells (Tregs) to counteract the suppressive role mediated by Tregs during allergic inflammation. The significance of ILC2s in allergen-specific therapy is highlighted. A comprehensive understanding of ILC2s biology establishes a robust foundation for unraveling the pathogenesis of AR and devising innovative therapeutic approaches for its management.Keywords: allergic rhinitis, group 2 innate lymphoid cells, cytokines, Treg cells, Th2 cells

Yihong Tian,1,2,&ast; Yanyue Tan,3,&ast; Ming Yang,1 Xiayang Lv,3 Yunhao Zheng,1 Qiang Zhang,4 Yanyu Sun,1 Jun Wang,1,2 Xin Xiong1,2 1State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chengdu, Sichuan, People’s Republic of China; 2Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Department of Nursing, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 4Department of Orthodontics, Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Wang; Xin Xiong, West China Hospital of Stomatology, Sichuan University, No. 14 section 3, Renmin South Road, Chengdu, 610041, People’s Republic of China, Email wangjunv@scu.edu.cn; drxiongxin@scu.edu.cnObjective: This study aimed to thoroughly explore the relationship between individual oral behavior and the differing numbers of temporomandibular disorder (TMD) symptom in the general population.Methods: A total of 565 participants were recruited and completed a questionnaire containing demographic characteristics, eight specific oral behaviors, and five major TMD symptoms (5Ts) checklist. Multivariate linear regression analysis was performed to assess the relationship between individual oral behavior and the number of TMD symptoms, after controlling for confounders.Results: The prevalence of TMD symptoms was up to 38.2% in the general population, with 64.6% of the participants engaging in one or more oral behaviors. Female participants showed a stronger positive association with most oral behaviors than males. Moreover, wake oral behaviors exhibited a higher correlation coefficient value with TMD symptom number than sleep oral behaviors. Among the eight oral behaviors, bruxism in sleep exhibited no significant correlation with the of TMD symptom number (P> 0.05). Seven other specific oral behaviors were significantly correlated with the number of TMD symptoms by multivariate linear regression analysis (P< 0.01). The associations between the seven oral behaviors and TMD symptom number remained significant in sleep posture pressuring jaw (β: 0.165, 95% CI: 0.080– 0.250), bruxism in awake (β: 0.341, 95% CI: 0.132– 0.550), teeth clenching (β: 0.422, 95% CI: 0.264– 0.580), pressing, holding, or touching teeth together (β: 0.282, 95% CI: 0.169– 0.395), holding or tightening muscles without clenching (β: 0.447, 95% CI0.304– 0.589), holding jaw forward or to the side (β: 0.694, 95% CI0.526– 0.861), and holding jaw in rigid or tense position (β: 0.571, 95% CI0.418, 0.724) after adjustment for demographic factors (P< 0.01).Conclusion: There was a positive association between seven specific oral behaviors and TMD symptom number. Individuals with higher frequency of specific oral behaviors are more likely to suffer from more TMD symptoms. Sleep bruxism exhibited no association with TMD symptoms and symptom number.Keywords: oral behaviors, temporomandibular disorders, TMD symptom number, cross-sectional study

Xiong Lv, Chun Xiang, Yan Zheng, Wan-Xuan Zhou, Xu-Ling Lv Department of Plastic Surgery, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Xiong Lv, Email 13157056997@163.comAbstract: Skin photoaging, resulting from prolonged exposure to ultraviolet (UV) radiation, is characterized by intricate biological changes involving oxidative damage and structural alterations. Despite an increasing demand for effective interventions, the current therapeutic options for treating skin photoaging are limited. We discovered through literature data search on PubMed that recent research has shifted its focus to the application of microneedle patches as an innovative approach to address this concern. Microneedle patches, serving as a novel transdermal delivery system, exhibit the potential to deliver bioactive substances such as cytokines, cellular vesicles, gene fragments and even alive algae to mitigate the effects of skin photoaging. This review aims to provide a comprehensive overview of recent advancements in research about utilizing microneedle patches for the treatment of skin photoaging and potential future directions in leveraging microneedle patches as clinical therapeutic agents for skin rejuvenation. Ultimately, we believe that microneedle patches have a broader application prospect in the fields of medical cosmetology and anti-photoaging. Keywords: skin photoaging, antioxidants, microneedle patch, transdermal delivery, skin rejuvenation

Kun Qin,1,2,&ast; Ting Gong,3,&ast; Shi-Fan Ruan,1,&ast; Min Lin,1 Xinhong Su,1 Xiaoqing Lv,1 Bo Cheng,1,4 Chao Ji1,4 1Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350000, People’s Republic of China; 2Department of Dermatology, Jiangmen Central Hospital, Jiangmen, Guangdong, 529000, People’s Republic of China; 3Central Laboratory, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350000, People’s Republic of China; 4Key Laboratory of Skin Cancer of Fujian Higher Education Institutions, The Fujian Medical University, Fuzhou, Fujian, 350000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chao Ji; Bo Cheng, Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Taijiang District, Fuzhou, Fujian, 350000, People’s Republic of China, Tel +86 18651619908 ; Tel +86 13859024296, Email jichaofy@fjmu.edu.com; chengbo630415@126.comPurpose: Immune checkpoint inhibitors (ICIs) can cause life-threatening Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Large-scale original research on ICI-induced SJS/TEN is limited. This study aimed to explore the unique clinical characteristics and potential pathophysiological mechanisms of SJS/TEN induced by ICIs.Methods: This cross-sectional study compared the clinical features of SJS/TEN induced by ICIs and non-ICIs, and reviewed the case characteristics of ICI-induced SJS/TEN. Clinical features were analyzed using independent t-tests, Mann–Whitney U-tests, and multivariable regression models.Results: This study enrolled 41 cases of ICI-induced SJS/TEN and 107 non-ICI-induced cases from January 22, 2015, to May 28, 2024. ICI-induced SJS/TEN patients exhibited a trend towards a longer latency period (β: 17, 95% CI: − 1.49 to 35.48), a smaller affected body surface area (BSA) (β: − 40.68, 95% CI: − 71.59 to − 9.77), and milder oral and ocular mucositis than non-ICI-induced cases. A literature review identified PD-1 inhibitors as the primary ICIs involved and systemic corticosteroids as the most frequent intervention. No statistically significant difference in mortality rate was observed between patients treated with systemic corticosteroids alone and those receiving combination therapies (P= 0.85). The mortality rate for ICI-induced SJS/TEN was 24.5%.Conclusion: This study offered the largest comparative analysis to date, highlighting the unique clinical features of ICI-induced SJS/TEN, including a smaller affected BSA, a prolonged latency period trend, and milder oral and ocular mucositis. We described the epidemiology, clinical presentation, and therapeutic strategies for ICI-induced SJS/TEN. These findings not only contribute to a deeper understanding of the complex immune-inflammatory pathways in severe immune-related cutaneous adverse events (ircAEs) but also may inform the development of more targeted and effective treatments.Keywords: comparative analysis, clinical characteristic, latency period, body surface area, treatment

