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Siwei Xia, Xiaoyan Gu, Gaojian Wang, Yizhi Zhong, Fengjie Ma, Qinxue Liu, Junran Xie Department of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of ChinaCorrespondence: Junran Xie, Department of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China, Email xiejunran@zju.edu.cnAbstract: Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a common and serious clinical lung disease characterized by extensive alveolar damage and inflammation leading to impaired gas exchange. Alveolar macrophages (AMs) maintain homeostatic properties and immune defenses in lung tissues. Several studies have reported that AMs are involved in and regulate ALI/ARDS onset and progression via different regulated cell death (RCD) programs, such as pyroptosis, apoptosis, autophagic cell death, and necroptosis. Notably, the effects of RCD in AMs in disease are complex and variable depending on the environment and stimuli. In this review, we provide a comprehensive perspective on how regulated AMs death impacts on ALI/ARDS and assess its potential in new therapeutic development. Additionally, we describe the crosstalk between different RCD types in ALI, and provide new perspectives for the treatment of ALI/ARDS and other severe lung diseases.Keywords: alveolar macrophage, apoptosis, autophagic cell death, necroptosis, pyroptosis, acute lung injury

Manjia Zheng,1 Ziwei Chen,1 Jiling Xie,1 Qiyuan Yang,1 Minhua Mo,1 Jia Liu,2 Liangjiao Chen1 1Department of Orthodontics, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction & Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Stomatological Hospital, Southern Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Jia Liu, Stomatological Hospital, Southern Medical University, No. 366 jiangnan Road South, Guangzhou, Guangdong, 510280, People’s Republic of China, Email liujia1988@smu.edu.cn Liangjiao Chen, Department of Orthodontics, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction & Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, No. 31 huangsha Road, Guangzhou, Guangdong, 510145, People’s Republic of China, Email 2010686017@gzhmu.edu.cnAbstract: Silica nanoparticles (SiNPs) are widely used in biomedical fields, such as drug delivery, disease diagnosis, and molecular imaging. An increasing number of consumer products containing SiNPs are being used without supervision, and the toxicity of SiNPs to the human body is becoming a major problem. SiNPs contact the human body in various ways and cause damage to the structure and function of genetic material, potentially leading to carcinogenesis, teratogenicity and infertility. This review summarizes SiNPs-induced genetic and epigenetic toxicity, especially to germ cells, and explore their potential mechanisms. SiNPs cause genetic material damage mainly by inducing oxidative stress. Furtherly, the molecular mechanisms of epigenetic toxicity are discussed in detail for the first time. SiNPs alter DNA methylation, miRNA expression, histone modification and inhibit chromatin remodeling by regulating epigenetic-related enzymes and transcription factors. This review is beneficial for investigating potential solutions to avoid toxicity and provide guidance for better application of SiNPs in the biomedical field.Keywords: silica nanoparticles, genotoxicity, epigenetic, DNA damage, germ cells

Xinqia Huang,1,* Ziquan Zhao,1,* Weiqiang Zhan,1 Mingzhu Deng,1 Xuyang Wu,1 Zhoutao Chen,1 Jiahao Xie,2 Wei Ye,3 Mingyan Zhao,1,4 Jiaqi Chu3,4 1Orthopaedic Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524001, People’s Republic of China; 2Department of Dermatology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524001, People’s Republic of China; 3Department of Obstetrics and Gynecology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524001, People’s Republic of China; 4Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jiaqi Chu; Mingyan Zhao, Affiliated Hospital of Guangdong Medical University, No. 57 Renmin Avenue South Road, Zhanjiang, Guangdong, 524001, People’s Republic of China, Email chujiaqi@gdmu.edu.cn; mingyan.zhao@gdmu.edu.cnPurpose: To investigate the osteogenic potential of human embryonic stem cell-derived exosomes (hESC-Exos) and their effects on the differentiation of human umbilical cord mesenchymal stem cells (hUCMSCs).Methods: hESC-Exos were isolated and characterized using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting. hUCMSCs were cultured with hESC-Exos to assess osteogenic differentiation through alizarin red staining, quantitative PCR (qPCR), and Western blotting. miRNA profiling of hESC-Exos was performed using miRNA microarray analysis. In vivo bone regeneration was evaluated using an ovariectomized rat model with bone defects treated with exosome-loaded scaffolds.Results: hESC-Exos significantly promoted the osteogenic differentiation of hUCMSCs, as evidenced by increased alizarin red staining and the upregulation of osteogenesis-related genes and proteins (ALP, RUNX2, OCN). miRNA analysis revealed that miR-21-5p is a key regulator that targets YAP1 and activates the Wnt/β-catenin signaling pathway. In vivo, hESC-Exos enhanced bone repair in ovariectomized rats, as demonstrated by increased bone mineral density and improved bone microarchitecture compared to those in controls.Conclusion: hESC-Exos exhibit significant osteogenic potential by promoting the differentiation of hUCMSCs and enhancing bone regeneration in vivo. This study revealed that the miR-21-5p-YAP1/β-catenin axis is a critical pathway, suggesting that the use of hESC-Exos is a promising therapeutic strategy for bone regeneration and repair. Keywords: human embryonic stem cells, exosomes, osteogenic differentiation, bone regeneration, miR-21-5p, YAP1

