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Lixin Xie,1,* Lihua Feng,1,* Xiaomin Tang,1 Yunping Xu,1 Hengyi Xu,2 Yang Liu1 1Department of Pediatrics, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of China; 2State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hengyi Xu, State Key Laboratory of Food Science and Resources, Nanchang University, 235 Nanjing East Road, Nanchang, 330047, People’s Republic of China, Tel +0086-791-8830-4447-ext-9520, Fax +0086-791-8830-4400, Email kidyxu@163.com; HengyiXu@ncu.edu.cn Yang Liu, Department of Pediatrics, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1 minde Road, Nanchang, 330006, People’s Republic of China, Tel +86-791-8631-1209, Email ocean3166@yeah.netPurpose: To evaluate the therapeutic effect of oral administration of Lactiplantibacillus plantarum P101 (P101) on skeletal injury in young rats exposed to titanium dioxide nanoparticles (TiO2 NPs), and explore the potential mechanism.Methods: Four-week-old male rats were orally administration to TiO2 NPs and supplemented with P101 2 hours later for 4 weeks. The growth and development, food intake, bone metabolism and serum inflammatory markers of the rats were evaluated. Their tibias were observed and evaluated using microcomputed tomography (micro-CT), tartrate-resistant acid phosphatase (TRAP) staining, immunohistochemistry (IHC) and real-time quantitative PCR (RT-qPCR). We observed the tibia growth plate using safranin and fast green staining. 16S rDNA sequence analysis of fecal samples was performed to observe changes in the gut microbiota.Results: Our results showed that TiO2 NPs can lead to bone growth inhibition and osteoporosis, induce intestinal flora imbalance, and induce inflammation in young rats. Further mechanistic studies suggested that TiO2 NPs disrupts intestinal flora and increases serum IL-1β levels, which increased the expression of RANKL in bone, thereby enhancing osteoclast differentiation and function, leading to bone loss. Through a P101 supplementation experiment, we found that P101 ameliorated the inflammation and osteoporosis on bone caused by TiO2 NPs.Conclusion: This study showed that the mechanism by which P101 alleviates bone damage caused by TiO2 NPs may be through restoring intestinal microbial homeostasis and inhibiting inflammatory response. Keywords: TiO2 NPs, P101, young rats, intestinal flora, bone injury, IL-1&#x03B2

Shenghao Zhang,1,* Zhejianyi Gao,2,* Lina Feng,1,3 Mingquan Li1 1Department of Neurology, The Third Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, Jilin Province, 130021, People’s Republic of China; 2Department of Orthopaedics, Fushun Hospital of Chinese Medicine, Fushun, Liaoning Province, 113008, People’s Republic of China; 3Shandong Key Laboratory of TCM Multi-Targets Intervention and Disease Control, The Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong Province, 271000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lina Feng; Mingquan Li, Department of Neurology, the Third Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, Jilin, 130117, People’s Republic of China, Tel +86-15543120222 ; +86-15948000577, Email Fenglina0001@163.com; Limingquan0001@126.comAbstract: Alzheimer’s disease (AD) is a fatal neurodegenerative disease characterized by its insidious onset and progressive development, making it the most common form of dementia. Despite its prevalence, the exact causes and mechanisms responsible for AD remain unclear. Recent studies have highlighted that inflammation in the central nervous system (CNS) plays a crucial role in both the initiation and progression of AD. Neuroinflammation, an immune response within the CNS triggered by glial cells in response to various stimuli, such as nerve injury, infection, toxins, or autoimmune reactions, has emerged as a significant factor alongside amyloid deposition and neurofibrillary tangles (NFTs) commonly associated with AD. This article aims to provide an overview of the most recent research regarding the involvement of neuroinflammation in AD, with a particular focus on elucidating the specific mechanisms involving microglia and astrocytes. By exploring these intricate processes, a new theoretical framework can be established to further probe the impact of neuroinflammation on the development and progression of AD. Through a deeper understanding of these underlying mechanisms, potential targets for therapeutic interventions and novel treatment strategies can be identified in the ongoing battle against AD.Keywords: alzheimer’s disease, neuroinflammation, microglia, astrocyte, review

Min Zhao,1 Liuxiang Feng,2 Wenhua Li3 1School of Medicine, Lijiang University of Culture and Tourism, Lijiang, Yunnan, 674100, People’s Republic of China; 2People’s Hospital of Yulong Naxi Autonomous County of Lijiang City, Lijiang, Yunnan, 674112, People’s Republic of China; 3School of Medicine, Xizang Minzu University, Xianyang Shaanxi, 712082, People’s Republic of ChinaCorrespondence: Min Zhao, School of Medicine, Lijiang University of Culture and Tourism, Lijiang, Yunnan, 674100, People’s Republic of China, Email 1398606492@qq.comObjective: To employee network pharmacology to predict the components and pathways of SanQi-DanShen (SQDS) in treating coronary heart disease, followed by in vitro experiments to validate the molecular mechanism of SQDS in treating coronary heart disease.Methods: We sourced the active ingredients and targets of Panax notoginseng and Danshen from the Traditional Chinese Medicine Systems Pharmacology database. Coronary heart disease related genes were retrieved from the OMIM, Genecards, and Therapeutic Target databases. Using Cytoscape 3.7.2 software, we constructed a network diagram illustrating the components and targets of SQDS. The associated targets were then imported into the STRING database to build a protein-protein interaction network. The Metascape database and WeChat software were utilized for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Lastly, we performed molecular docking between the key components and related targets using AutoDock Vina. To validate the potential mechanism of SQDS in treating coronary heart disease, we established an acute coronary heart disease rat model via tail vein injection of pituitrin.Results: Network pharmacology analysis revealed that 65 active ingredients and 167 targets of SQDS are implicated in the treatment of coronary heart disease. The key targets identified include AKT1, TNF, TP53, IL6, and VEGFA. Notably, the PI3K/AKT signaling pathway emerged as the primary pathway. Furthermore, animal experiments showed that, compared to the model group, SQDS significantly reduced levels of TNF-α, IL-6, Bax, and cardiac troponin I, while increasing Bcl-2 content. It also notably suppressed the expression of p-PI3K and p-AKT, thereby offering protection to myocardial tissue.Conclusion: Through the integrated approach of network pharmacology and molecular docking, we have established that SQDS exerts a multi-component, multi-target, and multi-pathway synergistic therapeutic effect on coronary heart disease. Its mechanism may involve the inhibition of the PI3K/AKT signaling pathway and the reduction of inflammatory factor expression.Keywords: SQDS, cardiac troponin I, PI3K/AKT signaling pathway, coronary heart disease, experiment validation

Liwei Feng,1 Pei Liu,2 Meilin Huang,3 Linjie Tian,4 Xiaolin Bu5 1School of Gongli Hospital Medical Technology, University of Shanghai for Science and Technology, Shanghai, People’s Republic of China; 2Department of Imaging, Gongli Hospital of Shanghai Pudong New Area, Shanghai, People’s Republic of China; 3Department of Dermatology, Zhoupu Hospital, Shanghai Medical College of Health Sciences, Shanghai, People’s Republic of China; 4The Graduate School, Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China; 5Laboratory of Laser and Medical Innovation Application, Department of Dermatology, Gongli Hospital of Shanghai Pudong New Area, Shanghai, People’s Republic of ChinaCorrespondence: Xiaolin Bu, Email xiaolinbu@yeah.netAbstract: The patient, a 77-year-old Asian male presented with herpes zoster in the left lumbar and abdominal regions 9 weeks before presentation. The infection dried up after 2 weeks but was followed by an erythematous scaly rash in the same region with left-sided abdominal elevation. Pathological examination revealed continuous parakeratosis and Munro microabscesses. Abdominal computer tomography revealed no abnormalities, suggesting psoriasis with herpes zoster and Wolf’s isotopic response to the pseudohernia of the abdominal wall.Keywords: herpes zoster, psoriasis, Wolf’s isotopic response, abdominal wall pseudo-inguinal hernia

Peiran Guo,1,2,&ast; Yuting Tan,1,2,&ast; Li Feng,3 Cui Liu,4 Jin Sun,5 Rong Cheng,1,2 Yanling Xiao,1 Xingxin Zhan,6 Lingjie Yang,1 Zhixia Zhang1 1Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Wuhan University of Science and Technology School of Medicine, Institute of Nursing Research, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan, Hubei, People’s Republic of China; 3School of Public Health and Nursing, Hubei University of Science and Technology, Xianning, Hubei, People’s Republic of China; 4Geriatric Hospital Affiliated with Wuhan University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 5Yiling Hospital of Yichang City, Yichang, Hubei, People’s Republic of China; 6School of Public Health, Xinyu University, Xinyu, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhixia Zhang, Tianyou Hospital, Wuhan University of Science and Technology, No. 9, Tujialing, Dingzhiqiao, Wuchang District, Wuhan, Hubei, People’s Republic of China, Tel +8613476805827, Email zzx13476805827@126.comPurpose: The development of “Internet + nursing services” can effectively solve the problem of population aging, and grassroots nurses are the primary providers of such services in rural areas. This study aimed to analyze the factors affecting grassroots nurses’ risk perception of “Internet + nursing services” and construct a predictive model.Patients and Methods: A multicenter cross-sectional study of 2220 nurses from 27 secondary hospitals and 36 community health centers in Hubei Province was conducted from August to December 2023 using a multi-stage cluster sampling method. Information was collected through a structured anonymous questionnaire. A Chi-square test, a Welch t-test, and binary logistic regression analyses were employed to determine independent risk factors for grassroots nurses’ risk perception of “Internet + nursing services”, and a nomogram was constructed. Receiver operating characteristic curves, calibration curves, and decision curves were plotted to evaluate the discrimination, calibration, and clinical effectiveness of the nomogram.Results: A total of 2050 valid questionnaires were collected, demonstrating that 51.95% of grassroots nurses thought that “Internet + nursing services” was a medium-high risk. Age, other sources of income, knowledge about “Internet + nursing services”, personal safety, physical function, occupational exposure, social psychosocial, and time risk (P< 0.05) were independent risk factors for grassroots nurses’ risk perception. The area under the receiver operating characteristic curve of the nomogram was 0.939. The calibration and decision curve analyses demonstrated good calibration ability and clinical application values.Conclusion: The prediction model constructed in this study has good prediction ability. Most grassroots nurses believe that “Internet + nursing services” are risky and influenced by several factors. It is suggested that the government and hospitals should formulate a unified charging standard, improve the safety guarantee, and gradually eliminate the concerns of grassroots nurses.Keywords: grassroots nurse, Internet + nursing services, risk perception, predictive model

Rui Shi,1,&ast; Wenbo Xu,1 Lei Feng,2,&ast; Dan Ye,1 Beibei Luo,1 Yanmei Liu,2,3 Huiying Cao,1 Lingtong Tang1 1Department of Laboratory, The Sixth Affiliated Hospital of Kunming Medical University, Yuxi City, Yunnan Province, People’s Republic of China; 2Clinical Laboratory, Yan’an Hospital of Kunming City, Kunming City, Yunnan Province, People’s Republic of China; 3Department of Laboratory Medicine, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenbo Xu, Department of Laboratory, The Sixth Affiliated Hospital of Kunming, Medical University, Yuxi City, Yunnan Province, People’s Republic of China, Tel +86 877 2014128, Email xwb103196@sina.com Lei Feng, Clinical Laboratory, Yan’an Hospital of Kunming City, Kunming City, Yunnan Province, People’s Republic of China, Tel +86 871 63612494, Email fngj2004@163.comAim: This investigation aims to assess the predictive value of the glycemic dispersion index (GDI), calculated by incorporating glycated hemoglobin, fasting plasma glucose, and 2-hour postprandial plasma glucose, in predicting major adverse cardiovascular events (MACE) within a 12-month timeframe for diabetic patients with concomitant acute coronary syndrome (ACS).Methods: A retrospective study was conducted on 3261 diabetic patients with ACS who were hospitalized in the Department of Cardiology, the Sixth Affiliated Hospital of Kunming Medical University, from January 2016 to July 2022. Based on the inclusion and exclusion criteria, 512 patients were ultimately enrolled in the study. Their general information and laboratory test indicators were collected, and the occurrence of MACE within 12 months after admission was followed up and recorded for the enrolled patients, With the last follow-up having been concluded on July 31, 2023. The enrolled patients were stratified into four groups (Q1, Q2, Q3, Q4) based on their GDI values, from the lowest to the highest. Cox proportional hazards regression analysis and Kaplan-Meier survival analysis were employed to investigate the risk factors associated with MACE occurrence across these groups and to assess the cumulative risk of MACE over time within each group.Results: The percentages of enrolled patients experiencing MACE in groups Q1 to Q4 were 10.16%, 12.50%, 15.63%, and 16.41%, respectively. GDI independently predicted the hazards for MACE in enrolled patients. The cumulative risk of MACE over time was considerably more significant in those with a GDI> 4.21 than those with a GDI≤ 4.21.Conclusion: The elevated GDI is correlated with an augmented risk of MACE in diabetic patients with concomitant ACS, thereby serving as an early indicator for assessing the unfavorable clinical prognosis of patients. This study offers novel insights into glycemic variability monitoring, enhancing prevention and treatment strategies for cardiovascular disease in people with diabetes.Keywords: diabetes, acute coronary syndrome, major adverse cardiovascular events, glycemic dispersion index, glycemic variability