Longqing Xia,1 Mengmeng Yang,1 Nan Zang,1– 4 Jia Song,1– 4 Jun Chen,1– 4 Huiqing Hu,1 Kewei Wang,1 Yingyue Xiang,1 Jingwen Yang,1 Liming Wang,1 Ying Zou,1 Xiaoyu Lv,1 Xinguo Hou,1– 4 Li Chen1– 4 1Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, 250012, People’s Republic of China; 2Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, 250012, People’s Republic of China; 3Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, 250012, People’s Republic of China; 4Jinan Clinical Research Center for Endocrine and Metabolic Disease, Jinan, 250012, People’s Republic of ChinaCorrespondence: Li Chen, Department of Endocrinology, Qilu Hospital of Shandong University, Shandong, People’s Republic of China, Email chenli3@email.sdu.edu.cnBackground: The depletion of β cell mass is widely recognized as a significant contributor to the progression of type 2 diabetes mellitus (T2DM). Exosomes derived from mesenchymal stem cells (MSC-EXOs) hold promise as cell-free therapies for treating T2DM. However, the precise effects and mechanisms through which MSC-EXO affects β cell function remain incompletely understood, and the limited ability of MSC-EXO to target β cells and the short blood circulation time hampers its therapeutic effectiveness.Methods: The effects of MSC-EXO were investigated in T2DM mice induced by a high-fat diet combined with STZ. Additionally, the high glucose-stimulated INS-1 cell line was used to investigate the potential mechanism of MSC-EXO. Michael addition reaction-mediated chemical coupling was used to modify the surface of the exosome membrane with a β-cell-targeting aptamer and polyethylene glycol (PEG). The β-cell targeting and blood circulation time were evaluated, and whether this modification enhanced the islet-protective effect of MSC-EXO was further analyzed.Results: We observed that the therapeutic effects of MSC-EXO on T2DM manifested through the reduction of random blood glucose levels, enhancement of glucose and insulin tolerance, and increased insulin secretion. These effects were achieved by augmenting β cell mass via inhibiting nuclear factor erythroid 2–related factor 2 (NRF2)-mediated ferroptosis. Mechanistically, MSC-EXOs play a role in the NRF2-mediated anti-ferroptosis mechanism by transporting active proteins that are abundant in the AKT and ERK pathways. Moreover, compared to MSC-EXOs, aptamer- and PEG-modified exosomes (Apt-EXOs) were more effective in islet protection through PEG-mediated cycle prolongation and aptamer-mediated β-cell targeting.Conclusion: MSC-EXO suppresses NRF2-mediated ferroptosis by delivering bioactive proteins to regulate the AKT/ERK signaling pathway, thereby improving the function and quantity of β cells. Additionally, Apt-EXO may serve as a novel drug carrier for islet-targeted therapy.Keywords: exosome, type 2 diabetes mellitus, β-cell-targeting, polyethylene glycol modification, ferroptosis

Sheng Wang,1– 3,&ast; Wufei Ye,1,3,&ast; Kui Yang,1,3 Xiongwen Lv,2 Jiajie Luan1,3 1Department of Pharmacy, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui, 241001, People’s Republic of China; 2The Key Laboratory of Anti-Inflammatory and Immune Medicines, Ministry of Education, Anhui Province Key Laboratory of Major Autoimmune Diseases, School of Pharmacy, Institute for Liver Disease of Anhui Medical University, Hefei, Anhui, 230032, People’s Republic of China; 3School of Pharmacy, Wannan Medical College, Wuhu, Anhui, 241002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiongwen Lv, The Key Laboratory of Anti-inflammatory and Immune medicines, Ministry of Education, Anhui Province Key Laboratory of Major Autoimmune Diseases, School of Pharmacy, Institute for Liver Disease of Anhui Medical University, Hefei, Anhui, 230032, People’s Republic of China, Email xiongwen_lv2019@163.com Jiajie Luan, Department of Pharmacy, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui, 241001, People’s Republic of China, Email luanjiajie775@163.comObjective: Hepatocellular carcinoma (HCC) is the predominant form of liver cancer. Hypoxia can be involved in HCC tumor growth, invasion and metastasis through inducing angiogenesis. Nevertheless, the assessment of the impact of hypoxia and angiogenesis on the prognosis of HCC remains inadequate.Methods: According to hypoxia-angiogenesis-related genes (HARGs) expression information and clinical data from patients within the Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) cohort, we constructed a prognostic model (HARG-score) using bioinformatic tools. In addition to assessing the predictive ability of this prognostic model in both Liver Cancer-Riken-Japan (LIRI-JP) and GSE14520 cohorts, we analyzed the correlation between HARG-score and clinical characteristics, immune infiltration and immunotherapy efficacy. Moreover, we investigated the exact role and underlying mechanism of key HARGs through molecular experiments.Results: We constructed a 5-gene prognostic model HARG-score consisting of hypoxia-inducible lipid droplet-associated (HILPDA), erythropoietin (EPO), solute carrier family 2 member 1 (SLC2A1), proteasome subunit alpha type 7 (PSMA7) and cAMP responsive element-binding protein 1 (CREB1) through differentially expressed HARGs. The findings demonstrated that HARG-score was a good predictor of the prognosis of HCC patients from distinct cohorts and was correlated with clinical characteristics and immune infiltration. Furthermore, the HARG-score was identified as an independent prognostic factor. Lower HARG-score implied greater immunotherapy efficacy and better response. The expression and prognostic significance of these 5 genes were additionally validated in clinical data. In addition, experimental data revealed that the key gene HILPDA contributes to the progression of HCC through facilitating angiogenesis and affecting the expression of cytotoxic T-lymphocyte-associated protein 4 (CTLA4).Conclusion: HARG-score has promising applications in prognosis prediction of HCC patients, in which HILPDA may be a latent prognostic biomarker and therapeutic target, providing a foundation for further research and treatment of HCC.Keywords: hepatocellular carcinoma, hypoxia-angiogenesis, HILPDA, prognosis, immunotherapy efficacy

Liang Shan,1– 4 Fengling Wang,1 Dandan Zhai,1 Xiangyun Meng,1 Jianjun Liu,1 Xiongwen Lv2– 4 1Department of Pharmacy, The Second People’s Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, Anhui, 230011, China; 2Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, 230032, China; 3Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, Anhui, 230032, China; 4The Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, 230032, ChinaCorrespondence: Jianjun Liu, Department of Pharmacy, The Second People’s Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, Anhui, 230011, China, Tel/Fax +86 0551 62965335, Email Jianjun_liu2020@163.com Xiongwen Lv, Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, 230032, China, Tel/Fax +86 0551 65161000, Email Xiongwen_lv2019@163.comBackground: Biliary atresia (BA) is a severe neonatal progressive cholangiopathy of unknown etiology. A timely Kasai portoenterostomy (KPE) improves survival of the native liver in patients with BA, although liver transplantation remains the ultimate treatment for most (60%– 80%) patients. However, postoperative adverse effects of liver transplantation may be significant. In addition, patients require lifelong immunosuppressive therapy after liver transplantation.Case Summary: Here, we report a case of a newborn female baby (birthday: 10– 03-2018) with congenital BA (confirmed at 76 days of life) who survived KPE (first surgery at 85 days of life) and underwent successful living-related liver transplantation (LRLT) (second surgery at 194 days of life). Additionally, we reviewed the existing literature on BA. After KPE (at 85 days of life), the liver function of the baby did not improve, and the indicators of liver and kidney function showed a trend of aggravation, indicating that the liver function had been seriously damaged before KPE (at 85 days of life), demonstrating the urgent need for liver transplantation surgery. The female baby survived after part of her father’s liver was successfully transplanted into her body (at 194 days of life). The patient recovered successfully. No other diseases were found at the 4-year follow-up, and all indices of liver and kidney functions tended to be normal.Conclusion: This case highlights the following. Postoperative alkaline phosphatase was consistently above the normal range, although the reason for this was unclear; neither tacrolimus nor cyclosporine A has formulations designed specifically for infants, which does not meet the needs of clinical individualized medication, suggesting that these anti-rejection drugs are future development directions. Only one case of congenital BA has been found thus far in Hefei, and this case has extremely important reference significance for the prevention, treatment, and diagnosis of BA in Hefei, Anhui province. Keywords: biliary atresia, Kasai portoenterostomy, living-related liver transplantation, immunosuppressive drug, therapeutic drug monitoring

