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Guanlian Hu,1,2,* Xue Zhao,1,* Yiren Wang,1 Xiaoyan Zhu,1,3 Zhan Sun,1,2 Xiaoxiao Yu,1,2 Jiahui Wang,4 Qian Liu,1 Jing Zhang,1 Yingna Zhang,1 Junhong Yang,4 Ting Chang,5 Zhe Ruan,5 Jie Lv,1 Feng Gao1 1Department of Neuroimmunology, Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China; 2BGI College, Zhengzhou University, Zhengzhou, People’s Republic of China; 3Department of Neurology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 4Department of Encephalopathy, First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 5Department of Neurology, Second Affiliated Hospital, Air Force Medical University, Xi’an, People’s Republic of China*These authors contributed equally to this workCorrespondence: Feng Gao; Jie Lv, Department of Neuroimmunology, Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China, Email gaoyuanshan@126.com; LJQ19972006@126.comAbstract: Myasthenia gravis (MG) is a typical autoimmune disease of the nervous system. It is characterized by skeletal muscle weakness and fatigue due to impaired neuromuscular junction transmission mediated by IgG autoantibodies. Muscle-specific receptor tyrosine kinase-associated MG (MuSK-MG), a rare and severe subtype of MG, is distinguished by the presence of anti-MuSK antibodies; it responds poorly to traditional therapies. Recent research on MuSK-MG treatment has focused on specific targeted therapies. Since B cells play a critical pathogenic role in producing autoantibodies and inflammatory mediators, they are often considered the preferred target for treating MuSK-MG. Currently, various B cell-targeted drugs have been developed to treat MuSK-MG; they have shown good therapeutic effects. This review explores the evolving landscape of B cell-targeted therapies in MuSK-MG, focusing on their mechanisms, efficacy, and safety, and the current limitations associated with their use. We discuss current B cell-targeted therapies aimed at depleting or modulating B cells via both direct and indirect approaches. Furthermore, we focus on novel and promising strategies such as Chimeric Autoantibody Receptor T cell therapy, which explicitly targets MuSK-specific B cells without compromising general humoral immunity. Finally, this review provides an outlook on the potential benefits and limitations of B cell-targeted therapy in developing new therapies for MuSK-MG. We conclude by discussing future research efforts needed to optimize these therapies, expand treatment options, and improve long-term outcomes in MuSK-MG management.Keywords: MuSK-MG, B cell-targeted therapy, direct targeting, indirect targeting, MuSK-CAR-T, MuSK-CAAR-T

Pingzhi Wang,1 Zhengtao Wang,1 Junyan Zhang,2 Caiqin Lan,1 Yani Zhao,1 Xiaoqing Chen,1 Yu Li,1 Qi Mei,3 Huijing Feng,3 Shuang Wei,4 Zhifeng Xue,4 Fang Gao,5 Xiaolei Liu,6,7 Ying Liang1 1Department of Rehabilitation Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of Clinical Epidemiology and Evidence-Based Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 3Cancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 5Department of Prevention Care in HealthCare, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 6Department of Neurology, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 7Yunnan Provincial Clinical Research Center for Neurological Diseases, Kunming, People’s Republic of ChinaCorrespondence: Ying Liang; Xiaolei Liu, Email Kfkliangying@126.com; ring@vip.163.comObjective: The aim of this study was to evaluate the impact of hyperbaric oxygen therapy (HBOT) on patients with SARS-CoV-2 infection and determine its efficacy and safety in reducing treatment failure events.Methods: A retrospective cohort study involving patients with COVID-19 was conducted. Inverse probability of treatment weighting (IPTW) was used to balance covariates between the HBOT and non-HBOT groups. The primary endpoint was the occurrence of a clinical treatment failure event, defined as all-cause mortality, abandonment of treatment, or transfer to the Intensive Care Unit due to worsening condition.Results: A total of 720 patients with COVID-19 were enrolled in the study, with 27 patients receiving HBOT and 693 patients not receiving HBOT. The occurrence of treatment failure was significantly lower in the HBOT group compared to the non-HBOT group, with no treatment failure events in the HBOT group versus 36 events in the non-HBOT group. The IPTW database analysis results showed that in comparison to the non-HBOT group, the hazard ratio (HR) for treatment failure in the HBOT group was less than 0.001 (95% CI: < 0.001 ~ < 0.001, p< 0.001). Lymphocyte count > 0.8× 109/L and HBOT was associated with a significantly lower risk of treatment failure. Glucocorticoid use was associated with a higher risk of treatment failure. The incidence of venous thrombosis events was significantly higher in the HBOT group compared to the non-HBOT group.Conclusion: This study revealed that adjunctive HBOT significantly reduces the risk of treatment failure in patients with COVID-19 and is associated with satisfactory safety. HBOT shows promise as a beneficial therapy for improving outcomes in COVID-19-infected patients.Keywords: hyperbaric oxygen therapy, COVID-19, retrospective cohort, inverse probability of treatment weighting, SARS-CoV-2 infection

Yongjiao Zhang,1,2 Xiaolei Xuan,2 Diwen Ye,1,2 Dong Liu,2 Yufan Song,2 Fei Gao,2 Sumei Lu2 1School of Medical Laboratory, Shandong Second Medical University, Weifang, Shandong, People’s Republic of China; 2Department of Laboratory Medicine, The First Affiliated Hospital of Shandong First Medical University, Jinan, People’s Republic of ChinaCorrespondence: Sumei Lu; Fei Gao, Email lsmqianyi@126.com; 448617003@qq.comAbstract: Absent in melanoma 2 (AIM2) is a protein encoded by the AIM2 gene located on human chromosomes, AIM2 can recognize and bind to double stranded DNA (dsDNA), leading to the assembly of the AIM2 inflammasome. The AIM2 inflammasome plays important proinflammation role in many diseases, and can induce pyroptotic cell death. It has also been closely linked to the development and progression of metabolic diseases and can be activated in obesity, diabetes, nonalcoholic fatty liver disease, and atherosclerosis. In this article, we mainly review the role of AIM2 in glucose metabolism, especially in obesity-related disorders of glucose and lipid metabolism, and provide insights to better understand the role of AIM2 in the pathogenesis, and clinical treatment of metabolic disease.Keywords: AIM2, obesity, metabolic diseases, diabetes, glucose metabolism disorders

Fei Gao,1,&ast; Siqi He,1,&ast; Jing Li,1 Xiaoyue Wang,2 Xiaoting Chen,2 Xiaoning Bu1 1Department of Respiratory and Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoning Bu, Department of Respiratory and Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, No. 119 South 4th Ring Road West, Fengtai District, Beijing, 100070, People’s Republic of China, Tel +8613641000837, Email 13641000837@163.comPurpose: Systemic Immune-Inflammation Index (SII), calculated by (neutrophils count × platelet count)/lymphocytes count, is a novel index of the local immune response and systemic inflammation response. The SII has been shown to play an important role in the prognosis of many diseases, including cardiovascular diseases, cancer and COPD. However, its role in the prognosis of bronchiectasis remains unclear and requires further investigation. This study aimed to investigate the association between SII and readmissions in patients with acute exacerbations of bronchiectasis.Patients and Methods: We conducted a retrospective cohort study of all bronchiectasis patients admitted to the respiratory ward in Beijing Chaoyang Hospital from January 2020 to January 2022. Patients were classified into four groups according to the quartiles of log2(SII) at admission. The primary endpoint was readmission at 1-year follow up. Univariate and multivariate cox regression models were applied to investigate the relationship between SII and readmissions at 1-year follow up in patients with bronchiectasis.Results: A total of 521 patients were included in our study. The median (IQR) SII at admission were 506.10 (564.84). Patients with higher SII tended to be older, male, past and current smokers, have lower BMI, and more dyspnea symptoms. They also had higher inflammatory markers and received a greater spectrum of antibiotics and more intravenous glucocorticoids. Higher SII at admission were independently associated with readmission in patients with acute exacerbations for bronchiectasis following confounder adjustment (OR =1.007; 95% CI, 1.003– 1.011; p < 0.001).Conclusion: Patients with elevated SII levels were typically older males, often smokers, with lower BMI and increased dyspnea. They received more antibiotics and intravenous glucocorticoids. Higher SII at admission are associated with readmission in patients with acute exacerbations of bronchiectasis. SII has potential clinical value as a predictive biomarker for clinical outcomes in bronchiectasis, offering a valuable tool for management strategies.Keywords: chronic respiratory disease, inflammation, prognosis

Feiyu Gao,&ast; Tao Xu,&ast; Fangnan Zang, Yuanyuan Luo, Defeng Pan Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanyuan Luo; Defeng Pan, Email luoyuanyuanxyfy@126.com; xzdefengpan@xzhmu.edu.cnAbstract: With the continuous refinement of therapeutic measures, the survival rate of tumor patients has been improving year by year, while cardiovascular complications related to cancer therapy have become increasingly prominent. Exploring the mechanism and prevention strategy of cancer therapy-related cardiovascular toxicity (CTR-CVT) remains one of the research hotspots in the field of Cardio-Oncology in recent years. Cardiotoxicity of anticancer drugs involves heart failure, myocarditis, hypertension, arrhythmias and vascular toxicity, mechanistically related to vascular endothelial dysfunction, ferroptosis, mitochondrial dysfunction and oxidative stress. To address the cardiotoxicity induced by different anticancer drugs, various therapeutic measures have been put in place, such as reducing the accumulation of anticancer drugs, shifting to drugs with less cardiotoxicity, using cardioprotective drugs, and early detection. Due to the very limited treatments available to ameliorate anticancer drugs-induced cardiotoxicity, a few innovations are being shifted from animal studies to human studies. Examples include mitochondrial transplantation. Mitochondrial transplantation has been proven to be effective in in vivo and in vitro experiments. Several recent studies have demonstrated that intercellular mitochondrial transfer can ameliorate doxorubicin(DOX)-induced cardiotoxicity, laying the foundation for innovative therapies in anticancer drugs-induced cardiotoxicity. In this review, we will discuss the current status of anticancer drugs-induced cardiotoxicity in terms of the pathogenesis and treatment, with a focus on mitochondrial transplantation, and we hope that this review will bring some inspiration to you. Keywords: cancer therapy-related cardiovascular toxicity, CTR-CVT, mitochondrial dysfunction, oxidative stress, ferroptosis, mitochondrial transplantation

Shuai Guo,1,&ast; Zhaoting Gong,1,&ast; Xiaona Sun,2 Fei Gao,1 Xiang Li,1 Xiaolin Zu,1 Chao Qu,1 Hongliang Zhang,3 Hai Gao1 1Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Cardiology, Laizhou City People’s Hospital, Laizhou, People’s Republic of China; 3Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hai Gao, Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of China, Email gaohai1221@mail.ccmu.edu.cn Hongliang Zhang, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100037, People’s Republic of China, Email 13810694497@163.comBackground: Ischemic cardiomyopathy (ICM) significantly contributes to global disease burden, while the role of ferroptosis in ICM remains underexplored.Methods: We identified differentially expressed ferroptosis-related genes (DEFRGs) by analyzing the GSE57338 dataset and cross-referencing with FerrDb. Consensus clustering was then used to identify ferroptosis-associated clusters within the ICM samples. A ferroptosis-specific predictive signature was developed using the least absolute shrinkage and selection operator (LASSO) method and validated with the GSE5406 dataset. Additionally, quantitative real-time PCR (qRT-PCR) experiments were performed to validate the 11 feature genes in a rat ICM model.Results: We identified 15 DEFRGs in GSE57338, which distinguished two patient clusters with distinct ferroptosis gene expression, pathway enrichment profiles, and metabolic characteristics. All DEFRGs were upregulated in cluster 2. Potential therapeutic targets were also identified for different ICM patient clusters. The 11-gene predictive signature (TXNRD1, STEAP3, STAT3, SCL2A1, PLIN2, NQO1, NNMT, IL33, ENPP2, ARRDC3, ALOX5) showed robust predictive power in both training and validation sets. High-risk patients exhibited increased infiltration of CD8+ T cells, CD4+ naïve T cells, M0/M1 macrophages, and resting mast cells, along with significant enrichment in epithelial mesenchymal transition and interferon responses. Low-risk patients had higher infiltration of regulatory T cells and monocytes. Results of qPCR analysis confirmed the bioinformatic analysis, validating the expression of the 11 feature genes in the rat ICM model.Conclusion: We identified two ferroptosis-related clusters in ICM patients and developed a predictive signature based on ferroptosis-related genes. Our findings highlight the importance of ferroptosis in ICM and offer new insights for its diagnosis and treatment.Keywords: ischemic cardiomyopathy, ferroptosis, bioinformatics analysis, predictive signature

