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Wendao Han, Nating Xiong, Renkai Zhong, Zhongyi Pan Department of Blood Transfusion, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of ChinaCorrespondence: Wendao Han, Department of Blood Transfusion, Meizhou People’s Hospital, Meizhou, People’s Republic of China, Email 443567914@qq.comObjective: Atherosclerosis (AS) is a sustained chronic vascular inflammatory response caused by lipid metabolism disorders and immune response disorders and is the main cause of premature (men ≤ 55 years old, women ≤ 65 years old) myocardial infarction (PMI). Cytochrome P450 2C19 (CYP2C19) (related to vascular function and lipid metabolism) and peripheral immune cell levels and plays an important role in the course of AS. The association CYP2C19 polymorphisms, comprehensive immunoinflammatory indices with PMI susceptibility is unclear.Methods: This study included 485 PMI patients, and 639 age-matched non-PMI individuals as controls, from January 2019 to March 2024. The relationship between CYP2C19 polymorphisms, peripheral immunoinflammatory indices (pan-immune inflammation value (PIV), systemic immune inflammation index (SII), and system inflammation response index (SIRI)) and PMI risk were analyzed.Results: The inflammatory indices levels in PMI patients were higher than those in controls (all p< 0.05). The frequencies of the CYP2C19 &ast;1/&ast;2 and &ast;2/&ast;2 genotypes were higher, while the frequency of the &ast;1/&ast;1 genotype was lower in the PMI patients than those in controls. The cut-off values of TC, TG, LDL-C, PIV, SII, and SIRI were 5.065, 1.305, 2.805, 410.485, 869.645, and 1.495 for distinguishing PMI, respectively. Logistic regression analysis showed that male (odds ratio (OR): 1.607, 95% confidence interval (CI): 1.134– 2.277, p=0.008), history of smoking (OR: 7.108, 95% CI: 4.351– 11.614, p< 0.001), diabetes mellitus (OR: 4.906, 95% CI: 3.333– 7.223, p< 0.001), CYP2C19 poor metabolizer (PM) (&ast;2/&ast;2, &ast;2/&ast;3, and &ast;3/&ast;3) (OR: 2.147, 95% CI: 1.279– 3.603, p=0.004), and high TG (≥ 1.305 vs < 1.305, OR: 2.598, 95% CI: 1.864– 3.623, p< 0.001) and SIRI level (≥ 1.495 vs < 1.495, OR: 2.495, 95% CI: 1.432– 4.349, p=0.001) were independent risk factors for PMI.Conclusion: CYP2C19 PM phenotype, high SIRI level (≥ 1.495) and TG level (≥ 1.305), male, history of smoking, and diabetes mellitus were independently associated with PMI susceptibility.Keywords: premature myocardial infarction, system inflammation response index, CYP2C19, polymorphism

Nating Xiong,1 Wendao Han,1 Zhikang Yu2,3 1Department of Blood Transfusion, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 2Institute of Basic Medical Sciences, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 3Guangdong Engineering Technological Research Center of Clinical Molecular Diagnosis and Antibody Drugs, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of ChinaCorrespondence: Zhikang Yu, Institute of Basic Medical Sciences, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China, Email 392244719@qq.comBackground: Lymph node metastasis (LNM) is an important prognostic factor for breast cancer. Inflammatory stimulation can change tumor microenvironment and lead to LNM, but the relationship between LNM and peripheral immunoinflammatory indices has not been clarified in breast cancer.Methods: The clinical information of 1918 patients with breast cancer admitted to Meizhou People’s Hospital from October 2017 to December 2023 were retrospectively analyzed. The relationship of clinicopathological features (age, body mass index (BMI), ABO blood types, family history of cancer, tumor site, disease stage, LNM, distant metastasis, and molecular subtypes) and peripheral immunoinflammatory indices (pan-immune inflammation value (PIV), systemic immune inflammation index (SII), and system inflammation response index (SIRI)) were analyzed.Results: There were 935 (48.7%) patients had no LNM and 983 (51.3%) had LNM. There were statistically significant differences in the distributions of ABO blood groups (p=0.022) and molecular subtypes (p< 0.001) between the two groups. PIV, SII, and SIRI levels in patients with LNM were significantly higher than those without LNM (all p< 0.05). The proportions of LNM in patients with high PIV, SII, and SIRI levels were higher than those with low PIV, SII, and SIRI levels, respectively. Logistic regression analysis showed that non-O blood type (non-O blood type vs O blood type, odds ratio (OR): 1.327, 95% confidence interval (CI): 1.056– 1.667, p=0.015), luminal B subtype (luminal B vs luminal A, OR: 2.939, 95% CI: 2.147– 4.022, p< 0.001), HER2+ subtype (HER2+ vs luminal A, OR: 2.044, 95% CI: 1.388– 3.009, p< 0.001), and high SIRI level (≥ 0.875 vs < 0.875, OR: 1.572, 95% CI: 1.092– 2.265, p=0.015) were independently associated with LNM.Conclusion: Non-O blood type, luminal B and HER2+ subtypes, and high SIRI level (≥ 0.875) have potential role in predicting the status of LNM in breast cancer patients.Keywords: breast cancer, lymph node metastasis, system inflammation response index, ABO blood group

Yinxue Zhou,1,&ast; Tingyu Wu,2,&ast; Jiaxing Sun,1 Huanhuan Bi,1 Yuting Xiao,1 Yanmei Shao,1 Weizhong Han,1 Hongmei Wang1 1Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 2Department of Joint Surgery, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiaxing Sun; Hongmei Wang, Email jiaxing20022001@163.com; dor.whm@163.comBackground: EGFR-TKI resistance poses a significant challenge in the treatment landscape of non-small cell lung cancer (NSCLC), prompting extensive research into mechanisms and therapeutic strategies. In this study, we conduct a bibliometric analysis to elucidate evolving research hotspots and trends in EGFR-TKI resistance, offering insights for clinical interventions and scientific inquiries.Methods: Publications spanning from 1996 to 2024, focusing on EGFR-TKI resistance in NSCLC, were sourced from the Web of Science Core Collection. Utilizing VOSviewer 1.6.19, CiteSpace 6.2. R2, and Scimago Graphica 1.0.35, we analyzed these articles to identify countries/regions and institutions, Journals, publications, key contributors, collaborations, and emerging topics.Results: An analysis of 8051 articles by 38,215 researchers from 86 countries shows growing interest in EGFR-TKI resistance mechanisms. Since 1996, publications have steadily increased, surpassing 500 per year after 2016, with a sharp rise in citations. Research articles make up 84% of publications, emphasizing scholarly focus. Global collaboration, especially among researchers in China, the US, and Japan, is strong. Leading institutions like Dana-Farber and Harvard, along with journals such as “Lung Cancer”, are key in sharing findings. Professors Yi-Long Wu and William Pao are prominent contributors. Keyword analysis reveals core themes, including first-generation EGFR-TKIs, emerging agents like osimertinib, and research on the T790M mutation.Conclusion: EGFR-TKI resistance remains a critical issue in NSCLC treatment, driving ongoing research efforts worldwide. Focusing future research on clear identification of resistance mechanisms will guide post-resistance treatment strategies, necessitating further exploration, alongside the validation of emerging drugs through clinical trials. Moreover, “chemo+” treatments following EGFR-TKI resistance require more clinical data and real-world evidence for assessing safety and patient outcomes. As research advances, a multidisciplinary approach will be key to overcoming these challenges. Continued innovation in treatment could greatly enhance patient survival and quality of life.Keywords: EGFR-TKI, resistance, lung cancer, bibliometric, citespace, VOSviewer

Wenze Han,1,2 Ran Zhang,1,2 Shuzhi Liu,1,2 Tong Zhang,1,2 Xuemin Yao,1,2 Yuxin Cao,1,2 Jiadi Li,1,2 Xiaoming Liu,1,2 Bing Li1,2 1Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, 030001, People’s Republic of China; 2Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, People’s Republic of ChinaCorrespondence: Xiaoming Liu; Bing Li, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, 030001, People’s Republic of China, Email lxming0912@163.com; libing1975vip@163.comAbstract: Whiskers are nanoscale, high-strength fibrous crystals with a wide range of potential applications in dentistry owing to their unique mechanical, thermal, electrical, and biological properties. They possess high strength, a high modulus of elasticity and good biocompatibility. Hence, adding these crystals to dental composites as reinforcement can considerably improve the mechanical properties and durability of restorations. Additionally, whiskers are involved in inducing the value-added differentiation of osteoblasts, odontogenic osteocytes, and pulp stem cells, and promoting the regeneration of alveolar bone, periodontal tissue, and pulp tissue. They can also enhance the mucosal barrier function, inhibit the proliferation of tumor cells, control inflammation, and aid in cancer prevention. This review comprehensively summarizes the classification, properties, growth mechanisms and preparation methods of whiskers and focuses on their application in dentistry. Due to their unique physicochemical properties, excellent biological properties, and nanoscale characteristics, whiskers show great potential for application in bone, periodontal, and pulp tissue regeneration. Additionally, they can be used to prevent and treat oral cancer and improve medical devices, thus making them a promising new material in dentistry.Keywords: whiskers, dentistry, growth mechanism, biomaterials

Weihua Han,1,&ast; Peiyao Zhou,2,&ast; Chun Chen,3,&ast; Chunyang Wu,2 Li Shen,1 Cailing Wan,4 Yanghua Xiao,4 Jiao Zhang,2 Bingjie Wang,1 Junhong Shi,1 Xinru Yuan,1 Haojin Gao,1 Hongxiu Wang,1 Ying Zhou,1 Fangyou Yu1 1Department of Clinical Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Cancer Center, Department of Pulmonary and Critical Care Medicine, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, People’s Republic of China; 4School of Public Health, Nanchang University, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Zhou; Fangyou Yu, Email 18702195157@163.com; wzjxyfy@163.comBackground: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are a great threat to public health worldwide. Ceftazidime-avibactam (CZA) is an effective β-lactam/β-lactamase inhibitors against CRKP. However, reports of resistance to CZA, mainly caused by Klebsiella pneumoniae carbapenemase (KPC) variants, have increased in recent years. In this study, we aimed to describe the resistance characteristics of KPC-12, a novel KPC variant identified from a CZA resistant K. pneumoniae.Methods: The K. pneumoniae YFKP-97 collected from a patient with respiratory tract infection was performed whole-genome sequencing (WGS) on the Illumina NovaSeq 6000 platform. Genomic characteristics were analyzed using bioinformatics methods. Antimicrobial susceptibility testing was conducted by the broth microdilution method. Induction of resistant strain was carried out in vitro as previously described. The G. mellonella killing assay was used to evaluate the pathogenicity of strains, and the conjugation experiment was performed to evaluate plasmid transfer ability.Results: Strain YFKP-97 was a multidrug-resistant clinical ST11-KL47 K. pneumoniae confers high-level resistance to CZA (16/4 μg/mL). WGS revealed that a KPC variant, KPC-12, was carried by the IncFII (pHN7A8) plasmids (pYFKP-97_a and pYFKP-97_b) and showed significantly decreased activity against carbapenems. In addition, there was a dose-dependent effect of blaKPC-12 on its activity against ceftazidime. In vitro inducible resistance assay results demonstrated that the KPC-12 variant was more likely to confer resistance to CZA than the KPC-2 and KPC-3 variants.Discussion: Our study revealed that patients who was not treated with CZA are also possible to be infected with CZA-resistant strains harbored a novel KPC variant. Given that the transformant carrying blaKPC-12 was more likely to exhibit a CZA-resistance phenotype. Therefore, it is important to accurately identify the KPC variants as early as possible.Keywords: carbapenem-resistant Enterobacterales, Klebsiella pneumoniae, ceftazidime-avibactam, KPC-12, carbapenemase

