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Chun Ling,1,2 Nengneng Cao,1 Huiping Wang,1 Yang Wan,1 Xue Liang,1 Jinjing Guo,1 Meng Xiao,1 Qiguo Zhang,2 Zhimin Zhai1 1Department of Hematology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230000, People’s Republic of China; 2Department of Hematology, Affiliated Chuzhou Hospital of Anhui Medical University, First People’s Hospital of Chuzhou, Chuzhou, Anhui, 239001, People’s Republic of ChinaCorrespondence: Zhimin Zhai, Department of Hematology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230000, People’s Republic of China, Email zzzm886@163.comBackground: Acute Myeloid Leukemia (AML) is a prevalent neoplastic disorder. The roles of E3 ubiquitin ligases and related genes in AML drug resistance and prognosis remain unclear.Methods: Genes were identified from GeneCards and UniProt databases, differentially expressed genes were selected based on transcriptional sequencing data from wild-type and Adriamycin-resistant HL60 (HL60/WT & HL60/ADR) cell lines, and the intersection of these three sources was taken. We then constructed a prognostic model comprising five genes (HBP1, RNF130, RMND5B, TRIM32, and UBE2L3) through univariate Cox and LASSO regression analyses in the TCGA cohort and validated it in the BeatAML2.0 cohort. Finally, the expression of UBE2L3 was verified in cell lines and clinical case specimens.Results: The model accurately predicted AML prognosis and identified the UBE2L3 gene within the model as a high-risk biomarker associated with drug resistance, significantly influencing AML outcomes.Conclusion: The high expression of UBE2L3 is a reliable biomarker for drug resistance and poor prognosis of acute myeloid leukemia.Keywords: E3 ubiquitin ligase, prognostic model, UBE2L3, acute myeloid leukemia, drug resistance

Yujing Li,1,2,* Xindie Ren,3,* Qianqian Wang,4,* Songying Shen,2,* Yihao Li,1,2 Xinling Qian,2 Yufei Tang,2 Jinguang Jia,2 Hao Zhang,2 Junjie Ding,2 Yinsen Song,1 Sisen Zhang,1 Shengfeng Wang,5 Yinghe Xu,6 Yongpo Jiang,6 Xuwei He,7 Muhua Dai,8 Lin Zhong,9 Yonghui Xiong,10 Yujie Pan,11 Mingqiang Wang,12 Huanzhang Shao,12 Hongliu Cai,3 Lingtong Huang,3 Hongyu Wang1,2 1Department of Critical Care Medicine, The Fifth Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou, Henan Province, People’s Republic of China; 2Department of Critical Care Medicine, People’s Hospital of Henan University of Chinese Medicine/People’s Hospital of Zhengzhou, Zhengzhou, Henan Province, People’s Republic of China; 3Department of Critical Care Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 4Department of Critical Care Medicine, The First Hospital of Jiaxing, Jiaxing, Zhejiang Province, People’s Republic of China; 5Department of Critical Care Medicine, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of China; 6Department of Critical Care Medicine, Taizhou Hospital of Zhejiang Province affiliated with Wenzhou Medical University, Taizhou, Zhejiang Province, People’s Republic of China; 7Department of Critical Care Medicine, Lishui People’s Hospital, Lishui, Zhejiang Province, People’s Republic of China; 8Department of Critical Care Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang Province, People’s Republic of China; 9Department of Critical Care Medicine, The First People’s Hospital of Pinghu, Pinghu, Zhejiang Province, People’s Republic of China; 10Department of Critical Care Medicine, Lanxi Hospital of Traditional Chinese Medicine, Lanxi, Zhejiang Province, People’s Republic of China; 11Department of Critical Care Medicine, Wenzhou Central Hospital, Wenzhou, Zhejiang Province, People’s Republic of China; 12Department of Critical Care Medicine, Henan Key Laboratory for Critical Care Medicine, Zhengzhou Key Laboratory for Critical Care Medicine, Henan Provincial People’s Hospital; Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, Henan Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lingtong Huang, Department of Critical Care Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China, Email lingtonghuang@zju.edu.cn Hongyu Wang, Department of Critical Care Medicine, People’s Hospital of Henan University of Chinese Medicine/People’s Hospital of Zhengzhou, Zhengzhou, Henan Province, People’s Republic of China, Email hongyu260@163.comBackground: Several predictive models for invasive pulmonary aspergillosis (IPA) based on clinical characteristics have been reported. Nevertheless, the significance of other concurrently detected microorganisms in IPA patients is equally noteworthy. This study aimed to develop a risk prediction model for IPA by integrating clinical and microbiological characteristics.Methods: This retrospective study was conducted in adult intensive care units (ICUs) of 17 medical centers in China. Clinical data were collected from patients with severe pneumonia who underwent clinical metagenomics of bronchoalveolar lavage fluid between January 1, 2019, and June 30, 2023. Subsequently, patients were randomly assigned to training and validation cohorts in a 7:3 ratio. In the training cohort, potential influencing factors were identified through univariate analysis, clinical practice, and existing literature, and a risk prediction model was constructed using multivariate logistic regression analysis. The performance of this model was then assessed and validated in the validation cohort.Results: Out of 1737 patients initially included in the study, 898 were ultimately analyzed, of which 100 (11%) were diagnosed with IPA. The risk prediction model for IPA, incorporating microbiological characteristics, identified six independent risk factors, namely age, immunosuppression, chronic kidney disease, connective tissue disease, liver failure, and cytomegalovirus positivity. The model demonstrated a superior discriminative ability, with area under the curve (AUC) values of 0.791 and 0.792 in the training and validation cohorts, respectively. Sensitivity and specificity reached 73.1% and 74.9%, respectively, and the model demonstrated good calibration.Conclusion: This study developed a novel risk prediction model for IPA incorporating microbiological characteristics based on clinical metagenomics. The model exhibited good discriminative ability and calibration.Keywords: CAP, community-acquired pneumonia, IPA, invasive pulmonary aspergillosis, prediction model, microbiological characteristics, clinical metagenomics

Shuaiyou Wang,1 Dingding Li,1 Chenjun Liu,1 Xueting Sun,1 Yage Shi,1 Hongru Wang,2 Huimin Zhang3 1School of Nursing, Xinxiang Medical University, Xinxiang, Henan, People’s Republic of China; 2Nursing of Department, Xinxiang First People’s Hospital, Xinxiang, Henan, People’s Republic of China; 3School of Nursing, Ningxia Medical University, Yinchuan, People’s Republic of ChinaCorrespondence: Huimin Zhang, School of Nursing, Ningxia Medical University, No.1160 Shengli South Street, Xingqing District, Yinchuan, 750001, People’s Republic of China, Email 35290915@qq.comBackground: Community integration (CI) is the ultimate goal of rehabilitation for individuals with disabilities. It plays a significant role in restoring their social functioning and facilitating their reintegration into community and family life. However, no studies have utilized bibliometric methods to explore community integration.Objective: To conduct a review about community integration of disabilities and to clarify the knowledge, hotspots, and trends through the bibliometric method.Methods: Studies on community integration from 1990 to 2023 were retrieved from the Web of Science Core Collection (WOSCC). CiteSpace 6.2.R4 and Microsoft Office Excel 2019 were applied. The CiteSpace node types involved in this study include keyword, reference, cited author, cited Journal, and the dual-map overlay of journals. CiteSpace presented the keyword cluster map, keywords timeline view map, keywords bursts map, and overlay map of journals. Microsoft Office Excel 2019 was used to present the trend of annual publications and draw up related tables and figures.Results: A total of 2239 hits were included. The number of publications related to community integration is increasing gradually. The three most frequent keywords is Brain Injury (571, 13%), Individuals (488, 11%), Quality of Life (434, 10%). Keyword cluster map and timeline map with eight clusters were obtained, and the current strongest citation burst keywords are social participation, substance use, experiences, interventions, and Afghanistan. Willer is the author with the most citations. McColl has the largest centrality in the first ten cited authors. The most cited reference is published by the World Health Organization (WHO). Archives of Physical Medicine and Rehabilitation is the journal with the highest co-citation frequency. The overlay map of journals presented four distinct paths: the journals in “psychology education, health” and “neurology, sports, ophthalmology” often cite journals in “health, nursing, medicine” and “psychology, education, social”.Conclusion: Community integration for individuals with disabilities is gradually becoming a hot topic. Research on community integration related to traumatic brain injury (TBI), stroke, children, and spinal cord injuries is current focus of community integration. Future research should explore the experiences and feelings of different groups of disabilities regarding community integration and develop more effective interventions for their community integration. Community integration is complex, and future research on community integration for individuals with disabilities needs to be explored more specifically.Keywords: community integration, community reintegration, disability, rehabilitation, quality of life, CiteSpace, bibliometric

Xiping Jiang,1,&ast; Cheng Xu,2,&ast; Chenrui Yuan,1,&ast; Wenliang Gao,3 Wencai Liu,1 Yifei Wang,1 Haiming Wang,1 Weilin Yu,1 Yaohua He1,4 1Department of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, People’s Republic of China; 2Department of Anesthesiology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, People’s Republic of China; 3Department of Orthopedics, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, Fujian, 364000, People’s Republic of China; 4Department of Orthopedic Surgery, Jinshan District Central Hospital Affiliated to Shanghai University of Medicine & Health Sciences, Jinshan Branch of Shanghai Sixth People’s Hospital, Shanghai, 201500, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weilin Yu; Yaohua He, Department of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, People’s Republic of China, Tel +86 021 64369181, Email yuweilin2008@163.com; heyaohua@sjtu.edu.cnPurpose: Arthroscopic rotator cuff repair (ARCR) commonly results in significant postoperative pain. Adjuncts like dexamethasone (DEX) and tranexamic acid (TXA) are used to enhance postoperative recovery. This study aimed to determine whether the combined application of TXA and DEX could improve postoperative recovery during the first 24 hours in ARCR patients. Our goal is to relieve the acute postoperative pain and promote fast recovery and rapid discharge for ARCR patients.Patients and Methods: Ninety-six patients who underwent ARCR from December 2023 to March 2024 were enrolled in this double-blinded, randomized control trial (Registration number, ChiCTR2300078507). Patients were randomized to intravenously receive 200mL of normal saline (control group), 200mL of 1g TXA in saline (TXA group), or 200 mL of 1g TXA and 5mg DEX in saline (TXA+DEX group) within 2 hours postoperatively. The primary outcome was the Quality of Recovery-15 (QoR-15) score at 24 hours post-surgery. Secondary outcomes included mean visual analog scale (VAS) scores every four hours within 24 hours, postoperative blood test results the day after surgery, and American Shoulder and Elbow Surgeons (ASES) score at 3 months postoperatively.Results: No significant differences in QoR-15 scores at 24 hours were observed among the groups [control, 127.0 (112.8, 138.0); TXA, 125.0 (116.5, 136.8); TXA+DEX, 132.0 (120.3, 140.8), p = 0.176]. VAS scores at 5– 8 (placebo vs TXA+DEX, p = 0.014; TXA vs TXA+DEX, p = 0.002), 9– 12 (placebo vs TXA+DEX, p = 0.008; TXA vs TXA+DEX, p < 0.001), and 13– 16 (placebo vs TXA+DEX, p = 0.035; TXA vs TXA+DEX, p = 0.013) hours postoperatively showed a significant decrease for the TXA+DEX group compared with the control or TXA group. There were no significant differences in postoperative blood test results and ASES score at 3 months postoperatively.Conclusion: Postoperative application of TXA alone could not facilitate postoperative recovery during the first 24 hours in ARCR patients. Although the combination of TXA and DEX presented better levels of postoperative pain between 5 and 16 hours than the control and TXA alone, it did not significantly improve postoperative recovery quality. Further large-scale and multi-center investigation is required to determine if the combined application of TXA and DEX or TXA alone is beneficial for postoperative recovery in ARCR patients.Keywords: postoperative pain, arthroscopy, rotator cuff tear, QoR-15, TXA, DEX

Huihui Zhang,1,&ast; Xiaojing Zhang,2,&ast; Yafeng Zheng,2,&ast; Xiao Gu,1 Zhongming Fu,1 Wei Gai,2 Huaying Wang1 1Department of Respiratory and Critical Care Medicine, The Affiliated People’s Hospital of Ningbo University, Yinzhou People’s Hospital, Ningbo, Zhejiang, 315040, People’s Republic of China; 2WillingMed Technology (Beijing) Co., Ltd, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Gai, WillingMed Technology (Beijing) Co., Ltd, No. 156 Jinghai 4th Road, Beijing Economic and Technological Development Zone, Beijing, 101103, People’s Republic of China, Email weigai@willingmed.com Huaying Wang, The Affiliated People’s Hospital of Ningbo University, Yinzhou People’s Hospital, No. 251, Baizhang East Road, Ningbo, 315040, People’s Republic of China, Email yingmeire@163.comPurpose: This study aimed to investigate the impact of herpesvirus detection by metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) on lower respiratory tract infections (LRTIs) patients’ lung microbiome composition and prognosis.Patients and methods: We initially enrolled 234 hospitalized patients with LRTIs who underwent BALF mNGS between February 2022 and May 2023. The study analyzed the clinical manifestations and the pulmonary microbial composition between herpesvirus detection (HD) and non-herpesvirus detection (non-HD) group.Results: After exclusions, a total of 201 patients were included, out of which 73 patients had herpesvirus detections (HD). The most frequently detected herpesviruses were Human herpesvirus 7 (HHV-7) (19.4%), Epstein-Barr virus (EBV) (12.4%), and cytomegalovirus (CMV) (10.4%). The HD group had a higher proportion of male patients (78.08% vs 55.04%, P = 0.001) and a greater incidence of hemoptysis and multilobar infiltrates compared non-HD group. Additionally, the HD group tended to have longer hospital stays compared to non-HD group, especially in immunosuppressed patients. Furthermore, in immunocompetent patients, there were significant differences in α diversity and β diversity between the HD group and non-HD group, but such differences were not observed in immunosuppressed patients.Conclusion: The presence of herpesvirus in patients with non-critical LRTI is associated with longer hospital stays and alterations in the lung’s microbial composition. Additionally, the impacts of herpesvirus presence are influenced by the immune status of the patients.Keywords: lower respiratory tract infections, herpesvirus detection, bronchoalveolar lavage fluid, microbial composition, mNGS

Juan Tan,1,&ast; Lin Wang,1,&ast; Hong Li,2 Honggang Wang,3 Xiaozhong Yang3 1Department of General Practice, The Affiliated Huai ‘an No. 1 People’s Hospital of Nanjing Medical University, Huai’an, Jiangsu, People’s Republic of China; 2Department of Health Management Center, The Affiliated Huai ‘an No. 1 People’s Hospital of Nanjing Medical University, Huai’an, Jiangsu, People’s Republic of China; 3Department of Gastroenterology, The Affiliated Huai ‘an No. 1 People’s Hospital of Nanjing Medical University, Huai’an, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Honggang Wang; Xiaozhong Yang, Email hayy_wanghg@163.com; hayy_yxzh@163.comPurpose: To investigate the relationship between serum uric acid (SUA) levels and femoral neck bone mineral density (BMD) in patients with metabolic dysfunction-associated fatty liver disease (MAFLD).Patients and Methods: This cross-sectional study included 597 adult inpatients with type 2 diabetes mellitus and ultrasonography-confirmed fatty liver disease. Participants were stratified into tertiles based on femoral neck BMD. Gender-stratified linear regression analyses were performed to assess the relationship between SUA and femoral neck BMD. Nonlinear associations were explored using generalized additive models and two-piece linear regression.Results: No significant linear association was observed between SUA and femoral neck BMD in either gender (all P > 0.05). However, after adjusting for confounders, a nonlinear relationship was identified in male patients, with a threshold at 388 μmol/L. The effect sizes for SUA levels below and above this threshold were 0.001 (95% CI: 0.000 to 0.002, P = 0.008) and − 0.000 (95% CI: − 0.002 to 0.000, P = 0.117), respectively. No nonlinear relationship was observed in female patients.Conclusion: In male MAFLD patients, SUA levels exhibit a nonlinear relationship with femoral neck BMD, with a positive association observed between 300 μmol/L and 388 μmol/L. This relationship was not observed in female patients, suggesting gender-specific effects of SUA on bone health in MAFLD.Keywords: metabolic dysfunction-associated fatty liver disease, type 2 diabetes, serum uric acid, bone mineral density

