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Tianhao Cong,1 Chao Yang,1 Qi Cao,2 Jinrui Ren,1 Yingen Luo,1 Pei Yuan,2 Bo Zheng,2 Yu Liu,1 Hongcai Yang,1 Wendi Kang,1 Aixin Ou,1 Xiao Li1 1Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Xiao Li, Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China, Tel +86-13910309111, Fax +86-028-88092354, Email simonlixiao@gmail.comPurpose: Transarterial chemoembolization (TACE) represents a significant therapeutic modality for hepatocellular carcinoma (HCC). We aimed to develop a gene signature to accurately predict patient TACE response and explore the underlying mechanisms.Methods: Three independent datasets were utilized, including GSE104580, GSE14520 and external validation from the Cancer Hospital Chinese Academy of Medical Sciences. GSE104580 was randomly partitioned into a training set and a validation set, whereas GSE14520 was categorized into a resection group and a TACE group. Logistic regression was used to develop a TACE effectiveness model. Immunohistochemistry is utilized to confirm the protein expression trends of the signature genes. Immune infiltration and functional enrichment analyses were conducted to investigate the potential underlying mechanisms.Results: A 2-gene signature consisting of glycine N-methyltransferase (GNMT) and matrix metalloproteinase-12 (MMP12) was constructed, and based on this, all the patients were assigned TACE effectiveness scores and categorized into high effectiveness (HE) and low effectiveness (LE) groups. The HE group exhibited a better prognosis than the LE group in the various cohorts (p < 0.05). In the external validation set, immunohistochemistry confirmed the expression of the signature genes exhibiting an upregulated trend of GNMT in the HE group and MMP12 in the LE group, the LE group also exhibited a poorer prognosis [for overall survival (OS), HE group: 881 days vs LE group: 273 days (p < 0.05), and for progression-free survival (PFS), HE group: 458 days vs LE group: 136 days (p < 0.05)]. Multivariate analysis in all the datasets identified LE status as an independent risk factor for OS, disease-free survival (DFS) and PFS. The infiltration level of M0 macrophages and activated mast cells in the LE group was significantly higher than in the HE group. The hypoxia signaling pathway and glycolysis pathway were significantly enriched in the LE group.Conclusion: The loss of GNMT and the overexpression of MMP12 may be critical factors influencing TACE efficacy.Keywords: hepatocellular carcinoma, transarterial chemoembolization, immune infiltration, mast cell, glucose metabolism, hypoxic microenvironment

Hongcai Yang,&ast; Tianhao Cong,&ast; Yingen Luo, Chao Yang, Jinrui Ren, Xiao Li Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao Li, Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China, Tel +86-13910309111, Fax +86-028-88092354, Email simonlixiao@gmail.comObjective: To investigated the association between sarcopenia and the prognosis and adverse events of hepatocellular carcinoma (HCC) patients undergoing interventional therapy combined with immunotherapy and targeted therapy.Methods: Between January 2019 and December 2022, patients with unresectable HCC who received interventional therapy combined with immunotherapy and targeted therapy were included in this study. Total skeletal muscle area at the L3 level was normalized for height in m2 as the skeletal muscle index (SMI). All patients were divided into low and high SMI group according to the median SMI.Results: Ninety-six consecutive patients were included eventually, with 49 patients in the high-SMI group and 47 patients in the low-SMI group. In the low-SMI group, the median overall survival (OS) was 459.00 days (95% CI, 334.76– 583.24 days), and the 3-, 6-, and 12-month OS rates were 100%, 89.4% and 68.1%, respectively. In the high-SMI group, the median OS was not reached, and the 3-, 6-, and 12-month OS rates were 100%, 98% and 79.5%, respectively (p< 0.05). SMI and Barcelona Clinic Liver Cancer (BCLC) C stage were independent prognostic factors for OS (p< 0.05). In the low-SMI group, 26 patients had treatment-related adverse events (TRAEs), resulting in dose adjustment or treatment suspension for 10 patients. In the high-SMI group, 33 patients had TRAEs, and 18 patients received dose adjustment or treatment suspension; the between-group difference was nonsignificant (p> 0.05).Conclusion: SMI is associated with the prognosis of HCC patients receiving interventional therapy combined with immunotherapy and targeted therapy, and sarcopenia is an independent risk factor for OS. However, sarcopenia does not seem to predict the occurrence of adverse events.Keywords: hepatocellular carcinoma, sarcopenia, immune checkpoint inhibitors, tyrosine kinase inhibitors, transarterial chemoembolization

Caixia Yang,1,2,&ast; Yuan Ding,1,2,&ast; Zhengwei Mao,3 Weilin Wang1,2 1Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, Zhejiang, People’s Republic of China; 3MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhengwei Mao, Department of Polymer Science and Engineering, Zhejiang University, No. 866 Yuhangtang Road, Hangzhou, Zhejiang, 310058, People’s Republic of China, Tel +86057187783820, Fax +86057187068001, Email zwmao@zju.edu.cn Weilin Wang, Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou, Zhejiang, 310009, People’s Republic of China, Email wam@zju.edu.cnAbstract: The overall cancer incidence and death toll have been increasing worldwide. However, the conventional therapies have some obvious limitations, such as non-specific targeting, systemic toxic effects, especially the multidrug resistance (MDR) of tumors, in which, autophagy plays a vital role. Therefore, there is an urgent need for new treatments to reduce adverse reactions, improve the treatment efficacy and expand their therapeutic indications more effectively and accurately. Combination therapy based on autophagy regulators is a very feasible and important method to overcome tumor resistance and sensitize anti-tumor drugs. However, the less improved efficacy, more systemic toxicity and other problems limit its clinical application. Nanotechnology provides a good way to overcome this limitation. Co-delivery of autophagy regulators combined with anti-tumor drugs through nanoplatforms provides a good therapeutic strategy for the treatment of tumors, especially drug-resistant tumors. Notably, the nanomaterials with autophagy regulatory properties have broad therapeutic prospects as carrier platforms, especially in adjuvant therapy. However, further research is still necessary to overcome the difficulties such as the safety, biocompatibility, and side effects of nanomedicine. In addition, clinical research is also indispensable to confirm its application in tumor treatment.Keywords: autophagy, tumor resistance, nanotechnology, combination therapy, co-delivery

Chunkun Yang,1,&ast; Qinwei Zhu,2,&ast; Yanbo Chen,3,&ast; Kui Ji,2 Shuanghong Li,2 Qian Wu,1 Qingquan Pan,2 Jun Li1 1Department of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Department of Emergency, Weifang Hospital of Traditional Chinese Medicine, Weifang, Shandong, People’s Republic of China; 3Department of Arrhythmia, Weifang People’s Hospital, Weifang, Shandong, People’s Republic of China&ast;These authors contributed equally to this workThese authors contributed equally to this workCorrespondence: Jun Li, Email gamyylj@163.comAbstract: Cardiovascular diseases (CVDs) are the most common cause of death worldwide and has been the focus of research in the medical community. Curcumin is a polyphenolic compound extracted from the root of turmeric. Curcumin has been shown to have a variety of pharmacological properties over the past decades. Curcumin can significantly protect cardiomyocyte injury after ischemia and hypoxia, inhibit myocardial hypertrophy and fibrosis, improve ventricular remodeling, reduce drug-induced myocardial injury, improve diabetic cardiomyopathy(DCM), alleviate vascular endothelial dysfunction, inhibit foam cell formation, and reduce vascular smooth muscle cells(VSMCs) proliferation. Clinical studies have shown that curcumin has a protective effect on blood vessels. Toxicological studies have shown that curcumin is safe. But high doses of curcumin also have some side effects, such as liver damage and defects in embryonic heart development. This article reviews the mechanism of curcumin intervention on CVDs in recent years, in order to provide reference for the development of new drugs in the future.Keywords: curcumin, intima, endothelial cells, vascular smooth muscle cell, cardiovascular diseases, inflammation, apoptosis

Chenkai Yang,1,&ast; Xiangqian Cao,1,&ast; Lei He,2,3,&ast; Cong Wu,2,&ast; Mengxin Zhao,2 Fei Duan,2 Zhiwen Qiu,2 Xiaodong Zhu,2 Yilin Yan,1 Shengzhou Li,1 Wei Li,2 Bing Shen1 1Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Nanomedicine & Shanghai Key Laboratory of Cell Engineering, Naval Medical University, Shanghai, People’s Republic of China; 3School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Li, Department of Nanomedicine & Shanghai Key Laboratory of Cell Engineering, Naval Medical University, 800 Xiangyin Road, Yangpu District, Shanghai, 200433, People’s Republic of China, Tel +86 21 81871644, Fax +86 21 81870801, Email liwei_dds@163.com Bing Shen, Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 85 Wujin Road, Hongkou District, Shanghai, 200080, People’s Republic of China, Tel/Fax +86 18017181979, Email urodrshenbing@shsmu.edu.cnIntroduction: Insufficient tumor permeability and inadequate nanoparticle retention continue to be significant limitations in the efficacy of anti-tumor drug therapy. Numerous studies have focused on enhancing tumor perfusion by improvement of tumor-induced endothelial leakage, often known as the enhanced permeability and retention (EPR) effect. However, these approaches have produced suboptimal therapeutic outcomes and have been associated with significant side effects. Therefore, in this study, we prepared tumor cell membrane-coated gold nanorods (GNR@TM) to enhance drug delivery in tumors through homogeneous targeting of tumor cell membranes and in situ real-time photo-controlled therapy.Methods: Here, we fabricated GNR@TM, and characterized it using various techniques including Ultraviolet-Visible (UV-Vis) spectrophotometer, particle size analysis, potential measurement, and transmission electron microscopy (TEM). The cellular uptake and cytotoxicity of GNR@TM were analyzed by flow cytometry, confocal laser scanning microscopy (CLSM), TEM, CCK8 assay and live/dead staining. Tissue drug distribution was determined by inductively coupled plasma mass spectrometry (ICP-MS) and immunofluorescence staining. Furthermore, to evaluate the therapeutic effect, mice bearing MB49 tumors were intravenously administered with GNR@TM. Subsequently, near-infrared (NIR) laser therapy was performed, and the mice’s tumor growth and body weight were monitored.Results: The tumor cell membrane coating endowed GNR@TM with extended circulation time in vivo and homotypic targeting to tumor, thereby enhancing the accumulation of GNR@TM within tumors. Upon 780 nm laser, GNR@TM exhibited excellent photothermal conversion capability, leading to increased tumor vascular leakage. This magnification of the EPR effect induced by NIR laser further increased the accumulation of GNR@TM at the tumor site, demonstrating strong antitumor effects in vivo.Conclusion: In this study, we successfully developed a NIR-triggered nanomedicine that increased drug accumulation in tumor through photo-controlled therapy and homotypic targeting of the tumor cell membrane. GNR@TM has been demonstrated effective suppression of tumor growth, excellent biocompatibility, and significant potential for clinical applications. Keywords: intratumor drug accumulation, photo-controlled therapy, homotypic targeting, tumor cell membrane, gold nanorods

Xiaodong Wang,1,2,&ast; Uet Yu,2,&ast; Chao Ding,2,3 Huiying Ye,2 Chunjing Wang,2 Chunlan Yang,2 Yue Li,2 Xiaohui Zhou,2 Qian Zhang,2 Sixi Liu,2 Feiqiu Wen1,2 1Department of Pediatrics, First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 2Department of Hematology and Oncology, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of China; 3Discipline of Pediatrics, China Medical University, Shenyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feiqiu Wen, Department of Pediatrics, First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China, Email fwen62@163.com Sixi Liu, Department of Hematology and Oncology, Shenzhen Children’s Hospital, 7019 Yitian Road, Futian, Shenzhen, 518038, People’s Republic of China, Email tiger647@126.comBackground: The COVID-19 pandemic presents challenges for healthcare systems globally, especially in vulnerable populations such as pediatric hematopoietic stem cell transplant (HSCT) recipients. This study examines the clinical characteristics and outcomes of COVID-19 infection in pediatric HSCT recipients within one year post-HSCT.Methods: Retrospective analysis was conducted on data from 247 pediatric patients. None of them had received SARS-CoV-2 vaccination or had prior infection. SARS-CoV-2 infection was confirmed using RT-PCR testing. COVID-19 disease severity was categorized according to established guidelines. Demographic, clinical, laboratory, imaging and treatment data were collected.Results: The median age of the cohort was 7± 3.7 years, with thalassemia major as the predominant underlying disease. Allogeneic HSCT was performed in the majority of cases, with haploidentical donors being the most common source of grafts. Nearly half of the patients developed COVID-19, with significantly higher infection rates observed in recipients over 100 days compared to recipients within 100 days post-HSCT (40.1% vs 21.7%, p< 0.05, Fisher’s Exact test). Fever (n=107, 43.2%) and cough (n=88, 35.6%) were the most common symptoms. While most patients had mild disease and did not require specific anti-viral treatment, a significant proportion required hospitalization (n=34, 13.8%). Various treatments were employed hospitalized patients, including Paxlovid (n=19, 55.9%), methylprednisolone (n=7, 20.6%), IL-6 antibody (n=2, 5.9%), mesenchymal stem cells (n=3, 8.8%), and exosomes nebulization therapy (n=2, 5.9%). Despite multidisciplinary approaches, one patient died from severe respiratory failure. However, overall survival of all patients remained high (99.53%; CI 96.72– 99.93%), indicating favorable outcomes in pediatric HSCT recipients with COVID-19.Conclusion: This study provides insights into clinical features, therapeutic measures, and outcomes of pediatric HSCT recipients following COVID-19 infection in a large HSCT center in China. These findings contribute to our understanding of COVID-19 in this population and inform strategies to mitigate the impact the pandemic’s impact on their care.Keywords: COVID-19, SARS-CoV2, hematopoietic stem cell transplantation, pediatrics