Tong Guo,1,2 Yuan Feng,1,2 Jingjing Zhou,1,2 Linghui Meng,1,2 Xuequan Zhu,1,2 Xu Chen,1,2 Le Xiao,1,2 Lei Feng,1,2 Ling Zhang,1,2 Yu-Tao Xiang,3,4 Yan-Jie Zhao,1,2 Gang Wang1,2 1Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, People’s Republic of China; 3Unit of Psychiatry, Department of Public Health and Medicinal Administration, Faculty of Health Sciences, Institute of Translational Medicine, University of Macau, Taipa, Macao SAR, People’s Republic of China; 4Centre for Cognitive and Brain Sciences, University of Macau, Taipa Macao SAR, People’s Republic of ChinaCorrespondence: Yan-Jie Zhao; Gang Wang, Email yzhao118@126.com; gangwangdoc@ccmu.edu.cnBackground: Understanding the dynamic relationship between depressive symptoms and quality of life (QOL) is essential in improving long-term outcomes for patients with Major Depressive Disorder (MDD). While previous studies often relied on cross-sectional data, there is a pressing need for stronger evidence based on longitudinal data to better inform the development of effective clinical interventions. By focusing on key depressive symptoms, such interventions have the potential to ultimately enhance QOL in individuals with MDD.Methods: This multi-center prospective study, conducted between 2016 and 2020, enrolled outpatients and inpatients diagnosed with MDD across twelve psychiatric hospitals in China. Longitudinal data on Patient Health Questionnaire – 9 (PHQ-9) and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) was analyzed using an Extended Bayesian Information Criterion (EBIC) graphical least absolute shrinkage and selection operator (gLASSO) network model to explore the connections between depressive symptom changes and QOL changes. Flow network was applied to investigate relationships between individual symptom changes and overall QOL score change, as well as daily functional independence.Results: This study included 818 participants with complete data after 8-week antidepressant treatment. Apart from the overlapping items from PHQ-9 and Q-LES-Q-SF, the three edges between “mood” (delta-QLES2) and “anhedonia” (delta-DEP1), between “physical health” (delta-QLES1) and “sleep problems” (delta-DEP3), and between “physical health” (delta-QLES1) and “sad mood” (delta-DEP2) were the most strong bridges between the cluster of depressive symptoms alleviation and the cluster of QOL change. “Anhedonia” (delta-DEP1), “sad mood” (delta-DEP2) and “loss of energy” (delta-DEP4) had the highest bridge strength between the alleviations of depressive symptoms and the total score change of Q-LES-Q-SF. Anhedonia had the greatest connection with participants’ satisfaction with function in daily life.Conclusion: This study highlighted the potential for developing highly effective interventions by targeting on central symptoms, thereby to ultimately improve QOL for patients with MDD.Keywords: network analysis, patients with MDD, acute phase treatment, depressive symptoms, quality of life

Tong Chen,1– 4 Yu Liu,2,3 Shiquan Wu,2 Siyu Long,2 Ling Feng,4,5 Wenqian Lu,6 Wenya Chen,2 Guoai Hong,2 Li Zhou,2 Fang Wang,2 Yuechan Luo,2 Hequn Zou,2,4,6 Weihua Liu7 1Department of Nephrology, Chongqing Key Laboratory of Prevention and Treatment of Kidney Disease, Chongqing Clinical Research Center of Kidney and Urology Diseases, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, 400037, People’s Republic of China; 2South China Hospital of Shenzhen University, Shenzhen, 518116, People’s Republic of China; 3Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National Regional Key Technology Engineering Laboratory for Medical Ultrasound School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, 518060, People’s Republic of China; 4Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 5Department of Nephrology, Shenzhen Hospital, Southern Medical University, Shenzhen, People’s Republic of China; 6School of Medicine, The Chinese University of Hong Kong, Shenzhen, People’s Republic of China; 7Department Nephrology of Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fujian, 350001, People’s Republic of ChinaCorrespondence: Weihua Liu, Department Nephrology of Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fujian, 350001, People’s Republic of China, Email lwh10280465@163.com Hequn Zou, School of Medicine, The Chinese University of Hong Kong, Shenzhen, People’s Republic of China, Email zouhequn@cuhk.edu.cnBackground: Obesity and insulin resistance (IR) are positively associated with chronic kidney disease (CKD). Previous studies have identified triglyceride-glucose index (TyG) as a valuable surrogate of insulin resistance. Recently, new indicators combining TyG and simple anthropometric indices have emerged, The objective of this study was to assess the diagnostic accuracy of TyG and newly TyG related indicators in detecting CKD and explore which indices were superior in associating with CKD in Chinese population.Methods: Correlation test, logistic regression analysis, and receiver operating characteristic (ROC) analyses were used to evaluate the optimal cut-off and value of TyG, TyG-body mass index (TyG-BMI), TyG-waist circumference (TyG-WC), TyG-waist to height ratio (TyG-WHtR) for predicting CKD.Results: TyG-WHtR, TyG-WC, and TyG-BMI correlated with several risk factors for CKD. After adjusting for confounders, TyG-WHtR and TyG-WC remained significantly associated with CKD, while TyG-BMI did not. The highest quartiles of TyG-WHtR and TyG-WC had 1.95- and 1.91-fold increased risk of CKD than the lowest quartiles (P< 0.05). TyG-WHtR had the largest AUC (0.687) for CKD detection, followed by TyG-WC (0.669), TyG (0.652), and TyG-BMI (0.648). A united model that involved TyG-WHtR and other risk variables had higher predictive performance (AUC=0.791) than a single TyG related indicator. However, TyG had the highest OR (2.713, 95% CI, 1.446– 5.090) for reduced eGFR in the fully adjusted model. A united model that involved TyG and WHtR separately had stronger predictive ability (AUC: 0.794) than the model that involved TyG-WHtR individually (AUC:0.791).Conclusion: This study found that TyG-WHtR had a better diagnostic value in the diagnosis of CKD, compared to other TyG related indicators, but none of the TyG related indicators showed a stronger association with CKD than TyG. Further research and more refined algorithms are needed to verify these new indicators.Keywords: chronic kidney disease, insulin resistance, obesity, TyG related indicators

Liping Feng,1,&ast; Wencong He,2,&ast; Zexuan Song,3,&ast; Bing Zhao,3 Chong Teng,3 Eryong Liu,3 Hanfang Zhu,1 Shaojun Pei,4 Lina Liu,5 Yuanyuan Song,3 Yang Zheng,3 Xiangyi Liu,2 Yanlin Zhao,3 Xichao Ou3 1Department of Microbiology, Hinggan League Center for Disease Control and Prevention, Ulanhot, 137499, People’s Republic of China; 2Department of Clinical Laboratory, Beijing Tongren Hospital, Capital Medical University, Beijing, 100176, People’s Republic of China; 3National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Center for Tuberculosis Control and Prevention, Chinese Centre for Disease Control and Prevention, Beijing, 102206, People’s Republic of China; 4School of Public Health, Peking University, Beijing, 100191, People’s Republic of China; 5Blood Transfusion Department, Hinggan League People’s Hospital, Ulanhot, 137400, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xichao Ou; Yanlin Zhao, Email ouxc@chinacdc.cn; zhaoyl@chinacdc.cnBackground: Tuberculosis remains a major public health concern in China, with varying prevalence and drug resistance profiles across regions. This study explores the genetic diversity and drug-resistant profiles of MTB strains in Hinggan League, a high TB burden in Inner Mongolia, China.Methods: This population-based retrospective study, encompassing all culture-positive TB cases from Jun. 2021 to Jun. 2023 in Hinggan League. Drug resistant profiles and genetic diversity of MTB strains were assessed using phenotypic drug susceptibility testing and whole-genome sequencing. Risk factors associated with drug resistance were analyzed using univariate and multivariate logistic regression models.Results: A total of 211 MTB strains were recovered successfully and included into final analysis. Lineage 2.2.1 (88.6%, 187/211) was the dominant sub-lineage, followed by lineage 4.5 (7.1%, 15/211) and lineage 4.4 (4.3%, 9/211). MTB strains exhibited the highest resistance rates to isoniazid (16.1%, 34/211), followed by rifampicin (10.0, 21/211). In addition, the MTB strains also showed relatively high rates of resistance against new and repurposed anti-TB drugs, with resistant rates of 2.4% (5/211) to delamanid and 1.9% (4/211) to bedaquiline. Overall, 25.6% (54/211) of MTB strains were DR-TB, and 14 MTB strains met the definition of MDR-TB, including 7 strains of simple-MDR-TB, 5 of pre-XDR-TB, and 2 of XDR-TB. Genetic analysis revealed that the dominant mutations of isoniazid-, rifampin-, ethambutol-, levofloxacin-/moxifloxacin-, and ethionamide- resistance were katG_Ser315Thr(46.4%), rpoB_Ser450Leu (47.4%), embB_Met306Val (25.0%), gyrA_Asp94Ala (40.0%), and fabG1_c15t (42.9%), respectively. Previously treated patients (AOR = 2.015, 95% CI: 1.052– 4.210) and male patients (AOR = 3.858, 95% CI: 1.416– 10.511) were identified as independent risk factors associated with DR-TB.Conclusion: Our study offers crucial insights into the genetic diversity and drug-resistant profiles of TB strains circulating in Hinggan League. These findings are valuable for DR-TB surveillance and for guiding treatment regimens and public health interventions in the region.Keywords: Mycobacterium tuberculosis, drug resistance, genetic diversity, whole-genome sequencing

Juying Zhang,1 Xia Luo,1 Xin Yang,1 Hanmei Li,1 Qiong Jiang,1 You Yang,1 Menglin Luo,1 Zijun Ma,1 Ping He,1 Linli Feng,1 Ling Li,1 Maochun Zhang,1 Yang Li,2,3 Jinhong Yu1,3 1Department of Ultrasound, Affiliated Hospital of North Sichuan Medical College, Innovation Centre for Science and Technology of North Sichuan Medical College, Nanchong, Sichuan, 637000, People’s Republic of China; 2Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, People’s Republic of China; 3Department of Ultrasound, Yuechi People’s Hospital, Guangan, Sichuan, 638300, People’s Republic of ChinaCorrespondence: Jinhong Yu, Email yujinhong@nsmc.edu.cnPurpose: The incidence of hepatocellular carcinoma (HCC) is continuously increasing, and the mortality rate remains high. Thus, more effective strategies are needed to improve the treatment of HCC.Methods: In this study, we report the use of a visualized glypican-3 (GPC3)-targeting nanodelivery system (named GC-NBs) in combination with sonodynamic therapy (SDT) to enhance the therapeutic efficacy for treating HCC. The obtained nanodelivery system could actively target hepatocellular carcinoma cells and achieve ultrasound imaging through phase changes into nanobubbles under low-intensity ultrasound irradiation. Meanwhile, the released chlorine e6 (Ce6) after the nanobubbles collapse could lead to the generation of reactive oxygen species (ROS) under ultrasound irradiation to induce SDT.Results: Both in vitro and in vivo experiments have shown that GC-NBs can accumulate in tumour areas and achieve sonodynamic antitumour therapy under the navigation action of glypican-3-antibody (GPC3-Ab). Furthermore, in vitro and in vivo experiments did not show significant biological toxicity of the nanodelivery system. Moreover, GC-NBs can be imaged with ultrasound, providing personalized treatment monitoring.Conclusion: GC-NBs enable a visualized antitumour strategy from a targeted sonodynamic perspective by combining tumour-specific targeting and stimuli-responsive controlled release into a single system. Keywords: Glypican-3, nanodelivery system, ultrasound imaging, sonodynamic therapy, hepatocellular carcinoma

Bei Li,1,2,&ast; Yuting Luo,1,2,&ast; Geng Liu,1,2 Maling Gou,3 Lei Feng,1,2 Xiwen Ye,1,2 Jianrong Xu,1,2 Yaotian Fan,1,2 Zhen You1,2 1Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China; 2Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China; 3Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhen You, Tel/Fax +86 028 85423823, Email youzhen@wchscu.cnIntroduction: Hepatocellular carcinomas (HCC) have a high morbidity and mortality rate, and is difficult to cure and prone to recurrence when it has already developed. Therefore, early detection and efficient treatment of HCC is necessary.Methods: In this study, we synthesized a novel NDI polymer with uniform size, long-term stability, and high near-infrared two-zone (NIR-II) absorption efficiency, which can greatly enhance the effect of photothermal therapy (PTT) after intravenous injection into Huh-7-tumor bearing mice.Results: The in vitro and in vivo studies showed that NDI polymer exhibited excellent NIR-guided PTT treatment, and the antitumor effect was approximately 88.5%, with obvious antimetastatic effects.Conclusion: This study developed an NDI polymer-mediated integrated diagnostic and therapeutic modality for NIR-II fluorescence imaging and photothermal therapy.Keywords: hepatocellular carcinoma, photothermal therapy, NDI polymer, NIR-II imaging

Huiying Yan,1,&ast; Wei Wang,2,&ast; Tingting Cui,1 Yanxin Shao,3 Mingquan Li,1 Limei Fang,1 Lina Feng1 1Department of Neurology, The Third Affiliated Clinical Hospital of the Changchun University of Chinese Medicine, Changchun, People’s Republic of China; 2Department of Intensive Care Unit, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, People’s Republic of China; 3Department of Neurology, The Second Affiliated Hospital of Shandong First Medical University, Taian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Limei Fang; Lina Feng, Department of Neurology, The Third Affiliated Clinical Hospital of the Changchun University of Chinese Medicine, Changchun, People’s Republic of China, Email fanglm008@163.com; Fenglina0001@126.comAbstract: Alzheimer’s disease (AD) is a fatal neurodegenerative disease with a subtle and progressive onset and is the most common type of dementia. However, its etiology and pathogenesis have not yet been fully elucidated. The common pathological manifestations of AD include extraneuronal β-amyloid deposition (Aβ), intraneuronal tau protein phosphorylation leading to the formation of ‘neurofibrillary tangles’ (NFTs), neuroinflammation, progressive loss of brain neurons/synapses, and glucose metabolism disorders. Current treatment approaches for AD primarily focus on the ‘Aβ cascade hypothesis and abnormal aggregation of hyperphosphorylation of tau proteins’, but have shown limited efficacy. Therefore, there is an ongoing need to identify more effective treatment targets for AD. The central nervous system (CNS) inflammatory response plays a key role in the occurrence and development of AD. Neuroinflammation is an immune response activated by glial cells in the CNS that usually occurs in response to stimuli such as nerve injury, infection and toxins or in response to autoimmunity. Neuroinflammation ranks as the third most prominent pathological feature in AD, following Aβ and NFTs. In recent years, the focus on the role of neuroinflammation and microglia in AD has increased due to the advancements in genome-wide association studies (GWAS) and sequencing technology. Furthermore, research has validated the pivotal role of microglia-mediated neuroinflammation in the progression of AD. Therefore, this article reviews the latest research progress on the role of neuroinflammation triggered by microglia in AD in recent years, aiming to provide a new theoretical basis for further exploring the role of neuroinflammation in the process of AD occurrence and development.Keywords: neuroinflammation, microglia, Alzheimer’s disease, review, Trem2