Xinfang Cao,1,2 Jun Zhang,2 Wei Han1 1Eye Centre, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China; 2Department of Ophthalmology, Hangzhou MSK Eye Hospital, Hangzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Wei Han, Eye Centre, Second Affiliated Hospital, School of Medicine, Zhejiang University, 1 Westlake Avenue, Hangzhou, Zhejiang Province, 310000, People’s Republic of China, Tel +86 13777451900, Email hanweidr@zju.edu.cnPurpose: To evaluate and compare the effect of femtosecond laser-assisted cataract surgery on corneal astigmatism in post-LASIK eyes and virgin eyes.Patients and Methods: Patients who underwent femtosecond laser-assisted cataract surgery were included in the study and categorized into two groups: Group A, consisting of patients with post-LASIK eyes, and Group B, consisting of patients with virgin eyes. Visual acuity, corneal astigmatism, and surgically induced astigmatism (SIA) were evaluated. Additionally, the correlation between SIA and preoperative corneal astigmatism, mean corneal curvature, and central corneal thickness was also analyzed.Results: A total of 168 eyes were enrolled in this study, with 62 eyes in Group A and 106 eyes in Group B. Significant differences in corneal astigmatism and SIA were observed between the two groups in the early postoperative period following cataract surgery (P< 0.05). However, there was no significant difference at 6 months postoperatively (P> 0.05). Corneal astigmatism demonstrated an against-The-rule shift in both groups postoperatively. No significant correlation was identified between SIA and preoperative corneal astigmatism, corneal curvature or corneal thickness. Additionally, there was no significant difference observed between the two groups in terms of uncorrected distance visual acuity (UDVA) at 6 months postoperatively.Conclusion: The effect of femtosecond laser-assisted cataract surgery on corneal astigmatism in post-LASIK eyes and virgin eyes was different in the early postoperative period. However, there was no significant difference at 6 months postoperatively. The post-LASIK eyes exhibited a delayed recovery compared to the virgin eyes.Keywords: LASIK, femtosecond laser-assisted, cataract surgery, corneal astigmatism, surgically induced astigmatism

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

Yanyi Wang,1,2,&ast; Juan Wen,1– 3,&ast; Tong Lu,1,2 Wei Han,2,4 Kai Jiao,5 Huang Li1,2 1Department of Orthodontics, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, People’s Republic of China; 2Medical School of Nanjing University, Nanjing, People’s Republic of China; 3Centre for Orofacial Regeneration, Reconstruction and Rehabilitation (COR3), School of Dentistry, The University of Queensland, Brisbane, Queensland, 4006, Australia; 4Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, People’s Republic of China; 5Department of Stomatology, Tangdu Hospital & State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Han, Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, 30 Central Road, Nanjing, 210008, People’s Republic of China, Email doctorhanwei@hotmail.com Huang Li, Department of Orthodontics, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, 30 Central Road, Nanjing, 210008, People’s Republic of China, Tel +86-25-83620173, Fax +86-25-83620200, Email lihuang76@nju.edu.cnAbstract: Extracellular vesicles (EVs) can deliver various bioactive molecules among cells, making them promising diagnostic and therapeutic alternatives in diseases. Mesenchymal stem cell-derived EVs (MSC-EVs) have shown therapeutic potential similar to MSCs but with drawbacks such as lower yield, reduced biological activities, off-target effects, and shorter half-lives. Improving strategies utilizing biotechniques to pretreat MSCs and enhance the properties of released EVs, as well as modifying MSC-EVs to enhance targeting abilities and achieve controlled release, shows potential for overcoming application limitations and enhancing therapeutic effects in treating bone-related diseases. This review focuses on recent advances in functionalizing MSC-EVs to treat bone-related diseases. Firstly, we underscore the significance of MSC-EVs in facilitating crosstalk between cells within the skeletal environment. Secondly, we highlight strategies of functional-modified EVs for treating bone-related diseases. We explore the pretreatment of stem cells using various biotechniques to enhance the properties of resulting EVs, as well as diverse approaches to modify MSC-EVs for targeted delivery and controlled release. Finally, we address the challenges and opportunities for further research on MSC-EVs in bone-related diseases.Keywords: extracellular vesicles, mesenchymal stem cells, functional modification, bone-related diseases

Wei Han School of Marxism, Nanchang University, Nanchang, 330030, People’s Republic of ChinaCorrespondence: Wei Han, Email hanwei@ncu.edu.cnIntroduction: In the past decade, China has witnessed a significant surge in the popularity of food delivery apps, with its industry now thrice the size of the U.S, employing approximately 7 million drivers navigating urban landscapes on electric bikes and scooters. Predominantly, the market is governed by two main players: Meituan Dianping (backed by Tencent) and Ele.me (supported by Alibaba). Notably, stress and absenteeism stand out as significant challenges in this service sector, with implications for occupational health that translate into considerable costs for both healthcare systems and companies. Existing research has largely overlooked how job demands affect the mental health of food delivery workers in China, and how resilience plays a role in this process. The present study addresses this gap by examining the direct impact of Workload Volume and Pace on the mental health of these workers, and by exploring how personal resilience can mediate this relationship. Furthermore, it delves into the mediating role of Resilience, a personal strength, in this relationship.Methods: Using a correlational design with 206 participants, multiple regression analysis suggested a notable variance in Mental Health Decline.Results: Subsequent bootstrapping-mediated analysis confirmed resilience’s mediating role, highlighting its importance in managing stress from workload.Discussion: The results underscore the critical role of personal strengths in managing work-related stress, which can significantly impact both job performance and mental well-being.Keywords: resiliency, job demands, mental health deterioration, food-delivery workers, China

Wei Han,1 Cheng Li,1 Yongheng Wang,1 Binliang Huo,1 Wenhan Li,1 Wen Shi2 1Department of Surgical Oncology, Shaanxi Provincial People’s Hospital, Xi’an, People’s Republic of China; 2Department of Gastroenterology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of ChinaCorrespondence: Wen Shi, Department of Gastroenterology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of China, Email shiwen02308@aliyun.comBackground: There is a strong correlation between consuming high amounts of heme and an elevated risk of developing various types of cancer, including colorectal cancer. However, the role of heme metabolism-related genes (HRGs) in colorectal cancer remains unclear. Our study aimed to identify prognostic markers for colorectal cancer patients based on these genes.Methods: The heme metabolism score was assessed using gene set variation analysis (GSVA). Potential prognostic HRGs were identified from the TCGA-COAD dataset using LASSO and COX regression analyses. The expression level of TENT5C was validated in the GEO database and clinical samples. To explore the association between TENT5C expression and immune cell infiltrations, we performed ESTIMATE and single-sample gene set enrichment analysis (ssGSEA).Results: The low level of heme metabolism score was associated with a poor prognosis in colorectal cancer patients. TENT5C is a prognostic gene and an independent prognostic biomarker for overall survival. Its expression was confirmed in multiple datasets and clinical samples, showing a positive correlation with immune cells and immune score. GSEA results suggested TENT5C’s significant role in regulating immune and inflammatory responses in colorectal cancer.Conclusion: TENT5C can be used as a biomarker in colorectal cancer. Additionally, TENT5C is associated with both prognosis and immune infiltration. These findings lay a strong groundwork for future research to delve into the specific role of TENT5C in the development and advancement of colorectal cancer.Keywords: colon cancer, immune cell infiltrations, prognosis, heme metabolism

Yihan Li,1 Tong Hu,1 Mingjie Lin,1,2 Qinhong Wang,1 Wenqiang Han,1 Jingquan Zhong1,2 1Department of Cardiology, Qilu Hospital of Shandong University, Jinan, Shandong Province, People’s Republic of China; 2Department of Cardiology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong Province, People’s Republic of ChinaCorrespondence: Jingquan Zhong, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, Shandong Province, People’s Republic of China, Tel: +008618560086597, Email 198762000778@email.sdu.edu.cnBackground: Dronedarone is an effective drug for maintaining the sinus rhythm in patients with atrial fibrillation (AF). The efficacy and safety of dronedarone versus amiodarone in patients with AF after catheter ablation (CA) needs more evidence. We retrospectively compared the efficacy and safety of dronedarone and amiodarone in our hospital.Methods: Patients who underwent CA from January 2021 to January 2022 and used dronedarone (n=229) or amiodarone (n=202) during the blind period were enrolled. The recurrence of AF in post-and during the blanking period was compared between the groups; the rehospitalization for re-ablation and adverse drug events (ADE) were also calculated.Results: During an average follow-up period of 14.28 months, the long-term recurrence rate of AF did not differ significantly between the amiodarone group and dronedarone group (22.71% vs 21.29%, hazard ratio [HR], 1.033, 95% confidence interval [CI], 0.661– 1.614; p=0.888). The recurrence rate in the blanking period also showed no statistically significant differences between the amiodarone group and dronedarone group (9.90% vs 14.41%, HR, 0.851; 95% CI, 0.463– 1.564; p=0.604). The re-hospitalization rates for re-ablation between two groups did not differ between the amiodarone group and dronedarone group (4.65% vs 13.46%; p =0.144). The incidence of ADE was higher in the dronedarone groups than that in the amiodarone group (16.59% vs 5.45%, p < 0.001). The main adverse drug events in the dronedarone and amiodarone groups were gastrointestinal (6.99%) and bradycardia (2.48%), respectively.Conclusion: Compared to the amiodarone group, the dronedarone group had a similar blank-period and long-term recurrence rate of AF and a higher incidence of ADE.Keywords: atrial fibrillation, catheter ablation, amiodarone, dronedarone