Yuan-Yuan Song,1,&ast; Ling Xu,2,&ast; Dan Liu,3 Mei Feng,2 Cui Yang,2 Yan Jiang,4 Ying Wu2 1Department of Critical Care Medicine, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China; 4Department of Nursing/Evidence-Based Nursing Center, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Wu, Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, No. 37, Guoxue Alley, Chengdu, Sichuan Province, People’s Republic of China, Email wuying0917@wchscu.cnPurpose: China lifted its strict zero-Covid approach on December 7, 2022. This study aimed to investigate depression and anxiety symptoms and their associations among Chinese residents after the change in public policy.Methods: A cross-sectional sample of 925 Chinese residents (726 females and 199 males) was recruited using convenience and snowball sampling approach between 16 and 25 December 2022. Participants completed online questionnaires on basic information, depression, anxiety, COVID-19 related perceptions, and protective behaviors change.Results: Mild and moderate-to-severe depression symptoms were reported by 35.6% and 19.1% of participants, respectively. Nearly 40% of participants reported mild anxiety and 18.7% reported moderate-to-severe anxiety. Results from multinomial logistic regression analysis indicated that male gender, younger age, the presence of chronic disease, poorer self-rated mental health status, perceived impact, and worry were risk factors for both depression and anxiety, while higher education and protective behaviors change were protective factors. Besides, living with or caring for children (4– 6 years), family members or other housemates currently with influenza-like symptoms, and perceived severity were also risk factors for depression.Conclusion: Our findings provided initial evidence that Chinese residents may face heightened depression and anxiety during the early stage after the policy was released. Furthermore, we identified some vulnerable populations in need of prioritizing mental health assistance and some potentially modifiable factors associated with depression and anxiety, which provides an important guide for developing timely and effective psychological interventions and preparing for future pandemics.Keywords: COVID-19, public policy, depression, anxiety, COVID-19 related perceptions, protective behaviors change

Chunmei Yang,1,&ast; Xiaoling Che,1,&ast; Yu Zhang,2 Didi Gu,1 Guidong Dai,1 Jian Shu,1 Lu Yang1 1Department of Radiology, The Affiliated Hospital of Southwest Medical University, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, Sichuan Province, People’s Republic of China; 2Department of Radiology, The First People’s Hospital of Yibin, Yibin, 644000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Shu; Lu Yang, Department of Radiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, People’s Republic of China, Tel +86 0830-18980253083 ; +86 0830-2504762, Email shujiannc@163.com; yanglu@swmu.edu.cnBackground: Development of versatile nanoplatform still remains a great challenge due to multistep synthesis and complicated compositions. Therefore, it is significant to develop a facile method to synthesize a nanocomposite to achieve multimodal imaging and even imaging-guided cancer therapeutics.Methods and Results: In our study, hyaluronic acid-functionalized iron (II) tungstate nanoparticles (HA-FeWO4 NPs) were successfully synthesized as a versatile nanoplatform by a facile one-pot hydrothermal procedure. The formed multifunctional HA-FeWO4 NPs were investigated via a series of characterization techniques, which demonstrated good biocompatibility, excellent dispersion, low cytotoxicity, active tumor-targeting ability and high photothermal efficiency. Furthermore, tumor was clearly visualized by HA-FeWO4 NPs with multimodal imaging of infrared thermal imaging, magnetic resonance imaging, computed tomography imaging in 4T1 tumor bearing mice. More importantly, HA-FeWO4 could achieve multimodal imaging-guided photothermal therapy of 4T1 tumors.Conclusion: The constructed HA-FeWO4 NPs have great potential as ideal nanotheranostic agents for multimodal imaging and even imaging-guided cancer theranostics in biological systems.Keywords: theranostics, multimodal imaging, photothermal therapy, diagnostic imaging, nanomedicine

Identifying biomarkers in non-small cell lung cancer (NSCLC) can improve diagnosis and patient stratification. We evaluated plasmas and sera for interleukins (IL)-11, IL-6, IL-8, IL-17A, and IL-33 as biomarkers in primary NSCLC patients undergoing surgical treatment against normal volunteers. Exhaled-breath condensates (EBCs), a potential source without invasive procedures, were explored in normal individuals. Due to separate recruitment criteria and intrinsic cohort differences, the NSCLC and control cohorts were not well matched for age (median age: 65 vs. 40 years; p < 0.0001) and smoking status (p = 0.0058). Interleukins were first assessed through conventional ELISA. IL-11 was elevated in NSCLC plasma compared to controls (49.71 ± 16.90 vs. 27.67 ± 14.06 pg/mL, respectively, p < 0.0001) but undetectable in sera and EBCs by conventional ELISA. Therefore, high-sensitivity PCR-based IL-11 ELISA was repeated, albeit with concentration discrepancies. IL11 gene and protein upregulation by RT-qPCR and immunohistochemistry, respectively, were validated in NSCLC tumors. The lack of detection sensitivity across IL-6, IL-8, IL-17A, and IL-33 suggests the need for further, precise assays. Surprisingly, biomarker concentrations can be dissimilar across paired plasmas and sera. Our results identified a need to optimize detection limits for biomarker detection and caution against over-reliance on just one form of blood sample for biomarker assessment.

Junjie Chen,1,&ast; Xiwen Liao,1,2 Yining Wu,1,&ast; Shenjian Ou,1 Wei Qin,1 Chengkun Yang,1,2 Yufeng Tan,1 Quan Lao,1 Minhao Peng,1 Tao Peng,1,2 Xinping Ye1 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China; 2Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinping Ye; Tao Peng, Tel +86-771-5356528, Fax +86-771-5350031, Email yexinping@gxmu.edu.cn; pengtaogmu@163.comAbstract: Hepatocellular carcinoma (HCC) recurrence, which encompasses both true recurrence resulting from cancer spread and de novo tumors developing within the same cancer-prone liver, presents a complication in approximately 70% of cases within a 5-year timeframe. The efficacy of neoadjuvant therapy for recurrence after hepatectomy for hepatocellular carcinoma is still unclear. We report a case of recurrent massive advanced hepatocellular carcinoma with pathological complete remission was treated by continuous hepatic arterial infusion chemotherapy (HAIC) and sequential transcatheter arterial embolization (TAE) combined with secondary operation. One month after resection, the patient recurred (massive type 141mm× 76mm). After 4 times of HAIC sequential TAE conversion therapy, the tumor shrank significantly (70mm× 29mm), alpha-fetoprotein(AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) levels decreased significantly, residual liver volume[left half liver accounted for 39.85% of standard liver volume(left half liver + right anterior lobe) accounted for 80.17% of standard liver volume] and Indocyanine green 15-minute retention(ICG R15 8.0%) complies with surgical requirement.The second operation was performed, and the tumor was completely resected after hepatic blood flow occlusion Requirement. The postoperative pathological results showed complete remission (PCR) of the tumor, and no recurrence was found during the follow-up of 16 months. In this case, HAIC sequential TAE conversion therapy has good short-term effect on patients with postoperative recurrence of hepatocellular carcinoma, tumor burden is significantly reduced, the second surgery pathology achieves complete remission, safety and tolerance, it is worthy of study and promotion.Keywords: hepatocellular carcinoma, recurrence after resection, two-stage hepatectomy, complete remission, sequential therapy

Dongmei Guo,1 Yue Huang,2 Kun Wang,2 Chenguang Yang,2 Lili Ma,2 Yu Zhang,2 Haiyang Yu,2 Manhua Cui,1 Zhaohui Tang2 1Department of Gynecology and Obstetrics, The Second Hospital of Jilin University, Changchun, Jilin Province, 130041, People’s Republic of China; 2Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, People’s Republic of ChinaCorrespondence: Manhua Cui, Department of Gynecology and Obstetrics, The Second Hospital of Jilin University, 218 Ziqiang Road, Changchun, Jilin Province, 130041, People’s Republic of China, Email cuimanhua@126.com Yue Huang, Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, People’s Republic of China, Tel/Fax +86 431 85262116, Email huangyue@ciac.ac.cnPurpose: Cervical cancer (CC) is a highly vascularized tumor with abundant abnormal blood vessel, which could be targeted by therapeutic strategies. Poly(L-glutamic acid)-g-methoxy poly(ethylene glycol)/combretastatin A4 (CA4)/BLZ945 nanoparticles (CB-NPs) have shown great potential as nano vascular disrupting agents (VDAs) in the realm of synergistic cancer therapy.Methods: In this study, we investigated the nanocharacteristics of CB-NPs, focusing on active pharmaceutical ingredients (API), as well as lyophilized samples combining API with protective agents (PAs). The in vivo efficacy of final sample (API + PAs) was evaluated.Results: The assembled sphere of API with complex core and thin-shell structure was confirmed. PAs were found to significantly influence in vivo efficacy. Collaborative efforts between API and PAs, namely mannitol and lactose, resulted in the most promising lyophilized sample, ie, the final sample (FS2) for CC therapy. Impressively, FS2 demonstrated an exceptional 100% cure rate on the CC U14-bearing mice model.Conclusion: FS2 has provided significant insights for cervical cancer therapy. It is also crucial to develop a comprehensive evaluation strategy for the formulation of nanomedicine, which has the potential to serve as a guideline for future clinical trials. Keywords: combretastatin A4, BLZ945, glutamic acid, nano character, cervical cancer

Jing Zhou, Chunsong Yang, Qichen Xv, Liyun Wang, Liangjun Shen, Qingwei Lv Department of Neurosurgery, Shengzhou People’s Hospital (the First Affiliated Hospital of Zhejiang University Shengzhou Branch), Shengzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Chunsong Yang, Department of Neurosurgery, Shengzhou People’s Hospital (the First Affiliated Hospital of Zhejiang University Shengzhou Branch), Shengzhou, Zhejiang, People’s Republic of China, Email ycs821005@163.comBackground: Translocator protein (TSPO) is a biomarker of neuroinflammation and brain injury. This study aimed to ascertain the potential of serum TSPO as a predictor of cognitive impairment after acute intracerebral hemorrhage (ICH).Methods: In this prospective observational cohort study, 276 patients with supratentorial ICH were randomly assigned to two groups (184 patients in the study group and 92 in the validation group) in a 2:1 ratio. Serum TSPO levels were gauged at admission, and cognitive status was assessed using the Montreal Cognitive Assessment Scale (MoCA) post-stroke 3 months. A MoCA score of < 26 was considered indicative of cognitive impairment.Results: Serum TSPO levels were inversely correlated with MoCA scores (ρ=− 0.592; P< 0.001). Multivariate linear regression analysis showed that serum TSPO levels were independently associated with MoCA scores (β, − 0.934; 95% confidence interval (CI), − 1.412--0.455; VIF, 1.473; P< 0.001). Serum TSPO levels were substantially higher in patients with cognitive impairment than in the remaining patients (median, 2.7 versus 1.6 ng/mL; P< 0.001). Serum TSPO levels were linearly correlated with the risk of cognitive impairment under a restricted cubic spline (P=0.325) and independently predicted cognitive impairment (odds ratio, 1.589; 95% CI, 1.139– 2.216; P=0.016). Subgroup analysis showed that the relationship between serum TSPO levels and cognitive impairment was not markedly influenced by other parameters, such as age, sex, drinking, smoking, hypertension, diabetes mellitus, body mass index, and dyslipidemia (all P for interaction > 0.05). The model, which contained serum TSPO, National Institutes of Health Stroke Scale scores and hematoma volume, performed well under the receiver operating characteristic curve, calibration curve and decision curve, and using the Hosmer–Lemeshow test. This model was validated in the validation group.Conclusion: Serum TSPO level upon admission after ICH was independently associated with cognitive impairment, substantializing serum TSPO as a reliable predictor of post-ICH cognitive impairment.Keywords: translocator protein, intracerebral hemorrhage, cognitive impairment, biomarkers

Chuang Yang,1 Xing Feng,1,2 Junfeng Li,1 Yuchan Jiang,1 Huan Zhang,1 Yidan Gao,1 Jinxiang Tan,1 Bolin Ran3 1Department of Breast and Thyroid Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Department of Hepatobiliary, Breast and Thyroid Surgery, the People’s Hospital of Liangping District, Chongqing, 405200, People’s Republic of China; 3Department of Medical Laboratory Science, Laboratory of Traditional Chinese Medicine Hospital of Shizhu County, Chongqing, 409100, People’s Republic of ChinaCorrespondence: Jinxiang Tan; Bolin Ran, Tel/Fax +86-23-89011496, Email tjx1202@163.com; 729297969@qq.comPurpose: Medical students play an essential role in providing disease consultation for patients. Despite the rapid increase in thyroid disease, there are few data on how well Chinese medical students master the knowledge of thyroid diseases. This study aims to evaluate the clinical knowledge, perception, and clinical communication confidence of medical students on thyroid cancer (TC).Patients and Methods: This cross-sectional study was carried out among medical students of Chongqing Medical University. An anonymous, self-administered questionnaire distributed from December 2022 to February 2023 included items on demographics and other information, the warning signs of cancer, perception regarding a person’s chance of developing cancer, and clinical communication confidence. Descriptive analysis, difference analysis, and correlation analysis were carried out.Results: A total of 226 medical students participated in the survey. Most students (n=191, 84.5%) had heard of TC, while only a few (n=10, 4.4%) regularly performed thyroid self-examination. One hundred and eighty-four students (81.4%) agreed that an unexplained lump or swelling could be a sign of cancer. There were significant differences in thyroid clinical knowledge in relation to gender (P< 0.001), major (P=0.026), and thyroid disease (P=0.030). Clinical communication confidence showed significant differences in year of study (P=0.002), major (P=0.048), and graduate major (P< 0.001). There was a correlation between clinical confidence and year of study (r=0.261, P< 0.001).Conclusion: Most medical students have sufficient clinical knowledge on TC prevention, but there are still misconceptions related to TC screening. In addition, medical students lack confidence in communicating with patients. Comprehensive communication training should be integrated into the medical curriculum and clinical activities should be initiated earlier.Keywords: thyroid cancer, cancer warning signs, clinical communication confidence, communication skills training, medical students