Wenjie Liu, Li Guo, Lizhen Feng, Jie Wang, Miao Zhang, Xiaobin Fan Department of Obstetrics and Gynecology, Xi’an No.3 Hospital, The Affiliated Hospital of Northwest University, Xi’an, 710018, People’s Republic of ChinaCorrespondence: Xiaobin Fan, Email liuwj0709@163.comObjective: To evaluate factors predictive of the success of a slow-release dinoprostone vaginal insert for cervical ripening.Methods: This retrospective study included 187 women who received dinoprostone vaginal inserts for cervical ripening. The participants were divided into two groups: the transvaginal delivery group (n = 87) and cesarean section termination group (n = 100). The correlation between the parameters present before cervical ripening with dinoprostone slow release and its success, as well as complications and adverse outcomes, was analyzed. Cesarean section predictors and area under the curve (AUC) were compared between the two Groups.Results: There were statistical differences between the two groups in body mass index (BMI), height, cervical Bishop score, cephalic position, time of medication use, and fetal head position at the time of medication use (P< 0.05). The optimal thresholds for identifying cesarean section in dinoprostone vaginal insert for cervical ripening were 162.5 for height (AUC = 0.61), 10.65 cm for amniotic fluid index (AUC = 0.6), S-2.5 for cephalic position (AUC = 0.61), 5.5 for bishop score of cervix (AUC = 0.65). The height, amniotic fluid index, cephalic position, and Bishop score of the cervix were included in the same model. The AUC value of the combined model was higher than the AUC value of the single factor.Conclusion: The combined model was a better predictor of cesarean section in dinoprostone vaginal inserts for cervical ripening and labor induction. The success of cervical ripening with a dinoprostone slow-release vaginal insert can be predicted by the factors that can be recognized at admission.Keywords: dinoprostone, cervical ripening, labor induction, predictive model

Purpose/Objectives: Retrospective analysis suggests that dose escalation to a biologically effective dose of more than 70 Gy may improve overall survival in patients with pancreatic ductal adenocarcinoma (PDAC), but such treatments in practice are limited by proximity of organs at risk (OARs). We hypothesized that CT-guided online adaptive radiotherapy (OART) can account for interfraction movement of OARs and allow for safe delivery of ablative doses. Materials/Methods: This is a single institution retrospective analysis of patients with PDAC treated with OART on the Ethos platform (Varian Medical Systems, a Siemens Healthineers Company, Palo Alto). All patients were treated to 40 Gy in 5 fractions. PTV overlapping with a 5 mm planning risk volume expansion on the stomach, duodenum and bowel received 25 Gy. Initial treatment plans were created conventionally. For each fraction, PTV and OAR volumes were recontoured with AI assistance after initial cone beam CT (CBCT). The adapted plan was calculated, underwent QA, and then compared to the scheduled plan. A second CBCT was obtained prior to delivery of the selected plan. Total treatment time (first CBCT to end of radiation delivery) and active physician time (first to second CBCT) were recorded. PTV_4000 V95 %, PTV_2500 V9 5%, and D0.03 cc to stomach, duodenum and bowel were reported for scheduled (S) and adapted (A) plans. CTCAEv5.0 toxicities were recorded. Statistical analysis was performed using a two-sided T test and α of 0.05. Results: 21 patients with unresectable or locally-recurrent PDAC were analyzed, with a total of 105 fractions. Average total time was 29 min and 16 s (16:36–49:40) and average active physician time was 19:41 min (9:25–39:34). All fractions were treated with adapted plans. 97 % of adapted plans met PTV_4000 V95.0 % >95.0 % coverage goal and 100 % of adapted plans met OAR dose constraints. Median follow up was 6.6 months. Only 1 patient experienced acute grade 3+ toxicity directly attributable to radiation. Only 1 patient experienced late grade 3+ toxicity directly attributable to radiation. Conclusions: Daily CT-based OART was associated with significantly reduced dose OARs while achieving superior PTV coverage. Given the relatively quick total treatment time, radiation delivery was generally well tolerated and easily incorporated into the clinic workflow. Our initial clinical experience demonstrates OART allows for safe dose escalation in the treatment of PDAC.

Shenglan Zhu,1 Junlin Ren,2 Ling Feng,1 Yi Jiang1 1Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China; 2Department of Computer Science, Huazhong University of Science and Technology, Wuhan, 430074, People’s Republic of ChinaCorrespondence: Yi Jiang; Ling Feng, Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095, Jiefang Avenue, Wuhan, Hubei, 430030, People’s Republic of China, Email einsmeer@foxmail.com; fltj007@163.comIntroduction: Previous studies have shown that pregnant women with systemic lupus erythematosus (SLE) tend to have a higher risk of adverse pregnancy outcomes, but the potential causal role remained unclear. In this study, we aimed to investigate the causal relationship between SLE and some common pregnancy complications and outcomes using two-sample Mendelian randomization (MR).Methods: The genetic tools were derived from genome-wide association studies of SLE and pregnancy complications and outcomes. MR analysis was performed using inverse variance weighting as primary method. Sensitivity analyses were performed to evaluate the robustness of the results. A retrospective analysis was conducted on 200 pregnant women with SLE and a control group of pregnant women delivering at Tongji Hospital.Results: In the results, we found that genetic susceptibility to SLE was associated with a higher risk of gestational diabetes mellitus (OR = 1.028, 95% CI: 1.006– 1.050), premature delivery (OR = 1.039, 95% CI: 1.013– 1.066), polyhydramnios (OR = 1.075, 95% CI: 1.004– 1.151) and premature rupture of membranes (OR = 1.030, 95% CI: 1.001– 1.060). Some of the retrospective analysis results align with the findings from the MR analysis, indicating that pregnant women with SLE have a higher risk of developing gestational diabetes mellitus and preterm birth. Additionally, although MR analysis did not reveal a causal relationship between SLE and preeclampsia/eclampsia, retrospective analysis discovered that SLE pregnant women are more susceptible to developing preeclampsia/eclampsia (OR = 2.935, 95% CI: 1.118– 7.620).Conclusion: Our study findings suggest a potential causal relationship between SLE and increased risks of gestational diabetes and preterm delivery. Clinical data indicate that pregnant women with SLE are more prone to developing preeclampsia/eclampsia. Clinicians need to be vigilant about the occurrence of these conditions when managing pregnant women with SLE.Keywords: systemic lupus erythematosus, pregnancy complications, Mendelian randomization, gestational diabetes mellitus, preeclampsia, retrospective analysis

Liwen Feng,1 Junbo Liang,1 Naiguo Wang,2 Qingyu Zhang2 1Department of Orthopedics, Weihaiwei People’s Hospital, Weihai, Shandong Province, 264200, People’s Republic of China; 2Department of Orthopedics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, 250021, People’s Republic of ChinaCorrespondence: Qingyu Zhang, Tel +86-13296402823, Email zqy2008512@163.com; zqy2008512@126.com; zhangqingyu@sdfmu.edu.cn Naiguo Wang, Tel +86-13505319917, Email naiguow@outlook.comPurpose: The purpose of this study is to preliminarily assess the change in perioperative systemic inflammatory markers and clinical outcomes between open TLIF and BE-TLIF procedures.Patients and Methods: In total, 38 patients who underwent single-level lumbar fusion surgery (L4-5 or L5-S1) were retrospectively reviewed. 19 patients were treated by the BE-TLIF technique, while the other patients were managed using open TLIF. The perioperative serum C-reactive protein (CRP), neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), and platelet/lymphocyte ratio (PLR) of the two groups were compared to determine if there was a statistical difference. Meanwhile, clinical evaluations were conducted to assess various factors including operative duration, estimated blood loss (EBL), drainage catheter stay, length of hospitalization, visual analogue scale (VAS), and Oswestry disability index (ODI) scores.Results: The perioperative analysis revealed that BE-TLIF cases experienced a longer operative duration than open TLIF cases (open TLIF: 138.63 ± 31.59 min, BE-TLIF: 204.58 ± 49.37 min, p < 0.001). Meanwhile, the EBL showed an increased trend in the BE-TLIF group (260.7 ± 211.9 mL) in comparison with the open TLIF group (200.9 ± 211.9 mL) (p =0.485). In terms of systemic inflammatory markers, the mean postoperative CRP, NLR, LMR, and PLR were lower in the BE-TLIF group than in the open TLIF group, although these differences were not statistically significant (p > 0.05). The VAS and ODI scores in both groups were significantly improved after surgery (p < 0.05).Conclusion: There was no significant difference found between BE-TLIF and open TLIF in terms of systemic inflammatory markers, and clinical outcomes. Overall, BE-TLIF can be considered a viable choice for lumbar canal decompression and interbody fusion for less invasion. It is worth noting that BE-TLIF does have a longer operation time, indicating that there is still potential for further improvement in this technique.Keywords: transforaminal lumbar interbody fusion, unilateral biportal endoscope, systemic inflammatory markers

Jiaxin Chen,1,2 Li Feng,1,2 Shiyin Li,2 Haiyan Wang,1,2 Xin Huang,1,2 Cunzhou Shen,1,2 Huiyu Feng1,2 1Department of Neurology and Neurointensive Care Unit, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, People’s Republic of ChinaCorrespondence: Huiyu Feng, Department of Neurology and Neurointensive Care Unit, the First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan Road 2, Guangzhou, 510080, People’s Republic of China, Tel +86-020-87755766, Email fenghuiy@mail.sysu.edu.cnBackground: Since there is no clear priority or selection principle in the guidelines for myasthenia crisis, therapeutic plasma exchange (TPE) and intravenous immunoglobulin are often administered randomly. However, it should be more prudent in taking TPE due to its higher cost and risk. Studying its early response factors is crucial for managing myasthenia crisis and can improve medical and economic benefits.Methods: A prospective observational study was conducted, and patients classified as having “impending myasthenia crisis” or experiencing a myasthenia crisis and treated by TPE were included. The primary endpoint was the response after TPE. Univariate logistic regression analysis and repeated measurement were performed to analyze factors related to TPE efficacy.Results: A total of 30 patients who treated with TPE as their fast-acting treatments were enrolled. After TPE, those whose QMGs and/or MGCs decreased by ≥ 5 points or ≥ 30% of the baseline were judged as “response group”, accounting for 66.67% (20/30). Respiratory symptoms had a response rate of 72.00% (18/25), showing the most remarkable improvement. Meanwhile, extraocular symptoms were the least sensitive, with only 8.00% (2/25) showing efficacy. Thymoma (100.00% vs 50.00%, P=0.002) and a high concentration of AChR-Ab (37.37 nmol/L vs 25.4 nmol/L, P=0.039) were common in the early response group. Repeated measures showed significant changes in AChR-Ab and CD19+ B cells before and after TPE (all with P < 0.05). After treatment, the CD19+ B cells tended to decrease in the response group.Discussion: These results indicated that, for AChR-Ab positive generalized MG, TPE can quickly improve respiratory symptoms. Thymoma and a high concentration of AChR-Ab before TPE predict an early better response. Additionally, TPE may work by decreasing AChR-Ab levels and inducing immune regulation. Future prospective and randomized controlled studies are needed.Keywords: plasma exchange, myasthenia gravis, crisis, efficacy, neuroimmunology

Lan-Fang Li,1 Ran Qi,1 Tian-Tian Wei,1 Lei Feng,1 Xin Zhang,1 Qiao Liu2 1Department of Clinical Pharmacy, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, 272029, People’s Republic of China; 2Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, People’s Republic of ChinaCorrespondence: Qiao Liu, Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China, Email liuqiao6767@csu.edu.cnPurpose: The IPSOS study provided evidence supporting the efficacy and tolerability of first-line atezolizumab compared to single-agent chemotherapy for non-small-cell lung cancer (NSCLC) patients ineligible for treatment with a platinum-containing regimen. This study aimed to assess the cost-effectiveness of atezolizumab specifically in this population, considering the perspective of the Chinese healthcare system.Patients and Methods: In this analysis, a three-state Markov model was utilized. The survival data were derived from the IPSOS clinical trial. Direct medical costs and utility values were collected from national authoritative database and published literature. The primary outcomes were costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER). To ensure the robustness of our model, both one-way and probabilistic sensitivity analyses were conducted.Results: Atezolizumab monotherapy led to an increase in costs of &dollar;4139.23 compared to single-agent chemotherapy. Additionally, it resulted in a gain of 0.14 QALYs, leading to an ICER of &dollar;29,365.79 per QALY, which was below the willingness-to-pay threshold of &dollar;36,066 per QALY used in the model. One-way sensitivity analyses revealed cost of atezolizumab and utility of progressive disease (PD) as major influencing factors for ICER. Furthermore, probabilistic sensitivity analyses confirmed our base-case results.Conclusion: From the perspective of the Chinese healthcare system, atezolizumab emerges as a cost-effective choice for the first-line treatment of NSCLC patients ineligible for platinum-based chemotherapy.Keywords: atezolizumab, cost-effectiveness, NSCLC, IPSOS

Jiechu Wang,1– 3,&ast; Yao Yu,1,&ast; Ya Gao,1– 3,&ast; Tingting Wan,1– 3 Zhukai Cong,1– 3 Zhengqian Li,1– 3 Yang Zhou,1– 3 Xiaoxiao Wang,4 Luyang Feng,1– 3 Yongzheng Han,1– 3 Jing Zhang,1– 3 Yinyin Qu,1– 3 Xiangyang Guo1– 3 1Department of Anesthesiology, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 2Beijing Center of Quality Control and Improvement on Clinical Anesthesia, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 3Anesthesia and Perioperative Medicine Branch of China International Exchange and Promotive Association for Medical and Health Care (CPAM), Beijing, 100191, People’s Republic of China; 4Research Center for Clinical Epidemiology, Peking University Third Hospital, Beijing, 100191, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangyang Guo; Yinyin Qu, Department of Anesthesiology, Peking University Third Hospital, North Garden Road 49, Haidian District, Beijing, 100191, People’s Republic of China, Email puthmzk@hsc.pku.edu.cn; quyinyin@bjmu.edu.cnBackground: Malignant hyperthermia (MH) is a hypermetabolic syndrome with high mortality rates. Early detection and prompt intravenous administration of dantrolene are crucial for effective management of MH. However, there is currently a lack of comprehensive nationwide surveys on the availability of dantrolene and anesthesiologists’ understanding of MH in China.Methods: A nationwide survey was conducted between January 2022 and June 2022. Online questionnaires on the cognition of MH among anesthesiologists in China were sent through social platforms to anesthesiologists in mainland China. Data regarding participants’ perception of MH-related knowledge, availability of domestic dantrolene, and reported MH cases were collected in this study.Results: Responses were collected from a total of 11,354 anesthesiologists representing 31 provinces across the Chinese mainland. Among the 11 scoring questions, the highest accuracy rates were observed for the question regarding therapeutic drugs for MH (99.3%) and the characteristics of MH (98.0%). Conversely, the question pertaining to the earliest clinical signs of MH had the lowest accuracy rate (23.5%). Significant variations were observed in the scores among different professional titles (P=0.003), academic degree (P< 0.001), hospital classification (P< 0.001), and urban hierarchy (P< 0.001). Of the respondents, 919 (8.1%) anesthesiologists reported dantrolene availability in their hospitals, and 631 (5.6%) indicated unclear. A total of 136 hospitals in this survey reported at least one previous case of MH.Conclusion: Mainland China faces challenges such as insufficient experience in diagnosing and treating MH, as well as difficulty in obtaining dantrolene. To improve the public awareness of MH, it is imperative to establish and promote a refined MH training system. Additionally, a streamlined and rapid dantrolene linkage emergency system should be implemented to ensure prompt access to the drug.Keywords: malignant hyperthermia, dantrolene, China, anesthesiologists, survey