Runcong Zhang,1,2,* Jing Fan,1,2,* Lu Han,3,4,* Juehui Mao,4,5 Liang Sun,1,2 Yuetian Yu,2,6,7 Weibin Fan,1,2 Jiao Xie,2,8 Bin Lin,1,2,7 Nengming Lin1,2,9 1Department of Pharmacy, Changxing People’s Hospital, Changxing, People’s Republic of China; 2Key Laboratory of Intelligent Pharmacy and Individualized Therapy of Huzhou, Changxing, People’s Republic of China; 3School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 4Department of Pharmacy, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 5School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China; 6Department of Critical Care Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 7Key Laboratory of Multiple Organ Failure (Zhejiang University), Ministry of Education, Hangzhou, People’s Republic of China; 8Department of Pharmacy, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 9Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bin Lin, Department of Pharmacy, Changxing People’s Hospital, Changxing, 313100, People’s Republic of China, Tel/Fax +86-572-6267652, Email lb_wzmc@126.com Nengming Lin, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou, 310006, People’s Republic of China, Tel/Fax +86-572- 56007905, Email lnm1013@zju.edu.cnPurpose: Nirmatrelvir/ritonavir (N/R) is the first drug to receive emergency authorization for the treatment of COVID-19 infection. We aimed to develop a population pharmacokinetic (PopPK) model to evaluate the effects of potential covariates and explore dosing regimen.Patients and Methods: Sparse data of serum concentrations of N/R were obtained from 129 patients with COVID-19 infection receiving oral 300/100 mg N/R twice daily for 5 days. Plasma samples were assayed using ultra-high-performance liquid chromatography–tandem mass spectrometry. The PopPK model was developed using a nonlinear mixed effects approach utilizing the NONMEM 7.4 software. Monte Carlo simulation was conducted to optimize the dosage regimen.Results: A one-compartment model with first-order absorption and first-order elimination provided the best fit for the data. Allometric scaling of parameters on creatinine clearance (CrCl) and body weight were identified as covariates that significantly influenced exposure-efficacy after oral administration of nirmatrelvir. Monte Carlo simulation using the final model generated concentration-time profiles for virtual patients (1,000 per group) with varying renal functions and body weight. Furthermore, we developed a web-based dashboard to visualize the dynamic changes in nirmatrelvir concentration and provide individualized dosage regimens.Conclusion: This study showed that dosing regimen optimization of nirmatrelvir should be based on CrCl and body weight. Moreover, a web-based dashboard has been developed to facilitate individualized pharmacotherapy.Keywords: population pharmacokinetics, nirmatrelvir, COVID-19, simulations, dosing regimen

Liang Chen,1,* Xiaomei Ying,2,* Haohao Wang,1,* Jiaheng Xie,3,* 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*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

The solenoidal large intensity device (SoLID) is a new experimental apparatus planned for Hall A at the Thomas Jefferson National Accelerator Facility (JLab). SoLID will combine large angular and momentum acceptance with the capability to handle very high data rates at high luminosity. With a slate of approved high-impact physics experiments, SoLID will push JLab to a new limit at the QCD intensity frontier that will exploit the full potential of its 12 GeV electron beam. In this paper, we present an overview of the rich physics program that can be realized with SoLID, which encompasses the tomography of the nucleon in 3D momentum space from semi-inclusive deep inelastic scattering, expanding the phase space in the search for new physics and novel hadronic effects in parity-violating DIS, a precision measurement of J/ψ production at threshold that probes the gluon field and its contribution to the proton mass, tomography of the nucleon in combined coordinate and momentum space with deep exclusive reactions, and more. To meet the challenging requirements, the design of SoLID described here takes full advantage of recent progress in detector, data acquisition and computing technologies. In addition, we outline potential experiments beyond the currently approved program and discuss the physics that could be explored should upgrades of CEBAF become a reality in the future.

Yongqiang Xiao,1– 3,&ast; Wanqing Chen,4,&ast; Wei Deng,1,&ast; Guoqing Zhu,1 Jin Xie,1 Laihui Luo,1 Liucong Lin,1 Jiahao Tao,1 Zhigao Hu,1 Renfeng Shan1 1Department of General Surgery, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of General Surgery, Ganjiang New Area People’s Hospital, Nanchang, Jiangxi, People’s Republic of China; 3Department of General Surgery, Ganjiang New Area Hospital of the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 4Department of Gastroenterology, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhigao Hu; Renfeng Shan, Department of General Surgery, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 17, Yongwaizheng Street, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel/Fax +86-791-88692522, Email 854189568@qq.com; srf1978@126.comPurpose: This study aimed to assess the prognostic significance of alpha-fetoprotein (AFP) response in patients with unresectable hepatocellular carcinoma (u-HCC) who underwent hepatic artery infusion chemotherapy (HAIC) combined with lenvatinib and camrelizumab.Methods: A retrospective review was conducted on patients with u-HCC receiving treatment with HAIC combined with lenvatinib and camrelizumab. Early AFP response was defined as a > 20% decrease in AFP within 4 weeks, and AFP response as a > 75% decrease in AFP within 8 weeks. The correlation between early AFP response, AFP response, therapeutic response, overall survival (OS), and progression-free survival (PFS) was investigated.Results: The study included 63 patients. AFP responders exhibited superior objective response rates compared to AFP non-responders, as determined by RECIST v1.1 or mRECIST criteria (45.5 vs. 18.2%, p=0.014, or 81.8 vs. 48.5%, p=0.013). Furthermore, early AFP responders demonstrated prolonged OS (not reached vs. 8.0 months, p< 0.001) and PFS (13.3 vs. 3.0 months, p= 0.018) relative to early AFP non-responders. Similarly, AFP responders exhibited improved OS (not reached vs. 9.0 months, p< 0.001) and PFS (19.3 vs. 5.1 months, p=0.002) compared to AFP non-responders. Multivariate analysis results indicated that both early AFP response and AFP response independently predicted OS [hazard ratio (HR) 2.963, 95% confidence interval (CI) 1.333– 6.585, p=0.008, and HR 6.182, 95% CI 1.780– 21.466, p=0.004] and PFS (HR 2.186, 95% CI 1.107– 4.318, p=0.024, and HR 3.078, 95% CI 1.407– 6.730, p=0.005), serving as significant prognostic values.Conclusion: Early AFP response and AFP response serve as predictive biomarkers for the effectiveness of HAIC combined with lenvatinib and camrelizumab in patients with u-HCC.Keywords: unresectable hepatocellular carcinoma, alpha-fetoprotein, hepatic arterial infusion chemotherapy, lenvatinib, camrelizumab