Yandan Zhou,1 Zhili Feng,2,3 Jie Wen,2,3 Chi Yang,2,3 Qiancheng Jing2,3 1Changsha Aier Eye Hospital, Aier Eye Hospital Group, Changsha, Hunan, People’s Republic of China; 2Department of Otolaryngology Head and Neck Surgery, the Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan, People’s Republic of China; 3Institute of Otolaryngology Head and Neck Surgery, Hengyang Medical School, University of South China, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Qiancheng Jing, Department of Otolaryngology-Head and Neck Surgery, the Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan, People’s Republic of China, Email 2022050001@usc.edu.cnBackground: Allergic rhinitis (AR) is a common allergic disease, and SLIT has shown effectiveness as a treatment method. This study focuses on the evaluation of serum TAM receptor tyrosine kinases (TYRO3, AXL, and MER) levels as potential indicators of disease severity and predictive markers for sublingual immunotherapy (SLIT) responsiveness in AR patients.Methods: A total of 160 AR subjects, including 40 mild AR (MAR) and 120 moderate-severe AR (MSAR) patients, and 40 healthy controls (HC) were recruited. Serum concentrations of TYRO3, AXL, and MER were measured and their relationships with disease severity were examined. In the MSAR group, 102 patients underwent SLIT, and the early efficacy was evaluated. The correlations between the baseline serum concentrations of TYRO3, AXL, and MER and the early responsiveness of SLIT were analyzed.Results: Serum concentrations of TYRO3, AXL, and MER were significantly reduced in AR patients, particularly in those MSAR subjects. Correlation analysis results indicated that serum TYRO3 and MER levels were negatively correlated with the visual analog scale (VAS) and the total nasal symptom score (TNSS). After one year of follow-up, 80 AR patients completed the treatment and were divided into effective and ineffective groups. Serum baseline levels of TYRO3 and MER were found to be lower in the effective group compared to the ineffective group. Additionally, there was a significant increase in serum TYRO3 and MER levels compared to baseline levels. Receiver operating characteristic (ROC) analysis revealed that circulating TYRO3 and MER had potential values for reflecting AR severity and predicting early SLIT responsiveness.Conclusion: Serum TYRO3 and MER concentrations were decreased in AR patients and negatively associated with disease severity. Circulating TYRO3 and MER seem to be promising indicators for monitoring the efficacy of SLIT in AR patients.Keywords: allergic rhinitis, sublingual immunotherapy, TAM receptor tyrosine kinases, TYRO3, AXL, MER

Tao Wang,1,2,&ast; Yanan Li,2,&ast; Shuai Miao,1,2 Chunxiao Yang,3 Wei Xie,1,2 Huijuan Yuan,3 Wenhao Bai,1,2 Han Xiao,1,2 Shengyuan Yu1,2 1Department of Neurology, the First Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Medical School of Chinese PLA, Beijing, People’s Republic of China; 3College of Medicine, Nankai University, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shengyuan Yu, Email yusy1963@126.comBackground: Migraine treatment research has made much great progress over the past decade. However, there have been few bibliometric studies conducted so far. In this study, bibliometric analysis was used to explore the current status and future trends of migraine treatment research.Methods: Migraine treatment-related articles were retrieved from the Web of Science Core Collection on December 7, 2022. Quantitative variables were analyzed by the R-tool bibliometrix and Excel 2020. VOS viewer and CiteSpace software were used to visualize citation, co-authorship, co-occurrence, and co-citation analysis of countries/regions, organizations, authors, references, and keywords.Results: A total of 3294 articles were included with the global publication output showing a slow upward trend. The United States was the most productive country with 1116 papers and gained the most citations. Albert Einstein College of Medicine was the most active institution with 176 papers. Headache published the most articles in this domain, while Cephalalgia was the most commonly co-cited journal. Lipton, RB published the most articles and had the most citations. Tepper S, 2017, Lancet neurology and Silberstein S, 2004, Cephalalgia were defined as classic articles. The current research mainly focuses on CGRP-related therapeutics, such as fremanezumab, erenumab and ubrogepant.Conclusion: Based on the analysis of bibliometric data on migraine treatment over the past decade, the trends and the knowledge graph of the country, organization, author, reference, and the keyword were identified, providing accurate and quick positioning of the critical information in the domain.Keywords: migraine, treatment, bibliometric analysis, research trends, hot spots

Chen Yang,1 Jiaxing Lei,1 Ximeng Kang,1 Peipei Zhang,1 Shaohua Zheng,2 Qingqing Li,1 Jiye Zhang1 1School of Pharmacy, Health Science Center, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of ChinaCorrespondence: Qingqing Li; Jiye Zhang, School of Pharmacy, Health Science Center, Xi’an Jiaotong University, No. 76 Yanta Westroad, Xi’an, People’s Republic of China, Email liqingqing0217@mail.xjtu.edu.cn; zjy2011@mail.xjtu.edu.cnIntroduction: The effect of traditional treatment for melanoma is quite limited, especially for its recurrence. As the major components of yeast cell wall, chitin and β-glucan exhibit good immune activation effect and are promising candidates for adjuvant. Therefore, melanoma cell membrane (CM) and indocyanine green (ICG) was loaded in a chitin and β-glucan hybrid hydrogel to achieve an enhanced anti-melanoma therapy.Methods: The novel hybrid hydrogel was prepared, and its physicochemical properties were examined. Its effect towards melanoma prevention and treatment was evaluated via a melanoma-bearing mice model.Results: The CM-ICG-hybrid hydrogel was successfully prepared with excellent injectability, self-healing, drug loading, rheological, in vitro and in vivo photothermal stability, and retention properties. It also exhibited good cellular and in vivo safety profiles. In the primary melanoma mice model, it quickly ablated the in-situ melanoma, effectively inhibited the tumor growth, increased the survival rate of melanoma-bearing mice, and increased the level of IFN-γ and TNF-α. In the distal secondary melanoma model, it efficiently prevented the reoccurrence of melanoma and activated the memory T cells. In both models, a synergistic effect of photothermal therapy and immune therapy was found. The hydrogel effectively recruited CD3+ CD4+ T cells and CD3+ CD8+ T cells, inhibited the proliferation of melanoma cells, and induced the apoptosis of melanoma cells.Conclusion: The hybrid hydrogel was successfully prepared, and it showed excellent efficacy towards melanoma prevention and treatment due to its efficient tumor ablation and immune activation capability.Graphical Abstract: Keywords: chitin, β-glucan, hybrid hydrogel, melanoma cell membrane, photo thermotherapy, immunotherapy

Doori Kim,1 Eun-San Kim,1 Yoon Jae Lee,1 Jee Young Lee,2 Kyong Sun Park,3 So Young Jung,4 Changsop Yang,5 Chang-Hyun Han,6,7 In-Hyuk Ha1 1Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul, 06110, Republic of Korea; 2Department of Korean Internal Medicine, Integrative Cancer Center, Cha Ilsan Medical Center, Goyang-si, Gyeonggi-do, Republic of Korea; 3Jaseng Hospital of Korean Medicine, Seoul, 06110, Republic of Korea; 4Clinical Research Coordinating Team, Korea Institute of Oriental Medicine, Daejeon, 34054, Republic of Korea; 5Clinical Medicine Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea; 6Korean Convergence Medical Science, University of Science & Technology (UST), School of Korea Institute of Oriental Medicine, Daejeon, 34054, Republic of Korea; 7KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon, 34054, Republic of KoreaCorrespondence: In-Hyuk Ha, Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, 540 Gangnam-daero, Gangnam-gu, Seoul, 06110, Republic of Korea, Tel +82-2-2222-2740, Fax +82-2-2222-2737, Email hanihata@gmail.com Chang-Hyun Han, KM Science Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon, 34054, Republic of Korea, Tel +82-(0)42-868-9498, Fax +82-(0)42-869-2775, Email chhan@kiom.re.krPurpose: We aimed to compare the efficacy, safety, and cost-effectiveness of non-pharmacological- and pharmacological treatment strategies for Lumbar disc herniation (LDH) in pragmatic clinical settings.Patients and Methods: This study was a pilot, two-armed, parallel pragmatic randomized controlled trial. Thirty patients aged 19– 70 years with a numeric rating scale (NRS) score ≥ 5 for sciatica and confirmed LDH on magnetic resonance imaging (MRI) were included. Participants were assigned in a 1:1 ratio to non-pharmacological (non-Phm) or pharmacological (Phm) treatment group. They were treated for 8 weeks and a total follow-up period was 26 weeks after randomization. Non-Phm treatment included acupuncture, spinal manual therapy, etc., Phm included medication, injection, nerve block, etc., The primary outcome was a numeric rating scale (NRS) of radiating leg pain. NRS for low back pain, Oswestry disability index, visual analog scale, Fear-Avoidance Beliefs Questionnaire, patient global impression of change, Short Form-12 Health Survey, version 2, 5-level European Quality of Life-5 dimensions (EQ-5D) were also measured. Linear mixed model was used to evaluated the difference in change of outcomes from baseline between two groups. An economic evaluation was conducted using incremental cost-effectiveness ratios.Results: There was no significant difference between the two groups in the intervention period, but non-Phm group showed significantly greater degree of improvement in follow-up of Week 14. Difference in the NRS for sciatica and ODI were 1.65 (95% CI 0.59 to 2.71, p=0.003) and 8.67 (95% CI 1.37 to 15.98, p=0.21), respectively in Week 14. The quality-adjusted life year (QALY) value calculated by EQ-5D and Short Form-6 Dimension were 0.006 (95% CI − 0.012 to 0.024, p=0.472) and 0.015 (95% CI − 0.008 to 0.038, p=0.195) higher in non-Phm group than in Phm group. The cost was lower in non-Phm group than in Phm group (Difference: − 682, 95% CI − 3349 to 1699, p=0.563).Conclusion: We confirmed that the non-Phm treatment could be more cost-effective treatments than Phm treatments and feasibility of a large-scale of main study in future.Keywords: conservative treatment, intervertebral disc displacement, low back pain, sciatica

Yunfei Zhang,1,2,&ast; Ruofan Sheng,1,2,&ast; Chun Yang,2 Yongming Dai,3 Mengsu Zeng1,2 1Shanghai Institute of Medical Imaging, Fudan University, Shanghai, 200032, People’s Republic of China; 2Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 3School of Biomedical Engineering, ShanghaiTech University, Shanghai, 200032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongming Dai, School of Biomedical Engineering, ShanghaiTech University, Shanghai, 200032, People’s Republic of China, Tel +86 13917166155, Email daiyongming5555@163.com Mengsu Zeng, Department of Radiology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People’s Republic of China, Tel +86-021-64041990, Email zengmengsu111@163.comPurpose: To assess the effectiveness of tri-exponential Intra-Voxel Incoherent Motion (tri-IVIM) MRI in preoperatively identifying microvascular invasion (MVI) in hepatocellular carcinoma (HCC).Patients and Methods: In this prospective study, 67 patients with HCC were included. Metrics from bi-exponential IVIM (bi-IVIM) and tri-IVIM were calculated. Subgroup comparisons were analyzed using the independent Student’s t-test or Mann–Whitney U-test. Logistic regression was performed to explore clinical risk factors. Diagnostic performance was assessed using receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis.Results: MVI-positive HCCs exhibited significantly lower true diffusion coefficient (Dt) from bi-IVIM, as well as fast-diffusion coefficients (Df) and slow-diffusion coefficients (Ds) from tri-IVIM, compared to MVI-negative HCCs (p < 0.05). Tumor size and alpha-fetoprotein (AFP) were identified as risk factors. The combination of tri-IVIM-derived metrics (Ds and Df) yielded higher diagnostic accuracy (AUC = 0.808) compared to bi-IVIM (AUC = 0.741). A predictive model based on a nomogram was constructed using Ds, Df, tumor size, and AFP, resulting in the highest diagnostic accuracy (AUC = 0.859). Decision curve analysis indicated that the constructed model, provided the highest net benefit by accurately stratifying the risk of MVI, followed by tri-IVIM and bi-IVIM.Conclusion: Tri-IVIM can provide information on perfusion and diffusion for evaluating MVI in HCC. Additionally, tri-IVIM outperformed bi-IVIM in identifying MVI-positive HCC. By integrating clinical risk factors and metrics from tri-IVIM, a predictive nomogram exhibited the highest diagnostic accuracy, potentially aiding in the noninvasive and preoperative assessment of MVI.Keywords: tri-exponential intra-voxel incoherent motion, diffusion weighted imaging, hepatocellular carcinoma, microvascular invasion