Lin Feng,1 Jiachen Li,1 Zhenbei Qian,2 Chenglong Li,3,4 Darui Gao,3,4 Yongqian Wang,3,4 Wuxiang Xie,3,4 Yutong Cai,5 Zhaohui Tong,2 Lirong Liang1 1Department of Clinical Epidemiology, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Heart and Vascular Health Research Center, Peking University Clinical Research Institute, Peking University First Hospital, Beijing, People’s Republic of China; 4Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, People’s Republic of China; 5Centre for Environmental Health and Sustainability, Department of Health Sciences, University of Leicester, Leicester, UKCorrespondence: Lirong Liang, Department of Clinical Epidemiology, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China, Email llrcruie@163.comPurpose: Patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) exhibit heterogeneous responses to corticosteroid treatment. We aimed to determine whether combining eosinophil levels with other routine clinical indicators can enhance the predictability of corticosteroid treatment outcomes and to come up with a scoring system.Patients and Methods: Consecutive patients admitted with AECOPD receiving corticosteroid treatment between July 2013 and March 2022 at Beijing Chao-Yang Hospital were retrospectively analyzed. Data on patients’ demographics, smoking status, hospitalization for AECOPD in the previous year, comorbidities, blood laboratory tests, in-hospital treatment and clinical outcomes were collected. Least absolute shrinkage and selection operator (LASSO) regression and backward logistic regression were used for predictor selection, and predictive nomograms were developed. The discrimination and calibration of the nomograms were assessed using the area under the receiver operating curve (AUC) and calibration plots. Internal validation was performed using the 500-bootstrap method, and clinical utility was evaluated using decision curve analysis (DCA).Results: Among the 3254 patients included, 804 (24.7%) had treatment failure. A nomogram of eosinophils, platelets, C-reactive protein (CRP), low density lipoprotein cholesterol, prognostic nutritional index (PNI), hospitalization for AECOPD in the previous year, ischemic heart diseases and chronic hepatic disease was developed to predict treatment failure for patients with a smoking history. For patients without a smoking history, a nomogram of CRP, PNI, ischemic heart diseases and chronic hepatic disease was developed. Although the AUCs of these two nomograms were only 0.644 and 0.647 respectively, they were significantly superior to predictions based solely on blood eosinophil levels.Conclusion: We developed easy-to-use comprehensive nomograms utilizing readily available clinical biomarkers related to inflammation, nutrition and immunity, offering modestly enhanced predictive value for treatment outcomes in corticosteroid-treated patients with AECOPD. Further investigations into novel biomarkers and additional patient data are imperative to optimize the predictive performance.Keywords: chronic obstructive pulmonary disease, glucocorticoids, prediction model, least absolute shrinkage and selection operator

Lei Feng,1,&ast; Ning Zhang,1,&ast; Lan Luo,1,&ast; Jie Liu,1,&ast; Yong Yao,1,&ast; Ming-Sheng Gao,1,&ast; Jin Pan,1,&ast; Cai He2 1The Division of Gastroenterology and Hepatology, Suining Central Hospital, Suining City, Sichuan Province, People’s Republic of China; 2The Division of Gastroenterology and Hepatology, Yibin Second People’s Hospital, Yibin City, Sichuan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Feng, The Division of Gastroenterology and Hepatology, Suining Central Hospital, Suining City, Sichuan Province, People’s Republic of China, Tel +8618008258982, Email fenglei822@163.comBackground: Several studies suggest that Proteasome 26S Subunit, ATPase (PSMC) family genes are of great importance in tumor progression and spreading, but the study for systematic evaluation of the function of PSMC genes in hepatocellular carcinoma (HCC) is currently lacking.Methods: The functions of PSMC genes in HCC were analyzed using multiple online databases, including the TCGA database, GEO database, HPA database, cBioPortal database, DAVID, and KEGG pathway. Experiments were later conducted to verify PSMC expression.Results: High levels of PSMC gene expression were detected in HCC tissues and PSMCs exhibited potentially powerful abilities in diagnosing HCC patients. All PSMC proteins are expressed to varying degrees in HCC tissues and high expression of the PSMC genes lead to poor prognosis in patients with HCC. Moreover, DNA methylation involves the regulation of the expression of PSMC2 and PSMC5 in HCC, and the levels of methylation of PSMC2 or PSMC5 correlate positively with patient overall survival in HCC patients. The copy number alteration and mutation of PSMC genes were observed and related to the expression of PSMCs in HCC. Functional enrichment analysis showed that many highly co-expressed genes of PSMCs had a potential role in tumor progression and metastasis, which merited further in-depth study. Functional network analysis also suggests that the primary biological function of PSMC genes is the regulation of protein homeostasis and energy metabolism in HCC. Moreover, the expression levels of PSMCs are related to immune cell infiltrates and immunomodulatory factors in HCC.Conclusion: Our study indicates that PSMC genes are the potential target for precision immunotherapy and novel prognostic biomarkers for HCC.Keywords: Proteasome 26s Subunit, ATPase, PSMC, hepatocellular carcinoma, prognostic biomarkers, therapeutic targets

Tong Chen,1– 3 Shiquan Wu,1 Ling Feng,4 SiYu Long,1 Yu Liu,1,2 WenQian Lu,5 Wenya Chen,1 Guoai Hong,1 Li Zhou,1 Fang Wang,1 Yuechan Luo,1 Hequn Zou1,3,5 1Department of Nephrology, South China Hospital of Shenzhen University, Shenzhen, People’s Republic of China; 2Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National Regional Key Technology Engineering Laboratory for Medical Ultrasound School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, People’s Republic of China; 3Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 4Department of Nephrology, Shenzhen Hospital, Southern Medical University, Shenzhen, People’s Republic of China; 5Department of Medicine, The Chinese University of Hong Kong, Shenzhen, People’s Republic of ChinaCorrespondence: Hequn Zou, School of Medicine, The Chinese University of Hong Kong, Shenzhen, People’s Republic of China, Email zouhequn@cuhk.edu.cnBackground: The annual prevalence of metabolic syndrome (MetS) is increasing. Therefore, early screening and recognition of MetS are critical. This study aimed to evaluate the association between high-density lipoprotein (HDL) subclasses and MetS and to examine whether they could serve as early indicators in a Chinese community-based population with normal high-density lipoprotein cholesterol (HDL-C) levels.Methods: We used microfluidic chip technology to measure HDL subclasses in 463 people with normal HDL levels in 2018. We assessed how HDL subclasses correlated with and predicted insulin resistance (IR) and metabolic syndrome (MetS), evaluated by homeostatic model insulin resistance index (HOMA-IR) and the 2009 International Diabetes Federation (IDF), the American Heart Association (AHA), and the National Heart, Lung, and Blood Institute (NHLBI) criteria, respectively. We used correlation tests and ROC curves for the analysis.Results: The results indicate that there was a negative association between HDL2b% and the risk of IR and MetS in both sexes. Subjects in the highest quartile of HDL2b% had a significantly lower prevalence of IR and MetS than those in the lowest quartile (P< 0.01). Correlation analysis between HDL2b% and metabolic risk factors showed that HDL2b% had a stronger association with these factors than HDL-C did in both sexes. ROC curve analysis also showed that HDL2b% had significant diagnostic value for IR and MetS compared to other lipid indicators.Conclusion: This study showed that MetS alters the distribution of HDL subclasses even when HDL-C levels are within the normal range. HDL-2b% has better diagnostic value for IR and MetS than HDL-C alone and may be a useful marker for early screening.Keywords: HDL subclass, insulin resistance, metabolic syndrome, normal HDL-C population

Jiaying Zhang,1,&ast; Bo Chen,1,&ast; Chunyuan Gan,1 Hongyan Sun,1 Jiaxin Zhang,2,3 Lin Feng1,4 1School of Mechanical Engineering and Automation, Beihang University, Beijing, 100191, People’s Republic of China; 2Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Institute of Liver Diseases, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beijing, 100191, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lin Feng; Jiaxin Zhang, Email linfeng@buaa.edu.cn; happyjiaxin@bucm.edu.cnAbstract: Small interfering RNA (siRNA) delivery by nanocarriers has been identified as a promising strategy in the study and treatment of cancer. Short nucleotide sequences are synthesized exogenously to create siRNA, which triggers RNA interference (RNAi) in cells and silences target gene expression in a sequence-specific way. As a nucleic acid-based medicine that has gained popularity recently, siRNA exhibits novel potential for the treatment of cancer. However, there are still many obstacles to overcome before clinical siRNA delivery devices can be developed. In this review, we discuss prospective targets for siRNA drug design, explain siRNA drug properties and benefits, and give an overview of the current clinical siRNA therapeutics for the treatment of cancer. Additionally, we introduce the siRNA chemical modifications and delivery systems that are clinically sophisticated and classify bioresponsive materials for siRNA release in a methodical manner. This review will serve as a reference for researchers in developing more precise and efficient targeted delivery systems, promoting ongoing advances in clinical applications. Keywords: small interfering RNA, cancer, chemical modifications, delivery systems, bioresponsive materials

Yulin Mo,1,&ast; Yanjun Yang,1,&ast; Jingqi Zeng,1 Weikun Ma,1 Yuxin Guan,1 Jingxi Guo,1 Xiaochun Wu,1 Dingkun Liu,1 Liang Feng,1,2 Xiaobin Jia,1,2 Bing Yang1,2 1School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, People’s Republic of China; 2State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 211198, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaobin Jia; Bing Yang, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, People’s Republic of China, Email jiaxiaobin2015@163.com; 15751151582@163.comPurpose: Asperosaponin VI (ASP VI) as an active ingredient of Dipsacus asperoides, which has a wide range of biological and pharmacological activity. However, its development and application are restricted due to the poor gastrointestinal permeability and oral bioavailability. This investigation aims to reveal the influence of the self-assembled structure by the interaction between ASP VI and endogenous components NaTC and/or DOPC in the gastrointestinal environment on its biopharmaceutical properties, and novelty elucidated the molecular mechanism for the formation of self-assembled nanomicelles.Methods: This change in phase state in gastrointestinal fluids is characterized by dynamic light scattering (DLS) and transmission electron microscope (TEM). UPLC-Q-TOF-MS was used to analyze the composition of phase components and the exposure of nanomicelles in vivo. Molecular dynamics simulation (MDS) was applied to preliminarily elucidate the self-assembly mechanism of ASP VI in the gastrointestinal environment. Furthermore, theS8 promoting absorption mechanism of nanomicelles were investigated through in vivo pharmacokinetic experiments, parallel artificial membrane permeability assay (PAMPA), quadruple single-pass intestinal perfusion in rats, and Caco-2 cell monolayer model.Results: We demonstrated that the ASP VI could spontaneously form dynamic self-assembled structures with sodium taurocholate (NaTC) and dipalmitoyl phosphatidylcholine (DOPC) during gastrointestinal solubilization, which promoted the gastrointestinal absorption and permeability of ASP VI and increased its exposure in vivo, thus improving the biopharmacological characteristics of ASP VI. Moreover, ASP VI-NaTC-DOPC-self-assembled nanostructures (ASP VI-NaTC-DOPC-SAN) manifested higher cellular uptake in Caco-2 cells as evidenced by flow cytometry and confocal microscopy, and this study also preliminarily revealed the mechanism of self-assembly formation of ASP VI with endogenous components NaTC and DOPC driven by electrostatic and hydrogen bonding interactions.Conclusion: This study provides evidence that the dynamic self-assembled phase transition may play a key role in improving the biopharmacological characteristics of insoluble or low permeability active ingredients during the gastrointestinal dissolution of Chinese medicines. Keywords: Asperosaponin VI, dynamic self-assembled structure, gastrointestinal environment, biopharmacological characteristics, oral bioavailability

Liao X, Shen M, Li T, et al. Int J Nanomedicine. 2023;18:5925–5942. The authors wish to advise, following publication of the article they identified errors were made during the collection and organization of data for Figures 3 and 4 on pages 5934 and 5935, respectively. The correct Figures 3 and 4 are as follows. Figure 3 Antioxidant properties of POM or hydrogel. (A) DCFH-DA assay showing intracellular ROS of MC3T3-E1 after incubation with POM in the presence of H2O2 (100 μM). (B) Quantification analysis of DCFH-DA staining (*And #Indicate p < 0.05 in comparison with the H2O2 group and GelMA group, respectively.) (C) Cell capacity of migration (scratch test). (D) Quantitative analysis of percent migration in scratch assay. (*And #Indicate p < 0.05 in comparison with the H2O2 group and GelMA group, respectively.) (E) Live/dead staining showing MC3T3-E1 cell viability after culturing on hydrogel in the presence of H2O2. (F) Quantification analysis of live cells. (*And #Indicate p < 0.05 in comparison with the H2O2 group and GelMA group, respectively.) (G) LSCM images showing MC3T3-E1 cultured on different hydrogels following H2O2 treatment. (n = 3, each group). (H2O2, cells cultured on the tissue culture plate with H2O2). Scale bar: 200 μm (A), 200 μm (C), 100 μm (E) and 100 μm (G). Figure 4 The osteogenesis properties of GelMA/POM hydrogel in vitro. In vitro assay of effects of hydrogel on ALP activity and extracellular calcium nodule production during osteogenesis differentiation of MC3T3-E1. (A) Alizarin red S staining. (B) Quantitative analysis of mineralized nodules. (C) Alkaline phosphatase activity. (D) Alkaline phosphatase staining. (*, # And a indicate p < 0.05 in comparison with the Control group, H2O2 group and GelMA group, respectively). (Control, cells cultured without H2O2). (n = 3, each group). Scale bar: 200 μm (A) and 200 μm (D). The authors advise these corrections do not significantly impact the overall findings and conclusions of the article or alter the interpretations or validity of the research. The authors apologize for any confusion these errors may have caused and appreciate the opportunity to rectify them.