Keting Min,&ast; Yu Wang,&ast; Di Feng,&ast; Tian Jin, Wanli Zhu, Ruowang Duan, Xin Lv Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xin Lv; Ruowang Duan, Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, 507 Zhengmin Road, Shanghai, 200032, People’s Republic of China, Tel +8613661869972 ; +8618019713255, Email xinlv@tongji.edu.cn; duanruowang@163.comBackground and Importance: Postoperative cough is a common complication of general anesthesia after bronchoscopy. The aim of the present study was to determine the safety profile and efficacy of piriform recess instillation with lidocaine in reducing the incidence of coughing.Objective: To what extent could piriform recess instillation with lidocaine decrease the incidence of cough at 10min after extubation?Outcome Measures and Analysis: Eighty-eight consecutive patients were equally randomized to a lidocaine group receiving piriform recess instillation with 2mL 2% lidocaine, and a normal saline group receiving piriform recess instillation with 2mL saline. The primary outcome was the incidence of cough after extubation, and the secondary outcomes were throat score at 10 min and 6 h after extubation assessed by the numerical rating scale, cough severity at 10 min and 6 h after extubation assessed by the Visual Analog Scale (VAS), 24 h 40-item Quality of Recovery Score (QoR-40), and subject-rated satisfaction score on a VAS.Main Results: Compared with saline group, the incidence of cough in lidocaine group was significantly lower (63.6% vs 86.4%, P=0.014). The sore throat score at 10 min after extubation was significantly lower (0[0,0] vs 1[0,2], P< 0.001). The subject-rated overall anesthesia satisfaction score was significantly higher (84.8[± 6.2] vs 76.6[± 8.6], P< 0.001). The severity of cough at 10 min after extubation was significantly lower (Mild: 36.4% vs 11.4%, P=0.006; Severe: 9.1% vs 43.2%, P< 0.001). There was no significant difference in the sore throat score at 6 h after extubation, severity of cough at 6 h after extubation, or QoR-40 at 24 h after extubation between the two groups.Conclusion: Piriform recess instillation with lidocaine before bronchoscopy is a simple and effective method for reducing early cough intensity and alleviating early sore throat. At 6 hours, there were no differences observed between the groups.Clinical Trial Registration: Chinese Clinical Trial Registry (identifier: ChiCTR2200067087).Keywords: piriform recess, lidocaine, general anesthesia, cough, bronchoscopy

Xianmei Lv,1,2,&ast; Gaochen Lan,3,&ast; Lujian Zhu,4,&ast; Qiusheng Guo1 1Department of Radiotherapy, Jinhua People’s Hospital, Jinhua, Zhejiang, 321000, People’s Republic of China; 2Department of Oncology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, People’s Republic of China; 3Department of Infectious Diseases, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, 321000, People’s Republic of China; 4Department of Medical Oncology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, 321000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiusheng Guo, Department of Medical Oncology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, 321000, People’s Republic of China, Email zhanluzhihun@126.comAbstract: Ferroptosis is a type of cell death that relies on iron and is distinguished by the occurrence of lipid peroxidation and the buildup of reactive oxygen species. Ferroptosis has been demonstrated to have a significant impact on the advancement and resistance to treatment of hepatocellular carcinoma (HCC), thereby highlighting its potential as a viable therapeutic target. Ferroptosis was observed in HCC tissues in contrast to normal liver tissue. The inhibition of ferroptosis has been found to increase the viability of HCC cells and decrease their susceptibility to various anticancer therapies, including chemotherapy, radiotherapy, and immune checkpoint blockade. The administration of drugs that directly modulate ferroptosis regulators or induce excessive production of lipid-reactive oxygen species has demonstrated the potential to enhance the responsiveness of drug-resistant HCC cells to treatment. However, the precise mechanism underlying this phenomenon remains ambiguous. This review presents a comprehensive overview of the crucial role played by ferroptosis in enhancing the efficacy of treatment for hepatocellular carcinoma (HCC). The main aim of this study is to examine the feasibility of utilizing ferroptosis as a therapeutic approach to improve the efficacy of HCC treatment and overcome drug resistance. Keywords: ferroptosis, hepatocellular carcinoma, chemotherapy, tyrosine kinase inhibitor, immunosuppressive therapy, radiotherapy

Min Lin,1,&ast; Ting Gong,2,&ast; Shifan Ruan,1,&ast; Xiaoqing Lv,1 Rongying Chen,1 Xinhong Su,1 Bo Cheng,1 Chao Ji1 1Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350000, People’s Republic of China; 2Department of Central Laboratory, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo Cheng; Chao Ji, Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Taijiang District, Fuzhou, 350000, People’s Republic of China, Tel +86 13859024296 ; +86 18651619908, Email bochengg@163.com; jichaofy@fjmu.edu.cnObjective: Anticancer drugs have revolutionized tumor therapy, with cutaneous toxicities such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) being common immune-related adverse events. The debate over the efficacy of systemic corticosteroids in treating these conditions persists, while tumor necrosis factor (TNF)-alpha inhibitors show promise. This study aims to evaluate the effectiveness and safety of combination therapy involving the TNF-α inhibitor adalimumab for SJS/TEN induced by anticancer drugs.Methods: A literature review of SJS/TEN cases induced by anticancer drugs from 1992 to 2023 was conducted, alongside an analysis of patients admitted to the First Affiliated Hospital of Fujian Medical University during the same period. Clinical characteristics, skin healing time, mortality, and adverse events were evaluated in two treatment groups: SJS/TEN patients treated with targeted anticancer therapies and immunotherapies.Results: Among the 27 patients studied (18 with SJS or SJS-TEN overlapping and 9 with TEN), combination therapy with adalimumab significantly reduced mucocutaneous reepithelization time and healing duration compared to corticosteroid monotherapy. Patients receiving adalimumab combined with corticosteroids had lower actual mortality rates than those on corticosteroid monotherapy. The combination therapy also showed a trend towards reducing standardized mortality rates based on the Score of Toxic Epidermal Necrolysis (SCORTEN).Conclusion: The findings suggest that adalimumab in combination with corticosteroids provides significant clinical benefits and is safer than corticosteroids alone for treating SJS/TEN induced by targeted anticancer therapies and immunotherapies. This study contributes valuable insights into potential treatment strategies for severe cutaneous adverse reactions to anticancer drugs, highlighting the importance of exploring alternative therapies such as TNF-α inhibitors in managing these conditions effectively.Keywords: anti-TNF-α, adalimumab, treatment, Stevens-Johnson syndrome, toxic epidermal necrolysis

Wei Li,1,2 Jun Wang,1,2 Chao Tang,1,2 Xuan Lv,1,2 Suijun Zhu1,2 1Department of Neurosurgery, First People’s Hospital of Linping District, Hangzhou, People’s Republic of China; 2Department of Neurosurgery, Linping Campus, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Suijun Zhu, Department of Neurosurgery, First People’s Hospital of Linping District, Hangzhou, People’s Republic of China, Email chaolinaweiminfu@126.comBackground: Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 1 (NLRP1) participates in neuroinflammation. This study aimed to identify serum NLRP as a potential prognostic biomarker of acute intracerebral hemorrhage (ICH).Methods: This prospective cohort study enrolled 145 patients with supratentorial ICH and 51 healthy controls. Serum NLRP1 levels were quantified on admission of all 145 patients, on days 1, 3, 5, 7, and 10 after stroke in 51 of 145 patients and at entry into the study of controls. Poststroke 6-month modified Rankin Scale (mRS) scores of 3– 6 signified a poor prognosis.Results: Compared to controls, patients had prominently increased serum NLRP1 levels until day 10 after ICH, with the highest levels at days 1 and 3. Serum NLRP1 levels were independently correlated with National Institutes of Health Stroke Scale (NIHSS) scores, hematoma volume and six-month mRS scores, and independently predicted six-month bad prognosis. A linear relationship was observed between serum NLRP1 levels and the risk of poor prognosis in a restricted cubic spline. Under the receiver operating characteristic (ROC) curve, serum NLRP levels efficiently discriminated poor prognosis. Serum NLRP1, NIHSS, and hematoma volume were merged into a prognosis prediction model, which was portrayed using a nomogram. Good performance of the model was verified using calibration curve, decision curve, and ROC curve.Conclusion: Serum NLRP1 levels are elevated during the early period following ICH and are independently related to hemorrhagic severity and poor prognosis, suggesting that serum NLRP1 may represent a promising prognostic biomarker of ICH.Keywords: intracerebral hemorrhage, NLRP1, prognosis, severity, biomarkers