Kyoung Sun Park,1 Changnyun Kim,2 Joo Won Kim,3 Sang‐Don Kim,4 Jee Young Lee,5 Yoon Jae Lee,5 Jinho Lee,1 Min Ji Kim,6 Young Eun Choi,6 Changsop Yang,7 Chang-Hyun Han,7,8,&ast; In-Hyuk Ha5,&ast; 1Jaseng Hospital of Korean Medicine, Seoul, Republic of Korea; 2Daejeon Jaseng Hospital of Korean Medicine, Daejeon, Republic of Korea; 3Bucheon Jaseng Hospital of Korean Medicine, Bucheon, Republic of Korea; 4Haeundae Jaseng Hospital of Korean Medicine, Busan, Republic of Korea; 5Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul, Republic of Korea; 6Clinical Research Coordinating Team, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea; 7Clinical Medicine Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea; 8Korean Convergence Medical Science, Korea Institute of Oriental Medicine School, University of Science & Technology, Daejeon, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Chang-Hyun Han, Clinical Medicine Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea, Tel +82 42 868 9498, Email chhan@kiom.re.kr In-Hyuk Ha, Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul, Republic of Korea, Tel +82 2 2222 2740, Email hanihata@gmail.comPurpose: Chronic lower back pain (LBP) is a major global health concern. Pharmacopuncture has been widely used to treat LBP in Korea; however, randomized clinical trials (RCT) or active control have not been conducted to evaluate its effectiveness. Therefore, this RCT aimed to compare the effectiveness of pharmacopuncture and physical therapy (PT) for the treatment of chronic LBP.Patients and Methods: A two-arm, parallel, and multicenter RCT was conducted at four hospitals of Korean medicine. Participants with chronic LBP were randomly assigned at a 1:1 ratio using block randomization to undergo 10 sessions of pharmacopuncture or PT over 5 weeks and followed up for 25 weeks. The numerical rating scale (NRS) and visual analog scale scores of LBP and radiating leg pain and the Oswestry disability index (ODI), 5-level EuroQol-5 dimension (EQ-5D-5L), and the patient global impression of change were recorded at baseline and at 6, 13, and 25 weeks. An intention-to-treat analysis was conducted as the primary analysis using a linear mixed model.Results: One-hundred patients (mean age, 49.27 years; 58 women) were recruited. At 6 weeks after randomization, pharmacopuncture showed statistically superior results compared with PT in LBP (difference in NRS, 1.54; 95% CI, 0.94– 2.13), function (difference in ODI, 4.52%; 95% CI, 0.93– 8.11%), and quality of life (difference in EQ-5D-5L) scores (− 0.05; 95% CI, − 0.08 to − 0.01). This effect persisted for 25 weeks. In the survival analysis for participants with at least a 50% reduction in the NRS scores of LBP during the 182-day follow-up, the pharmacopuncture group showed significantly faster recovery than the PT group (P< 0.001, Log rank test).Conclusion: Pharmacopuncture significantly reduced pain and improved functional outcomes and quality of life in patients with low back pain compared with physical therapy. Based on the findings of this study, pharmacopuncture could be recommended as a treatment for patients with chronic low back pain.Keywords: low back pain, pharmacopuncture, physiotherapy, Oswestry disability index, Roland–Morris disability questionnaire, pragmatic randomized controlled trial

Jiong Zhang,1,2,&ast; Juan Chen,3,&ast; Qing Jiang,1,&ast; Rui Feng,2 Xiaohu Zhao,2 Haolin Li,2 Cheng Yang,2 Xiaoliang Hua1 1Department of Urology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Urology, the First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 3The Ministry of Education Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Cheng Yang, Department of Urology, the First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Shushan District, Hefei, 230022, People’s Republic of China, Tel +86 0551 6292 3440, Fax +86 551 6363 3742, Email chengyang_md@163.com Xiaoliang Hua, Department of Urology, the Second Affiliated Hospital of Chongqing Medical University, No. 74 Linjiang Road, Yuzhong District, Chongqing, 400010, People’s Republic of China, Tel\Fax +86 023 6369 3222, Email hua_xiaoliang@cqmu.edu.cnBackground: Resolvin D1 (RvD1), a member of the specialized pro-resolving lipid mediators family, has a potent anti-inflammatory effect and alleviates tissue damage. The purpose of the current research was to study the effect of RvD1 on CP/CPPS and the underlying mechanisms using a mouse model of experimental autoimmune prostatitis (EAP) mice.Materials and Methods: The EAP mouse model was successfully established, and was used to test the therapeutic effect of RvD1. Hematoxylin-eosin staining and dihydroethidium staining were used to evaluate the histological changes and oxidative stress levels of prostate tissues. Chronic pelvic pain was assessed by applying von Frey filaments to the lower abdomen. The superoxide dismutase enzyme and malondialdehyde levels were detected using enzyme-linked immunosorbent assay (ELISA). The levels of inflammation-related cytokines, including IL-1β, IL-6, and TNF-α were detected by ELISA.Results: RvD1 treatment ameliorated prostatic inflammation and the pelvic pain of EAP mice. RvD1 treatment could inhibit activation of the NLRP3 inflammasome and oxidative stress. RvD1 treatment could activate Nrf2/HO-1 signaling in mice with EAP. Blockade of Nrf2/HO-1 signaling abolished the RvD1-mediated inhibition of oxidative stress, NLRP3 inflammasome activation and the anti-inflammatory effect of RvD1 in EAP.Conclusion: RvD1 treatment can reduce inflammatory cell infiltration in prostate tissue and attenuate pelvic pain associated with EAP by inhibiting oxidative stress and NLRP3 inflammasome activation via the Nrf2/HO-1 pathway. These results provide new insights that RvD1 has the potential as an effective agent in the treatment of EAP.Keywords: chronic prostatitis and chronic pelvic pain syndrome, CP/CPPS, resolvin D1, inflammation, NLRP3 inflammasome, oxidative stress

Chengyu Yang,1,2,&ast; Li Yang,3,4,&ast; Lei Yang,5 Shuiming Li,5 Ling Ye,1,6 Jinfeng Ye,5 Chengshui Chen,3,4,7 Yiming Zeng,8 Mengchan Zhu,1 Xiaoping Lin,8 Qing Peng,9 Yun Wang,5,10 Meiling Jin1,6 1Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Huadong Hospital, Fudan University, Shanghai, 200040, People’s Republic of China; 3Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325015, People’s Republic of China; 4Key Laboratory of Interventional Pulmonology of Zhejiang Province, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325015, People’s Republic of China; 5Longhua Innovation Institute for Biotechnology, Shenzhen University, Shenzhen, Guangdong, 518055, People’s Republic of China; 6Department of Allergy, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 7Department of Pulmonary and Critical Care Medicine, the Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Zhejiang, 324000, People’s Republic of China; 8Department of Pulmonary and Critical Care Medicine, the Second Affiliated Hospital of Fujian Medical University, Respiratory Medicine Center of Fujian Province, Quanzhou, Fujian, 362000, People’s Republic of China; 9Department of Pulmonary and Critical Care Medicine, Minhang Hospital, Fudan University, Shanghai, 201199, People’s Republic of China; 10Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, Guangdong, 515041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Meiling Jin, Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China, Email jin.meiling@zs-hospital.sh.cn Yun Wang, Longhua Innovation Institute for Biotechnology, Shenzhen University, Shenzhen, Guangdong, 518055, People’s Republic of China, Email yunw@szu.edu.cnBackground: Frequent exacerbation (FE) and infrequent exacerbation (IE) are two phenotypes of chronic obstructive pulmonary disease (COPD), of which FE is associated with a higher incidence of exacerbation and a serious threat to human health. Because the pathogenesis mechanisms of FE are unclear, this study aims to identify FE-related proteins in the plasma via proteomics for use as predictive, diagnostic, and therapeutic biomarkers of COPD.Methods: A cross-sectional study was conducted in which plasma protein profiles were analyzed in COPD patients at stable stage, and differentially expressed proteins (DEPs) were screened out between the FE and IE patients. FE-related DEPs were identified using data-independent acquisition-based proteomics and bioinformatics analyses. In addition, FE-related candidates were verified by enzyme-linked immunosorbent assay.Results: In this study, 47 DEPs were screened out between the FE and IE groups, including 20 upregulated and 27 downregulated proteins. Key biological functions (eg, neutrophil degranulation, extracellular exosome, protein homodimerization activity) and signaling pathways (eg, arginine and proline metabolism) were enriched in association with the FE phenotype. Receiver operating characteristic (ROC) analysis of the 11 combined DEPs revealed an area under the curve of 0.985 (p < 0.05) for discriminating FE from IE. Moreover, correlation and ROC curve analyses indicated that creatine kinase, M-type (CKM) and fat storage-inducing transmembrane protein 1 (FITM1) might be clinically significant in patients with the FE phenotype. In addition, plasma expression levels of CKM and FITM1 were validated to be significantly decreased in the FE group compared with the IE group (CKM: p < 0.01; FITM1: p < 0.05).Conclusion: In this study, novel insights into COPD pathogenesis were provided by investigating and comparing plasma protein profiles between the FE and IE patients. CKM, FITM1, and a combinative biomarker panel may serve as useful tools for assisting in the precision diagnosis and effective treatment of the FE phenotype of COPD.Keywords: chronic obstructive pulmonary disease, frequent exacerbation, data-independent acquisition, proteomics, bioinformatics analysis

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

Qiliang Liu,&ast; Yan Hu,&ast; Mei Lei, Chunlin Mei, Chengqing Yang Wuhan Pulmonary Hospital, Wuhan Institute for Tuberculosis Control, Wuhan, Hubei, 430030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chengqing Yang, Wuhan Pulmonary Hospital, Wuhan Institute for Tuberculosis Control, Wuhan, Hubei, 430030, People’s Republic of China, Email 147391593@qq.comIntroduction: Tracheobronchopathia osteochondroplastica (TO) is a relatively rare benign tracheobronchial disease, which is often misdiagnosed or missed. To date, there is no specific treatment for TO. The aim of this study was to investigate the clinical manifestations, imaging features, bronchoscopy results, pathological findings, and diagnostic points of TO.Patients and methods: A total of 33 patients diagnosed with TO were enrolled. Clinical data were collected using retrospective methods in the period from January 2021 and November 2022. Descriptive analysis was used.Results: Patients included 17 (51.5%) male and 16 (48.5%) female, with a median age of 54 years. The main clinical manifestations included cough in 15 cases, fever in 6 cases, chest tightness in 4 cases, haemoptysis in 3 cases, and chest pain in 4 cases. The time from the onset of symptoms to diagnosis was 1 week to 96 months. Some patients were diagnosed with other lung diseases, including 16 patients with tuberculosis, 2 patients with lung cancer, 3 patients with nontuberculous mycobacteriosis, 3 patients with tuberculous pleurisy, 2 patients with bronchiectasis, and 1 patient with pneumonia. Chest computed tomography (CT) scan demonstrated calcified nodules in 10 (30.3%) patients. In bronchoscopy, entire tracheal involvement was found in 21 (63.6%) patients, 12 (36.4%) patients were found to have involvement of only part of the trachea. The patients were divided into three groups according to the bronchoscopic presentation, the largest proportion was stage II (19/33), followed by stage I (8/33) and stage III (6/33). Histopathological findings showed squamous metaplasia, cartilaginous, and bony tissues.Conclusion: TO is a slowly progressing disease with non-specific clinical symptoms and a low positive rate of imaging diagnosis, making it susceptible to misdiagnosis and missed diagnosis. The disease needs to be diagnosed by combining imaging features, fiberoptic bronchoscopy, and pathological findings.Keywords: benign tracheobronchial disease, tuberculosis, misdiagnosis, bronchoscopy

Tao Yang,1– 4 Haiqiong Liu,1,3,4 Chaobo Yang,1,3,4 Huaqiang Mo,1,3,4 Xianbao Wang,1,3,4 Xudong Song,1,3,4 Luping Jiang,2 Ping Deng,2 Ran Chen,2 Pengcui Wu,2 Aihua Chen,1,3,4 Jing Yan1,3,4 1Department of Cardiology, Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Cardiovascular Medicine, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, People’s Republic of China; 3Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 4Guangdong Provincial Key Laboratory of Shock and Microcirculation, Southern Medical University, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Jing Yan; Aihua Chen, Department of Cardiology, Heart Center, Zhujiang Hospital, Southern Medical University, NO. 253, Gongye Avenue, Guangzhou, 510282, People’s Republic of China, Tel/Fax +86-2061643686, Email yanve1008@126.com; chenaha@126.comPurpose: Myocardial ischemic reperfusion injury (MIRI) is a crucial clinical problem globally. The molecular mechanisms of MIRI need to be fully explored to develop new therapeutic methods. Galangin (Gal), which is a natural flavonoid extracted from Alpinia Officinarum Hance and Propolis, possesses a wide range of pharmacological activities, but its effects on MIRI remain unclear. This study aimed to determine the pharmacological effects of Gal on MIRI.Methods: C57BL/6 mice underwent reperfusion for 3 h after 45 min of ischemia, and neonatal rat cardiomyocytes (NRCs) subjected to hypoxia and reoxygenation (HR) were cultured as in vivo and in vitro models. Echocardiography and TTC-Evans Blue staining were performed to evaluate the myocardial injury. Transmission electron microscope and JC-1 staining were used to validate the mitochondrial function. Additionally, Western blot detected ferroptosis markers, including Gpx4, FTH, and xCT.Results: Gal treatment alleviated cardiac myofibril damage, reduced infarction size, improved cardiac function, and prevented mitochondrial injury in mice with MIRI. Gal significantly alleviated HR-induced cell death and mitigated mitochondrial membrane potential reduction in NRCs. Furthermore, Gal significantly inhibited ferroptosis by preventing iron overload and lipid peroxidation, as well as regulating Gpx4, FTH, and xCT expression levels. Moreover, Gal up-regulated nuclear transcriptive factor Nrf2 in HR-treated NRCs. Nrf2 inhibition by Brusatol abolished the protective effect of Gal against ferroptosis.Conclusion: This study revealed that Gal alleviates myocardial ischemic reperfusion-induced ferroptosis by targeting Nrf2/Gpx4 signaling pathway.Keywords: galangin, ferroptosis, myocardial ischemia/reperfusion injury, Nrf2, Gpx4