Bing Yang,1,&ast; Xiaochun Wu,1,&ast; Jingqi Zeng,1 Jinjing Song,1 Tianhao Qi,1 Yanjun Yang,1 Dingkun Liu,1 Yulin Mo,1 Miao He,2 Liang Feng,1 Xiaobin Jia1 1School of Traditional Chinese Pharmacy, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 211198, People’s Republic of China; 2College of Pharmacy, Dali University, Dali, Yunnan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaobin Jia; Liang Feng, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, People’s Republic of China, Email jiaxiaobin2015@163.com; wenmoxiushi@163.comPurpose: Enhancing the dissolution, permeation and absorption of active components with low solubility and poor permeability is crucial for maximizing therapeutic efficacy and optimizing functionality. The objective of this study is to investigate the potential of natural polysaccharides as carriers to improve the biopharmaceutical properties of active components.Methods: In this study, we employed four representative flavonoids in Astragali Radix, namely Calycosin-7-O-β-D-glucoside (CAG), Ononin (ON), Calycosin (CA) and Formononetin (FMN), as a demonstration to evaluate the potential of Astragalus polysaccharides (APS) as carriers to improve the biopharmaceutical properties, sush as solubility, permeability, and absorption in vivo. In addition, the microstructure of the flavonoids-APS complexes was characterized, and the interaction mechanism between APS and flavonoids was investigated using multispectral technique and molecular dynamics simulation.Results: The results showed that APS can self-assemble into aggregates with a porous structure and large surface area in aqueous solutions. These aggregates can be loaded with flavonoids through weak intermolecular interactions, such as hydrogen bonding, thereby improving their gastrointestinal stability, solubility, permeability and absorption in vivo.Conclusion: We discovered the self-assembly properties of APS and its potential as carriers. Compared with introducing external excipients, the utilization of natural polysaccharides in plants as carriers may have a unique advantage in enhancing dissolution, permeation and absorption. Keywords: astragalus polysaccharides, flavonoids, self-assembly, solubility, permeability, natural carrier

Huiying Yan,1 Lina Feng,2 Mingquan Li1 1Department of Neurology, the Third Affiliated Clinical Hospital of the Changchun University of Chinese Medicine, Changchun, Jilin Province, People’s Republic of China; 2Shandong Key Laboratory of TCM Multi-Targets Intervention and Disease Control, the Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong Province, People’s Republic of ChinaCorrespondence: Lina Feng, The Second Affiliated Hospital of Shandong First Medical University, Yingsheng Road 2, Taian, Shandong Province, 271000, People’s Republic of China, Tel +86-15543120222, Email fenglina0001@163.com Mingquan Li, The Third Affiliated Clinical Hospital of the Changchun University of Chinese Medicine, Boshuo Road, Changchun, Jilin, 130117, People’s Republic of China, Tel +86-15948000577, Email Limingquan0001@126.comAbstract: Alzheimer’s disease is a prevalent form of dementia among elderly individuals and is characterized by irreversible neurodegeneration. Despite extensive research, the exact causes of this complex disease remain unclear. Currently available drugs for Alzheimer’s disease treatment are limited in their effectiveness, often targeting a single aspect of the disease and causing significant adverse effects. Moreover, these medications are expensive, placing a heavy burden on patients’ families and society as a whole. Natural compounds and extracts offer several advantages, including the ability to target multiple pathways and exhibit high efficiency with minimal toxicity. These attributes make them promising candidates for the prevention and treatment of Alzheimer’s disease. In this paper, we provide a summary of the common natural products used in Chinese medicine for different pathogeneses of AD. Our aim is to offer new insights and ideas for the further development of natural products in Chinese medicine and the treatment of AD.Keywords: Alzheimer’s disease, β-amyloid deposition, tau-protein hyperphosphorylation, natural products, Chinese herbal medicine, review

Pascal Owusu-Agyemang,1,2 Lei Feng,3 Juan P Cata1,2 1Department of Anesthesiology and Perioperative Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA; 2Anesthesiology and Surgical Oncology Research Group, Houston, TX, USA; 3Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, USACorrespondence: Pascal Owusu-Agyemang, Department of Anesthesiology and Perioperative Medicine, the University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 0401, Houston, TX, 77030, USA, Tel + 1 832 465 8964, Email poagyemang@mdanderson.orgPurpose: Sustained opioid use is a well-known complication after surgery. Our objective was to determine whether there is any association between a patient’s race or ethnicity and the sustained use of opioids in the year following surgery. Opioid use over the initial 3, 6, and 12 postoperative months was categorized as “sustained early”, persistent, and chronic, respectively.Patients and Methods: Single-institution retrospective study of adults (≥ 18 years) who had undergone open abdominal surgery for cancer. Multivariable logistic regression was used to evaluate the association between race/ethnicity and opioid use.Results: Of the 3523 patients included in the study, 2543 (72.2%) were non-Hispanic (NH) White, 476 (13.5%) were Hispanic or Latino, 262 (7.4%) were NH-Black, 186 (5.3%) were Asian, and 56 (1.6%) belonged to other racial or ethnic groups. The overall rates of sustained early, persistent, and chronic opioid use were 15.9%, 7.1%, and 2.6%, respectively. In the multivariable analysis, patient race/ethnicity was associated with sustained early postoperative opioid use (p-value=0.037), with Hispanics/Latinos having significantly higher odds than NH-Whites (OR = 1.382 [95% CI: 1.057– 1.808]; p = 0.018). However, neither persistent nor chronic opioid use was associated with race/ethnicity (p = 0.697 and p = 0.443, respectively).Conclusion: In this retrospective study of adults who had undergone open abdominal surgery, patient race/ethnicity was not consistently associated with the development of sustained opioid use over the first 12 postoperative months.Keywords: race, ethnicity, persistent, chronic, opioids, cancer

Beibei Luo,1 Wenbo Xu,1 Lei Feng,2 Jingyi Chen,1 Rui Shi,3 Huiying Cao2 1Clinical Laboratory, People’s Hospital of Yuxi City, Yuxi City, Yunnan Province, People’s Republic of China; 2Clinical Laboratory, Yan’an Hospital of Kunming City, Kunming City, Yunnan Province, People’s Republic of China; 3Department of Laboratory, The Sixth Affiliated Hospital of Kunming Medical University, Yuxi City, Yunnan Province, People’s Republic of ChinaCorrespondence: Wenbo Xu, Clinical Laboratory, People’s Hospital of Yuxi City, Yuxi City, Yunnan Province, People’s Republic of China, Email xwb103196@sina.comIntroduction: Obesity is a risk factor for the development of type 2 diabetes (T2DM) as well as its associated metabolic complications. Central obesity, characterized by an increased visceral fat area (VFA), is contributed to the development of T2DM. However, the relationship between VFA and HbA1c is not particularly clear.Methods: A total of 3173 patients with T2DM participated in the study at the Metabolic Management Center (MMC), with anthropometric and biochemical measurements recorded. To examine the association between HbA1c and VFA, fitting curves were plotted, facilitating a comprehensive observation of their relationship.Results: HbA1c was inversely associated with VFA (β − 1.79, 95% CI − 2.34~− 1.24, P < 0.001). The fitted curve shows that VFA increased with the increase of HbA1c when it was less than 8.62%. When it was greater than 8.62%, VFA decreased as HbA1c increased. Using linear inflection point analysis, we found that its inflection point interval falls within 8.36%~8.88%.Conclusion: VFA was positively associated with HbA1c in individuals with T2DM. Furthermore, the relationship between the two variables was an inverted U-shaped association.Keywords: HbA1c, obesity, diabetes mellitus

Xin Zhang,1,&ast; Huixian Zhang,1,&ast; Lan-Fang Li,1 Lei Feng,1 Qiao Liu2 1Department of Clinical Pharmacy, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, People’s Republic of China; 2Department of Pharmacy, The Second Xiangya Hospital of Central South University, Central South University, Changsha, Hunan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiao Liu, Department of Pharmacy, The Second Xiangya Hospital of Central South University, Central South University, Changsha, Hunan, People’s Republic of China, Email liuqiao6767@csu.edu.cnPurpose: The five-year update data from the KEYNOTE-407 study have unveiled noteworthy improvements in survival outcomes achieved with pembrolizumab plus chemotherapy (Pembro+Chemo) compared to placebo plus chemotherapy (Placebo+Chemo) for patients with previously untreated metastatic squamous non-small cell lung cancer (NSCLC). Building upon this finding, our study sought to evaluate the cost-effectiveness of Pembro+Chemo, utilizing the latest available data, from the perspective of the Chinese health care system.Patients and Methods: A Markov model was employed to compare the quality-adjusted life-year (QALY), life-year (LY), total cost, and incremental cost-effectiveness ratio (ICER) between Pembro+Chemo and Placebo+Chemo. The clinical and safety data were derived from the five-year update date of the KEYNOTE-407 study. Sensitivity analyses were conducted to assess the uncertainty of the model, and additional subgroup analyses were performed to explore specific subpopulations.Results: For patients with previously untreated metastatic squamous NSCLC, the utilization of Pembro+Chemo resulted in a improvement of 0.61 quality-adjusted life years (QALYs) along with a cost reduction of &dollar;17,491.52 when compared to Placebo+Chemo. Notably, across various subgroups with different tumor proportion scores (TPS), Pembro+Chemo demonstrated enhanced QALYs and lower total costs.Conclusion: From the perspective of the Chinese health care system, first-line Pembro+Chemo emerges as a dominant treatment option over Placebo+Chemo for the treatment of metastatic squamous NSCLC.Keywords: pembrolizumab, cost-effectiveness, squamous NSCLC, KEYNOTE-407

Weiling Zhou,1 Qian Gao,1 Lianjing Wang,2 Weijing Li,2 Cuiying He,2 Yanting Li,3 Lei Feng,1 Wei Liu,2 Lihong Liu,2 Yuan Wang1 1Department of Endocrine and Metabolic Diseases, The Fourth Hospital of Hebei Medical University, Shijiazhuang, HeBei Province, 050000, People’s Republic of China; 2Department of Hematology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, HeBei Province, 050000, People’s Republic of China; 3Department of Glandular Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, HeBei Province, 050000, People’s Republic of ChinaCorrespondence: Lihong Liu, Department of Hematology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, HeBei Province, 050000, People’s Republic of China, Email liulihong111222@163.com Yuan Wang, Department of Endocrine and Metabolic Diseases, The Fourth Hospital of Hebei Medical University, Shijiazhuang, HeBei Province, 050000, People’s Republic of China, Email wyuan1111122222@163.comBackground: Diffuse large B-cell lymphoma (DLBCL) involving the breast, spleen, and bone in a male patient with hepatitis B virus (HBV) infection is extremely rare in clinical practice.Case Presentation: We report a case of DLBCL involving the breast, spleen, and bone (triple expression of Bcl-2+, Bcl-6+, and 70% positive C-mcy) in a male patient with HBV admitted to our hospital. The patient was treated with EPOCH× 4, lenalidomide+EPOCH× 2 chemotherapy, intermittent methotrexate intrathecal injections to prevent central invasion, and autologous stem cell transplantation (ASCT). The patient is currently in complete remission, and the follow-up time was 43 months.Conclusion: A patient with DLBCL involving the breast, spleen, and bone can be treated with a combination of multiple regimens. If the patient’s economic conditions permit it, ASCT can be considered.Keywords: breast, viral hepatitis B, diffuse large B-cell lymphoma, triple expression, autologous stem cell transplantation

Ling Feng, Rongyan Wei, Zhenwei Zhai Department of Endocrinology and Metabolism, Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of ChinaCorrespondence: Ling Feng; Zhenwei Zhai, Department of Endocrinology and Metabolism, Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, No. 6, Taoyuan Road, Nanning, Guangxi, 530021, People’s Republic of China, Email lingfeng0526@163.com; 1334684753@qq.com

Shuai Shao,1,&ast; Zhijin Zhang,1,&ast; Lin Feng,2 Lirong Liang,2 Zhaohui Tong1 1Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China; 2Department of Clinical Epidemiology, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhaohui Tong, Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, NO. 8, Gong Ti South Road, Chao-Yang District, Beijing, 100020, People’s Republic of China, Email tongzhaohuicy@sina.comPurpose: To discover potential inflammatory biomarkers, which can compare favorably with traditional biomarkers, and their best cut-offs at first admission to predict clinical outcomes (short-term and long-term) and the risk of readmission among acute exacerbations of chronic obstructive pulmonary disease (AECOPD) patients.Patients and Methods: Novel inflammatory biomarkers (such as the neutrophil–lymphocyte ratio [NLR], platelet–lymphocyte ratio [PLR], etc.) were compared with traditional biomarkers by Pearson’s correlation test. Logistic regression analysis and receiver operating characteristic (ROC) curves were applied to judge the accuracy of these novel biomarkers to predict in-hospital mortality.Results: Surviving AECOPD patients had lower NLR, PLR, and lymphocyte-to-monocyte ratios than non-survival patients (all P < 0.001). According to Pearson’s correlation test, there was a linear correlation between novel and traditional biomarkers (all P < 0.05). In terms of a single biomarker, the AUC value of NLR was the largest, which was not inferior to C-reactive protein (Z-P = 0.064), and superior to erythrocyte sedimentation rate (Z-P = 0.002) and other novel single inflammatory biomarkers (all Z-P < 0.05). The mortality of patients with NLR ≥ 4.43 was 2.308-fold higher than that of patients with NLR < 4.43. After dividing patients into a higher or lower NLR group, pooled results showed that patients with NLR ≥ 4.43 had a higher rate of treatment failure, intensive care unit admission, longer hospital length of stay, one-year mortality after the index hospitalization, and overall mortality than patients with NLR < 4.43 (all P < 0.001). Patients with NLR ≥ 4.43 were associated with higher and earlier first readmission due to AECOPD than patients with lower NLR.Conclusion: NLR was the best to forecast the clinical prognosis and readmission risk among AECOPD patients, which was not inferior to CRP, and the best cut-off value of NLR was 4.43.Keywords: acute exacerbations of chronic obstructive pulmonary disease, neutrophil–lymphocyte ratio, mortality, inflammatory biomarkers, readmission rate, treatment failure rate