Wendao Han,1,2 Nating Xiong,1,2 Renkai Zhong,1,2 Zhongyi Pan1,2 1Department of Blood Transfusion, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 2Center for Precision Medicine, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of ChinaCorrespondence: Wendao Han, Meizhou People’s Hospital, Meizhou, People’s Republic of China, Email 443567914@qq.comObjective: Apolipoprotein E (APOE) plays an important role in the lipid metabolism. APOE polymorphisms have been implicated in susceptibility to diabetes mellitus (DM). However, the association between APOE polymorphisms and the risk of DM among the hypertensive patients remains unclear. Our study aimed to evaluate this relationship to provide clues for further developing DM in hypertensive patients.Methods: The study included 808 hypertensive patients with DM and 1226 hypertensive patients without DM as controls. The APOE 388T>C (rs429358) and 526C>T (rs7412) polymorphisms were genotyped by polymerase chain reaction (PCR) - microarray. Differences in APOE genotypes between subjects and controls were compared. To analyze the relationship between APOE genotypes and DM risk, multiple logistic regression analysis was performed after adjusting for gender, age, smoking history, and drinking history.Results: The APOE E2/E4, E3/E3 genotype and &epsiv;2, &epsiv;3 allele frequency had significant difference between DM patients and controls (P< 0.05). The DM patients with ɛ4 allele had lower level in high-density lipoprotein cholesterol (HDL-C) and higher level in apolipoprotein B (ApoB) than those with ɛ2 allele. The results of logistic regression analysis indicated that the APOE genotype of E2/E3 with adjusted OR=1.350 (95% Cl=1.009– 1.806, P=0.043) and E3/E4 with adjusted OR=1.325 (95% Cl=1.034– 1699, P=0.026) may be independent risk factors for DM.Conclusion: APOE E2/E3 and E3/E4 genotypes may be risk factors for developing diabetes mellitus in hypertensive patients.Keywords: Apolipoprotein E, polymorphism, hypertension, diabetes mellitus

Mingping He,1,&ast; Wenzheng Han,1,&ast; Chuan Shi,1 Ming Wang,1 Junheng Li,2 Wei He,2 Xinxin Xu,3 Qian Gan,1 Shaofeng Guan,1 Liang Zhang,1 Yang Chen,1 Xifeng Chang,1 Tianqi Li,1 Xinkai Qu1 1Department of Cardiology, Huadong Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 2Department of Nuclear Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 3Clinical Research Center for Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenzheng Han; Xinkai Qu, Department of Cardiology, Huadong Hospital Affiliated to Fudan University, No. 221, Yan’an Road (W), Shanghai, People’s Republic of China, Email wzhan_cardiology@foxmail.com; qxkchest@126.comBackground: Microvascular dysfunction in patients with non-obstructive epicardial coronary may aggravate patient’s symptoms or lead to various clinical events.Objective: To investigate the correlation between dynamic single photon emission computed tomography (D-SPECT) derived coronary flow reserve (CFR) and TIMI frame count (TFC) in patients with non-obstructive epicardial coronary patients.Methods: Patients with suspected or known stable CAD who were recommended to undergo invasive coronary angiography were prospectively enrolled in this study. Those who had non-obstructive coronary received TIMI frame count (TFC) and D-SPECT. A cut-off value of > 40 was defined as slow flow referred to TFC.Results: A total of 47 patients diagnosed with non-obstructive coronary were enrolled. The mean age of patients was 66.09 ± 8.36 years, and 46.8% were male. Dynamic SPECT derived coronary flow reserve (CFR) was significantly correlated with TIMI frame count in 3 epicardial coronary (LAD: r=− 0.506, P = 0.0003; LCX: r= − 0.532, P = 0.0001; RCA: r= − 0.657, P < 0.0001). The sensitivity and specificity of CFR in identifying abnormal TIMI frame count < 40 was 100.0% and 57.6% in LAD, 62.5% and 87.0% in LCX, 83.9% and 75.0% in RCA, respectively. The optimal CFR cut-off values were 2.02, 2.47, and 1.96 among the three vessels.Conclusion: In patients with non-obstructive coronary, CFR derived from D-SPECT was strongly correlated with TFC. This study demonstrates that that CFR may be an alternative non-invasive method for identifying slow flow in non-obstructive coronary.Keywords: dynamic single photon emission computed tomography, thrombolysis in myocardial infarction frame count, slow flow, non-obstructive coronary, coronary flow reserve

Xiteng Yin,1,2 Hongbo Zhang,1,2 Zheng Wei,2,3 Yufeng Wang,1,2 Shengwei Han,1,2 Meng Zhou,4 Wenguang Xu,1,2 Wei Han1,2 1Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China; 2Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China; 3Pediatric Dentistry, Nanjing Stomatology Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China; 4Department of Oral and Maxillofacial Surgery, the Affiliated Stomatological Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of ChinaCorrespondence: Wei Han; Wenguang Xu, Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China, Tel/Fax +86 25 8362 0140 ; +86-025-83620202, Email doctorhanwei@hotmail.coml; wenguang.xu@foxmail.comPurpose: Lysine crotonylation, an emerging posttranslational modification, has been implicated in the regulation of diverse biological processes. However, its involvement in oral squamous cell carcinoma (OSCC) remains elusive. This study aims to reveal the global crotonylome in OSCC under hypoxic conditions and explore the potential regulatory mechanism of crotonylation in OSCC.Methods: Liquid-chromatography fractionation, affinity enrichment of crotonylated peptides, and high-resolution mass spectrometry were employed to detect differential crotonylation in CAL27 cells cultured under hypoxia. The obtained data were further subjected to bioinformatics analysis to uncover the involved biological processes and pathways of the dysregulated crotonylated proteins. A site-mutated plasmid was utilized to investigate the effect of crotonylation on Heat Shock Protein 90 Alpha Family Class B Member 1 (HAP90AB1) function.Results: A large-scale crotonylome analysis revealed 1563 crotonylated modification sites on 605 proteins in CAL27 cells under hypoxia. Bioinformatics analysis revealed a significant decrease in histone crotonylation levels, while up-regulated crotonylated proteins were mainly concentrated in non-histone proteins. Notably, glycolysis-related proteins exhibited prominent up-regulation among the identified crotonylated proteins, with HSP90AB1 displaying the most significant changes. Subsequent experimental findings confirmed that mutating lysine 265 of HSP90AB1 into a silent arginine impaired its function in promoting glycolysis.Conclusion: Our study provides insights into the crotonylation modification of proteins in OSCC under hypoxic conditions and elucidates the associated biological processes and pathways. Crotonylation of HSP90AB1 in hypoxic conditions may enhance the glycolysis regulation ability in OSCC, offering novel perspectives on the regulatory mechanism of crotonylation in hypoxic OSCC and potential therapeutic targets for OSCC treatment.Keywords: crotonylation, hypoxia, oral squamous cell carcinoma, glycolysis, heat shock protein 90 alpha family class B member 1

Mingzhen Li,1 Bing Zhang,2 Lichuan Guo,2 Yuan Zhang,2 Xiaoyan Du,3 Bingyi Wang,3 Zheng Xu,4 Ning Sun,4 Ruibin Chen,4 Wanwen Han,4 Liming Chen,1 Zhenqiang Song1 1Department of Endocrinology, NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, People’s Republic of China; 2Department of Information Management, NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, People’s Republic of China; 3Department of Medical, Happy Life Technology Co Ltd, Beijing, People’s Republic of China; 4Department of Yutang, Andon Health Co., Ltd, Tianjin, People’s Republic of ChinaCorrespondence: Zhenqiang Song, Department of Endocrinology, NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, No. 6 North Huanrui Road, Beichen District, Tianjin, People’s Republic of China, Tel +86-18602276218, Fax +86-022-59562017, Email zsong@tmu.edu.cnBackground: Our previous study demonstrated that digital diabetes care model (DDCM) created by multidisciplinary care team (MDCT) can improve glycemic control for patients with diabetes than usual care. Therefore, we aimed to explore long-term glycemic control with DDCM and influencing factors in type 2 diabetic cohort, in order to make a portrait for diabetes with goal-achieved HbA1c in clinics.Methods: A total of 1198 outpatients with type 2 diabetes using DDCM for at least 12 months were recruited as a cohort. Medical records and specific DDCM indexes were collected. The influencing factors for glycemic control were explored by multivariate logistic regression analysis, followed by an internal and external validation.Results: A total of 887 patients were finally included. HbA1c target-achieving rate was increased from 39.83% at baseline to 71.79% after 3-month follow-up. A shorter duration of diabetes, more frequent self-monitoring of blood glucose, lower HbA1c level at baseline, and less frequent emergency out-of-hospital follow-ups were influencing factors for HbA1c < 7% at 12-month follow-up. AUC of the prediction model was 0.790, with a sensitivity of 69.7% and specificity of 76.1%. Internal and external validation in patients using the DDCM monitored by MDCT indicated that the DDCM was robust (AUC =0.783 and 0.723, respectively).Conclusion: Our findings made a portrait for T2DM with goal-achieved HbA1c in our DDCM. It is important to recognize associated factors for health providers to make personalized intervention in clinical practice.Keywords: digital diabetes care model, glycemic control, type 2 diabetes management

Qirong Lu,1,&ast; Wantong Han,1,&ast; Defeng Wen,1,&ast; Pu Guo,1 Yu Liu,1 Zhongyuan Wu,1 Shulin Fu,1 Chun Ye,1 Xu Wang,2 Yinsheng Qiu1 1Hubei Key Laboratory of Animal Nutrition and Feed Science, School of Animal Science and Nutritional Engineering, Wuhan Polytechnic University, Wuhan, 430023, People’s Republic of China; 2National Reference Laboratory of Veterinary Drug Residues (HZAU) and Ministry of Agriculture Key Laboratory for the Detection of Veterinary Drug Residues in Foods, Huazhong Agricultural University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pu Guo; Yinsheng Qiu, Wuhan Polytechnic University, Wuhan, Hubei, 430023, People’s Republic of China, Email guopu@whpu.edu.cn; qiuyinsheng6405@whpu.edu.cnBackground: At present, the treatment and prevention of Pasteurella multocida infections in pigs mainly rely on antibiotics and vaccines, but inflammatory injury cannot be eliminated. The compound 18β-glycyrrhetinic acid (GA), a pentacyclic triterpenoid extracted from Glycyrrhiza glabra L. root (liquorice) and with a chemical structure similar to that of steroidal hormones, has become a research focus because of its anti-inflammatory, antiulcer, antimicrobial, antioxidant, immunomodulatory, hepatoprotective and neuroprotective effects, but its potential for the treatment of vascular endothelial inflammatory injury by P. multocida infections has not been evaluated. This study aimed to investigate the effects and mechanisms of GA intervention in the treatment of vascular endothelial inflammatory injury by P. multocida infections.Materials and Methods: Putative targets of GA intervention in the treatment of vascular endothelial inflammatory injury by P. multocida infections were identified using network pharmacological screening and molecular docking simulation. The cell viability of PIEC cells was investigated via the CCK-8 assay. The mechanism of GA intervention in the treatment of vascular endothelial inflammatory injury by P. multocida infections were investigated using cell transfection and western blot.Results: Through network pharmacological screening and molecular docking simulation, this study found that PARP1 may be a core target for GA to exert anti-inflammatory effects. Mechanistically, GA alleviates P. multocida-induced vascular endothelial inflammation by PARP1-mediated NF-κB and HMGB1 signalling suppression.Conclusion: These findings, for the first time, demonstrate the potential therapeutic relationship among GA, PARP1 and inflammatory injury, providing a candidate drug, therapeutic targets and explanation for treating vascular endothelial inflammatory injury caused by P. multocida infection.Keywords: network pharmacology, GA, PARP1, inflammatory injury, P. multocida infection