Jing Shang,1,&ast; Qi Xia,1,&ast; Yuji Sun,2 Hongtao Wang,2 Jia Chen,1 Yue Li,1 Feng Gao,2 Peihao Yin,1,3,4 Zeting Yuan1– 4 1Interventional Cancer Institute of Chinese Integrative Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, People’s Republic of China; 2Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, People’s Republic of China; 3Shanghai Putuo Central School of Clinical Medicine, Anhui Medical University, Shanghai, 200062, People’s Republic of China; 4The Fifth School of Clinical Medicine, Anhui Medical University, Hefei, 230032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zeting Yuan; Peihao Yin, Interventional Cancer Institute of Chinese Integrative Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, People’s Republic of China, Email yuan340202@163.com; yinpeihao@shutcm.edu.cnPurpose: Compared with traditional photothermal therapy (PTT, > 50°C), mild PTT (≤ 45°C) is a promising strategy for tumor therapy with fewer adverse effects. Unfortunately, its anti-tumor efficacy is hampered by thermoresistance induced by overexpression of heat shock proteins (HSPs). In our previous study, we found bufalin (BU) is a glycolysis inhibitor that depletes HSPs, which is expected to overcome thermotolerance of tumor cells. In this study, BU-loaded multifunctional nanoparticles (NPs) were developed for enhancing the mild PTT of colorectal cancer (CRC).Methods: Fe3O4 NPs coated with the polydopamine (PDA) shell modified with polyethylene glycol (PEG) and cyclic arginine-glycyl-aspartic peptide (cRGD) for loading BU (Fe3O4@PDA-PEG-cRGD/BU NPs) were developed. The thermal variations in Fe3O4@PDA-PEG-cRGD/BU NPs solution under different conditions were measured. Glycolysis inhibition was evaluated by measuring the glucose uptake, extracellular lactate, and intracellular adenosine triphosphate (ATP) levels. The cellular cytotoxicity of Fe3O4@PDA-PEG-cRGD/BU NPs was analyzed using a cell counting kit-8 assay, Calcein-AM/PI double staining, and flow cytometry in HCT116 cells. The magnetic resonance imaging (MRI) performance and anti-tumor therapeutic efficacy of Fe3O4@PDA-PEG-cRGD/BU NPs were evaluated in HCT116-tumor bearing mice.Results: Fe3O4@PDA-PEG-cRGD/BU NPs had an average diameter of 260.4± 3.5 nm, the zeta potential of – 23.8± 1.6 mV, the drug loading rate of 1.1%, which had good thermal stability, photothermal conversion efficiencies and MRI performance. In addition, the released BU not only killed tumor cells but also interfered with glycolysis by targeting the steroid receptor coactivator 3 (SRC-3)/HIF-1α pathway, preventing intracellular ATP synthesis, and combating HSP-dependent tumor thermoresistance, ultimately strengthening the thermal sensitivity toward mild PTT both in vitro and in vivo.Conclusion: This study provides a highly effective strategy for enhancing the therapeutic effects of mild PTT toward tumors. Keywords: mild photothermal therapy, glycolysis metabolism, bufalin, HIF-1α, SRC-3

Hongyuan Liu,1,&ast; Yaodi Wei,1,&ast; Zhenyi Xu,2,&ast; Hao Lin,2,&ast; Yu Zhao,1 Shiyu Wang,1 Fengbao Gao,1 Ninghan Feng,2 Alan J Wolfe,3 Fengping Liu1 1Wuxi School of Medicine, Jiangnan University, Wuxi, People’s Republic of China; 2Department of Urology, Affiliated Wuxi No. 2 Hospital, Nanjing Medical University, Wuxi, People’s Republic of China; 3Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA&ast;These authors contributed equally to this workCorrespondence: Alan J Wolfe, Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA, Email awolfe@luc.edu Fengping Liu, Wuxi School of Medicine, Jiangnan University, Wuxi, People’s Republic of China, Email liulaoshiyc@jiangnan.edu.cnPurpose: Patients with recurrent urinary tract infections face complex management challenges. Fecal microbiota transplantation is a superior treatment for chronic infectious diseases, but limited patient knowledge affects treatment decisions. This study aims to identify factors associated with hesitancy towards fecal microbiota transplantation among patients with recurrent urinary tract infections, to help physicians and nurses in providing accurate and useful information to patients.Patients and Methods: A descriptive qualitative approach was employed, utilizing semi-structured interviews conducted with patients experiencing recurrent urinary tract infections who expressed hesitancy towards fecal microbiota transplantation. The interviews took place between September 2021 and December 2022. Thematic analysis was conducted on the semi-structured interviews to identify perceived facilitators and barriers associated with fecal microbiota transplantation.Results: The analysis included interviews with thirty adult female patients with recurrent urinary tract infections. Four facilitators influencing patients’ decision-making regarding fecal microbiota transplantation were identified: (1) the motivating role of hope and expectations for active patient participation; (2) the influence of healthcare providers, as well as family members and friends on patients’ decisions to pursue fecal microbiota transplantation; (3) the patients’ perception of fecal microbiota transplantation as a low-risk treatment option; and (4) the dedication to the advancement of medical treatments. In contrast, two primary barriers to accepting fecal microbiota transplantation were identified: (1) that conventional treatment controls disease activity, while fecal microbiota transplantation effects remain uncertain; and (2) that safety concerns surrounding fecal microbiota transplantation.Conclusion: Comprehensive information about fecal microbiota transplantation, including donor selection, sample processing, the procedure, and potential discomfort, is essential for patients and families to make informed treatment decisions.Registration: CHiCTR2100048970.Keywords: barriers, decision making, facilitators, fecal microbiota transplantation, qualitative study, recurrent urinary tract infections

Fang Gao,1,&ast; Xialin Zhang,2,&ast; Xiaolan Wang,2 Junyan Zhang,3 Fang Wang,1 Yan Zhou,4 Jing Wang,1 Xuewen Li,5 Ruijuan Zhang2 1Department of Prevention Care in Healthcare, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of Hematology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 3Department of Clinical Epidemiology and Evidence-Based Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 4Department of Laboratory, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 5Department of Cardiology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ruijuan Zhang; Xuewen Li, Email 13593169668@163.com; xuewenli1010@126.comPurpose: To determine the current status of vitamin D status and the associated factors for its deficiency among Chinese hospital staff.Methods: The physical examination data of 2509 hospital staff members was analyzed alongside that of 1507 patients who visited the hospital during the corresponding period of the examination. Serum concentration of 25-hydroxyvitamin D (25(OH)D) were measured in the participants. The hospital staff also completed surveys about general information, laboratory examination, and occupational characteristics.Results: The median vitamin D status (serum 25(OH)D concentration) of the participants was 9.0 ng/mL, ranging from 6.5 to 44.7 ng/mL, and the prevalence of deficiency (< 12.3 ng/mL) was 81.47% (2044/2509). The multivariable logistic regression revealed that nurses (OR = 1.54, 95% CI 1.09– 2.19, p = 0.015), BMI below 18 (OR = 2.39, 95% CI 1.02– 5.58, p = 0.045) associated with higher prevalence of vitamin D deficiency. In the contrast, age above 30 (OR = 0.69, 95% CI 0.53– 0.91, p = 0.009) and a high level of uric acid (OR = 0.56, 95% CI 0.41– 0.78, p = 0.001) associated with lower prevalence of vitamin D deficiency. The prevalence of vitamin D deficiency was higher among the hospital staff (81.47%) compared to the patients who visited the hospital during the same time period (65.69%). A substantial disparity was observed in the propensity score matching dataset (69.14% vs 79.94%, p < 0.001).Conclusion: Hospital staff are a high-risk group for vitamin D deficiency. Paying attention to vitamin D status and supplementation of this vitamin are pertinent aspects of hospital staff health care. Outdoor activities, vitamin D supplementation, and foods rich in vitamin D should be advocated.Keywords: vitamin D deficiency, 25-hydroxyvitamin D, hospital staff, cross-sectional

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

Yifu Chen,1– 3 Yu Xia,1,3,4 Menghao Ren,1,3,4 Wei Zheng,2 Xiao Wang,2 Feng Gao2 1Center for Mind and Brain Sciences, Hunan Normal University, Changsha, 410081, People’s Republic of China; 2Hunan Railway Professional Technology College, Zhuzhou, 412001, People’s Republic of China; 3China Research Center for Mental Health Education of Hunan Province, Hunan Normal University, Changsha, 410081, People’s Republic of China; 4Cognition and Human Behavior Key Laboratory of Hunan Province, Hunan Normal University, Changsha, 410081, People’s Republic of ChinaCorrespondence: Feng Gao, Hunan Railway Professional Technology College, Zhuzhou, 412001, People’s Republic of China, Email 542322378@qq.comPurpose: We aim to explore the relationship between overparenting and social avoidance among emerging adults, and the mediating effects of peer attachment and gender differences.Participants and Methods: A total of 1161 Chinese college students completed the questionnaire. The structural equation model was established to validate the main effect model and the mediation model.Results: The results found that both paternal and maternal overparenting positively predicted social avoidance among emerging adults. Both attachment avoidance and attachment anxiety played a significant mediating role in the relationship between paternal overparenting and social avoidance. Attachment anxiety played a significant mediating role in the relationship between maternal overparenting and social avoidance, while, the mediating effect of attachment avoidance was not significant. In addition, gender differences were found in the mediating effects of peer attachment. The mediating effect of attachment anxiety in males’ families had an opposite-gender matching effect, while in females’ families, the mediating effect of attachment avoidance had an opposite-gender matching effect.Conclusion: This study contributes to the understanding of the effects of overparenting on emerging adults, enriching empirical research in related fields.Keywords: overparenting, social avoidance, peer attachment, gender differences, emerging adults

Yunhao Zhang,1 Xuejiao Zhu,1 Fuer Gao,1 Shulan Yang2 1College of Nursing, Hangzhou Normal University, Hangzhou, People’s Republic of China; 2Department of Nursing, Zhejiang Hospital, Hangzhou, People’s Republic of ChinaCorrespondence: Xuejiao Zhu, College of Nursing, Hangzhou Normal University, Hangzhou, 311121, People’s Republic of China, Email jj_ice@163.comPurpose: Coronary artery disease (CAD) patients frequently face readmissions due to suboptimal disease management. Prediction models are pivotal for detecting early unplanned readmissions. This review offers a unified assessment, aiming to lay the groundwork for enhancing prediction models and informing prevention strategies.Methods: A search through five databases (PubMed, Web of Science, EBSCOhost, Embase, China National Knowledge Infrastructure) up to September 2023 identified studies on prediction models for coronary artery disease patient readmissions for this review. Two independent reviewers used the CHARMS checklist for data extraction and the PROBAST tool for bias assessment.Results: From 12,457 records, 15 studies were selected, contributing 30 models targeting various CAD patient groups (AMI, CABG, ACS) from primarily China, the USA, and Canada. Models utilized varied methods such as logistic regression and machine learning, with performance predominantly measured by the c-index. Key predictors included age, gender, and hospital stay duration. Readmission rates in the studies varied from 4.8% to 45.1%. Despite high bias risk across models, several showed notable accuracy and calibration.Conclusion: The study highlights the need for thorough external validation and the use of the PROBAST tool to reduce bias in models predicting readmission for CAD patients.Keywords: coronary artery disease, readmission, prediction model, systematic review

Yufei Wang,1,&ast; Xiaoteng Ma,1,&ast; Zhiqiang Yang,1,2 Qiuxuan Li,1 Yujie Zhou,1,3 Fei Gao,1,3 Zhijian Wang1,3 1Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Ministry of Education, Beijing, People’s Republic of China; 2Cardio-Metabolic Medicine Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3The Key Laboratory of Remodeling-Related Cardiovascular Disease, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhijian Wang; Fei Gao, Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, the Key Laboratory of Remodeling-related Cardiovascular Disease, Beijing Institute of Heart Lung and Blood Vessel Disease, Anzhen Avenue &num;2, Chaoyang District, Beijing, 100029, People’s Republic of China, Email zjwang1975@hotmail.com; fgaomd@163.comBackground and Aims: Elevated eosinophils typically indicate hypersensitive inflammation; however, their involvement in cardiovascular events remains incompletely understood. We investigated the association between the absolute eosinophil count (AEC) and major adverse cardiovascular and cerebrovascular events (MACCEs) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Additionally, we determine whether the integration of AEC with the SYNTAX II score could improve predictive ability.Methods and Results: The AECs of 1711 patients with ACS undergoing PCI from June 2016 to November 2017 were analyzed on admission. All recruitments were splitted into three groups based on AEC tertiles and 101 participants underwent one or more noteworthy outcomings. The association between AEC and MACCEs (defined as a composite of cardiovascular death, myocardial infarction [MI], and stroke) was tested by Cox proportional-hazards regression analysis. After adjusting for confounders, AEC was independently associated with MACCEs (HR 11.555, 95% CI: 3.318– 40.239). Patients in the lowest AEC tertile (T1) as a reference, those in the higher tertiles had an incrementally higher risk of MACCEs (T3: HR 1.848 95% CI: 1.157– 2.952; P for trend=0.008). Inclusion of AEC enhanced the predictive accuracy of the SYNTAX II score for MACCEs (AUC: from 0.701 [95% CI: 0.646– 0.756] to 0.728 [95% CI: 0.677– 0.780]; DeLong’s test, P = 0.020).Conclusion: AEC is independently linked to MACCEs in ACS patients who underwent PCI, and adds incremental predictive information to the SYNTAX II score.Keywords: absolute eosinophil count, SYNTAX I score, SYNTAX II score, cardiovascular and cerebrovascular events, acute coronary syndrome, percutaneous coronary intervention