Zhiyuan Zhang,1– 3,&ast; Heyan Wang,4,&ast; Ruiyu Wang,5 Zeyu She,6 Xingyue Liang,6 Huiyi Liu,7 Xuemeng Kou,1 Shipeng Wang1– 3 1Department of Cardiology, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China; 2Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China; 3State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China; 4Department of Cardiology, Central Hospital of Dalian University of Technology, Dalian, Liaoning Province, People’s Republic of China; 5Department of Cardiology, the First Affiliated Hospital of Medical School, Xi’an Jiaotong University, Xi’an, Shaanxi Province, People’s Republic of China; 6School of Basic Medicine, Harbin Medical university, Harbin, Heilongjiang Province, People’s Republic of China; 7Department of Cardiology, the First Affiliated Hospital of Peking University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shipeng Wang, Department of Cardiology, 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, 150086, People’s Republic of China, Tel +86 13654504286, Fax +86 86296225, Email guoyunqaz@126.comObjective: An association between white blood cell count (WBC-C) before percutaneous coronary intervention (PCI) and prognosis has been established in patients undergoing PCI. However, the effect of WBC-C after PCI on the long-term prognosis of patients with unstable angina pectoris (UA) is unclear.Methods: A retrospective cohort study was conducted in 1811 consecutive patients with UA. The changes of WBC and subgroup counts before and in the early postoperative stages after PCI were observed by paired Wilcoxon signed-rank test. The Kaplan–Meier method and COX proportional regression model were used to evaluate the association between the incidence of 5-year endpoint events and post-PCI leukocytosis.Results: Leukocytosis and neutrocytosis within 24 hours after PCI were observed in majority of patients with UA, while lymphocyte count significantly decreased after PCI in those patients. There were no significant differences in 5-year all-cause mortality and major adverse cardiovascular and cerebrovascular events (MACCE) between patients in the post-PCI leukocytosis and the control group. However, the 5-year incidence of major adverse cardiovascular events (MACE) was significantly increased in the post-PCI leukocytosis group (p = 0.017, Log rank test). Leukocytosis after PCI was independently associated with the occurrence of MACE (hazard ratio: 1.36; 95% confidence interval: 1.06– 1.75; p = 0.015).Conclusion: Peripheral WBC and neutrophil counts within 24 hours after PCI significantly increased in response to PCI in patients with UA, while lymphocyte count significantly decreased after PCI in those patients. The post-PCI leukocytosis offered predictive value for an increased risk of MACE for up to 5 years in patients with UA.Keywords: white blood cell count, percutaneous coronary intervention, unstable angina pectoris, leukocytosis, major adverse cardiovascular events

Ziyang Wang,1 Wen Xu,2 Dan Liu,3 Xiuqi Li,1 Shupeng Liu,1 Xiaofei Wu,1 Hongyun Wang1 1Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2CSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd, Shijiazhuang, People’s Republic of China; 3College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of ChinaCorrespondence: Hongyun Wang, Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China, Tel +8610-69154637, Email wanghy@pumch.cnAbstract: Food-Drug Interaction (FDI) refers to the phenomenon where food affects the pharmacokinetic or pharmacodynamic characteristics of a drug, significantly altering the drug’s absorption rate or absorption extent. These Interactions are considered as a primary determinant in influencing the bioavailability of orally administered drugs within the gastrointestinal tract. The impact of food on drug absorption is complex and multifaceted, potentially involving alterations in gastrointestinal physiology, increases in splanchnic blood flow rates, and shifts in the gut microbiota’s composition. Up to now, extensive research has focused on the interactions between food composition (such as proteins, fats, and vitamins) and drug absorption. In contrast, the impact of food physical properties (such as viscosity, volume, and pH) has received less attention in drug development. This article reviewed the impact of food properties on oral drug absorption based on a comprehensive literature search, focusing on the influence of food volume and food viscosity. From the perspective of pharmacokinetics, we examined interaction trends between food properties and drugs across different classification based on the Biopharmaceutics Classification System (BCS). In addition, we introduced the practical application of physiologically based pharmacokinetic (PBPK) modeling in predicting oral drug absorption under the influence of food Properties.Plain language summary: In the development of new drugs, understanding how food affects drug absorption is crucial. Although scientists have deeply studied the role of food components–such as proteins, fats, and carbohydrates–in drug absorption, the impact of food’s physical properties, like viscosity, volume, and temperature, on drug safety is often overlooked. Dietary differences across cultures, such as the sticky porridge and steamed buns in China versus bread and milk in the West, suggest that food properties may differentially affect drug absorption. We emphasize the key role of food properties in drug absorption and review how these properties influence gastrointestinal function and drug bioavailability. Additionally, we discuss the specific interactions between different types of drugs and food properties, emphasizing the importance of incorporating food properties into the construction of drug absorption models.Keywords: food properties, food-drug interactions, PBPK models, biopharmaceutics classification system

Hailin Liu,1,&ast; Chao Huang,1,&ast; Yanjiao Du,1 Jiacheng Liu,1,2 Xiangyang Ren,1 Huilin Wang,1 Jingna Ye,1 Haitao Zhou,1 Zhihui Duan1 1Department of Neurology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang Cerebrovascular Disease (Stroke) Clinical Medical Research Center, Regional Medical Center for Neurological Diseases of Henan Province, Luoyang, People’s Republic of China; 2Xinxiang Medical College, Xinxiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhihui Duan, Department of Neurology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang Cerebrovascular Disease (Stroke) Clinical Medical Research Center, Regional Medical Center for Neurological Diseases of Henan Province, Xigong District, Luoyang, Henan, 471000, People’s Republic of China, Tel/Fax +0086-0379-63892044, Email 54487843@qq.comIntroduction: Transthyretin protein-related familial amyloidosis polyneuropathy (TTR-FAP) is an autosomal dominant genetic disease caused by mutations in the TTR gene. The disease is characterized primarily by peripheral and autonomic nerve damage. Disease progression is associated with frequent involvement of the heart, lungs, kidneys, eyes, and other organs. The most common TTR mutation is c.148G>A (p.Val50Met), although the FAP resulting from the mutation rarely involves the spinal cord.Patient Concerns: A 68-year-old man was diagnosed with the TTR c.148G>A (p.Val50Met) mutation by ultrasound, pathological, and genetic analyses. He presented with a late-onset, complicated spinal cord injury. The diagnostic process was tortuous, and despite the administration of regular treatment (conventional drugs, cardiac pacemaker, and the specific drug clofenadifen), the patient died.Interventions: To confirm TTR-FAP, ultrasound, MRI, pathological, and genetic tests were performed.Outcomes: The patient ultimately died of heart failure 7.5 years after the initial onset of symptoms.Conclusion: The patient presented with unusual symptoms of spinal cord injury, and despite a long and arduous diagnostic process and administration of standard treatment for over seven years, the outcome was poor. It is thus recommended that clinicians pay attention to the identification of rare diseases with timely imaging, pathological, and genetic testing, to avoid poor outcomes.Keywords: transthyretin familial amyloid polyneuropathy, myelopathy, case

Huaichong Wang,1 Liujie Gao,2 Xinjun Cai,1 Jinmeng Li,1 Yuying Lang,1 Ren Zheng,1 Shengya Yang3 1Department of Pharmacy, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang Province, People’s Republic of China; 2Department of Oncology, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang Province, People’s Republic of China; 3Tuberculosis Diagnosis and Treatment Center, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Shengya Yang, Tuberculosis Diagnosis and Treatment Center, Hangzhou Red Cross Hospital, East Huancheng Road No. 208, Hangzhou, Zhejiang Province, People’s Republic of China, Email 15967116949@163.comBackground: Immune checkpoint inhibitors (ICIs) have emerged as the first-line treatment for driver-negative advanced non-small cell lung cancer (NSCLC). However, there is uncertainty regarding the availability and timing of ICI initiation in patients with NSCLC combined with pulmonary tuberculosis (TB). Additionally, the implementation of dual therapy for anti-TB and anti-tumor treatment poses significant challenges in terms of avoiding drug–drug interactions and reducing adverse reactions during clinical diagnosis and treatment.Case Description: A 65-year-old male patient was admitted to our designated TB hospital following an out-of-hospital TB diagnosis. Relevant examinations were completed after admission, and chest computed tomography revealed that the patient had lung squamous cell carcinoma with multiple metastases in lymph nodes and liver. A multidisciplinary team (MDT) consisting of oncologists, pulmonologists, and clinical pharmacists followed evidence-based practices to determine treatment options. They evaluated the benefits and risks of ICIs and performed therapeutic drug monitoring for the dual treatment of anti-TB and anti-tumor drugs. After 18 days of anti-TB treatment, the patient successfully received ICIs combined with chemotherapy for NSCLC while continuing anti-TB therapy. The patient’s anti-TB treatment plan was adjusted due to gastrointestinal reactions, bone marrow suppression, and liver function injury. Ultimately, both NSCLC and pulmonary TB were effectively controlled.Conclusion: For patients with NSCLC complicated by pulmonary TB, after 2– 4 weeks of effective anti-TB treatment, anti-tumor therapies, including ICIs, can be simultaneously implemented with the anti-TB treatment. Therapeutic drug monitoring is beneficial for avoiding serious adverse effects and ensuring the timely treatment of both diseases.Keywords: anti-tumor therapy, immunotherapy, Mycobacterium tuberculosis, adverse effects

Lingzhao Zhang,1,2 Jiangshan Pi,1,2 Jinsong Wang,3 Jingsi Chen,1 Yunxuan Zhang,1,2 Jie Li,4 Lingling Wang,1,2 Yue Li,1,2 Anwei Chen,1 Xiaoyan Luo,1,5,&ast; Hua Wang1,2,5,&ast; 1Department of Dermatology, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Key Laboratory of Child Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Gastroenterology, Chongqing Dongnan Hospital, Chongqing, People’s Republic of China; 4Department of Pediatrics, Chongqing Jiangjin District Maternal and Child Health Hospital, Chongqing, People’s Republic of China; 5Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hua Wang; Xiaoyan Luo, Department of Dermatology, Children’s Hospital of Chongqing Medical University, No. 136 Zhongshan Second Road, Yuzhong District, Chongqing, 400015, People’s Republic of China, Tel +8615123380348, Email huawang@hospital.cqmu.edu.cn; xyluo@hospital.cqmu.edu.cnBackground: Dupilumab is a safe and effective treatment for moderate to severe atopic dermatitis (AD), but real-world data in pediatric patients in China are limited. Currently, there is no exploration of changes in blood cell counts derived indexes in pediatric patients, especially under 6 years old.Purpose: To investigate the changes in blood cell counts derived indexes before and after dupilumab treatment in Chinese children with AD, the relationship with clinical scores, and the potential role of these indexes on treatment efficacy.Patients and Methods: We conducted a retrospective study of 109 children with moderate to severe AD treated with dupilumab. Derived inflammatory indexes, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), eosinophil-to-lymphocyte ratio (ELR), eosinophil-to-neutrophil Ratio (ENR), monocyte-to-lymphocyte ratio (MLR), inflammation response index (SIRI), systemic inflammation index (SII), and aggregate inflammation systemic index (AISI) were calculated. The correlation between clinical scores and inflammatory indexes at different treatment time points were analyzed. Logistic regression and ROC curve was employed to explore factors associated with treatment efficacy.Results: Baseline ELR and ENR were positively correlated with the baseline Eczema Area and Severity Index (EASI) and the Scoring Atopic Dermatitis (SCORAD). Additionally, baseline ENR levels showed a positive correlation with the baseline Peak Pruritus Numeric Rating Scale (PP-NRS). At 4 and 16 weeks of treatment, the percentage reduction in ELR was significantly associated with the percentage reduction in EASI and PP-NRS. Logistic regression results indicated that high baseline ELR could predict a poor response to dupilumab treatment.Conclusion: ELR was significantly correlated with disease severity score during the treatment with dupilumab. Baseline ELR could act as a predictor of the efficacy of dupilumab in the treatment of children with atopic dermatitis under 6 years of age.Keywords: atopic dermatitis, dupilumab, eosinophil-to-lymphocyte ratio, blood cell count

Bo Liu, Ling Wei, Lirui Wu, Huiying Wang, Hongli Wang, Qian Yu Department of Gynecology, Hebei Petro China Center Hospital, Langfang, People’s Republic of ChinaCorrespondence: Ling Wei, Email 74037604@qq.comObjective: To analyze the relationship and predictive value of Netrin-1 expression and ultrasonic blood flow parameters with the severity of cervical intraepithelial neoplasia (CIN).Methods: A retrospective analysis was performed on 115 patients diagnosed with CIN and 37 patients with chronic cervicitis, all of whom underwent surgical intervention. The expression levels of Netrin-1 were evaluated through immunohistochemical staining and quantitative fluorescence PCR. Doppler ultrasound was employed to quantify flow index (FI), vascularization index (VI), and vascularization flow index (VFI) using VOCAL software. Statistical analyses, including correlation analysis, logistic regression, and receiver operating characteristic (ROC) curve analysis, were conducted to assess the predictive value of Netrin-1 expression and ultrasound-derived blood flow parameters.Results: FI, VI, and VFI increased with CIN grade, showing significant differences between CIN II, CIN III, and the control group (P < 0.05). Netrin-1 levels were negatively correlated with FI, VI, and VFI (correlation coefficients of − 0.287, − 0.309, and − 0.298; P < 0.05). Logistic regression indicated that Netrin-1 positivity was a protective factor against CIN III, while FI, VI, and VFI were risk factors. The AUC for Netrin-1 was 0.712, with sensitivity and specificity of 76.4% and 79.5% (P < 0.05).Conclusion: Netrin-1 expression is significantly reduced in CIN patients, whereas Doppler ultrasound-derived blood flow parameters—FI, VI, and VFI—are markedly elevated. Both Netrin-1 levels and these ultrasound parameters exhibit a strong correlation with the severity of cervical lesions. Notably, Netrin-1 is negatively correlated with FI, VI, and VFI. Furthermore, Netrin-1 positivity serves as a protective factor against CIN III lesions, while elevated levels of FI, VI, and VFI are associated with increased risk for these lesions. The expression levels of both Netrin-1 and ultrasound parameters provide valuable predictive insights for the early screening, diagnosis, and prevention of cervical cancer.Keywords: Netrin-1, ultrasonic blood flow parameters, cervical intraepithelial neoplasia, severity, predictive value