Bo Jiang,1 Dong Lu,2 Jiaying Dai,3 Kunfeng Li,4 Qianqian Du,1 Bo Xie,5 Jun Xie,6 Xianhai Zhu,2 Xiang Xie1 1Department of Interventional Ultrasound, The Second Affiliated Hospital, Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China; 2Department of Interventional Radiology, The First Affiliated Hospital of USTC, Division of Life Sciences & Medicine, University of Science & Technology of China, Hefei, 230001, People’s Republic of China; 3Department of Interventional Radiology, Anqing Municipal Hospital, Anqing, Anhui, 246000, People’s Republic of China; 4Department of Radiology, Tongling People’s Hospital, Tongling, Anhui, 244300, People’s Republic of China; 5Department of Interventional Radiology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, 233000, People’s Republic of China; 6Department of Radiology, Fuyang People’s Hospital, Fuyang, Anhui, 236600, People’s Republic of ChinaCorrespondence: Xiang Xie, Department of Interventional Ultrasound, The Second Affiliated Hospital, Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China, Email 15956922618@163.comObjective: To develop a simple and effective prognostic scoring system to predict the efficacy of drug-eluting bead-transcatheter arterial chemoembolization (DEB-TACE) in the treatment of hepatocellular carcinoma (HCC).Methods: Data were retrospectively collected from 230 patients with HCC who received DEB-TACE treatment at six medical centers between January 2019 and December 2022. We developed a predictive score based on independent risk factors for overall survival (OS), validated the model using a validation cohort, and compared its prognostic accuracy with commonly used HCC staging systems.Results: The number of tumors, albumin-bilirubin levels, alpha-fetoprotein levels, and portal vein thrombus grade were identified as independent factors influencing OS. Based on these factors, we established the DEB-TACE treatment of HCC (DTH) scoring system. The DTH score correlated well with OS, which decreased as the DTH score increased. According to the DTH score, patients were categorized into three risk groups: low-risk (DTH-A, 0– 4 points), medium-risk (DTH-B, 5– 6 points), and high-risk (DTH-A, 7 points). The OS of each risk group was 18.73± 0.62 months, 12.73± 0.10 months, and 6.93± 0.19 months, respectively (p< 0.001). The external cohort validation confirmed the accuracy of the DTH score, demonstrating superior predictive performance compared to other commonly used HCC scoring systems.Conclusion: The DTH-HCC scoring system effectively predicts the outcomes of HCC patients undergoing DEB-TACE as initial treatment. This model can aid in the initial planning and decision-making process for DEB-TACE treatment in HCC patients.Keywords: hepatocellular carcinoma, transcatheter arterial chemoembolization, prognosis prediction model

Yadong Sun,1 Yanjie Shan,1 Jiaqiong Xie,1 Ke Chen,1 Jia Hu2 1Faculty of Social Sciences, Chongqing University, Chongqing, People’s Republic of China; 2Institute for Advanced Studies in Humanities and Social Science, Chongqing University, Chongqing, People’s Republic of ChinaCorrespondence: Ke Chen; Jia Hu, Chongqing University, Shapingba, Chongqing, People’s Republic of China, 400044, Tel +86-13628362626, Email chenke197729@163.com; hujia827@cqu.edu.cnPurpose: With the development of information technology and various social media, recommendation algorithms have increasingly more influence on users’ social media usage. To date, there has been limited research focused on analyzing the impact of recommendation algorithms on social media use and their corresponding role in the development of problematic behaviors. The present study analyzes the impact of recommendation algorithms on college students’ information sharing and internalizing, externalizing problem behaviors to address the aforementioned shortcomings.Methods: An online questionnaire survey was conducted among 34,752 college students in China. A latent profile analysis was conducted to explore the various behavioral patterns of Chinese college students’ information sharing across the three social media platforms identified for this study. The Bolck–Croon–Hagenaars (BCH) method Regression Mixture Modeling was then used to analyze the differences in internalizing and externalizing problem behaviors among the different subgroups of Chinese college students.Results: The level of information sharing by college students across different social media platforms could be divided into “WeChat Moments low-frequency information sharing”, “middle-frequency comprehensive information sharing”, “TikTok high-frequency information sharing”, and “Sina Weibo high-frequency information sharing”. Significant differences were observed regarding internalizing and externalizing problem behaviors among college students in different information-sharing subgroups.Conclusion: This study identified four subgroups with different information-sharing characteristics using latent profile analysis. Among them, college students who are in subgroup of social media information sharing influenced by recommendation algorithms exhibit higher frequency of information sharing and higher level of internalizing and externalizing problematic behaviors. These results expand our understanding of college students’ social media usage and problem behaviors from a technological perspective. In future, the negative impacts of recommendation algorithms on college students can be reduced by improving their awareness of these algorithms and optimizing the algorithms themselves.Keywords: user-generated content, recommendation algorithms, latent profile analysis, internalizing problem behaviors, externalizing problem behaviors