Tingting Li,1,2 Wenjing Han,1,2 Xinlu Yang,1 Yu Wang,1 Li Peng,1 Lingwei He,1 Lianjia Hu,1 Jiayuan Liu,1 Min Xia,1 Sheng Wang1,2 1Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China; 2Department of Anesthesiology, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, People’s Republic of ChinaCorrespondence: Sheng Wang, Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, No. 17 Lujiang Road, Luyang District, Hefei, Anhui Province, People’s Republic of China, Tel +86 191 5600 7726, Email iamsheng2020@ustc.edu.cnPurpose: This study aimed to explore the effects of different injection rates of propofol on postoperative cognition in elderly patients undergoing laparoscopic inguinal hernia repair.Methods: A total of 180 elderly patients who planned to undergo laparoscopic inguinal hernia repair were randomly divided into three groups: slow injection of propofol (VS-Group, 30 mg kg− 1 h− 1); medium injection of propofol (VM-Group, 100 mg kg− 1 h− 1) or fast injection of propofol (VF-Group, 300 mg kg− 1 h− 1). Propofol was induced by microinfusion pump, and the depth of anesthesia was monitored by bispectral index (BIS). Propofol and remifentanil were continuously infused during anesthesia maintenance and adjusted according to BIS. The primary outcome was the use of the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) to measure the incidence of postoperative cognitive decline (POCD) in elderly patients on the first and seventh postoperative day. Secondary outcomes included induced dose of propofol, incidence of burst suppression and maximum electroencephalographic (EEG) effect of propofol (BIS-min) during induction.Results: The incidence of POCD on the first and seventh day postoperatively was similar among the three groups (P > 0.05). However, with the increase of propofol injection rate, induced dose of propofol, incidence of burst suppression and BIS-min during induction, the number of patients requiring vasoactive agents were significantly increased (P < 0.001). Multivariate regression analysis showed that the brief duration of burst suppression during induction did not affect the occurrence of POCD, while age and duration of hospitalization were risk factors for POCD.Conclusion: For elderly patients undergoing laparoscopic inguinal hernia repair, lowering the injection rate of propofol (such as 30 mg kg− 1 h− 1) cannot decrease the incidence of early POCD, but reduces induction dose of propofol and use of vasoactive drugs, making the patient’s hemodynamics more stable.Keywords: propofol, injection rate, bispectral index, burst suppression, elderly, postoperative cognitive decline

Factor VII (FVII) is an important, vitamin K-dependent clotting factor. Acquired FVII deficiency is a rare entity that is associated with serious bleeding complications. We report a case of acquired FVII deficiency in a patient with recurrent chronic myeloid leukemia in blast crisis who developed bilateral retinal hemorrhages. The coagulopathy was corrected with the initiation of chemotherapy and subsequent reduction in peripheral blast count.

Several studies have identified mutations in the MYD88L265P gene as a key driver mutation in several B-cell lymphomas. B-cell lymphomas that harbor the MYD88L265P mutation form a complex with phosphorylated Bruton’s tyrosine kinase (BTK) and are responsive to BTK inhibition. However, BTK inhibition in B-cell lymphomas rarely results in a complete response and most patients experience eventual disease relapse. Persistent survival signaling though downstream molecules such as interleukin 1 receptor-associated kinase 4 (IRAK-4), an integral part of the “myddosome” complex, has been shown to be constitutively active in B-cell lymphoma patients treated with BTK inhibitors. Emerging evidence is demonstrating the therapeutic benefit of IRAK-4 inhibition in B-cell lymphomas, along with possibly reversing BTK inhibitor resistance. While MYD88 gene mutations are not present in myeloid malignancies, downstream overexpression of the oncogenic long form of IRAK-4 has been found in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), particularly in AML and MDS that harbor mutations in splicing factors U2AF1 and SF3B1. These data suggest that the anti-leukemic activity of IRAK-4 inhibition can be exploited in relapsed/refractory (R/R) AML/MDS. In this review article, we discuss the currently available pre-clinical and clinical data of emavusertib, a selective, orally bioavailable IRAK-4 inhibitor in the treatment of R/R B-cell lymphomas and myeloid malignancies.

Yuan Cao,1– 3 Yulin Li,1– 3 Wenqiang Han,1– 3 Xu Jia,1– 3 Ping Zhu,1– 3 Bin Wei,4 Xiaoyan Cong,5,6 Zhihao Wang7,8 1Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Jinan, People’s Republic of China; 2State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Jinan, People’s Republic of China; 3Department of Cardiology, Qilu Hospital, Shandong University, Jinan, People’s Republic of China; 4Shandong Asia-Pacific Highvarve Organisms Science and Technology Co, Ltd, Jinan, People’s Republic of China; 5Institute of Animal Science and Veterinary Medicine, Shandong Key Laboratory of Animal Disease Control and Breeding, Shandong Academy of Agricultural Sciences, Jinan, People’s Republic of China; 6Jinan Kuoda Biotechnology Co, Ltd, Jinan, People’s Republic of China; 7Department of Geriatric Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 8Key Laboratory of Cardiovascular Proteomics of Shandong Province, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Xiaoyan Cong; Zhihao Wang, Email xycong@163.com; wangzhihaosdu@126.comPurpose: Sarcopenia has been described as a new complication of type 2 diabetes mellitus (T2DM). T2DM and sarcopenia impact each other, resulting in a variety of adverse outcomes such as frailty, disability, poor quality of life and increased mortality. Sodium butyrate (NaB) is reported to play a protective role against T2DM. The present study aimed to investigate whether NaB could ameliorate T2DM-related sarcopenia and the underlying mechanisms.Materials and Methods: The male db/db mice at 7-weeks were used as T2DM-related sarcopenia animal model with C57BL/6J mice as control. Mice were grouped according to whether they received NaB orally as follows: C57BL/6J+water group, C57BL/6J+NaB group, db/db+water group, and db/db+NaB group. Then, db/db mice receiving NaB orally were administered with inhibitors of group 2 innate lymphocytes (ILC2s), anti-CD90.2 by intraperitoneal injection divided into db/db+NaB+PBS group and db/db+NaB+anti-CD90.2 group. NaB dissolved in water at 150 mM. The skeletal muscle mass was measured by dural X-ray (DXA) test. ILC2s in spleen and skeletal muscle were evaluated by flow cytometry. The expressions of IL-33, IL-13, STAT3, P-STAT3, GATA-3 and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) were assessed by ELISA or WB. The morphology of skeletal muscle fibers was assessed by immunofluorescence staining.Results: The proportion of ILC2s and the expressions of ILC2s markers IL-13 and GATA-3 were all significantly decreased in db/db mice, and these changes were improved by NaB. NaB increased the proportion of slow-twitch fibers in gastrocnemius, thus partially reversing the reduced exercise capacity of db/db mice. The expression of slow-twitch fibers marker PGC-1α induced by NaB was increased via activation of ILC2s/IL-13/STAT3 pathway. On the other way, IL-33 was not necessary for the activation of ILC2s/IL-13/STAT3 pathway. After depletion of ILC2s by anti-CD90.2, the ameliorating effect of NaB on T2DM-related sarcopenia was partially antagonized.Conclusion: These results indicated that NaB could ameliorate type 2 diabetes-related sarcopenia by activating IL-33-independent ILC2s/IL-13/STAT3 signaling pathway.Keywords: diabetes mellitus, sarcopenia, ILC2s, sodium butyrate, IL-13

Xuegang Wang,1,&ast; Weiquan Li,2,&ast; Ning Lou,3,&ast; Weiwei Han,3 Bo Hai,2 Wen Xiao,2 Xiaoping Zhang2 1Department of Urology, The First Affiliated Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, People’s Republic of China; 2Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 3Department of Urology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wen Xiao; Bo, Hai, Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei Province, 430022, People’s Republic of China, Tel +86-17088353610, Fax +86 85776343, Email xiaowenx11@163.com; Haibo2022@hust.edu.cnBackground: Invasion and metastasis led to poor prognosis and death of clear cell renal cell carcinoma (ccRCC) patients. The deoxynucleotidyl transferase terminal interacting protein 1 (DNTTIP1) was reported to promote multiple tumor progression. However, there is no research about DNTTIP1 in ccRCC.Methods: Kaplan–Meier survival analysis, multivariate analysis demonstrated the prognostic indicator in overall survival (OS) and disease-free survival (DFS) of ccRCC with DNTTIP1 expression in the Cancer Genome Atlas Kidney Clear Cell Carcinoma (TCGA-KIRC). Receiver operator characteristic (ROC) curve analyzed diagnostic ability of DNTTIP1 in TCGA-KIRC and validation dataset. The quantitative real-time polymerase chain reaction (qRT-PCR) detected the DNTTIP1 expression in renal cancer tissues, and the Office of Cancer Clinical Proteomics Research (CPTAC) verified the protein expression of DNTTIP1. Moreover, nomogram predicted the role of DNTTIP1 in ccRCC patient. Single-sample Gene Set Enrichment Analysis (SsGSEA) and GSEA evaluated the pathogenesis role of DNTTIP1 in TCGA-KIRC.Results: DNTTIP1 expression was higher in ccRCC tumor tissues. High expression of DNTTIP1 was associated with poor OS (HR = 1.618, P < 0.0001), and poor DFS (HR = 1.789, P < 0.0001). SsGSEA and GSEA showed DNTTIP1 was associated with hypoxia, epithelial-mesenchymal transition (EMT), angiogenesis, G2M checkpoint. DNTTIP1 had a positive correlation with EMT biomarkers in ccRCC, and might be an effective target for ccRCC.Conclusion: This study provided that higher expression of DNTTIP1 predicted poor prognosis in ccRCC, and DNTTIP1 might be a novel detection biomarker and therapeutic target of tumor malignant in the future.Keywords: DNTTIP1, ccRCC, gene therapy, prognostic indicator

