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Danni Song,1 Weiwei Jiang,1 Shuang Hu,1 Rong Zhu,1 Congshan Pu,1 Yiting Wang,1 Chunjian Shan,1 Chun Zhao2 1Department of Obstetrics, Women’s Hospital of Nanjing Medical University (Nanjing Women and Children’s Healthcare Hospital), Nanjing, 210004, People’s Republic of China; 2Reproductive Center, Women’s Hospital of Nanjing Medical University (Nanjing Women and Children’s Healthcare Hospital), Nanjing, 210004, People’s Republic of ChinaCorrespondence: Chunjian Shan, Department of Obstetrics, Women’s Hospital of Nanjing Medical University (Nanjing Women and Children’s Healthcare Hospital), Nanjing, 210004, People’s Republic of China, Email shanchunjian@njmu.edu.cn Chun Zhao Reproductive center, Women’s Hospital of Nanjing Medical University (Nanjing Women and Children’s Healthcare Hospital), Nanjing, 210004, People’s Republic of China, Email zhaochun2008@yeah.netBackground: There are multiple psychological symptoms in women undergoing assisted reproductive technology, which seriously affect health-related quality of life and even cause patients to stop treatment.Aim: This study aimed to identify psychological symptom clusters and their influencing factors in women undergoing assisted reproductive technology.Methods: A cross-sectional survey was conducted from June to November 2023 at the reproductive centers of Nanjing Women and Children’s Healthcare Hospital. Data on demographic and clinical characteristics and Symptom Checklist-90 were collected. Exploratory factor analysis was performed to identify psychological symptom clusters. Univariate logistic regression analysis and multivariate logistic regression analysis were performed to explore influencing factors.Results: A total of 213 patients were recruited. The study found that the included participants scored higher on all SCL scales than the general Chinese females. The three most common were trouble remembering things (81.7%), feeling easily annoyed or irritated (81.2%), and feeling low in energy or slowed down (70.9%). Six symptom clusters were identified: paranoid ideation, depression, obsessive-compulsive disorder, interpersonal sensitivity, somatization, and sleep disorders. Multivariate logistic regression analysis showed that duration of infertility treatment (> 12 months) was identified as a risk factor for sleep disorder cluster (OR=2.833, 95% CI:1.355~5.922), adverse pregnancy history was identified as a risk factor for paranoid ideation cluster (OR=2.961,95% CI:1.406~6.253), depression cluster (OR=2.404,95% CI:1.240~4.660), and obsessive-compulsive cluster (OR=1.810, 95% CI:1.016~3.233), financial burden during treatment was identified as risk factors for all symptom clusters[(OR=5.869, 95% CI:1.717~20.057),(OR=6.490,95% CI:2.210~19.063),(OR=3.034,95% CI:1.560~5.898),(OR=7.078,95% CI:2.420~20.698),(OR=4.532,95% CI:1.845~10.397),(OR=2.151,95% CI:1.129~4.098)].Conclusion: Women undergoing ART experience various psychological symptoms that are interrelated and exist in the form of symptom clusters. More attention should be paid to the psychological status of patients with longer duration of infertility treatment, adverse pregnancy history, and financial burden during treatment. This study guides the development of targeted and effective psychological interventions to facilitate symptom management in women undergoing ART.Keywords: assisted reproductive technology, psychological symptom, symptom clusters, exploratory factor analysis

Chong Zhao,* Shuaiqi Zhu,* Yan Liang, Shuai Xu Department of Spinal Surgery, Peking University People’s Hospital, Peking University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan Liang; Shuai Xu, Department of Spinal Surgery, Peking University People’s Hospital, Peking University, Beijing, People’s Republic of China, Tel +86-010-88324110 ; +86-18811792718, Email liangyan7503@163.com; xushuairmyy@pku.edu.cnPurpose: To characterize the asymmetrical loss of bone mass and identify the association between scoliosis and osteopenia in patients with adolescent idiopathic scoliosis (AIS).Methods: Demographic information, Cobb angle, and Hounsfield unit (HU) of the neutral vertebra (NV) and apical vertebra (apex) of the major curve were collected retrospectively in 54 AIS patients. For 84 control subjects, HU values were measured at T12 and L5. Propensity score matching was performed to balance the interference of age and BMI.Results: In the AIS group, the concave and convex lateral HU of the NV and the convex lateral HU of the apex were negatively correlated with the Cobb angle. The AIS patients had lower bilateral HU. The mean HU and the apex-convex HU were also lower in the AIS group, while the apex-concave HU was slightly higher. After matching, the apex-convex HU of the AIS group remained lower, while the apex-concave HU was higher.Conclusion: Patients with AIS exhibit osteopenia, particularly on the convex side. The severity of scoliosis was found to be directly proportional to the severity of bone loss and the degree of bilateral osteopenia asymmetry. Appropriate intervention for bone loss may be able to curb the progression of scoliosis.Keywords: adolescent idiopathic scoliosis, osteopenia, osteoporosis, Hounsfield unit, propensity score matching

Yuya Wen,1 Chenling Zhao,1 Jie Chen,1 Liwei Tian,1 Bojin Wu,1 Wenting Xie,1 Ting Dong1,2 1Department of Neurology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, 230031, People’s Republic of China; 2Key Laboratory of Xin’An Medicine, Ministry of Education, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, 230031, People’s Republic of ChinaCorrespondence: Ting Dong, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, 230031, People’s Republic of China, Tel +13965107566, Email dongting2002@sina.comPurpose: Neuroinflammation is a main cause of neurological damage in Wilson’s disease (WD). Ferroptosis is present in the WD pathological process, which is also closely related to the neuroinflammation. LCN2, a ferroptosis-related gene in WD, is linked with the activation of NLRP3 inflammasome. Our group has previously demonstrated that Gandouling (GDL) can effectively improve neuroinflammation in WD. This study aims to investigate the protective effect of GDL on neuroinflammation in animal and cell models of WD, and whether the pharmacological mechanism is related to the LCN2/NLRP3 signaling pathway.Methods: Toxic milk (TX) mice and HT22 cells stimulated by copper ions were selected as models. The pathology of hippocampal tissues in TX mice were observed by HE staining and transmission electron microscopy. High-throughput sequencing analysis was conducted to screen ferroptosis-related genes in WD. The expression of LCN2 and GPX4 in hippocampus of TX mice were detected by immunohistochemical. The expression of LCN2, NLRP3, GPX4, and SLC7A11 was determined in TX mice and HT22 cells by Western blotting and RT-qPCR. The levels of Fe2+, inflammatory factor indicators TNF-α, IL-1β and IL-6 and oxidative stress indicators 4-HNE, MAD, SOD, GSH and ROS were detected in each group by ELISA.Results: The results showed that GDL ameliorated pathological and mitochondrial damages in hippocampus of TX mice. The analysis of bioinformatics showed that LCN2 was a differential gene associated with ferroptosis in WD. The results of Western blotting and RT-qPCR indicated that GDL reduced the expression of LCN2 and NLRP3, and enhanced the expression of GPX4 and SLC711 in TX mice and HT22 cells. The ELISA results showed that GDL decreased the expression of Fe2+ and inflammatory factors TNF-α, IL-1β and IL-6 in TX mice with ferroptosis inducer intervention and copper ion-loaded HT22 cells. GDL decreased the expression of oxidative stress indicators ROS, 4-HNE and MDA, and increased the expression of oxidative stress indicators GSH and SOD in TX mice and copper ion-loaded HT22 cells.Conclusion: GDL has anti-inflammatory and antioxidant effects. LCN2 is a differential gene associated with ferroptosis in WD. GDL may alleviate ferroptosis by inhibiting the LCN2/NLPR3 signaling pathway, thereby improving neuroinflammatory responses and exerting neuroprotective effects in WD. Keywords: neuroinflammation, ferroptosis, Wilson’s disease, LCN2, NLRP3

Peijie Zhou,&ast; Shangshang Yu,&ast; Xuan Wang,&ast; Xiaofei Zhang, Dongyan Guo, Chongbo Zhao, Jiangxue Cheng, Jing Wang, Jing Sun Department of Pharmaceutics, College of Pharmacy, The Key Laboratory of Basic and New Drug Research of Traditional Chinese Medicine, Shaanxi Provincial Engineering Technology Research Center for Traditional Chinese Medicine Decoction Pieces, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Sun, Email ph.175@163.comBackground: Cerebral ischaemia-reperfusion injury (CIRI) could worsen the inflammatory response and oxidative stress in brain tissue. According to previous studies, ferulic acid methyl ester (FAME), as the extract with the strongest comprehensive activity in the traditional Chinese medicine Huang Hua oil dot herb, has significant anti-oxidative stress and neuroprotective functions, and can effectively alleviate CIRI, but its mechanism of action is still unclear.Methods: Firstly, the pharmacological effects of FAME were investigated by in vitro oxidative stress and inflammatory experiments. Secondly, evaluate the therapeutic effects of FAME in the treatment of CIRI by brain histopathological staining and cerebral infarct area by replicating the in vivo MACO model. Thirdly, RNA-Seq and network pharmacology were utilized to predict the possible targets and mechanisms of FAME for CIRI at the molecular level. Finally, the expression of key target proteins, as well as the key regulatory relationships were verified by molecular docking visualization, Western Blotting and immunohistochemistry.Results: The results of in vitro experiments concluded that FAME could significantly reduce the content of TNF-α, IL-1β and ROS, inhibiting COX-2 and iNOS protein expression in cells(p< 0.01). FAME was demonstrated to have anti-oxidative stress and anti-inflammatory effects. The results of in vivo experiments showed that after the administration of FAME, the area of cerebral infarction in rats with CIRI was reduced, the content of Bcl-2 and VEGF was increased(p< 0.05). Network pharmacology and RNA-Seq showed that the alleviation of CIRI by FAME may be through PI3K-AKT and HIF-1 signaling pathway. Enhanced expression of HIF-1α, VEGF, p-PI3K, p-AKT proteins in the brain tissues of rats in the FAME group was verified by molecular docking and Western Blotting.Conclusion: FAME possesses significant anti-inflammatory and anti-oxidative stress activities and alleviates CIRI through the PI3K/HIF-1α/VEGF signaling pathway. Keywords: ferulic acid methyl ester, cerebral ischemia-reperfusion injury, WGCNA, RNA-Seq, network pharmacology, molecular docking techniques

Junyi Li,1,2,&ast; Zugui Wu,3,&ast; Bin Lu,2,&ast; Congcong Li,1 Shuai Wang,1 Jiahao Zhang,1 Xingxing Shen,1 Ruian Xiang,1 Jiahao Chen,1 Tao Jiang,1 Chuanxi Zhao,1 Wengang Liu,1 Xuemeng Xu1 1Department of Orthopedics and Traumatology, The Fifth Clinical College of Guangzhou University of Chinese Medicine, Guangdong Provincial Second Hospital of Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Research and Development in Traditional Chinese Medicine, Guangzhou, People’s Republic of China; 2Department of Osteoarthropathy II, Luoyang Orthopedic-Traumatological Hospital of Henan Province (Henan Provincial Orthopedic Hospital), Luoyang, People’s Republic of China; 3Department of Orthopedics and Traumatology, The Third Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming Municipal Hospital of Traditional Chinese Medicine, Kunming, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuemeng Xu; Wengang Liu, Department of Orthopedics and Traumatology, The Fifth Clinical College of Guangzhou University of Chinese Medicine, Guangdong Provincial Second Hospital of Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Research and Development in Traditional Chinese Medicine, No. 60 Hengfu Road, Guangzhou, 510030, People’s Republic of China, Email xuxuemeng@163.com; 914194079@qq.comPurpose: Our study aims to evaluate differences in muscle parameters of the quadriceps muscles in patients with knee osteoarthritis (KOA) in older adults.Methods: The study included 40 patients diagnosed with unilateral knee osteoarthritis in the KOA group (KG) and 40 asymptomatic elderly individuals in the control group (CG). Muscle ultrasonic mean echo intensity and shear modulus, as well as tone and stiffness of the rectus femoris (RF), vastus medialis (VM), and vastus lateralis (VL) were analyzed. Additionally, clinical correlations were performed.Results: In the KG group, there were significant differences in echo intensity, shear modulus, and tone between the affected and unaffected sides for RF (p=0.003, 0.019, 0.014), while VM showed significant differences in shear modulus and tone (p=0.006, 0.002). Additionally, VL exhibited significant differences in echo intensity, shear modulus, and stiffness (p=0.007, 0.006, 0.010). Compared to the CG group, the KG group showed significant differences in echo intensity of the affected side RF (p=0.001). VM exhibited statistically significant differences in echo intensity and shear modulus (p < 0.001, p=0.008), while VL showed statistically significant differences in echo intensity, tone, and stiffness (p < 0.001, p=0.028, p < 0.001). The correlation results showed that patients with unilateral KOA, VM, and VL echo intensity were correlated with K-L grade (r = 0.443, p=0.004; r = 0.469, p=0.002). The tone of VL was correlated with VAS and WOMAC (r = 0.327, p=0.039; r = 0.344, p=0.030).Conclusion: The parameters of the quadriceps femoris muscle exhibit asymmetry between the affected and unaffected sides in patients with unilateral KOA, as well as a difference between the dominant side of healthy older individuals and the affected side of KOA.Keywords: knee osteoarthritis, quadriceps femoris, ultrasound, muscle tone, stiffness