Qingxiang Liu,1,&ast; Fei Peng,1,&ast; Haitao Liu,2,&ast; Qin Sun,1 Hui Chen,1 Xinyi Xu,1 Zihan Hu,1 Xing Zhou,1 Kai Jin,1 Jianfeng Xie,1 Yingzi Huang,1 Wei Huang,1 Yi Yang1 1Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, People’s Republic of China; 2School of Life Science, Fudan University, Shanghai, 200000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Huang; Yi Yang, Email whuang@seu.edu.cn; yiyiyang2004@163.comBackground: Natural killer (NK) cells are key regulators of immune defense in sepsis-induced acute respiratory distress syndrome (ARDS), yet the characteristics of NK cell clusters in ARDS remain poorly understood.Methods: A prospective and observational study enrolled septic patients with ARDS or not was conducted to determine the percentage of NK cells via flow cytometry. The transcriptomes of peripheral blood mononuclear cells (PBMCs) from healthy controls, patients with sepsis only, and patients with sepsis-induced ARDS were profiled. Vitro experiments were performed to confirm the mechanism mediating MX1+NK cell infiltration.Results: A total of 115 septic patients were analyzed, among whom 63 patients developed ARDS and 52 patients did not. Decreased NK percentages were found in sepsis with ARDS patients (%, 7.46± 4.40 vs 11.65± 6.88, P=0.0001) compared with sepsis-only patients. A lower percentage of NK cells showed a significant increase in 28-day mortality. Single-cell sequencing analysis revealed distinct characteristics of NK cells in sepsis-induced ARDS, notably the identification of a unique cluster defined as MX1+NK cells. Flow cytometry analysis showed an elevated percentage of MX1+NK cells specifically in individuals with sepsis-induced ARDS, compared with patients with sepsis only. Pseudo-time analysis showed that MX1+NK cells were characterized by upregulation of type I interferon-induced genes and other pro-inflammatory genes. MX1+NK cells can respond to type I interferons and secrete type I interferons themselves. Ligand–receptor interaction analysis also revealed extensive interaction between MX1+NK cells and T/B cells, leading to an uncontrolled inflammatory response in ARDS.Conclusion: MX1+NK cells can respond to type I interferons and secrete type I interferons themselves, promoting the development of sepsis-induced ARDS. Interfering with the infiltration of MX1+NK cells could be a therapeutic approach for this disease. Due to the limited sample size, a larger sample size was needed for further exploration.Keywords: ARDS, inflammation, natural killer cells, sepsis

Rui Zhou,1,2,&ast; Lijuan Fu,2,&ast; Shu Liu,2,&ast; Sanjie Gao,2 Zhifu Zhao,2 Wencai Jiang,2 Li Liu,2 Weiqiao Ren,2 Dongmei Xiang,2 Xing You,2 Chunyong Tang,2 Yukai Zhou,2 Yanqing Song,2 Juan Xie,2 Li Xie,2 Ru Yu,2 Xianjie Zhang,2 Dan Zhou,2 Jia Han,2 Leqiang Xia,2 Lize Xiong1 1Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Translational Research Institute of Brain and Brain-Like Intelligence, Clinical Research Center for Anesthesiology and Perioperative Medicine, Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200434, People’s Republic of China; 2Department of Anesthesiology, Deyang People’s Hospital, Deyang, 618000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Leqiang Xia, Department of Anesthesiology, Deyang People’s Hospital, No. 173, Section 1, North Taishan Road, Deyang, Sichuan, 618000, People’s Republic of China, Tel +8613547098458, Email xialq123184@163.com Lize Xiong, Shanghai Fourth People’s Hospital, No. 1279, Sanmen Road, Shanghai, 200434, People’s Republic of China, Tel +86-21-55603002, Fax +86-21-56660851, Email mzkxlz@126.com; lizexiong@tongji.edu.cnPurpose: To compare the influences of propofol, ciprofol and remimazolam on dreaming during painless gastrointestinal endoscopy.Methods: This study was a single-center, prospective, parallel-design, double-blind, randomized clinical trial. Between May 2023 and October 2023, patients undergoing elective painless gastrointestinal endoscopy were recruited and randomly allocated into one of the three groups. Demographic data, intraoperative information, incidence of dreaming, insufficient anesthesia and intraoperative awareness, type of dream, patient satisfaction score, adverse events, and improvement of sleep quality were collected.Results: The difference in incidence of dreaming among the three groups was not significant (33.33% vs 48.33% vs 41.67%, p=0.061). The number of patients with intraoperative hypotension in the propofol group was larger than that of the remimazolam group (32 vs 12, p=0.001). However, the cases of intraoperative hypotension between propofol group and ciprofol group or ciprofol group and remimazolam group were comparable (32 vs 22, p=0.122; 22 vs 12, p=0.064). The percentage of insufficient anesthesia between propofol group and remimazolam group was significant (13.33% vs 1.67%, p=0.001), while no statistical difference was detected between propofol group and remimazolam group or ciprofol group and remimazolam group (13.33% vs 5.00%, p=0.025; 5.00% vs 1.67%, p=0.150). The ability of propofol to improve sleep quality at 1st post-examination day was significantly better than that of remimazolam (86.21% vs 72.88%, p=0.015), while it was not significant between propofol group and ciprofol group or ciprofol group and remimazolam group (86.21% vs 80.36%, p=0.236; 72.88% vs. 72.88%, p=0.181). Incidence of intraoperative awareness, intraoperative hypoxia, type of dream, satisfaction score, adverse events during recovery, and sleep improvement on the 7th post-examination day was not significant among the groups.Conclusion: Anesthesia with propofol, ciprofol and remimazolam, respectively, for gastrointestinal endoscopy did not induce statistical difference in the incidence of dreaming, despite that all of them are more likely to induce pleasant dreams.Keywords: propofol, ciprofol, remimazolam, endoscopic sedation, dreaming