Yanhai Wang,1 Yupeng Shi,2 Zhongwei Wu,1 Jiangfeng Gao,3 Jing Wang,3 Lei Li,4 Yugang Wan,4 MuGu Lang A,1 Jianwen Zhang,1 Hongbo Wang,3 Yu Hou3,5 1Department of Clinical Laboratory, Hohhot First Hospital, Hohhot, 010030, People’s Republic of China; 2Zhejiang Digena Diagnosis Technology CO., LTD, Zhejiang, 310030, People’s Republic of China; 3Cardiology Department, Hohhot First Hospital, Hohhot, 010030, People’s Republic of China; 4Network Management, Hohhot First Hospital, Hohhot, 010030, People’s Republic of China; 5Cardiology Department, Inner Mongolia People’s Hospital, Hohhot, 010017, People’s Republic of ChinaCorrespondence: Yu Hou, Cardiology Department, Inner Mongolia People’s Hospital, No. 26, Zhaoda Road, Saihan District, Hohhot, Inner Mongolia Autonomous Region, 010017, People’s Republic of China, Tel +86-471-5281258, Email houyucardiac@163.comPurpose: This study aimed to investigate the distribution patterns of PLA2G7 gene variants in Han Chinese patients with coronary heart disease (CHD), and their relationships with serum lipoprotein-associated phospholipase A2 (Lp-PLA2) levels and lipid profiles.Methods: A total of 93 han Chinese CHD patients were recruited. Serum Lp-PLA2 levels were determined using enzyme-linked immunosorbent assay (ELISA), while comprehensive analysis of PLA2G7 gene polymorphisms was conducted through whole-exome sequencing. Concurrently, multiple lipid parameters were measured and analyzed.Results: Among these Han Chinese CHD patients, the PLA2G7 gene rs1051931 (c.1136T>C p.Val379Ala) rare variant was highly prevalent (variant rate: 94.62%) among the study population, and showed negative correlation with serum Lp-PLA2 activity. The rs1765208290 (c.233G>A p.Gly78Asp) rare variant showed positive correlation with TG, ApoA, ApoB, HDL, LDL and TCHO levels in the serum. Strong linkage disequilibrium was observed between the rs1805018 (c.593T>C p.Ile198Thr) and rs76863441 (c.835G>T p.Val279Phe), both of which were related to lower Lp-PLA2 activity.Conclusion: In these Han Chinese CHD patients, the rs1051931 (c.1136T>C p.Val379Ala) rare variant in the PLA2G7 gene is closely linked to decreased Lp-PLA2 activity, whereas the rs1765208290 (c.233G>A p.Gly78Asp) rare variant influences lipid homeostasis. The strong LD between rs1805018 (c.593T>C p.Ile198Thr) and rs76863441 (c.835G>T p.Val279Phe) loci may act synergistically to reduce Lp-PLA2 activity.Keywords: PLA2G7 gene, coronary artery atherosclerotic heart disease, serum Lp-PLA2, lipid profile

Songdi Wang, Hong Wang, Xuemei Chen, Min Li, Danyang Xu Department of Anesthesiology, Affiliated Hospital of Chifeng University, Chifeng, 024000, People’s Republic of ChinaCorrespondence: Xuemei Chen, Email Chenxuemei.1968@163.comPurpose: Thoracic surgery is among the most painful surgeries, postoperative pain can lead to a poor prognosis. This study aimed to explore the analgesic effect of ultrasound-guided continuous rhomboid intercostal and sub-serratus (RISS) plane block Comparison of thoracoscopic intercostal nerve block (ICNB) on postoperative pain management and recovery in patients who underwent Video-Assisted Thoracic Surgery (VATS) Lobectomy.Methods: This prospective randomized controlled study enrolled patients after VATS Lobectomy who received ultrasound-guided continuous RISS plane block (RISS group) or ICNB (Control group) for postoperative pain. The primary outcome was the visual analogue scale (VAS) score. The secondary outcomes included non-invasive blood pressure (NIBP), heart rate (HR), the time to ambulation after surgery, the timing of drain removal, and the duration of postoperative hospitalization.Results: A total of 98 participants were collected (53.08 ± 13.63; 43 (43.88%) males); each group included 49 patients. The RISS group displayed significantly lower visual analogue scale (VAS) scores during rest and when coughing at postoperative 12, 24, and 48h compared to the Control group (P < 0.001). The total consumption of sufentanil and remifentanil was smaller in the RISS group than in the control group. The NIBP,HR in the RISS group were significantly lower than in the Control group at immediately after skin incision (T1), upon entering the thoracic cavity (T2), 5 min after entering the thoracic cavity (T3) (P < 0.001). The patients in the RISS group were more likely to exhibit a shorter time to the first postoperative ambulation compared to the Control group (8.84 ± 2.87,15.43 ± 4.50, P < 0.001).Conclusion: Continuous RISS may be a safe and effective strategy for postoperative pain management after thoracoscopic surgery.Keywords: postoperative pain, thoracoscopic surgery, rhomboid intercostal and sub-serratus plane block, intercostal nerve block

Qiaolifanayi Nuermaimaiti,1– 6,&ast; Mulalibieke Heizhati,1– 6,&ast; Qin Luo,1– 6 Nanfang Li,1– 6 Lin Gan,1– 6 Ling Yao,1– 6 Wenbo Yang,1– 6 Mei Li,1– 6 Xiufang Li,1– 6 Xiayire Aierken,1– 6 Jing Hong,1– 6 Hui Wang,1– 6 Miaomiao Liu,1– 6 Adalaiti Maitituersun,1– 6 Aketilieke Nusufujiang,1– 6 Li Cai1– 6 1Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, 830001, People’s Republic of China; 2Xinjiang Hypertension Institute, Urumqi, Xinjiang, 830001, People’s Republic of China; 3NHC Key Laboratory of Hypertension Clinical Research, Urumqi, Xinjiang, 830001, People’s Republic of China; 4Key Laboratory of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, 830001, People’s Republic of China; 5Hypertension Research Laboratory, Urumqi, Xinjiang, 830001, People’s Republic of China; 6Xinjiang Clinical Medical Research Center for Hypertension (Cardio-Cerebrovascular) Diseases, Urumqi, Xinjiang, 830001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qin Luo; Nanfang Li, Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, No. 91 Tianchi Road, Urumqi, Xinjiang, 830001, People’s Republic of China, Tel/Fax +86 0991 8564816, Email luoqin2@sina.cn; lnanfang2016@sina.comBackground: Multimorbidity, defined as the coexistence of two or more chronic diseases, is highly prevalent among the elderly population and is associated with adverse outcomes. However, little is known about its relationship with sleep issues, particularly in this demographic. Therefore, this study aimed to investigate its association with sleep quality and duration among the elderly.Methods: This cross-sectional study was conducted in Emin County, Xinjiang, China, which included a population aged 60 years and above. We employed the Pittsburgh Sleep Quality Index (PSQI) score to assess sleep quality and duration. Multimorbidity was determined through self-reports, physical examination, blood tests, and imaging. Logistic regression analyses were used to explore the association between multimorbidity and sleep patterns, adjusting for confounders.Results: A total of 8205 elderly participants were included, of whom 66.8% suffered from multimorbidity. Participants with multimorbidity exhibited higher total PSQI scores [6 (3,9)], and a higher percentage of poor sleep quality (50.6%), compared to those without multimorbidity. Multimorbidity was significantly associated with the presence of poor sleep quality (OR = 1.27, 95% CI: 1.14– 1.41, P < 0.001) before and after adjusting for confounders. The risk of having poor sleep quality significantly increased as the number of multimorbidities increased. The OR (95% CI) values were 1.16 (1.02,1.32) for two diseases, 1.54 (1.26,1.90) for ≥ 5 diseases. In the adjusted model for total participants, having four diseases (OR = 1.26, 95% CI: 1.05– 1.51, p = 0.013) and five or more diseases (OR = 1.29, 95% CI: 1.03– 1.61, p = 0.029) were associated with shorter sleep duration. Furthermore, those with five or more diseases associated with longer sleep duration (OR = 1.40, 95% CI: 1.00– 1.95, p = 0.057).Conclusion: There is a significant association between multimorbidity and poor sleep quality in older community dwellers, which may provide clues for disease prevention.Keywords: multimorbidity, sleep quality, sleep duration, elderly

Zhen Ci,1,2,&ast; Hanchi Wang,1,2,&ast; Jiaxin Luo,1,2 Chuqiao Wei,1,2 Jingxia Chen,1,2 Dongyang Wang,2,3 Yanmin Zhou1,2 1Department of Oral Implantology, Hospital of Stomatology, Jilin University, Changchun, 130021, People’s Republic of China; 2Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, Changchun, 130021, People’s Republic of China; 3Department of Oral Biology, Hospital of Stomatology, Jilin University, Changchun, 130021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanmin Zhou, Department of Oral Implantology, Hospital of Stomatology, Jilin University, Changchun, 130021, People’s Republic of China, Email zhouym@jlu.edu.cn Dongyang Wang, Department of Oral Biology, Hospital of Stomatology, Jilin University, Changchun, 130021, People’s Republic of China, Email dyang314@jlu.edu.cnAbstract: Chronic inflammation is a common characteristic of all kinds of diseases, including autoimmune diseases, metabolic diseases, and tumors. It is distinguished by the presence of low concentrations of inflammatory factors stimulating the body for an extended period, resulting in a persistent state of infection. This condition is manifested by the aggregation and infiltration of mononuclear cells, lymphocytes, and other immune cells, leading to tissue hyperplasia and lesions. Although various anti-inflammatory medications, including glucocorticoids and non-steroidal anti-inflammatory drugs (NSAIDs), have shown strong therapeutic effects, they lack specificity and targeting ability, and require high dosages, which can lead to severe adverse reactions. Nanoparticle drug delivery mechanisms possess the capacity to minimize the effect on healthy cells or tissues due to their targeting capabilities and sustained drug release properties. However, most nanosystems can only target the inflammatory sites rather than specific types of immune cells, leaving room for further improvement in the therapeutic effects of nanomaterials. This article reviews the current research progress on the role of diverse immune cells in inflammation, focusing on the functions of neutrophils and macrophages during inflammation. It provides an overview of the domestic and international applications of nanomaterials in targeted therapy for inflammation, aiming to establish a conceptual foundation for the utilization of nanomaterials targeting immune cells in the treatment of chronic inflammation and offer new perspectives for the avoidance and management of inflammation. Keywords: nanomaterials, periodontitis, chronic inflammation, target therapy, neutrophil, macrophage

Xi Liu,1,2 Yang Zhao,3,4 Tianya Da,1,2 Shilong Zhang,1,2 Haipeng Wang,1,2 Hui Li1,2 1Center for Health Management and Policy Research, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 2NHC Key Laboratory of Health Economics and Policy Research, Shandong University, Jinan, People’s Republic of China; 3The George Institute for Global Health, University of New South Wales, Sydney, Australia; 4The George Institute for Global Health, Beijing, People’s Republic of ChinaCorrespondence: Haipeng Wang; Hui Li, Email wanghaipeng@sdu.edu.cn; huili@sdu.edu.cnPurpose: Multimorbidity and polypharmacy have emerged as significant global issues, heightening the risks of potentially inappropriate medications (PIMs). This necessitates medication optimization through deprescribing. Understanding patients’ decision-making preferences regarding medication cessation is crucial for mitigating medication-related risks. This study aims to capture the attitude of patients with multimorbidity towards deprescribing in rural China and to ascertain whether individual characteristics were linked to these attitudes.Patient and Methods: A cross-sectional study employing the validated Patients’ Attitudes Towards Deprescribing (PATD) questionnaire was performed in rural regions of Eastern China. The PATD Questionnaire was utilized to investigate patients’ attitudes towards the concurrent use of multiple medications, with response elicited on a 5-point Likert scale. Utilizing multistage random sampling, a total of 560 participants with multimorbidity were randomly selected from two counties in Shandong Province. Descriptive statistics were reported on participant characteristics. Binary logistic regression analysis was conducted to identify the factors that influenced participants’ willingness to discontinue or reduce their medication.Results: The median age of patients was 69.5 years (SD=8.2 years), and 314 were female. Nearly one in four patients experienced polypharmacy, while 42.2% had two chronic diseases. More than half of the participants (55.2%) reported that they would be willing to stop one or more medications if their physicians agreed, and 52.9% of participants agreed to reduce the medications taken. Participants with two chronic conditions (OR=3.038, 95% CI=1.342– 6.881), taking less than 10 tablets (OR=2.994, 95% CI=1.113– 8.054), having their own source of healthcare expenditure (OR=0.639, 95% CI=0.432– 0.945), and hospitalization in the prior year (OR=0.636, 95% CI=0.429– 0.944) were significantly associated with patients’ attitudes toward deprescribing.Conclusion: Over half of patients with multimorbidity expressed a willingness to have one or more of their medicines deprescribed. Physicians can be trained in the integrated care of chronic diseases and encouraged to engage in discussions about deprescribing with patients having multimorbidity and polypharmacy during their routine practice.Keywords: deprescribing, patient perspective, polypharmacy, potentially inappropriate medication

Yajing Liu,1 Chunming Li,2 Xiaoya Yang,1 Shufen Guo,1 Zhaobo Cui,1 Hongshan Kang,1 Zhen Ma,1 Huiqing Wang1 1Intensive Care Unit, Hengshui People’s Hospital (Harrison International Peace Hospital), Hengshui, 053000, People’s Republic of China; 2Department of Pain, Hengshui Second People’s Hospital, Hengshui, 053000, People’s Republic of ChinaCorrespondence: Yajing Liu; Hongshan Kang, Intensive Care Unit, Hengshui People’s Hospital (Harrison International Peace Hospital), 180 Renmin East Road, Taocheng District, Hengshui, Hebei, 053000, People’s Republic of China, Tel +8618732891639, Email liuyajingbs@163.com; kanghongshan@163.comObjective: We assessed the predictive value of blood neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18) in predicting the onset of acute kidney injury (AKI) in sepsis patients in the intensive care unit (ICU).Methods: In this retrospective analysis, we examined the medical records of sepsis patients admitted to the ICU. After ICU admission, blood samples were taken at 0 h, 6 h, 12 h, 24 h, and 48 h. Using an enzyme-linked immunosorbent assay, the concentrations of serum creatinine, NGAL, and IL-18 were determined.Results: This study comprised a total of 197 participants, 104 of whom had AKI and 93 of whom did not. Blood concentrations of NGAL and IL-18 increased prior to serum creatinine levels. Between 6– 48 hours after ICU administration, NGAL and IL-18 levels in the AKI group were considerably higher than those in the non-AKI group, and creatinine levels between the two groups were significantly different after 48 hours. Based on receiver operating characteristic (ROC) curve analysis, the area under the curve of NGAL and IL-18 for predicting AKI was 0.781 and 0.883, respectively.Conclusion: Blood NGAL and IL-18 are potential biomarkers for the early prediction of AKI in sepsis patients in the ICU.Keywords: acute kidney injury, intensive care unit, interleukin-18, neutrophil gelatinase-associated lipocalin sepsis