Bo Yang, Chaoyue Zhao, Yao Zhu, Xianchun Li School of Psychology and Cognitive Science, East China Normal University, Shanghai, People’s Republic of ChinaCorrespondence: Bo Yang, School of Psychology and Cognitive Science, East China Normal University, Shanghai, People’s Republic of China, Email 52163200021@stu.ecnu.edu.cnPurpose: Numerous empirical studies consistently support the detrimental impact of job insecurity (JI) on employees. However, a new perspective suggests that individuals perceiving JI may proactively take measures to protect their positions. Drawing from the conservation of resources theory, this study argues that perceived resource loss due to JI motivates employees to engage in ingratiating behaviors for expanding their social capital. Additionally, this study empirically establishes the mediating role of emotional exhaustion and the moderating effect of power distance.Methods: A daily diary design was used to examine the relationship between daily JI and next-day ingratiation. Our analyses of data collected from 134 full‐time employees across 10 consecutive working days using multi-level model.Results: Our results showed that daily JI was found to affect next-day ingratiation (γ = 0.14, p < 0.01), and this relationship was mediated by emotional exhaustion (indirect effect = 0.07, p < 0.05, 95% CI [0.01, 0.13]). Power distance moderated the relationship between emotional exhaustion and ingratiation (γ = 0.25, p < 0.001), and further moderated the indirect effect of JI on ingratiation via emotional exhaustion.Conclusion: Our study has revealed that JI serves as a catalyst for employees to engage in resource creation behavior, thereby contributing to a deeper understanding of the implications of JI as an independent variable for both scholars and businesses.Keywords: job insecurity, emotional exhaustion, power distance, ingratiation

Baocheng Pan,1 Chengli Zhao,1 Yizhao Gong,1 Jiaxuan Miao,1 Bingda Zhang,2 Yan Li1 1Shanghai Institute of Early Childhood Education, Shanghai Normal University, Shanghai, People’s Republic of China; 2College of Economics and Management, Shanghai Zhongqiao Vocational and Technical University, Shanghai, People’s Republic of ChinaCorrespondence: Yan Li, Shanghai Institute of Early Childhood Education, Shanghai Normal University, 100 Guilin Road, Xuhui District, Shanghai, People’s Republic of China, Email liyan@shnu.edu.cnBackground: Depression, a severe mental disorder, not only jeopardizes the health of mothers but also significantly negative impacts on families and their children. This study investigates the correlation between household chaos and maternal depression.Methods: This study adopted a cross-sectional design and used the Confusion, Hubbub, and Order Scale, Dyadic Adjustment Scale, Parent-Child Relationship Scale, and Beck Depression Inventory to assess 1947 mothers of children in seven kindergartens in Shanghai, China.Results: The findings revealed a significant positive correlation between household chaos, marital conflict, and maternal depression. Marital conflict also showed a significantly positively correlated with maternal depression. Marital conflict mediates the relationship between household chaos and maternal depression. Parent-child relationships moderated the direct effect of household chaos on maternal depression. When parent-child relationships were low, household chaos had a greater predictive effect on maternal depression. Conversely, when parent-child relationships were high, the predictive effect of household chaos on maternal depression was reduced.Conclusion: This study reveals that parent-child relationships play a protective role in the impact of household chaos on maternal depression. This study significantly contributes to enriching the social support buffering model.Keywords: household chaos, marital conflict, parent-child relationships, maternal depression

Lan Hong,1,&ast; Huihui Xu,2,&ast; Jiaqi Zheng,2 Xiujian Lin,2 Lijun Wang,2 Chengjia Zhao,3 Xiaolian Tu,4 Jingjing Zhang,5 Ke Zhao,1,6 Guohua Zhang6,7,&ast; 1Lishui Second People’s Hospital Affiliated to Wenzhou Medical University, Lishui, 323000, People’s Republic of China; 2School of Mental Health, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 3School of Education, Renmin University of China, Beijing, 100872, People’s Republic of China; 4School of Renji, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 5School of Nursing, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 6Zhejiang Provincial Clinical Research Center for Mental Disorders, The Affiliated Wenzhou Kangning Hospital, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 7Institute Of Aging, Key Laboratory Of Alzheimer’s Disease Of Zhejiang Province, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guohua Zhang, Zhejiang Provincial Clinical Research Center for Mental Disorders, The Affiliated Wenzhou Kangning Hospital, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China, Email zghcnu@wmu.edu.cn Ke Zhao, Lishui Second People’s Hospital Affiliated to Wenzhou Medical University, Lishui, 323000, People’s Republic of China, Email cocozk1986@163.comBackground: Bedtime procrastination (BP) has become an important factor affecting individual well-being. This study aimed to assess the stability and changes in BP and examine risk and protective factors.Methods: The study recruited 1423 respondents. Latent profile analysis was used to identify subgroups of BP and latent transition analysis to determine transition probabilities for each subgroup. Logistic regression examined associations between identified classes and related factors.Results: Three subgroups of BP were identified. In terms of stability and changes, the moderate bedtime procrastination group showed the highest stability (66%), followed by the severe bedtime procrastination group (62.4%), and the mild bedtime procrastination group had a 52% probability of switching to moderate bedtime procrastination. In terms of influencing factors, more problematic phone use (PSU) (OR: 1.08; 95% CI = 1.05– 1.12), more depression (OR: 1.17; 95% CI = 1.06– 1.29) and anxiety (OR: 1.16; 95% CI = 1.05– 1.28) are all factors that aggravate the transition from mild to moderate sleep procrastination. Similarly, PSU (OR: 1.15; 95% CI = 1.12– 1.19), anxiety (OR: 1.10; 95% CI = 1.06– 1.14), and depression (OR: 1.10; 95% CI = 1.06– 1.14) increased the risk of severe bedtime procrastination. Self-control emerged as a protective factor against BP.Conclusion: This study identified three subgroups of BP at two time points and the rule of transition for each subgroup. Our findings indicate that BP were relatively stable, with some changes over time. The results also highlight the important function that PSU, depression, anxiety, and self-control can play in preventing and intervening in BP.Keywords: bedtime procrastination, latent profile analysis, latent transition analysis, problematic smartphone use, depression, anxiety, self-control

Qianfeng Li,1,&ast; Bo Wang,2,&ast; Jun Yang,3 Yuan Wang,1 Faliang Duan,1 Ming Luo,1 Chungang Zhao,4 Wei Wei,2 Lei Wang,3 Sha Liu2,5 1Department of Neurosurgery, Wuhan No.1 Hospital, Wuhan, People’s Republic of China; 2Brain Research Center, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 3Huanggang Central Hospital of Yangtze University, Huanggang, People’s Republic of China; 4Jilin Jianda Modern Agricultural Research Institute, Changchun, People’s Republic of China; 5Department of General Practice, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Wang; Sha Liu, Email wanglei@hgyy.org.cn; sha.liu@whu.edu.cnBackground: Aging is recognized as the key risk for intracerebral hemorrhage (ICH). The detailed mechanisms of aging in ICH warrant exploration. This study aimed to identify potential aging-related genes associated with ICH.Methods: ICH-specific aging-related genes were determined by the intersection of differentially expressed genes (DEGs) between perihematomal tissues and corresponding contralateral parts of four patients with ICH (GSE24265) and 349 aging-related genes obtained from the Aging Atlas database. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) analyses were performed to identify the potential biological functions and pathways in which these ICH-specific aging-related genes may be involved. Then, PPI network was established to identify the hub genes of ICH-specific aging-related genes. Meanwhile, miRNA-mRNA and transcription factor (TF)-mRNA regulatory networks were constructed to further explore the ICH-specific aging-related genes regulation. The relationship between these hub genes and immune infiltration was also further explored. Additional single-cell RNA-seq analysis (scRNA-seq, GSE167593) was used to locate the hub genes in different cell types. Besides, expression levels of the hub genes were validated using clinical samples from our institute and another GEO dataset (GSE206971).Results: This study identified 24 ICH-specific aging-related genes, including 22 up-regulated and 2 down-regulated genes. The results of GO and KEGG suggested that the ICH-specific aging-related genes mainly enriched in immunity and inflammation-related pathways, suggesting that aging may affect the ich pathogenesis by regulating inflammatory and immune-related pathways.Conclusion: Our study revealed 24 ICH-specific aging-related genes and their functions highly pertinent to ICH pathogenesis, providing new insights into the impact of aging on ICH.Keywords: intracerebral hemorrhage, aging, immune infiltration, single-cell RNA sequencing, molecular docking

Lang Liu,1,&ast; Binghua Zhang,1,&ast; Zhenwei Zhou,2 Jie Yang,1 Ailin Li,1 Yongji Wu,1 Zeyu Peng,1 Xiangyan Li,2 Zhonghua Liu,3 Xiangyang Leng,1 Changwei Zhao,4 Haisi Dong,2 Wenhai Zhao4 1College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, People’s Republic of China; 2Northeast Asia Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, People’s Republic of China; 3Department of Orthopaedics, The Third Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, People’s Republic of China; 4Affiliated Hospital of Changchun University of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haisi Dong, Northeast Asia Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin, 130117, People’s Republic of China, Tel/Fax +86 431-18604361976, Email adonghaisi@163.com Wenhai Zhao, Affiliated Hospital of Changchun University of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin, 130021, People’s Republic of China, Tel/Fax +86 431-86177836, Email zwh9899@163.comBackground: Knee osteoarthritis (KOA) is a persistent degenerative condition characterized by the deterioration of cartilage. The Chinese herbal formula Radix Rehmanniae Praeparata- Angelica Sinensis-Radix Achyranthis Bidentatae (RAR) has often been used in effective prescriptions for KOA as the main functional drug, but its underlying mechanism remains unclear. Therefore, network pharmacology and verification experiments were employed to investigate the impact and mode of action of RAR in the treatment of KOA.Methods: The destabilization of the medial meniscus model (DMM) was utilized to assess the anti-KOA effect of RAR by using gait analysis, micro-computed tomography (Micro-CT), and histology. Primary chondrocytes were extracted from the rib cartilage of a newborn mouse. The protective effects of RAR on OA cells were evaluated using a CCK‐8 assay. The antioxidative effect of RAR was determined by measuring reactive oxygen species (ROS), superoxide dismutase (SOD), and glutathione (GSH) production. Furthermore, network pharmacology and molecular docking were utilized to propose possible RAR targets for KOA, which were further verified through experiments.Results: In vivo, RAR significantly ameliorated DMM-induced KOA characteristics, such as subchondral bone sclerosis, cartilage deterioration, gait abnormalities, and the degree of knee swelling. In vitro, RAR stimulated chondrocyte proliferation and the expression of Col2a1, Comp, and Acan. Moreover, RAR treatment significantly reduced ROS accumulation in an OA cell model induced by IL-1β and increased the activity of antioxidant enzymes (SOD and GSH). Network pharmacology analysis combined with molecular docking showed that Mapk1 might be a key therapeutic target. Subsequent research showed that RAR could downregulate Mapk1 mRNA levels in IL-1β-induced chondrocytes and DMM-induced rats.Conclusion: RAR inhibited extracellular matrix (ECM) degradation and oxidative stress response via the MAPK signaling pathway in KOA, and Mapk1 may be a core target.Keywords: knee osteoarthritis, RAR, cartilage degeneration, network pharmacology, Mapk1