Lihong Bao,1,&ast; Chunfen Peng,2,&ast; Jingting He,2 Chengqin Sun,1 Lijuan Feng,1 Yang Luo1 1Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Luo; Jingting He, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China, Email yangluo@hust.edu.cn; hejingting@hust.edu.cnBackground: The role of fear-avoidance beliefs (FAB) in patients with chronic pain has been widely confirmed. However, few conclusions have been drawn about its role in postoperative patients.Objective: To explore the characteristics of FAB in postoperative patients after lung surgery as well as the effect of threat learning on FAB.Methods: Between May and September 2022, this study recruited 150 participants who had undergone thoracoscopic surgery. Variables such as age, gender, education, chronic pain, fear of pain, surgery method, pain intensity, FAB, cough, ambulation and threat learning were collected and subjected to correlation analysis and stepwise regression.Results: The correlation analysis revealed that FAB was associated with age (r = − 0.183, p < 0.05), gender (r = − 0.256, p < 0.01), and preoperative FOP-9 (r = 0.400, p < 0.01). Postoperative variables such as pain intensity (r = 0.574, p < 0.01), initiation day of ambulation (r = 0.648, p < 0.01), total numbers of ambulation (r = − 0.665, p < 0.01), and cough performance (r = − 0.688, p < 0.01) were correlated with FAB. Furthermore, FAB was highly correlated with indicators of threat learning: direct (r = 0.556, p < 0.01), observation (r = 0.655, p < 0.01), and instruction (r = 0.671, p < 0.01). The highest variance explanation model of stepwise regression which explained 52.8% of the variance including instruction (B=1.751; p< 0.01), direct (B=1.245; p< 0.01), observation (B=0.768; p< 0.01), age (B=− 0.085; p< 0.01), and surgery method (B=1.321; p< 0.05).Conclusion: Patients commonly experience FAB after lung surgery, which can directly affect their recovery behaviors such as ambulation and active coughing. The formation of FAB is influenced by threat learning, which suggests that controlling threat learning is important in preventing postoperative FAB.Keywords: fear-avoidance, threat learning, fear of pain, postoperative pain, lung surgery

JinLian Li,1,&ast; LiQing Feng,1,&ast; Xing Shui,1 Chengsong Deng,2 Ailing Hu3 1Department of Cardiac Care Unit, the Third Affiliated Hospital, SunYat-Sen University, Guangzhou, People’s Republic of China; 2Department of Neurology Medicine, Lingnan Hospital, the Third Affiliated Hospital, SunYat-Sen University, Guangzhou, People’s Republic of China; 3Department of Nursing, the Third Affiliated Hospital, SunYat-Sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ailing Hu, Department of Nursing, the Third Affiliated Hospital, SunYat-Sen University, Guangzhou, People’s Republic of China, Tel/Fax +86-13527658998, Email h-ailing@163.comBackground: Chronic heart failure (CHF) is a cardiovascular disease that seriously jeopardizes global human health. Studies indicate that good self-management can be effective in controlling disease symptoms. However, there is still insufficient evidence on the association between self-management and symptom burden among CHF patients. This study aimed to observe and assess the correlation of the self-management with the symptom burden and each dimension status in patients with CHF.Methods: This was a cross-sectional study. Data were collected in-hospital using convenience sampling, and 128 patients with CHF were included. A general data questionnaire was used to collect demographic and disease-related data. The Memorial Symptom Assessment Scale-Heart Failure was used to measure patients’ symptom burdens. The Heart Failure Self-Management Scale was used to measure the self-management level of patients. The correlation between self-management and symptom burden was analyzed using the Spearman correlation.Results: The total scores for symptom burden and self-management were 1.26 ± 0.49 and 49.97 ± 7.14, respectively. The total score of self-management was negatively correlated with that of symptom burden. The univariate linear regression analysis indicated that age, place of residence, smoking, residence status, New York Heart Association grade of cardiac function, and attitude toward the disease were risk factors for symptom burden. The multiple linear regression analysis indicated that the regression model with symptom burden as a dependent variable included three variables: drug management, symptom management, and attitude toward the disease.Conclusion: Hospitalized patients with CHF had heavy overall symptom burdens, and their self-management levels were moderate to low. There was a negative correlation between the total self-management score and each dimension of symptom burden.Keywords: chronic heart failure, symptom burden, self-management

Qian Gao, Lei Feng, Weiling Zhou, Xiaoli Li, Lanzi Yin, Yuan Wang Department of Endocrine and Metabolic Diseases, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050000, People’s Republic of ChinaCorrespondence: Yuan Wang, Department of Endocrine and Metabolic Diseases, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang City, Hebei Province, People’s Republic of China, Tel +86 18531116018, Email wyuan1111122222@163.comObjective: This study aims to investigate the predictive value of non-traditional blood lipid indices for metabolism dysfunction-associated fatty liver disease (MAFLD) in non-overweight/obese patients with type 2 diabetes mellitus (T2DM).Methods: A retrospective observational study was conducted, including non-overweight/obese patients with T2DM who visited the Fourth Hospital of Hebei Medical University between August 2018 and August 2022. The low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C) ratio, the triacylglycerol-glucose index (TyG) multiplied by body mass index (BMI), and TyG/HDL-C ratio were calculated.Results: The study involved 190 participants, of whom 34 were diagnosed with MAFLD (24 males and 10 females), while 156 did not have MAFLD (64 males and 92 females). Multivariable analysis revealed that aspartate transaminase (AST) (OR=1.216, 95% CI: 1.059– 1.374, P=0.006), blood uric acid (BUA) (OR=1.017, 95% CI: 1.002– 1.032, P=0.022), TyG&ast;BMI (OR=1.231, 95% CI: 1.051– 1.442, P=0.010), and TyG/HDL-C (OR=3.162, 95% CI: 1.228– 8.141, P=0.017) were independently associated with MAFLD. The TyG&ast;BMI index exhibited an area under the ROC curve (AUC) of 0.812, with 91.2% sensitivity and 69.2% specificity for MAFLD. The TyG/HDL-C index had an AUC of 0.929, with 85.3% sensitivity and 88.5% specificity for MAFLD.Conclusion: The results indicate that TyG&ast;BMI and TyG/HDL-C are independently associated with MAFLD in non-overweight/obese patients with T2DM.Keywords: metabolism dysfunction-associated fatty liver disease, body mass index, type 2 diabetes mellitus, cholesterol, LDL-C, HDL-C, obesity, TyG

Jiachen Li,1 Lirong Liang,1 Lin Feng,1 Siyu Cao,2 Yutong Samuel Cai,3 Xiaobo Li,4 Zhenbei Qian,2 Christopher E Brightling,5 Zhaohui Tong2 1Department of Clinical Epidemiology, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Centre for Environmental Health and Sustainability, Department of Population Health Sciences, University of Leicester, Leicester, UK; 4Beijing Key Laboratory of Environmental Toxicology, School of Public Health, Capital Medical University, Beijing, People’s Republic of China; 5Institute for Lung Health, NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, UKCorrespondence: Lirong Liang, Department of Clinical Epidemiology, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, No. 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel +86 010-85231547, Email llrcruie@163.comPurpose: Blood eosinophil is a promising biomarker for phenotyping patients with acute exacerbation of COPD (AECOPD). We aimed to evaluate the prognostic value of eosinophil on short- and long-term outcomes stratified by corticosteroid treatment among AECOPD inpatients.Patients and Methods: In this retrospective cohort study, we included patients hospitalized for AECOPD from July 2013 to June 2021 in Beijing, China. Clinical data were collected from electronic medical records. The blood eosinophil count was measured within 24h after admission. Eosinophilic AECOPD was defined as having an eosinophil percentage ≥ 2%. The study outcomes were length of stay (LOS), treatment failure, and AECOPD readmission risk within 3 years of discharge. Multivariable models were used to analyze the associations between blood eosinophil count and outcomes stratified by corticosteroid treatment during hospitalization.Results: A total of 2406 AECOPD patients were included. The median LOS of AECOPD patients was 10 (interquartile range: 8– 14) days. The eosinophil percentage was negatively associated with LOS (P-trend=0.014). Compared with the non-eosinophilic AECOPD group, the eosinophilic group had a 58% lower risk of treatment failure (OR=0.42, 95% CI: 0.20– 0.89) in patients treated with systemic corticosteroids, but no association was observed in those treated with inhaled corticosteroids (ICS) only (OR=0.95, 95% CI: 0.60– 1.52). The eosinophilic group had an increased risk of 90-day re-admission in patients treated with ICS only (HR=1.51, 95% CI: 1.00– 2.29), but not in patients treated with systemic corticosteroids during hospitalization (HR=0.67, 95% CI: 0.39– 1.15). No statistically significant results were found for 180-day, 1-year, or 3-year readmission risk.Conclusion: Elevated blood eosinophils in AECOPD were associated with shorter length of stay and improved response to treatment with systemic corticosteroids, but not inhaled corticosteroids. Our study suggested that a therapeutic approach of using systemic corticosteroid may benefit patients present with eosinophilic AECOPD.Keywords: chronic obstructive pulmonary disease, eosinophilic inflammation, glucocorticoids, interaction

Yanqing Xing,1 Liting Feng,1 Yangdou Dong,2 Yupeng Li,1 Lulu Zhang,1 Qiannan Wu,1 Rujie Huo,1 Yanting Dong,1 Xinrui Tian,1 Xinli Tian3 1Department of Respiratory and Critical Care Medicine, The Second Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2College of Basic Medicine, Shanxi Medical University, Taiyuan, People’s Republic of China; 3Department of Cardiology, Chinese PLA General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Xinrui Tian, Department of Respiratory and Critical Care Medicine, The Second Hospital of Shanxi Medical University, No. 382, Wuyi Road, Xinghualing District, Taiyuan, People’s Republic of China, Tel +8613834575570, Email tianxr@126.com Xinli Tian, Department of Cardiology, Chinese PLA General Hospital, No. 7 Medical Center No. 5 Nanmencang, Dongsijiao, Dongcheng District, Beijing, People’s Republic of China, Email 18600501329@126.comPurpose: Asthma is a chronic inflammatory airway disease involving multiple mechanisms, of which ferroptosis is a form of programmed cell death. Recent studies have shown that ferroptosis may play a crucial role in the pathogenesis of asthma, but no specific ferroptosis gene has been found in asthma, and the exact mechanism is still unclear. The present study aimed to screen ferroptosis genes associated with asthma and find therapeutic targets, in order to contribute a new clue for the diagnosis and therapy of asthma.Methods: Ferroptosis-related differentially expressed genes (FR-DEGs) in asthma were selected by the GSE41861, GSE43696 and ferroptosis datasets. Next, the FR-DEGs were subjected by GO and KEGG enrichment, and the mRNA-miRNA network was constructed. Then, GSEA and GSVA enrichment analysis and Immune infiltration analysis were performed, followed by targeted drug prediction. Finally, the expression of FR-DEGs was confirmed using GSE63142 dataset and RT-PCR assay.Results: We found 13 FR-DEGs by the GSE41861, GSE43696 and ferroptosis database. Functional enrichment analysis revealed that the 13 FR-DEGs were enriched in oxidative stress, immune response, ferroptosis, lysosome, necrosis, apoptosis etc. Moreover, our results revealed the mRNA-miRNA network of the FR-DEGs and identified candidate drugs. Also, immune infiltration revealed that ELAVL1, CREB5, CBR1 and NR1D2 are associated with the immune cells and may be potential targets in asthma. Finally, 10 FR-DEGs were validated by the GSE63142 database. It was verified that 7 FR-DEGs were differentially expressed by collecting asthma patients and healthy controls.Conclusion: This study ultimately identified 7 FR-DEGs for the diagnosis and therapy of asthma. These 7 FR-DEGs contribute to oxidative stress and immune responses. This study provides potential therapeutic targets and biomarkers for asthma patients, shedding further light on the pathogenesis of asthma as well as providing new insights into the treatment of asthma.Keywords: asthma, bioinformatics, ferroptosis, GSEA, GSVA, immune microenvironment

Yanqing Xing,1 Yupeng Li,1 Liting Feng,1 Rujie Huo,1 Xinkai Ma,1 Yanting Dong,1 Dai Liu,1 Yuheng Niu,2 Xinrui Tian,1,&ast; Erjing Chen1,&ast; 1The Second Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2The First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinrui Tian; Erjing Chen, The Second Hospital of Shanxi Medical University, No. 382, Wuyi Road, Xinghualing District, Taiyuan, Shanxi, People’s Republic of China, Email tianxr@126.com; mayyoubehappy44@163.comPurpose: To analyze the clinical characteristics and prognosis of patients hospitalized with non-severe, severe pneumonia and death in Omicron COVID-19.Patients and Methods: We collected clinical data from 118 patients with COVID-19 in China from 18 December, 2022 and 5 February, 2023. According to the outcome, the patients were divided into non-severe group, severe group and death group. Subsequently, we statistically analyzed the general condition, clinical manifestations, laboratory parameters, NLR, MLR, PLR and HALP of these groups. We also retrospectively analyzed the possible factors affecting the prognostic regression of patients with COVID-19.Results: A total of 118 COVID-19 patients were enrolled in this study, including 64 non-severe patients, 38 severe patients and 16 death patients. Compared with the non-severe group, T lymphocytes, B lymphocytes, Th1, Th2, Th17, Treg cells, IgA, IgG, IgM in the severe and death groups decreased more significantly (P< 0.05). The levels of myocardial markers, ALT, AST, BUN, Cr, D-dimer, fibrinogen, NLR, MLR and PLR in the severe and death groups were significantly higher than those in the non-severe group (P< 0.05). The level of HALP was significantly lower than that of non-severe group (P< 0.05). MLR is not only an independent risk factor for the transition from non-severe to severe disease, but also an independent risk factor for predicting the possibility of death in COVID-19 patients.Conclusion: The analysis of COVID-19 patients in China showed that severe patients were older, more likely to have related complications, lower lymphocyte count, liver and kidney function disorder, glucose and lipid metabolism disorders, myocardial injury, and abnormal coagulation function, suggesting the need for early anticoagulant therapy. In addition, NLR, MLR, PLR and HALP can be used as biomarkers to evaluate the severity and prognosis of COVID-19 patients.Keywords: COVID-19, omicron, clinical characteristics, lymphocyte subpopulation, Shanxi