Xingchi Hu,1,2 Hongwei Wang,1,2 Haitao Sun,3 Jingxin Zhang,3 ZhenXiong Ye,4 Zhenhua Huang3 1Department of General Surgery, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School, Yancheng, Jiangsu, 224000, People’s Republic of China; 2Department of General Surgery, The First People’s Hospital of Yancheng, Yancheng, Jiangsu, 224000, People’s Republic of China; 3Department of General Surgery, The Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212002, People’s Republic of China; 4Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, 200090, People’s Republic of ChinaCorrespondence: Xingchi Hu, Department of General Surgery, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School, Yancheng, Jiangsu, 224000, People’s Republic of China, Email xingchihu@163.com Zhenhua Huang Department of General Surgery, The Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212002, People’s Republic of China, Email zhenhuahuangzj@163.comBackground: Transient receptor potential canonical 6 (TRPC6), a key member of the TRPC family, is involved in diverse physiological and pathological processes. Although previous studies have implicated TRPC6 in the progression of stomach adenocarcinoma (STAD), its precise functions and mechanisms remain unclear. Understanding TRPC6’s role in STAD may provide insights into its prognostic and therapeutic potential.Methods: Using transcriptional and clinical data from The Cancer Genome Atlas (TCGA) database, we assessed the expression and prognostic value of TRPC6 in STAD through Kaplan-Meier survival curve analysis and correlation studies. Immune-related parameters, including immune cell infiltration and immune checkpoint gene expression, were also evaluated. Additionally, drug response analyses explored TRPC6’s association with therapeutic agents. In vitro experiments were conducted to investigate TRPC6’s role in STAD cell proliferation, migration, and invasion, focusing on its regulation of the PI3K-Akt signaling pathway.Results: TRPC6 was significantly overexpressed in STAD tissues compared to normal tissues, with high TRPC6 expression associated with poor overall survival. TRPC6 expression correlated strongly with immune cell infiltration, immune checkpoint genes, and sensitivity to therapies such as Lapatinib, anti-CTLA4, and anti-PD1 treatments. Functional assays confirmed that TRPC6 promotes STAD cell proliferation, migration, and invasion by activating the PI3K-Akt signaling pathway.Conclusion: This study highlights the prognostic significance of TRPC6 in STAD and its potential as a therapeutic target. TRPC6’s involvement in immune regulation and cancer cell progression underscores its dual role in STAD pathogenesis and treatment, offering new avenues for targeted therapy development.Keywords: TRPC6, stomach adenocarcinoma, immunotherapy, biomarkers

Qianyuan Li,1 Li Li,1 Xianyi He,2 Huilin Wang3 1School of Physical Education, Hunan University of Science and Technology, Xiangtan, 411201, People’s Republic of China; 2College of Physical Education, Hunan Normal University, Changsha, 410017, People’s Republic of China; 3School of Business, Hunan University of Science and Technology, Xiangtan, 411201, People’s Republic of ChinaCorrespondence: Huilin Wang, School of Business, Hunan University of Science and Technology, Xiangtan, 411201, People’s Republic of China, Email 1150141@hnust.edu.cnBackground: The lack of physical activity poses a major challenge to adolescents’ healthy physical and mental development. Despite growing attention, research on how the school physical activity climate affects Chinese adolescents’ participation in moderate-to-vigorous physical activity (MVPA) remains scarce. This study explores this relationship through the lens of ecological systems theory, focusing on the mediating roles of physical education satisfaction and perceived barriers. It also proposes strategies to promote MVPA among Chinese adolescents.Methods: This cross-sectional study employed convenience and snowball sampling methods to examine the impact of the school physical activity climate on adolescent participation in MVPA. It also explored the mediating roles of physical education satisfaction and perceived barriers. Four variables in the study were measured using established scales: Physical Activity Climate, Perceived Barriers to Physical Activity, Physical Education Satisfaction, and Physical Activity Assessment. The data were analyzed using AMOS v.23 to construct and test a structural equation model.Results: A total of 612 adolescents aged 12 to 18 from six key middle schools in central China participated in the study. The findings showed that a positive school physical activity climate significantly promotes MVPA participation. Physical education satisfaction positively correlated with MVPA (β = 0.322, p < 0.001), while perceived barriers negatively correlated with both physical education satisfaction (β = − 0.449, p < 0.001) and MVPA (β = − 0.366, p < 0.001). Satisfaction with physical education and perceived barriers mediated the relationship between the school climate and MVPA, emphasizing their importance in shaping adolescent physical activity behavior. Confirmatory factor analysis (CFA) results (χ²/df = 1.928, GFI = 0.969, AGFI = 0.956, NFI = 0.962, CFI = 0.981, RMSEA = 0.037) confirmed the model’s robustness and good fit.Conclusion: Adolescents in a positive physical activity climate are more likely to overlook perceived barriers, enjoy higher satisfaction in PE classes, and actively engage in MVPA. Schools and educators are advised to foster a supportive physical activity environment to boost adolescent MVPA participation, considering the unique context of China’s educational system.Keywords: adolescents, physical activity climate, perceived barriers, physical education satisfaction, moderate-to-vigorous physical activity

Hujie Wang,1 Martina Buljac-Samardzic,1 Jeroen David Hendrikus van Wijngaarden,1 Joris van de Klundert1,2 1Erasmus School of Health Policy & Management, Erasmus University Rotterdam, Rotterdam, the Netherlands; 2School of Business, Universidad Adolfo Ibáñez, Santiago, ChileCorrespondence: Hujie Wang, Erasmus School of Health Policy & Management, Erasmus University Rotterdam, Burgemeester Oudlaan 50, Rotterdam, 3062PA, the Netherlands, Email wang@eshpm.eur.nlIntroduction: Although the importance of leader–member relationships in teamwork is acknowledged in literature, a deeper understanding of this relationship is lacking, especially in rural areas. The impact of leader–member relationships on team outcomes is especially important in rural Chinese hospitals as improving teamwork forms a national health reform priority in these hospitals. This study investigates how leader-member relationships (ie leader-member perceived similarity and power distance orientation) influence team outcomes (ie perceived quality of care and job satisfaction) via speaking up and silence.Methods: An online questionnaire was completed by 1017 team members (ie doctors, nurses and other healthcare professionals) of 300 teams in four rural Chinese hospitals in October 2022. The questionnaire measured leader-member perceived similarity, power distance orientation, speaking up, silence, perceived quality of care, job satisfaction and control variables. Multilevel mediation analysis was conducted to test the hypotheses.Results: Leader–member perceived similarity and power distance orientation are positively related to speaking up (β=0.61, p< 0.01; β=0.17, p< 0.01 respectively) and to silence (β=0.41, p< 0.01; β=0.63, p< 0.01 respectively). Speaking up is positively related to the perceived quality of care (β=0.24, p< 0.01; β=0.46, p< 0.01) and job satisfaction (β=0.30, p< 0.01; β=0.54, p< 0.01), while the impact of silence is not significant. Finally, speaking up mediates the associations of both leader-member perceived similarity and power distance orientation with perceived quality of care (β=0.15, p< 0.01; β=0.08, p< 0.01 respectively) and job satisfaction (β=0.30, p< 0.01; β=0.54, p< 0.01 respectively).Conclusion: Speaking up, rather than silence, contributes to team functioning by mediating the impact of leader–member relationships to team outcomes. Hospital management may therefore seek to stimulate speaking up by focussing on leader-member relationships: increasing leader-member similarity and promoting members’ power distance orientation. However, any unintended effect of increased silence through these leader–member relationships is an important area of future research, which can adopt multidimensional models of speaking up and silence.Keywords: leader-member relationship, leader-member perceived similarity, power distance orientation, speaking up, silence

Junli Feng,1,&ast; Ningsi Xu,1,&ast; Linhua Wang,2 Haixing Wang,3 Yi Zhou,3 Qing Shen4,5 1Collaborative Innovation Center of Seafood Deep Processing, Zhejiang Province Joint Key Laboratory of Aquatic Products Processing, Institute of Seafood, Zhejiang Gongshang University, Hangzhou, 310012, People’s Republic of China; 2Hangzhou Linping Hospital of Traditional Chinese Medicine, Linping, Zhejiang, 311106, People’s Republic of China; 3Key Laboratory of Drug Monitoring and Control of Zhejiang Province, National Narcotics Laboratory Zhejiang Regional Center, Hangzhou, 310053, People’s Republic of China; 4The Joint Innovation Center for Health & Medicine, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou, 324000, People’s Republic of China; 5Laboratory of Food Nutrition and Clinical Research, Zhejiang Gongshang University, Hangzhou, 310012, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Zhou; Qing Shen, Email zhouyi2013@zju.edu.cn; leonqshen@163.com; sq@zjgsu.edu.cnBackground: Opioid-based medications are powerful analgesics commonly prescribed for pain management, but they are also highly addictive. The over-prescription of opioids analgesics has triggered current opioid crisis, which now has expanded to heroin and illicit synthetic opioids like fentanyl and its analogues. The side effects of fentanyl abuse have been well recognized, yet the underlying molecular adaptations across brain regions upon fentanyl exposure remain elusive.Methods: The transmission electron microscopy (TEM) and next-generation RNA-sequencing (RNA-seq) were used to investigate the ultrastructure synaptic alterations and transcriptional profiling changes of reward and sensory brain regions in mice after fentanyl exposure.Results: The naloxone-precipitated acute withdrawal symptoms were observed in mice exposed to fentanyl. Results of TEM showed an increase in the number of synapses, widening of synaptic gaps, and thickening of postsynaptic density in the NAc of the fentanyl addiction mice, accompanied by obvious mitochondrial swelling. RNA-seq identified differentially expressed genes (DEGs) in prefrontal cortex of mice brains after fentanyl exposure, and the expression of some addiction-related genes such as Calm4, Cdh1, Drd1/2/3/4, F2rl2, Gabra6, Ht2cr, Oprk1 and Rxfp3 showed the most striking changes among experimental groups. KEGG enrichment analysis indicated that these DEGs were related to the development of addiction behavior, dopaminergic/GABAergic/serotonergic synapse, synapse assembly/synaptic plasticity/synaptic vesicle cycle, cAMP/MAPK signaling pathway, neuroactive ligand-receptor interactions. These transcriptomic changes may be correlated with the structural and behavioral changes observed in fentanyl-exposed mice.Discussion: The findings of this study contribute to a better understanding of the molecular mechanism of addiction behavior, which is essential for the development of optimized therapy strategies for addicts.Keywords: fentanyl, addiction, synaptic plasticity, gene expression, transcriptional profiles

Mengze Li,1,&ast; Qiannan Jia,1,&ast; Tifei Yuan,2 Lin Zhang,3 Huizhong Wang,1 Jamie Ward,4 Yinchuan Jin,1 Qun Yang1 1Department of Military Medical Psychology, Air Force Medical University, Chinese People’s Liberation Army (PLA), Xi’an, People’s Republic of China; 2Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 3Outpatient Department, 986th Hospital Affiliated to Air Force Medical University, Xi’an, People’s Republic of China; 4School of Psychology, University of Sussex, Brighton, UK&ast;These authors contributed equally to this workCorrespondence: Qun Yang; Yinchuan Jin, Email yangqun1125@hotmail.com; jyc_fmmu@163.comBackground: Public health emergencies pose threats to mental health, and cognitive emotional regulation can be a crucial coping strategy. This study explored the relationship between cognitive emotion regulation strategies and mental health among university students during the COVID-19 pandemic using network analysis.Methods: 1100 university students completed questionnaires assessing depression, anxiety, somatization, and cognitive emotion regulation strategies. Network analysis was conducted to identify network structures and bridge symptoms.Results: (1) In the depression network, the strongest edge is D1 (Little interest)-D2 (Feeling down), while D2 emerged as the node with the highest centrality. C1 (Self-blame), C8 (Catastrophizing), D6 (Feeling bad), and D9 (Suicide) are bridge symptoms. (2) In the anxiety network, A2 (Uncontrollable worrying)-A3 (Worrying too much) were identified as the strongest edge, and A2 exhibiting the highest centrality. C1 (Self-blame), C8 (Catastrophizing), and A6 (Easy annoyance) are bridge symptoms. (3) In the somatization network, the strongest edge is S14 (Fatigue)-S15 (Sleep disturbances) and S9 (Palpitations) exhibited the highest centrality. C1 (Self-blame), C3 (Rumination), C8 (Catastrophizing), S9 (Palpitations), and S14 (Fatigue) are bridge symptoms.Conclusion: Self-blame and catastrophizing are important bridge symptoms for cognitive emotion regulation strategies and mental health networks, so cognitive behavioral therapy, focusing on self-blame and catastrophizing as intervention targets, could most effectively improve mental health during public health emergencies.Keywords: cognitive emotion regulation, mental health, network analysis, public health emergency, COVID-19

Ling Zhou,1 Shuhua Zhao,1 Jiahuan Luo,1 Meng Rao,1 Shuangjuan Yang,2 Huawei Wang,1 Li Tang1 1Department of Reproduction and Genetics, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 2The Core Technology Facility of Kunming Institute of Zoology (KIZ), Chinese Academy of Sciences (CAS), Kunming, People’s Republic of ChinaCorrespondence: Li Tang, Department of Reproduction and Genetics, The First Affiliated Hospital of Kunming Medical University, No. 295, Xichang Road, Wuhua District, Kunming, People’s Republic of China, Email tanglikm@163.comObjective: This study aims to investigate alterations in immune cell counts within preovulatory follicles of patients with poor ovarian response (POR) during assisted reproductive technology (ART), classified according to the POSEIDON criteria.Methods: This single-centre cross-sectional study included 543 women undergoing IVF/ICSI treatment, selected based on specific inclusion and exclusion criteria: 292 with normal ovarian response and 251 with poor response. Follicular fluid (FF) was collected on the day of oocyte retrieval and analysed by flow cytometry to determine the proportions of macrophages (M&phis;s), M1 and M2 M&phis;s, T cells (CD4 and CD8 T cells), dendritic cells (DCs), including type 1 conventional dendritic cells (cDC1) and type 2 conventional dendritic cells (cDC2), and neutrophils. Multivariable logistic regression assessed the relationship between immune cell counts and POR, Pearson correlation determined associations with the number of retrieved oocytes, and receiver operating characteristic (ROC) curves evaluated the predictive power of immune cell counts for POR.Results: Immune cells accounted for 52.57% (± 23.90%) of the total cell population in the follicular microenvironment, which was approximately equal to that of granulosa cells, with M&phis;s being the most abundant, followed sequentially by T cells, DCs, and neutrophils. In patients with POR, overall M&phis;s infiltration in the follicular microenvironment decreased, whereas M1 and M2 polarization increased. T cell infiltration increased, with a decrease in the CD4/CD8 ratio. Both cDC1 and cDC2 were significantly elevated. Moreover, multivariable logistic regression revealed that the total macrophage count, CD4 T cell count, and cDC2 count were independent predictors of POR. Notably, cDC2 showed the largest area under the ROC curve, suggesting its strong potential as a biomarker for predicting POR.Conclusion: The proportion of immune cells in preovulatory follicles were significantly altered in patients with POR. These findings suggest that immune cell dynamics in the follicular microenvironment may play a crucial role in determining ovarian response and prognosis, indicating that targeted immunomodulatory strategies could be considered in future therapeutic approaches.Keywords: follicular fluid, immune cells, macrophages, T cells, dendritic cells, number of oocytes retrieved, low prognosis