Chaoping Yang,1,&ast; Jing Xie,2,&ast; Qianjun Chen,2 Qiongyin Yuan,3 Jianping Shang,4 Haibo Wu,5 Youhua Yang,6 Mingfang Wang,7 Xiaolan Shu,8 Jing Yue,9 Danna Tu,10 Ying Lin,1,&ast; Ronghao Zheng,4,&ast; Xiaolin Wu4 1Nursing Department, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Pediatric Nephrology, Rheumatology, and Immunology, Maternal and Child Health Hospital of Hubei Province, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of China; 3Obstetrical department, Huanggang Maternal and Child Health Hospital, Hubei, People’s Republic of China; 4Department of Pediatric Nephrology, Rheumatology, and Immunology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 5School of Health and Nursing, Wuchang University of Technology, Wuhan, People’s Republic of China; 6Department of Basic Medical Sciences, School of Medicine, Jianghan University, Wuhan, People’s Republic of China; 7Department of Pediatric Gastroenterology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 8Department of Pediatric Intensive Care Unit (PICU), Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 9Emergency Department, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 10Department of Pediatric Cardiology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ronghao Zheng, Department of Pediatric Nephrology, Rheumatology, and Immunology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, 745 Wu Luo Road, Hongshan District, Wuhan, Hubei Province, 430070, People’s Republic of China, Email hytwo2001@126.com Ying Lin, Nursing department, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China, Email 523933025@qq.comPurpose: The knowledge, attitude, and practices (KAP) concerning antibiotics by healthcare students have the potential impact on controlling antibiotic abuse and antimicrobial resistance (AMR) growth. This study aims to evaluate the levels and explore the associated factors with KAP on antibiotic use and AMR in Chinese nursing students.Methods: A cross-sectional survey using a self-administered questionnaire consisting of demographics and selected features and KAP on antibiotic use and AMR was conducted to measure KAP levels among nursing students at various universities in Hubei Province, China. The logistic regression analyses were performed to analyze the potential factors associated with the KAP.Results: The survey eventually included a total of 1959 nursing students. The mean scores for KAP were 57.89 ± 26.32, 55.00 ± 12.50, and 71.88 ± 15.63, respectively. Regarding knowledge, 54.3% of participants were unaware that antibiotic was ineffective against viral infections. Regarding attitude, 36% of participants agreed that current antibiotic abuse existed; 96.2% of participants thought it necessary to set up a special course on antibiotics. Regarding practice, only 48.4% of participants usually purchased antibiotics with a prescription. Multivariable analyses indicated that lack of discussion on AMR in school courses was an independent risk factor against KAP, respectively. The main knowledge sources of antibiotic being outside the classroom was an independent risk factor related to knowledge and practice. The average score > 80 points was an independent protective factor related to knowledge and practice.Conclusion: The KAP level on antibiotic use and AMR among Hubei nursing students was general and required further strengthening. Nursing students with risk factors should be prioritized in educational interventions. The findings of our study pointed out some directions for tailored interventions to improve the training on antibiotics.Keywords: antibiotic use, antimicrobial resistance, knowledge, attitude, practice, nursing students