Qian-Qian Liao,1,&ast; Yan-Ju Mo,2,&ast; Ke-Wei Zhu,3,4,&ast; Feng Gao,2 Bin Huang,2 Peng Chen,4 Feng-Tian Jing,5 Xuan Jiang,6 Hong-Zhen Xu,1 Yan-Feng Tang,7 Li-Wei Chu,8 Hai-Ling Huang,1 Wen-Li Wang,8 Fang-Ning Wei,9 Dan-Dan Huang,9 Bin-Jing Zhao,9 Jia Chen,9 Hao Zhang1 1Department of Pharmacy, People’s Hospital of Guilin, Guilin, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, People’s Hospital of Guilin, Guilin, People’s Republic of China; 3GuangZhou BaiYunShan Pharmaceutical Holdings CO.,LTD. BaiYunShan Pharmaceutical General Factory, Guangzhou, People’s Republic of China; 4Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 5Department of Respiratory Medicine, Xing An County People’ Hospital, Guilin, People’s Republic of China; 6Department of Hospital Infection Management, People’s Hospital of Guilin, Guilin, People’s Republic of China; 7Department of Geriatrics, People’s Hospital of Guilin, Guilin, People’s Republic of China; 8Department of Laboratory Medicine, People’s Hospital of Guilin, Guilin, People’s Republic of China; 9School of Clinical Pharmacy, Guilin Medical University, Guilin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ke-Wei Zhu, GuangZhou BaiYunShan Pharmaceutical Holdings CO.,LTD. BaiYunShan Pharmaceutical General Factory, No. 88 Yunxiang Road Tonghe Street, Baiyun District, Guangzhou, Guangdong Province, 510515, People’s Republic of China, Tel +86-020-87062636, Fax +86-020-87095309, Email zhukew2018@outlook.comPurpose: The study comprehensively evaluated the prognostic roles of the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), basophil-to-lymphocyte ratio (BLR), and eosinophil-to-lymphocyte ratio (ELR) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).Patients and Methods: Six hundred and nineteen patients with AECOPD and 300 healthy volunteers were retrospectively included into the study. The clinical characteristics of the patients with AECOPD and the complete blood counts (CBCs) of the healthy volunteers were collected. The associations of PLR, NLR, MLR, BLR, and ELR with airflow limitation, hospital length of stay (LOS), C-reactive protein (CRP), and in-hospital mortality in patients with AECOPD were analyzed.Results: Compared with the healthy volunteers, PLR, NLR, MLR, BLR, and ELR were all elevated in COPD patients under stable condition. PLR, NLR, MLR, and BLR were further elevated while ELR was lowered during exacerbation. In the patients with AECOPD, PLR, NLR, and MLR were positively correlated with hospital LOS as well as CRP. In contrast, ELR was negatively correlated with hospital LOS as well as CRP. Elevated PLR, NLR, and MLR were all associated with more severe airflow limitation in AECOPD. Elevated PLR, NLR, and MLR were all associated with increased in-hospital mortality while elevated ELR was associated with decreased in-hospital mortality. Binary logistic regression analysis showed that smoking history, FEV1% predicted, pneumonia, pulmonary heart disease (PHD), uric acid (UA), albumin, and MLR were significant independent predictors ofin-hospital mortality. These predictors along with ELR were used to construct a nomogram for predicting in-hospital mortality in AECOPD. The nomogram had a C-index of 0.850 (95% CI: 0.799– 0.901), and the calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) further demonstrated its good predictive value and clinical applicability.Conclusion: In summary, PLR, NLR, MLR, and ELR served as useful biomarkers in patients with AECOPD.Keywords: healthy volunteers, in-hospital mortality, length of stay, nomogram, pneumonia, pulmonary heart disease

Meng Luo,1,2,&ast; Xue Han,1,2,&ast; Huan Li,1,2 Guangyue Zhou,1,2 Haoxuan Chen,1,2 Fang Gao1,2 1Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 2Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fang Gao, Department of Anesthesiology, the Affiliated Hospital of Xuzhou Medical University, No. 99 Huaihai West Road, Xuzhou, Jiangsu, 221002, People’s Republic of China, Tel +86-18052268331, Email gaofangxz@126.comBackground: Remifentanil-induced hyperalgesia (RIH) increases the risk of persistent postoperative pain, making early postoperative analgesic therapy ineffective and affecting postoperative patient satisfaction. This study aimed to verify the effects of gradual withdrawal of remifentanil combined with postoperative pump infusion of remifentanil on postoperative hyperalgesia and pain in patients undergoing laparoscopic hysterectomy.Methods: This trial was a factorial design, double-blind, randomized controlled trial. Patients undergoing laparoscopic hysterectomy were randomly allocated to the control group, postoperative pump infusion of remifentanil group, gradual withdrawal of remifentanil group, or gradual withdrawal plus postoperative pump infusion of remifentanil group (n = 35 each). The primary outcome was postoperative mechanical pain thresholds in the medial forearm. The secondary outcomes included postoperative mechanical pain thresholds around the incision, pain numeric rating scale scores, analgesic utilization, awakening agitation or sedation scores, a 15-item quality of recovery survey, and postoperative complications.Results: Gradual withdrawal of remifentanil significantly increased postoperative pain thresholds versus abrupt discontinuation (P < 0.05), whereas postoperative infusion did not show significant differences compared to the absence of infusion (P > 0.05). The combined gradual withdrawal and postoperative infusion group exhibited the highest thresholds and had the lowest postoperative pain scores and analgesic requirements as well as the highest quality of recovery scores (P < 0.05). No significant differences were observed for agitation scores, sedation scores, or complication rates (P > 0.05).Conclusion: The novel combined gradual withdrawal and postoperative infusion of remifentanil uniquely attenuates postoperative hyperalgesia, pain severity, analgesic necessity, and improves recovery quality after laparoscopic hysterectomy.Keywords: opioid-induced hyperalgesia, remifentanil-induced hyperalgesia, laparoscopic hysterectomy, mechanical pain thresholds, postoperative recovery

Bai-Bing Gao,1,2,&ast; Qing-qing Zhang,1,&ast; Shu-qin Dong,1,2 Fei Gao,1,2 Xia Liu,3 Jing Wei,3 Yu Lu1 1Department of Endocrinology, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, 225300, People’s Republic of China; 2Dalian Medical University, Dalian, Liaoning, 116044, People’s Republic of China; 3Department of Obstetrics and Gynecology, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, 225300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu Lu; Jing Wei, Email luyu_666@126.com; qlm_weijin@163.comAim: We investigate the association of mammalian sterile line 20-like kinase 1 (MST1) in the first trimester with the risks of gestational diabetes mellitus (GDM) and adverse pregnancy outcomes.Methods: Pregnancies were recruited during their first antenatal care visit between 8 and 12 gestational weeks. These pregnancies underwent an oral glucose tolerance test between 24 and 28 gestational weeks and were followed up until delivery. Serum MST1 levels at 8– 12 gestational weeks and 24– 28 gestational weeks were measured using an enzyme-linked immunosorbent assay (ELISA) kit. Logistic regression models were used to evaluate the association between MST1 levels in the first trimester and the risks of GDM and adverse pregnancy outcomes.Results: This cohort study enrolled a total of 231 pregnancies. GDM was present in 42 (18.18%) women. Compared to the normal glucose tolerance (NGT) group, the GDM group had higher levels of FPG, HOMA-IR, and MST1 both in the first and second trimesters, but had lower HOMA-β levels only in the second trimester. Then participants were classified according to the median MST1 value in the first trimester. Incidences of GDM, composite adverse pregnancy outcomes, preterm birth, and macrosomia increased in women with higher MST1 values. Serum MST1 in the first trimester was correlated with FPG, 1hr PG, 2hr PG, and HOMA-IR, while inversely correlated with HOMA-β in the second trimester. Furthermore, after adjusting for traditional risk factors, women with higher first-trimester MST1 values had greater odds of GDM, composite adverse pregnancy outcomes, preterm birth, and macrosomia (aOR 2.276, P=0.030; aOR 2.690, P=0.003; aOR 3.210, P=0.048; aOR 5.488, P=0.010).Conclusion: Elevated levels of MST1 in the first trimester of pregnancies are associated with increased risks of GDM and adverse pregnancy outcomes.Keywords: mammalian sterile line 20-like kinase 1, gestational diabetes mellitus, adverse pregnancy outcome, blood glucose

Jiangnan Wu,1,&ast; Chao Zhang,2,&ast; Feng He,3,&ast; Yuan Wang,4 Liangnan Zeng,5 Wei Liu,6 Di Zhao,7 Jingkun Mao,1 Fei Gao8 1Department of Artificial Intelligence, Tianjin University of Technology, Tianjin, People’s Republic of China; 2Sixth Department of Oncology, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 3The Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 4Department of Neurosurgery, Tangshan Gongren Hospital, Tangshan, People’s Republic of China; 5Department of Nursing, Chengdu Fifth People’s Hospital, The Fifth People’s Hospital Affiliated to Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 6Hebei Psychological Counselor Association, Shijiazhuang, People’s Republic of China; 7Department of Neurosurgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 8Hebei General Hospital, Shijiazhuang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Di Zhao; Fei Gao, Tel +86-13363833833 ; +86-13933173693, Email 179381749@qq.com; 27909361@qq.comBackground: The intention to leave among intensive care unit (ICU) healthcare professionals in China has become a concerning issue. Therefore, understanding the factors influencing the intention to leave and implementing appropriate measures have become urgent needs for maintaining a stable healthcare workforce.Objective: This study aims to investigate the current status of intention to leave among ICU healthcare professionals in China, explore the relevant factors affecting this intention, and provide targeted recommendations to reduce the intention to leave among healthcare professionals.Methods: A cross-sectional survey was conducted, involving ICU healthcare professionals from 3-A hospitals of the 34 provinces in China. The survey encompassed 22 indicators, including demographic information (marital status, children, income), work-related factors (weekly working hours, night shift frequency, hospital environment), and psychological assessment (using Symptom Checklist-90 (SCL-90)). The data from a sample population of 3653 individuals were analyzed using the extreme gradient boosting (XGBoost) method to predict intention to leave.Results: The survey results revealed that 62.09% (2268 individuals) of the surveyed ICU healthcare professionals expressed an intention to leave. The XGBoost model achieved a predictive accuracy of 75.38% and an Area Under the Curve (AUC) of 0.77.Conclusion: Satisfaction with income was found to be the strongest predictor of intention to leave among ICU healthcare professionals. Additionally, factors such as years of experience, night shift frequency, and pride in hospital work were found to play significant roles in influencing the intention to leave.Keywords: ICU healthcare professionals, intention to leave, cross-sectional survey, extreme gradient boosting, XGBoost

Lu Chen,1,&ast; Yu Zhong,2,&ast; Yong-Sheng Li,3 He Zhuang,4 Xin Li,5 Sheng-Ping Liu,5 Jing-Gang Li,5 Qiu Lin,4 Fei Gao5 1Department of Paediatrics, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics and Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350000, People’s Republic of China; 2Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou, 350122, People’s Republic of China; 3Department of Urology, Fujian Medical University Union Hospital, Fuzhou, 350001, People’s Republic of China; 4Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou, 350001, People’s Republic of China; 5Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou, 350001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fei Gao, Email xuzhougaofei@126.comBackground: Accurate, sensitive, and rapid identification of leukemia cells in blood and bone marrow is of paramount significance for clinical diagnosis. An integrative technique combining traditional cytomorphology with immunophenotyping was proposed to improve the diagnostic efficiency in leukemia. On account of high photostability, biocompatibility, and signal-to-background ratio, upconversion nanoparticles (UCNPs) as luminescent labels have drawn substantial research scrutiny in immunolabeling.Methods: To achieve simultaneous determination, NaYF4:Yb,Er UCNPs were coupled with CD38 antibodies to construct immunofluorescence probes that were developed to bind to diffuse large B cell lymphoma (DLBCL) cells, followed by Wright’s staining that has been widely used in clinical work for morphological diagnosis. Further, the experimental conditions were optimized, such as medium, slice-making method, antibody dosage, incubation time, etc.Results: The cell morphology and immunolabeling could be observed simultaneously, and its simple operation rendered it a possibility for clinical diagnosis. The developed immunolabeling assay could achieve DLBCL cell counting with high reproducibility and stability, and the detection limit was as low as 1.54 cell/slice (> 3 σ/s). Moreover, the proposed method also realized real blood and bone marrow sample analysis, and the results were consistent with the clinical diagnosis.Conclusion: Overall, this strategy can be carried out after simple laboratory training and has prospective biomedical applications in leukemia classification, diagnosis validation, and differential diagnostics.Graphical Abstract: Keywords: leukemia, upconversion nanoparticle, immunofluorescence probe, Wright’s staining, cytomorphology