Hao Wang,1,2 Song Wei,1,2 Lijun Wang,3 Zhihong Zhang1,2 1Department of Respiratory Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230031, People’s Republic of China; 2Department of Respiratory Oncology, Anhui Provincial Cancer Hospital, Hefei, Anhui, 230031, People’s Republic of China; 3Department of Respiratory Disease, Building 8 of Tongling People’s Hospital, Tongling, Anhui, 244000, People’s Republic of ChinaCorrespondence: Lijun Wang; Zhihong Zhang, Email junliy890@163.com; ahszlyyhxk@163.comBackground: Non-smoking women with lung adenocarcinoma(NSWLA) is a significant health problem globally; the carcinogenesis and prognostic signature remain poorly understood. Circular RNAs (circRNAs) are gradually implicated in cancer formation through sponging miRNAs to regulate mRNAs.Methods: Tumor and paracancerous specimens from non-smoking women after lung adenocarcinoma surgery were collected for high-throughput sequencing of circRNA. miRNA and mRNA datasets were downloaded from TCGA. A circRNA-miRNA-mRNA network was built using differentially expressed circRNAs (DEcircRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs). Following that, GSEA was applied to analyze the biological function of mRNAs in the ceRNA network. Utilizing the mRNAs associated with prognosis, we created an original prognostic risk score model. The expression of DEmRNA in the ceRNA network was verified by mRNA-seq and scRNA-seq data (GSE131907). The expression of BTBD3 and EIF4EBP2 was then verified by immunohistochemistry.Results: 16 pairs of adenocarcinoma tissues and their corresponding para-tumor samples were collected from thoracic surgery. We created a circRNA related ceRNA in NSWLA. The hsa_circ_0002346 regulation of the cancer cell proliferation may through the hsa_circ_0002346/miR-96-5p/EIF4EBP2 axis. Hsa_circ_0072309 may affect proliferation of lung adenocarcinoma and activate Nature Killer cells by targeting miR-32-5p to regulate PCMTD1 expression. Based upon mRNA (BTBD3, CFL2, EIF4EBP2, EVI5, PCMTD1, SYDE2) related to overall survival, we also created a predictive signature. According to mRNA-seq, scRNA-seq, and immunohistochemical data, the expression of BTBD3 and EIF4EBP2 was lower in tumor samples than in normal tissues nearby.Conclusion: The circRNA related mRNAs played an important role in predicting the overall survival of NSWLA. The circRNA in the ceRNA network might unravel the pathogenesis and be potential novel targets for NSWLA.Keywords: women, lung adenocarcinoma, circRNA, miRNA, ceRNA, prognosis

HanYu Wang,1,&ast; BoWen Yang,2,&ast; XiaoYu Zeng,1,&ast; ShiPeng Zhang,1 Yanjie Jiang,3 Lu Wang,1 Chao Liao1,4 1Clinical Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 2Dongguan Hospital, Guangzhou University of Chinese Medicine, Dongguan, Guangdong, People’s Republic of China; 3Department of Neurology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 4Department of Otorhinolaryngology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chao Liao, Department of Otorhinolaryngology, Hospital of Chengdu University of Traditional Chinese Medicine, No. 37 on the Street of Shi Er Bridge, City Chengdu, Province Sichuan, People’s Republic of China, Email lc_cdutcm@163.comBackground: Obesity is a significant risk factor for obstructive sleep apnea (OSA). The weight-adjusted-waist index (WWI) reflects weight-independent centripetal obesity. Our study aims to evaluate the relationship between WWI and OSA.Methods: The data used in the current cross-sectional investigation are from the National Health and Nutrition Examination Survey (NHANES), which was carried out between 2017 and 2020. We utilized weighted multivariable-adjusted logistic regression to evaluate the relationship between WWI and the risk of OSA. In addition, we applied various analytical methods, including subgroup analysis, smoothing curve fitting, threshold effect analysis and the receiver operating characteristic (ROC) curve. To further explore the relationship, we conducted a MR study using genome-wide association study (GWAS) summary statistics. We performed the main inverse variance weighting (IVW) method along with other supplementary MR methods. In addition, a meta-analysis was conducted to provide an overall evaluation.Results: WWI was positively related to OSA with the full adjustment [odds ratio (OR)=1.14, 95% confidence interval (95% CI): 1.06– 1.23, P< 0.001]. After converting WWI to a categorical variable by quartiles (Q1-Q4), compared to Q1 the highest WWI quartile was linked to an obviously increased likelihood of OSA (OR=1.26, 95% CI: 1.06– 1.50. P=0.01). Subgroup analysis revealed the stability of the independent positive relationship between WWI and OSA. Smoothing curve fitting identified a saturation effect of WWI and OSA, with an inflection point of 11.62. In addition, WWI had the strongest prediction for OSA (AUC=0.745). Sensitivity analysis was performed to verify the significantly positive connection between WWI and stricter OSA (OR=1.18, 95% CI: 1.05– 1.32, P=0.005). MR meta-analysis further supported our results (OR=2.11, 95% CI: 1.94– 2.30, P< 0.001). Sensitivity analysis confirmed the robustness and reliability of these findings.Conclusion: WWI was significantly associated with the risk of OSA, suggesting that WWI could potentially serve as a predictor for OSA.Keywords: weight-adjusted waist circumference index, WWI, obstructive sleep apnea, OSA, National Health and Nutrition Examination Survey, NHANES, Mendelian randomization analysis, cross-sectional study

Chengbin Zheng,1 Leilei Liang,1 Marhaba Kiyum,1 Tongshuang Yuan,1 Junsong Fei,1 Huimin Wang,1 Jiaying Gao,1 Xiaoying Liu,1 Songli Mei,1 Na Du2 1Department of Social Medicine and Health Management, School of Public Health of Jilin University, Changchun, 130021, People’s Republic of China; 2Center of Infectious Disease and Pathogen Biology, Department of Infectious Diseases, The First Hospital of Jilin University, Changchun, 130061, People’s Republic of ChinaCorrespondence: Songli Mei, Jilin University, Department of Social Medicine and Health Management, School of Public Health of Jilin University, Changchun, 130021, People’s Republic of China, Email meisongli@sina.com Na Du, The First Hospital of Jilin University, Center of Infectious Disease and Pathogen Biology, Department of Infectious Diseases, The First Hospital of Jilin University, Changchun, 130061, People’s Republic of China, Email du_na@jlu.edu.cnBackground: With the increasing popularity of ARVs, physical symptoms of people living with HIV/AIDS (PLWHA) have been effectively improved. Improving mental health and quality of life has gradually become the focus of attention in the treatment. The aim of this study is to explore the association between death anxiety and depression in men living with HIV/AIDS (MLWHA) from the perspective of network analysis.Methods: This study recruited 701 MLWHA in Jilin Province, China. Participants were asked to complete a questionnaire. The average age of the participants was 37.4 years old. Among them, there were 54 heterosexual participants, 494 homosexual participants, 139 bisexual participants, and 14 asexual/other participants. Network analysis was used to identify central symptoms, key bridge symptoms, and the strongest edge among symptoms in the death anxiety and depression network.Results: In this study, 18.1% of MLWHA may suffer from severe depression. The severity of depression in homosexual MLWHA was severer than in heterosexuals. Death anxiety was severer among unmarried and married/cohabiting MLWHA compared to divorced/separated/widowed MLWHA. This study found that item DAS10 (The topic of post death is very confusing to me) was the most central symptom. The edge DAS2 – PHQ9 (Rarely think of death – Suicide ideation) was the strongest edge between death anxiety and depression. Item DAS2 (Rarely think of death) was the strongest bridge symptom.Conclusion: Psychological symptoms such as distress over the topic of death, thoughts of death, and suicidal ideation play an important influential and connecting role in the death anxiety-depression network among MLWHA. Implementing appropriate interventions for these symptoms—such as popularizing correct knowledge of death and providing more psychological counseling services for this group—can effectively reduce the co-occurrence of death anxiety and depression, thereby improving the mental health of MLWHA.Keywords: death anxiety, depression, men living with HIV/AIDS, network analysis, comorbid psychological symptoms

Xin Tang,1,2,&ast; Gaoyangzi Huang,1,2,&ast; Qifu Li,1,2 Siwen Zhao,1,2 Ruqin Yang,1,2 Hongyang Wang,1,2 Yuanzheng Deng,1,2 Zili Liu,2 Taipin Guo,1,2 Fanrong Liang3 1Yunnan Key Laboratory of Integrated Traditional Chinese and Western Medicine for Chronic Disease in Prevention and Treatment, Yunnan University of Chinese Medicine, Kunming, People’s Republic of China; 2School of Second Clinical Medicine/The Second Affiliated Hospital, Yunnan University of Chinese Medicine, Kunming, People’s Republic of China; 3School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Taipin Guo, School of Second Clinical Medicine/The Second Affiliated Hospital, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Chenggong District, Kunming City, Yunnan Province, People’s Republic of China, Email gtphncs@126.com Fanrong Liang, School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, 37 Jinniu District, Chengdu City, Sichuan Province, People’s Republic of China, Email acuresearch@126.comBackground: Appetite plays a crucial role in obesity and weight loss outcomes. while conventional therapies reduce appetite, They often have limitations. Acupoint Catgut Embedding (ACE) is widely used for weight loss, but its impact on subjective appetite, especially across different appetite status, remains underexplored.Objective: To evaluate the differential impact of ACE on the subjective appetite of overweight and obese adults with strong and moderate appetites.Methods: This secondary analysis used data from a multicenter, double-blind, parallel randomized clinical trial of the ACE intervention. A total of 122 overweight and obese patients aged 18– 60 were randomly assigned to the ACE and Non-acupoint Catgut Embedding (NACE) groups, each receiving six sessions over 12 weeks and a 4-week follow-up. Appetite was measured using the Visual Analogue Scale (VAS), and a generalized linear mixed-effects model assessed changes in appetite scores. Bonferroni corrections were applied for multiple comparisons (P < 0.05).Results: Participants with strong appetite in the ACE group showed a significant reduction in appetite VAS score from 7.78 (0.66) at baseline to 5.00 (0.72) at 16 weeks (P < 0.05), compared to a reduction from 7.97 (0.93) to 6.54 (1.17) in the NACE group. The adjusted relative rate ratio between the two groups was 0.411 (95% CI, 0.210 to 0.534; P < 0.05). In participants with moderate appetite, no significant difference was observed between the two groups (P > 0.05). The significant baseline difference in appetite scores between participants with strong and moderate appetite (P < 0.05) became non-significant by week 16 (P > 0.05).Conclusion: This study reveals the stratified effect of ACE on appetite, with greater reduction in those with strong appetite and no significant change in those with moderate appetite. This suggests ACE reduces appetite effectively without excessive suppression, supporting its potential as a sustainable obesity management strategy.Keywords: acupoint catgut embedding, appetite, overweight, obesity, randomized controlled trial

Xiangxiang Peng,1,&ast; Changwei Guo,2,&ast; Jie Yang,2 Shitao Fan,2 Xu Xu,2 Jinfu Ma,2 Zhixi Wang,2 Shihai Yang,2 Wenjie Zi,2 Xianjun Huang,1 Hongjun Wang3 1Department of Neurology, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui Province, People’s Republic of China; 2Department of Neurology, Xinqiao Hospital and The Second Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, People’s Republic of China; 3Department of Neurology, Chongqing Fengdu People’s Hospital, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xianjun Huang, Department of Neurology, Yijishan Hospital of Wannan Medical College, No. 92 Zheshan Road, Wuhu, Anhui Province, 241000, People’s Republic of China, Tel +86-553-5739543, Email doctorhuangxj@hotmail.com Hongjun Wang, Department of Neurology, Chongqing Fengdu People’s Hospital, No. 214, West Section of Pingdu Avenue, Sanhe Town, Fengdu County, Chongqing, 408200, People’s Republic of China, Email whj13364012222@163.comPurpose: To investigate the relationship between intravenous tirofiban, the number of retrieval attempts and symptomatic intracranial hemorrhage (sICH) in patients with successful EVT.Patients and Methods: We used the data from the Endovascular Treatment With versus Without Tirofiban for Patients with Large Vessel Occlusion Stroke (RESCUE BT) Trial. The primary outcome was sICH, which was defined according to the Heidelberg Bleeding Classification. The association between the number of retrieval attempts and the rate of sICH was investigated using multivariable logistic regression.Results: A total of 866 patients were included in our analysis. In overall cohort, tirofiban (OR: 1.853, 95% CI: 1.039– 3.307) and more than 2 passes (3 versus 0– 1: OR: 2.482, 95% CI: 1.124– 5.481; 2 versus 0– 1: OR: 0.813, 95% CI: 0.389– 1.696) were significantly associated with the occurrence of sICH. A significant interaction between the use of tirofiban and the increasing number of attempts was found (p for interaction = 0.02), whereby the presence of sICH was significantly associated with tirofiban (OR: 5.534, 95% CI: 1.586– 19.315) in the subgroup of multiple passes (> 2 passes group), while none was seen in the subgroup of 0– 2 passes. The results of the sensitivity analysis also showed that more than 2 passes (3 versus 1: OR: 2.841, 95% CI: 1.102– 7.323; 2 versus 1: OR: 0.852, 95% CI: 0.346– 2.097) were significantly associated with the occurrence of sICH in the tirofiban group but not in the placebo group.Conclusion: In patients with multiple attempts, intravenous tirofiban may increase the risk of sICH. Further research and individualized risk assessment are necessary to determine the most appropriate strategy of intravenous tirofiban for EVT patients, especially considering details of thrombectomy procedures.Registration: : URL: http:// www.chictr.org.cn; Unique identifier: ChiCTR-INR-17014167.Keywords: tirofiban, hemorrhage, endovascular treatment, stroke

Yang Chen,1,&ast; Lijie Sun,1,&ast; Minghui Chen,1,&ast; Hui Zhang,2 Bing Song,3 Hongxiao Wang,3 Aijun Jiang,1,4 Li Zhang,5 Sumei Li,1 Jumei Wang,1 Wei Wang,1 Haoqiang Zhang1 1Department of Endocrinology, Centre for Leading Medicine and Advanced Technologies of IHM, 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; 2Henan Key Laboratory of Rare Diseases, Endocrinology and Metabolism Center, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, People’s Republic of China; 3Department of Endocrinology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, People’s Republic of China; 4University of Science and Technology of China, Hefei, People’s Republic of China; 5ShuCheng People’s Hospital, Luan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Wang; Haoqiang Zhang, Email hfww2001@ustc.edu.cn; drhqzhang@ustc.edu.cnPurpose: Our objective is to investigate the potential involvement of free triiodothyronine (FT3), a key bioactive compound found in thyroid hormones (THs) in the pathogenesis of diabetic peripheral neuropathy (DPN) in patients diagnosed with type 2 diabetes mellitus (T2DM).Patients and Methods: A total of 121 T2DM patients were recruited. And then, they were divided into the control group and the DPN group. Clinical parameters were collected for each patient. Additionally, nerve conduction velocity was tested using neurophysiological methods. Correlation and regression analyses were employed to examine the relationship between the concentrations of FT3 and DPN.Results: Compared to 57 patients without DPN, 64 patients with DPN showed increased HbA1c and low-density lipoprotein cholesterol (LDL-C) levels (P=0.001 and 0.042), as well as decreased concentrations of FT3 (P=0.042). Additionally, FT3 levels are positively associated with the motor and sensory fibers conduction velocity of the Ulnar nerve, as well as the motor conduction velocity of the Tibial nerve, with (R=0.205, P=0.025; R=0.191, P=0.038; R=0.220, p=0.016) or without (R=0.257, P=0.004; R=0.227, P=0.012; R=0.227, p=0.012) adjustment for HbA1c and LDL-C. Furthermore, multiple linear regression analysis suggests that decreased FT3 levels may influence the motor and sensory fibers conduction velocity of the Ulnar nerve (β=0.795, P=0.025 and β=0.909, P=0.038), as well as the motor conduction velocity of the Tibial nerve (β=0.727, P=0.016). Moreover, our study demonstrated that decreased FT3 levels are one of the risk factors for DPN in T2DM patients, as determined by binary logistic regression analysis (OR=0.542, P=0.022).Conclusion: Lower concentrations of FT3 are one of the risk factors for DPN in patients with T2DM. Additionally, decreased FT3 levels may influence peripheral neuropathy, particularly affecting the motor and sensory fibers conduction velocity of the ulnar nerve, as well as the motor fiber conduction velocity of the tibial nerve.Keywords: free triiodothyronine, diabetic peripheral neuropathy, type 2 diabetes mellitus, thyroid hormone, conduction velocity of nerve