Xiaojie Chen,1,2 Jianteng Xie,2 Yifan Zhang,2 Shaogui Zhang,2 Sheng Li,2 Min Lu,2 Danfeng Liu,2 Weiting He,2 Hokhim Yau,2 Runli Jia,2 Yaxi Zhu,2 Wenjian Wang2 1Department of Nephrology, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, Guangdong, People’s Republic of China; 2Department of Nephrology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangdong, People’s Republic of ChinaCorrespondence: Wenjian Wang, Department of Nephrology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, 106 Zhongshan Er Road, Main Building, Room 1436, Guangzhou, Guangdong, 510080, People’s Republic of China, Tel +86 (20)83827812-61421, Email wangwenjian@gdph.org.cnObjective: Diabetic kidney disease (DKD) patients with anemia face an elevated risk of glomerular filtration rate decline. However, the association between hemoglobin and estimated Glomerular Filtration Rate (eGFR) progression remains to be elucidated.Methods: A retrospective cohort of 815 subjects with DKD was followed from January 2010 to January 2023. A Cox proportional hazard regression model was utilized to explore the predictive role of hemoglobin in renal outcomes. Renal outcomes were defined as a composite endpoint, including a 50% decline in eGFR from baseline or progression to End-Stage Renal Disease (ESRD). To unveil any nonlinear relationship between hemoglobin and renal outcomes, Cox proportional hazard regression with cubic spline functions and smooth curve fitting was conducted. Additionally, subgroup analyses were performed to identify specific patient populations that might derive greater benefits from higher hemoglobin.Results: Among the 815 DKD subjects, the mean age was 56.482 ± 9.924 years old, and 533 (65.4%) were male. The mean hemoglobin was 121.521± 22.960 g/L. The median follow-up time was 21.103± 18.335 months. A total of 182 (22.33%) individuals reached the renal composite endpoint during the study period. After adjusting for covariates, hemoglobin was found to exert a negative impact on the renal composite endpoint in patients with DKD (HR 0.975, 95% CI [0.966, 0.984]). A nonlinear relationship between hemoglobin and the renal composite endpoint was identified with an inflection point at 109 g/L. Subgroup analysis unveiled a more pronounced association between hemoglobin and renal prognosis in males.Conclusion: Hemoglobin emerges as a predictive indicator for the renal prognosis of diabetic kidney disease in China. This study reveals a negative and non-linear relationship between hemoglobin levels and the renal composite endpoint. A substantial association is noted when hemoglobin surpasses 109 g/L in relation to the renal composite endpoint.Keywords: hemoglobin, eGFR decline, ESRD, diabetic kidney disease, non-linear, Cox proportional-hazards regression

Yushan Xu, Miaomiao Li, Mengjiao Lin, Dawei Cui, Jue Xie Department of Blood Transfusion, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, People’s Republic of ChinaCorrespondence: Jue Xie; Dawei Cui, Tel +86571-87236391 ; +86571-87236390, Email zyyyxj2011@zju.edu.cn; daweicui@zju.edu.cnAbstract: CD4+ T cells play a critical role in the pathogenesis of viral diseases, which are activated by the internal metabolic pathways encountering with viral antigens. Glutaminolysis converts glutamine into tricarboxylic acid (TCA) circulating metabolites by α-ketoglutaric acid, which is essential for the proliferation and differentiation of CD4+ T cells and plays a central role in providing the energy and structural components needed for viral replication after the virus hijacks the host cell. Changes in glutaminolysis in CD4+ T cells are accompanied by changes in the viral status of the host cell due to competition for glutamine between immune cells and host cells. More recently, attempts have been made to treat tumours, autoimmune diseases, and viral diseases by altering the breakdown of glutamine in T cells. In this review, we will discuss the current knowledge of glutaminolysis in the CD4+ T cell subsets from viral diseases, not only increasing our understanding of immunometabolism but also providing a new perspective for therapeutic target in viral diseases.Keywords: CD4+ T cells, viral diseases, glutamine, glutaminolysis, immune response

Linqi Zhou,1 Changyuan Qiao,1 Jialing Huang,2 Jian Lin,2 Haisheng Zhang,2 Jian Xie,2 Yonggui Yuan,3 Changchun Hu2 1School of the Fourth Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2Department of Clinical Psychology, Affiliated Hangzhou First People’s Hospital, Westlake University School of Medicine, Hangzhou, People’s Republic of China; 3Department of Psychosomatics and Psychiatry, Zhong Da Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of ChinaCorrespondence: Changchun Hu, Department of Clinical Psychology, Affiliated Hangzhou First People’s Hospital, Westlake University School of Medicine, No. 261 Huansha Road, Shangcheng District, Hangzhou, 310002, People’s Republic of China, Tel +86-571-56006902, Email chuntianjs@163.comBackground: Previous studies have demonstrated a strong association between recent stressful life events and non-suicidal self-injury (NSSI) among adolescents. Internalizing symptoms and difficulty in emotion regulation (DER) may mediate this relationship. This study aimed to investigate the relationship between recent stressful life events and NSSI severity in adolescents and the potential moderating role of internalizing symptoms and DER.Methods: A total of 224 adolescent inpatients (78.6% female) participated in the study, with an age range of 12– 18 years old. Data on recent stressful life events, internalizing symptoms, DER, and NSSI behaviors were collected using a clinician-rated questionnaire. A structural equation model was used to test the hypothesized model.Results: The rate of NSSI reporting among adolescents in the past 12 months was 65.18%. Recent stressful life events were found to be directly associated with NSSI severity (β = 0.128, P = 0.023). A chain-mediating effect between recent stressful life events and NSSI was also confirmed (β = 0.034, P = 0.023), with DER and internalizing symptoms playing a chain-mediating role and DER having a significantly indirect association with NSSI through internalizing symptoms.Conclusion: Recent stressful life events appear to play a role in the etiology of NSSI, particularly punishment and interpersonal relationship events that warrant special attention. DER and internalizing symptoms play a chain-mediating role in the relationship between life events and NSSI. Reducing recent stressful life events, screening for internalizing symptoms, and improving emotion regulation may decrease NSSI behavior among adolescents.Keywords: non-suicidal self-injury, adolescents, recent stressful life events, internalizing symptoms, difficulty in emotion regulation, structural equation model