Shanshan Li,1,&ast; Cheng Yang,1,&ast; Junqiang Li,1,&ast; Chao Zhang,1 Liaoliao Zhu,1 Yang Song,1 Yongdong Guo,1 Ronglin Wang,1 Dongxue Gan,1 Jingjie Shi,1 Peixiang Ma,1 Fei Gao,2 Haichuan Su1 1Department of Oncology, The Second Affiliated Hospital, Air Force Medical University, Xi’an City, People’s Republic of China; 2Center for Peptide Functional Materials and Innovative Drugs, Institute of Translational Medicine, Shanghai University, ShangHai City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haichuan Su, Department of Oncology, The Second Affiliated Hospital, Air Force Medical University, No. 569 Xinsi Road, Baqiao District, Xi’an City, People’s Republic of China, Email suhc@fmmu.edu.cn Fei Gao, Center for Peptide Functional Materials and Innovative Drugs, Institute of Translational Medicine, Shanghai University, No. 99 ShangDa Road, BaoShan District, ShangHai City, People’s Republic of China, Email flyhightly@shu.edu.cnAbstract: Pluronic F127 hydrogel biomaterial has garnered considerable attention in wound healing and repair due to its remarkable properties including temperature sensitivity, injectability, biodegradability, and maintain a moist wound environment. This comprehensive review provides an in-depth exploration of the recent advancements in Pluronic F127-derived hydrogels, such as F127-CHO, F127-NH2, and F127-DA, focusing on their applications in the treatment of various types of wounds, ranging from burns and acute wounds to infected wounds, diabetic wounds, cutaneous tumor wounds, and uterine scars. Furthermore, the review meticulously examines the intricate interaction mechanisms employed by these hydrogels within the wound microenvironment. By elucidating the underlying mechanisms, discussing the strengths and weaknesses of Pluronic F127, analyzing the current state of wound healing development, and expanding on the trend of targeting mitochondria and cells with F127 as a nanomaterial. The review enhances our understanding of the therapeutic effects of these hydrogels aims to foster the development of effective and safe wound-healing modalities. The valuable insights provided this review have the potential to inspire novel ideas for clinical treatment and facilitate the advancement of innovative wound management approaches.Keywords: Pluronic F127, F127-CHO, F127-NH2, F127-DA, wound healing and repair

Fei Gao,1,&ast; Yang Zhou,2,3,&ast; Xiaoming Yan,4,&ast; Haozhang Huang,2,3,5 Guoxiao Liang,2,3 Yongyi Xie,6 Qijiong Zhu,7 Ziming Chen,8 Bo Wang,2,3 Huanqiang Li,2,3 Ziling Mai,2,3,9 Ming Ying,2,3 Jin Liu,2,3 Shiqun Chen,2,3 Jiyan Chen2,3,10 1Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China; 3Department of Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China; 4Department of Information Technology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China; 5The Second School of Clinical Medicine, Southern Medical University, Guangzhou, People’s Republic of China; 6School of Pharmacy, Guangdong Medical University, Dongguan, People’s Republic of China; 7School of Public Health, Guangdong Medical University, Dongguan, People’s Republic of China; 8School of Foreign Studies, Southern Medical University, Guangzhou, People’s Republic of China; 9School of Biology and Biological Engineering, South China University of Technology, Guangzhou, People’s Republic of China; 10Guangdong Provincial People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shiqun Chen, Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China, Email shiqunchen@126.com Jiyan Chen, Department of Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China, Tel +86 2083827812-10528, Fax +86 2083851483, Email chenjiyandr@126.comBackground: Diabetes mellitus (DM) patients with increased urinary albumin creatinine ratio (uACR) have higher risk of mortality, while it is unclear in DM patients with atherosclerotic cardiovascular disease (ASCVD).Methods: We analysed 2832 DM patients with ASCVD in this multi-center registry cohort study Cardiorenal ImprovemeNt II (CIN-II) in 5 Chinese tertiary hospitals from 2007 to 2020. Patients were divided into 3 groups according to their uACR level (normal group: uACR < 30mg/g, moderately increased group: 30mg/g≤ uACR < 300mg/g, severely increased group: 300mg/g≤ uACR). The main outcome of the study was cardiovascular mortality and all-cause mortality.Results: During a median follow-up of 2.1 years, among 2832 patients (mean age: 63.3 ± 9.9 years, 29.1% women), 434 patients (15.3%) had moderately increased uACR, and 203 patients (7.2%) had severely increased uACR. Compared to patients in normal group, patients had higher cardiovascular mortality in moderately increased group and severely increased group (2.5% vs 9.9% vs 16.7%, P < 0.001), as well as all-cause mortality. After adjusting confounders, the risk of cardiovascular mortality remained higher in moderately increased group (adjusted hazard ratio [aHR]: 3.13; 95% confidence interval [CI]: 2.04– 4.81) and severely increased group (aHR: 4.54; 95% CI: 2.58– 8.01) than in normal group, as well as all-cause mortality.Conclusion: In our study, we found nearly a quarter of DM patients with ASCVD had increased uACR, and they have over 2- or 3-fold risk of cardiovascular mortality than those with normal uACR. UACR is a helpful indicator for risk stratification and treatment target for DM patients with ASCVD.Keywords: diabetes mellitus, atherosclerotic cardiovascular disease, urinary albumin creatinine ratio, cardiovascular mortality

Chen T, Gao F, Yang T, et al. Cancer Manag Res. 2020;12:4379–7390. We, the Editors and Publisher of Cancer Management and Research, have retracted the following article. Following publication of the article, concerns were raised about the duplication of images from Figures 2, 5, 6, and 7 with images from other unrelated articles. Specifically, Images for Figures 2C and 7B have been duplicated with images for Figure 2C and Figure 6A from Zhang RN, Wu DM, Wu LP, Gao GW. LncRNA LINC00337 sponges mir-1285-3p to promote proliferation and metastasis of lung adenocarcinoma cells by upregulating YTHDF1. Cancer Cell Int. 2021;21:550. https://doi.org/10.1186/s12935-021-02253-8; Figure 3D from Zhang K, Shao CX, Zhu JD, et al. Exosomes function as nanoparticles to transfer miR-199a-3p to reverse chemoresistance to cisplatin in hepatocellular carcinoma. Biosci Rep. 2020;40(7):BSR20194026. doi: https://doi.org/10.1042/BSR20194026 (RETRACTED) and Figure 7A from Jiang X, Chen D. Circular RNA hsa_circ_0000658 inhibits osteosarcoma cell proliferation and migration via the miR-1227/IRF2 axis. J Cell Mol Med. 2021;25:510–520. https://doi.org/10.1111/jcmm.16105. Images for Figure 5B have been duplicated with images for Figure 5E from Du C, Zhang J, Wang Y, et al. The Long Non-coding RNA LINC01705 Regulates the Development of Breast Cancer by Sponging miR-186-5p to Mediate TPR Expression as a Competitive Endogenous RNA. Front Genet. 2020;11:779. https://doi.org/10.3389/fgene.2020.00779. Images for Figure 6E have been duplicated with images for Figure 5f from Shi X, Liu Z, Liu Z, et al. Long noncoding RNA PCAT6 functions as an oncogene by binding to EZH2 and suppressing LATS2 in non-small-cell lung cancer. EBioMedicine. 2018;37:177-187. https://doi.org/10.1016/j.ebiom.2018.10.004. In addition, the image for Figure 3B, H1650, sh-NC has been duplicated with the image for Figure 7C, H1650(sh-HOTAIRM1), anti-miR-498. The authors did not respond to our queries and were unable to provide an explanation for the duplicated images or provide data for the study. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article and the authors were notified of this. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

GuiYing Dai,1,&ast; JunYu Wang,1 FengLi Gao,2 WenHong Liu,1 Ping Li,1 Bing Wei,1 Jun Yang1,&ast; 1Emergency Medicine Clinical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, & Beijing Key Laboratory of Cardiopulmonary Cerebral Resuscitation, Beijing, People’s Republic of China; 2Nursing Department, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Yang, Emergency Medicine Clinical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, & Beijing Key Laboratory of Cardiopulmonary Cerebral Resuscitation, Beijing, People’s Republic of China, Tel +86-13581846750, Fax +86-51718170, Email yangjun26@sina.comPurpose: To investigate the nursing prediction value of Barthel score, sequential organ failure assessment (SOFA) score and D-dimer on non-ST-elevation myocardial infarction (NSTEMI) inpatients.Methods: The clinical data of 358 NSTEMI patients admitted to the emergency department were analyzed using logistic regression equation and a ROC curve was drawn. The area under ROC curve (AUC) of different indicators was compared. A COX regression model was created, and a survival curve was drawn.Results: There were significant differences in age, D-dimer, WBC, NT-proBNP, EF (%), BI score, MEWS score, and SOFA score between the 28-day death group and the survival group (P

Cuiliu Li, Yunna Zhang, Fang Gao The Second Department of Endocrinology, Cangzhou Central Hospital, Cangzhou, 061001, People’s Republic of ChinaCorrespondence: Cuiliu Li, Tel +8603172075935, Email licuiliu1989@163.comPurpose: To assess changes in pigment epithelium-derived factor (PEDF) levels in patients with metabolic syndrome (MetS) and to investigate sexual dimorphism in serum PEDF levels and their relationships with estradiol.Methods: A total of 318 individuals (145 men, 173 women) who underwent health examinations in our department were selected. Serum PEDF, estradiol and other metabolic parameters were determined. Homeostasis model assessment of insulin resistance (HOMA- IR) and homeostasis model assessment of β-cell function (HOMA-β) were calculated to evaluate insulin resistance and β-cell function, respectively. Multiple linear regression analysis was used to analyse the factors influencing serum PEDF.Results: Serum PEDF levels were significantly higher in subjects with MetS in both men and women (12.09± 2.75 vs 8.97± 3.19 μg/mL in men and 11.31± 2.79 vs 8.40± 2.32 μg/mL in women, MetS vs non-MetS, P< 0.001). Correlation analysis showed that serum PEDF levels were significantly correlated with body mass index (BMI), waist circumference, waist-to-hip ratio, diastolic blood pressure (DBP), fasting and 2-h postprandial glucose, fasting and 2-h postprandial insulin, HOMA-β, HOMA-IR, hemoglobin A1c (HbA1c), alanine aminotransferase (ALT), aspartate aminotransferase (AST), uric acid (UA), triacylglycerol (TG) and high-density lipoprotein cholesterol (HDL-C). Elevated ALT, HOMA-IR and TG were significant predictors of increased PEDF concentrations. In women, estradiol was inversely correlated with PEDF levels (r=− 0.25, P=0.011), and the association was no longer significant after adjustment for ALT.Conclusion: PEDF could be used as a biomarker of MetS in both men and women. This study reported for the first time that circulating PEDF displays sexual dimorphism, which could be related to estrogen. The association between estrogen and circulating PEDF levels was attenuated after adjusting for ALT.Keywords: pigment epithelium-derived factor, metabolic syndrome, sexual dimorphism, estradiol, alanine aminotransferase

Fei Gao,&ast; Cheng Li,&ast; Jiahui Peng, Wei Lu, Wei Zhu, Jian Zhou, Jingyi Lu, Xiaojing Ma Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingyi Lu; Xiaojing Ma, Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 600 Yishan Road, Shanghai, 200233, People’s Republic of China, Tel +86-21-64369181, Fax +86-21-64368031, Email lujingy1@126.com; maxiaojing@sjtu.edu.cnAim: Dickkopf-1 (DKK-1) is a major inhibitor of Wingless protein signaling pathway, which is involved in glucose metabolism and cardiovascular diseases. The aim of the study was to investigate the changes of serum DKK-1 levels after hypoglycemic treatments and the relationship between DKK-1 and clinical parameters.Materials and Methods: The study was a sub-study of a previously published clinical trial (the effect of Acarbose on glycemic variability in patients with type 2 diabetes mellitus using premixed insulin compared to metformin). All subjects underwent anthropometric and biochemical assessments at baseline and endpoint. Serum DKK-1 levels of 92 subjects were measured at baseline and after 12-week hypoglycemic treatment.Results: DKK-1 levels were significantly decreased after hypoglycemic treatment for 12 weeks (P < 0.001). ΔDKK-1 levels were not correlated with improvement of metabolic parameters (all P > 0.05) but were negatively correlated with baseline DKK-1 levels (r = − 0.263, P = 0.011). Spearman correlation showed that baseline DKK-1 levels were positively related to baseline total cholesterol (r = 0.226, P = 0.030) and low-density lipoprotein cholesterol (LDL-C) (r = 0.277, P = 0.007). Compared with the higher baseline DKK-1 group (≥ 3700 pg/mL), subjects in the lower baseline DKK-1 group (< 3700 pg/mL) had significantly lower baseline glycated hemoglobin A1c levels (P = 0.008) and LDL-C levels (P = 0.048). Systolic and diastolic pressure were decreased more significantly in the lower baseline DKK-1 group than that in the higher baseline DKK-1 group (both P < 0.05).Conclusion: Serum DKK-1 levels were decreased after hypoglycemic treatments. Patients with lower baseline DKK-1 levels were featured by more favorable cardiometabolic factors.Keywords: cardiovascular risk factor, dickkopf-1, hypoglycemic treatment, type 2 diabetes mellitus