Hongli Wang,1,2,* Mingzhu Wang,1,2,* Tengyue Wang,1,2 Xuanlin Li,1,2 Chengping Wen,1,2 Zhexing He,1,2 Lin Huang1,2 1Research Institute of Chinese Medical Clinical Foundation and Immunology, School of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 2Key Laboratory of Chinese Medicine Rheumatology of Zhejiang Province, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lin Huang; Zhexing He, College of Basic Medical Science, Zhejiang Chinese Medical University, 548 Binwen Road, Binjiang District, Hangzhou, People’s Republic of China, Email huanglin@zcmu.edu.cn; hzx2015@zcmu.edu.cnBackground: Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation and bone destruction, leading to severe complications. Previous research has suggested that high humidity conditions may exacerbate RA, however, the underlying mechanisms remain unclear. Furthermore, there is a lack of evidence linking humidity to the worsening of RA symptoms in animal models.Methods: The Collagen-induced arthritis (CIA) mouse model was established using C57BL/6 mice. The arthritis status of the mice was evaluated under two distinct humidity conditions (50% and 80%). The aim of the present study was to investigate the impact of elevated humidity levels on the types of splenic cells present using mass spectrometry flow. Additionally, the study utilized MDSCs, which are significantly upregulated by high humidity, to assess the levels of oxidative stress and conducted mRNA sequencing of sorted MDSCs to investigate their impact on arthritis in CIA mice.Results: Compared to normal humidity, high humidity exacerbated arthritis incidence in mice, resulting in increased arthritis scores, swelling, serum autoantibodies (anti-COII and anti-CCP), and upregulation of pro-inflammatory cytokines. Significant variations were observed in the spleen index under high humidity condition, accompanied by noticeable inflammatory alterations. Moreover, elevated humidity levels induced a substantial modulation in MDSCs population in the spleen of CIA mice, along with alterations in oxidative stress markers such as heightened serum ROS levels, and increased expression of COX, SOD, and Nrf2 mRNA. Following successful sorting of MDSCs, mRNA sequencing revealed a decrease in the expression of Rap1 signaling pathway under high humidity environment, which may contribute to the increase of MDSCs cells and aggravate the progression of RA disease.Conclusion: A comprehensive analysis of the available data reveals a detrimental impact of high humidity on MDSCs numbers within spleen tissue, with potential implications for the development of RA.Keywords: rheumatoid arthritis, high humidity environment, myeloid-derived suppressor cells, Rap1 signaling pathway

Jianmeng Zhu,1 Hongqin Wang,1 Kaiqiang Li,2 Xiuze Yuan,3 Wenzhong Hong1 1Clinical Laboratory of Chun’an First People’s Hospital, Zhejiang Provincial People’s Hospital Chun’an Branch, Hangzhou, Zhejiang, People’s Republic of China; 2Laboratory Medicine Center, Allergy Center, Department of Transfusion Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 3Pharmacy Department of Chun’an First People’s Hospital, Zhejiang Provincial People’s Hospital Chun’an Branch, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Kaiqiang Li, Laboratory Medicine Center, Allergy Center, Department of Transfusion Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, 158 Shangtang Road, Hangzhou, Zhejiang, 310014, People’s Republic of China, Tel/Fax +86 571 8589 3270, Email likaiqiang@hmc.edu.cnBackground: Conventional treatments for hepatocellular carcinoma (HCC) lack efficacy and targeting abilities. Photodynamic therapy (PDT) has emerged as a promising alternative for targeted and minimally invasive tumor treatments. However, many biomaterials used in PDT pose biosafety concerns and insufficient enzyme activity often leads to limited reactive oxygen species (ROS) production, resulting in poor PDT efficacy. Single-atom nanoenzymes have attracted much research attention as a novel type of high-performance nanoenzymes.Methods: In this study, we prepared black phosphorus nanosheets (BP) with good biocompatibility as a platform and loaded single-atom gold nanoenzymes onto BP nanosheets to treat HCC. To enhance the stability and targeting ability of the nanohybrid, it was PEGylated and modified with folate (FA) targeting molecules.Results: The designed BP/single-atom nanoenzyme platform can target tumor tissues and generate substantial amounts of reactive oxygen species (ROS), demonstrating biocompatibility and improved catalytic activity.Conclusion: The nanoplatform effectively targets HCC and enhances PDT efficacy by increasing ROS production, offering a promising approach for HCC treatment.Keywords: tumor treatment, photodynamic therapy, hepatocellular carcinoma, black phosphorus, single-atom gold

Yanlin Zhu,1,2 Shuwei Qiao,2,3 Yuxuan Pang,2,3 Huimin Wang,2,3 Yanmin Zhou1,2 1Department of Dental Implantology, Hospital of Stomatology, Jilin University, Changchun, People’s Republic of China; 2Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, Changchun, People’s Republic of China; 3Department of Prosthodontics, Hospital of Stomatology, Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Yanmin Zhou, Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, 1500 Qinghua Road, Changchun, Jilin Province, 130021, People’s Republic of China, Tel +8618943971001, Email zhouym@jlu.edu.cnPurpose: Although the anti-inflammatory properties of the hypoxia-mimetic drug deferoxamine (DFO) have been reported, its potential as a treatment for periodontitis remains unknown. This study investigated the therapeutic benefits of DFO on osteoclastogenesis and inflammation in periodontitis progression.Methods: RAW264.7 cells were pretreated with DFO before stimulation with lipopolysaccharides from Porphyromonas gingivalis (P.g-LPS). Hypoxia-inducible factor-1α (HIF-1α) and inflammatory factors were measured, followed by analysis of relevant inflammatory pathways. Immunofluorescence and molecular biology methods were employed to assess osteoclast differentiation in RAW264.7 cells after nuclear factor-κB ligand (RANKL) induction. A rat model of periodontitis was es\lished using ligature wires, and alveolar bone loss was assessed via micro-computed tomography. Osteoclastogenesis and periodontal inflammation were assessed through immunohistochemistry as well as hematoxylin and eosin staining.Results: DFO reduced the P.g-LPS-induced inflammatory factor expression (P < 0.0001) and upregulated HIF-1α (P = 0.0278) in RAW264.7 cells. DFO suppressed NF-κB signaling by inhibiting NF-κB p65 nuclear translocation and phosphorylation. DFO pretreatment inhibited osteoclast development by decreasing F-actin rings synthesis, reducing the number of mature osteoclasts (P < 0.0001) and downregulating osteoclast-specific markers (P < 0.05). In rat periodontitis models, DFO treatment reduced tissue inflammation, osteoclastogenesis, and alveolar bone loss (P < 0.05).Conclusion: DFO effectively prevented osteoclast development, alveolar bone loss, and inflammation associated with periodontitis.Keywords: deferoxamine, periodontitis, inflammation, osteoclast differentiation

Chao Wu,&ast; Chunxia He,&ast; Haimeng Wang, Wenming Wang, Hongzhong Jin Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongzhong Jin, Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy Medical Science and Peking Union Medical College, No. 1 Shuai Fu Yuan Street, Beijing, 100730, People’s Republic of China, Fax +86-10-6915-1502, Email jinhongzhong@263.netPurpose: This prospective observational study investigated whether interleukin (IL)-17A inhibitors could reduce serum uric acid (SUA) levels in psoriatic patients with hyperuricemia. It also explored the risk factors for hyperuricemia in psoriatic patients and the effectiveness of IL-17A inhibitors for the skin lesions of psoriatic patients with hyperuricemia.Methods: Patients aged ≥ 18 years with moderate to severe plaque psoriasis along with concomitant hyperuricemia (defined as an SUA level > 416 μmol/L in men and > 357 μmol/L in women) at baseline were treated with either secukinumab or ixekizumab. SUA levels were longitudinally assessed over 1 year. We evaluated the changes in SUA level and factors associated with SUA changes. Binary logistic regression was conducted to identify risk factors for hyperuricemia in psoriatic patients. Additionally, we examined effectiveness of IL-17A inhibitors for patients with psoriasis and hyperuricemia including Psoriasis Area Severity Index (PASI) 75, 90, and 100 response rates at 1 year.Results: Our study included 196 individuals diagnosed with psoriasis and hyperuricemia. The mean SUA levels were 481± 68 μmol/L at baseline and 442± 78 μmol/L after 1 year of treatment with IL-17A inhibitors (p< 0.001). Subgroup analysis revealed a consistent and significant decrease in SUA levels across different genders, age groups (30– 39, 40– 49, ≥ 50 years), BMI categories, baseline PASI scores, PASI improvement rates, and among patients treated with different IL-17A inhibitors. Patients aged ≥ 50 years and with a BMI < 24 exhibited a higher SUA reduction rate. Male gender, age under 40 years, obesity, hypertension, hypertriglyceridemia, and a PASI score of ≥ 20 were independent risk factors for hyperuricemia in patients with psoriasis. The PASI 75, 90, and 100 response rates in psoriatic patients with hyperuricemia were 88.3%, 60.2%, and 28.6%, respectively, after 1 year of treatment with IL-17A inhibitors.Conclusion: Our findings suggest that SUA levels decrease significantly under IL-17A inhibitors treatment in psoriatic patients with hyperuricemia. Patients aged ≥ 50 years and with a BMI < 24 had greater benefits. This study provides a theoretical basis for the selection of biologics to treat psoriatic patients with hyperuricemia.Keywords: psoriasis, uric acid, hyperuricemia, IL-17A inhibitor

Liang Chen,1,&ast; Xiaomei Ying,2,&ast; Haohao Wang,1,&ast; Jiaheng Xie,3,&ast; Qikai Tang,4 Wen Liu1 1Department of Hepatobiliary and Pancreatic Surgery, Conversion Therapy Center for Hepatobiliary and Pancreatic Tumors, First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People’s Republic of China; 2Department of General Surgery, Suzhou Hospital of Anhui Medical University, Suzhou, Anhui, People’s Republic of China; 3Department of Plastic and Cosmetic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, People’s Republic of China; 4Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wen Liu, Department of Hepatobiliary and Pancreatic Surgery, Conversion therapy center for Hepatobiliary and Pancreatic Tumors, First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People’s Republic of China, Email nickwen2006@163.comBackground: The role of cellular senescence in the tumor microenvironment of pancreatic cancer (PC) remains unclear, particularly regarding its impact on prognosis and immunotherapy outcomes.Methods: We utilized single-cell sequencing datasets (GSE155698 and GSE154778) for pancreatic cancer from the Gene Expression Omnibus (GEO) database and bulk RNA-seq data from the University of California, Santa Cruz (UCSC) and International Cancer Genome Consortium (ICGC) repositories, creating three patient cohorts: The Cancer Genome Atlas (TCGA) cohort, PAAD-AU cohort, and PAAD-CA cohort. Dimensionality reduction cluster analysis processed the single-cell data, while weighted gene co-expression network analysis (WGCNA) and differential expression gene analysis were applied to bulk RNA-seq data. Prognostic models were developed using Cox proportional hazards (COX) and least absolute shrinkage and selection operator (LASSO) regression, with validation through survival analysis, decision curve analysis, and principal component analysis (PCA). Tumor mutation data were analyzed using the “maftools” package, and the immune microenvironment was assessed with TIMER2 data.Results: We developed a senescence-related (SENR) six-gene prognostic signature for PC, which stratifies patients by risk, with high-risk groups showing poorer prognoses. This model also offers predictive insights into tumor mutations and immune microenvironment characteristics. Caveolin-1 (CAV1) emerged as a significant prognostic biomarker, with functional validation showing its role in promoting cancer cell proliferation and migration, highlighting its potential as a therapeutic target.Conclusion: This study provides a novel senescence-related prognostic tool for PC, enhancing patient stratification for prognosis and immunotherapy, and identifies CAV1 as a key gene with clinical significance for targeted interventions.Keywords: pancreatic cancer, cellular senescence, prognosis, biomarker, immunotherapy

Changhong Xu,1,&ast; Yun Deng,1,&ast; Xinyi Gong,2,&ast; Huabin Wang,1 Jiangwei Man,1 Hailong Wang,1 Kun Cheng,1 Huiming Gui,1 Shengjun Fu,1 Shenghu Wei,3 Xiaoling Zheng,4 Tuanjie Che,4 Liyun Ding,3 Li Yang1 1Department of Urology, Institute of Urology, Gansu Province Clinical Research Center for Urinary System Disease, Lanzhou University Second Hospital, Lanzhou, Gansu, 730030, People’s Republic of China; 2The Second Clinical Medical College of Lanzhou University, Lanzhou, Gansu, 730030, People’s Republic of China; 3School of Physical Science and Technology, Lanzhou University, Lanzhou, 730000, People’s Republic of China; 4Innovation Center of Functional Genomics and Molecular Diagnostics Technology of Gansu Province, Lanzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Yang; Liyun Ding, Email ery_yangli@lzu.edu.cn; dingly@lzu.edu.cnBackground: Renal ischemia-reperfusion injury (RIRI) is a significant cause of acute kidney injury, complicating clinical interventions such as kidney transplants and partial nephrectomy. Recent research has indicated the role of cuproptosis, a copper-dependent cell death pathway, in various pathologies, but its specific involvement in RIRI remains insufficiently understood. This study aims to investigate the role of cuproptosis-related genes in RIRI and establish robust diagnostic models.Methods: We analyzed transcriptomic data from 203 RIRI and 188 control samples using bioinformatics tools to identify cuproptosis-related differentially expressed genes (CRDEGs). The relationship between CRDEGs and immune cells was explored using immune infiltration analysis and correlation analysis. Gene Set Enrichment Analysis (GSEA) was conducted to identify pathways associated with CRDEGs. Machine learning models, including Least Absolute Shrinkage and Selection Operator(LASSO) logistic regression, Support Vector Machine Recursive Feature Elimination (SVM-RFE), Clustering analysis, and weighted gene co-expression network analysis (WGCNA), were used to construct diagnostic gene models. The models were validated using independent datasets. Experimental validation was conducted in vivo using a mouse bilateral RIRI model and in vitro using an HK-2 cell hypoxia-reoxygenation (HR) model with copper chelation intervention. HE, PAS, and TUNEL staining, along with plasma creatinine and blood urea nitrogen (BUN) measurements, were used to evaluate the protective effect of the copper chelator D-Penicillamine (D-PCA) on RIRI in mice. JC-1 and TUNEL staining were employed to assess apoptosis in HK-2 cells under hypoxia-reoxygenation conditions. Immunofluorescence and Western blot (WB) techniques were used to verify the expression levels of the SDHB and NDUFB6 genes.Results: A total of 18 CRDEGs were identified, many of which were significantly correlated with immune cell infiltration. GSEA revealed that these genes were involved in pathways related to oxidative phosphorylation and immune response regulation. Four key cuproptosis marker genes (LIPA, LIPT1, SDHB, and NDUFB6) were incorporated into a Cuproptosis Marker Gene Model(CMGM), achieving an area under the curve (AUC) of 0.741– 0.834 in validation datasets. In addition, a five-hub-gene SVM model (MOAP1, PPP2CA, SYL2, ZZZ3, and SFRS2) was developed, demonstrating promising diagnostic performance. Clustering analysis revealed two RIRI subtypes (C1 and C2) with distinct molecular profiles and pathway activities, particularly in oxidative phosphorylation and immune responses. Experimental results showed that copper chelation alleviated renal damage and cuproptosis in both in vivo and in vitro models.Conclusion: Our study reveals that cuproptosis-related genes are significantly involved in RIRI, particularly influencing mitochondrial dysfunction and immune responses. The diagnostic models developed showed promising predictive performance across independent datasets. Copper chelation demonstrated potential therapeutic effects, suggesting that cuproptosis regulation may be a viable therapeutic strategy for RIRI. This work provides a foundation for further exploration of copper metabolism in renal injury contexts.Keywords: cuproptosis, renal ischemia-reperfusion injury, RIRI, gene diagnostic models, copper chelators, bioinformatics analysis