Bo Li,1 Weiqing Wu,1 Aijun Liu,1 Lifeng Feng,1 Bin Li,1 Yong Mei,1 Li Tan,1 Chaoyang Zhang,2 Yangtao Tian1 1Department of Pancreatic Surgery, Shangluo Center Hospital, Shangluo, Shaanxi, 726000, People’s Republic of China; 2Department of Ultrasound Medicine, Shangluo Center Hospital, Shangluo, Shaanxi, 726000, People’s Republic of ChinaCorrespondence: Yangtao Tian, Department of Pancreatic Surgery, Shangluo Center Hospital, 37 Shangyang, Shangzhou, Shangluo, Shaanxi, 726000, People’s Republic of China, Email 928763821@qq.comBackground: Severe acute pancreatitis (SAP) can progress to lung and kidney dysfunction, and blood clotting within 48 hours of its onset, and is associated with a high mortality rate. The aim of this study was to establish a reliable diagnostic prediction model for the early stage of severe pancreatitis.Methods: The clinical data of patients diagnosed with acute pancreatitis from October 2017 to June 2022 at the Shangluo Central Hospital were collected. The risk factors were screened by least absolute shrinkage and selection operator (LASSO) regression analysis. A novel nomogram model was then established by multivariable logistic regression analysis.Results: The data of 436 patients with acute pancreatitis, 45 (10.3%) patients had progressed to SAP. Through univariate and LASSO regression analyses, the neutrophils (P < 0.001), albumin (P < 0.001), blood glucose (P < 0.001), serum calcium (P < 0.001), serum creatinine (P < 0.001), blood urea nitrogen (P < 0.001) and procalcitonin (P = 0.005) were identified as independent predictive factors for SAP. The nomogram built on the basis of these factors predicted SAP with sensitivity of 0.733, specificity of 0.9, positive predictive value of 0.458 and negative predictive value of 0.967. Furthermore, the concordance index of the nomogram reached 0.889 (95% CI, 0.837– 0.941), and the area under the curve (AUC) in receiver operating characteristic curve (ROC) analysis was significantly higher than that of the APACHEII and ABISAP scoring systems. The established model was validated by plotting the clinical decision curve analysis (DCA) and clinical impact curve (CIC).Conclusion: We established a nomogram to predict the progression of early acute pancreatitis to SAP with high discrimination and accuracy.Keywords: acute pancreatitis, prediction model, risk factor, nomogram, decision curve analysis

Beibei Luo,1 Lei Feng,2 Qianye Bi,1 Rui Shi,1 Huiying Cao,1 Yanbi Zhang1 1Department of Laboratory, The Sixth Affiliated Hospital of Kunming Medical University, Yuxi City, Yunnan Province, 653100, People’s Republic of China; 2Intensive Care Unit, People’s Hospital of Yuxi City, Yuxi City, Yunnan Province, 653100, People’s Republic of ChinaCorrespondence: Lei Feng, Department of Laboratory, The Sixth Affiliated Hospital of Kunming Medical University, 21 Nieer Road, Yuxi City, Yunnan Province, 653100, People’s Republic of China, Email fngj2004@163.comIntroduction: Hypertension (HTN) is a significant risk factor for cardiovascular disease. Identifying new risk factors for hypertension is crucial. This study aims to determine the predictive value of fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) in the development of hypertension.Methods: In this study, we examined 16,026 individuals without diabetes and other cardiovascular risk factors who were underwent annual screening at the People’s Hospital of Yuxi, Yunnan, China from 2013 to 2016. The participants were divided into two groups: normoglycemic and prediabetic. Normoglycemia was defined as having an HbA1c level of less than 5.7% and an FPG level of less than 5.6 mmol/ L. Prediabetes was defined according to the ADA criteria, which includes having an HbA1c level between 5.7% and 6.5%, or an impaired fasting glucose level between 5.6 mmol/L and 7.0 mmol/L. The participants were further divided into four subgroups based on their FPG and HbA1c levels: normoglycemia, impaired HbA1c only, FPG only, and both parameters impaired.Results: The cohort study was conducted on 16,026 participants from Yunnan, China, consisting of 60.6% males and 39.4% females, with a mean age of 44.6 ± 12.5 years. The study revealed that prediabetes was independently associated with an increased risk for HTN (OR 1.53, 95% CI 1.41~1.67, P < 0.001). The analysis of different subgroups of HbA1c and FPG showed that FPG was a better predictor of HTN than HbA1c, regardless of the group.Conclusion: FPG and HbA1c were significantly associated with the future development of HTN in individuals with prediabetes.Keywords: glycated hemoglobin, glucose, hypertension

Qiao Zhu,1,&ast; Qingkai Zhao,2,&ast; Ping Ping,3,&ast; Qian Zhang,4,&ast; Li Gong,5 Long Feng,6 Yali Zhao,1 Shihui Fu7,8 1Central Laboratory, Hainan Hospital of Chinese People’s Liberation Army General Hospital, Sanya, People’s Republic of China; 2Department of Health Medicine, Hainan Hospital of Chinese People’s Liberation Army General Hospital, Sanya, People’s Republic of China; 3General Station for Drug Instrument Supervision and Control, Joint Logistic Support Force of Chinese People’s Liberation Army, Beijing, People’s Republic of China; 4Department of Neurology, Hainan Hospital of Chinese People’s Liberation Army General Hospital, Sanya, People’s Republic of China; 5Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi’an, People’s Republic of China; 6Department of Anesthesiology, Hainan Hospital of Chinese People’s Liberation Army General Hospital, Sanya, People’s Republic of China; 7Department of Cardiology, Hainan Hospital of Chinese People’s Liberation Army General Hospital, Sanya, People’s Republic of China; 8Department of Geriatric Cardiology, Chinese People’s Liberation Army General Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shihui Fu, Department of Cardiology, Hainan Hospital of Chinese People’s Liberation Army General Hospital, Sanya, Hainan, 572013, People’s Republic of China, Email xiaoxiao0915@126.com Yali Zhao, Central Laboratory, Hainan Hospital of Chinese People’s Liberation Army General Hospital, Sanya, Hainan, 572013, People’s Republic of China, Email zhaoyl301@163.comBackground: Hair chemical elements reflect physical condition over time. Collection, transporting, and storing hair is more convenient than handling blood. Hair elements show higher levels for a long time, which allows for more accurate and sensitive results than using blood. Studies explored the relationships between elements and age, without full consideration of nutritional status, in older people. This study explored the relationships between hair chemical elements and Geriatric Nutritional Risk Index (GNRI) in oldest-old and centenarian populations to provide an updated reference for nutritional evaluation of older people.Methods: A total of 152 participants over 80 years old underwent home interviews and physical examinations. An inductively coupled plasma mass spectrometer was used to detect hair chemical elements.Results: Women accounted for 77.0% of participants. Women had lower levels of zinc, and higher levels of selenium, manganese, lead, iron, and copper than men (P< 0.05 for all). Ninety-two participants formed the 80– 99 year group, and 60 participants formed the 100+ year group. Centenarians had lower levels of selenium, lead, iron, and copper than those aged 80– 99 years (P< 0.05 for all). Hair selenium levels were positively associated with GNRI (odds ratio: 11.55, 95% confidence interval: 3.42– 19.68, P < 0.05) based on a multivariate linear regression analysis. Other chemical elements had no significant associations with GNRI based on a multivariate linear regression analysis.Conclusion: Chemical elements and nutrient status were altered based on age and gender, and an association existed between hair selenium and nutritional status in older people. Chemical elements may influence and indicate nutritional status in older people.Keywords: centenarian, oldest-old, hair chemical elements, nutritional status, selenium

Jihong Li,1,&ast; Lili Zhang,2,&ast; Xiaohui Yang,2 Pan Wang,2 Lijie Feng,2 Erkun Guo,3 Yuan Chen2 1Department of Laboratory Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China; 2Department of Pediatrics, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China; 3Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuan Chen, Department of Pediatrics, The Second Hospital of Hebei Medical University, 215 Heping West Road, Shijiazhuang, 050000, Hebei, People’s Republic of China, Tel +86-311-66002936, Email ychen1974@126.comBackground: Cerebrospinal fluid (CSF) pathogen culture suffers from the drawbacks of prolonged cycle time and a low positivity rate in diagnosing intracranial infections in children. This study aims to investigate the diagnostic potential of targeted next-generation sequencing (tNGS) in pediatric neurosurgery for central nervous system (CNS) infections.Methods: A retrospective study was conducted on children under 14 with suspected intracranial infections following craniocerebral trauma or surgery between November 2018 and August 2020. Routine, biochemical, smear, and pathogen culture tests were performed on CSF during treatment. The main parameters of CSF analysis encompassed white blood cells (WBC, × 106/L) count, percentage of multinucleated cells (%), protein levels (g/L), glucose concentration (GLU, mmol/L), chloride levels (mmol/L), and pressure (mmH2O). The outcomes of tNGS were assessed through the Receiver Operating Characteristic (ROC) curve and pertinent diagnostic parameters.Results: Among the 35 included pediatric patients, 22 were clinically diagnosed with CNS infection in neurosurgery, tNGS was confirmed in 18 cases. The sensitivity and specificity of tNGS were 81.8% and 76.9%, respectively, while the traditional method of CSF cultures and smears exhibited a sensitivity of 13.6% and a specificity of 100%. ROC curve analysis indicated an area under the curve (AUC) of 0.794 for tNGS and 0.568 for the CSF cultures and smears. CSF analysis indicated that the two groups exhibited statistically significant differences in terms of WBC count [330.0 (110.00– 2639.75) vs 14.00 (4.50– 26.50), P< 0.001] and percentage of multinuclear cells (%) [87.50 (39.75– 90.00) vs 0 (0– 10.00), P< 0.001]. However, the remaining parameters did not statistically significant differences between the groups (all P> 0.05).Conclusion: tNGS demonstrates a high degree of diagnostic accuracy when detecting infections within the CNS of pediatric neurosurgery patients. tNGS can effectively establish for diagnosing CNS infections by detecting pathogenic microorganisms and their corresponding virulence and/or resistance genes within the test samples.Keywords: targeted next-generation sequencing, neurosurgery, central nervous system infections, cerebrospinal fluid, diagnostic

Pengqi Zhang,1 Tianye Wang,1 Xiaoting Zhu,2 Lina Feng,1 Jiale Wang,1 Yunqiang Li,1 Xinyue Zhang,1 Tingting Cui,1 Mingquan Li2 1College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin Province, People’s Republic of China; 2Neurology Department, Third Affiliated Clinical Hospital of Changchun University of Traditional Chinese Medicine, Changchun, Jilin Province, People’s Republic of ChinaCorrespondence: Mingquan Li, Neurology Department, Third Affiliated Clinical Hospital of Changchun University of Traditional Chinese Medicine, Changchun, 130033, People’s Republic of China, Tel +86-15543120222, Email liminhquan0001@126.comObjective: The objective of this study was to explore the neuroprotective mechanism of JDYZF in treating AD from the perspective of inflammation and intestinal microflora.Methods: A total of 24 APP/PS1 mice were randomly divided into four groups: model (n = 6), JDYZF low-dose (n = 6), JDYZF high-dose (n = 6), and positive drug (n = 6), six C57 mice were used as the control group. The body weights and diets of all mice were examined daily. After 8 weeks of administration, the learning and memory of mice were evaluated by the Morris water maze test. The histopathological changes of hippocampus, liver and kidney in mice were observed by HE staining after being euthanized. The expression of p-tau in hippocampus tissue was detected by immunohistochemistry. After that, 16S rDNA sequencing was used to investigate the relationship between JDYZF and intestinal microbiota. Finally, a comparison of TLR4, p65, p-p65, iκB, p-iκB, and IL-1β protein expression in the hippocampus tissue of mice in each group was measured by Western blot.Results: The results showed that APP/PS1 mice taking JDYZF orally were generally in good condition. Compared with the control group, JDYZF significantly improved learning and memory ability in ethology. Histology showed that JDYZF improved the hippocampal structure of mice and inhibited the deposition of p-tau. JDYZF treatment could regulate the gut microbiota of APP/PS1 mice by increasing the richness of Lachnospiraceae, Ruminococcaceae, and Actinobacteria and reducing that of Alistipes and Muribaculaceae. It also significantly inhibited the activation of the TLR4/NF-κB signaling pathway in the brain. In addition, no obvious toxic reactions were found in the liver and kidney of APP/PS1 mice after taking JDYZF for 8 weeks.Conclusion: The findings revealed that JDYZF improved cognitive ability and alleviated the TLR4/NF-κB signaling pathway in APP/PS1 mice, and the modulating the gut microbiota presented here may help illuminate its activation mechanism.Keywords: Jiedu Yizhi Formula, Alzheimer’s disease, fecal microbial diversity, NF-κB, APP/PS1 mice