Xiaolong Ma,1,&ast; Xiaodong Lv,1,&ast; Sihan Feng,1 Ruishan Liu,2,3 Hao Fu,2 Feng Gao,1 Hao Xu2 1Department of Respiratory Medicine, the First Hospital of Jiaxing (Affiliated Hospital of Jiaxing University), Jiaxing, People’s Republic of China; 2Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 3Department of Laboratory Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China&ast;These authors have contributed equally to this workCorrespondence: Feng Gao, Department of Respiratory Medicine, the First Hospital of Jiaxing (Affiliated Hospital of Jiaxing University), No. 1882 South Zhonghuan Road, Jiaxing, 314000, People’s Republic of China, Tel +86 573 825 198 70, Fax +86 573 820 830 06, Email guti-gf@163.com Hao Xu, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79 Qing chun Road, Hangzhou, 310003, People’s Republic of China, Tel +86 571 872 364 23, Fax +86 571 872 364 21, Email xuhao0523@zju.edu.cnPurpose: To investigate the phenotypic and genomic characteristics of the multi-drug resistant and hypervirulent Klebsiella pneumoniae strain recovered from bacteremia.Methods: Antimicrobial susceptibility testing (AST) was performed by the microdilution method. Antimicrobial resistance genes, virulence-associated genes, multilocus sequence typing (MLST), and plasmid replicon were characterized by next-generation sequencing (NGS) and nanopore sequencing. S1 nuclease-pulsed field gel electrophoresis (S1-PFGE) and Southern blotting were performed to characterize the plasmid profile.Results: The hypervirulent colistin- and carbapenem-resistant K. pneumoniae strain DY2009 was identified as ST5571, co-carrying mcr-1, blaNDM-1, and blaOXA-10. In silico analysis found that it was K2 serotype. AST results revealed that DY2009 was resistant to carbapenems, cephalosporins, ciprofloxacin, chloramphenicol, and colistin but remained susceptible to aztreonam, gentamicin, amikacin, and tigecycline. Through the whole-genome analysis, a variety of virulence determinants were identified, including rmpA. Plasmid analysis confirmed that the mcr-1 and blaNDM-1 gene harbored a ∼ 33 kb IncX4 plasmid and a ∼ 44 kb IncX3 plasmid. In contrast, blaOXA-10 was encoded by chromosome.Conclusion: To the best of our knowledge, we first report the clinical hypervirulent K. pneumoniae isolate co-producing MCR-1, NDM-1, and OXA-10 causing bacteremia. We found that mcr-1 and blaNDM-1 genes were located on two self-conjugative epidemic plasmids, contributing to the widespread MCR-1 and NDM-1 in China. The results of this work improve our understanding of the genetic background of colistin- and carbapenem-resistant K. pneumoniae isolate from bacteremia and the resistance mechanisms. Our findings highlight the urgent need for infection control of such strain to prevent it from becoming an extensive-drug resistant clone.Keywords: Klebsiella pneumoniae, NDM-1, MCR-1, OXA-10, rmpA, bacteremia

Hui Xu,1 Shanshan Wang,1 Feng Gao,2 Caihong Li3 1Department of Fundamental Nursing, The Nursing and Health College of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 3Department of Development Planning, Aviation General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Caihong Li, Department of Development Planning, Aviation General Hospital, No. 4, Beiyuan Road, Chaoyang District, Beijing, 100012, People’s Republic of China, Tel +86 10-59520205 ; +86 13811048937, Email lchdct@163.comPurpose: This research intended to investigate vitamin B6, B9, and B12 consumption in relation to the risk of low cognitive performance (LCP) among elderly adults.Patients and Methods: We analyzed data of 2421 participants retrieved from the National Health and Nutrition Examination Survey (NHANES) 2011– 2014 database in this cross-sectional study. Cognitive performance was evaluated by the Consortium to Establish a Registry for Alzheimer’s disease (CERAD) word learning and recall modules, the animal fluency test (AF), and the digit symbol substitution test (DSST). Participants who scored the lowest 25th percentile were categorized in the LCP group. The Dietary Interview-Total Nutrient Intakes dataset was used to determine the dietary intake of B vitamins in the participants. The low intake group and adequate intake group were differentiated based on the recommended dietary allowance. Subgroup analyses were conducted to assess the relations between 3 B vitamins and cognitive performance among different sex, race, and age groups.Results: Compared with low vitamin B6 intake (< 1.7 mg/day), adequate vitamin B6 intake (≥ 1.7 mg/day) corresponded to a 31.7% decrease in LCP odds in the DSST tests. Participants who consumed adequate B9 (≥ 400 mcg/day) were associated with 31.2%, 33.8%, and 46.5% declines in the risk of LCP in the CERAD, AF, and DSST tests in contrast to those having low B9 intake (< 400 mcg/day). Adequate vitamin B12 intake (≥ 2.4 mcg/day) correlated with a lower LCP occurrence in the CERAD, AF, and DSST tests, with 30.5%, 21.5%, and 33.3% reductions, respectively. Further, the relations between 3 B vitamins and cognitive performance varied across different sex, race, and age groups of people.Conclusion: Adequate dietary vitamin B9 and B12 intakes are significantly associated with a better cognitive performance in immediate and delayed memory recall, categorical verbal fluency, processing speed, sustained attention, and working memory among elders assessed in the CERAD, AF, and DSST tests.Keywords: vitamin B6, pyridoxine, B9, folate, B12, cobalamin, cognition, National Health and Nutrition Examination, NHANES, dietary intake

Lu Chen,1 Shan-Yong Zhou,2 Wei Zhu,3 Sheng-Ping Liu,4 Jing-Xi Zhang,5 He Zhuang,5 Jing-Ling Zhang,5 Yong-Sheng Li,6 Fei Gao4 1Department of paediatrics, Fujian Maternity and Child Health Hospital, Fuzhou, 350000, People’s Republic of China; 2Fujian Key Laboratory of Nanomaterials, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, 350002, People’s Republic of China; 3Department of Urology, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, People’s Republic of China; 4Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou, 350001, People’s Republic of China; 5Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou, 350001, People’s Republic of China; 6Department of Urology, Fujian Medical University Union Hospital, Fuzhou, 350001, People’s Republic of ChinaCorrespondence: Fei Gao; Yongsheng Li, Tel/Fax +86 591-83357896-8242, Email xuzhougaofei@126.com; Lysdr163@163.comIntroduction: Cardiac troponin I (cTnI) has been regarded as a gold standard for early diagnosis and prognosis monitoring of acute myocardial infarction (AMI) in clinical practice. Owing to its low concentration in blood, accurate determination of cTnI often requires high sensitivity. However, current established point-of-care (POC) assays are insufficient to meet clinically analytical requirements due to their low sensitivity.Methods: To this end, we established a highly sensitive and reliable POC lateral flow strip based on lanthanide-doped nanoparticles (NPs) for cTnI determination in human blood samples. The capture of cTnI on the lateral flow strip was performed in a sandwich assay, where Eu3+-doped vanadate nanoparticles (GdVO4:30% Eu NPs) were used as luminescent probes to allow quantification.Results: Our platform realized the analytical sensitivity enhancement with limit-of-detection (LOD) as low as 17 pg mL− 1 for cTnI detection, which was lower than the commercial counterpart; meanwhile, it displayed high specificity, excellent reproducibility and outstanding accuracy for analyzing clinical serum samples.Conclusion: Overall, this strategy provided an ultrasensitive, cost-effective and user-friendly platform for on-site cTnI detection, demonstrating the prospect of lanthanide-doped NPs-based POC diagnosis of disease-related biomarkers.Keywords: cardiac troponin I, GdVO4:30% Eu NPs, lateral flow test strip, point-of-care test

No thermodynamic description was performed for the Co-Mg binary system according to literature review. Consequently, this binary system has been investigated by means of CALPHAD (CALculation of PHAse Diagrams) approach in the present work. The experimental phase diagram and thermodynamic data available in the literature were critically assessed. Based on the reliable literature data, a new set of self-consistent thermodynamic parameters for the Co-Mg system is obtained. The calculated results agree well with the experimental data from the literature, indicating the reasonability of the present thermodynamic optimization.

Bing Xu, Mengmeng Yan, Fei Zhou, Desheng Cai, Wenbo Guo, Xiaohui Jia, Runping Liu, Tao Ma, Tong Li, Feng Gao, Penglong Wang, Haimin Lei School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of ChinaCorrespondence: Penglong Wang; Haimin Lei Email wpl581@126.com; hm_lei@126.comBackground: The clinical utility of camptothecin (CPT) is restricted by poor aqueous solubility, high lipophilicity, active lactone ring instability, and off-targeted toxicities. We report here a prostate-specific membrane antigen (PSMA) and esterase dual responsive self-assembled nanoparticles (CPT-WT-H NPs) for highly efficient CPT delivery and effective cancer therapy.Methods and Results: In this study, smart self-assembled nanoparticles CPT-WT-H NPs were elaborately designed and synthesized by combing hydrophobic CPT with hydrophilic PSMA-responsive penta-peptide via a cleavable ester bond. This dual responsive nanoparticle with negatively charged surface first respond to the extracellular PSMA and then to the intracellular esterase, achieving a programmable release of CPT at the tumor site and producing the byproducts of biocompatible glutamic acid and aspartic acid. Our data demonstrated that CPT-WT-H NPs exhibited greatly improved water solubility and stability. Results from MTT and flow cytometry showed CPT-WT-H NPs exhibited significantly higher cytotoxicity as well as apoptosis-inducing activity against PSMA-expressing LNCaP-FGC cells than the non-PSMA-expressing cancer cells, showing excellent cytotoxic selectivity. Moreover, the unique nanostructure provided the efficient transportation of CPT to tumor site, which resulted in the effective inhibition of tumor growth and low systemic toxicity in vivo.Conclusion: CPT-WT-H NPs exhibited excellent in vitro PSMA-response ability and in vivo antitumor activity and safety, holding the promise to become a new and potent anticancer drug. The current research presents a promising strategy for efficient drug delivery.Keywords: CPT prodrug, dual responsive, sequential drug release, prostate-specific membrane antigen, self-assembly

Changjuan Li,1,2 Jianwei Mi,1 Fulai Gao,1 Xinying Zhu,1 Miao Su,1 Xiaoli Xie,1 Dongqiang Zhao1 1Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei Province, People’s Republic of China; 2Department of Gastroenterology, The First Hospital of Handan City, Handan, 056002, Hebei Province, People’s Republic of ChinaCorrespondence: Dongqiang ZhaoDepartment of Gastroenterology, The Second Hospital of Hebei Medical University, No. 215, He ping West Road, Xinhua District, Shijiazhuang, Hebei Province, 050000, People’s Republic of ChinaTel +86 0311 66636179Email hbzdq1998@163.comPurpose: We aimed to compare the histological and/or cytological diagnostic outcomes of EUS-FNA using 19G and 22G needles for solid pancreatic lesions and to evaluate the feasibility and safety of 19G needle.Patients and Methods: Data from patients with solid pancreatic lesions, who underwent EUS-FNA, were retrospectively retrieved from a single tertiary center from June 2017 to January 2021. The sensitivity, specificity, and accuracy of diagnosis, sample adequacy, number and time of punctures, and adverse events, were compared between the 19G and 22G groups. Univariate and multivariate logistic regression analyses were used to identify optimal factors for a correct histological diagnosis.Results: A total of 186 patients (19G group, n = 90; 22G group, n = 96) were analyzed in the study. The higher sensitivity and accuracy were observed in 19G group than those in the 22G group both in histological evaluation (89.3% vs 76%, p = 0.031; 91.1% vs 79.2%, p = 0.023; respectively) and in the combined histological and cytological evaluations (93.3% vs 81.3%, p = 0.027; 94.4% vs 84.3%, p = 0.027, respectively). However, there were no significant differences in specificity, positive predictive value (PPV), and negative predictive value (NPV). The number of needle passes and the puncture time were significantly lower in the 19G group than that in the 22G group (1.66 ± 0.07 vs 2.25 ± 0.08, p < 0.001; 125.4 ± 4.93s vs 169.0 ± 5.6s p < 0.001; respectively). Only 2 cases were failed in the 19G group and no serious complications occurred. Univariate and multivariate logistic analyses suggested that CA199 levels and needle types are related to the accuracy of the EUS-FNA histological diagnosis.Conclusion: EUS-FNA using a 19G needle is effective and safe for solid pancreatic lesions. Compared with the 22G needle, EUS-FNA with a 19G needle can obtain a better histological diagnostic accuracy of solid pancreatic lesions, and with fewer needle passes and in a shorter time.Keywords: sensitivity, specificity, diagnostic accuracy, histology, cytology