Hao Wang,1 Miao Yu,1 Meihua Chen,2 Hui Li,1 Shiwei Liu1 1Department of Breast, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610042, People’s Republic of China; 2Department of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610042, People’s Republic of ChinaCorrespondence: Shiwei Liu, Department of Breast, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610042, People’s Republic of China, Tel/Fax +86-02885420456, Email liushiwei@scszlyy.org.cnPurpose: Human epidermal growth factor receptor 2 (HER2)-low breast cancer, consisted of carcinomas with HER2 protein 1+ or 2+ without gene amplification, has been considered a biologically heterogeneous disease. Limited research separately investigated the prognostic significance of HER2 2+ without gene amplification, and no evidence can be identified in older patients. In this dedicated cohort of older patients with HER2-negative and high-risk breast cancer, we analyzed the real-world prognosis after standard adjuvant chemotherapy, and investigated the associations of survival with HER2 2+ without gene amplification.Patients and Methods: From January 2016 to December 2021, older patients (≥ 65 years) with breast cancer were reviewed, and HER2-negative/high-risk disease receiving standard adjuvant chemotherapy was included. HER2-negativity was defined as immunohistochemistry (IHC) score 0, 1+ or 2+ without gene amplification by fluorescent in situ hybridization (FISH). Cox proportional hazards regression analyses were performed to assess the associations of HER2 2+/FISH-negativity with disease-free survival (DFS), which was estimated by the Kaplan–Meier method and compared by the Log rank test.Results: This cohort consisted of 121 consecutive older patients. With a median follow-up of 46 months, 12 patients had a DFS event. By univariate and multivariate analyses, HER2 2+/FISH-negativity was the only independent predictor for worse DFS (hazard ratio 5.56; P=0.046). Patients with HER2 2+/FISH-negativity had significantly poorer DFS compared with those with HER2 0 or 1+ (Log rank test, P=0.029). In both hormone receptor (HR)-positive (Log rank test, P=0.052) and HR-negative (Log rank test, P=0.125) subgroups, HER2 2+/FISH-negativity showed a marginally significant adverse influence on DFS.Conclusion: In older patients with HER2-negative/high-risk breast cancer undergoing standard adjuvant chemotherapy, our findings suggest that HER2 2+/FISH-negativity has an independent negative impact on prognosis.Keywords: breast cancer, older patients, HER2-low, HER2 2+, prognosis

Hanrui Wang,1– 4,&ast; Xiaoyu Song,1– 4,&ast; Yao Wang,1– 4 Ting Yang,1– 4 Wanchen Liu,1– 4 Yakui Mou,1– 4,&ast; Chao Ren,1– 5 Xicheng Song1– 4 1Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China; 2Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation, Yantai Yuhuangding Hospital, Yantai, People’s Republic of China; 3Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Yantai, People’s Republic of China; 4Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China; 5Department of Neurology, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xicheng Song; Chao Ren, Yantai Yuhuangding Hospital, Qingdao University, No. 20, East Road, Zhifu District, Yantai, 264000, People’s Republic of China, Tel +86535 6691999, Fax +86535 6240341, Email drxchsong@163.com; renchaotg@126.comBackground: The nasal mucosal epithelial barrier is the primary site of allergic rhinitis (AR). Interleukin-1β (IL-1β), as a crucial factor in immune inflammation, not only plays a crucial role in hypersensitivity reactions but also affects the digestive mucosa and skin epithelial barrier. However, the role of IL-1β in the nasal mucosal epithelial barrier in AR has not been reported, and this study aimed to investigate the effect and possible mechanisms involved.Methods: Dermatophagoides pteronyssinus 1 was used as an allergen to construct an AR mouse model and stimulate human nasal mucosal epithelial cells (HNEpCs) and observe the expression changes of IL-1β and epithelial barrier indicators CLDN1 and OCLN in mouse nasal mucosa and HNEpCs. Then, the possible mechanisms of action were explored via exogenous IL-1β stimulation and pharmacological inhibition of IL-1β or its receptor interleukin-1 receptor type 1 (IL-1R1).Results: The results showed that Dermatophagoides pteronyssinus 1-primed mouse nasal mucosa or human HENpCs had increased expression of IL-1β and decreased CLDN1 and OCLN, and IL-1β could directly lead to reduced expression of epithelial barrier indexes in HNEpCs. In addition, inhibition of IL-1β or IL-1R1 can effectively alleviate the damage to the epithelial barrier.Conclusion: IL-1β has a destructive effect on the nasal mucosal epithelial barrier in AR, and inhibition of IL-1β or its receptor IL-1R1 can effectively protect the nasal mucosal barrier. IL-1β is a potential target for the treatment of AR.Keywords: interleukin-1β, allergic rhinitis, nasal mucous membrane, epithelial barrier, DerP1

Jiaxin Chen,1 Honglong Li,2 Yang Xin,3 Haijun Wang4 1School of Public Health, Qiqihar Medical University, Qiqihar, Heilongjiang, People’s Republic of China; 2School of Mental Health, Qiqihar Medical University, Qiqihar, Heilongjiang, People’s Republic of China; 3College of Chemistry and Chemical Engineering, Qiqihar University, Qiqihar, Heilongjiang, People’s Republic of China; 4School of General Medicine and Continuing Education, Qiqihar Medical University, Qiqihar, Heilongjiang, People’s Republic of ChinaCorrespondence: Haijun Wang, School of General Medicine and Continuing Education, Qiqihar Medical University, 333 Bukui Street, Jianhua District, Qiqihar, 161000, People’s Republic of China, Tel/Fax +86452-2663418, Email whj4830369@163.comPurpose: Job satisfaction among faculty in standardized residency training programs has been underexplored. The objective of this study is to investigate job satisfaction among these faculty members and identify associated determinants.Methods: An online cross-sectional survey was conducted with 4581 teachers in Heilongjiang Province from 18 to 30 May 2022, using a census method. The survey collected demographic information and assessed satisfaction using the Minnesota Satisfaction Questionnaire-Short Form. Predictors of job satisfaction were identified using multiple linear regression analysis in SPSS 24.0.Results: The survey achieved a 91.12% response rate (4174/4581). The average satisfaction score of the respondents teachers was 4.30± 0.70. The top three items with the highest satisfaction scores were “the chance to work alone on the job” (4.46± 0.68), “the way my job provides for steady employment” (4.45± 0.68), and “the freedom to use my own judgment” (4.43± 0.69). The lowest-scoring items “the chances for advancement on this job” (4.02± 1.03), “my pay and the amount of work I do” (4.08± 0.96), and “the praise I get for doing a good job” (4.10± 0.93). Multiple linear regression analysis revealed that geographical area, registered general subjects, age, administrative position, monthly income, daily working hours, and overtime frequency were significant factors influencing job satisfaction (P < 0.05).Conclusion: The level of job satisfaction among standardized residency training faculty in Heilongjiang Province was generally high. High satisfaction was associated with residing in economically developed areas, having registered general subjects, holding administrative positions, earning high income, working shorter few hours daily and having a low frequency of overtime.Keywords: medical education, job burnout, job satisfaction, standardized residency training

Hua Wang,1 Jichong Ying,2 Jianlei Liu,2 Tianming Yu,2 Dichao Huang2 1Department of Medical Imaging, Ningbo No.6 hospital, Ningbo, People’s Republic of China; 2Department of Orthopedics, Ningbo No.6 hospital, Ningbo, People’s Republic of ChinaCorrespondence: Dichao Huang, Department of Orthopedics, Ningbo No.6 hospital, Ningbo, People’s Republic of China, Email hsdichaohuang@163.comBackground: Ankle fractures are common injuries with substantial implications for patient mobility and quality of life. Traditional imaging methods, while standard, have limitations in detecting subtle fractures and distinguishing them from complex bone structures. The advent of 3D Convolutional Neural Networks (3D-CNNs) offers a promising avenue for enhancing the accuracy and reliability of ankle fracture diagnoses.Methods: In this study, we acquired 1453 high-resolution CT scans and processed them through three distinct 3D-CNN models: 3D-Mobilenet, 3D-Resnet101, and 3D-EfficientNetB7. Our approach involved meticulous preprocessing of images, including normalization and resampling, followed by a systematic comparative evaluation of the models based on accuracy, Area Under the Curve (AUC), and recall metrics. Additionally, the integration of Gradient-weighted Class Activation Mapping (Grad-CAM) provided visual interpretability of the models’ predictive focus points.Results: The 3D-EfficientNetB7 model outperformed the other models, achieving an accuracy of 0.91 and an AUC of 0.94 after 20 training epochs. It demonstrated particularly effective in the accurate detection and localization of subtle and complex fractures. Grad-CAM visualizations confirmed the model’s focus on clinically relevant areas, aligning with expert assessments and enhancing trust in automated diagnostics. Spatial localization techniques were pivotal in improving interpretability, offering clear visual guidance for pinpointing fracture sites.Conclusion: Our findings highlight the effectiveness of the 3D-EfficientNetB7 model in diagnosing ankle fractures, supported by robust performance metrics and enhanced visualization tools.Keywords: 3d convolutional neural networks, ankle fractures, diagnostic accuracy, Grad-CAM, image processing, machine learning, medical imaging, orthopedic diagnostics

Weiming Yan,1,&ast; Qiurui He,2,&ast; Pan Long,3,&ast; Lei Zhang,4 Haiyan Wang,4 Tao Chen5 1Department of Ophthalmology, Fuzong Clinical Medical College of Fujian Medical University, Dongfang Hospital Affiliated to Xiamen University, Fuzhou, People’s Republic of China; 2Department of Cardiovascular Intervention, The Third Hospital of Zhangzhou, Zhangzhou, People’s Republic of China; 3Department of Ophthalmology, The General Hospital of Western Theatre Command, PLA, Chengdu, People’s Republic of China; 4Department of Ophthalmology, The Shaanxi Eye Hospital, Xi’an People’s Hospital (Xi’an Fourth Hospital), Xi’an, People’s Republic of China; 5Center of Clinical Aerospace Medicine, Air Force Military Medical University, Xi’an, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weiming Yan; Tao Chen, Email ywming@fjmu.edu.cn; baiidtf0506@126.comObjective: With the aids of ophthalmic imaging techniques for animals, the spatiotemporal characterization of MNU-induced retinitis pigmentosa (RP) rats were performed.Methods: Sprague-Dawley (SD) rats were randomly divided into normal group (N), MNU-low-dose group (L) and MNU-high-dose group (H). Rats in the L and H group were given intraperitoneally injection with 40 and 60 mg/kg of MNU, a kind of alkylating agent, respectively. The body weight, electroretinogram (ERG) and retinal structure were observed on day one (D1), D3, and D7 after MNU administration. FFA, OCT, TUNEL staining, and immunostaining of Iba1 were also performed.Results: After MNU injection, the weight and ERG amplitudes of rats in both L and H groups decreased gradually, compared to those of the normal group (P

Yang Zheng,1,2,&ast; Limei Cui,1,2,&ast; Haoran Lu,1,2,&ast; Zhen Liu,1,2 Zhaoxue Zhai,2,3 Huikang Wang,1,2 Liting Shao,1,2 Zhaoyang Lu,2,3 Xicheng Song,1,2,4 Yu Zhang1,2,4 1Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China; 2Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, People’s Republic of China; 3Second Clinical Medicine College, Binzhou Medical University, Yantai, People’s Republic of China; 4Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation, Yantai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu Zhang, Department of Otolaryngology, Head and Neck Surgery. Yantai Yuhuangding Hospital, Qingdao University, No. 20, East Road, Zhifu District, Yantai, 264000, People’s Republic of China, Tel +86535 6691999, Fax +86535 6240341, Email superzhang013@163.com Xicheng Song, Department of Otolaryngology, Head and Neck Surgery. Yantai Yuhuangding Hospital, Qingdao University, Yantai, 264000, People’s Republic of China, Tel +86535 6691999, Fax +86535 6240341, Email drxchsong@163.comAbstract: The intranasal (IN) route of drug delivery can effectively penetrate the blood-brain barrier and deliver drugs directly to the brain for the treatment of central nervous system (CNS) disorders via intra-neuronal or extra-neuronal pathways. This approach has several advantages, including avoidance of first-pass metabolism, high bioavailability, ease of administration, and improved patient compliance. In recent years, an increasing number of studies have been conducted using drugs encapsulated in solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), and delivering them to the brain via the IN pathway. SLNs are the first-generation solid lipid nanocarriers, known for their excellent biocompatibility, high drug-loading capacity, and remarkable stability. NLCs, regarded as the second-generation SLNs, not only retain the advantages of SLNs but also exhibit enhanced stability, effectively preventing drug leakage during storage. In this review, we examined in vivo studies conducted between 2019 and 2024 that used SLNs and NLCs to address CNS disorders via the IN route. By using statistical methods to evaluate pharmacokinetic parameters, we found that IN delivery of SLNs and NLCs markedly enhanced drug accumulation and targeting within the brain. Additionally, pharmacodynamic evaluations indicated that this delivery method substantially improved the therapeutic effectiveness of the drugs in alleviating symptoms in rat models of CNS diseases. In addition, methods for enhancing the efficacy of nose-to-brain delivery of SLNs and NLCs are discussed, as well as advances in clinical trials regarding SLNs and NLCs.Plain Language Summary: Traditional drug administration routes for the treatment of central nervous system diseases have many limitations due to the existence of the blood-brain barrier (BBB). The intranasal drug administration route crosses the BBB through intra-neuronal pathways as well as extra-neuronal pathways and delivers drugs directly to the brain. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are a type of nanoparticles whose surface is covered by amphoteric surfactants and whose interior is filled with a lipid core. They have the advantages of good biocompatibility, strong drug loading capacity, and strong stability, and can be obtained through a variety of reliable preparation methods. Encapsulating therapeutic drugs into SLNs and NLCs for intranasal delivery can significantly increase drug delivery efficiency and enhance efficacy. In addition, there are various ways to further enhance drug delivery of SLNs and NLCs, such as using gel systems such as chitosan to encapsulate the nanoparticles, piggybacking cell-penetrating peptides onto the surface of the nanoparticles, and modifying the nanoparticles, surface charge of particles, etc. Keywords: solid lipid nanoparticle, nanostructured lipid carrier, intranasal delivery, central nervous system diseases

Yan Chu,1,&ast; Xiaomin Wang,2,&ast; Min Dou,1 Jin Wang,2 Baoqian Wang,1 Hairong Wang,1 Shasha Lv,1 Shuihua Lu,2,&ast; Tongxia Li1,&ast; 1Qingdao Chest Hospital, Qingdao, Shandong, People’s Republic of China; 2National Clinical Research Center for Infectious Diseases, Shenzhen Third People’s Hospital, Shenzhen, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tongxia Li; Shuihua Lu, Email qdlitx@163.com; lushuihua66@126.comObjective: To analyze the clinical characteristics, species distribution and drug resistance of patients with non-tuberculous mycobacteria (NTM) lung disease in Qingdao, China.Methods: Clinical data of patients with NTM lung disease and pulmonary tuberculosis (TB) treated at Qingdao Chest Hospital from July 2021 to July 2023 were retrospectively analyzed.Results: The prevalence of NTM lung disease was 8.03%, with a high rate of drug resistance during the study period. Patients with NTM lung disease had higher rates of older age, bronchiectasis, malignancy, HIV infection and bronchial dilatation shadow and lower rates of hollow shadow compared to patients with pulmonary TB.Conclusion: Comprehensive understanding of NTM lung disease, improved laboratory testing techniques and appropriate treatment regimens are essential for the management of NTM lung disease.Keywords: non-tuberculous mycobacteria, pulmonary tuberculosis, clinical characteristics, drug resistance