Xuejie Fang,1,&ast; Zhengtong Qiao,2,&ast; Xinjuan Yu,3,4,&ast; Rujin Tian,5 Kai Liu,5 Wei Han3 1School of Clinical Medicine, Weifang Medical University, Weifang, People’s Republic of China; 2School of Rehabilitation Medicine, Binzhou Medical University, Yantai, People’s Republic of China; 3Department of Respiratory and Critical Medicine, Respiratory Disease Key Laboratory of Qingdao, University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao Municipal Hospital), Qingdao, People’s Republic of China; 4Clinical Research Center, University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao Municipal Hospital), Qingdao, People’s Republic of China; 5Department of Rehabilitation Medicine, University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao Municipal Hospital), Qingdao, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Han, Department of Respiratory and Critical Medicine, Respiratory Disease Key Laboratory of Qingdao, University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao Municipal Hospital), No. 5 Donghaizhong Road, Qingdao, 266071, People’s Republic of China, Tel +86 532 85937579, Email hanw@qdu.edu.cn Kai Liu, Department of Rehabilitation Medicine, University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao Municipal Hospital), No. 5 Donghaizhong Road, Qingdao, 266071, People’s Republic of China, Tel +86 532 85937671, Email liukaidpt@126.comBackground: Chronic obstructive pulmonary disease (COPD) is a chronic lung disease which feature is progressive airflow obstruction. Singing is a popular and convenient activity that requires people to manage their lung volumes and airflow actively. Despite the well-known benefits of singing to healthy people, the specific effect still remains unclear.Objective: To investigate the mental and psychological benefits of singing in patients with stable COPD.Search Methods: We used Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines (PRISMA) on randomized controlled trials (RCTs) including singing exercise as the main intervention in stable COPD. We searched 8 electronic databases, including Web of Science, PubMed, Embase, Cochrane Library, Clinical Trials.gov, and the Physical Therapy Evidence Database (PEDro), CNKI, and Wanfang Database from inception until May 2022. The searching languages was English or Chinese. Data extraction using standardized templates was performed by two independent reviewers. The quality of the studies was assessed using the PEDro scale. Data synthesis was performed with Revman 5.4. The pooled effect sizes are reported by MD and 95% CI.Results: Five RCTs involving 333 patients with stable COPD were included in this meta-analysis. Singing was regarded as the main intervention in the experimental group. Meta-analysis revealed that singing improves quality of life on Short Form 36 physical component summary (SF-36 PCS) (MD = 12.63, 95% CI: 5.52 to 19.73, P < 0.01) and respiratory muscle in maximal expiratory pressure (PEmax) (MD = 14.30, 95% CI: 0.87 to 27.73, P = 0.04) in patients with COPD. However, it has limited effects on Short Form 36 mental component summary (SF-36 MCS), lung function, exercise capability, and adverse mental state.Conclusion: Based on results of the meta-analysis, singing could be used to improve quality of life (SF-36 PCS) and respiratory muscles (PEmax) in patients with COPD.Keywords: COPD, singing, pulmonary function, pulmonary rehabilitation

Wen Bao,1,&ast; Deqing Wu,1,&ast; Wei Han,1 Rui Kong,1 Nan Wang,1 Jie Lu2 1Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University, Shanghai, 200072, People’s Republic of China; 2Department of Gastroenterology, Gongli Hospital, School of Medicine, Shanghai University, Shanghai, 200135, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Lu, Email kennisren@hotmail.comBackground: Extracorporeal shock wave lithotripsy (ESWL) and endoscopic retrograde cholangiopancreatography (ERCP) are the main treatments for chronic calcific pancreatitis (CCP). However, clinical outcomes remain unclear for patients underwent different interventional therapies based on these two techniques.Methods: A total of 125 patients with CCP who underwent ESWL, ERCP or a combined treatment at two medical centers from January 2019 to January 2020 were considered. Patients were divided into four groups according to intervention types (ESWL-alone, ERCP-alone, ESWL-ERCP and ERCP-ESWL). A retrospective survey with a follow-up for 2 years was conducted. The main outcome measures were postoperative complications, abdominal pain and re-intervention during the follow-up. Possible prognostic factors were evaluated by multivariate analysis.Results: Patients in ESWL-ERCP group had the highest complete pain relief rate (49.28%), the lowest pain frequency (1 time/year) and intensity (VAS-score, 1.84± 1.93) during the follow-up, which were statistically significant compared with the other three groups. ESWL-ERCP group also had the lowest postoperative complication rate (6%), while the highest complication rate (16%) was observed in ESWL-alone group. Both ESWL-alone and ESWL-ERCP group had significant lower frequencies of re-interventions (0.44 ± 0.73, 0.57± 0.98, respectively) after the initial treatments. An analysis of treatment-based prognostic factors found significant interactions between age, course of CCP, max pancreatic duct stone diameter, calcium, glycosylated hemoglobin (HbA1c) and triglyceride.Conclusion: ESWL-ERCP was considered as the most effective interventional therapy for CCP with a better safety in a two-year follow-up. Prognostic factors may help to determine the patients who benefit by this technique.Keywords: chronic calcific pancreatitis, ESWL, ERCP, follow-up

Abstract The Society for Cardiovascular Magnetic Resonance (SCMR) is an international society focused on the research, education, and clinical application of cardiovascular magnetic resonance (CMR). “Cases of SCMR” is a case series hosted on the SCMR website ( https://www.scmr.org ) that demonstrates the utility and importance of CMR in the clinical diagnosis and management of cardiovascular disease. The COVID-19 Case Collection highlights the impact of coronavirus disease 2019 (COVID-19) on the heart as demonstrated on CMR. Each case in series consists of the clinical presentation and the role of CMR in diagnosis and guiding clinical management. The cases are all instructive and helpful in the approach to patient management. We present a digital archive of the 2021 Cases of SCMR and the 2020 and 2021 COVID-19 Case Collection series of nine cases as a means of further enhancing the education of those interested in CMR and as a means of more readily identifying these cases using a PubMed or similar literature search engine.

Immune checkpoint inhibitors (ICIs) and brentuximab vedotin (BV) are novel agents for classic Hodgkin lymphoma, including relapse after autologous stem cell transplant (ASCT). However, their impact on survival post-ASCT relapse, in comparison with conventional therapy, is less known due to the lack of randomized controlled trials. Clinical characteristics and outcomes of 115 patients with relapse (or progression) after ASCT are studied. After a median follow-up of 8.59 years from post-ASCT relapse, the median progression-free survival (PFS) and overall survival (OS) were 0.91 and 5.07 years, respectively. Median lines of therapy after post-ASCT relapse was 2 (range, 1–12). The median PFS was not reached (NR) versus 1.11 versus 0.50 versus 0.85 versus 0.78 years (P = 0.006) and OS was NR versus 7.60 versus 3.08 versus 3.51 versus 3.17 years (P = 0.28) in patients first treated with ICIs versus BV versus investigational agents versus chemotherapy versus radiation therapy (RT). First-line treatment with novel agents (ie, ICIs and BV) was associated with superior outcomes compared with investigational agents and chemotherapy/RT with a median PFS of 1.65 versus 0.50 versus 0.79 years (P = 0.003) and a median OS of 7.60 versus 3.08 versus 3.32 years (P = 0.08). Regardless of lines of therapy, the treatment with ICIs had the most favorable outcome with a median PFS and OS of 3.98 and NR years, respectively. Allogeneic stem cell transplant (allo-SCT) was done in 23 patients (20%), and the median post-allo-SCT PFS and OS were 1.31 and 2.35 years, respectively. In conclusion, survival following post-ASCT relapse improves significantly when patients receive novel agents.

Huanrong Ruan,1,2 Hailong Zhang,1– 3 Zhenzhen Feng,1– 3 Xuanlin Li,1,2 Weihong Han,1,2 Yimei Si,1,2 Jiansheng Li1– 3 1Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou, Henan, 450046, People’s Republic of China; 2Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, Henan, 450046, People’s Republic of China; 3Department of Respiratory Diseases, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, 450003, People’s Republic of ChinaCorrespondence: Jiansheng Li, Henan University of Chinese Medicine, No. 156 Jinshui East Road, Zhengzhou, 450046, People’s Republic of China, Tel +86 371 65676568, Fax +86 371 65944307, Email li_js8@163.comObjective: To assess the completeness of reporting in randomized controlled trials (RCTs) of acupuncture therapy (AT) for chronic obstructive pulmonary disease (COPD).Methods: We systematically searched PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Chongqing VIP (CQVIP), WANFANG Data, and China Biology Medicine (CBM) for studies published from their inception to May 8, 2021. The completeness of reporting was evaluated by CONSORT statement and STRICTA guidelines. Univariate and multivariate regression analyses were performed to preliminarily explore the factors related to completeness of reporting.Results: A total of 44 RCTs were included. The overall quality score (OQS) based on the CONSORT statement and STRICTA guidelines ranged from 3 to 26 and 7 to 14, with a median of 10 and 11, respectively. Among the 35 items of the CONSORT statement, 10 items were fully reported with reporting rate > 70%, and 11 items were poorly reported at a rate < 5%. Among the 17 items of the STRICTA guidelines, 10 items were adequately reported with > 70%, and only 3 items were incompletely reported at a rate < 20%. The agreement of most items was determined as “good”, “substantial”, or “moderate”. By regression analysis, publication language (β coefficient: 6.432, 95% CI: 3.202 to 9.663, P < 0.001) and funding source (β coefficient: 3.159, 95% CI: 1.045 to 5.273, P =0.004) acted as independent predictors of completeness of reporting according to the CONSORT statement. However, no variables associated with the STRICTA guidelines were identified.Conclusion: The completeness of reporting of AT for COPD was inadequate. The condition relatively improved for trials with publication in the English language and funding source. By recommendation, reports should be strictly standardized in accordance with the CONSORT statement and STRICTA guidelines to improve the clinical research evidence of AT for COPD.Keywords: chronic obstructive pulmonary disease, acupuncture therapy, randomized controlled trials, completeness of reporting

Weiwei Qin,1,2 Ting Wang,2 Guangwei Liu,3 Lixin Sun,1 Wei Han,4 Youhe Gao2 1Department of Anesthesiology, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266071, People’s Republic of China; 2Department of Biochemistry and Molecular Biology, Gene Engineering Drug and Biotechnology Beijing Key Laboratory, Beijing Normal University, Beijing, 100875, People’s Republic of China; 3Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Institute of Cell Biology, College of Life Sciences, Beijing Normal University, Beijing, 100875, People’s Republic of China; 4Department of Respiratory Medicine, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266071, People’s Republic of ChinaCorrespondence: Youhe Gao; Wei Han Tel +86 10 58804382; +86 532 85937809Email gaoyouhe@bnu.edu.cn; sallyhan1@163.comBackground: In this work, we aim to investigate dynamic urinary proteome changes during asthma development and to identify potential urinary protein biomarkers for the diagnosis of asthma.Methods: An ovalbumin (OVA)-induced mouse model was used to mimic asthma. The urinary proteome from asthma and control mice was determined using data-independent acquisition combined with high-resolution tandem mass spectrometry.Results: Overall, 331 proteins were identified, among which 53 were differentially expressed (26, 24, 14 and 20 on days 2, 8, 15 and 18, respectively; 1.5-fold change, adjust P< 0.05). Gene Ontology annotation of the differential proteins showed that the acute-phase response, innate immune response, B cell receptor signaling pathway, and complement activation were significantly enriched. Protein–protein interaction network revealed that these differential proteins were partially biologically connected in OVA-induced asthma, as a group. On days 2 and 8, after two episodes of OVA sensitization, six differential proteins (CRAMP, ECP, HP, F2, AGP1, and CFB) were also reported to be closely associated with asthma. These proteins may hold the potential for the early screening of asthma. On days 15 and 18, after challenged with 1% OVA by inhalation, seven differential proteins (VDBP, HP, CTSE, PIGR, AAT, TRFE, and HPX) were also reported to be closely associated with asthma. Thus, these proteins hold the potential to be biomarkers for the diagnosis of asthma attack.Conclusion: Our results indicate that the urinary proteome could reflect dynamic pathophysiological changes in asthma progression.Keywords: OVA-induced asthma, mice, urine, proteome, data-independent acquisition