Bao Fu,1,2,&ast; Hui Feng,1,3,&ast; Fei Gao,1,2 Xiaoyun Fu1,2 1Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi City, Guizhou Province, People’s Republic of China; 2Severe Acute Pancreatitis Diagnosis and Treatment Center of Guizhou Province, Zunyi City, Guizhou Province, People’s Republic of China; 3Department of Critical Care Medicine, Renhuai People’s Hospital, Renhuai City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoyun FuDepartment of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Dalian Road149, Zunyi City, Guizhou Province, People’s Republic of ChinaTel +8618108522207Fax +8685128608615Email zyyxyfxy@163.comObjective: To observe the relationship between the extrapancreatic necrosis volume and outcomes in patients with severe acute pancreatitis (SAP).Methods: We retrospectively analyzed 125 patients with SAP admitted to Severe Acute Pancreatitis Treatment Center of Guizhou Province from August 2013 to August 2018. All patients had extrapancreatic necrosis. The general clinical data of patients, C-reactive protein (CRP) value within 72 hours of onset, Ranson score, organ failure within 3 days after onset, complications, outcomes, CT severity index (CTSI), extrapancreatic necrosis volume and other information were collected. The correlation between extrapancreatic necrosis volume and hospitalization time, ICU stay, hospitalization cost, and CRP value was analyzed. The incidence of complications was obtained from the electronic medical record system.Results: The mean extrapancreatic necrosis volume was 680 ± 473 mL. The median length of hospital stay was 18.2 (3– 76) days, and the ICU stay was 13.5 (3– 66) days. The extrapancreatic necrosis volume was positively correlated with hospitalization time, ICU stay time, cost of hospitalization and CRP (P < 0.05). The extrapancreatic necrosis volume in organ failure group was significantly higher than that in non-organ failure group (P < 0.05). The extrapancreatic necrosis volume in patients with death was also higher than that in survival (P < 0.05). With the increase of extrapancreatic necrosis volume, the incidence of complications increased significantly. On the basis of extrapancreatic necrosis volume, the ROC curves yielded an AUC of 0.92 (95% CI: 0.83, 0.99) in predicting the mortality, which was higher than Ranson score (0.90, 95% CI 0.82– 0.96) and CTSI (0.85, 0 95% CI 0.77– 0.91).Conclusion: With the increase of extrapancreatic necrosis volume, the incidence of complications increased significantly. The extrapancreatic necrosis volume has the potential to be used as a valuable tool to predict the poor outcome of acute pancreatitis.Keywords: acute pancreatitis, acute necrotic collection, CTSI, Ranson score

Jia Jie Lu, Munila Maimaiti, Huan Liu, Wei Dong Liu, Wen Jia Hui, Xiao Ling Huang, Feng Gao Department of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang Uygur Autonomous Region, People’s Republic of ChinaCorrespondence: Feng GaoDepartment of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, No. 91 Tianchi Road, Urumqi, 830001, Xinjiang Uygur Autonomous Region, People’s Republic of ChinaEmail xjgf0991@163.comBackground: Ulcerative colitis (UC) is one of the main subtypes of inflammatory bowel disease (IBD). The incidence of UC in the Xinjiang region is relatively high in China and the manifestations of UC in Uyghur and Han patients are usually differential. This study aimed to identify potential biomarkers of UC.Methods: All miRNA and mRNA were extracted from the tissue samples obtained from participants in Xinjiang. Differential expression analysis was performed on all mRNAs and miRNAs. The target genes of miRNAs were predicted via three databases. The clusterProfiler package was used for GO and KEGG pathway enrichment analysis.Results: Preliminarily, four miRNAs and 15 genes were associated with the differential manifestations of UC in Uyghur and Han patients. Through the co-expression network construction and further screening in more samples, two miRNAs (hsa-miR-141-5p and hsa-miR-378a-5p) and three genes (ARNTL2, CLDN1 and SLC6A14) were found to be more crucial. These 15 genes were enriched in tight junction, NF-κB, and several other pathways.Conclusion: Two miRNAs (hsa-miR-141-5p and hsa-miR-378a-5p) and three genes (ARNTL2, CLDN1, and SLC6A14) associated with the differential manifestations of UC in Uyghur and Han population were identified, which were potential biomarkers.Keywords: ulcerative colitis, miRNA, biomarkers, Uyghur, Han

Fei Gao,1,&ast; Lingtong Shan,2,&ast; Chong Wang,3,&ast; Xiaoqi Meng,4 Jiapeng Chen,5 Lixiang Han,6 Yangyang Zhang,3 Zhi Li6 1Cardiovascular Department, Huaiyin Hospital of Huai’an City, Huai’an, Jiangsu, People’s Republic of China; 2Department of Thoracic Surgery, Sheyang County People’s Hospital, Yancheng, Jiangsu, People’s Republic of China; 3Department of Cardiovascular Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 4The Second Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 5Xinglin College, Nantong University, Nantong, Jiangsu, People’s Republic of China; 6Department of Cardiovascular Surgery, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhi LiDepartment of Cardiovascular Surgery, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People’s Republic of ChinaTel +86 13770606815Email zhili_cths@163.comYangyang ZhangDepartment of Cardiac Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 Huaihai West Road, Shanghai, 200120, People’s Republic of ChinaTel +86 13818132320Email zhangyangyang_wy@vip.sina.comObjective: To evaluate the powers of European Heart Surgery Risk Assessment System II (EuroSCORE II) and the Society of Thoracic Surgeons (STS) score in predicting in-hospital and medium-term mortality of patients undergoing coronary artery bypass grafting (CABG).Methods: Totally 1628 Chinese patients were included between January 2000 and January 2018. Their perioperative clinical data were collected and the patients were closely followed up. According to the length of follow-up time, the total cohort was divided into 1-year, 2-year, 3-year, 4-year and 5-year groups. The in-hospital and medium-term risk prediction of EuroSCORE II and STS score were comparatively assessed by calibration, discrimination, decision curve analysis (DCA), net reclassification index (NRI), integrated discrimination improvement (IDI) and Bland-Altman analysis.Results: About 36 (2.21%) patients died during hospitalization. Both EuroSCORE II and STS score performed extremely well in predicting in-hospital mortality (area under curve = 0.900 and 0.879, respectively). However, calibration and discrimination analyses showed gradual decrease when these two risk evaluation systems were used to predict mortality during the follow-up period. At the same time, the predictive ability of EuroSCORE II was better than STS score. DCA curves showed that the performances of the two evaluation systems were roughly equal between the threshold probability of 0% to 20%. The percentage of correct reclassification of EuroSCORE II was 21.64% higher than that of STS score in predicting 2-year postoperative mortality. The IDI index showed that the predictive capabilities of these two systems were roughly equivalent. Bland-Altman analysis showed no significant difference between the values of the two systems.Conclusion: EuroSCORE II and STS score have excellent predictive powers in predicting in-hospital mortality of patients undergoing CABG. In particular, EuroSCORE II is superior in calibration and discrimination. The prediction efficiency of the two risk evaluation systems is still acceptable for two-year postoperative mortality, but decreases year by year.Keywords: EuroSCORE II, STS score, coronary artery bypass grafting, in-hospital mortality, medium-term prognosis

Hao Pang, Yongting Zhou, Jie Wang, Hao Wu, Xueyi Liu, Feng Gao, Zhibo Xiao Department of Plastic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, People’s Republic of ChinaCorrespondence: Zhibo XiaoDepartment of Plastic Surgery, The Second Affiliated Hospital of Harbin Medical University, No. 246 Xuefu Avenue, Harbin, Heilongjiang, 150086, People’s Republic of ChinaEmail xiaozhibodoctor@126.comObjective: Human adipose-derived mesenchymal stem cells (ADSCs) have the potential to be applied to solid organ treatments. However, tissue regeneration is limited by the death of transplanted cells. Ischemia is the main cause of the poor outcome. This study aimed to investigate the effect of berberine (BBR) on ADSCs after fat grafting.Methods: The antioxidant BBR on apoptosis and autophagy of ADSCs in vitro ischemia model was induced by hypoxia and serum deprivation (HY/SD). The autophagy promoter rapamycin and autophagy inhibitor 3-MA were incubated separately to investigate the crosstalk between autophagy and apoptosis. Pathway inhibitors further verified whether the autophagy and apoptosis were regulated by AMPK/mTor signaling pathway. Fat survival, fibrosis, level of inflammatory cell infiltration, and the effect of angiogenesis after BBR treatment were observed in vivo.Results: BBR could reduce ROS production and reverse the decreasing cell survival rate. HY/SD would induce apoptosis and autophagy in ADSCs, and BBR could alleviate these processes. After interfering with the level of autophagy, we also proved that apoptosis was regulated by autophagy and changed accordingly. The results also indicated that BBR could protect against autophagy and apoptosis of ADSCs through AMPK/mTor pathway. The treated human-derived adipose tissue was transplanted into BALB/c nude mice, and with the intervention of BBR, the fat grafting had a higher survival rate, lower inflammatory cell infiltration and fibrosis level.Conclusion: Our present study revealed that BBR was a promising anti-autophagy and apoptosis agent for improving the survival rate of ADSCs during cell transplantation.Keywords: adipose derived mesenchymal stem cells, berberine, autophagy, apoptosis, fat grafting

Fan Gao,1,&ast; Hongyan Wang,2,&ast; Xia Li,2 Fanfan Guo,2 Yufei Yuan,2 Xiaona Wang,2 Yidan Zhang,2 Guiqin Bai2 1Clinical Research Center, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guiqin BaiDepartment of Gynecology and Obstetrics, The First Affiliated Hospital of Xi’an Jiaotong University, 277 Yanta West Road, Xi’an, 710061, Shaanxi, People’s Republic of ChinaTel +86-18991232517Email baigq@126.comPurpose: The aim of this study was to compare the differences in the immune microenvironment between HBV-infected pregnant women with a high HBV viral load and healthy pregnant women, with an emphasis on T cell subset alteration.Patients and Methods: We compared the differences of cellular and molecular signatures between HBV-infected and healthy pregnant women by performing single-cell RNA and T cell receptor sequencing of peripheral blood mononuclear cells from 51,836 women in the mid-trimester pregnancy stage. Specific trajectories of the different T clusters throughout the course of T cell differentiation were investigated. Flow cytometry was used to validate the proportion of different T cell subtypes.Results: We identified nine cellular subtypes and found an increased proportion of effector/memory CD8+ T cells in HBV-infected pregnant women. Both CD4+ and CD8+ effector/memory T cells in HBV-related samples expressed higher levels of metallothionein (MT)-related genes (MT2A, MTIE, MTIF, MTIX), metal ion pathways, and multiple inflammatory responses. Among CD8+ T cell clusters, we identified a particular subset of effector/memory CD8+ T cells (CD8-cluster 2) with MTs as the top-ranking genes, which may be enriched in HBV-related samples. These cells showed an increased clonal expansion in HBV infection. Moreover, we found more active immune responses, according to cellular interaction patterns, between immune cell subsets in HBV-infected samples.Conclusion: This study shows significant differences between HBV-infected and healthy samples, including cell clusters, dominant gene sets, T cell function, clonal expansion, and V/J gene usage of T cell clonotypes, and identifies a distinct CD8+ T cell cluster with immune-active and antiviral properties. These findings pave the way for a deeper understanding of the impact of HBV infection on the immune microenvironment during pregnancy.Keywords: single-cell RNA sequencing, HBV infection, pregnancy, immune cells, CD8+ T cells