Liang Shan,1– 4,&ast; Ning Zhao,2– 4,&ast; Fengling Wang,1 Dandan Zhai,1 Jianjun Liu,1 Xiongwen Lv2– 4 1Department of Pharmacy, the Second People’s Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, Anhui, 230011, People’s Republic of China; 2Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, 230032, People’s Republic of China; 3Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, 230032, People’s Republic of China; 4The Key Laboratory of Major Autoimmune Diseases, Hefei, Anhui Province, 230032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianjun Liu, Department of Pharmacy, the Second People’s Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, Anhui, 230011, People’s Republic of China, Tel +86 551 62965335, Fax +86 551 62965335, Email Jianjun_liu2020@163.com Xiongwen Lv, Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, 230032, People’s Republic of China, Tel +86 55165161000, Fax +86 551 65161000, Email Xiongwen_lv2019@163.comAbstract: The use of caffeine in treating various liver diseases has made substantial progress in the past decade owing to advances in science, technology, and medicine. However, whether caffeine has a preventive effect on hepatocellular carcinoma (HCC) and its mechanism are still worth further investigation. In this review, we summarize and analyze the efficacy and safety of caffeine in the prevention of HCC. We conducted a review of articles published in PubMed and Web of Science in the past 2 decades until December 6, 2023, which were searched for using the terms “Caffeine” and “Hepatocellular Carcinoma.” Studies have found that coffee intake is negatively correlated with HCC risk, especially caffeinated coffee. Recent studies have found that caffeine has beneficial effects on liver health, decreasing levels of enzymes responsible for liver damaging and slowing the progression of hepatic fibrosis and cirrhosis. Caffeine also acts against liver fibrosis through adenosine receptors (ARs), which promote tissue remodeling by inducing fibrin and collagen production. Additionally, new studies have found that moderate consumption of caffeinated beverages can decrease various the levels of various collagens in patients with chronic hepatitis C. Furthermore, polyphenolic compounds in coffee can improve fat homeostasis, reduce oxidative stress, and prevent liver steatosis and fibrosis. Moreover, many in vitro studies have shown that caffeine can protect liver cells and inhibit the activation and proliferation of hepatic stellate cells. Taken together, we describe the benefits of caffeine for liver health and highlight its potential values as a drug to prevent various hepatic diseases. As a protective agent of liver inflammation, non-selective AR inhibitor caffeine can inhibit the growth of HCC cells by inhibiting adenosine and AR binding to initiate immune response, providing a basis for the future development of caffeine as an adjuvant drug against HCC.Keywords: coffee, caffeine, hepatocellular carcinoma, adenosine, adenosine receptor

Xiaoyu Lv,1 Hui Wang,1 Chongyang Chen,1 Yangting Zhao,1 Kai Li,1 Yawen Wang,1 Liting Wang,1,2 Songbo Fu,1,2 Jingfang Liu1,2 1The First Clinical Medical College, Lanzhou University, Lanzhou, Gansu, People’s Republic of China; 2Department of Endocrinology, The First Hospital of Lanzhou University, Lanzhou, Gansu, People’s Republic of ChinaCorrespondence: Jingfang Liu, Department of Endocrinology, The First Hospital of Lanzhou University, Lanzhou, Gansu, 730000, People’s Republic of China, Tel +86 0931-8356242, Email ljf824168@126.comAim: To explore the effects of Tirzepatide (TZP), a new hypoglycemic drug, on weight, blood lipids and blood pressure in overweight/obese patients with type 2 diabetes mellitus (T2DM).Methods: Relevant studies investigating the influence of TZP therapy on weight, lipid profiles and blood pressure in overweight/obese T2DM patients were selected from the PubMed, Embase, Web of Science and Cochrane databases from establishment until November 2022. A systematic review and meta-analysis were conducted to evaluate the effect of TZP on weight, blood lipids and blood pressure in overweight/obese patients with T2DM.Results: Eight randomized controlled trials (RCTs), comprising 7491 patients with T2DM, were included in the meta-analysis. Results showed that compared with the glucagon-like peptide-1 receptor agonist (GLP-1RA), insulin, and placebo groups, body weight, triglycerides (TG), very low-density lipoprotein cholesterol (VLDL-C), total cholesterol (TC), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), and glycosylated hemoglobin (HbA1c) levels were significantly decreased in the TZP-treated groups, while high-density lipoprotein cholesterol (HDL-C) levels increased. With the gradual increase of TZP doses, the proportions of T2DM patients with weight loss > 5% gradually increased. The 10 mg and 15 mg TZP doses had a stronger effect on the levels of TG, VLDL-C, and HDL-C. Moreover, the reduction in SBP levels in the 15 mg TZP-treated group was more pronounced than those in the 10 mg and 5 mg TZP-treated groups [MD=− 2.07, 95% CI (− 2.52, − 1.63) and MD=− 3.14, 95% CI (− 4.42, − 1.87)]. Compared with GLP-1RA, insulin, and placebo groups, the proportions of patients with HbA1c< 7% in 10mg and 15mg TZP-treated groups were significantly higher than in the 5mg TZP-treated group [OR=1.53, 95% CI (1.25, 1.8)], OR=1.7, 95% CI (1.15, 2.50)].There was no significant difference regarding the risk of adverse reactions.Keywords: tirzepatide, T2DM, weight, lipid metabolism, meta-analysis

Xinna Lv,1,&ast; Ye Li,1,&ast; Botao Cai,2 Wei He,1 Ren Wang,1 Minghui Chen,1 Junhua Pan,1 Dailun Hou1 1Department of Radiology, Beijing Chest Hospital, Capital Medical University, Beijing, 101149, People’s Republic of China; 2Department of Radiology, Harbin Chest Hospital, Harbin, 150000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junhua Pan; Dailun Hou, Department of Radiology, Beijing Chest Hospital, Capital Medical University, Beijing, 101149, People’s Republic of China, Tel +8613901097074 ; +8618001286699, Email 13901097074@139.com; hou.dl@mail.ccmu.edu.cnBackground: Sputum culture result at the sixth month is essential for predicting therapeutic response to longer multidrug-resistant tuberculosis (MDR-TB) regimens. This study aimed to construct a predictive model using cavity-based radiomics to predict sputum status at the sixth month for MDR-TB patients treated with longer regimens.Methods: This retrospective study recruited 315 MDR-TB patients treated with longer regimens from two centers (250 patients from center 1 and 65 patients from center 2), who were divided into persistently positive and conversion to negative sputum culture groups according to sputum results. Radiomics features were extracted based on the cavity, and a radiomics model was selected and established using a random forest classifier. The clinical characteristics and primary CT signs with significant differences were integrated to build a clinical model. A combined model was generated using the radiomics and clinical model. ROC curves, F1-score and DCA curves were used to assess the predictive performance of the models.Results: Twenty-eight radiomics features were selected to build a radiomics model for predicting the sputum status. The radiomics model achieved good performance, with AUCs of 0.892 and 0.839 in the training and testing cohort, respectively, which was similar to the performance of the combined model (0.913 and 0.815) and much higher than that of the clinical model (0.688 and 0.525) in the two cohorts.Conclusion: The cavity-based radiomics model has the potential to predict sputum culture status for MDR-TB patients receiving longer regimens, which could guide follow-up treatment effectively.Keywords: machine learning, radiomics, tuberculosis, drug-resistance, therapeutic response