Wenhao Chen,1 Yuanliang Liu,2 Xunwei Deng,3 Bin Li,1 Hao Wang,1 Guoliang Wei,1 Kehui Chen,1 Shen Wang1 1Center for Cardiovascular Diseases, Meizhou People’s Hospital, Meizhou, People’s Republic of China; 2Department of Computer Tomography, Meizhou People’s Hospital, Meizhou, People’s Republic of China; 3Research Experimental Center, Meizhou People’s Hospital, Meizhou, People’s Republic of ChinaCorrespondence: Wenhao Chen, Center for Cardiovascular Diseases, Meizhou People’s Hospital, Meizhou, People’s Republic of China, Email 18319255493@163.comObjective: Cytochrome P450 2C19 (CYP2C19) is a major enzyme involved in the biotransformation and metabolism of various substances. Loss-of-function of the CYP2C19 gene represents downregulation of CYP2C19 enzyme indication limited or no enzymatic function, which may be, in turn, associated with some disease susceptibility. The relationship between CYP2C19 polymorphisms and susceptibility to premature coronary artery disease (PCAD) is not fully understood. This study aimed to assess this relationship.Methods: This study included 635 PCAD patients, and 548 age-matched non-CAD individuals as controls, from November 2019 to August 2023. The CYP2C19 rs4244285 (681G > A, &ast;2) and rs4986893 (636G > A, &ast;3) were genotyped, and the distribution of CYP2C19 polymorphisms between patients and controls and the relationship between CYP2C19 polymorphisms and PCAD risk were analyzed.Results: A total of 442 (37.4%), 543 (45.9%), and 198 (16.7%) individuals had CYP2C19 extensive metabolizer (EM) (&ast;1/&ast;1), intermediate metabolizer (IM) (&ast;1/&ast;2 and &ast;1/&ast;3), and poor metabolizer (PM) (&ast;2/&ast;2, &ast;2/&ast;3, and &ast;3/&ast;3) phenotypes, respectively. CYP2C19 &ast;2/&ast;2 genotype frequency was higher, &ast;1/&ast;1 genotype was lower in PCAD patients than controls. Individuals with CYP2C19 PM phenotype had higher triglyceride (TG) levels than those with CYP2C19 EM or IM phenotypes. Logistic regression analysis showed that body mass index (BMI) ≥ 24.0 kg/m2 (≥ 24.0 kg/m2 vs 18.5– 23.9 kg/m2, odds ratio (OR): 1.326, 95% confidence interval (CI): 1.041– 1.688, p = 0.022), smoking (OR: 1.974, 95% CI: 1.283– 3.306, p = 0.002), hypertension (OR: 1.327, 95% CI: 1.044– 1.687, p = 0.021), diabetes mellitus (OR: 1.390, 95% CI: 1.054– 1.834, p = 0.020), CYP2C19 PM phenotype (PM phenotype vs EM phenotype, OR: 1.701, 95% CI: 1.200– 2.411, p = 0.003), and CYP2C19 IM+PM phenotypes (IM+PM vs EM phenotype, OR: 1.369, 95% CI: 1.077– 1.740, p = 0.010) were associated with PCAD.Conclusion: CYP2C19 PM or IM+PM phenotypes, overweight, smoking, hypertension, and diabetes mellitus were associated with PCAD.Keywords: premature coronary artery disease, cytochrome P450, CYP2C19, loss-of-function

Zijun Wu,1,&ast; Ruijing Wang,1,&ast; Yuanjun Liu,1 Bin Yang,2 Huiping Wang1 1Department of Dermatovenereology, Tianjin Medical University General Hospital/Tianjin Institute of Sexually Transmitted Disease, Tianjin, People’s Republic of China; 2Department of Burn and Plastic Surgery, General Hospital of Central Theater Command, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Yang, Department of Burn and Plastic Surgery, General Hospital of Central Theater Command, Wuhan, Hubei, People’s Republic of China, Email sszxkyb1@163.com Huiping Wang, Department of Dermatovenereology, Tianjin Medical University General Hospital/Tianjin Institute of Sexually Transmitted Disease, Tianjin, People’s Republic of China, Email huiping1208@163.comBackground: Psoriasis is characterized by accelerated proliferation of epidermal keratinocytes. IL-27 is relevant to psoriasis pathogenesis. We previously found that IL-27 stimulates the proliferation of keratinocytes. However, the mRNAs involved in the process have not been fully studied. This study aims to identify potential pathways and hub genes associated with proliferation in keratinocytes with IL-27 intervention by bioinformatics analysis.Methods: The mRNA expression profiles from HaCaT cells with or without IL-27 treated were analyzed by bioinformatics tools. The protein–protein interaction (PPI) network was constructed to screen gene clusters and hub genes associated with proliferation. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to identify the function of the mRNAs. The GEO database and quantitative real-time PCR (qPCR) were used to verify the expression levels of hub genes in psoriatic skin lesions and IL-27-treated psoriasiform keratinocytes, respectively.Results: We found 1257 differentially expressed genes and screened 2 crucial gene clusters. GO analysis revealed that Cluster 1 was mainly enriched in “Mitotic sister chromatid segregation” and “Spindle”. Cluster 2 was mainly enriched in the “Pyruvate metabolic process” and “Oxidoreductase complex”. KEGG analysis showed that Cluster 1 and Cluster 2 were mainly enriched in “Cell cycle” and “Glycolysis/Gluconeogenesis”, respectively. We then identified 6 hub genes enriched in the two pathways, including CCNB1, PTTG1, CDC20, PLK1, PKM, and LDHA. GSEA complemented the role of the mitochondrial “Oxidative phosphorylation” pathway. Moreover, we found that 6 hub genes were upregulated in psoriasis skin lesions and IL-27 elevated the hub genes expression in M5-induced psoriasiform keratinocytes.Conclusion: IL-27 possibly promotes glycolysis, mitochondrial oxidative phosphorylation, and cell cycle progression in keratinocytes. Additionally, we identified CCNB1, PTTG1, CDC20, PLK1, PKM, and LDHA as hub genes that may be involved in the mechanism of IL-27 facilitating keratinocyte proliferation in psoriasis.Keywords: psoriasis, glycolysis, oxidative phosphorylation, bioinformatics

Mingyi Li,1,&ast; Meng Jin,2,&ast; Hao Peng,3 Haitao Wang,1 Qian Shen,2 Lei Zhang1,4 1Department of Pulmonary and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 3Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 4Xianning Medical College, Hubei University of Science & Technology, Xianning, Hubei, 437000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Zhang, Department of Pulmonary and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China, Email zhl930223@qq.com Qian Shen, Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China, Email shenqianoncology@163.comAbstract: Lung cancer is the leading cause of mortality worldwide, and non-small cell lung cancer accounts for the majority of lung cancer cases. Chemotherapy and radiotherapy constitute the mainstays of lung cancer treatment; however, their associated side effects involving the kidneys, nervous system, gastrointestinal tract, and liver further add to dismal outcomes. The advent of antibody‒drug conjugates (ADCs) could change this situation. Trophoblast surface antigen 2 (TROP-2), a human trophoblast surface antigen, is a tumor-associated antigen that is expressed at low levels in normal tissues and is overexpressed in a variety of malignant tumors. The differential expression of the TROP-2 protein in a variety of tumors makes tumor immunotherapy with ADCs targeting TROP-2 a promising approach. Previous studies have shown that the expression of TROP-2 is related to the prognosis of patients with lung cancer and that TROP-2 expression is different across different histological types; however, research on TROP-2 and TROP-2 ADCs in patients with lung cancer is not comprehensive. The aims of this study were to review the mechanism of action and clinical efficacy of TROP-2 and related drugs in the treatment of lung cancer, to elucidate the prognostic value of TROP-2 in lung cancer, and to discuss the future prospects of TROP-2 ADCs to provide a reference for the precise treatment of lung cancer.Keywords: TROP-2, antibody‒drug conjugates, lung cancer

Haoyi Wang,&ast; Zhen Ni,&ast; Yinghao Chang Department of Infectious Disease, The General Hospital of Western Theater Command, Chengdu, 610083 People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yinghao Chang, Department of Infectious Disease, The General Hospital of Western Theater Command, Chengdu, 610083, People’s Republic of China, Email cyh19920913@126.comAbstract: Japanese spotted fever (JSF) is a neglected and potentially fatal infectious disease. Delays in diagnosis and treatment of JSF are important causes of poor prognosis. We report a case of JSF in a 75-year-old farmer who, following autumn field work in Sichuan, China, presented with an atypical triad of clinical symptoms: high fever, petechial rash, and notably no eschar. Without appropriate diagnosis and treatment, she developed septic shock and acute respiratory distress syndrome. The diagnosis of JSF was confirmed by the identification of Rickettsia japonica by metagenomic next-generation sequencing (mNGS) of the blood. After one week of treatment with doxycycline, the patient’s clinical symptoms subsided without any complaints of discomfort.Keywords: atypical triad of clinical symptoms of Japanese spotted fever, Rickettsia japonica, mNGS

Minjie Jiang,1,2 Yulong Yang,2 Haoyan Wang1 1Department of Respiratory and Critical Care Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, 100032, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Hebei Yanda Hospital, Langfang, Hebei, 065201, People’s Republic of ChinaCorrespondence: Haoyan Wang, Department of Respiratory and Critical Care Medicine, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong’an Road, Xicheng District, Beijing, 100032, People’s Republic of China, Email haoyanw@126.comBackground: More studies have focused on the clinical value of the measurement of the neutrophil-to-lymphocyte ratio (NLR) in acute exacerbations of chronic obstructive pulmonary disease (AECOPD). This study aims to assess the stability of NLR in hospitalized AECOPD patients and its relationship with clinical prognosis.Methods: This retrospective observational study recruited patients hospitalized with AECOPD from January 2020 to December 2023. Using receiver operating characteristic curves, we determined the optimal NLR cutoff, categorizing NLR stability into four groups: persistent high (NLR ≥ 3.8), increased (NLR < 3.8 at admission but ≥ 3.8 at discharge), decreased (NLR ≥ 3.8 at admission but < 3.8 at discharge), and persistent low (NLR < 3.8). Adverse hospital outcomes included hospital mortality, transfer to the intensive care unit (ICU), invasive mechanical ventilation (IMV), and length of hospital stay (LOS) ≥ 14 days. The associations between NLR stability and these outcomes were analyzed using multivariable logistic regression and Cox hazard analysis.Results: Among 841 patients hospitalized for AECOPD, the mean age was 72.1± 9.5 years, with 644 males (76.6%) and 197 females (23.4%). The proportions and distribution for groups: persistent high, decreased, increased, and persistent low groups were 109 (12.9%), 175 (20.8%), 216 (25.7%), and 341 (40.5%), respectively. The persistent high group had the worst outcomes, including higher IMV use, ICU transfer, LOS > 14 days, and hospital cost, compared to the persistent low group. Compared to the persistent high group, the persistent low group (HR: 0.13; 95% CI: 0.10– 0.24) and the decreased group (HR: 0.40; 95% CI: 0.22– 0.73) are statistically significant for the risk of death, while the increased group (HR: 0.63; 95% CI: 0.37– 1.04) does not show a statistically significant difference.Conclusion: AECOPD patients who have persistent low NLR group face a low risk of adverse hospital outcomes and mortality after 6 months after discharge. The stability of NLR may serve as a novel biomarker for identifying AECOPD patients at increased risk of poor hospital outcomes.Keywords: neutrophil-to-lymphocyte ratio, acute exacerbations of chronic obstructive pulmonary disease, outcomes

Guangtong Cao,1 Mingmin Ye,2 Haiyan Wang,3 Yi Liu,1,&ast; Mengzhi Li4,&ast; 1Department of Burns and Plastic Surgery & Wound Repair Surgery, Second Hospital of Lanzhou University, Lanzhou, Gansu, 730030 People’s Republic of China; 2Department of Plastic Surgery, Gansu Provincial Hospital, Lanzhou, Gansu, People’s Republic of China; 3Department of Ultrasound Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 4Department of Hand, Foot, and Microsurgical Reconstruction, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Liu; Mengzhi Li, Email liuyi196402@163.com; sweetlife00@163.comAbstract: Pathological scars, including hypertrophic scar and keloid are the result of excessive tissue repair and are influenced by biomechanical forces like tension, mechanical pressure, and stiffness. These forces significantly impact scar development and progression, affecting wound healing, collagen deposition, and tissue remodeling. Understanding how these mechanical stimuli contribute to scar development is essential for devising effective therapeutic interventions. Clinically, reducing wound tension and applying mechanical pressure are key strategies for managing pathological scars. Techniques like super-tension-reduction suturing, stress-shielding polymers, and force-modulating tissue bridges (FMTB) have been shown to effectively alleviate tension and reduce scar proliferation. Additionally, Pressure Garment Therapy (PGT) is widely used to treat hypertrophic scars by reducing tissue stiffness, limiting collagen buildup, and promoting collagen realignment. Despite challenges such as discomfort and uneven pressure application, ongoing research focuses on enhancing these therapies through mechanosensitive technologies to improve both efficacy and patient comfort. This review highlights the role of biomechanical forces in scar formation and discusses therapeutic approaches that target these forces to improve clinical outcomes.Keywords: pathological scars, biomechanical forces, hypertrophic scar, keloid, tissue remodeling

Yue Fang,1,2,&ast; Yi Yue,3,&ast; Sensen Hao,1 Ying Zhang,4 Nan Liu,1 Shengling Wang,1 Yan Li,1 Hongzhi Wang1 1Galactophore Oncology Center, Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei City, Anhui Province, People’s Republic of China; 2Science Island Branch, Graduate School of University of Science and Technology of China, Hefei City, Anhui Province, People’s Republic of China; 3The Second Clinical College, Anhui Medical University, Hefei City, Anhui Province, People’s Republic of China; 4Department of Pathology, First Affiliated Hospital of Anhui Medical University, Hefei City, Anhui Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongzhi Wang, Email wanghz@hfcas.ac.cnBackground: Serpin B9 is highly expressed in breast cancer, melanoma, and various malignant cells and inhibits NK cell killing through the Serpin B9-GrB axle. However, the current studies have only validated the role of Serpin B9 in vivo and vitro, and lack of systematic studies on the expression of Serpin B9 in patients’ tumor tissues and its prognostic implications. In this study, we propose to further validate the role of Serpin B9 by comparing its expression level in tissues of lung adenocarcinoma patients and its correlation with the efficacy of immunotherapy.Methods: This study included 200 patients with LUAD between Feb 2022 and Feb 2023. IHC scoring assessed Serpin B9 expression in the tumor and adjacent tissues, with an H-score of 2 as the cutoff value. Patients were divided into high- and low-expression groups. T-tests were used to compare Serpin B9 expression and treatment efficacy between the tumor and adjacent tissues in both groups. Baseline characteristics were compared using X2 tests. Prognostic risk factors were identified using Cox regression and Kaplan-Meier survival curves.Results: The expression level of Serpin B9 in LUAD tumor tissues are higher than adjacent tissues and positively correlated with the TNM stage and negative correlated with PFS in patients with LUAD. Additionally, immunotherapy efficacy was inversely correlated with Serpin B9 expression.Conclusion: The increased expression of Serpin B9 in LUAD tumor tissues is negatively linked to prognosis and immunotherapy efficacy. This underscores their potential as prognostic and therapeutic targets.Keywords: serine proteinase inhibitor B9, lung adenocarcinoma, progression free survival, PD-1/PD-L1