Yanhua Liu,1,2,&ast; Fuxing Li,1,2,&ast; Youling Fang,2,3 Qiaoshi Zhong,1,2 Yanping Xiao,1,2 Yunwei Zheng,1,2 Junqi Zhu,2,3 Chuwen Zhao,2,3 Xingwei Cao,1,2 Jianqiu Xiong,4 Longhua Hu1,2 1The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Jiangxi, Nanchang, People’s Republic of China; 2Department of Jiangxi Provincial Key Laboratory of Medicine, Clinical Laboratory of the Second Affiliated Hospital of Nanchang University, Jiangxi, Nanchang, People’s Republic of China; 3School of Public Health, Nanchang University, Jiangxi, Nanchang, People’s Republic of China; 4Department of Nursing, the Second Affiliated Hospital of Nanchang University, Jiangxi, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianqiu Xiong, Department of Nursing, The Second Affiliated Hospital of Nanchang University, Mingde Road No. 1, Jiangxi, Nanchang, 330006, People’s Republic of China, Email 1773014059@qq.com Longhua Hu, Department of Jiangxi Provincial Key Laboratory of Medicine, Clinical Laboratory of the Second Affiliated Hospital of Nanchang University, Mingde Road No. 1, Jiangxi, Nanchang, 330006, People’s Republic of China, Email longhuahu@163.comObjective: This research aimed to analyze the clinical characteristics, prognosis, and antimicrobial treatment of bloodstream infections (BSI) caused by Enterobacter cloacae complex (ECC).Methods: The clinical data of patients with bloodstream infections caused by Enterobacter cloacae complex from April 2017 to June 2023 were collected retrospectively. These data were then analyzed in subgroups based on the detection results of extended-spectrum β-lactamase (ESBL), 30-day mortality, and the type of antimicrobial agent used (β-lactam/β-lactamase inhibitor combinations (BLICs) or carbapenems).Results: The proportion of ESBL-producing Enterobacter cloacae complex was 32.5% (37/114). Meanwhile, ICU admission, receiving surgical treatment within 3 months, and biliary tract infection were identified as risk factors for ESBL-producing ECC-BSI. Additionally, immunocompromised status and Sequential Organ Failure Assessment (SOFA) score ≥ 6.0 were identified as independent risk factors of 30-day mortality in patients with ECC-BSI (n = 108). Further analysis in BSI patients caused by non-ESBL-producing ECC revealed that patients treated with BLICs (n = 45) had lower SOFA scores and lower incidence of hypoproteinemia and sepsis compared with patients treated with carbapenems (n = 20). Moreover, in non-ESBL-producing ECC-BSI patients, the univariate Cox regression analysis indicated a significantly lower 30-day mortality rate in patients treated with BLICs compared to those treated with carbapenems (hazard ratios (HR) [95% CI] 0.190 [0.055– 0.662], P = 0.009; adjusted HR [95% CI] 0.106 [0.013– 0.863], P = 0.036).Conclusion: This study investigated the factors influencing the susceptibility to infection by ESBL-producing strains and risk factors for 30-day mortality in ECC-BSI patients. The results revealed that ESBL-negative ECC-BSI patients treated with BLICs exhibited significantly lower 30-day mortality compared to those treated with carbapenems. BLICs were found to be more effective in ECC-BSI patients with milder disease (ESBL-negative and SOFA ≤ 6.0).Keywords: Enterobacter cloacae complex, extended-spectrum β-lactamase, bloodstream infection, risk factors, β-lactam/β- lactamase inhibitor combinations, carbapenems

Guizhong Huang,1,&ast; Pu Xi,1,&ast; Zehui Yao,1,&ast; Chongyu Zhao,2,&ast; Xiaohui Li,1 Zexian Chen,3 Xiaojun Lin1 1Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 2Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Army Medical University, Chongqing, 400037, People’s Republic of China; 3Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaojun Lin, Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China, Tel +8620-8734-1639, Email linxj@sysucc.org.cnBackground: Intrahepatic cholangiocarcinoma (ICC) correlates with poor outcomes, necessitating the identification of prognostic factors from an inflammation-nutritional perspective in locally advanced ICC patients after R0 resection.Methods: We retrospectively reviewed the medical records of 159 locally advanced ICC patients from Sun Yat-sen University Cancer Center. Univariate and multivariate Cox regression analysis, as well as competing risk analysis, were conducted to explore prognostic variables for locally advanced ICC following surgery. To validate the robustness of our findings, we performed propensity score matching (PSM) analyses to evaluate survival differences based on inflammation-nutritional indexes.Results: Considering non-cancer-specific death as competing risk factors, both systemic immune-inflammation index (SII, HR: 1.934) and prognostic nutrition index (PNI, HR: 0.604) emerged as significant prognostic variables for locally advanced ICC after R0 resection (P < 0.05). After PSM, the survival benefit between the low and high PNI sets remained clear (median survival time: 15.7 months vs 35.1 months, P = 0.002). Although the 5-year overall survival (OS) rate of the low SII group was higher than that of the high SII group, the difference was not statistically significant (17.5% VS 27.4%, P = 0.112). Other influencing factors included tumor number, tumor diameter, preoperative carcinoembryonic antigen (CEA)and carbohydrate antigen 19– 9 (CA19-9) levels, and postoperative adjuvant therapy.Conclusion: Individual inflammatory and nutritional status significantly impact the prognosis of locally advanced ICC undergoing R0 hapectomy. Oncologists should consider incorporating inflammation-nutritional conditions into the decision-making process for this subset of advanced ICC.Keywords: locally advanced intrahepatic cholangiocarcinoma, inflammation, nutrition, competing risk analysis, propensity matching analysis

Quan Hu,1,&ast; Yingxiao Li,2,&ast; Zhaochen Lin,3 Hao Zhang,4 Haoyue Chen,4 Cui Chao,3 Chuanliang Zhao5 1Department of Neurosurgery, The Affiliated Taian City Central Hospital of Qingdao University, Tai’an City, Shandong, 271000, People’s Republic of China; 2Department of Gynecology, The Affiliated Taian City Central Hospital of Qingdao University, Tai’an City, Shandong, 271000, People’s Republic of China; 3Hydrogen Medical Research Center, The Affiliated Taian City Central Hospital of Qingdao University, Tai’an City, Shandong, 271000, People’s Republic of China; 4Department of Rehabilitation Medical Center, The Affiliated Taian City Central Hospital of Qingdao University, Tai’an City, Shandong, 271000, People’s Republic of China; 5Department of Orthopedics, the Affiliated Taian City Central Hospital of Qingdao University, Tai’an City, Shandong, 271000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chuanliang Zhao, Department of Orthopedics, The Affiliated Taian City Central Hospital of Qingdao University, Tai’an City, Shandong, 271000, People’s Republic of China, Tel +8615621539631, Email zhaochuanliang2003@163.comAbstract: Hydrogen, which is a novel biomedical molecule, is currently the subject of extensive research involving animal experiments and in vitro cell experiments, and it is gradually being applied in clinical settings. Hydrogen has been proven to possess anti-inflammatory, selective antioxidant, and antiapoptotic effects, thus exhibiting considerable protective effects in various diseases. In recent years, several studies have provided preliminary evidence for the protective effects of hydrogen on spinal cord injury (SCI). This paper provides a comprehensive review of the potential molecular biology mechanisms of hydrogen therapy and its application in treating SCI, with an aim to better explore the medical value of hydrogen and provide new avenues for the adjuvant treatment of SCI.Keywords: hydrogen, spinal cord injury, selective antioxidant, anti-inflammatory

Jingqian Zhao,1,2,&ast; Chenyu Zhao,1,3,&ast; Tianrong Xun,1 Xiaokang Wang,1 Sui Wei,1,3 Chunxiao Ye,1 Mimi Zhang,1 Dan Guo,4 Xixiao Yang1 1Department of Pharmacy, Shenzhen Hospital, Southern Medical University, Shenzhen, People’s Republic of China; 2School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, People’s Republic of China; 3School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, People’s Republic of China; 4Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dan Guo; Xixiao Yang, Email nfyyyxb@smu.edu.cn; yaxx@smu.edu.cnPurpose: This study aims to investigate the effects of Huang Gan formula (HGF), a Chinese herbal prescription used for chronic kidney disease (CKD), on the regulation of the gut microbiota and colonic microenvironment of CKD.Methods: CKD rats were induced by 150 mg/kg adenine gavage for 4 weeks, then orally treated with or without 3.6 g/kg or 7.2 g/kg of HGF for 8 weeks. The renal function and structure were analyzed by biochemical detection, hematoxylin and eosin, Masson’s trichrome, Sirius red and immunochemical staining. Average fecal weight and number in the colon were recorded to assess colonic motility. Further, the changes in the gut microbiota and colonic microenvironment were evaluated by 16S rRNA sequencing, RT-PCR or immunofluorescence. The levels of inflammatory cytokines, uremic toxins, and NF-κB signaling pathway were detected by RT-PCR, ELISA, chloramine-T method or Western blotting. Redundancy analysis biplot and Spearman’s rank correlation coefficient were used for correlation analysis.Results: HGF significantly improved renal function and pathological injuries of CKD. HGF could improve gut microbial dysbiosis, protect colonic barrier and promote motility of colonic lumens. Further, HGF inhibited systemic inflammation through a reduction of TNF-α, IL-6, IL-1β, TGF-β 1, and a suppression of NF-κB signaling pathway. The serum levels of the selected uremic toxins were also reduced by HGF treatment. Spearman correlation analysis suggested that high-dose HGF inhibited the overgrowth of bacteria that were positively correlated with inflammatory factors (eg, TNF-α) and uremic toxins (eg, indoxyl sulfate), whereas it promoted the proliferation of bacteria belonging to beneficial microbial groups and was positively correlated with the level of IL-10.Conclusion: Our results suggest that HGF can improve adenine-induced CKD via suppressing systemic inflammation and uremia, which may associate with the regulations of the gut microbiota and colonic microenvironment.Keywords: chronic kidney disease, systemic inflammation, colonic microenvironment, gut-kidney axis