Manjiao Zhuang,1,&ast; Lei Rao,2,3,&ast; Yadi Chen,1 Shangying Xiao,1 Haishan Xia,1 Jiangyong Yang,2 Xiaohua Lv,1 Dongyun Qin,1 Chunjie Zhu1 1Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, and School of Pharmacy, Guangdong Medical University, Dongguan, 523808, People’s Republic of China; 2Medical College, Shaoguan University, Shaoguan, 512026, People’s Republic of China; 3Department of Biomedicine, Chengdu Medical College, Chengdu, 610500, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Manjiao Zhuang, Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, and School of Pharmacy, Guangdong Medical University, Dongguan, 523808, People’s Republic of China, Email manjiao@163.com Chunjie Zhu, School of Basic Medicine, Guangdong Medical University, Dongguan, 523808, People’s Republic of China, Email zhuchunjie718@163.comIntroduction: Quercetin has an ideal therapeutic effect on islet function improvement in type 2 diabetes mellitus (T2DM). However, the therapeutic benefit of quercetin is hindered by its poor bioavailability and limited concentration in pancreatic islets. In this study, superparamagnetic iron oxide nanoparticle (SPION)-modified exosomes were prepared to load quercetin, hoping to endow quercetin with enhanced water solubility and active targeting capacity with the help of magnetic force (MF).Methods: Transferrin-modified SPIONs (Tf-SPIONs) were synthesized by exploiting N-hydroxysuccinimidyl (NHS) conjugation chemistry, and quercetin-loaded exosomes (Qu-exosomes) were acquired by electroporation. Tf-SPION-modified quercetin-loaded exosomes (Qu-exosome-SPIONs) were generated by the self-assembly of transferrin (Tf) and the transferrin receptor (TfR). The solubility of quercetin was determined by high-performance liquid chromatography (HPLC) analysis. The pancreatic islet targeting capacity and insulin secretagogue and antiapoptotic activities of Qu-exosome-SPIONs/MF were evaluated both in vitro and in vivo.Results: The Qu-exosome-SPIONs were well constructed and harvested by magnetic separation with a uniform size and shape in a diameter of approximately 86.2 nm. The water solubility of quercetin increased 1.97-fold when loaded into the SPION-modified exosomes. The application of SPIONs/MF endowed the Qu-exosomes with favorable targeting capacity. In vitro studies showed that Qu-exosome-SPIONs/MF more effectively inhibited or attenuated β cell apoptosis and promoted insulin secretion in response to elevated glucose (GLC) compared with quercetin or Qu-exosome-SPIONs. In vivo studies demonstrated that Qu-exosome-SPIONs/MF displayed an ideal pancreatic islet targeting capacity, thereby leading to the restoration of islet function.Conclusion: The Qu-exosome-SPIONs/MF nano-delivery system significantly enhanced the quercetin concentration in pancreatic islets and thereby improved pancreatic islet protection.Keywords: quercetin, exosome, SPION, solubility, targeted delivery, islet function

Haiyan He,1,&ast; Hang Ma,1,&ast; Zhuo Chen,2 Jingliang Chen,1 Dandan Wu,1 Xuedong Lv,1 Jie Zhu1 1Department of Respiratory Medicine, The Second Affiliated Hospital of Nantong University, Nantong First People’s Hospital, Nantong, Jiangsu, 226001, People’s Republic of China; 2Department of Invasive Technology, The Second Affiliated Hospital of Nantong University, Nantong First People’s Hospital, Nantong, Jiangsu, 226001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuedong Lv; Jie Zhu, The Second Affiliated Hospital of Nantong University, Nantong First People’s Hospital, 6 North Road Hai’er Xiang, Nantong, 226001, Jiangsu, People’s Republic of China, Email xuedonglv@126.com; zhujie123123@126.comPurpose: Chromosomal abnormalities represent genomic signatures linked to cancer prognosis and responses to chemotherapy, immunotherapy, and drug resistance. This study aimed to investigate the impact of chromosome copy number variants (CNVs) on the efficacy of tyrosine kinase inhibitors (TKIs) in EGFR-mutated non-small cell lung cancer (NSCLC) patients, as well as its prognostic implications for progression-free survival (PFS) and overall survival (OS) in EGFR wild-type patients.Methods: A total of 110 patients with advanced NSCLC were enrolled in this study and categorized into EGFR-mutated and wild-type groups. Utilizing next-generation sequencing (NGS) technology, we assessed 24 genes and chromosome CNVs associated with lung cancer pathways in patients’ tissue samples.Results: Within the EGFR-mutated group, patients with a gain in Chr 1p13.3-p13.1 exhibited poor TKI responses, a high relapse rate, and shortened PFS (P = 0.002). Conversely, EGFR-mutated patients with a gain in 14q31.1-q31.3 demonstrated favorable TKI responses and relatively extended PFS (P = 0.005). Among EGFR wild-type patients, the presence of 7q31.1-q31.31 CNV emerged as an independent factor influencing both PFS and OS (P = 0.013, P = 0.004). Notably, patients with a gain in 7q31.1-q31.31 exhibited prolonged PFS and OS. Additionally, independent prognostic significance for OS in EGFR wild-type patients was observed for CNVs in 9q21.31-q22.2 and 11p11.11-q12.1 regions (P = 0.001). Patients with gains in these regions experienced extended OS, while losses were predictive of poorer outcomes.Conclusion: Our results suggested that chromosomal copy number variation is a practical indicator for predicting the response of EGFR-targeted therapy and prognosis for NSCLC patients.Keywords: copy number variations, non-small cell lung cancer, EGFR-TKI response, prognosis

Wildfire plays an important role in restructuring bacterial and protist taxonomic and functional communities in forest ecosystems. Yet, the recovery of bacterial and protist communities following wildfire has not been rigorously investigated across long-term wildfire chronosequences. We compared changes in bacterial and protist alpha diversity, community composition, co-occurrence networks and determinant edaphic factors between burnt and unburnt (reference) soils at 11 different sites representing a 76-year wildfire chronosequence in Canadian boreal forests. The fire increased bacterial and protist alpha diversity and altered community composition (beta diversity) as compared to the site-specific controls during the early recovery stage (30 years) recovery stages. Bacterial and protist communities showed similar patterns of change across the wildfire chronosequence. The post-fire recovery of bacterial communities was associated with changes in soil chemical properties (e.g., nutrient status and pH) and vegetation succession. The protist community assembly was co-influenced by changes in bacterial communities and vegetation succession/soil properties. The concurrent recovery of bacterial and protist communities, and their influencing factors of vegetation and soil properties, imply the above- and belowground living communities are strongly linked in wildfire-perturbed forest ecosystems.

Biaobiao Wang,&ast; Xiuqing Lv,&ast; Jingrui Huang Department of Obstetrics, Xiangya Hospital Central South University, Changsha, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingrui Huang, Department of Obstetrics, Xiangya Hospital Central South University, 87 Xiangya Road, Changsha, 410008, People’s Republic of China, Email jingruihuang@hotmail.com; huangjingrui@csu.edu.cn

Zhizheng Li,1 Li Li,1 Xiaohui Lv,1 Yingqian Hu,1 Kun Cui2 1Department of Respiratory and Critical Care Medicine, Tangshan Gongren Hospital, Tangshan, People’s Republic of China; 2Respiratory Medicine, Tangshan Gongren Hospital, Tangshan, People’s Republic of ChinaCorrespondence: Kun Cui, Email cuikun1988@126.comObjective: Cigarette smoke exposure is one of the major risk factors for the development of chronic obstructive pulmonary disease (COPD). Ginseng saponin Rb1 (Rb1) is a natural extract from ginseng root with anti-inflammatory and anti-oxidant effects. However, the underlying mechanism of the Rb1 in COPD remains unknown. Therefore, we sought to explore the role of Rb1 in cigarette smoke-induced damage and to reveal the potential mechanism.Methods: The cell viability and lactose dehydrogenase (LDH) activity were analyzed using cell counting kit-8 (CCK-8) and LDH release assays. We further investigated the inflammation, apoptosis and oxidative stress markers and analyzed the nuclear factor-kappa B (NF-κB) and nuclear factor erythroid-2-related factor 2 (Nrf2) pathways in BEAS-2B cells and COPD rat model following cigarette smoke extract (CSE) exposure.Results: Our results showed that CSE promoted inflammation, apoptosis and oxidative stress in BEAS-2B cells. Rb1 suppressed the inflammatory response by inhibiting expression of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1β and inhibiting the NF-κB signaling pathway. Rb1 possessed the ability to hinder cell apoptosis induced by CSE. In addition, Rb1 concurrently reduced CSE-induced oxidative reactions and promoted Nrf2 translocation to nucleus. For in vivo study, Rb1 treatment alleviated CSE-induced lung injury, apoptosis, reactive oxygen species (ROS) release and inflammatory reactions. Also, Rb1 treatment activated Nrf2 signaling and inactivated NF-κB signaling in COPD rats.Conclusion: Rb1 attenuates CSE-induced inflammation, apoptosis and oxidative stress by suppressing NF-κB and activating Nrf2 signaling pathways, which provides novel insights into the mechanism underlying CSE-induced COPD.Keywords: ginseng saponin Rb1, cigarette smoking exposure, inflammation, oxidative stress, NF-κB, Nrf2