Jiaqi Xu, Kun Cheng, Hai Lin, Wei Han, Tieying He, Xiaohan Nie, Yonghui Sun, Sulidankazha Qiuman, Yilidan Reheman, Qilong Chen Department of Pancreatic Surgery, Centre of Digestive and Vascular Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, People’s Republic of ChinaCorrespondence: Qilong Chen Email chenqilong651003@sohu.comBackground: Pancreatic cancer (PC) presents a phenomenal disease burden worldwide. The GATA transcription factor family is associated with a variety of human malignancies. However, the relation between GATA family members (GATAs) and PC has not been elucidated.Methods: This study integrates large-scale bioinformatics database resources to analyze the expression patterns of GATAs in PC patients and explore their underlying function mechanism and relevance to immune infiltration and other different cell types in the tumor microenvironment in pancreatic cancer. First, the expression pattern of GATAs in pancreatic cancer was detected by the Oncomine database and the Gene Expression Profile Interaction Analysis (GEPIA2) database and verified through other datasets in the R2 platform. Then, we used the cBioPortal database and the Human Protein Atlas to assess the correlation between GATAs and clinicopathological features of PC. Then, survival analyses were performed to identify candidate prognostic factors in the GATA family in PC patients. Further, we performed gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, protein-protein interaction (PPI) network, immune-infiltration correlation analysis, and cell type analysis of the tumor microenvironment at the single-cell level to explain the function of GATAs in pancreatic cancer.Results: We found that GATA3 and GATA6 were highly expressed in pancreatic cancer, and the expression levels of GATA4 and GATA6 correlated with the pathological stage, differentiation grade, and molecular subtype of pancreatic cancer. The survival analysis revealed that lower GATA4 of PC patients was associated with better outcomes, and higher GATA6 might be associated with longer OS. In addition, GATA3 was associated with immune cell infiltration of PC, and GATA6 was mainly distributed in the epithelial cells with ductal phenotype.Conclusion: This work tentatively identified GATA3, GATA4, and GATA6 in the GATA family associated with pancreatic cancer. GATA4 may serve as a prognostic factor for PC patients, and GATA6 may act as a subtype marker for PC. In addition, GATA3 may reflect the immune-infiltration status of PC.Keywords: pancreatic cancer, GATA transcriptional factor, prognosis, tumor microenvironment, bioinformatics analysis

Abstract The Society for Cardiovascular Magnetic Resonance (SCMR) is an international society focused on the research, education, and clinical application of cardiovascular magnetic resonance (CMR). Case of the week is a case series hosted on the SCMR website ( https://www.scmr.org ) that demonstrates the utility and importance of CMR in the clinical diagnosis and management of cardiovascular disease. Each case consists of the clinical presentation and a discussion of the condition and the role of CMR in diagnosis and guiding clinical management. The cases are all instructive and helpful in the approach to patient management. We present a digital archive of the 2020 Case of the Week series of 11 cases as a means of further enhancing the education of those interested in CMR and as a means of more readily identifying these cases using a PubMed or similar search engine.

Zhidan Li,1 Xiaojuan Bai,2 Lulu Han,2 Wen Han,2 Weina Hu3 1Department of Ultrasound, The Fourth Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of Gerontology and Geriatrics, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China; 3Department of Cardiology, The Fourth Affiliated Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Weina HuDepartment of Cardiology, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, People’s Republic of ChinaEmail weina_hu2021@126.comXiaojuan BaiDepartment of Gerontology and Geriatrics, Shengjing Hospital of China Medical University, Shenyang, 110004, People’s Republic of ChinaEmail xiaojuan_Bai@126.comBackground: Electromechanical coupling may play a significant role in the association between abnormal myocardial mechanics and heterogeneity of repolarization. This study sought to assess the potential relationship between the left atrial volume index (LAVI), which is an important marker of cardiac diastolic function, and ventricular repolarization variables, such as the QT interval, Tpeak-to-Tend (Tpe) interval and Tpe/QT ratio, in an apparently healthy Chinese population.Methods: This was a community-based cross-sectional study conducted in Shenyang, China. A total of 414 healthy subjects aged 35– 91 years, including 186 men (44.9%), were enrolled. In addition to performing clinical and laboratory measurements, all subjects underwent comprehensive echocardiography and standard 12-lead electrocardiography. Echocardiographic and electrocardiographic results were analysed separately and in a blinded fashion. Correlation and regression analyses were applied to determine associations.Results: Subjects were divided into four groups according to quartile of LAVI levels (< 16.0, 16.0– 18.9, 19.0– 22.5 and > 22.5 mL/m2). Ventricular repolarization variables, such as QT interval and QTc interval, gradually increased with the progression from low to high LAVI levels (P< 0.05). LAVI was positively and significantly correlated with the QT interval, the QTc interval, and the Tpe interval (P< 0.01). After adjusting for age and other possible confounders, LAVI showed significant and independent associations with the QT interval and the QTc interval (P< 0.001; P=0.003).Conclusion: Echocardiographic LAVI is linearly associated with ventricular repolarization variables even in healthy people.Keywords: left atrial volume index, QT interval, Tpe interval, diastolic dysfunction, ventricular repolarization

Kai Liu,1,* Xinjuan Yu,2,* Xuefen Cui,2 Yi Su,2 Lixin Sun,3 Jiulong Yang,4 Wei Han2 1Department of Rehabilitation, Qingdao Municipal Hospital, Qingdao University, Qingdao, People’s Republic of China; 2Department of Respiratory and Critical Medicine, Respiratory Disease Key Laboratory of Qingdao, Qingdao Municipal Hospital, Qingdao University, Qingdao, People’s Republic of China; 3Department of Anesthesia, Qingdao Municipal Hospital, Qingdao University, Qingdao, People’s Republic of China; 4Hospital Office, Qingdao Municipal Hospital, Qingdao University, Qingdao, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei HanDepartment of Pulmonary and Critical Care Medicine, Qingdao Municipal Hospital, Qingdao University, No. 5 Donghaizhong Road, Qingdao, Shandong, 266071, People’s Republic of ChinaTel +86 532 85937579Email hanw@qdu.edu.cnJiulong YangHospital Office, Qingdao Municipal Hospital, Qingdao University, No. 5 Donghaizhong Road, Qingdao, Shandong, 266071, People’s Republic of ChinaTel +86 532 88905509Email qdyxkp@163.comBackground: The proprioceptive neuromuscular facilitation (PNF) stretching could improve the contractile capacity of respiratory muscles, but the effect on pulmonary function, when it is combined with aerobic training, remains unknown.Objective: To evaluate the effect of PNF combined with aerobic training on respiratory symptoms, pulmonary function and neck/shoulder mobility in patients with COPD.Design: Randomized controlled trial.Participants: Fifty-five COPD patients were randomly divided into PNF group (n=28) and control group (n=27).Intervention: On the basis of conventional treatment, the control group performed 30 min aerobic training on a treadmill, while the PNF group added 10-minute PNF stretching 3 times every training day. Both groups did their training in 5 days per week for 6 weeks.Measures: Measures were taken before and after 6 weeks of training. COPD Assessment Test (CAT), dyspnea Visual Analog Scale (VAS), forced vital capacity (FVC), forced expiratory volume in first second (FEV1), inspiratory capacity (IC), inspiratory reserve volume (IRV), 6-minute walk test (6MWT), the range of motion (ROM) of head protraction, shoulder flexion, and the non-dominant pectoralis minor muscle (PmM) length were measured.Results: All the indicators of both groups were significantly improved after 6 weeks of intervention except for FVC, FEV1 and PmM length. Compared to the control group, the PNF group showed significant improvement in the CAT score, dyspnea VAS score, IC, IRV, 6MWT, as well as head protraction ROM and shoulder flexion ROM. Furthermore, IC was positively correlated with the head protraction ROM and PmM length (r=0.415, 0.579, P=0.028, 0.001); IRV was positively correlated with the shoulder flexion ROM (r=0.405, P=0.032) in the PNF group.Conclusion: PNF stretching combined with aerobic training reduces dyspnea and improves some pulmonary function measures, which is associated with neck/shoulder mobility, in COPD patients.Keywords: chronic obstructive pulmonary disease, proprioceptive neuromuscular facilitation stretching, aerobic training, pulmonary function

Shuyi Qin,1,2,* Xinjuan Yu,1,2,* Qianli Ma,3,* Li Lin,4 Qinghai Li,1,2 Hong Liu,1,2 Lei Zhang,5 Shuguang Leng,6 Wei Han1,2 1Department of Pulmonary and Critical Care Medicine, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, Shandong, People’s Republic of China; 2Respiratory Disease Key Laboratory of Qingdao, Qingdao Municipal Hospital, Qingdao, Shandong, People’s Republic of China; 3Department of Radiology, Qingdao Municipal Hospital, Qingdao, Shandong, People’s Republic of China; 4Department of Pulmonary Medicine, Shandong Provincial Chest Hospital, Jinan, Shandong, People’s Republic of China; 5Department of Hospital Infection, Qingdao Municipal Hospital, Qingdao, Shandong, People’s Republic of China; 6Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM, USA*These authors contributed equally to this workCorrespondence: Wei HanDepartment of Pulmonary and Critical Care Medicine, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No. 5 Donghaizhong Road, Qingdao, Shandong, People’s Republic of ChinaTel +86 532 85937579Email hanw@qdu.edu.cnShuguang LengDepartment of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM, USATel +1 505 3489465Email sleng@salud.unm.eduPurpose: To explore a practical marker for quantitatively analyzing the small airway remodeling in COPD by HRCT.Patients and Methods: Twenty-four patients with COPD (GOLD I, n = 7; GOLD II, n = 8; GOLD III+IV, n = 9) and 14 healthy controls (7 normal pulmonary function; 7 small-airway disease (SAD)) were enrolled in the study as five groups, GOLD I, GOLD II, GOLD III+IV, normal and SAD. All subjects underwent HRCT and spirometry. With ISP 9.0, whole emphysema index (EI) and the airway parameters, including wall area (WA), lumen area (LA), airway area (AA) of the 3rd, 5th and 9th generations of bronchi, were measured successively. The ratio of LA/AA and WA/AA in the 3rd, 5th and 9th generations of bronchi were calculated and compared among groups.Results: For the five groups, EI was increased only in GOLD III+IV group (P < 0.05), while the ratio of LA/AA (9-LA/AA) and WA/AA (9-WA/AA) in 9th generation of bronchi have significantly changed since SAD group (P < 0.05). There were significant correlation between FEV1generations of bronchi (r3 = 0.429, r5 = 0.583, r9 = 0.592, respectively, P < 0.05); FEV1% and WA/AA (r3 = – 0.428, r5 = – 0.532, r9 = – 0.570, respectively, P < 0.05); as well as MMEF% and LA/AA (r3 = 0.421, r5 = 0.566, r9 = 0.610, respectively, P < 0.05); MMEF% and WA/AA (r3 = – 0.421, r5 = – 0.529, r9 = – 0.593, respectively, P < 0.05).Conclusion: Small airway remodeling has occurred in the early stage of COPD, while emphysema in the late stage of COPD. The 9-LA/AA and 9-WA/AA are accurate and practical markers for small airway remodeling of COPD.Keywords: COPD, high-resolution CT, emphysema index, pulmonary function test

Abstract IgG4‐related disease (IgG4RD) with intracranial involvement is rare. We report a 56‐year‐old male who had an excellent response to rituximab and dexamethasone after going undiagnosed for 5 years. After 3 years of rituximab maintenance, he has no evidence of disease on brain MRI.