Lingchun Zhang,1,&ast; Yani Ma,2,&ast; Chenglong Zhao,1 Shujuan Zhao,1 Lulu Zhao,3 Yuxin Yang,4 Yuhan Wang,5 Haiyang Meng,6 Jun Sun1 1Department of Pharmacy, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou, People’s Republic of China; 2Department of Pharmacy, the First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 3Department of Pharmacy, Gongyi People’s Hospital, Zhengzhou, People’s Republic of China; 4Department of Pharmacy, Anyang Ophthalmic Hospital, Anyang, People’s Republic of China; 5Department of Pharmacy, Henan Integrative Medicine Hospital, Zhengzhou, People’s Republic of China; 6Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Sun, Department of Pharmacy, Henan Provincial People’s Hospital, No. 7 Weiwu Road, Zhengzhou, People’s Republic of China, Tel +86 13683827203, Email Jun_84@163.comPurpose: Carbapenem-Resistant Klebsiella pneumoniae (CRKP) is a significant public health threat, because it is associated with substantial morbidity and mortality. However, the risk factors associated with treatment failure of ceftazidime-avibactam (CAZ-AVI) and the need for CAZ-AVI-based combination remain unclear.Methods: We conducted a retrospective study of critically ill patients (age: > 18 years) diagnosed with CRKP infections and treated with CAZ-AVI for at least 24 h between June 2020 and December 2022 at Henan Provincial People’s Hospital.Results: This study included a total of 103 patients who received CAZ-AVI. Of these, 91 (88.3%) patients received the standard dosage of 2.5 g every q8h, while only 20 (19.4%) received monotherapy. The Kaplan–Meier curves showed that the all-cause 30-day mortality was significantly higher among patients who experienced septic shock than those who did not. There was no significant difference in mortality between monotherapy and combination therapy. Dose reduction of CAZ-AVI was associated with a significantly increased mortality rate. Independent risk factors for the 30-day mortality included higher APACHE II score (HR: 1.084, 95% CI: 1.024– 1.147, p = 0.005) and lower lymphocyte count (HR: 0.247, 95% CI: 0.093– 0.655, p = 0.005). Conversely, a combination therapy regimen containing carbapenems was associated with lower mortality (HR: 0.273, 95% CI: 0.086– 0.869, p = 0.028).Conclusion: Our study suggests that CAZ-AVI provides clinical benefits in terms of survival and clinical response in critically ill patients with CRKP infection. A higher APACHE II score and lower lymphocyte count were associated with 30-day mortality, while the combination therapy regimen containing carbapenems was the only protective factor. CAZ-AVI dose reduction was associated with an increased mortality rate. Futher large-scale studies are needed to validate these findings.Keywords: carbapenem-resistant Klebsiella pneumoniae, ceftazidime-avibactam, retrospective study, combination therapy

Songli Ruan,1,&ast; Xin Wang,2,&ast; Chengjia Zhao,3,&ast; Qian Li,2 Wing Ming Li,2 Guohua Zhang,4,5 Jianshe Pan,4 Xue Yang2 1Mental Health Education and Guidance Center of College Students, Henan University of Urban Construction, Pingdingshan, People’s Republic of China; 2JC School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China; 3School of Mental Health, Wenzhou Medical University, Wenzhou, People’s Republic of China; 4Department of Psychiatry, The Affiliated Kangning Hospital, Wenzhou, People’s Republic of China; 5Zhejiang Provincial Clinical Research Center for Mental Disorders, The Affiliated Wenzhou Kangning Hospital, Wenzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xue Yang, JC School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China, Email sherryxueyang@cuhk.edu.hkBackground: Enhancing abstinence motivation of drugs is an effective strategy for the rehabilitation of people who used drugs and prevention of drug use relapse. However, little is known about its risk and protective factors. This study aimed to examine the potential intrapersonal (ie, impulsivity, depression, anxiety, sleep quality) and interpersonal factors (ie, perceived social support) of abstinence motivation among people who completed the community rehabilitation treatment.Methods: A total of 222 participants (mean age = 43; male = 89.2%) were recruited from eleven communities located in Wenzhou, China. Data were collected using a self-reported questionnaire in counselling room settings between April and June 2021.Results: The proportions of participants with depression, anxiety, and poor sleep quality were 38.8%, 19.5%, and 21.2%, respectively. Age and family history of physical disease were significant background factors of abstinence motivation. Impulsivity, depressive symptoms, anxiety symptoms, and poor quality of sleep were negatively associated with abstinence motivation. Perceived social support from family and important others was positively associated with abstinence motivation. Structural equation modeling fitted the data well in which impulsivity and perceived social support were both associated with abstinence motivation indirectly through mental health problems.Conclusion: The identified psychosocial factors should be addressed in community rehabilitation treatment and follow-up service to enhance abstinence motivation and the long-term effectiveness of the treatment.Keywords: abstinence motivation to drugs, mental health problems, personality, social support, community-based rehabilitation treatment, Chinese people who used drugs

Zhao H, He Y, Li H, et al. Cancer Manag Res. 2019;11:4569–4576. We, the Editor and Publisher of the journal Cancer Management and Research have retracted the published article. Following publication, concerns were raised regarding the use of non-verifiable cell lines described in the article. The concerns related specifically to the use of cell lines which were found to be either contaminated, wrongly identified, improperly indexed, unavailable through external cell line repositories, and/or lacking publications describing their establishment. Overall, these concerns raised doubts about the validity of the findings described in the article. The corresponding author did not respond to our queries and was unable to provide information relating to the use of these cell lines or provide original data relating to the study. As verifying the validity of published work is core to the integrity of the scholarly record, the Publisher and Editor requested to retract the article and the corresponding author was notified of this decision. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Yan Chen,1,&ast; Han Du,1,&ast; Xin Wang,1,&ast; Baixing Li,1 Xuzhuo Chen,2 Xiao Yang,1 Changqing Zhao,1 Jie Zhao1 1Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People’s Republic of China; 2Department of Oral Surgery, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Changqing Zhao; Xiao Yang, Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People’s Republic of China, Email zhaocq9hospital@163.com; walkingweapon@outlook.comIntroduction: The crosstalk between intervertebral disc degeneration (IVDD) and type 2 diabetes mellitus (T2DM) has been investigated. However, the common mechanism underlying this phenomenon has not been clearly elucidated. This study aimed to explore the shared gene signatures of IVDD and T2DM.Methods: The expression profiles of IVDD (GSE27494) and T2DM (GSE20966) were acquired from the Gene Expression Omnibus database. Five hub genes including ANGPTL4, CCL2, CCN3, THBS2, and INHBA were preliminarily screened. GO (Gene Ontology) enrichment analysis, functional correlation analysis, immune filtration, Transcription factors (TFs)-mRNA-miRNA coregulatory network, and potential drugs prediction were performed following the identification of hub genes. RNA sequencing, in vivo and in vitro experiments on rats were further performed to validate the expression and function of the target gene.Results: Five hub genes (ANGPTL4, CCL2, CCN3, THBS2, and INHBA) were identified. GO analysis demonstrated the regulation of the immune system, extracellular matrix (ECM), and SMAD protein signal transduction. There was a strong correlation between hub genes and different functions, including lipid metabolism, mitochondrial function, and ECM degradation. The immune filtration pattern grouped by disease and the expression of hub genes showed significant changes in the immune cell composition. TFs-mRNA-miRNA co-expression networks were constructed. In addition, pepstatin showed great drug-targeting relevance based on potential drugs prediction of hub genes. ANGPTL4, a gene that mediates the inhibition of lipoprotein lipase activity, was eventually determined after hub gene screening, validation by different datasets, RNA sequencing, and experiments.Discussion: This study screened five hub genes and ANGPTL4 was eventually determined as a potential target for the regulation of the crosstalk in patients with IVDD and T2DM.Keywords: ANGPTL4, biomarker, functional analysis, intervertebral disc degeneration, type 2 diabetes mellitus

Chuwen Zhao,1,2,&ast; Yunwei Zheng,1,&ast; Yaping Hang,1 Yanhui Chen,1 Yanhua Liu,1 Junqi Zhu,1,2 Youling Fang,1,2 Jianqiu Xiong,3 Longhua Hu1 1Department of Jiangxi Provincial Key Laboratory of Medicine, Clinical Laboratory of the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2School of Public Health, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 3Department of Nursing, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Longhua Hu, Department of Jiangxi Provincial Key Laboratory of Medicine, Clinical Laboratory of the Second Affiliated Hospital of Nanchang University, Mingde Road No. 1, Nanchang, Jiangxi, 330006, People’s Republic of China, Email longhuahu@163.com Jianqiu Xiong, Department of Nursing, the Second Affiliated Hospital of Nanchang University, Mingde Road No. 1, Nanchang, Jiangxi, 330006, People’s Republic of China, Email 1773014059@qq.comObjective: Escherichia coli and Klebsiella pneumoniae are prevalent Gram-negative microorganisms responsible for pneumonia, as well as the primary Enterobacteriaceae pathogens causing bacteremic pneumonia. The objective of this research is to analyze the risk factors associated with bacteremic pneumonia caused by these pathogens and develop a predictive model.Patients and Methods: This retrospective investigation encompassed a cohort of 252 patients diagnosed with Escherichia coli or Klebsiella pneumoniae-induced bacteremic pneumonia between 2018 and 2022. The primary endpoint was 30-day mortality, which was analyzed using multifactorial logistic regression, nomogram construction, and Bootstrap validation.Results: Among the 252 patients diagnosed with Escherichia coli and Klebsiella pneumoniae, 65 succumbed to the disease while 187 survived. The overall 30-day mortality was found to be 25.8%. A multifactorial logistic regression analysis revealed that diastolic blood pressure, cerebrovascular diseases/transient ischemic attacks (TIA), immunosuppression, blood urea nitrogen, Pitt score, and CURB-65 score were statistically significant factors. The Nomogram model demonstrated an AUC of 0.954, which closely aligns with the Bootstrap-derived mean AUC of 0.953 (95% CI: 0.952– 0.954).Conclusion: In patients with bacteremic pneumonia caused by Escherichia coli and Klebsiella pneumoniae, Low diastolic blood pressure (≤ 61 mmHg), pre-existing cerebrovascular disease/ transient ischemic attacks (TIA), immunosuppression status, elevated blood urea nitrogen levels (≥ 8.39 mmol/L), high Pitt score (≥ 3), and a high CURB-65 score (≥ 2) are all independent risk factors for Escherichia coli and Klebsiella pneumoniae bacteremic pneumonia, among which the first three warrant particular attention.Keywords: Klebsiella pneumoniae, Escherichia coli, bacteremic pneumonia, 30-day mortality, nomogram

Ning Xu,1,&ast; Guanzheng Cui,1,&ast; Shengyin Zhao,1 Yu Li,1 Qian Liu,2 Xuchang Liu,1 Chuanliang Zhao,3 Rongjie Feng,1 Mingjie Kuang,1 Shijie Han1 1Department of Orthopedic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, 250014, People’s Republic of China; 2Department of Pain, Qilu Hospital of Shandong University, Jinan, 250012, People’s Republic of China; 3Department of Orthopedic Surgery, The Affiliated Taian City Central Hospital of Qingdao University, Taian, 271000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shijie Han; Mingjie Kuang, Department of Orthopedic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250014, People’s Republic of China, Email hanshijie@sdfmu.edu.cn; doctorkmj@tmu.edu.cnIntroduction: Osteoporosis is a common bone disease in which the bone loses density and strength and is prone to fracture. Bone marrow mesenchymal stem cells (BMSCs) are important in bone-related diseases. Exosomes, as mediators of cell communication, have potential in cell processes. Previous studies have focused on muscle factors’ regulation of bone remodeling, but research on exosomes is lacking.Methods: In order to confirm the therapeutic effect of mechanically stimulated myocytes (C2C12) derived exosomes (Exosome-MS) on the Glucocorticoid-induced osteoporosis(GIOP) compared with unmechanically stimulated myocytes (C2C12) derived exosomes (Exosomes), we established a dexamethasone-induced osteoporosis model in vivo and in vitro. Cell viability and proliferation were assessed using CCK8 and EDU assays. Osteogenic potential was evaluated through Western blotting, real-time PCR, alkaline phosphatase activity assay, and alizarin red staining. Differential expression of miRNAs was determined by high-throughput sequencing. The regulatory mechanism of miR-92a-3p on cell proliferation and osteogenic differentiation via the PTEN/AKT pathway was investigated using real-time PCR, luciferase reporter gene assay, Western blotting, and immunofluorescence. The therapeutic effects of exosomes were evaluated in vivo using microCT, HE staining, Masson staining, and immunohistochemistry.Results: In this study, we found that exosomes derived from mechanical stress had a positive impact on the proliferation and differentiation of bone marrow mesenchymal stem cells (BMSCs). Importantly, we demonstrated that miR-92a-3p mimics could reverse dexamethasone-induced osteoporosis in vitro and in vivo, indicating that mechanical stress-induced mouse myoblast-derived exosomes could promote osteogenesis and prevent the occurrence and progression of osteoporosis in mice through miR-92a-3p/PTEN/AKT signaling pathway.Conclusion: Exosomes derived from mechanical stress-induced myoblasts can promote the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells through miR-92a-3p/PTEN/AKT signaling pathway, and can have a therapeutic effect on glucocorticoid-induced osteoporosis in mice in vivo. Keywords: Human bone marrow mesenchymal stem cells, Mechanical stimulation, Exosome, miR-92a-3p, AKT signaling