Xingyu Mu,1,&ast; Wen Li,2,&ast; Ming Zhang,2 Changxiao Yang,2 Xianxu Yang,2 Dan Li,2 Yan Ding3 1The First Clinical College of Hainan Medical University, Haikou, Hainan, People’s Republic of China; 2Department of Dermatology, The Fifth People’s Hospital of Hainan Province, Haikou, Hainan, People’s Republic of China; 3Department of Dermatology, Affiliated Dermatology Hospital of Hainan Medical University, The Fifth People’s Hospital of Hainan Province, Haikou, Hainan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dan Li, Department of Dermatology, The Fifth People’s Hospital of Hainan Province, No. 8 Longhua Road, Longhua District, Haikou, Hainan, People’s Republic of China, Tel +8613807656023, Email hn1380765@163.com Yan Ding, Department of Dermatology, Affiliated Dermatology Hospital of Hainan Medical University, The Fifth People’s Hospital of Hainan Province, No. 8 Longhua Road, Longhua District, Haikou, Hainan, People’s Republic of China, Tel +8618689980361, Email annymilk@126.comAbstract: Eruptive pruritic papular porokeratosis (EPPP) is a rare subtype of porokeratosis that presents as an acute exacerbation of an annular papule with a distinct peripheral hyperkeratotic ridge border and severe pruritus. EPPP is mainly reported in elderly East Asian men. Its etiology and pathogenesis are unknown. We hereby present a case report of EPPP in a 68-year-old Chinese male with persistent circumscribed papules on the extremities, accompanied by severe pruritus for one year. After the patient was given conventional medication, a new rash appeared on the patient’s extremities and he felt intense itching in the area of the rash. The patient was switched to oral tofacitinib treatment. The patient felt that the pruritus had largely disappeared after one month of oral dosing, leaving only brown pigmentation on the erythema of the extremities. The patient has been off the drug for 2 months. There was no pruritus or new rash during the follow-up period.Keywords: eruptive pruritic papular porokeratosis, porokeratosis, tofacitinib

Fei Wu,1,2,&ast; Haitao Sun,1,2,&ast; Zhang Shi,1,2 Changwu Zhou,1– 3 Peng Huang,1,2 Yuyao Xiao,1,2 Chun Yang,1,2 Mengsu Zeng1– 3 1Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Shanghai Institute of Medical Imaging, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mengsu Zeng, Department of Radiology, Zhongshan Hospital, Fudan University; Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, People’s Republic of China, Tel +86 13501922963, Email zeng.mengsu@zs-hospital.sh.cn Chun Yang, Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, People’s Republic of China, Tel +86 18702135336, Email dryangchun@hotmail.comObjective: To determine the preoperative clinicoradiological factors to predict microvascular invasion (MVI) in patients with resectable multinodular hepatocellular carcinoma (mHCC), and further to establish and validate a stratified risk scoring system.Methods: Two hundred and seventy-three patients with pathologically confirmed mHCC (≥ 2 lesions) without major vascular invasion and biliary tract tumor thrombosis, who underwent preoperative contrast-enhanced MRI and hepatectomy, were consecutively enrolled (training/validation cohort=193/80). Preoperative clinicoradiological variables were collected and analyzed. The multivariable logistic regression was performed to determine the independent predictors of MVI and create a risk score system. The C-index, calibration curve and decision curve were used to evaluate the performance of the risk score. A risk score-based prognostic stratification system was performed in mHCC patients. The risk score system was further verified in the validation cohort.Results: AFP > 400 ng/mL, presence of satellite nodule, mosaic architecture and increased total tumor diameter were independent predictors of MVI while fat in mass was an independent protective factor of MVI. The risk score yielded satisfactory C-index values (training/validation cohort: 0.777/0.758) and fitted well in calibration curves. Decision curve analysis further confirmed its clinical utility. Based on the risk score, mHCC patients were stratified into high-/low-MVI-risk subgroups with significantly different recurrence-free survival (both P < 0.001).Conclusion: The presented risk score incorporating clinicoradiological parameters could stratify mHCC patients into high-risk and low-risk subgroups and predict prognosis in patients with resectable mHCC.Keywords: hepatocellular carcinoma, prognosis, magnetic resonance imaging, statistical model

Chunkun Yang,1,&ast; Jiawen Cheng,1,&ast; Qinwei Zhu,2 Qingquan Pan,2 Kui Ji,2 Jun Li1 1Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Department of Emergency, Weifang Hospital of Traditional Chinese Medicine, Weifang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Li, Email gamyylj@163.comAbstract: Cardiovascular disease (CVD) is one of the leading causes of death in the world. Paeonol(Pae) is a phenolic component extracted from peony bark, peony root and Xu Changqing. Studies have shown that Pae can protect cardiomyocytes by inhibiting oxidative stress, promoting mitochondrial fusion, regulating mitochondrial autophagy and inhibiting inflammation. In addition, Pae improves ventricular remodeling by inhibiting myocardial apoptosis, hypertrophy and fibrosis. Pae also has a good protective effect on blood vessels by inhibiting vascular inflammation, reducing the expression of adhesion molecules, inhibiting vascular proliferation, and inhibiting oxidative stress and endoplasmic reticulum stress(ERS). Pae also has the effect of anti-endothelial cell senescence, promoting thrombus recanalization and vasodilating. In conclusion, the molecular targets of Pae are very complex, and the relationship between different targets and signaling pathways cannot be clearly explained, which requires us to use systems biology methods to further study specific molecular targets of Pae. It has to be mentioned that the bioavailability of Pae is poor, and some nanotechnology-assisted drug delivery systems improve the therapeutic effect of Pae. We reviewed the protective mechanism of paeonol on the cardiovascular system, hoping to provide help for drug development in the treatment of CVD.Keywords: paeonol, oxidative stress, inflammation, mitochondrial fusion, adhesion, autophagy

Yikuan Du,1,&ast; Xiaolin Cai,2,3,&ast; Bijun Xu,2,3 Yuqing Wu,2,3 Mianhai Chen,2,3 Jinjin Wang,2,3 Bing Yuan,2,3 Weichui Zhang,2,3 Jinfeng Zhu,2,3 Chun Yang2,3 1Central Laboratory, The Tenth Affiliated Hospital of Southern Medical University, Dongguan, 523059, People’s Republic of China; 2Dongguan Key Laboratory of Chronic Inflammatory Diseases, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, 523808, People’s Republic of China; 3Dongguan Key Laboratory of Stem Cell and Regenerative Tissue Engineering, Guangdong Medical University, Dongguan, 523808, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chun Yang, Dongguan Key Laboratory of Chronic Inflammatory Diseases, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, People’s Republic of China, Tel +86 150 1915 9295, Email yangchunangel@163.comBackground: Fascial pathological pain is the main type of chronic pain in older adults today, and studying the relationship between fascia and pain can help in the clinical search for effective treatments. However, in the face of the vast amount of research findings, there is no systematic assessment of the relationship between fascia and pain in a bibliometric analysis. Therefore, the purpose of this study is to analyze studies on fascia and pain using CiteSpace and VOSviewer to identify research hotspots and future directions.Materials and Methods: A total of 744 papers related to fascia and pain from 2013 to 2022 were collected from the core collection database of Web of Science, and the authors, countries, institutions, keyword co-occurrence, keyword clustering, and keyword emergence were analyzed by CiteSpace and VOSviewer to construct a knowledge map.Results: Literature publication has shown an overall upward trend over the past decade, but there have been some fluctuations. Carmelo Pirri, Caterina Fede, and Raffaele De Caro are the top three authors with the most articles. The United States, China, and Spain are major contributors to fascial and pain research. The University of Padua, Universidad Complutense and Harvard Medical School are leading institutions in this field. However, it is noteworthy that the collaboration between authors, countries and institutions is not active. Keyword analysis showed that hot spots and trends in research on fascia and pain focused on hot diseases, major interventions, and mechanism exploration.Conclusion: This analysis identifies the most influential authors, institutions, and countries in the field of fascial and pain research and provides a reference for assessing their academic impact. The analysis of keywords and co-cited literature is useful for analyzing research hotspots and their evolution, as well as for predicting future trends.Keywords: fascia, pain, bibliometrics analysis, knowledge graph, research progress

Several investigations have demonstrated the association of MTSS1 with left ventricular (LV) structure and function. A recently published study has even revealed that rs35006907 was associated with both MTSS1 expression and the risk of dilated cardiomyopathy (DCM).

Wenqian Chen,1 Dali Zheng,2 Changyi Yang1 1Department of Neonatology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 2Key Laboratory of Stomatology of Fujian Province, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, People’s Republic of ChinaCorrespondence: Changyi Yang, Department of Neonatology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, 350001, People’s Republic of China, Tel +86 15959000599, Fax +86 87279676, Email yangchangyi@fjmu.edu.cnAbstract: Ferroptosis is a novel type of programmed cell death involved in many diseases’ pathological processes. Ferroptosis is characterized by lipid peroxidation, reactive oxygen species accumulation, and iron metabolism disorder. Newborns are susceptible to ferroptosis due to their special physiological state, which is prone to abnormal iron metabolism and the accumulation of reactive oxygen species. Recent studies have linked ferroptosis to a variety of diseases in the neonatal period (including hypoxic-ischemic encephalopathy, bronchopulmonary dysplasia, and necrotizing enterocolitis). Ferroptosis may become an effective target for the treatment of neonatal-related diseases. In this review, the ferroptosis molecular mechanism, metabolism characteristics of iron and reactive oxygen species in infants, the relationship between ferroptosis and common infant disorders, and the treatment of infant diseases targeted for ferroptosis are systematically summarized.Keywords: ferroptosis, neonatal disease, reactive oxygen species, iron metabolism, lipid peroxidation

Huang Y, Chen J, Yang S, et al. Drug Des Devel Ther. 2020;14:4625–4637. We, the Editor and Publisher of the journal Drug Design, Development and Therapy, have retracted the following article. Following publication of the article, concerns were raised about the duplication of images from Figures 4 and 6. Specifically, Images for Figure 4F, MG63, control and 80 µM, have been duplicated. Images for Figure 4J, MG63, 12H, control and 100 µM, have been duplicated. Images for Figure 6D, Osteosarcoma, Blank (x 200) and 75 mg/kg (x 200) have been duplicated. Images for Figure 6E, p-Akt (Ser473), 50 mg/kg (x 400) and 75 mg/kg (x 400) have been duplicated. The authors responded to our queries but were unable to provide a satisfactory explanation for the duplicated images or provide satisfactory 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”.

Jin-ning Wang,1,&ast; Wei Xie,2,&ast; Da-Wei Song,1,&ast; Jun Zou,1 Qi Yan,1 Tao Feng,1 Sheng-yang Jin,1 Chao Yang,1 Zong-ping Luo,1,3 Jun-jie Niu1 1Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Department of Orthopaedics, Suzhou Ninth People’s Hospital, Suzhou, Jiangsu, People’s Republic of China; 3Orthopedic Institute, Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zong-ping Luo, Orthopedic Institute, Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China, Tel +86-512-67781351, Email zongping_luo@yahoo.com Jun-jie Niu, Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China, Tel +86-512-67780111, Email jjnewzzzx@sina.comBackground: Recurrent of local kyphosis after percutaneous kyphoplasty (PKP) is rarely reported and discussed. Literatures reported that re-kyphosis is usually a consequence of refractures of augmented or adjacent vertebra. However, whether re-kyphosis should be considered as a complication of refractures and has an impact on clinical efficacy of PKP during follow-up time is unknown. The purpose of this study is to evaluate the related risk factors and clinical significance of the recurrent of local kyphosis in osteoporotic vertebral fracture (OVF) patients without refractures.Patients and Methods: A total of 143 patients who underwent single-level PKP were recruited and assigned into the re-kyphosis group and non-re-kyphosis group. Clinical and radiographic data were collected and compared between the two groups. Then, multivariate logistic regression analyses were conducted to identify the related risk factors.Results: During follow-up, 16 of the 143 patients presented postoperative re-kyphosis. The average local kyphosis angle increased from 11.81± 8.60° postoperatively to 25.13± 8.91° at the final follow-up which showed a statistically significant difference (p< 0.05). Both groups had significant improvements in postoperative visual analogue scale (VAS) and Oswestry Disability Index (ODI) scores compared to their preoperative values (p< 0.05). However, in the re-kyphosis group at final follow-up, the VAS and ODI scores showed worsening compared to the postoperative scores. Logistic regression analysis showed that disc–endplate complex injury (OR=17.46, p=0.003); local kyphosis angle correction (OR=1.84, p< 0.001); and vertebral height restoration (OR=1.15, p=0.003) were risk factors for re-kyphosis.Conclusion: Re-kyphosis is not rare in patients with osteoporotic vertebral fracture and tends to have an inferior prognosis following PKP surgery. Patients with disc–endplate complex injury and more correction of vertebral height and kyphosis angle are at a higher risk for re-kyphosis after PKP surgery than others.Keywords: percutaneous kyphoplasty, risk factors, re-kyphosis, disc–endplate complex injury, clinical efficacy