Sisi Chang,1 Yahui Zhu,2 Yutan Xi,2 Fuyan Gao,2 Juanjuan Lu,2 Liang Dong,1 Chunzheng Ma,1 Honglin Li1 1Department of Oncology, Henan Provincial Hospital of Traditional Chinese Medicine (The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine), Zhengzhou, Henan Province, People’s Republic of China; 2Department of Oncology, Henan University of Traditional Chinese Medicine, Zhengzhou, Henan Province, People’s Republic of ChinaCorrespondence: Chunzheng Ma; Honglin LiHenan Provincial Hospital of Traditional Chinese Medicine (The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine), Zhengzhou, Henan Province, People’s Republic of ChinaTel +86-18801611544Email mchzh666@126.com; 46991701@qq.comPurpose: To evaluate the role of DSCC1 in LUAD.Patients and Methods: Based on TCGA and GTEx, the Wilcoxon rank-sum test was used to compare the expression differences of DSCC1 between the normal samples of GTEx combined TCGA and the unpaired tumor samples of TCGA, and to compare DSCC1 expression values between tumor tissues and paired normal LUAD tissues in the TCGA cohort. Kruskal–Wallis rank-sum test, Wilcoxon rank-sum test, and logistics regression were used to compare the relationship between the expression of DSCC1 and the clinicopathological parameters. The biological function of DSCC1 was annotated by GSEA and ssGSEA, while Kaplan–Meier and Cox regression analysis were used to evaluate the prognostic value of DSCC1. Furthermore, the time-dependent ROC curve was used to analyze the diagnostic efficacy of DSCC1 in LUAD.Results: We downloaded the RNA-Seq data of 513 LUAD cases. The expression of DSCC1 was significantly correlated with T stage (OR = 1.04(1.02– 1.07), P = 0.002), pathological stage (OR=1.03 (1.01– 1.05), P = 0.008) and TP53 status (OR=1.10 (1.07– 1.14), P < 0.001). The high expression of DSCC1 was significantly correlated with DSS (HR=1.56 (1.07– 2.26), P = 0.021) and OS (HR=1.53 (1.14– 2.05), P = 0.004). Moreover, ROC curve analysis (AUC=0.845, CI (0.820-0.870)) indicated DSCC1 as a potential diagnostic molecule for LUAD. In the group with high DSCC1 expression phenotype, down-regulation of EGFR signal, reduction of IL-6 deprivation, cell cycle, and p53 signal pathway were significantly abundant. Spearman correlation analysis showed that the expression of DSCC1 was positively correlated with the infiltration of Th2 cells, T Helper cells.Conclusion: Our results suggest that DSCC1 may be an important biomarker for the treatment of LUAD.Keywords: DSCC1, LUAD, GSEA, prognosis, biomarker

ObjectiveConventional second window indocyanine green (SWIG) technique has been widely attempted in near-infrared fluorescence (NIRF) imaging for intraoperative navigation of tumor radical resection. Nevertheless, the overuse of indocyanine green (ICG) led to an increased risk of drug lethal allergy and high medical cost. This prospective study was to explore clinical application of modified low-dose SWIG technique in guiding dermatofibrosarcoma protuberans (DFSPs) radical resection.MethodPatients with DFSPs were randomly assigned to control and experimental group. The ICG was injected intravenously 24 h before surgery, at a dose of 3.5 mg/kg in the control group and 25 mg/patient in the experiment group, respectively. Intraoperative NIRF imaging included serial views of gross tumor, tumor bed and cross-sectional specimen.ResultsAlthough NIRF imaging of gross tumor and tumor bed in the experimental group demonstrated similar sensitivity and negative predictive value, the specificity and positive predictive value were obviously higher compared to control group. The tumor-to-background ratios of cross-sectional specimens in the experimental group was significantly higher than in the control group (P = 0.000). Data in both groups displayed that there was a positive correlation of tumor size in cross-sections between integrated histopathologic photomicrographs and NIRF imaging of specimen views (P = 0.000). NIRF imaging of cross-sectional specimens had a significant decrease in time cost, and an increase in the ability of examining more surgical margins (P = 0.000).ConclusionThis is the first study to demonstrate that a low-dose SWIG technique could improve the accuracy of near-infrared fluorescence image-guided dermatofibrosarcoma protuberans resection.Clinical Trial Registration: ChiCTR2100050174; date of registration: August 18, 2021 followed by “retrospectively registered”

BackgroundThe goal of the current study was to explore the application of preoperative three-dimensional reconstruction (3DR) based on thin-slice magnetic resonance imaging (MRI) in the simultaneous guidance of en bloc tumor resection and adjacent perforator flap elevation.MethodsThe prospective cohort included 35 patients diagnosed with either soft tissue sarcoma or squamous cell skin cancer between 2019 and 2021. The preoperative 3DR based on thin-slice MRI illustrated the spatial anatomical relationship among the tumor, underlying muscle, adjacent perforator vessels, and bone around the surgical region. The accuracy of preoperative imaging data was verified by intraoperative vessel dissection and postoperative pathological measurements.ResultsTumor size from 3DR data showed relatively high concordance rates with pathological measurements within the 95% limits of agreement. An average of three perforators (range: 1–7) with a mean diameter of 0.32 cm (range: 0.18–0.74 cm) from the 3DR were present in our study. The average distance between tumor boundary and perforator piercing sites on the 3DR was 2.2 cm (range: 1.2–7.7 cm). The average length of artery perforator coursing along the subcutaneous tissue was 5.8 cm (range: 3.3–25.1 cm). The mean flap harvest time was 55 mins (range: 36–97 min). The average flap size was 92.2 cm2 (range: 32–126 cm2). One perforator flap occurred distal partial necrosis.ConclusionA thorough understanding of anatomical structures in the surgical region according to full-field 3DR based on thin-slice MRI can improve the performance of radical resection of the tumor and adjacent perforator flap transfer, especially for junior surgeons with a poor experience.

Zhigang Wang,1,2 Tianlin Liu,1 Chunping Yin,1 Yanan Li,1 Fang Gao,1 Lili Yu,1 Qiujun Wang1 1Department of Anesthesiology, The Third Hospital of Hebei Medical University, Shijiazhuang City, Hebei, People’s Republic of China; 2Department of Anesthesiology, Handan Central Hospital, Handan, Hebei, People’s Republic of ChinaCorrespondence: Qiujun Wang Tel +86 311 8860 2072Email wangqiujunsy@163.comObjective: Postoperative cognitive dysfunction (POCD) after anesthesia and surgery (AS) is a common complication in the elderly population. A cholinergic-dependent signal, the alpha7-nicotinic acetylcholine receptor (α 7-nAChR), has been suggested to regulate cognitive processes in a variety of neurologic diseases. In the current study, we determined whether electroacupuncture (EA) pretreatment ameliorates AS-induced POCD in aged rats, as well as the underlying mechanism.Methods: Male Sprague-Dawley rats (20 months old) were randomly assigned to the following 5 groups (n=12): vehicle; POCD (tibial fracture surgery); EA plus POCD; EA plus POCD and alpha-bungarotoxin (α-BGT); and POCD plus α-BGT groups. Alpha-bungarotoxin (1 μg/kg), a selective antagonist of α 7-nAChR, was administrated via intraperitoneal injection before EA. Thirty days post-AS, the Morris water maze and a novel objective recognition test were used to evaluate cognitive function. Neuronal amount, apoptosis, microglial activation, percentage of high mobility group box 1 (HMGB1)- and nuclear factor-κB (NF-κB)-positive microglia, and levels of HMGB-1 downstream factors, including NF-κB, interleukin-6 (IL-6), and IL-1β, were detected by Nissl staining, immunofluorescence, and Western blot assays.Results: EA pretreatment significantly increased crossing platform times and elevated the time with a novel object, restored the quantity of neurons, decreased TUNEL-positive neurons, alleviated activation of microglia, downregulated expression of HMGB1 and NF-κB in the microglia, and reduced levels of phosphor-NF-κB, IL-6, and IL-1β 35 days after AS, while α-BGT partially reversed these changes.Conclusion: EA pretreatment improved AS-induced POCD in aged rats, and the underlying mechanism may be associated with inhibition of HMGB1–NF-κB via an α 7-nAChR signal in the microglia.Keywords: electroacupuncture, EA, postoperative cognitive dysfunction, POCD, α 7-nicotinic acetylcholine receptor, α 7-nAChR, microglia, high mobility group box 1, HMGB1

Liang Gu,1,2 Yangchen Liu,2 Hongxue Ye,2 Fei Gao,2 Xiaoxiang Yin,2 Ying Zhao,2 Ye Tian1 1Department of Radiation Oncology, The Second Affiliated Hospital of Soochow University, Su Zhou, 215004, Jiang Su Province, People’s Republic of China; 2Department of Radiation Oncology, Taixing People’s Hospital, Tai Xing, 225400, Jiang Su Province, People’s Republic of ChinaCorrespondence: Ye TianDepartment of Radiation Oncology, The Second Affiliated Hospital of Soochow University, 1005 Sanxiang Road, Su Zhou, 215004, Jiang Su Province, People’s Republic of ChinaEmail dryetian@126.comBackground: There are no standard therapeutic strategies for local lymph node (LN) recurrence after radical resection of oesophageal squamous cell carcinoma (ESCC), and prognostic risk factors remain controversial. We assessed clinical outcomes and prognostic factors of chemoradiotherapy (CRT) or radiotherapy (RT) for LN recurrence of ESCC after curative resection.Methods: A total of 117 ESCC patients with LN recurrence after radical resection receiving salvage treatment at our hospital were retrospectively reviewed from 2014 to 2017. Overall survival (OS) was estimated using the Kaplan–Meier method; clinical characteristics were assessed using the Log rank test in the univariate analysis. Multivariate prognostic analysis was performed using the Cox proportional hazard model.Results: With a median follow-up of 19 months, the 1-, 2- and 3-year OS rates were 75.2%, 40.2% and 27.4%, respectively. The median survival time (MST) was 19.0 months. On univariate analysis for OS, pathological TNM stage, number of LN metastasis, LN maximum (Max) diameter, salvage treatment mode and tumor response were significantly associated with OS (P = 0.0074, P = 0.015, P = 0.0011, P = 0.028, P < 0.000, respectively). On multivariate analysis, tumor response [Response vs No-response hazard ratio (HR), 2.43; 95% confidence interval (CI), 1.53– 3.90, P < 0.000] and LN Max diameter (≤ 28 mm vs > 28 mm HR, 2.07; 95% CI, 1.33– 3.32, P = 0.012) were independent prognostic factors.Conclusion: Salvage CRT or RT was safe and effective for treating LN recurrence after radical resection in ESCC. Patients with the small LN Max diameter (≤ 28 mm) and obtained response after salvage therapy appeared to achieve long-term OS.Keywords: oesophageal cancer, lymph node recurrence, chemoradiotherapy

Tianlin Liu,1,2 Chunping Yin,1 Yanan Li,1 Fang Gao,1 Lili Yu,1,2 Zhigang Wang,1 Qiujun Wang1 1Department of Anesthesiology, The Third Hospital of Hebei Medical University, Shijiazhuang City, Hebei, People’s Republic of China; 2Department of Anesthesiology, Cangzhou Central Hospital, Cangzhou, Hebei, People’s Republic of ChinaCorrespondence: Qiujun Wang Tel +86 311 8860 2072Email wangqiujunsy@163.comBackground: Postoperative cognitive decline (POCD) in the old ages seriously delays the rapid recovery. Here, we aimed to investigate the effects of transcutaneous electrical acupoint stimulation (TEAS) against POCD in elderly patients undergoing laparoscopic radical colon cancer surgery, as well as the potential mechanism.Methods: A prospective, single-center, parallel-group, randomized trial was designed. A total of 100 patients (age ≥ 65 years) undergoing laparoscopic radical resection of colon cancer were involved and randomly divided into TEAS (Group T) and control (Group C) groups. The patients in Group T were performed with percutaneous acupoint electrical stimulation in bilateral Hegu, Neiguan and Zusanli points from 30 minutes before anesthesia induction to the end of surgery. A Z-score based on Mini-Mental State Exam (MMSE) was used to assess the incidence of POCD. The levels of serum IL-6, hs-CRP, CGRP at 0 min before TEAS (T0), 1 h after beginning of surgery (T1) and the end of surgery (T2) were evaluated.Results: Our data showed that the cumulative duration of POCD on postoperative day 2 and 3 in Group T was significantly decreased compared to Group C (P < 0.05). Compared with T0, the levels of serum IL-6, hs-CRP, and CGRP in both Group T and C were statistically elevated at T1 and T2 (P < 0.05). Moreover, the levels of serum IL-6 and hs-CRP were decreased, but the level of CGRP was increased in Group T compared to Group C at T1 and T2 (P < 0.05).Conclusion: TEAS is associated with a lower cumulative duration of POCD in elderly patients undergoing laparoscopic radical colon cancer surgery, which may be related to the regulation of inflammatory factors and neuropeptides interacted with gut–brain axis.Keywords: cognitive decline, gut–brain axis, transcutaneous electrical acupoint stimulation, colon cancer, elder