Wantong Han,1– 3 Lingzhong Xu,1– 3 Aimin Niu,4 Yurong Jing,1– 3 Wenzhe Qin,1– 3 Jiao Zhang,1– 3 Xiang Jing,5 Yali Wang6 1Centre for Health Management and Policy Research, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 2NHC Key Laboratory of Health Economics and Policy Research, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 3Center for Health Economics Experiment and Public Policy Research, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 4Department of Public Health, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 5Yuncheng Central Hospital, Yuncheng, Shanxi, People’s Republic of China; 6Henan Provincial Center for Disease Control and Prevention, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Lingzhong XuSchool of Public Health, Cheeloo College of Medicine, Shandong University, Mailbox No. 110, 44 Wenhuaxi Road, Jinan, 250012, Shandong, People’s Republic of ChinaTel +86-0531-8838-2648Fax +86-0531-88382533Email lzxu@sdu.edu.cnAimin NiuDepartment of Public Health, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324 Jingwu Road, Huaiyin District, Jinan, 250021, People’s Republic of ChinaTel +86-1866-370-2722Fax +86-0531-87921022Email nam1106@163.comPurpose: Studies have suggested that public health emergencies can have many psychological effects on college students, therefore, the aim of this study is to investigate current situation of college students’ anxiety and its determinants in the time of an unexpected pandemic.Patients and Methods: We conducted convenience sampling to collect the data through network-based online questionnaires in February 2020, a total of 17,876 college students were included in the analysis. Chi-square test and multivariate logistic were used to identify the associations between the outbreak experiences and anxiety detection.Results: This study found that detection rate of anxiety among college students was 18.2%. The differences in male students, students whose self-perceived risk of infection were high, who were greatly affected by the outbreak, eager to go back to school, reluctant to leave home and stay at home enough were of statistical significance among different anxiety level (OR> 1, P< 0.05). And the severe anxiety rate of students who living in cities was significantly higher (2.337[1.468, 3.721]).Conclusion: Although our results show that anxiety among college students was at a low level, various universities should focus on the online activities and develop appropriate epidemic management plans to prevent their feelings of worry, tension and panic.Keywords: anxiety, college students, network-based, COVID-19

Wei Han,1– 3,* Desong Kong,2,* Qin Lu,4 Wei Zhang,5 Zhimin Fan4 1Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2Chinese Medicine Modernization and Big Data Research Center, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 3General Surgery Department, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 4Proctology Department, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 5Anesthesiology Department, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhimin FanProctology Department, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, No. 157 Daming Avenue, Qinhuai District, Nanjing City, Jiangsu Province, 210012, People’s Republic of ChinaTel +86-2552276501Email fanzhimin_zhmf@163.comBackground: Aloperine can regulate miR-296-5p/Signal Transducer and Activator of Transcription 3 (STAT3) pathway to inhibit the malignant development of colorectal cancer (CRC), but the regulatory mechanism is unclear. This study explored the upstream mechanism of Aloperine in reducing CRC damage from the perspective of the circRNA-miRNA-mRNA regulatory network.Methods: After treatment with gradient concentrations of Aloperine (0.1 mmol/L, 0.2 mmol/L, 0.4 mmol/L, 0.8 mmol/L and 1 mmol/L) for 24 hours, changes in CRC cell proliferation and apoptosis were detected by functional experiments. Data of the differential expression of miR-296-5p in CRC patients and healthy people were obtained from Starbase. The effects of Aloperine on 12 differentially expressed circRNAs were detected. The binding of miR-296-5p with NOP2/Sun RNA methyltransferase 2 (circNSUN2) and STAT3 was predicted by TargetScan and confirmed through dual-luciferase experiments. The expressions of circNSUN2, miR-296-5p and STAT3 as well as apoptosis-related genes in CRC cells were detected by qRT-PCR and Western blot as needed. Rescue experiments were conducted to test the regulatory effects of circNSUN2, miR-296-5p and STAT3 on CRC cells.Results: Aloperine at a concentration gradient inhibited proliferation and promoted apoptosis in CRC cells. The abnormally low expression of miR-296-5p in CRC could be upregulated by Aloperine. Among the differentially expressed circRNAs in CRC, only circNSUN2 not only targets miR-296-5p, but also can be regulated by Aloperine. The up-regulation of circNSUN2 offset the inhibitory effect of Aloperine on cancer cells. The rescue experiments finally confirmed the regulation of circNSUN2/miR-296-5p/STAT3 axis in CRC cells.Conclusion: By regulating the circNSUN2/miR-296-5p/STAT3 pathway, Aloperine prevents the malignant development of CRC cells.Keywords: colorectal cancer, aloperine, NOP2/Sun RNA methyltransferase 2, miR-296-5p, signal transducer and activator of transcription 3

Ming Zhang,1– 3 Wei Han,3,4 Yuhao Xu,3,4 Dapeng Li,3 Qun Xue1 1Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, People’s Republic of China; 2Department of Geriatric Psychiatry, Changzhou Dean Hospital, Changzhou, Jiangsu 213000, People’s Republic of China; 3Department of Central Laboratory, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, People’s Republic of China; 4Department of Neurology, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, People’s Republic of ChinaCorrespondence: Qun XueDepartment of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, People’s Republic of ChinaTel + 86- 13013813620Email qxue_sz@163.comBackground: Although numerous microRNAs (miRNAs) have been discovered to participate in the progression of Alzheimer’s disease (AD), they are still difficult to apply in clinical work. Thus, the identification of novel miRNAs and clarification of their clinical significance are importing for improving the diagnosis and treatment of AD. The purpose of this study was to analyze the expression of miR-128 and its diagnostic value in patients with AD.Patients and Methods: In this study, 117 AD patients and 106 controls were enrolled, and the demographic data, biochemical parameters and serum miR-128 levels were collected. These data were then used to build a logistic regression model, and receiver operating characteristic (ROC) curves were drawn to evaluate the diagnostic value of miR-128. The relationships between miR-128 and inflammatory factors (IL-1β/TNF-α) were also analyzed from clinical serum data.Results: Our study found that miR-128 was significantly upregulated in the serum samples of AD patients compared with controls, and that this upregulation was negatively correlated with Mini-Mental State Examination (MMSE) scores (r = − 0.687, P< 0.01). ROC curve showed that the area under the curve of miR-128 was 0.831. Logistic regression analyses showed that glycosylated hemoglobin (HbA1c) levels, low-density lipoprotein (LDL) levels, MMSE scores and serum miR-128 levels were statistically significant (P< 0.01), and the ROC curve of the combined detection of these variables was 0.906. The serum miR-128 levels in AD patients were positively correlated with the serum IL-1β (r=0.798, P< 0.01) and serum TNF-α levels (r=0.733, P< 0.01).Conclusion: Serum miR-128 is a candidate diagnostic biomarker in AD patients who achieved good diagnostic performance when used alone or in combination with other factors and may have the potential to be a novel therapeutic target for neuroinflammation.Keywords: Alzheimer’s disease, miR-128, logistic regression, ROC curve

Yu Sun,* Weiying Han,* Yongxi Song, Peng Gao, Yuchong Yang, Dehao Yu, Yu Wang, Zhenning Wang Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, First Hospital of China Medical University, Shenyang City 110001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhenning WangDepartment of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, First Hospital of China Medical University, Shenyang 110001, People’s Republic of ChinaTel +86-24-83283556Fax +86-24-22703578 Email josieon826@sina.cnBackground: The prognostic role of preoperative fibrinogen in colorectal cancer (CRC) patients remains controversial. Therefore, we assessed the predictive value of preoperative fibrinogen and developed a tool for predicting the survival of CRC patients.Methods: This retrospective study evaluated 1869 patients who underwent curative resection for CRC. Univariate and multivariate survival analyses were conducted to identify the factors correlated with overall survival (OS) and cancer-specific survival (CSS). Nomograms were developed as a graphical representation of the Cox proportional hazards regression models. The performance of the nomograms was assessed by Harrell’s concordance index (c-index) and calibration plots.Results: The preoperative fibrinogen levels were correlated with age, tumor differentiation, tumor location, pT category, and TNM stage. In the multivariate analysis, elevated fibrinogen level was independently correlated with worse OS and CSS (OS: hazard ratio [HR] = 0.777, 95% confidence interval [95% CI] = 0.630– 0.958, P = 0.018; CSS: HR = 0.757, 95% CI = 0.605– 0.947, P = 0.015). The nomograms could predict outcomes with a c-index for OS and CSS of 0.79 and 0.81, respectively. The nomograms also had a good calibration.Conclusion: Preoperative fibrinogen level was an independent marker of poor prognosis in patients with nonmetastatic CRC, and there was a threshold level for the use of fibrinogen as a prognostic factor. Furthermore, nomograms may help predict the individual risk of OS and CSS in patients treated for CRC.Keywords: colorectal cancer, fibrinogen, prognosis, TNM staging, nomogram

Abstract ALK‐positive ALCL can lead to rapid irreversible destruction of the optic pathway. Early treatment should be instituted in patients with CNS involvement or those at increased CNS risk.