Yuan Li,1,2,&ast; Wanni Li,1,&ast; Ming Zhang,1 Xianxu Yang,1 Changxiao Yang,1 Dan Li1 1Dermatology Department, The Fifth People’s Hospital of Hainan Province, Haikou, Hainan, People’s Republic of China; 2Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Changxiao Yang; Dan Li, Dermatology Department, The Fifth People’s Hospital of Hainan Province, No. 8 Longhua Road, Longhua District, Haikou, Hainan, 570100, People’s Republic of China, Email 13648641216@163.com; hn1380765@163.comAbstract: Our report concerns a 72-year-old female patient who presented with nodular ulcers on her right lower extremity and foot for a duration of 5 months. Based on the results of a dermatological examination, histopathological examination of the lesions, and immunohistochemical findings, we were able to diagnose the patient with Mari-type pseudocaposi sarcoma. Further research allowed us to clarify the distinction between this type of sarcoma and Kaposi’s sarcoma, which will be crucial in devising an effective treatment plan for the patient as we continue to monitor her progress during clinical supervision.Keywords: pseudo-Kaposi’s sarcoma, Kaposi’s sarcoma, immunohistochemistry, CD34

Cantao Yang,1,&ast; Zhaohong Lu,1,&ast; Yinyin Xia,1 Jun Zhang,2,3 Zhen Zou,2,3 Chengzhi Chen,1,3 Xiaoliang Wang,4 Xin Tian,5 Shuqun Cheng,1,3 Xuejun Jiang3,6 1Department of Occupational and Environmental Health, School of Public Health, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Molecular Biology Laboratory of Respiratory Diseases, Institute of Life Sciences, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 3Research Center for Environment and Human Health, School of Public Health, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 4Medical Sciences Research Center, University-Town Hospital of Chongqing Medical University, Chongqing, 401331, People’s Republic of China; 5Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 6Center of Experimental Teaching for Public Health, Experimental Teaching and Management Center, Chongqing Medical University, Chongqing, 400016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shuqun Cheng; Xuejun Jiang, Research Center for Environment and Human Health, School of Public Health, Chongqing Medical University, Number 1, Yixueyuan Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel +86-23-68485008, Fax +86-23-68485207, Email 100077@cqmu.edu.cn; xuejunjiang@cqmu.edu.cnPurpose: The widespread use of zinc oxide nanoparticles (ZnONPs) has raised concerns about its potential toxicity. Melatonin is a neurohormone with tremendous anti-toxic effects. The enterochromaffin cells are an essential source of melatonin in vivo. However, studies on the effects of ZnONPs on endogenous melatonin are minimal. In the present study, we aimed to investigate the effects of ZnONPs exposure on gut-derived melatonin.Methods: In the present study, 64 adult male mice were randomly and equally divided into four groups, and each group was exposed to ZnONPs (0, 6.5, 13, 26 mg/kg/day) for 30 days. Subsequently, the neurobehavioral changes were observed. The effects of ZnONPs on the expression of melatonin-related genes arylalkylamine N-acetyltransferase (Aanat), melatonin receptor1A (Mt1/Mtnr1a), melatonin receptor1B (Mt2/Mtnr1b), and neuropeptide Y (Npy) on melatonin synthesis and secretion in duodenum, jejunum, ileum and colon during day and night were also assessed.Results: The results revealed that oral exposure to ZnONPs induced impairments of locomotor activity and anxiety-like behavior in adult mice during the day. The transcriptional analysis of brain tissues revealed that exposure to ZnONPs caused profound effects on genes and transcriptional signaling pathways associated with melatonin synthesis and metabolic processes during the day and night. We also observed that, in the duodenum, jejunum, ileum and colon sites, ZnONPs resulted in a significant reduction in the expression of the gut-derived melatonin rate-limiting enzyme Aanat, the membrane receptors Mt1 and Mt2 and Npy during the day and night.Conclusion: Taken together, this is the first study shows that oral exposure to ZnONPs interferes with melatonin synthesis and secretion in different intestinal segments of adult mice. These findings will provide novelty insights into the neurotoxic mechanisms of ZnONPs and suggest an alternative strategy for the prevention of ZnONP neurotoxicity.Graphical Abstract: Keywords: gut-derived melatonin, neurobehavioral impairment, transcriptome sequencing, zinc oxide nanoparticle exposure

Mei Fu,1 Jun Li,2 Mingchong Liu,1 Chensong Yang,1 Qidong Wang,1 Hongrui Wang,3 Bingdi Chen,2 Qingge Fu,3 Guixin Sun1 1Department of Traumatic Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Institute for Regenerative Medicine, Shanghai East Hospital, The Institute for Biomedical Engineering & Nano Science, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 3Department of Orthopedic Trauma, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, People’s Republic of ChinaCorrespondence: Guixin Sun; Qingge Fu, Email sunguixin@tongji.edu.cn; fqg7821@163.comBackground: Immune responses and osteogenesis differentiation induced by implants are crucial for bone tissue regeneration. Consideration of only one of those properties is not sufficient. To investigate the synergistic actions, we designed alginate/graphene oxide/sericin/nanohydroxyapatite (Alg/GO/Ser/nHAP) nanocomposite hydrogels with both osteoimmunomodulatory and osteoinductive activities. This study aimed to explore the effect of hydrogel with osteoimmunomodulatory properties on promoting osteogenesis of bone marrow stem cells (BMSCs).Methods: Alg/GO/Ser/nHAP nanocomposite hydrogel was fabricated and was characterized by SEM, FTIR, XRD, stress-strain, rheology, swelling and degradation. After the impact of sericin on M2 macrophage polarization was identified, the BMSCs viability and adhesion were evaluated by CCK8 assay, live/dead staining, cytoskeleton staining. The cell osteogenic differentiation was observed by ALP/ARS staining, immunofluorescence staining, RT-PCR, and Western blotting, respectively. Rat cranial defect model was used to assess osteoimmunomodulatory effects of scaffolds in vivo by micro‑computed tomographic, histological, and immunohistochemical analyses after 8 weeks of healing.Results: In vitro experiments revealed that the hydrogel presented desirable mechanical strength, stability, porosity, and biocompatibility. Significantly, sericin and nHAP appeared to exert synergistic effects on bone regeneration. Sericin was observed to inhibit the immune response by inducing macrophage M2-type polarization to create a positive osteoimmune microenvironment, contributing to improving osseointegration at the bone-implant interface to promote osteogenesis. However, the osteogenic differentiation in rat BMSCs was further enhanced by combining nHAP and sericin in the nanocomposite hydrogel. Eventually, the hydrogel was implanted into the rat cranial defect model, assisting in the reduction of local inflammation and efficient bone regeneration.Conclusion: The nanocomposite hydrogel stimulated bone formation by the synergistic effects of immunomodulation of macrophage polarization by sericin and direct osteogenic induction by nHAP, demonstrating that such a scaffold that modulates the osteoimmune microenvironment to promote osteogenesis is a promising approach for the development of bone tissue engineering implants in the future.Graphical Abstract: Keywords: hydrogel, nano-hydroxyapatite, sericin, osteoimmunomodulation, osteoinduction, bone regeneration

Jun Shen,1,&ast; Huanhuan Yan,1,&ast; Congying Yang,2 Haiyue Lin,2 Fan Li,1 Jun Zhou1 1Department of Breast Surgery, The First People’s Hospital of Lianyungang, The First Affiliated Hospital of Kangda College of Nanjing Medical University, Lianyungang, Jiangsu, 222002, People’s Republic of China; 2Department of Pathology, The First People’s Hospital of Lianyungang, The First Affiliated Hospital of Kangda College of Nanjing Medical University, Lianyungang, Jiangsu, 222002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Zhou, Department of Breast surgery, The First People’s Hospital of Lianyungang, The First Affiliated Hospital of Kangda College of Nanjing Medical University, No. 6 Zhenhua East Road, High-Tech Square, Lianyungang, Jiangsu Province, 222002, People’s Republic of China, Tel +86 18961326373, Email zhoujunzj91@126.comObjective: To explore the validation of a disease-free survival (DFS) model for predicting disease progression based on the combination of ubiquitin-conjugating enzyme E2 C (UBE2C) levels and clinical indicators in breast cancer patients.Methods: We enrolled 121 patients with breast cancer, collected their baseline characteristics and follow-up data, and analyzed the UBE2C levels in tumor tissues. We studied the relationship between UBE2C expression in tumor tissues and disease progression events of patients. We used the Kaplan-Meier method for identifying the disease-free survival rate of patients, and the multivariate Cox regression analysis to study the risk factors affecting the prognosis of patients. We sought to develop and validate a model for predicting disease progression.Results: We found that the level of expression of UBE2C could effectively distinguish the prognosis of patients. In the Receiver Operating Characteristic (ROC) curve analysis, the Area under the ROC Curve (AUC) = 0.826 (0.714– 0.938) indicating that high levels of UBE2C was a high-risk factor for poor prognosis. After evaluating different models using the ROC curve, Concordance index (C-index), calibration curve, Net Reclassification Index (NRI), Integrated Discrimination Improvement Index (IDI), and other methods, we finally developed a model for the expression of Tumor-Node (TN) staging using Ki-67 and UBE2C, which had an AUC=0.870, 95% CI of 0.786– 0.953. The traditional TN model had an AUC=0.717, and 95% CI of 0.581– 0.853. Decision Curve Analysis (DCA) and Clinical Impact Curve (CIC) analysis indicated that the model had good clinical benefits and it was relatively simple to use.Conclusion: We found that high levels of UBE2C was a high-risk factor for poor prognosis. The use of UBE2C in addition to other breast cancer-related indicators effectively predicted the possible disease progression, thus providing a reliable basis for clinical decision-making.Keywords: breast cancer, nomograms, prediction model, prognosis, UBE2C

Peiru Si,1 Jiaxing Lei,1 Chen Yang,1 Peipei Zhang,1 Xiaojiao Li,2 Shaohua Zheng,3 Qingqing Li,1 Jiye Zhang1 1School of Pharmacy, Health Science Center, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Biobank, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 3Department of Anesthesiology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of ChinaCorrespondence: Qingqing Li; Jiye Zhang, School of Pharmacy, Health Science Center, Xi’an Jiaotong University, No. 76 Yanta Westroad, Xi’an, People’s Republic of China, Email liqingqing0217@xjtu.edu.cn; zjy2011@xjtu.edu.cnIntroduction: Hepatic ischemia-reperfusion injury (HIRI) is the main reason for liver dysfunction or failure after liver resection and liver transplantation. As excess accumulation of reactive oxygen species (ROS) is the leading factor, ceria nanoparticle, a cyclic reversible antioxidant, is an excellent candidate for HIRI.Methods: Manganese doped mesoporous hollow ceria nanoparticles (MnOx-CeO2 NPs) were prepared, and the physicochemical characteristics, such as particle size, morphology, microstructure, etc. were elucidated. The in vivo safety and liver targeting effect were examined after i.v. injection. The anti-HIRI was determined by a mouse HIRI model.Results: MnOx-CeO2 NPs with 0.40% Mn doped exhibited the strongest ROS-scavenging capability, which may due to the increased specific surface area and surface oxygen concentration. The nanoparticles accumulated in the liver after i.v. injection and exhibited good biocompatibility. In the HIRI mice model, MnOx-CeO2 NPs significantly reduced the serum ALT and AST level, decreased the MDA level and increased the SOD level in the liver, prevent pathological damages in the liver.Conclusion: MnOx-CeO2 NPs were successfully prepared and it could significantly inhibit the HIRI after i.v. injection.Graphical Abstract: Keywords: hepatic ischemia reperfusion injury, Mn-doped mesoporous hollow cerium oxide nanoparticles, oxidative stress

Yubo Li,1– 4 Xiaoyan Ni,2– 4 Xinai Liu,1 Chun Yang,2– 4 Yi Wang,2,4 Xin Lu,2– 4 Changwu Zhou2– 4 1Department of MRI, Henan Provincial Hospital of Traditional Chinese Medicine (the Second Affiliated Hospital of Henan University of Traditional Chinese Medicine), Zhengzhou, People’s Republic of China; 2Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Shanghai Institute of Medical Imaging, Shanghai, People’s Republic of China; 4Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Xin Lu; Changwu Zhou, Shanghai Institute of Medical Imaging; Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, People’s Republic of China, Tel +86 18702135336 ; +86 13912121145, Email luxcn@163.com; changwu83@163.comObjective: The prognostic value of the Liver Imaging Reporting and Data System (LI-RADS) 2018 in differentiating hepatocellular carcinoma (HCC) from other primary liver cancers (PLC) with cirrhosis is unclear. We aim to evaluate the value of LI-RADS 2018 with agent-enhanced MRI in the postoperative prognosis of PLC patients with cirrhosis.Methods: Between 2016 and 2021, 432 patients with cirrhosis and surgically proven single primary liver cancer were retrospectively evaluated. Two radiologists evaluated the preoperative MRI features independently and assigned each lesion a LI-RADS category. Overall survival (OS), recurrence-free survival (RFS), and their associated factors were evaluated by using the Kaplan-Meier method, Log rank test, and Cox proportional hazards model.Results: The mean age of 432 patients (239 HCCs, 93 ICCs, and 100 cHCC-CCAs) was 57.27± 10.92 years. The LR-M category showed poorer OS and RFS than the LR-4 or LR-5 category did for all primary liver cancers (P < 0.001 for both), and so did HCCs with tumor size less than 30mm (P =0.003 and P =0.04, respectively). In the multivariable analysis, the LI-RADS category and tumor size > 30 mm had independent correlations with OS and RFS (all P < 0.05). Multivariable Cox analysis identified rim arterial phase hyperenhancement (APHE) as independent determinants of poor OS and RFS in primary liver cancers (all P < 0.05).Conclusion: The LI-RADS categories can predict the postsurgical prognosis of primary liver cancers independently.Keywords: hepatocellular carcinoma, magnetic resonance imaging, prognosis, liver cirrhosis