Jie Wang,1,&ast; Lei Deng,2,&ast; Zihao Ding,3,&ast; Yaosheng Zhang,3 Yao Zhang,1 Kangpeng Li,1 Changsong Zhao,1 Qiang Zhang1 1Department of Orthopedics, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China; 2Department of First School of Clinical Medicine, Henan University of Chinese Medicine, Henan, 450003, People’s Republic of China; 3Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiang Zhang, Department of Orthopedics, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China, Email zhangqianggk@sina.comObjective: The clinical efficacy of perioperative chemotherapy regimen (rifampicin, doxycycline, levofloxacin, ceftriaxone) was evaluated for lumbar brucellosis spondylitis patients with neurological injury.Methods: In Beijing Ditan Hospital affiliated with Capital Medical University, 32 patients with lumbar brucellosis spondylitis underwent surgery and triple perioperative chemotherapy (rifampicin, doxycycline, levofloxacin) between 2011 and 2021 due to neurological injury, and 34 patients matched up with the triple group underwent rifampicin, doxycycline, levofloxacin, and ceftriaxone. Both groups were compared in terms of changes in inflammation index, low back/leg pain, lumbar function, neurological function, and adverse drug reactions.Results: There was no significant difference in erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), low back pain visual analogue scale (VAS), leg pain VAS, lumbar Oswestry disability index (ODI) and nerve function injury rate between the two groups before chemotherapy (P> 0.05). The ESR, CRP at 1 week and 2 weeks after chemotherapy and 1 week, 2 weeks, 1 month postoperatively in the quadruple group were significantly lower than those in the triple group, which is the same to ESR 3 months postoperatively (P< 0.05). The low back pain VAS, leg pain VAS and lumbar ODI in the quadruple group were significantly lower than those in the triple group at 1 month and 3 months postoperatively (P< 0.05). The recovery rate of neurological function in the quadruple group was significantly higher than that in the triple group at 3 and 6 months postoperatively (P< 0.05). Both groups did not experience significantly different perioperative and postoperative adverse reactions (P> 0.05).Conclusion: For lumbar brucellosis spondylitis with neurological injury, quadruple perioperative chemotherapy of rifampicin, doxycycline, levofloxacin and ceftriaxone can significantly reduce perioperative inflammation, and improve low back/leg pain, as well as promoting neurological function recovery in the short term.Keywords: lumbar brucellosis spondylitis, neurological injury, perioperative chemotherapy, efficacy

Dongyan Chai,1,2,&ast; Zhihui Liu,3,&ast; Liuyi Wang,3 Hongyan Duan,2,3 Chenglong Zhao,1 Chengyang Xu,2 Dongyan Zhang,1 Qiongrui Zhao,4 Peizhi Ma1 1Department of Pharmacy, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, Henan People’s Republic of China; 2International Medical Center of Henan Province, Henan Provincial People’s Hospital, Zhengzhou, Henan, People’s Republic of China; 3Department of General Practice, Henan Provincial People’s Hospital, Zhengzhou, Henan, People’s Republic of China; 4Department of Clinical Research Service Center, Henan Provincial People’s Hospital, Zhengzhou, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peizhi Ma, Department of Pharmacy, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Weiwu Road 7, Zhengzhou, Henan, People’s Republic of China, Tel +86 18538298188, Fax +86 037165580803, Email ma18539298188@163.comBackground: Implementing medication reconciliation (MR) was complex and challenging because of the variability in the guidance provided for conducting. The processes of MR adopted in China were different from that recommended by the World Health Organization. A pilot study to inform the design of a future randomized controlled trial to determine the effectiveness of these two workflows was undertaken.Methods: Patients taking at least one home/regular medication for hypertension, diabetes, or coronary heart disease were recruited at admission, and then were randomized using a computer-generated random number in a closed envelope. In the study group, the pharmacist reviewed electronic medical record systems before communication with patients. In the control group, pharmacists communicated with patients at patient’s admission. The time investment of pharmacists for MR process, the number of unintended medication discrepancies, and physician acceptance were tested as outcome measures.Results: One hundred and forty adult patients were randomized, of which 66 patients in the intervention received MR within 24 hours, while 58 patients in control received MR at some point during admission. The most common condition in the study group was hypertension (coronary heart disease in the control group). The workflow of the study group can save an average 7 minutes per patient compared with the WHO recommended process [17.5 minutes (IQR 14.00, 28.25) vs 24.5 minutes (IQR17.75, 35.25), p = 0.004]. The number of unintended discrepancies was 42 in the study group and 34 in the control group (p = 0.33). Physicians’ acceptance in the study and control groups were 87.5% and 92.3%, respectively (p = 0.87).Conclusion: The results suggest that changes in outcome measures were in the appropriate direction and that the time limit for implementing MR can be set within 48 hours. A future multi-centre RCT study to determine the effectiveness of MR is feasible and warranted.Keywords: medication reconciliation, workflow, prospective studies, pharmacist, randomized controlled trial

Jinpeng Shi,1,&ast; Jiayu Li,1,&ast; Haowei Wang,1,&ast; Xuefei Li,2 Qi Wang,1 Chao Zhao,2 Lei Cheng,2 Ruoshuang Han,1 Peixin Chen,1 Haoyue Guo,1 Zhuoran Tang,1 Caicun Zhou,1 Zhemin Zhang,1 Fengying Wu1 1Department of Medical Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fengying Wu; Zhemin Zhang, Department of Medical Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, School of Medicine, Tongji University, No. 507, Zheng Min Road, Shanghai, 200433, People’s Republic of China, Tel +86 21 6511 5006, Email fywu@163.com; zhemindoc@163.comPurpose: Neutrophils act as a non-negligible regulator in the initiation and progression of malignancies, playing bifacial roles in the process. Thus, to understand the heterogeneity of tumor-associated neutrophils (TANs) comprehensively in advanced non-small cell lung cancer (NSCLC) at single-cell resolution is necessary and urgent.Materials and Methods: We applied single-cell RNA-sequencing (scRNA-seq) to portray the subtype-specific transcriptome landscape of TANs in advanced NSCLC using nine freshly obtained specimens. The scRNA-seq data were further processed for pseudo-time analysis to depict the developmental trajectory of TANs. Meanwhile, the interplay between TANs and other cell types within tumor microenvironment (TME) was revealed by intercellular interaction analysis.Results: Seven distinct TAN subtypes were defined, of which, the N3 cluster was considered inflammatory phenotype expressing genes encoding multiple chemotactic cytokines, and correlated with inferior overall survival, indicating that N3 might be a pro-tumorigenic TAN subtype. N1 and N5 clusters were considered to be well differentiated and mature neutrophils based on CXCR2 expression and pseudo-time patterns, and both accounted for relatively high proportions in lung adenocarcinoma. In addition, genes related to neutrophil differentiation were discovered. We also found that TAN subtypes interacted most closely with macrophages through chemokine signaling pathways within TME.Conclusion: Our study refined TAN subtypes and mapped the transcriptome landscape of TANs at single-cell resolution in advanced NSCLC, collectively indicating the heterogeneity of TANs in NSCLC. Neutrophil differentiation- and maturation-related genes were also discovered, which shed light on different functions of TAN subclones in tumor immune escape, and may further provide novel targets for immunotherapy. Keywords: tumor-associated neutrophil, single-cell RNA-sequencing, non-small cell lung cancer, tumor microenvironment, heterogeneity

Xinrui Feng,1,2,&ast; Yan Liu,1,&ast; Yang Zhao,3 Zhe Sun,1,4 Ning Xu,5 Chen Zhao,1 Wei Xia4 1College of Public Health, Jilin Medical University, Jilin, 132013, People’s Republic of China; 2Medical College, Yanbian University, Yanji, 136200, People’s Republic of China; 3Department of Emergency and Intensive Medicine, No. 965 Hospital of PLA Joint Logistic Support Force, Jilin, 132013, People’s Republic of China; 4College of Medical Technology, Beihua University, Jilin, 132013, People’s Republic of China; 5State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, 130062, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chen Zhao; Wei Xia, Email zhaochen0115@jlmu.edu.cn; xiawei4016@126.comAbstract: Recent, outbreaks of new emergency zoonotic diseases have prompted an urgent need to develop fast, accurate, and portable screening assays for pathogen infections. Recombinase polymerase amplification (RPA) is sensitive and specific and can be conducted at a constant low temperature with a short response time, making it especially suitable for on-site screening and making it a powerful tool for preventing or controlling the spread of zoonoses. This review summarizes the design principles of RPA-based biosensors as well as various signal output or readout technologies involved in fluorescence detection, lateral flow assays, enzymatic catalytic reactions, spectroscopic techniques, electrochemical techniques, chemiluminescence, nanopore sequencing technologies, microfluidic digital RPA, and clustered regularly interspaced short palindromic repeats/CRISPR-associated systems. The current status and prospects of the application of RPA-based biosensors in zoonoses screening are highlighted. RPA-based biosensors demonstrate the advantages of rapid response, easy-to-read result output, and easy implementation for on-site detection, enabling development toward greater portability, automation, and miniaturization. Although there are still problems such as high cost with unstable signal output, RPA-based biosensors are increasingly becoming one of the most important means of on-site pathogen screening in complex samples involving environmental, water, food, animal, and human samples for controlling the spread of zoonotic diseases. Keywords: recombinase polymerase amplification, biosensor, zoonoses, rapid detection, nanomaterials

Huajun Ma, Chenhui Zhao School of Business Administration, Zhongnan University of Economics and Law, Hubei, Wuhan, 430073, People’s Republic of ChinaCorrespondence: Chenhui Zhao, Email chzhao2000@163.comPurpose: Successful aging at work is a new idea for enterprises to develop and utilize older employees under the background of population aging. However, there is a lack of research on the effect of family-work conflict on successful aging at work. This study explored how family-work conflict affective successful aging at work through the mediating roles of occupational future time perspective and the moderating role of flexible work arrangements perception.Methods: In study 1 (scenario-based experiment, N=107) recruited full-time employees working through the Credamo platform as experimental subjects, tested the causal relationship between family-work conflict and successful aging at work. In study 2 (questionnaire survey, N=349), questionnaires were distributed to large manufacturing enterprises in North China, and a two-wave time-lagged survey design was used to test the full model.Results: The results show that family-work conflict has a negative impact on successful aging at work; occupational future time perspective plays a mediating role in the relationship between family-work conflict and successful aging at work; flexible work arrangements perception moderated the mediating path via occupational future time perspective, and the indirect effect of occupational future time perspective decreased when flexible work arrangements perception increased.Discussion: This study enriches the research on the relationship between family-work conflict and successful aging at work in theory, and has important guiding significance for enterprises to build an inclusive and aging human resource management system in practice.Keywords: family-work conflict, successful aging at work, occupational future time perspective, flexible work arrangements perception