Yun Zhao,1,&ast; Lijun Zhao,1,&ast; Zhaohuang Wang,1 Shuhui Cui,1 Chenchen Ren,2 Li Yang,2 Yang Bai,2 Yuanhang Zhu,2 Jingyan Xie,3 Yujuan Li,3 Xiaoqing Wu,3 Jing Feng,3 Shanqing Man,4 Longmei Huang,4 Xiaoqi Li,4 Xiaotian Yu,4 Jianliu Wang1 1Department of Obstetrics and Gynecology, Peking University People’s Hospital, Beijing, People’s Republic of China; 2Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, National Clinical Research Center for Obstetrics and Gynecology, Zhengzhou Key Laboratory of Cervical Disease, Zhengzhou Key Laboratory of Endometrial Disease Prevention and Treatment, Zhengzhou, Henan, People’s Republic of China; 3Department of Obstetrics and Gynecology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 4Hangzhou New Horizon Health Technology Co. Ltd, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianliu Wang, Department of Obstetrics and Gynecology, Peking University People’s Hospital, 11 Xizhimen South Street, Xicheng District, Beijing, 100044, People’s Republic of China, Tel +8618901086568, Email wangjianliu1203@163.comObjective: The objective of this study is to assess the clinical performance of a urine-based high-risk human papillomavirus (hrHPV) test for the detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+).Methods: Between September and December 2021, women aged 20 to 65 years referred to colposcopy clinic were prospectively recruited at three clinical centers in China. Paired urine and cervical specimens from all enrolled women were obtained for hrHPV DNA fluorescence quantitative PCR test. The results of liquid-based cytology (LBC), colposcopy and diagnostic biopsies were collected. We evaluated the sensitivity and specificity for CIN and assessed the agreement/kappa value.Results: A total of 732 women (median age, 40 years) with valid results were included in the study, and 130 (17.8%) women were histologically confirmed as CIN2+. The sensitivity of urine and cervical test for CIN2+ and CIN3+ were 87.69% and 85.45%, respectively. The specificity of urine test performed better than cervical test in women with

Junhui He,1,&ast; Jiaxiu Xie,1,&ast; Guili Zhou,2,&ast; Chunlian Jia,2 Dongbo Han,2 Dongmei Li,1 Jie Wei,1 Yi Li,1 Renshan Huang,1 Chunlian Li,1 Bo Wang,3 Chao Wei,3 Qibiao Su,4 Kedao Lai,1 Guining Wei1 1Department of Pharmacology, Key Laboratory of Quality Standards, Guangxi Institute of Chinese Medicine & Pharmaceutical Science, Nanning, 530022, People’s Republic of China; 2Department of Pharmacology, Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 3Guangxi Shuangyi Pharmaceutical Co., Ltd, Nanning, Guangxi, 530021, People’s Republic of China; 4College of Health Science, Guangdong Pharmaceutical University, Guangzhou, 510006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guining Wei, Department of Pharmacology, Guangxi Institute of Chinese Medicine & Pharmaceutical Science, Nanning, 530022, People’s Republic of China, Email weiguining2013@163.com Qibiao Su, College of Health Science, Guangdong Pharmaceutical University, Guangzhou, 510006, People’s Republic of China, Tel +8618376664440, Email suqibiao@163.comPurpose: Neuroinflammation is a significant etiological factor in the development of depression. Traditional Chinese medicine (TCM) has demonstrated notable efficacy in the treatment of inflammation. Our previous study surfaces that the active fraction of Polyrhachis vicina Roger (AFPR) has antidepressant and anti-neuroinflammatory effects, but the specific mechanisms remain to be elucidated. The objective of this study was to examine the impact of AFPR on inflammation in depression via the FTO/miR-221-3p/SOCS1 axis.Methods: Chronic unpredictable stress (CUMS)-induced rats and LPS-induced BV2 cells were employed to simulate depression models in vivo and in vitro. The levels of inflammatory factors were detected using the ELISA assay. The expression of genes and proteins was detected using qRT-PCR and Western blot. Gene interactions were detected using the dual luciferase reporter gene. Protein-RNA interactions were investigated using RNA methylation immunoprecipitation (MeRIP) and RNA immunoprecipitation (RIP). Neuroinflammation in the brain was examined through H&E staining, while neuronal apoptosis was assessed using TUNEL staining.Results: The results showed that AFPR ameliorated depression induced inflammation by increasing SOCS1 expression. However, SOCS1 was identified as a target of miR-221-3p. Overexpression of miR-221-3p decreased the expression of SOCS1 and increased the levels of NF-κB, IL-7, and IL-6. In addition, we found that miR-221-3p was regulated by FTO-mediated m6A modification through MeRIP and RIP experiments. Interference with miR-221-3p and overexpression of FTO resulted in increased SOCS1 gene expression and decreased levels of NF-κB, IL-7, and IL-6, which were reversed by AFPR.Conclusion: AFPR inhibits the maturation of pri-miR-221-3p through FTO-mediated m6A modification, reduces the production of miR-221-3p, increases the expression of SOCS1, and reduces the level of inflammation, thereby improving depressive symptoms. Keywords: depression, FTO, SOCS1, inflammation, Polyrhachis vicina Roger