Tingting Li,1,&ast; Yilan Zeng,2,&ast; Xianrong Fan,3,&ast; Jing Yang,4 Chengying Yang,4 Qingyun Xiong,5 Ping Liu2 1Department of Science and Education, Changsha Hospital Affiliated to Xiangya Medical College, Central South University, Changsha, Hunan Province, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Changsha Hospital Affiliated to Xiangya Medical College, Central South University, Changsha, Hunan Province, People’s Republic of China; 3Department of Hospital Office, The Maternal and Child Health Hospital of Yongchuan, Chongqing, People’s Republic of China; 4Department of Obstetrics and Gynecology, Changsha Hospital Affiliated to Xiangya Medical College, Central South University, Changsha, Hunan Province, People’s Republic of China; 5Department of Ultrasonography, Changsha Hospital of Traditional Chinese Medicine, Changsha, Hunan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ping Liu, Department of Respiratory and Critical Care Medicine, Changsha Hospital Affiliated to Xiangya Medical College, Central South University, 311 Yingpan Road, Kaifu District, Changsha, Hunan Province, 410005, People’s Republic of China, Tel +86 15973136512, Email liuping_3356@126.com Qingyun Xiong, Department of Ultrasonography, Changsha Hospital of Traditional Chinese Medicine, No. 22, Xingsha Avenue, Changsha County, Changsha City, Hunan Province, 410100, People’s Republic of China, Tel +86 731-85259000, Email xiongqy1100@21cn.comObjective: This study aimed to bibliometrically analyse the main features of the 100 top-cited articles on the midwifery index on the Web of Science.Methods: Academic articles on midwifery’ research published from 1985 to 2020 were included. VOSviewer 1.6.15, SPSS 22.0 software and a homemade applet were used to identify, analyse and visualise the citation ranking, publication year, journal, country and organisation of origin, authorship, journal impact factor and keywords along with the total link strength of countries, organisations and keywords.Results: Among the 100 top-cited articles, the highest number of citations of the retrieved articles was 484. The median number of citations per year was 5.16 (interquartile range: 3.74– 8.38). Almost two-thirds of the included articles (n = 61) centred on nursing and obstetrics/gynaecology. The top-cited articles were published in 38 different journals, the highest number of which was published by Midwifery (15%). Australia was the most productive country (24%). According to the total link strength, the sequence ran from the United States (28) to England (28) to Australia (19). The University of Technology Sydney and La Trobe University in Australia topped the list with four papers each. Hunter B was the most productive author (n = 4), and the average citations were positively related to the number of authors (r = 0.336, p < 0.05).Conclusion: This study identified the most influential articles on midwifery and documented the core journals and the most productive countries, organisations and authors along with future research hotspots for this field; the findings may be beneficial to researchers in their publication and scientific cooperation endeavours.Keywords: bibliometric analysis, citation, midwifery, total link strength

Jingjing Zhong, Ming Wei, Chunxia Yang, Yudong Yin, Yu Bai, Ran Li, Li Gu Department of Infectious Diseases and Clinical Microbiology, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Li Gu, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100000, People’s Republic of China, Email guli2013227@foxmail.comPurpose: Since community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) was recognized, the molecular epidemiology of CA-MRSA in China has been diverse. It is unclear whether different sites of CA-MRSA infection differ in antimicrobial resistance and clinical characteristics. The purpose of this study was to identify the molecular types, virulence factors and antimicrobial resistance of CA-MRSA strains and to analyze the clinical characteristics of different sites of CA-MRSA infection.Methods: 26 CA-MRSA strains were screened from Beijing Chao-Yang Hospital from 2014 to 2022. SCCmec type, MLST type, spa type, Panton–Valentine leukocidin (PVL), hemolysin α (Hla), phenolic soluble regulatory protein α (PSMα), toxic shock syndrome toxin-1 (TSST-1), and enterotoxin (SE) A to E were detected by PCR and gene sequencing. Antimicrobial susceptibility tests and the clinical features of CA-MRSA infection cases were collected for statistical analysis.Results: The predominant type of CA-MRSA was ST59-t437-IV. New non-epidemic types, SCCmec VII, were also found. PVL was seen in 65.4% of CA-MRSA strains and TSST-1 was only be detected in 3.8% of CA-MRSA strain which caused poor prognosis. There were three types of infections: pneumonia (61.5%), infective endocarditis (7.7%), and skin and soft tissue infections (SSTIs) (30.8%). CA-MRSA pneumonia cases were secondary to influenza infection (37.5%). Patients with CA-MRSA-associated infective endocarditis were more likely to have underlying cardiac diseases. Patients with CA-MRSA-associated SSTIs were more likely to have a history of diabetes mellitus, and strains in this group were more susceptible to erythromycin and clindamycin.Conclusion: ST59-t437-IV was the primary CA-MRSA type in our research and in China. We proposed that TSST-1 might be one of the indicators to predict the severity and prognosis of CA-MRSA infection. Different sites of CA-MRSA infection had difference in antibiotics susceptibility testing and underlying diseases of patients. It could provide a new perspective on treating different types of CA-MRSA infection.Keywords: community, acquired methicillin, resistant Staphylococcus aureus, staphylococcal chromosomal cassette mec type, Panton-Valentine leukocidin, antibiotic resistance, pneumonia

Uet Yu,1 Ke Cao,2 Chunlan Yang,1 Chunjing Wang,1 Yue Li,1 Xiaohui Zhou,1 Qian Zhang,1 Yuanxiang Wang,3 Feiqiu Wen,1 Sixi Liu,1 Xiaodong Wang1 1Department of Hematology and Oncology, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of China; 2Department of Laboratory Medicine, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of China; 3Department of Cardiothoracic Surgery, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of ChinaCorrespondence: Xiaodong Wang; Sixi Liu, Email donlevin@live.cn; tiger647@126.comAbstract: Invasive fungal infections (IFIs) are among the most severe complications in recipients of hematopoietic stem cell transplantation (HSCT) recipients and in patients with hematological malignancies. An increasing number of uncommon fungal infections have been reported in this era of antifungal prophylaxis. Coprinopsis cinerea is a rare pathogen that causes opportunistic infections in the immunocompromised patients, including HSCT recipients and is associated with very high mortality rates. Herein, we present a successfully treated pediatric HSCT patient with breakthrough pulmonary IFI caused by Coprinopsis cinerea despite posaconazole, prophylaxis using multidisciplinary approaches.Keywords: Coprinopsis cinerea, Hormographiella aspergillata, invasive fungal infection, hematopoietic stem cell transplantation, leukemia, case report

Jing Wang,1 Shuanghu Fang,1 Chunying Yang,2 Xiaobin Tang,3 Luosha Zhu,3 Yu Nie4 1School of Educational Science, Anhui Normal University, Wuhu, People’s Republic of China; 2School of Special Education, Zhengzhou Normal University, Zhengzhou, People’s Republic of China; 3School of Marxism, Anhui Normal University, Wuhu, People’s Republic of China; 4Office of Student Affairs, Anhui Normal University, Wuhu, People’s Republic of ChinaCorrespondence: Shuanghu Fang, Email fsh9075@163.comPurpose: To explore the potential classification of psychological flexibility (PF) among Chinese college students, analyze whether there is group heterogeneity in PF, and discuss the differences in the latent profile of PF in the negative emotions of depression, anxiety, and stress.Methods: A total of 1769 college students were investigated using the Psychological Flexibility Questionnaire and Depression-Anxiety-Stress Self-rating Scale, and heterogeneity was tested by latent profile analysis.Results: The PF of college students can be divided into three latent profiles: self-contradiction group (19.2%), high PF group (34.1%), and low PF group (46.7%). The scores of depression, anxiety, and stress are significantly different among the groups.Conclusion: There is obvious group heterogeneity in the PF of college students, and they can be divided into the self-contradiction group, the high PF group, and the low PF group. The self-contradiction and low PF groups score significantly higher on the negative emotions of depression, anxiety, and stress than the high PF group.Keywords: acceptance and commitment therapy, psychological flexibility, negative emotions, latent profile analysis

Yining Wu,1,&ast; Shenjian Ou,1,&ast; Xiwen Liao,1,2 Chuangye Han,1,2 Chengkun Yang,1,2 Wei Qin,1 Yufeng Tan,1 Quan Lao,1 Tao Peng,1,2 Xinping Ye1 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China; 2Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinping Ye; Tao Peng, Tel +86-771-5356528, Fax +86-771-5350031, Email yexinping@gxmu.edu.cn; pengtaogmu@163.comAbstract: Situs inversus totalis (SIT) is a rare congenital condition in which abdominal and thoracic organs are transposed from normal positions. Two-stage hepatectomy (TSH) combined with translational therapy for hepatocellular carcinoma (HCC) with SIT has been rarely reported. We report a 41-year-old man with giant hepatocellular carcinoma (71 mm × 55 mm × 51 mm) whose future residual liver (FLR) and standard liver volume (SLV) ratio at first diagnosis was 37.4%. Preoperative volume assessment of portal vein ligation (PVL) revealed inadequate hypertrophy of FLR. After a multidisciplinary group discussion (MDT), the patient decided to follow conversion therapy. Three months later, ratio of the FLR/SLV increased from 37.4% to 71% after operation, which met the surgical requirements. Second hepatectomy, right lobectomy was successful. There was no recurrence after six months of follow-up. In our case, conversion therapy appears to be effective in maintaining residual liver hyperplasia, reducing tumor load, and preventing tumor progression in patients with large HCC during TSH.Keywords: situs inversus totalis, two-stage hepatectomy, hepatocellular carcinoma, future residual liver, multidisciplinary group discussion

Peng Huang,1,2,&ast; Xiaoyan Ni,1,2,&ast; Changwu Zhou,1– 3 Zhang Shi,1,2 Fei Wu,1,2 Yuyao Xiao,1,2 Chun Yang,1,2 Mengsu Zeng1– 3 1Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Shanghai Institute of Medical Imaging, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mengsu Zeng, Shanghai Institute of Medical Imaging, Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, People’s Republic of China, Tel +86 13501922963, Email zeng.mengsu@zs-hospital.sh.cn Chun Yang, Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, People’s Republic of China, Tel +86 18702135336, Email dryangchun@hotmail.comObjective: To compare the pathologic diagnosis and survival of patients with subcentimeter and 1– 2 cm nodules that present with diagnostic hallmarks of hepatocellular carcinoma (HCC).Methods: Diagnostic hallmarks of HCC were defined as hyperintensity on T2 weighted imaging, restricted diffusion, arterial phase hyperenhancement, washout on portal venous phase, and hypointensity on hepatobiliary phase. We retrospectively included 139 patients undergoing curative resection with single nodules ≤ 2 cm that present imaging features described above on gadoxetic acid-enhanced MRI. The final diagnosis was confirmed by histopathological assessment. Recurrence-free survival (RFS) was compared using Kaplan–Meier analysis with the Log-rank test. Factors associated with overall and early recurrence were identified using Cox regression analysis.Results: Among 139 nodules (49 nodules < 1 cm), there was no significant difference in the percentage of HCC between subcentimeter and 1– 2 cm nodules (94.0% vs 94.4%, P > 0.999). Microvascular invasion (MVI) was less common in subcentimeter HCC (4.3% vs 17.6%, P = 0.032). There were 27 recurrences during a median follow-up time of 46.7 months. Patients with subcentimeter HCC achieved less recurrence, with a 5-year RFS rate of 87.3%. The MVI-positive patients had more early and overall recurrence. A tumor size < 1 cm was associated with lower overall recurrence (HR, 0.336; P = 0.047). No factors were independently associated with early recurrence.Conclusion: Subcentimeter nodules with diagnostic hallmarks of HCC are highly associated with HCC diagnosis and achieve less tumor recurrence after resection. Early diagnosis and treatment of subcentimeter HCC may be more appropriate.Keywords: carcinoma, hepatocellular, magnetic resonance imaging, gadolinium ethoxybenzyl DTPA