Wenyu Zhou,1,&ast; Song Hu,1,2,&ast; Yutong Wu,1,&ast; Huan Xu,1,&ast; Lina Zhu,1 Huimin Deng,1 Sheng Wang,1 Yuanli Chen,1 Huanping Zhou,1 Xin Lv,1 Quanfu Li,1 Hao Yang1 1Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 200433, People’s Republic of China; 2Graduate School, Wannan Medical College, Wuhu, AnHui, 241002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Yang, Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, 507 Zhengmin Road, Shanghai, 200433, People’s Republic of China, Email yanghaozunyi@sina.com Quanfu Li, Department of Anesthesiology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507 Zhengmin Road, Shanghai, 200433, People’s Republic of China, Email quanfuli185@163.comBackground: Mesenchymal stem cell-derived exosomes (MSC-exosomes) have been found to effectively improve the systemic inflammatory response caused by acute lung injury and acute respiratory distress syndrome (ALI/ARDS), regulate systemic immune disorders, and help injured cells repair. The purpose of this study was to take a holistic view of the current status and trends of MSC-exosomes research in ALI/ARDS.Methods: Bibliometrix, Citespace and VOSviewer software were used for bibliometric analysis of the data. We analysed the world trends, country distribution, institution contribution, most relevant journals and authors, research hotspots, and research hotspots related to Coronavirus Disease 2019 (COVID-19) based on the data collected.Results: China possessed the largest number of publications, while the USA had the highest H-index and the number of citations. Both China and the USA had a high influence in this research field. The largest number of publications in the field of MSC-exosomes and ALI/ARDS were mainly from the University of California system. Stem Cell Research & Therapy published the largest number of papers in this scope. The author with the greatest contribution was LEE JW, and ZHU YG published an article in Stem Cell with the highest local citation score. The most frequent keyword and the latest research hotspot were “NF-κB” and “Coronavirus Disease 2019”. Furthermore, our bibliometric analysis results demonstrated that MSC-exosomes intervention and treatment can effectively alleviate the inflammatory response caused by ALI/ARDS.Conclusion: Our bibliometric study suggested the USA and China have a strong influence in this field. COVID-19-induced ALI/ARDS had become a hot topic of research.Keywords: acute respiratory distress syndrome, mesenchymal stem cells, exosome, bibliometrix, Citespace, VOSviewer

Sheng Liu,1,&ast; Guanyun Shi,1 Zhengbo Pan,1 Weisong Cheng,1 Linfei Xu,1 Xingzhang Lin,1 Yongfeng Lin,1 Liming Zhang,1 Guanghua Ji,1 Xin Lv,1 Dongguo Wang2,&ast; 1Department of Urinary Surgery, Taizhou Municipal Hospital Affiliated with Taizhou University, Taizhou, Zhejiang Province, People’s Republic of China; 2Department of Central Laboratory, Taizhou Municipal Hospital Affiliated with Taizhou University, Taizhou, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongguo Wang, Department of Central Laboratory, Taizhou Municipal Hospital Affiliated with Taizhou University, 381-1 Eastern Road of Zhongshan, Taizhou, Zhejiang Province, 318000, People’s Republic of China, Tel +86-13566871738, Email wdgtzs@163.comPurpose: The overall survival of clear cell renal cell carcinoma (ccRCC) is poor. Markers for early detection and progression could improve disease outcomes. This study aims to reveal the potential pathogenesis of ccRCC by integrative bioinformatics analysis and to further develop new therapeutic strategies.Patients and Methods: RNA-seq data of 530 ccRCC cases in TCGA were downloaded, and a comprehensive analysis was carried out using bioinformatics tools. Another 14 tissue samples were included to verify the expression of selected lncRNAs by qRT-PCR. DGIdb database was used to screen out potential drugs, and molecular docking was used to explore the interaction and mechanism between candidate drugs and targets.Results: A total of 58 differentially expressed lncRNAs (DElncRNAs) and 660 differentially expressed mRNAs (DEmRNAs) were identified in ccRCC. LINC02038, FAM242C, LINC01762, and PVT1 were identified as the optimal diagnostic lncRNAs, of which PVT1 was significantly correlated with the survival rate of ccRCC. GO analysis of cell components showed that DEmRNAs co-expressed with 4 DElncRNAs were mainly distributed in the extracellular area and the plasma membrane, involved in the transport of metal ions, the transport of proteins across membranes, and the binding of immunoglobulins. Immune infiltration analysis showed that MDSC was the most correlated immune cells with PVT1 and key mRNA SIGLEC8. Validation analysis showed that GABRD, SIGLEC8 and CDKN2A were significantly overexpressed, while ESRRB, ELF5 and UMOD were significantly down-regulated, which was consistent with the expression in our analysis. Furthermore, 84 potential drugs were screened by 6 key mRNAs, of which ABEMACICLIB and RIBOCICLIB were selected for molecular docking with CDKN2A, with stable binding affinity.Conclusion: In summary, 4 key lncRNAs and key mRNAs of ccRCC were identified by integrative bioinformatics analysis. Potential drugs were screened for the treatment of ccRCC, providing a new perspective for disease diagnosis and treatment.Keywords: clear cell renal cell carcinoma, bioinformatics analysis, lncRNA, mRNA, drugs prediction, molecular docking

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

Methods of optical dynamic nuclear polarization open the door to the replenishable hyperpolarization of nuclear spins, boosting their nuclear magnetic resonance/imaging signatures by orders of magnitude. Nanodiamond powder rich in negatively charged nitrogen vacancy defect centers has recently emerged as one such promising platform, wherein 13C nuclei can be hyperpolarized through the optically pumped defects completely at room temperature. Given the compelling possibility of relaying this 13C polarization to nuclei in external liquids, there is an urgent need for the engineered production of highly “hyperpolarizable” diamond particles. Here, a systematic study of various material dimensions affecting optical 13C hyperpolarization in diamond particles is reported on. It is discovered surprisingly that diamond annealing at elevated temperatures ∼1720 °C has remarkable effects on the hyperpolarization levels enhancing them by above an order of magnitude over materials annealed through conventional means. It is demonstrated these gains arise from a simultaneous improvement in NV− electron relaxation/coherence times, as well as the reduction of paramagnetic content, and an increase in 13C relaxation lifetimes. This work suggests methods for the guided materials production of fluorescent, 13C hyperpolarized, nanodiamonds and pathways for their use as multimodal (optical and magnetic resonance) imaging and hyperpolarization agents.