Long Feng,1,&ast; Di Wu,2,&ast; Ping Ping,3,&ast; Jieqiong Lin,4,&ast; Yali Zhao,5 Yao Yao,6,7 Pei Zhang,8 Shihui Fu2,9 1Department of Anesthesiology, Hainan Hospital of Chinese People’s Liberation Army General Hospital, Sanya, People’s Republic of China; 2Department of Cardiology, Hainan Hospital of Chinese People’s Liberation Army General Hospital, Sanya, People’s Republic of China; 3General Station for Drug and Instrument Supervision and Control, Joint Logistic Support Force of Chinese People’s Liberation Army, Beijing, People’s Republic of China; 4Department of Pathology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, People’s Republic of China; 5Central Laboratory, Hainan Hospital of Chinese People’s Liberation Army General Hospital, Sanya, People’s Republic of China; 6Center for the Study of Aging and Human Development and Geriatrics Division, Medical School of Duke University, Durham, NC, USA; 7Center for Healthy Aging and Development Studies, National School of Development, Peking University, Beijing, People’s Republic of China; 8School of Life Science, Beijing Institute of Technology, Beijing, People’s Republic of China; 9Department of Geriatric Cardiology, Chinese People’s Liberation Army General Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shihui Fu, Department of Cardiology, Hainan Hospital of Chinese People’s Liberation Army General Hospital, Sanya, People’s Republic of China, Email xiaoxiao0915@126.com Yali Zhao, Central Laboratory, Hainan Hospital of Chinese People’s Liberation Army General Hospital, Sanya, People’s Republic of China, Email zhaoyl301@163.comPurpose: Age related cognitive function (ARCF) is of increasing concern in an aging population. Few studies have examined the relationships between ARCF and antibody expression or blood pressure, particularly in older populations. Large sample sizes are needed to elucidate these relationships to inform better strategies for identification and prevention of cognitive decline. The present study was designed to investigate these relationships in Chinese oldest-old and centenarian adults.Patients and Methods: A household survey was performed that included 436 centenarians and 520 oldest-old adults (80– 99 years) residing in 16 cities and counties of Hainan province, China. ARCF was assessed using the mini-mental state examination.Results: The median age of participants in this study was 92 years, with a range of 80 to 116 years. Females accounted for 68.5% (655) of the participant pool. Multivariate linear regression analysis showed that age [Exp(B): − 0.220, 95% confidence interval (CI): − 0.270–-0.169], female gender [Exp(B): − 3.459, 95% CI:-4.458–-2.460], Han ethnicity [Exp(B): − 1.732, 95% CI: − 2.693–-0.772], serum creatinine [Exp(B): − 0.019, 95% CI: − 0.037–-0.001], immunoglobulin light chain KAP [Exp(B): − 0.008, 95% CI: − 0.015– 0.000], and anti-ribonucleoprotein antibody [Exp(B): − 6.393, 95% CI: − 10.898–-1.887] were negatively associated with ARCF (P < 0.05). Coronary artery disease [Exp(B): 1.957, 95% CI: 0.170– 3.744] and diastolic pressure [Exp(B): 0.041, 95% CI: 0.002– 0.079] were positively associated with ARCF (P < 0.05).Conclusion: ARCF was positively associated with diastolic pressure and negatively associated with antibody expression in Chinese oldest-old and centenarian adults.Keywords: age related cognitive function, antibody expression, centenarian, diastolic pressure, oldest-old

Dan Yuan,&ast; Yan Zhang,&ast; Yiping Li, Ling Li, Hong Yang, Wei Yang, Hang Yu, Liao Feng, Shu Liang Center for AIDS/STD Control and Prevention, Sichuan Center for Disease Control and Prevention, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shu Liang; Liao Feng, Email Liangshu523@163.com; 58539976@qq.comBackground: Choosing patients with HIV/AIDS (PLWH) with virologic failure observed in the course of treatment, and analyzing the CD4(+) T cell count of PLWH with different subtypes of virus and the risk factors of CD4 (+) T cell count recoveryMethods: Analyze and evaluate the change of median CD4(+) T cell count of PLWH infected with different HIV-1 subtypes in Sichuan Province after treatment by rank sum test. Univariate and multivariate logistic regression models were used to analyze the risk factors on CD4(+) T cell count growth after PLWH treatment.Results: A total of 4977 cases were analysed, including CRF07_BC 2358 cases (47.38%), CRF01_AE 1507 cases (30.28%), CRF08_BC 577 cases (11.59%), CRF85_BC 303 cases (6.09%) and other subtypes 232 cases (4.66%). PLWH infected with CRF85_BC had lower median CD4(+) T cell count after treatment (p < 0.05). It was found that protective factors to increase CD4(+) T cell count (p < 0.05) including females, Yi people, married or cohabiting, educational level at primary school or above, initial and recent treatment with Tenofovir + Lamivudine + Nevirapine Wellen, the second-line regimen with lopinavir/ritonavir (LPV/r) and the treatment time is more than 24 months. However, over 50 years old, the disease course is in AIDS stage, the infection of CRF01_AE and CRF85_BC virus was the risk factor on CD4(+) T cell count increase (p < 0.05). PLWH with higher initial CD4 level had a lower ratio of CD4(+) T cell count increase (≥ 50 cells/μL) (p < 0.05).Conclusion: Age, sex, ethnicity, marriage, education, disease status, treatment protocols, treatment time, initial CD4(+) T cell count, and virus subtype are the influencing factors of PLWH CD4(+) T cell count increase. The poor recovery of CD4(+) T cell count after treatment was observed in PLWH infected with CRF85_BC virus.Keywords: HIV, AIDS, antiretroviral therapy, CD4(+) T cells count

Mengxin Xu,1 Changrui Qian,2 Huaiyu Jia,1 Luozhu Feng,3 Shiyi Shi,1 Ying Zhang,3 Lingbo Wang,1 Jianming Cao,3 Tieli Zhou,1 Cui Zhou1 1Department of Clinical Laboratory, the First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, Wenzhou, People’s Republic of China; 2School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Department of Medical Laboratory Science, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, People’s Republic of ChinaCorrespondence: Tieli Zhou; Cui Zhou, Department of Clinical Laboratory, the First Affiliated Hospital of Wenzhou Medical University; Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, Wenzhou, 325035, People’s Republic of China, Tel +86 0577 8668 9885, Email wyztli@163.com; ZHOUCUI0826@163.comIntroduction: Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a serious threat to human public health. Ceftazidime–avibactam (CZA) is currently one of the few effective antibiotics for carbapenem-resistant Enterobacteriaceae (CRE).Methods and Results: Here, we analyzed two longitudinal Klebsiella pneumoniae clinical isolates (FK8578, FK8695) that were isolated from an ICU patient during antimicrobial treatment. Broth microdilution method, whole-genome sequencing (WGS) and comparative genomic analysis were used to elucidate the dynamics and mechanisms of antibiotic resistance. String test, quantification of capsule, biofilm inhibition test and Galleria mellonella (G. mellonella) infection model were used to explore the changes in virulence of the two clinical isolates. During antibiotic treatment, CRKP FK8578 underwent a series of drug resistance and virulence changes, including CZA resistance, carbapenem susceptibility and virulence attenuation. The results of WGS showed that mutation of blaKPC-2 to blaKPC-33 was responsible for the change of drug resistance phenotype between FK8578 and FK8695. pLVPK-like virulence plasmid without siderophore synthesis operon was identified in the two strains. On the other hand, the loss of hypermucoviscosity phenotype in the FK8695 strain may be related to a single nucleotide deletion of the rmpA gene, which would further lead to a decrease in virulence. Virulence results showed that compared with FK8578, FK8695 was negative in the string test, with decreased capsular production, smaller amounts of biofilm formation and higher survival rate of G. mellonella.Conclusion: This is the first report of CZA resistance and decreased virulence in ST11 CRKP strains during antimicrobial treatment. It is urgent to monitor CZA resistance and timely adjust anti-infective treatment strategies.Keywords: ceftazidime–avibactam, carbapenem-resistantKlebsiella pneumoniae, whole-genome sequencing, hypermucoviscosity, pLVPK-like plasmid, virulence attenuation

Dan Li, Jiayin Liu, Xue Zhang, Jing Han, Hui Jin, Long Wang, Li Feng, Zhisong Fan, Jing Zuo, Yudong Wang Department of Medical Oncology, The Fourth Hospital of Hebei Medical University and Hebei Provincial Tumor Hospital, Shijiazhuang, People’s Republic of ChinaCorrespondence: Yudong Wang, Department of Medical Oncology, The Fourth Hospital of Hebei Medical University and Hebei Provincial Tumor Hospital, 12 Jiankang Road, Shijiazhuang, People’s Republic of China, Tel +86 15931166600, Email 15931166600@126.comBackground: Lorlatinib has been suggested as the therapeutic option for patients with ROS1-rearranged non-small-cell lung cancer (NSCLC) after ROS1 tyrosine kinase inhibitor (TKI) failure. However, the mechanism mediating lorlatinib resistance has not been well elucidated in ROS1-rearranged NSCLC. Post- lorlatinib therapeutic options remain scarce.Case Presentation: Herein, we describe a 31-year-old female patient with stage IVB ROS1-rearranged NSCLC. She received 2nd line treatment with crizotinib after chemotherapy failure and achieved a partial response lasting for 15 months. An NF1 p.G127Ter mutation emerged as a potential crizotinib resistance mechanism. She subsequently received lorlatinib treatment and achieved a progression-free survival (PFS) of seven months. Based on the emergence of a resistant BRAF V600E, the patient was switched to a combinatorial targeted therapy with lorlatinib, dabrafenib, and trametinib and attained stable disease. She continued the treatment with a time-to-treatment failure of 5.5 months. The acquisition of NRAS p.Q61R and NTRK amplification may confer resistance to the combinatorial targeted therapy.Conclusion: To the best of our knowledge, we reported the first case demonstrating that BRAF p.V600E can mediate the lorlatinib resistance in ROS1-rearranged NSCLC and the combinational targeted therapy of ROS1 TKI with dabrafenib and trametinib may serve as an efficient therapeutic option for subsequent treatment.Keywords: NSCLC, ROS1 rearrangement, BRAF V600E, lorlatinib combined with dabrafenib and trametinib, case report

Yi Jiang,1 Lijie Wei,1 Huiting Zhang,1 Yuting Chen,1 Peng Gao,1 Jingyi Zhang,1 Xuan Zhou,1 Shenglan Zhu,1 Yuanyuan Du,1 Chenyun Fang,1 Jiaqi Li,2 Ling Feng,1 Mengzhou He,1 Shaoshuai Wang,1 Jun Yu1 1Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China; 2Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 33006, People’s Republic of ChinaCorrespondence: Jun Yu, Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Qiaokou District, Wuhan, Hubei Province, People’s Republic of China, Email yjtj2010@163.comIntroduction: Gestational diabetes mellitus (GDM) is one of the common metabolic disorders of pregnancy and results in poor pregnancy outcomes for both mother and fetus. MiR-17-5p is considered as the strongest predictor of metabolic syndrome status, but the relationship between GDM and miR-17-5p remains unclear. TXNIP, which leads to activation of NLRP3, is considered as a potential target of miR-17-5p, and the miR-17-5p/TXNIP/NLRP3 axis has been shown to play a major role in the occurrence and development of many metabolic diseases but has not been validated in GDM.Methods: MiR-17-5p was detected by RT-qPCR. The expression of TXNIP and NLRP3 in placenta was detected by immunofluorescence, RT-qPCR and Western blot. To explore the effect of miR-17-5p on TXNIP and NLRP3 and glucose uptake of HTR8/SVneo cells, miR-17-5p mimic and miR-17-5p inhibitor were transfected to achieve overexpression and inhibition. The interaction between miR-17-5p and TXNIP was confirmed by dual-luciferase reporter assay. Besides, glucose consumption of trophoblast cells was detected by glucose assay kit.Results: MiR-17-5p expression was down-regulated, while the expression of TXNIP and NLRP3 was up-regulated in GDM placental tissues. MiR-17-5p targeted TXNIP and inhibited its expression. MiR-17-5p also regulated NLRP3 expression and glucose uptake of HTR8/SVneo cells, which could be reversed by overexpression of TXNIP, suggesting that miR-17-5p improved glucose uptake of HTR8/SVneo cells by TXNIP/NLRP3 axis. The results were consistent with the above findings in high-glucose treated HTR8/SVneo cells.Conclusion: Our results suggested that miR-17-5p ameliorates the glucose uptake of HTR8/SVneo cells by TXNIP/NLRP3 axis, which may provide a new idea for offspring health of GDM patients.Keywords: diabetes, gestational, microRNAs, pregnancy, inflammation

Lingsong Feng, Guodong Ding, Yang Zhou, Haiyuan Zhu, Huiming Jiang Department of Urology, Meizhou People’s Hospital, Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translational Research of Hakka Population, Meizhou, People’s Republic of ChinaCorrespondence: Huiming Jiang, Tel +86-13560990839, Email jianghm0228@163.comBackground: Clear cell renal cell carcinoma (ccRCC), the most prevalent kidney cancer subtype, has a high mortality rate. Crystallin lambda 1 (CRYL1) encodes an enzyme that catalyzes the dehydrogenation of L-gulonate into dehydro-L-gulonate in uronate cycle. CRYL1 dysregulation has been linked to the progression of several cancers. This research aimed to evaluate the prognostic significance of CRYL1 expression in ccRCC prognosis.Methods: Clinical data and gene expression profiles on ccRCC were retrieved from the University of California Santa Cruz Xena platform. Differences (variations) in the expression profiles of CRYL1 in ccRCC and healthy tissues were found using RNA-sequencing data, and these findings were validated using qPCR with real-world samples. CRYL1 expression levels were also linked to clinicopathological characteristics, survival, and immune microenvironments. The potential pathway via which CRYL1 expression levels impact the prognosis of patients with ccRCC was investigated using gene set enrichment analysis (GSEA).Results: In ccRCC tissues, CRYL1 expression levels were lower compared to healthy renal tissues in TCGA cohort (n = 535, P < 0.001), which was validated in another real-world cohort (n = 14, P < 0.001). Lower CRYL1 expression levels were linked to unfavorable clinicopathological characteristics and prognoses (P < 0.001). According to multivariate Cox regression analysis (P < 0.001), CRYL1 expression levels in patients with ccRCC could serve as an independent prognostic indicator. Furthermore, a strong link between CRYL1 expression levels and immune microenvironment was observed (P < 0.001). Finally, GSEA revealed that CRYL1 expression levels (P < 0.001) were associated with fatty acid metabolism, G2M checkpoint delays, and epithelial-mesenchymal transitions in ccRCC.Conclusion: Our study found that lower levels of CRYL1 expression were linked to unfavorable clinicopathological characteristics and worse prognoses, and CRYL1 could serve as a new target for the treatment of ccRCC, which is useful for personalized medicine.Keywords: clear cell renal cell carcinoma, CRYL1, prognosis, biomarker