Xinjian Xu,1,* Yiwen Ding,1,* Tianfan Pan,1 Feng Gao,1 Xiangzhong Huang,1 Qiulian Sun2 1Department of Interventional Radiology, Jiangyin People’s Hospital, Jiang Yin City, Jiangsu Province, 214400, People’s Republic of China; 2Department of Radiology, Zhejiangtaizhou Hospital, Taizhou City, Zhejiang Province, 317000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiangzhong Huang; Qiulian Sun Email hxzdoc@163.com; sql947435865@163.comPurpose: To investigate the efficacy and safety of CT-guided 125I brachytherapy in the treatment of hepatocellular carcinoma (HCC) refractory to conventional transarterial chemoembolization (TACE).Methods: Nineteen patients with TACE-refractory HCC treated with CT-guided 125I brachytherapy between June 2017 and June 2020 at Jiangyin People’s Hospital were enrolled in this study. In addition, we used the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria to evaluate the treatment response after 125I brachytherapy.Results: Twenty-one tumours were treated with CT-guided 125I brachytherapy in nineteen patients. Twelve tumours (57.1%) showed a complete response, and a partial response was observed in seven tumours (33.3%). The six-month objective response rate was 90.5% (19/21). The adverse effects of CT-guided 125I brachytherapy were tolerable.Conclusion: Our preliminary clinical experience demonstrated that CT-guided 125I brachytherapy was effective and well tolerated for the treatment of TACE-refractory HCC, suggesting that CT-guided 125I brachytherapy has the potential to become an effective alternative treatment for TACE-refractory HCC.Keywords: 125I brachytherapy, TACE, refractory, hepatocellular carcinoma

Xiaohui Huang,1,* Ze Yu,2,* Shuhong Bu,1 Zhiyan Lin,1 Xin Hao,3 Wenjun He,2 Peng Yu,2 Zeyuan Wang,2 Fei Gao,2 Jian Zhang,1 Jihui Chen1 1Department of Pharmacy, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Beijing Medicinovo Technology Co. Ltd., Beijing, People’s Republic of China; 3Dalian Medicinovo Technology Co. Ltd., Dalian, Liaoning Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jihui Chen; Jian ZhangDepartment of Pharmacy, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of ChinaTel +86-2125077155; +86-2125077150Email chenjihui@xinhuamed.com.cn; zhangjian@xinhuamed.com.cnPurpose: This study aimed to establish an optimal model to predict vancomycin trough concentrations by using machine learning.Patients and Methods: We enrolled 407 pediatric patients (age < 18 years) who received vancomycin intravenously and underwent therapeutic drug monitoring from June 2013 to April 2020 at Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine. The median (interquartile range) age and weight of the patients were 2 (0.63– 5) years and 12 (7.8– 19) kg. Vancomycin trough concentrations were considered as the target variable, and eight different algorithms were used for predictive performance comparison. The whole dataset (407 cases) was divided into training group and testing group at the ratio of 80%: 20%, which were 325 and 82 cases, respectively.Results: Ultimately, five algorithms (XGBoost, GBRT, Bagging, ExtraTree and decision tree) with high R 2 (0.657, 0.514, 0.468, 0.425 and 0.450, respectively) were selected and further ensembled to establish the final model and achieve an optimal result. For missing data, through filling the missing values and model ensemble, we obtained R 2=0.614, MAE=3.32, MSE=24.39, RMSE=4.94 and a prediction accuracy of 51.22% (predicted trough concentration within ± 30% of the actual trough concentration). In comparison with the pharmacokinetic models (R 2=0.3), the machine learning model works better in model fitting and has better prediction accuracy.Conclusion: Therefore, the ensemble model is useful for the vancomycin concentration prediction, especially in the population of children with great individual variation. As machine learning methods evolve, the clinical value of the ensemble model will be demonstrated in the clinical practice.Keywords: machine learning, XGBoost, prediction, vancomycin, trough concentration, pediatric patients

Kangfa Huang,1 Chengde Li,1 Fenglei Gao,2 Yushan Fan,1 Fanwen Zeng,1 Li Meng,1 Li Li,1 Shouquan Zhang,1 Hengxi Wei1 1National Engineering Research Center for Breeding Swine Industry, Guangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, 510642, People’s Republic of China; 2Department of Tropical Agriculture and Forestry, College of Guangdong Agriculture Industry Business Polytechnic, Guangzhou, Guangdong, 510507, People’s Republic of ChinaCorrespondence: Hengxi WeiNational Engineering Research Center for Breeding Swine Industry, Guangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, 510642, People’s Republic of ChinaTel +86-20-85284869Email weihengxi@scau.edu.cnPurpose: Epigallocatechin-3-gallate (EGCG) is a major ingredient of catechin polyphenols and exerts protective effects because of its strong antioxidant properties. As far as we know, there is still a lack of systematic research on the effects of EGCG on the in vitro maturation (IVM) and in vitro fertilization (IVF) of porcine oocytes. The present study aimed to determine the effects of EGCG on the IVM and IVF of porcine oocytes.Methods: Porcine oocytes were treated with different concentrations of EGCG (5, 10 and 20 μM), and the cumulus cell expansion, oocyte maturation rate, reactive oxygen species (ROS), glutathione (GSH) and malondialdehyde (MDA) levels, total antioxidant capacity were determined. The mRNA expression levels of oxidative stress- and apoptosis-associated genes were determined by quantitative real-time PCR. The cleavage rate and blastocyst rate of oocytes after 10 μM EGCG treatment during IVM and IVF were also evaluated.Results: EGCG at 5, 10 and 20 μM significantly promoted cumulus cell expansion, and EGCG at 10 μM increased the oocyte maturation rate. EGCG (10 μM) treatment reduced the ROS and MDA levels, while increased the antioxidant capacity and GSH concentrations in the mature oocytes. The qRT-PCR results showed that EGCG treatment up-regulated the mRNA expression of catalase, glutathione peroxidase and superoxide dismutase in the mature oocytes. In addition, EGCG treatment also decreased the mRNA expression levels of Bax and caspase-3 and increased the Bcl-2 mRNA expression level in the mature oocytes. In addition, the cleavage rate and blastocyst rate of oocytes treated with 10 μM EGCG during IVM and IVF were significantly higher than those of the control group.Conclusion: Our results suggest that EGCG promotes the in vitro maturation and embryo development following IVF of porcine oocytes. The protective effects of EGCG on the oocytes may be associated with its antioxidant and anti-apoptosis properties.Keywords: EGCG, porcine oocytes, IVM, antioxidant, anti-apoptosis, IVF

Ting Yang1 1, Yaqun Zhou1 1, Wen Zhang1 1, Longqing Zhang1 1, Shuping Chen1 1, Chao Chen1 1, Feng Gao1 1, Hui Yang1 1, Anne Manyande2 2, Jie Wang3 3, Yuke Tian1 1, Xuebi Tian1 1 1Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2School of Human and Social Sciences, University of West London, London, UK; 3State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Key Laboratory of Magnetic Resonance in Biological Systems, Wuhan Center for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, Hubei, People’s Republic of ChinaCorrespondence: Xuebi TianDepartment of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue 1095#, Wuhan, Hubei, 430030, People’s Republic of ChinaTel +862783663423Fax +862783662853Email Tianxb@hust.edu.cnIntroduction: Cancer-induced bone pain (CIBP) is acknowledged as a multifactorial chronic pain that tortures advanced cancer patients, but existing treatment strategies for CIBP have not been satisfactory yet. Investigators have demonstrated that the activation of α 7-nAChRs exerts analgesic effects in some chronic pain models. However, the role of spinal α 7-nAChRs in CIBP remains unknown. This study was designed to investigate the role of α 7-nAChRs in a well-established CIBP model induced by Walker 256 rat mammary gland carcinoma cells.Methods: The paw withdrawal threshold (PWT) of the ipsilateral hind paw was measured using von Frey filament. The expressions of spinal α 7-nAChRs and NF-κB were measured with Western blotting analysis. Immunofluorescence was employed to detect the expression of α 7-nAChRs and co-expressed of α 7-nAChRs with NeuN or GFAP or Iba1.Results: Experiment results showed that the expression of spinal α 7-nAChRs was significantly downregulated over time in CIBP rats, and in both CIBP rats and sham rats, most of the α 7-nAChRs located in neurons. Behavioral data suggested PNU-282,987, a selective α 7-nAChRs agonist, dose-dependently produced analgesic effect and positive allosteric modulator could intensify its effects. Further, repeated administration of PNU-282,987 reversed the expression of α 7-nAChRs, inhibited the nuclear factor kappa B (NF-κB) signaling pathway, and attenuates CIBP-induced mechanical allodynia state as well.Conclusion: These results suggest that the reduced expression of spinal α 7-nAChRs contributes to the maintenance of CIBP by upregulating NF-κB expression, which implying a novel pharmacological therapeutic target for the treatment of CIBP.Keywords: cancer-induced bone pain, α 7-nAChR, NF-κB, PNU-282,987

Shengyu Zhou,1,2,* Jiawei Xu,1,* Wenqing Sun,3 Jintao Zhang,1 Fayan Zhang,4 Xuesong Zhao,5 Ximing Wang,6 Wei Zhang,7 Yu Li,1 Kang Ning,8 Yun Pan,1 Tian Liu,1 Jiping Zhao,1 Jiguang Yu,9 Yunbo Sun,10 Feng Gao,11 Rumin Zhang,12 Chunsheng Fu,13 Yu Sun,14 Xiuhe Ouyang,15 Fusen Zhang,16 Qing Hu,17 Haifeng Teng,18 Yun Li,19 Chunke Zhang,20 Wei Tan,21 Jinlai Li,22 Lixia Yin,23 Liang Dong,1 Chunting Wang5 1Department of Respiratory and Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 2Clinical Nursing Department, School of Nursing, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 3Intensive Care Unit, Shandong Provincial Chest Hospital, Jinan, People’s Republic of China; 4College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 5Department of Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 6Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong University, Jinan, People’s Republic of China; 7Department of Lung Disease, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 8The First Affiliated Hospital of Shandong First Medical University Shandong Provincial Qianfoshan Hospital, Jinan, People’s Republic of China; 9Department of Infectious Diseases, Qishan Hospital, Yantai, People’s Republic of China; 10Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 11Department of Infectious Disease, Linyi People’s Hospital, Linyi, People’s Republic of China; 12Department of Critical Care Medicine, Zibo Central Hospital, Zibo, People’s Republic of China; 13Liaocheng Contagion Hospital, Liaocheng, People’s Republic of China; 14Jining Hospital of Infectious Diseases, Jining, People’s Republic of China; 15Department of Respiratory and Critical Medicine, Binzhou People’s Hospital, Binzhou, People’s Republic of China; 16Intensive Care Unit, Taian City Central Hospital, Taian, People’s Republic of China; 17Department of Respiratory Medicine, Heze Municipal Hospital, Heze, People’s Republic of China; 18Weihai Municipal Hospital, Weihai, People’s Republic of China; 19Jinan Central Hospital, Jinan, People’s Republic of China; 20Weihai Central Hospital, Weihai, People’s Republic of China; 21Department of Respiratory Medicine, Weifang People’s Hospital, Weifang, People’s Republic of China; 22Intensive Care Unit, Zaozhuang Municipal Hospital, Zaozhuang, People’s Republic of China; 23Department of Respiratory Medicine, Dezhou People’s Hospital, Dezhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liang Dong; Chunting Wang Email dl5506@126.com; wcteicu@126.comBackground: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel pathogen, has caused an outbreak of coronavirus disease 2019 (COVID-19) that has spread rapidly around the world. Determining the risk factors for death and the differences in clinical features between severely ill and critically ill patients with SARS-CoV-2 pneumonia has become increasingly important.Aim: This study was intended to provide insight into the difference between severely ill and critically ill patients with SARS-CoV-2 pneumonia.Methods: In this retrospective, multicenter cohort study, we enrolled 62 seriously ill patients with SARS-CoV-2 pneumonia who had been diagnosed by March 12, 2020. Clinical data, laboratory indexes, chest images, and treatment strategies collected from routine medical records were compared between severely ill and critically ill patients. Univariate and multivariate logistic regression analyses were also conducted to identify the risk factors associated with the progression of patients with severe COVID-19.Results: Of the 62 patients with severe or critical illness, including 7 who died, 30 (48%) patients had underlying diseases, of which the most common was cardiovascular disease (hypertension, 34%, and coronary heart disease, 5%). Compared to patients with severe disease, those with critical disease had distinctly higher white blood cell counts, procalcitonin levels, and D-dimer levels, and lower hemoglobin levels and lymphocyte counts. Multivariate regression showed that a lymphocyte count less than 109/L (odds ratio 20.92, 95% CI 1.76– 248.18; p=0.02) at admission increased the risk of developing a critical illness.Conclusion: Based on multivariate regression analysis, a lower lymphocyte count (< 109/L) on admission is the most critical independent factor that is closely associated with an increased risk of progression to critical illness. Age, underlying diseases, especially hypertension and coronary heart disease, elevated D-dimer, decreased hemoglobin, and SOFA score, and APACH score also need to be taken into account for predicting disease progression. Blood cell counts and procalcitonin levels for the later secondary bacterial infection have a certain reference values.Keywords: SARS-CoV-2, COVID-19, clinical features, severely ill patients, critically ill patients