Yun-E Xu,1,&ast; Di-Shu Ao,1,&ast; Xin Sun,1 Wei Chen,2 Xue Luo,1 Can Zhao,1 Sheng-Yu Wang,1 Hong Song1 1Department of Microbiology, School of Basic Medical Sciences, Zunyi Medical University, Zunyi, 563000, People’s Republic of China; 2Department of Hepatobiliary Surgery, Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi), Zunyi, 563000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Song, Department of Microbiology, School of Basic Medical Sciences, Zunyi Medical University, Zunyi, 563000, People’s Republic of China, Tel +86-18985259977 ; +86-0851-28643582, Email hongsong@zmu.edu.cnPurpose: Hydrogels containing the nano-self-assembling peptide RADA16-I (Nanogels) were utilized as scaffolds to establish airway organoids and an adenovirus-infected model. The results support in vitro adenovirus studies, including isolation and culture, pathogenesis research, and antiviral drug screening.Methods: HSAEC1-KT, HuLEC-5a and HELF cells were cocultured in RADA16-I hydrogel scaffolds to construct an airway organoid model. Adenovirus was used to infect this model for adenovirus-related studies. The morphological characteristics and the proliferation and activity of airway organoids before and after adenovirus infection were evaluated. The expression of the airway organoid marker proteins CC10, KRT8, AQP5, SPC, VIM and CD31 was detected. TEM and qPCR were used to detect adenovirus proliferation in airway organoids.Results: HSAEC1-KT, HuLEC-5a and HELF cells cocultured at 10:7:2 self-assembled into airway organoids and maintained long-term proliferation in a RADA16-I hydrogel 3D culture system. The organoids stably expressed the lumen-forming protein KRT8 and the terminal airway markers AQP5 and SPC. Adenoviruses maintained long-term proliferation in this model.Conclusion: An airway-organoid model of adenovirus infection was constructed in vitro from three human lung-derived cell lines on RADA16-I hydrogels. The model has potential as a novel research tool for adenovirus isolation and culture, pathogenesis research, and antiviral drug screening.Keywords: nano-self-assembling peptide, RADA16-I hydrogels, airway organoids, adenovirus

Chunlong Zhao,1,2,&ast; Zipeng Xu,1,&ast; Weidong Hu,1,&ast; Chen Ge,1 Zhengwei Zhang,1 Zhengxing Dai,3 Shuo Zhang,4 Neng Tang,4 Weiguo Wang,3 Jiayu Gu,3 Chaobo Chen,1,4,5 Songbing He2 1Department of General Surgery, Xishan People’s Hospital of Wuxi City, Wuxi, People’s Republic of China; 2Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 3Department of Interventional and Vascular Surgery, Xishan People’s Hospital of Wuxi City, Wuxi, People’s Republic of China; 4Department of Hepatic-Biliary-Pancreatic Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China; 5Department of Immunology, Ophthalmology & ORL, Complutense University School of Medicine, Madrid, Spain&ast;These authors contributed equally to this workCorrespondence: Chaobo Chen; Songbing He, Email bobo19820106@gmail.com; hesongbing1979@suda.edu.cnBackground: Laparoscopic cholecystectomy (LC) with laparoscopic common bile duct exploration (LCBDE) is convenient in treating cholelithiasis and choledocholithiasis due to its advantage of accelerated recovery. This retrospective study aimed to summarize the experience of cholelithiasis and choledocholithiasis treatment via three-port approach of LCBDE in Eastern China.Methods: Patients diagnosed with cholelithiasis and choledocholithiasis between July 2019 and October 2021 were included. Patients who received LC+LCBDE+primary suturing of the common bile duct (CBD) via a three-port approach were assigned to the LCBDE-P group, and those who received LC+LCBDE+T-tube drainage of CBD comprised the LCBDE-T group. The measurement data were compared between the two groups. P-values < 0.05 indicated statistical significance.Results: A total of 88 patients were divided into two groups: LCBDE-P (n=50) and LCBDE-T (n=38). Multiple logistic regression analysis showed that LCBDE-P is associated with a shorter length of stay (OR=0.115, 95% CI: 0.040– 0.329, P< 0.001) and lower hospitalization costs (OR=0.120, 95% CI: 0.041– 0.357, P< 0.001). No significant differences between the two groups were detected in the operation time, intraoperative hemorrhage, clearance rate of CBD stones, postoperative liver function, and postoperative complications (P> 0.05).Conclusion: The three-port approach of LCBDE is a safe and feasible strategy for managing cholelithiasis and choledocholithiasis. Compared to LCBDE-T, LCBDE-P reduces the length of hospital stay and medical costs during hospitalization.Keywords: cholelithiasis, choledocholithiasis, laparoscopic cholecystectomy, laparoscopic common bile duct exploration, primary suture, T-tube drainage

Zipeng Xu,1,&ast; Yong Zhao,2,&ast; Xu Fu,3,&ast; Weidong Hu,1 Chunlong Zhao,1 Chen Ge,1 Hui Ye,4,5 Chaobo Chen1,3,5 1Department of General Surgery, Xishan People’s Hospital of Wuxi City, Wuxi, 214105, People’s Republic of China; 2Department of General Surgery, Wuxi Rehabilitation Hospital, Wuxi, 214007, People’s Republic of China; 3Department of General Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical school, Nanjing, 210008, People’s Republic of China; 4Department of Anesthesiology, ZhongDa Hospital, Southeast University, Nanjing, 210009, People’s Republic of China; 5Department of Immunology, Ophthalmology & ORL, Complutense University School of Medicine, Madrid, 28040, Spain&ast;These authors contributed equally to this workCorrespondence: Chaobo Chen; Hui Ye, Email bobo19820106@gmail.com; carciapene@126.comObjective: Although laparoscopic repair has been widely carried out and promoted due to its minimally invasive advantages, open surgery is still popular compared to elderly patients. This study aims to compare the outcomes of laparoscopic (LIHR) vs open repair of inguinal hernias (OIHR) in elderly patients.Methods: A retrospective analysis of the database was performed to identify elderly patients, from January 2021 through December 2022, who underwent surgery for an inguinal hernia. After a 1:1 propensity score matching (PSM) with a caliper of 0.1 was conducted to balance potential bias, binary logistic regressions were used for categorical and continuous outcomes.Results: After PSM, 78 pairs of elderly patients were enrolled in this study, and there were no significant differences in baseline between LIHR and OIHR groups. Compared to OIHR, univariable and multivariable logistic regression analysis showed that LIHR was independently affected for reducing intraoperative hemorrhage (OR = 0.06, 95% CI: 0.02– 0.18, P < 0.001) and shortening postoperative hospitalization time (OR = 0.29, 95% CI: 0.15– 0.57, P < 0.001) in elderly patients. Furthermore, LIHR (OR = 0.28, 95% CI: 0.14– 0.57, P < 0.001) and age (OR = 0.89, 95% CI: 0.82– 0.96, P = 0.002) were independent affecting factors for relieving postoperative pain. Meanwhile, no obvious differences were detected in postoperative complications [LIHR 7.7% (6/78) vs OIHR 14.1% (11/78), P = 0.199].Conclusion: LIHR was closely associated with reducing intraoperative hemorrhage and shortening postoperative hospitalization time. Whilst LIHR and age were independently affecting factors for relieving postoperative pain.Keywords: inguinal hernia, propensity score matching, elderly patient, laparoscopy, retrospective study

Changtai Zhao,1,&ast; Guang Yang,2,&ast; Bingzhou Ji,2 Hongfu Jin,2 Shinen Naranmandakh,3 Yusheng Li2,4 1Xiangya School of Medicine, Central South University, Changsha, Hunan, 410008, People’s Republic of China; 2Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China; 3Department of Chemistry, School of Arts and Sciences, National University of Mongolia, Ulaanbaatar, 14201, Mongolia; 4National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yusheng Li; Shinen Naranmandakh, Email liyusheng@csu.edu.cn; smandakh@num.edu.mnBackground: Osteoarthritis (OA) is a painful and complex joint disease. The unique mechanisms and potential interventions of OA-induced pain have attracted researchers’ attention in recent years. Bibliometric and visualization analysis is a comprehensive scientific method that integrates mathematical and statistical approaches to explore research priorities in a specific field. However, there are few studies on OA pain using bibliometric analysis.Purpose: This study aimed to explore research trends and hotspots in OA pain research field, offer practical guidance to researchers looking for top-notch scholars/institutions/countries, and provide suggestions for journal submissions by analyzing the existing literature.Methods: Raw data were extracted from Web of Science Core Collection. Microsoft Excel, the R package “bibliometrix”, VOSviewer and CiteSpace software were used to analyze data and visualize relevant results.Results: A total of 2493 articles were included for further bibliometric and visualization analysis. During the investigated period, 2021 with 343 publications was the most productive year. Fillingim, Roger B. and Bennell, Kim L. with 32 articles were the most productive authors. Most publications were from the USA (797 articles, 20,727 citations). Rehabilitation and treatment of OA pain were the hotspots in OA pain research area. The top-contributing journal was Osteoarthritis and Cartilage. Boston University (91 articles; 4050 citations) was the most active institution.Conclusion: The total publications of OA pain generally increasing over the time in the last decade, and the escalating rate remained a high level. This is the first comprehensive bibliometric study in OA pain research field, and it will offer practical guidance to researchers in this field.Graphical Abstract: Keywords: osteoarthritis pain, bibliometric analysis, research trends, VOSviewer, CiteSpace

Chenghao Zhao,&ast; Zhanwang Xiang,&ast; Mingan Li, Haofan Wang, Huan Liu, Huzheng Yan, Mingsheng Huang Department of Interventional Radiology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingsheng Huang; Huzheng Yan, Tel/Fax +86-20-85253416, Email huangmsh@mail.sysu.edu.cn; yanhzh8@mail.sysu.edu.cnPurpose: Combined transarterial chemoembolization (TACE) and Lenvatinib (LEN) treatment (LEN-TACE) has been shown to be beneficial. We aimed to evaluate retrospectively Atezolizumab plus Bevacizumab (Atezo/Bev)-TACE compared with LEN-TACE as a first-line therapy for unresectable HCC.Patients and Methods: From October 2020 to October 2022, data from 98 consecutive HCC patients were analyzed. After propensity score matching, two cohorts of 34 patients who received either Atezo/Bev-TACE or LEN-TACE were studied. We compared overall survival (OS), progression-free survival (PFS), duration of response, objective response rate (ORR) and disease control rate (DCR) based on RECIST 1.1 and mRECIST, as well as safety outcome between the two cohorts.Results: The 6-month and 12-month OS rates were 85.3% (95% CI 73.5– 97.0) and 75.4% (95% CI 53.6– 85.7) in the Atezo/Bev-TACE group, and 88.2% (95% CI 76.5– 97.1) and 79.2% (95% CI 63.6– 90.9) in the LEN-TACE group, respectively. The hazard ratio for death in the Atezo/Bev-TACE group compared to the LEN-TACE group was 1.09 (95% CI 0.47– 2.51; P = 0.837). The median PFS was 7.03 months (95% CI 3.89– 10.17) in the Atezo/Bev-TACE group and 6.03 months (95% CI 0– 14.14) in the LEN-TACE group (HR 1.21; 95% CI 0.66– 2.21; P = 0.545). No significant difference in ORR and DCR between the two groups was observed either according to RECIST 1.1 or mRECIST standards. Incidence rates of hand-foot skin reaction (35.3% vs 5.9%, P = 0.003) and proteinuria (17.9% vs 2.9%, P = 0.046) were significantly higher in the LEN-TACE group.Conclusion: Atezo/Bev-TACE and LEN-TACE showed comparable efficacy and safety as first-line therapies for unresectable HCC patients.Keywords: atezolizumab plus bevacizumab, lenvatinib, transarterial chemoembolization, hepatocellular carcinoma, efficacy