Tang-Jiang Li,1,2 Min Xiang,3 Xin Lv1,2 1Department of Pediatric Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, People’s Republic of China; 2Department of Pediatric Surgery, Guizhou Children’s Hospital, Zunyi, 563000, People’s Republic of China; 3Department of Electrocardiogram Room, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, People’s Republic of ChinaCorrespondence: Tang-Jiang Li, Department of Pediatric Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, People’s Republic of China, Tel +86 13984277525, Email litangjiang@126.comBackground: Bee sting injuries in children are accidental and occur in rural areas in summer and autumn. They have the characteristics of rapid onset, rapid change, many complications, complex treatment, and high disability rate. Patients experience various symptoms, such as vomiting, diarrhea, dyspnea, angioedema, multiple neuritis, myocardial infarction, acute renal failure, hypotension, and collapse. Systemic complications of the nervous system are rare. However, some cases of stroke, optic neuritis, and acute disseminated encephalomyelitis are related to bee stings. There are many cases of systemic multiple organ dysfunctions after bee sting injury, but there are few reports of facial nerve injury. The case presented here was caused by bee venom. This report is important because there are few instances of facial paralysis in the large number of notified bee sting cases. After active treatment, the facial paralysis of the child recovered gradually.Case Presentation: The patient was a 6-year-old boy. The bee stings by bee swarm induced pain in many parts of the body for 8 h. After the injury, he had skin itching, rash, swelling, and pain in the head and face. The boy had soy sauce-colored urine later and was transferred to the Affiliated Hospital of Zunyi Medical University from a lower-level hospital for treatment. On the seventh day after transfer, the child suddenly suffered from deviated mouth, which was considered a delayed facial nerve injury. After active treatment, he recovered from facial paralysis and was discharged from the hospital.Conclusion: This case report adds the clinical manifestation of facial paralysis after bee stings. They require close observation and being alert to possible clinical manifestations, as well as carrying out active intervention treatment.Keywords: children, bee sting, facial nerve injury, combined treatment

Yugang Lu,&ast; Qing Zhou,&ast; Yu Fu,&ast; Zongmei Wen, Xin Lv Department of Anesthesiology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zongmei Wen; Xin Lv, Department of Anesthesiology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507 Zhengmin Road, Shanghai, 200433, People’s Republic of China, Tel/Fax +86 21 65115006, Email wzm1103@126.com; xinlvg@126.comPurpose: Simultaneous bilateral pulmonary resection via uniportal video-assisted thoracoscopic surgery (UVATS) was safe and feasible for the treatment of bilateral multiple pulmonary nodules. But, it should be noted that considerable postoperative pain at the bilateral surgical site was a crucial issue. The safety and efficacy of bilateral thoracic paravertebral block (TPVB) have been reported for postoperative analgesia. But, whether bilateral sequential TPVB can be safely and effectively used in simultaneous bilateral UVATS remains unknown. Therefore, this study aimed to determine the analgesic efficacy and safety of bilateral sequential TPVB after simultaneous bilateral UVATS.Study Design and Methods: In this study, 80 participants scheduled for UVATS will be randomly allocated to the bilateral sequential TPVB group (G2) and the control group (G1). The patient of G2 will be performed bilateral TPVB at 2 time-points: before the start of the first side of pulmonary resection and before the start of the contralateral pulmonary resection. G1 will only receive standard analgesia protocol. The primary outcome is the numeric rating scale score during coughing at 24 h postoperatively. The secondary outcomes include the Prince Henry Pain Score scores, sufentanil consumption, postoperative nausea and vomiting, levels of inflammatory factors, and the Quality of Recovery-40 scores at different time points, as well as chronic pain at postoperative day (POD) 90.Discussion: This is the first prospective trial to determine the safety and effectiveness of ultrasound-guided bilateral sequential TPVB for postoperative analgesia following simultaneous bilateral UVATS. This study also intended to evaluate the effect of this intervention on postoperative quality of recovery and inflammation levels. The final results will provide clinical evidence related to bilateral sequential TPVB, and promote the application of that acting as a more appropriate analgesic method for simultaneous bilateral UVATS.Keywords: thoracic surgery, video-assisted, multiple pulmonary nodules, nerve block, pain measurement

The origins of spin lifetimes in quantum systems is a matter of importance in several areas of quantum information. Spectrally mapping spin relaxation processes provides insight into their origin and motivates methods to mitigate them. In this paper, we map nuclear relaxation in a prototypical system of [Formula: see text] nuclei in diamond coupled to Nitrogen Vacancy (NV) centers over a wide field range (1 mT-7 T). Nuclear hyperpolarization through optically pumped NV electrons allows signal measurement savings exceeding million-fold over conventional methods. Through a systematic study with varying substitutional electron (P1 center) and [Formula: see text] concentrations, we identify the operational relaxation channels for the nuclei at different fields as well as the dominant role played by [Formula: see text] coupling to the interacting P1 electronic spin bath. These results motivate quantum control techniques for dissipation engineering to boost spin lifetimes in diamond, with applications including engineered quantum memories and hyperpolarized [Formula: see text] imaging.

The origins of spin lifetimes in quantum systems is a matter of importance in several areas of quantum information. Spectrally mapping spin relaxation processes provides insight into their origin and motivates methods to mitigate them. In this paper, we map nuclear relaxation in a prototypical system of [Formula: see text] nuclei in diamond coupled to Nitrogen Vacancy (NV) centers over a wide field range (1 mT-7 T). Nuclear hyperpolarization through optically pumped NV electrons allows signal measurement savings exceeding million-fold over conventional methods. Through a systematic study with varying substitutional electron (P1 center) and [Formula: see text] concentrations, we identify the operational relaxation channels for the nuclei at different fields as well as the dominant role played by [Formula: see text] coupling to the interacting P1 electronic spin bath. These results motivate quantum control techniques for dissipation engineering to boost spin lifetimes in diamond, with applications including engineered quantum memories and hyperpolarized [Formula: see text] imaging.

Multichannel imaging -- the ability to acquire images of an object throughmore than one imaging mode simultaneously -- has opened interesting newperspectives in areas ranging from astronomy to medicine. Visible optics andmagnetic resonance imaging (MRI) offer complementary advantages of resolution,speed and depth of penetration, and as such would be attractive in combination.In this paper, we take first steps towards marrying together optical and MRimaging in a class of biocompatible particulate materials constructed out ofdiamond. The particles are endowed with a high density of quantum defects(Nitrogen Vacancy centers) that under optical excitation fluoresce brightly inthe visible, but also concurrently electron spin polarize. This allows thehyperpolarization of lattice 13C nuclei to make the particles over three-ordersof magnitude brighter than in conventional MRI. Dual-mode optical and MRimaging permits immediate access to improvements in resolution andsignal-to-noise especially in scattering environments. We highlight additionalbenefits in background-free imaging, demonstrating lock-in suppression byfactors of 2 and 5 in optical and MR domains respectively. Ultimate limitscould approach as much as two orders of magnitude in each domain. Finally,leveraging the ability of optical and MR imaging to simultaneously probeFourier-reciprocal domains (real and k-space), we elucidate the ability toemploy hybrid sub-sampling in both conjugate spaces to vastly acceleratedual-image acquisition, by as much as two orders of magnitude in practicallyrelevant sparse-imaging scenarios. This is accompanied by a reduction inoptical power by the same factor. Our work suggests interesting possibilitiesfor the simultaneous optical and low-field MR imaging of targeted diamondnanoparticles.

We describe the construction of a fast field cycling device capable of sweeping a 4-order-of-magnitude range of magnetic fields, from ∼1 mT to 7 T, in under 700 ms, and which is further extendable to a 1 nT-7 T range. Central to this system is a high-speed sample shuttling mechanism between a superconducting magnet and a magnetic shield, with the capability to access arbitrary fields in between with high resolution. Our instrument serves as a versatile platform to harness the inherent dichotomy of spin dynamics on offer at low and high fields-in particular, the low anisotropy, fast spin manipulation, and rapid entanglement growth at low field as well as the long spin lifetimes, spin specific control, and efficient inductive measurement possible at high fields. Exploiting these complementary capabilities in a single device opens up applications in a host of problems in quantum control, sensing, and information storage, besides in nuclear hyperpolarization, relaxometry, and imaging. In particular, in this paper, we focus on the ability of the device to enable low-field hyperpolarization of 13C nuclei in diamond via optically pumped electronic spins associated with nitrogen vacancy defect centers.