Zhenghua Zhu,1,&ast; Xiang Wang,1,&ast; Jinhong Zhao,1 Zuozhou Xie,1 Chen Yang,1 Lingyi Li,2 Yi Liu1 1Department of Respiration, The Second People’s Hospital of Kunming, Kunming, People’s Republic of China; 2Department of Medical, Hangzhou Matridx Biotechnology Co., Ltd, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lingyi Li, Department of Medical, Hangzhou Matridx Biotechnology Co., Ltd, No. 2073 Jinchang Road, Yuhang District, Hangzhou, Zhejiang Province, 311100, People’s Republic of China, Tel +8613888173009, Email 001lly@sina.com Yi Liu, Department of Respiration, the Second People’s Hospital of Kunming, No. 871 Longquan Road, Panlong District, Kunming City, Yunnan Province, 650051, People’s Republic of China, Tel +8613648898773, Email 13648898773zzh@sina.comAbstract: The incidence of psittacosis infection has gradually increased in recent years. Metagenomic next-generation sequencing (mNGS) can be used to comprehensively identify the total DNA and RNA content of the microbiome, as well as identify both known and unexpected pathogens within 24 hours. We diagnosed and treated six patients with psittacosis infection using mNGS, two of whom developed severe disease and most of whom presented with pulmonary symptoms. One of the young female patients also presented with irregular vaginal bleeding and myocarditis. Patients with underlying gastric disorders first showed gastrointestinal symptoms, which is a rare manifestation in patients with psittacosis. Older patients with underlying disease usually showed more severe symptoms. However, rare complications can also occur in immunocompetent young people and develop into severe disease. All patients showed significant congestion at bronchial lumen lesions, which may be associated with a severe inflammatory response to mucosal Chlamydia psittaci (C. psittaci) infection. Overall, mNGS is a rapid and effective tool for the clinical diagnosis of psittacosis caused by C. psittaci, and early diagnosis and treatment can prevent psittacosis from developing into a serious illness.Keywords: Chlamydia psittaci, diagnosis, evolutionary tree, metagenomic next-generation sequencing, serotype

Lijuan Xiong,1,&ast; Xu Long,1,&ast; Lijun Ni,2,&ast; Lili Wang,2 Yang Zhang,1 Lili Cui,1 Jian Guo,2 Chunying Yang1 1Department of Laboratory Medicine, the Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guizhou, People’s Republic of China; 2Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Guo, Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, No. 1800 Yuntai Road, Pudong New Area, Shanghai, People’s Republic of China, Tel +86-17701810639, Email guojian1110@126.com Chunying Yang, Department of Laboratory Medicine, the Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, No. 83 Feishan Street, Yunyan District, Guiyang City, Guizhou Province, People’s Republic of China, Tel +86-13658504875, Email 2590470591@qq.comPurpose: Matrix-assisted laser desorption-ionization-time of flight mass spectrometry (MALDI-TOF) has recently been widely used in clinical microbiology laboratories, with the advantages of being reliable, rapid, and cost-effective. Here, we reported the performance of two MALDI-TOF MS instruments, EXS3000 (Zybio, China) and Autof ms1000 (Autobio, China), which are commonly used in clinical microbiology field.Methods: A total of 209 common clinical common isolates, including 70 gram-negative bacteria strains, 58 gram-positive bacteria strains, 33 yeast strains, 15 anaerobic bacteria strains, and 33 mold strains, and 19 mycobacterial strains were tested. All strains were identified by EXS3000 (Zybio, China) and Autof ms1000 (Autobio, China). Sequence analysis of 16S rRNA or ITS regions was used to verify all strains.Results: Current study found that species-level discrimination was found to be 191 (91.39%) and 190 (90.91%) by EXS3000 and Autof ms1000, respectively. Genus-level discrimination was 205 (98.09%) by the EXS3000 and 205 (98.09%) by the Autof ms1000, respectively. The correct results at species level of the EXS3000 were 91.43% (64/70) for gram-negative bacteria, 93.1% (54/58) for gram-positive cocci, 93.94% (31/33) for yeast, 100% (15/15) for anaerobes and 81.82% (27/33) for filamentous fungi. The correct results at species level of the Autof ms1000 were 92.86% (65/70) for gram-negative bacteria, 91.38% (53/58) for gram-positive cocci, 93.94% (31/33) for yeast, 100% (15/15) for anaerobes and 78.79% (26/33) for filamentous fungi.Conclusion: Although the results show that the EXS3000 and Autof ms1000 systems are equally good choices in terms of analytical efficiency for routine procedures, the test result of EXS3000 is slightly better than Autof ms1000. It’s worth mentioning that the target plate of the EXS 3000 instrument is reusable, but the target plate of the Autof ms1000 is disposable, making the EXS3000 more effective in reducing costs.Keywords: evaluation, MALDI-TOF mass spectrometry, EXS3000, Autof ms1000, clinical isolates, identification, gram-negative bacteria, gram-positive bacteria, mycobacteria, yeast, anaerobic bacteria

Xueping Wang, Zhixing Guo, Xingping Wu, Da Chen, Fang Wang, Lewei Yang, Min Luo, Shaocong Wu, Chuan Yang, Lamei Huang, Liwu Fu State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Guangdong Esophageal Cancer Institute; Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People’s Republic of ChinaCorrespondence: Liwu Fu, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Guangdong Esophageal Cancer Institute; Cancer Center, Sun Yat-sen University, 651 Dongfengdong Road, Guangzhou, 510060, People’s Republic of China, Email fulw@mail.sysu.edu.cnIntroduction: Various studies have reported that anti-PD-1/PD-L1 treatment may lead to the rapid development of tumors called hyperprogressive disease (HPD). A nomogram for HPD prediction in NSCLC patients is urgently needed.Methods: This retrospective cohort study included 176 cases for establishing a model of HPD prediction and 85 cases for validation in advanced NSCLC patients treated with PD-1/PD-L1 inhibitors. HPD was defined as tumor growth rate (TGR, ≥ 2), tumor growth kinetics (TGK, ≥ 2) or time to treatment failure (TTF, ≤ 2 months). Univariate and multivariate logistic regression were used to estimate the specified factors associated with HPD. Then, the nomogram was developed and validated.Results: Anti-PD-1/PD-L1 therapy resulted in a 9.66% (17/176) incidence of HPD in advanced NSCLC. The overall survival (OS) and progression-free survival (PFS) in patients with HPD were significantly shorter than those in patients without HPD (OS: 7.00 vs 12.00 months, P< 0.01; PFS: 2.00 vs 5.00 months, P< 0.001, respectively). The HPD prediction nomogram included APTT (P< 0.01), CD4+ CD25+ CD127-low cells (Treg cells) (P< 0.01), the presence of liver metastasis (P< 0.05), and more than two metastatic sites (P< 0.05). Then, patients were divided into two groups by the “HPD score” calculated by the nomogram. The C-index was 0.845, while the area under the curve (AUC) was 0.830 (sensitivity 75.00%, specificity 91.70%). The calibration plot of HPD probability showed an optimal agreement between the actual observation and prediction by the nomogram. In the validation cohort, the AUC was up to 0.960 (sensitivity 88.70%, specificity 89.80%).Conclusions: The nomogram was constructed with the presence of liver metastasis, more than two metastatic sites, lengthened APTT and a high level of Treg cells, which could be used to predict HPD risk.Keywords: PD-1/PD-L1 inhibitors, hyperprogressive disease, non-small cell lung cancer, nomogram

Chengkai Yang,1 Xiaoya Wu,2 Jianyong Liu,3 Huaxiang Wang,1 Yi Jiang,3 Zhihong Wei,3 Qiucheng Cai3 1The Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, 350025, People’s Republic of China; 2Eastern Hospital Affiliated to Xiamen University, Fuzhou, 350025, People’s Republic of China; 3Department of Hepatobiliary Surgery, 900 Hospital of The Joint Logistics Team, Fuzhou, 350025, People’s Republic of ChinaCorrespondence: Qiucheng Cai; Zhihong Wei, Department of Hepatobiliary Surgery, 900 Hospital of The Joint Logistics Team, No. 156 The Second West Ring Road, Fuzhou, Fujian, 350025, People’s Republic of China, Tel +86 13514072408 ; +86 18059055977, Email caiqiucheng2211@163.com; 779349357@qq.comPurpose: In this study, we developed a nomogram based on the platelet–albumin–bilirubin (PALBI) score to predict recurrence-free survival (RFS) after curative resection in alpha-fetoprotein (AFP)-negative (≤ 20 ng/mL) hepatocellular carcinoma (HCC) patients.Patients and Methods: A total of 194 pathologically confirmed AFP-negative HCC patients were retrospectively analyzed. Univariate and multivariate Cox regression analyses were performed to screen the independent risk factors associated with RFS, and a nomogram prediction model for RFS was established according to the independent risk factors. The receiver operating characteristic (ROC) curve and the C-index were used to evaluate the accuracy and the efficacy of the model prediction. The correction curve was used to assess the calibration of the prediction model, and decision curve analysis was performed to evaluate the clinical application value of the prediction model.Results: PALBI score, MVI, and tumor size were independent risk factors for postoperative tumor recurrence (P < 0.05). A nomogram prediction model based on the independent predictive factors was developed to predict RFS, and it achieved a good C-index of 0.704 with an area under the ROC curve of 0.661 and the sensitivity was 73.2%. Patients with AFP-negative HCC could be divided into the high-risk group or the low-risk group by the risk score calculated by the nomogram, and there was a significant difference in RFS between the two groups (P < 0.05). Decision curve analysis (DCA) showed that the nomogram increased the net benefit in predicting the recurrence of AFP-negative HCC and exhibited a wider range of threshold probabilities than the independent risk factors (PALBI score, MVI, and tumor size) by risk stratification.Conclusion: The nomogram based on the PALBI score can predict RFS after curative resection in AFP-negative HCC patients and can help clinicians to screen out high-risk patients for early intervention.Keywords: hepatocellular carcinoma, platelet–albumin–bilirubin score, alpha-fetoprotein-negative, recurrence-free survival, nomogram

Gaizhi Li,1,2 Lei Lei,1 Chunxia Yang,1 Zhifen Liu,1 Ke-Rang Zhang1,2 1Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of Psychiatry, First Clinical Medical College, Shanxi Medical University, Taiyuan, People’s Republic of ChinaCorrespondence: Zhifen Liu; Ke-Rang Zhang, Department of Psychiatry, First Hospital of Shanxi Medical University, Shanxi Medical University, No. 85 Jiefang Nan Road, Taiyuan, Shanxi, 030001, People’s Republic of China, Tel +86 13703586547 ; +86 18135078183, Email liuzhifen5518@163.com; krzhang_sxmu@vip.163.comObjective: Repetitive transcranial magnetic stimulation (rTMS) is an effective and evidence-based treatment for major depressive disorder (MDD). This retrospective study aimed to explore the efficacy of add-on iTBS treatment in MDD in real-world clinical practice.Methods: One hundred and fifty-nine inpatients with MDD in a general hospital were included in this study. These patients were treated with at least 8 sessions of iTBS, in addition to antidepressants and supportive psychotherapy. Symptoms of depression and anxiety were assessed with the Hamilton Depression Rating Scale (HDRS) and the Hamilton Rating Scale for Anxiety (HAMA) at baseline and after 2– 4 weeks of treatment. The improvement degree of depressive and anxious symptoms was compared between the first-episode MDD (n=107) and recurrent MDD (n=52) groups.Results: Depressive and anxious symptoms were reduced significantly after the add-on iTBS treatment; the response and remission rates in the first-episode MDD group were 55.14% and 28.97%, which were 63.46% and 28.85% for the recurrent MDD group, respectively (P> 0.05). The response rate and remission rate of anxiety in the first-episode MDD group was 64.13% and 57.45% for HAMA, and 66.67% and 62.50% for the recurrent MDD group (P> 0.05).Conclusion: Our findings indicated that antidepressant and anti-anxiety efficacy of add-on iTBS treatment remains equivocal in real-world clinical practice, regardless of a first-episode depression diagnosis or recurrent depression.Keywords: depression, anxious, add-on iTBS, real world, efficacy

Kai Yue,1,2 Chao Yang,1 Yu You,1,2 Xueying Wang,3 Xinxin Zhang1 1School of Energy and Environmental Engineering, University of Science and Technology Beijing, Beijing, 100083, People’s Republic of China; 2Shunde Graduate School of University of Science and Technology Beijing, Shunde, Guangdong Province, 528399, People’s Republic of China; 3School of Chemistry and Chemical Engineering, University of Jinan, Jinan, Shandong Province, 250022, People’s Republic of ChinaCorrespondence: Kai Yue, Email yuekai@ustb.edu.cnBackground: A good understanding of the adhesion behaviors of the nanocarriers in microvessels in chemo-hyperthermia synergistic therapy is conducive to nanocarrier design for targeted drug delivery.Methods: In this study, we constructed an artificial blood vessel system using gelatins with a complete endothelial monolayer formed on the inner vessel wall. The numbers of adhered NPs under different conditions were measured, as well as the interaction forces between the arginine–glycine–aspartic acid (RGD) ligands and endothelial cells.Results: The experimental results on the adhesion of ligand–coated nanoparticles (NPs) with different sizes and morphologies in the blood vessel verified that the gelatin-based artificial vessel possessed good cytocompatibility and mechanical properties, which are suitable for the investigation on NP adhesion characteristics in microvessels. When the temperature deviated from 37 °C, an increase or decrease in temperature resulted in a decrease in the number of adhered NPs, but the margination probability of NP adhesion increased at high temperatures due to the enhanced Brownian movement and flow disturbance. It is found that the effect of cooling was less than that of heating according to the observed changes in cell morphology and a decrease in cell activity under the static and perfusion culture conditions within the temperature range of 25 °C– 43 °C. Furthermore, the measurement results of change in the RGD ligand-cell interaction with temperature showed good agreement with those in the number of adhered NPs.Conclusion: The Findings suggest that designing ligands that can bind to the receptor and are least susceptible to temperature variation can be an effective means to enhance drug retention.Keywords: artificial vessel, drug delivery, nanoparticle, temperature variation, particle–wall adhesion