Jieyao Xie, Tingjun Pan, Weiwen Luo, Songsheng Zhang, Yuquan Fang, Zhou Xu Intensive Care Unit, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of ChinaCorrespondence: Jieyao Xie, Intensive Care Unit, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, No. 63 Huangtang Road, Meijiang District, Meizhou, People’s Republic of China, Email X1275014370@163.comBackground: Vascular diseases such as atherosclerosis usually affect multiple organs. Genetic factors have a certain proportion in the risk factors of atherosclerosis. The purpose was to investigate the relationship of cytochrome P450 2C19 (CYP2C19) polymorphisms with multi-site atherosclerosis.Methods: The study included 410 patients with single-site atherosclerosis and 529 patients with multi-site atherosclerosis. The relationship between CYP2C19 rs4244285 and rs4986893 polymorphisms and single-site atherosclerosis and multi-site atherosclerosis was analyzed.Results: The proportion of CYP2C19 rs4244285 A allele (35.9% vs 29.9%, P=0.007) and rs4986893 G allele (97.7% vs 94.8%, P=0.001) in multi-site atherosclerosis group was significantly higher than that in single-site atherosclerosis group. The distribution of CYP2C19 genotypes was significantly different between the two groups (P=0.002). The results of univariate logistic regression indicated that CYP2C19 &ast;1/&ast;3 genotype (&ast;1/&ast;3 vs &ast;1/&ast;1: odds ratio (OR) 0.456, 95% confidence interval (CI): 0.231– 0.902, P=0.024) may decrease risk of multi-site atherosclerosis, while &ast;2/&ast;2 genotype (&ast;2/&ast;2 vs &ast;1/&ast;1: OR 1.780, 95% CI: 1.100– 2.880, P=0.019) may increase risk of multi-site atherosclerosis. Multivariate logistic regression (adjusted for gender, age, smoking, drinking, hypertension, and diabetes) indicated that CYP2C19 &ast;1/&ast;3 genotype (&ast;1/&ast;3 vs &ast;1/&ast;1: OR 0.459, 95% CI: 0.231– 0.909, P=0.026) may be an independent protective factor for multi-site atherosclerosis, while &ast;2/&ast;2 genotype (&ast;2/&ast;2 vs &ast;1/&ast;1: OR 1.767, 95% CI: 1.091– 2.864, P=0.021) may be an independent risk factor for multi-site atherosclerosis.Conclusion: CYP2C19 &ast;1/&ast;3 genotype may be an independent protective factor for multi-site atherosclerosis, while &ast;2/&ast;2 genotype may be an independent risk factor for multi-site atherosclerosis.Keywords: CYP2C19, genotype, multi-site atherosclerosis, polyvascular disease

Yongqiang Xiao,&ast; Guoqing Zhu,&ast; Jin Xie,&ast; Laihui Luo, Wei Deng, Liucong Lin, Jiahao Tao, Zhigao Hu, Renfeng Shan Department of General Surgery, the First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhigao Hu; Renfeng Shan, Department of General Surgery, the First Affiliated Hospital of Nanchang University, No. 17, Yongwaizheng Street, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel/Fax +86-791-88692522, Email 854189568@qq.com; srf1978@126.comPurpose: This study aimed to assess the prognostic significance of the neutrophil-lymphocyte ratio (NLR) in patients with unresectable hepatocellular carcinoma (u-HCC) treated with hepatic artery infusion chemotherapy (HAIC) combined with lenvatinib and camrelizumab.Patients and Methods: We conducted a retrospective cohort study involving patients diagnosed with u-HCC who underwent HAIC combined with lenvatinib and camrelizumab. Patients were stratified into two cohorts using the median NLR as the cutoff point. We then assessed treatment response, overall survival (OS), progression-free survival (PFS), and adverse events in these patient groups.Results: Between October 2020 and April 2022, a total of 88 patients were enrolled in the study. The overall cohort exhibited a median PFS of 7.9 months, while the median OS was not reached, and a median NLR of 3.46. Notably, the group with NLR< 3.46 demonstrated significantly superior OS (not reached vs 9.6 months, p = 0.017) and PFS (18.3 vs 5.3 months, p = 0.0015) compared to the NLR≥ 3.46 group. Furthermore, multivariate analysis revealed that an alpha-fetoprotein (AFP) ≥ 400 ng/mL [hazard ratio (HR), 2.133; 95% confidence interval (CI), 1.102– 4.126; p = 0.024], Barcelona Clinical Hepatocellular Carcinoma (BCLC) stage C (HR, 2.319; 95% CI, 1.128– 4.764; p = 0.022), and NLR ≥ 3.46 (HR, 2.35; 95% CI, 1.239– 4.494; p = 0.009) were identified as independent risk factors for OS. Additionally, multivariate analysis demonstrated that AFP ≥ 400 ng/mL, BCLC stage C, and NLR ≥ 3.46 were independent negative factors of PFS.Conclusion: NLR can be associated with outcomes in patients with u-HCC treated with HAIC combined with lenvatinib and camrelizumab.Keywords: unresectable hepatocellular carcinoma, neutrophil-to-lymphocyte ratio, hepatic arterial infusion chemotherapy, lenvatinib, camrelizumab