Zhiyuan Zhang,&ast; Nan Zhang,&ast; Jing Yu,&ast; Wenting Xu, Jiameng Gao, Xin Lv, Zongmei Wen Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 200433, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xin Lv; Zongmei Wen, Department of Anesthesiology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507 Zhengmin Road, Shanghai, 200433, People’s Republic of China, Email xinlvg@126.com; wzm1103@126.comAbstract: Podoplanin is a small cell-surface mucin-like glycoprotein that participates in multiple physiological and pathological processes. Podoplanin exerts an important function in the immune response and is upregulated in fibroblasts, macrophages, T helper cells, and epithelial cells during inflammation. Herein, we summarize the latest knowledge on the functional expression of podoplanin in the immune system and review the contribution of podoplanin to several inflammatory diseases. Furthermore, we discuss podoplanin as a novel therapeutic target for various inflammatory diseases.Keywords: podoplanin, immune system, inflammation

Bo Wang,1,&ast; Song Gong,2,&ast; Lizhi Han,2 Wenkai Shao,2 Zilin Li,2 Jiawei Xu,2 Xiao Lv,2 Baojun Xiao,2 Yong Feng2 1Department of Rehabilitation, Wuhan No.1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Baojun Xiao; Yong Feng, Email drxiao999@sohu.com; fengyong@hust.edu.cnBackground: Histone deacetylase 9 (HDAC9) is a member of the HDAC gene family that plays essential roles in the organization of transcriptional regulation by catalyzing deacetylation of histone proteins. However, the effects of HDAC9 on osteonecrosis of femoral head (ONFH) have not been investigated. The present study aimed to reveal whether histone deacetylase 9 (HDAC9) regulated osteogenic differentiation.Methods: A lentiviral knockdown HDAC9 model was established in hBMSCs. Osteoblast-specific gene expression, such as Runx2, OCN was examined by qRT-PCR and Western blot, respectively. Though transcriptome sequencing and enrichment analysis, related signal pathways caused by down-regulation of HDAC9 were screened. The effect of HDAC9 on MAPK signaling pathway was determined by Western blot. Eventually, tert-Butylhydroquinone (tBHQ) was used to examine the effect of MAPK activation on osteogenesis in HDAC9 knockdown hBMSCs.Results: A lentiviral knockdown HDAC9 model was successfully established in hBMSCs. HDAC9 knockdown significantly inhibited osteoblast-specific gene expression, such as runt-related transcription factor 2 (Runx2), osteocalcin (OCN) and mineral deposition in vitro. Moreover, a total of 950 DEGs were identified in HDAC9-knockdown hBMSCs. We discovered that the MAPK signaling pathway might be related to this process by pathway enrichment analysis. HDAC9 knockdown significantly reduced the expression level of phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2). Finally, the decreased osteogenesis due to HDAC9 knockdown was partly rescued by a MAPK signaling pathway activator.Conclusion: Taken together, these results suggest that HDAC9 knockdown inhibits osteogenic differentiation of hBMSCs, partially through the MAPK signaling pathway. HDAC9 may serve as a potential target for the treatment of ONFH.Keywords: HDAC9, hBMSCs, osteogenesis, MAPK signaling pathway

Ping Zheng,1 Kexing Zhang,2 Xifang Lv,1 Chuanhe Liu,3 Qiang Wang,1 Xuetao Bai1 1China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China; 2Department of Immunization Program, Xinwu District Center for Disease Control and Prevention, Wuxi, People’s Republic of China; 3Children’s Hospital, Capital Institute of Pediatrics, Beijing, People’s Republic of ChinaCorrespondence: Qiang Wang; Xuetao Bai, China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, 29 Nanwei Road, Xicheng District, Beijing, 100050, People’s Republic of China, Tel +86 10 50930251, Email wangqiang@nieh.chinacdc.cn; xuetaobai@163.comPurpose: This study aimed to investigate the characteristics of gut bacteria and the derived metabolites among allergic asthmatic children, non-allergic asthmatic children and healthy children without asthma.Methods: Fecal samples were collected from 57 participants, including 20 healthy children, 27 allergic asthmatic children, and 10 non-allergic asthmatic children. 16S rRNA gene sequencing was conducted for analyzing gut bacterial compositions and untargeted metabolomics was used to analyze the alterations of gut microbe-derived metabolites. The associations between gut bacterial compositions and metabolites were analyzed by the method of Spearman correlation.Results: The results showed that the compositions and metabolites of gut microbiome were altered both in allergic and non-allergic asthmatics compared with healthy controls. Chao1 (p = 0.025) index reflected a higher bacterial richness and Simpson (p = 0.024) index showed a lower diversity in asthma group. PERMANOVA analysis showed significant differences among the three groups based on unweighted UniFrac distance (p = 0.001). Both allergic and non-allergic asthmatics showed a higher relative abundance of Proteobacteria and a lower relative abundance of genera from Clostridia. More bacteria were altered in non-allergic asthmatics compared with allergic asthmatics. Metabolomics analysis identified that 42 metabolites were significantly associated with allergic asthma, and 58 metabolites were significantly associated with non-allergic asthma (multiple linear regression, p < 0.05). Histamine was 4 folds up-regulated only in the non-allergic asthma group. The relative abundance of Candidatus Accumulib was significantly correlated with the upregulation of histamine. The relative abundance of genera from Clostridia was significantly correlated with the downregulation of lipid and tryptophan metabolism.Conclusion: The altered gut microbes was associated with the mechanism of asthma attack through metabolites in allergic and non-allergic asthma group, respectively. The result suggested that gut microbiome had an impact on the development of both allergic and non-allergic asthma. The distinct gut microbiome and microbiome-derived metabolites in non-allergic asthma children suggested that gut microbiome might play a critical role in modulation of asthma phenotype.Keywords: gut microbiome, untargeted metabolomics, allergic childhood asthma, non-allergic childhood asthma, 16S rRNA gene sequencing

Yu Fu,1,&ast; Huimin Fu,2,&ast; Yugang Lu,1 Xin Lv1 1Department of Anesthesiology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Department of Anesthesiology, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yugang Lu; Xin Lv, Department of Anesthesiology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507 Zhengmin Road, Shanghai, 200433, People’s Republic of China, Tel/Fax +86 021 65115006, Email luyugang@tongji.edu.cn; xinlvg@126.comPurpose: It is pivotal to optimize perioperative analgesia in order to fit a transition in the surgical approach for removing mediastinal tumors, from sternotomy to trans-subxiphoid robotic thymectomy (TRT). Serratus anterior plane block (SAPB) is a safe, effective and easy to perform analgesic technology, which could provide analgesia in thoracic and upper abdominal surgery. However, the efficacy of SAPB analgesia in the patients undergoing TRT is unclear and has never been described in scientific literature. Therefore, this study aimed to determine the effect of ultrasonic-guided low SAPB on analgesia and the quality of recovery (QoR) following the TRT.Study Design and Methods: In this prospective double-blind, randomized controlled design trial, 40 adults scheduled for TRT will be randomly allocated to the low SAPB group (Group S) and placebo control group (Group C). The patient of Group S will be performed SAPB bilaterally at the level of T8–T9 under ultrasound guidance with 40 mL 0.375% ropivacaine after anesthesia induction. Group C will be administered normal saline at the same volume and timing. The primary study outcome is the global Quality of Recovery-40 (QoR-40) score on postoperative days (POD) 1. The secondary endpoints are numeric rating scale (NRS) scores and sufentanil consumption at different time points after surgery, QoR-40 scores on POD 2, 30 and 90, chronic pain at POD 90, and the incidence of perioperative adverse events.Discussion: This is the first prospective trial to shed light on the efficacy of ultrasonic-guided low SAPB on postoperative pain and recovery after TRT. The findings will provide a new strategy of perioperative pain management for TRT.Keywords: serratus anterior plane block, robot-assisted thoracic surgery, subxiphoid, thymectomy, postoperative analgesia