Chen Zhao,1,&ast; Haoyun Zhou,2,&ast; Shaowen Ge,1 Zhaojun Zhan,1 Shunhua Zhang,3 Shengkai Liao1 1Department of Stomatology, First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, People’s Republic of China; 2School of Public Health, Bengbu Medical College, Bengbu, 233030, People’s Republic of China; 3School of Medical Imaging, Bengbu Medical College, Bengbu, 233030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shengkai Liao, Department of Stomatology, First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, People’s Republic of China, Email lsk3166@163.comBackground and Purpose: The purpose of this study was to investigate the relationships among attitudes and practice about oral health, socioeconomic status, subjective oral symptoms, self-rated oral health, and oral health-related quality of life (OHRQoL) in a group of people from eastern China.Methods: Between January 2021 to February 2022, 2502 (87.4%) of the 2863 participants completed an online questionnaire. OHRQoL, Socio-demographics characteristics, attitudes and practice toward oral health, self-rated oral health and subjective oral symptoms were all covered by the questionnaires. Based on the hypothetical model, structural equation modeling with the bootstrap method was used to examine the interactions and the strength of the correlations between the measured variables.Results: The final model demonstrated acceptable data fit. Socioeconomic status (β = − 0.051), attitudes (β = − 0.100) and practice (β = − 0.127) toward oral health, self-rated oral health (β = − 0.493) and subjective oral symptoms (β = 0.294) were all significantly correlated with OHRQoL. Socioeconomic status was directly linked to attitudes (β = 0.046) and practice (β =0.070) about oral health, and attitudes play the role of intermediary between practice and socioeconomic status (β = 0.018). OHRQoL was indirectly linked with attitudes mediated by practice (β = − 0.092), practice mediated by subjective oral symptoms (β = − 0.107), subjective oral symptoms mediated by self-rated oral health (β = 0.031). OHRQoL was correlated with income, educational level, and socioeconomic status. Self-rated oral health was related to educational level and socioeconomic status.Conclusion: In a sample of eastern China residents, OHRQoL was influenced by socioeconomic status, attitudes and practice toward oral health, subjective oral symptoms, and self-rated oral health.Keywords: oral health-related quality of life, socioeconomic status, self-rated oral health, structural equation modeling, eastern China

Sohel Somani,1 Keyvan Koushan,2 Bijal Shah-Manek,3 Daniel Mercer,4 Thula Kanagenthiran,5 Changgeng Zhao,5 Ali Alobaidi5 1Department of Ophthalmology and Vision Sciences, University of Toronto and Uptown Eye Specialists, Brampton, Canada; 2Toronto Retina Institute, Toronto, Canada; 3Health Economics and Outcomes Research, Noesis Healthcare Technologies, Inc., Redwood City, CA, USA; 4Genesis Research, Hoboken, NJ, USA; 5Allergan, an AbbVie Company, Irvine, CA, USACorrespondence: Sohel Somani, Email sohel.somani@uptowneye.caPurpose: To understand the demographics, clinical characteristics, treatment patterns, visual and anatomic responses of patients with diabetic macular edema (DME) initially treated with anti-vascular endothelial growth factor (anti-VEGF) agents in the real-world clinical setting.Patients and Methods: This retrospective cohort study used electronic health records to identify consecutively presenting patients with DME who received their first documented anti-VEGF injection (index injection) on or after 1 October 2015 and before 30 September 2016 (index period) at 4 clinical sites in Ontario, Canada. Patients receiving anti-VEGF injections in the study eye were followed for ≥ 18 months. After the first 3 monthly injections, patients were classified as “responder” (≥ 20% reduction in central retinal thickness [CRT] from index date) or “nonresponder” (< 20% reduction in CRT) to anti-VEGF treatment.Results: At 12 months, change from baseline (CFB) in best visual acuity (BVA) of responders (n = 30) was mean (SD) 12.8 (13.00) letters; CFB in nonresponders (n = 56) was 3.2 (16.3) letters. Sensitivity analyses stratified by initial BVA were supportive. Mean (SD) change in CRT (μm) was − 160.4 (111.4) in responders and − 62.2 (98.6) in nonresponders. While changes in anti-VEGF therapy were lower in responders versus nonresponders (10.0% vs 23.2%), mean number of injections was similar (8.3 in each cohort).Conclusion: Despite receiving a substantial number of injections and requiring changes in therapy more frequently, nonresponders showed a lack of clinically meaningful change in BVA and CRT. Nonresponders could be identified after 3 anti-VEGF injections. There remains an unmet need for treatment options in patients with DME who show a nonresponse after 3 months of anti-VEGF treatment.Keywords: real-world evidence, diabetic macular edema, drug therapy, anti-vascular endothelial growth factor, visual acuity

Shebin Hong,1– 3,&ast; Weidong Jiang,1– 3,&ast; Qinfeng Ding,1– 3,&ast; Kaili Lin,1– 3 Cancan Zhao,1– 3 Xudong Wang1– 3 1Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2College of Stomatology, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xudong Wang; Cancan Zhao, Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, No. 639, Zhizaoju Road, Shanghai, 200011, People’s Republic of China, Tel +86-21-23271699, Fax +86-21-63136856, Email wang70@hotmail.com; cc.zhao@sjtu.edu.cnAbstract: Recently, programmable assembly technologies have enabled the application of DNA in the creation of new nanomaterials with unprecedented functionality. One of the most common DNA nanostructures is the tetrahedral DNA nanostructure (TDN), which has attracted great interest worldwide due to its high stability, simple assembly procedure, high predictability, perfect programmability, and excellent biocompatibility. The unique spatial structure of TDN allows it to penetrate cell membranes in abundance and regulate cellular biological properties as a natural genetic material. Previous studies have demonstrated that TDNs can regulate various cellular biological properties, including promoting cells proliferation, migration and differentiation, inhibiting cells apoptosis, as well as possessing anti-inflammation and immunomodulatory capabilities. Furthermore, functional molecules can be easily modified at the vertices of DNA tetrahedron, DNA double helix structure, DNA tetrahedral arms or DNA tetrahedral cage structure, enabling TDN to be used as a nanocarrier for a variety of biological applications, including targeted therapies, molecular diagnosis, biosensing, antibacterial treatment, antitumor strategies, and tissue regeneration. In this review, we mainly focus on the current progress of TDN-based nanomaterials for antimicrobial applications, bone and cartilage tissue repair and regeneration. The synthesis and characterization of TDN, as well as the biological merits are introduced. In addition, the challenges and prospects of TDN-based nanomaterials are also discussed.Graphical Abstract: Keywords: tetrahedral DNA nanostructure, carriers, antibacterial treatment, bone regeneration, cartilage regeneration

Yong Zhang,1 Kaisa Cui,2 Yaoxiang Yang,3 Bingxin Liu,4 Minzheng Zhu,1 Hanqing Chen,1 Chong Zhao,1 Youlian Zhou,1 Yuqiang Nie1 1Department of Gastroenterology and Hepatology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510006, People’s Republic of China; 2Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214062, People’s Republic of China; 3Department of Pathology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510006, People’s Republic of China; 4The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, 211166, People’s Republic of ChinaCorrespondence: Yuqiang Nie; Youlian Zhou, Department of Gastroenterology and Hepatology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Panfu Road 1, Yuexiu District, Guangzhou, Guangdong, 510006, People’s Republic of China, Tel/Fax +86 20 81048888, Email eynieyuqiang@scut.edu.cn; eyyoulianzhou@scut.edu.cnIntroduction: Immune checkpoint (IC) inhibitor-related immunotherapies have attracted considerable attention in hepatocellular carcinoma (HCC). High IC expression and high tumor infiltrating lymphocyte levels are the current indicators of sensitivity to IC inhibitors. Thus, it is imperative to apply precision medicine strategies for patient selection.Methods: Six independent HCC cohorts were used for analysis at the single-cell and tissue levels. Multiplex immunofluorescence and immunochemistry staining assays were used to validate our results. A series of methodologies were used for immune-related evaluations.Results: Herein, we uncovered a unique CD8+CD274+ cell subpopulation that is associated with tumor progression and poor survival in HCC at the single-cell level. We assessed this subset at the tissue level and found that the prognostic significance of CD274 is dependent on CD8A expression in HCC. Subsequently, we identified a unique high-risk subpopulation that showed high CD8A expression coupled with intense CD274 expression in multiple HCC cohorts. CD8AHighCD274High&ast; subgroup was correlated with malignant indexes and remained an independent prognostic factor when considering the influence of these indexes. Molecular characteristic analyses showed that the CD8AHighCD274High&ast; subgroup harbored more mutations, had higher immune response activity and presented enrichment of cancer-related biological processes. Moreover, this high-risk subpopulation in HCC was characterized by high immune cell infiltration, low tumor purity, and enrichment of cancer-related signatures. Finally, cases with this phenotype demonstrated higher immunomodulator and IC levels and greater sensitivity to IC inhibitors.Conclusion: Our findings illustrate that some HCC patients may have a poor prognosis despite high CD8+ T-cell infiltration. These patients would probably benefit from IC inhibitor-based combination treatment.Keywords: hepatocellular carcinoma, CD8A, CD274, molecular subtype, tumor microenvironment, immune overdrive

Zhao C, Li Y, Hu X, et al. Onco Targets Ther. 2020;13:11827–11838. At the author’s request, we, the Editors and Publisher of OncoTargets and Therapy, have retracted the following article. Following publication of the article, the authors raised concerns regarding the duplication of images from Figures 2 and 4 with images from other unrelated articles. Specifically, Images for Figure 2C have been duplicated with images for Figure 2D from Fu Y, Cai L, Lei X, et al. RETRACTED ARTICLE: Circular RNA ABCB10 promotes hepatocellular carcinoma progression by increasing HMG20A expression by sponging miR-670-3p. Cancer Cell Int. 2019;19:338. https://doi.org/10.1186/s12935-019-1055-z; Figure 3B from Xing Z, Zhang Z, Gao Y, et al. The lncRNA LINC01194/miR-486-5p Axis Facilitates Malignancy in Non-Small Cell Lung Cancer via Regulating CDK4. Onco Targets Ther. 2020;13:3151-3163. https://doi.org/10.2147/OTT.S235037 and Figure 3H from Peng Y, Li X, Liu H, et al. RETRACTED ARTICLE: microRNA-18a from M2 Macrophages Inhibits TGFBR3 to Promote Nasopharyngeal Carcinoma Progression and Tumor Growth via TGF-β Signaling Pathway. Nanoscale Res Lett. 2020;15:196. https://doi.org/10.1186/s11671-020-03416-8. Images for Figure 4B have been duplicated with images for Figure 5C from Zhang D, Ma Y, Ma Z, et al. Circular RNA SMARCA5 suppressed non-small cell lung cancer progression by regulating miR-670-5p/RBM24 axis. Acta Biochimica et Biophysica Sinica. 2020;52:1071-1080. https://doi.org/10.1093/abbs/gmaa099. The authors were cooperative and explained that after becoming aware of the concerns, they evaluated the study and were unable to verify the validity of the reported findings or explain how the images came to be duplicated. As verifying the validity of published work is core to the integrity of the scholarly record, the authors found it necessary to retract the article and we, the Editors and Publisher, agree with this decision. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Min Wang,1,2,&ast; Na Yang,1,2,&ast; Xu Wu,3 Ting Zou,3 Jiahui Zheng,3 Huaijun Zhu,1 Chongbo Zhao,3 Jing Wang3 1Department of Pharmacy, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China; 2China Pharmaceutical University Nanjing Drum Tower Hospital, Nanjing, People’s Republic of China; 3College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chongbo Zhao; Jing Wang, College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, People’s Republic of China, Email 2051077@sntcm.edu.cn; wangjing19890126@126.comBackground: Arisaematis Rhizome (AR) has been used as a damp-drying, phlegm-resolving, wind-expelling, pain-alleviating, and swelling-relieving drug for thousands of years. However, the toxicity limits its clinical applications. Therefore, AR is usually processed (Paozhi in Chinese) prior to clinical use. In this study, the integration of ultra-high performance liquid chromatography-quadrupole/ time-of-flight mass spectrometry-based metabolomics and network analysis was adopted to investigate the metabolic shifts induced by AR and explore the processing mechanism.Materials and Methods: Extracts of crude and processed AR products (1g/kg) were intragastrically administered to rats once daily for four consecutive weeks. The renal function was evaluated by blood urea nitrogen, creatinine, interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), super oxide dismutase (SOD), the ratio of glutathione/glutathione disulfide (GSH/GSSH), glutathione peroxidase (GSH-Px) and histopathological examination. Furthermore, the chemical composition of AR was clarified by ultra-high performance liquid chromatography-quadrupole/ time-of-flight mass spectrometry, after which the integration of metabolomics and network analysis was adopted to investigate the metabolic shifts induced by AR and explore the processing mechanism.Results: Crude AR caused renal damage by stimulating inflammation and oxidative stress, as confirmed by the increased production of IL-1β, TNF-α and MDA, and decreased levels of SOD, GSH/GSSH and GSH-Px. Processing with ginger juice, alumen and bile juice alleviated the damage to kidney. Metabolomics results showed that a total of 35 potential biomarkers enriched in amino acid metabolism, glycerophospholipid metabolism, fatty acid-related pathways, etc. were deduced to be responsible for the nephrotoxicity of AR and the toxicity-reducing effect of processing.Conclusion: This work provided theoretical and data support for the in-depth study of the processing mechanism, showing that processing reduces AR nephrotoxicity through multiple metabolic pathways.Graphical Abstract: Keywords: Arisaematis rhizome, nephrotoxicity, processing, UPLC-Q/TOF-MS, metabolomics