Peng Sun,1,2 Qichang Yang,1 Yanben Wang,2 Jiaxuan Peng,3 Kangxian Zhao,1 Yewei Jia,2 Tan Zhang,2 Xuanyuan Lu,2 Weiqi Han,2 Yu Qian1,2 1The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, People’s Republic of China; 2Department of Orthopedics, Shaoxing People’s Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, Zhejiang 312000, People’s Republic of China; 3Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of ChinaCorrespondence: Yu QianThe Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, No. 109, XueYuan Road, Wenzhou, Zhejiang 325000, People’s Republic of ChinaEmail doctor120@hotmail.comIntroduction: Osteoporosis is a metabolic bone disease characterized by reduced bone quantity and microstructure, typically owing to increased osteoclastogenesis and/or enhanced osteoclastic bone resorption, resulting in uncontrolled bone loss, which primarily affects postmenopausal women. In consideration of the severe side effects of current drugs for osteoporosis, new safe and effective medications are necessary. Pristimerin (Pri), a quinone methide triterpene extracted from Celastraceae and Hippocrateaceae members, exhibits potent antineoplastic and anti-inflammatory effects. However, its effect on osteoclasts remains unknown.Materials and Methods: We evaluated the anti-osteoclastogenic and anti-resorptive effect of Pri on bone marrow-derived osteoclasts and its underlying mechanism in vitro. In addition, the protective effect of Pri on ovariectomy model was also explored in vivo.Results: In vitro, Pri inhibited osteoclast differentiation and mature osteoclastic bone resorption in a time- and dose-dependent manner. Further, Pri suppressed the expression of osteoclast-related genes and the activation of key proteins. Pri also inhibited the early activation of ERK, JNK MAPK, and AKT signaling pathways in bone marrow-derived macrophages (BMMs), ultimately inhibiting the induction and activation of the crucial osteoclast transcriptional factor nuclear factor of activated T‐cell cytoplasmic 1 (NFATc1). In vivo, consistent with our in vitro data, Pri clearly prevented ovariectomy-induced bone loss.Conclusion: Our data showed that Pri inhibits the differentiation and activation of osteoclasts in vitro and in vivo, and could be a promising candidate for treating osteoporosis.Keywords: osteoclast, osteoporosis, ERK, JNK, AKT, Pri

Abstract This case illustrates an unusual presentation of paraneoplastic myositis in stage IV follicular lymphoma managed with high‐dose steroids, a previously unreported entity in the literature.

Peiqiang Jiang, Wei Han, Yu Fu, Qingmin Chen Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin, People’s Republic of ChinaCorrespondence: Qingmin ChenDepartment of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, No. 71 Xinmin Street, Changchun, Jilin 130021, People’s Republic of ChinaTel +86-431-81875133Email chenqingminchqm@163.comPurpose: Circular RNAs (circRNAs) play important roles in hepatocellular carcinoma (HCC) development. The circRNA hsa_circ_0091579 (circ_0091579) is dysregulated in HCC, while the mechanism of circ_0091579 in HCC development is largely unknown.Patients and Methods: Thirty paired cancer and adjacent normal tissues were harvested from HCC patients. SNU-387 and Huh7 cells were cultured in this study. circ_0091579, microRNA-940 (miR-940) and tachykinin-1 receptor (TACR1) abundances were measured via quantitative reverse transcription-polymerase chain reaction or Western blot. Cell viability, migration, invasion, colony ability, cell cycle distribution and apoptosis were assessed via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, transwell assay, colony formation assay and flow cytometry. The interaction among circ_0091579, miR-940 and TACR1 was tested via dual-luciferase reporter analysis. The anti-HCC role of circ_0091579 knockdown in vivo was investigated using xenograft model.Results: circ_0091579 expression was enhanced in HCC tissue samples and cells. circ_0091579 silence inhibited cell viability, migration, invasion and colony formation, induced cell cycle arrest at G0/G1 phase, and promoted apoptosis in HCC cells. miR-940 was targeted via circ_0091579 and miR-940 knockdown reversed the suppressive effect of circ_0091579 silence on HCC development. miR-940 targeted TACR1 to repress HCC development. circ_0091579 could regulate TACR1 expression by mediating miR-940. Down-regulation of circ_0091579 decreased xenograft tumor growth.Conclusion: Knockdown of circ_0091579 repressed HCC development by mediating miR-940/TACR1 axis, indicating a new pathogenesis of HCC.Keywords: hepatocellular carcinoma, hsa_circ_0091579, miR-940, TACR1

Chunmei Geng,1 Yujin Guo,1 Changshui Wang,2 Changmeng Cui,3 Wenxiu Han,1 Dehua Liao,4 Pei Jiang1 1Department of Pharmacy, Jining First People’s Hospital, Jining Medical University, Jining 272000, People’s Republic of China; 2Department of Clinical Translational Medicine, Jining Life Science Center, Jining 272000, People’s Republic of China; 3Department of Neurosurgery, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining 272000, People’s Republic of China; 4Department of Pharmacy, Hunan Cancer Hospital, Central South University, Changsha 410011, People’s Republic of ChinaCorrespondence: Pei JiangDepartment of Pharmacy, Jining First People’s Hospital, Jining Medical University, Jining 272000, People’s Republic of ChinaTel/Fax +86 537 2106208Email jiangpeicsu@sina.comPurpose: Substantial evidence indicates that lipopolysaccharide (LPS) exposure can lead to systemic inflammatory response syndrome (SIRS) and multiple organ failure. Previous metabolomic studies have mainly focused on LPS-induced depression or hepatic and renal effects. However, no comprehensive metabolomics-based analysis of the serum, liver, kidney, hippocampus, and heart following exposure to LPS has been undertaken to date.Material and Methods: Male Sprague–Dawley rats were randomly allocated to a control and a LPS-treated group (n=8). LPS for 2 weeks (0.5 mg/kg every other day) was given via intraperitoneal injection. Gas chromatography–mass spectrometry (GC–MS) was used for metabolite determination, while multivariate statistical analysis was performed to identify differentially expressed metabolites between the two groups.Results: Our study revealed that 24, 13, 12, 7, and 12 metabolites were differentially expressed between the LPS treatment group and the control group in the serum, liver, kidney, hippocampus, and heart, respectively. We further identified that these metabolic changes were mainly involved with aminoacyl-tRNA biosynthesis; glutathione metabolism; glyoxylate and dicarboxylate metabolism; glycine, serine, and threonine metabolism; arginine biosynthesis; bile acid biosynthesis; and glycerolipid metabolism.Conclusion: We have systematically elucidated the metabolic changes underlying LPS-induced SIRS, thereby providing insight into the mechanisms associated with these alterations.Keywords: systemic inflammatory response syndrome, metabolites, gas chromatography–mass spectrometry, multivariate statistical analysis

Jiaxuan Peng,1,* Kangxian Zhao,2,* Jiling Zhu,3,* Yanben Wang,4,5 Peng Sun,2 Qichang Yang,2 Tan Zhang,4 Weiqi Han,4 Wenjun Hu,4 Wanlei Yang,4 Jianwei Ruan,6 Yu Qian1,2,4 1Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi 530021, People’s Republic of China; 2The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, People’s Republic of China; 3Department of Clinical Medicine, Medical College of Shaoxing University, Shaoxing, Zhejiang 312000, People’s Republic of China; 4Department of Orthopaedics, Shaoxing People’s Hospital, Zhejiang University School of Medicine, Shaoxing 312000, Zhejiang, People’s Republic of China; 5Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 6Department of Orthopaedics, Taizhou Municipal Hospital, Taizhou 318000, Zhejiang, Republic of China*These authors contributed equally to this workCorrespondence: Yu QianDepartment of Orthopaedics, Shaoxing People’s Hospital, Zhejiang University School of Medicine, Shaoxing 312000, Zhejiang, People’s Republic of ChinaEmail doctor120@hotmail.comIntroduction: Osteoclasts are giant polynuclear cells; their main function is bone resorption. An increased number of osteoclasts and enhanced bone resorption exert significant effects on osteoclast-related bone-lytic diseases, including osteoporosis. Given the limitations of current therapies for osteolytic diseases, it is urgently required to develop safer and more effective alternatives. Sarsasapogenin, a major sapogenin from Anemarrhena asphodeloides Bunge, possesses potent antitumor effects and inhibits NF-κB and MAPK signaling. However, the manner in which it affects osteoclasts is unclear.Methods: We investigated the effects of anti-osteoclastogenic and anti-resorptive of sarsasapogenin on bone marrow-derived osteoclasts.Results: Sarsasapogenin inhibited multiple RANKL-induced signaling cascades, thereby inhibiting the induction of key osteoclast transcription factor NFATc1. The in vivo and in vitro results were consistent: sarsasapogenin treatment protected against bone loss in a mouse osteolysis model induced by lipopolysaccharide.Conclusion: Our research confirms that sarsasapogenin can be used as a new treatment for osteoclast-related osteolytic diseases.Keywords: sarsasapogenin, osteoclast, osteoclastogenesis, NF-κB, MAPK, NFATc1, therapeutics

Wenxiu Han,1 Zhijie Wei,2 Hailiang Zhang,1 Chunmei Geng,1 Ruili Dang,1 Mengqi Yang,1 Jun Zhang,3 Changshui Wang,1 Pei Jiang1 1Department of Pharmacy, Jining First People’s Hospital, Jining Medical University, Jining 272011, People’s Republic of China; 2Department of Medical Administration, Jining First People’s Hospital, Jining Medical University, Jining 272011, People’s Republic of China; 3Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People’s Republic of ChinaCorrespondence: Pei Jiang; Ruili DangJining First People’s Hospital, Jining Medical University, Jining, People’s Republic of ChinaTel/Fax +86 537 2106208Email jiangpeicsu@sina.com; rosydang@126.comPurpose: Inflammation is a key contributor to coronary heart disease (CHD). Sortilin is a sorting receptor and has been identified as a critical regulator of inflammatory response. Therefore, our study aimed to determine the link between circulating sortilin levels, proinflammatory cytokine levels, and the occurrence of CHD.Patients and Methods: Our study included 227 CHD patients and 101 matched healthy individuals. Circulating serum levels of sortilin and proinflammatory cytokines, including IL-1β, IL-6 and TNF-α, were assessed by a double-antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA). Linear regression and correlation analyses were used to estimate the associations between sortilin and proinflammatory cytokines. Moreover, six single-nucleotide polymorphisms (SNPs) spanning the sortilin and SORL1 genes were genotyped.Results: Elevated levels of sortilin (P=0.027) and proinflammatory cytokines IL-1β (P=0.013), IL-6 (P=0.000) and TNF-α (P=0.010) were observed in CHD patients compared to those in healthy controls. Furthermore, sortilin levels were significantly positively correlated with IL-1β (r=0.252, P=0.0001), IL-6 (r=0.250, P=0.0001) and TNF-α (r=0.180, P=0.0064) levels. Notably, sortilin polymorphisms were revealed to be associated with the occurrence of CHD and varying sortilin levels. Subjects with the rs599839 AA risk genotype for CHD had significantly higher sortilin levels than those with the GG and GA genotypes (P=0.000); the same tendency was also observed in the levels of the proinflammatory cytokines IL-1β (P=0.003) and TNF-α (P=0.000). Similarly, GG carriers of rs464218 with increased sortilin levels were found to be at increased risk for CHD (P=0.014). The levels of IL-1β (P=0.025) and IL-6 (P=0.015) were also increased in these patients.Conclusion: Our findings reveal that high sortilin levels may interact with inflammatory response to contribute to the occurrence of CHD. Considering that our clinical evidence suggests for the first time that sortilin involves in inflammatory response in CHD, the mechanistic role of sortilin in the progression of CHD deserves detailed investigation.Keywords: sortilin, inflammation, SORL1, polymorphism, coronary heart disease