The mechanism of accumulation of Cd compounds and the migration of its mobile forms in the soil are considered. The method of sampling soil and plants, as well as the method of morphometric research, was explained. The process of determining the content of cadmium in plants and soil was analyzed. The analysis of the experiment shows that high concentrations of Cd salts significantly inhibit all growth processes. This is manifested in growth retardation, color change, reduction in the number of leaves, occurrence of chlorosis and necrosis, which leads to a decrease in the accumulation of phytomass. With an increase in the amount of Cd, we observe suppression of plants and a sharp decrease in their height. A trend line is given based on the received data. The value of the reliability of the approximation is close to one and is R2=0.99, which indicates a close relationship between the increase in the concentration of cadmium in the soil and the decrease in the height of spring barley plants.

Jun-Peng Zhang,1,&ast; Jun Shen,2,3,&ast; Yun-Ting Xiang,1,&ast; Xiang-Xin Xing,4 Bing-Xin Kang,5 Chi Zhao,2 Jia-Jia Wu,4 Mou-Xiong Zheng,4,6 Xu-Yun Hua,4,6 Lian-Bo Xiao,2,3 Jian-Guang Xu1,4,7 1School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Orthopedic, Guanghua Hospital of Integrative Chinese and Western Medicine, Shanghai, People’s Republic of China; 3Arthritis Institute of Integrated Traditional Chinese and Western Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Department of Rehabilitation Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 5The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 6Department of Traumatology and Orthopedics, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 7Engineering Research Center of Traditional Chinese Medicine Intelligent Rehabilitation, Ministry of Education, Shanghai, China&ast;These authors contributed equally to this workCorrespondence: Jian-Guang Xu, School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, People’s Republic of China, Email xjg@shutcm.edu.cn Lian-Bo Xiao, Department of Orthopedic, Guanghua Hospital of Integrative Chinese and Western Medicine, 540 Xinhua Road, Changning District, Shanghai, People’s Republic of China, Email xiao_lianbo@163.comIntroduction: Osteoarthritis is a chronic, ongoing disease that affects patients, and pain is considered a key factor affecting patients, but the brain changes during the development of osteoarthritis pain are currently unclear. In this study, we used electroacupuncture (EA) to intervene the rat model of knee osteoarthritis and analyzed the changes in topological properties of brain networks using graph theory.Methods: Sixteen SD rat models of right-knee osteoarthritis with anterior cruciate ligament transection (ACLT) were randomly divided into electroacupuncture intervention group and control group. The electroacupuncture group was intervened on Zusanli (ST36) and Futu (ST32) for 20 min each time, five times a week for 3 weeks, while the control group was applied sham stimulation. Both groups were measured for pain threshold. The small-world properties and node properties of the brain network between the two groups after the intervention were statistically analyzed by graph theory methods.Results: The differences are mainly in the changes in node attributes between the two groups, such as degree centrality, betweenness centrality, and so on in different brain regions (P< 0.05). Both groups showed no small-world characteristics in the brain networks of the two groups. The mechanical thresholds and thermal pain thresholds were significantly higher in the EA group than in the control group (P< 0.05).Conclusion: The study demonstrated that electroacupuncture intervention enhanced the activity of nodes related to pain circuit and relieved pain in osteoarthritis, which provides a complementary basis for explaining the effect of electroacupuncture intervention on pain through graphical analysis of changes in brain network topological properties and helps to develop an imaging model for pain affected by electroacupuncture.Keywords: osteoarthritis, electroacupuncture, pain, spatio-temporal analysis, neural plasticity

Wei Zhang,1,&ast; Chunzhao Li,2,&ast; Chunmei Zhao,3 Nan Ji,2 Fang Luo3 1Department of Day Surgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China; 2Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China; 3Department of Day Surgery and Pain Management, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fang Luo, Department of Day Surgery and Pain Management, Beijing Tiantan Hospital, Capital Medical University, No. 119 West Road, South 4th Ring Road, Fengtai District, Beijing, 100070, People’s Republic of China, Tel +86 10 59976664, Fax +86 10 67050177, Email 13611326978@163.com Nan Ji, Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119 West Road, South 4th Ring Road, Fengtai District, Beijing, 100070, People’s Republic of China, Email jinan@mail.ccmu.edu.cnBackground: Pain after craniotomy remains a poorly controlled problem that is mainly caused by the inflammatory reaction at the incision site. Nowadays, systemic opioids use, as first-line analgesics, is often limited because of adverse effects. Flurbiprofen axetil (FA) is a non-steroidal anti-inflammatory drug merged into emulsified lipid microspheres, which represent a strong affinity to inflammatory lesions. Local administration of flurbiprofen into a surgical wound has induced enhanced analgesic efficacy and few systemic or local adverse effects after oral surgery. However, the impact of local FA, as a non-opioid pharmacologic alternative, remains elusive on postoperative pain in craniotomy. In this study, we presume that pre-emptive infiltration of scalp with FA as an adjuvant to ropivacaine can lead to less sufentanil consumption postoperatively in patient controlled intravenous analgesia (PCIA) compared with ropivacaine alone.Methods/Design: We design a multicenter, randomized controlled study that will enroll 216 subjects who are planned to receive supratentorial craniotomy. Patients will receive pre-emptive infiltration of scalp either with 50 mg FA and 0.5% ropivacaine, or with 0.5% ropivacaine alone. Primary outcome is total consumption of sufentanil with PCIA device at 48 h postoperatively.Discussion: This is the first study attempting to explore the analgesic and safety profile of local FA as an adjuvant to ropivacaine for incisional pain in patients undergoing craniotomy. It will provide additional insights into the opioid-sparing analgesia pathways by local administration of NSAIDs for neurosurgery.Keywords: flurbiprofen axetil, pre-emptive analgesia, scalp infiltration, opioid-sparing, craniotomy, postoperative pain

Wenli Hui, Wenhua Mu, Cong Zhao, Dan Xue, Zihua Zhong, Yani Fang, Ming Gao, Xiao Li, Shihao Gao, Kaiyue Liu, Kunping Yan College of Life Science, Northwest University, Xi’an City, Shaanxi Province, 710069, People’s Republic of ChinaCorrespondence: Kunping Yan, Email kpyan@nwu.edu.cnIntroduction: A limitation of hemoglobin-based oxygen carriers (HBOCs) as oxygen therapeutics is unpolymerized hemoglobin, which induces vasoconstriction leading to hypertension. The removal of unpolymerized hemoglobin from polymerized hemoglobin (PolyHb) is complex, expensive, and time-consuming.Methods: Herein, we developed a method to completely polymerize hemoglobin almost without unpolymerized hemoglobin. Hemoglobin was adsorbed on the anion-exchange resin Q Sepharose Fast Flow or DEAE Sepharose Fast Flow, and acetal, a crosslinker prepared from glutaraldehyde and ethylene glycol, was employed to polymerize the hemoglobin. The polymerization conditions, including reaction time, pH, resin type, and molar ratios of glutaraldehyde to ethylene glycol and hemoglobin to acetal, were optimized. The blood pressure and blood gas of mice injected with PolyHb were monitored as well.Results: The optimal polymerization condition of PolyHb was when the molar ratio of glutaraldehyde to ethylene glycol was 1:20, and the molar ratio of 10 mg/mL hemoglobin adsorbed on anion-exchange resin to glutaraldehyde was 1:300 for 60 min. Under optimized reactive conditions, hemoglobin was almost completely polymerized, with < 1% hemoglobin remaining unpolymerized, and the molecular weight of PolyHb was more centrally distributed. Furthermore, hypertension was not induced in mice by PolyHb, and there were also no pathological changes observed in arterial oxygen, blood gas, electrolytes, and some metabolic indicators.Conclusion: The findings of this study indicate that the use of solid-phase polymerization and acetal is a highly effective and innovative approach to HBOCs, resulting in the almost completely polymerized hemoglobin. These results offer promising implications for the development of new methods for preparing HBOCs.Graphical Abstract: Keywords: polymerized hemoglobin, glutaraldehyde, acetal, solid-phase adsorption, hemoglobin-based oxygen carriers, HBOCs

Mengqi Zhang,1,&ast; Shengxian Bao,2,&ast; Guanhua Qiu,2,&ast; Jingchen Liang,2 Qin Wang,2 Xiaoqi Zhu,2 Guchun Qin,1 Junjie Liu,2 Chang Zhao1 1Department of Interventional Therapy, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Ultrasound and Department of Radiology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junjie Liu; Chang Zhao, Email liujunjie197806@163.com; 710519137@qq.comPurpose: In this experiment, we constructed a magnetic targeting nano-diagnosis and treatment platform of doxorubicin (DOX) combined with iron nanoparticles, and explored their application value and mechanism in the treatment of Triple Negative Breast Cancer (TNBC), as well as its new diagnosis and treatment mode in Magnetic Resonance Imaging (MRI).Patients and Methods: Hollow mesoporous nanoparticles (HFON) were synthesized by solvothermal method, and loaded the drug DOX (DOX@HFON) to treat TNBC. The experiments in vivo and in vitro were carried out according to the characteristics of the materials. In vitro experiments, the killing effect of the drug on cells was verified by cell viability CCK8, ROS generation level, LPO evaluation and flow cytometry; the MRI effect and targeted anti-tumor therapy effect were studied by in vivo experiments; then the tumor tissue sections were detected by Ki-67, CD31, ROS, LPO and TUNEL immunofluorescence detection; H&E staining and blood biochemical tests were used to evaluate the biosafety of the materials.Results: Through a series of characterization tests, it is confirmed that the nano-materials prepared in this experiment have positive drug loading properties. MDA-MB-231 cells had great phagocytic ability to DOX@HFON under Confocal Laser Scanning Microscope (CLSM). Experiments in vitro confirmed that DOX and Fe were released and concentrated in cells, and a large number of ROS production and induction of LPO were detected by DCFH-DA and C11-BODIPY probes in cells. Apoptosis experiments further confirmed that DOX@HFON induced apoptosis, autophagy and ferroptosis. In the vivo experiment, the anti-tumor therapy effect of MAGNET@DOX@HFON group was the most significant, and in MRI also proved that the drug had great tendency and imaging ability in tumor tissue.Conclusion: The new magnetic targeting nano-diagnosis and treatment platform prepared in this experiment is expected to become a new treatment model for TNBC.Keywords: nanoparticles, DOX, Fenton, ROS

Guojun Zhang,1 Chuan Yang,2 Caixia Zhao,1 Feng Xian,3 Dong Qing,1 Qiyu Guo,1 Junmei Song,1 Xilin Liu,1 Jun Bie1 1Department of Oncology, Nanchong Central Hospital and The Second Clinical Medical College of North Sichuan Medical College, Nanchong, People’s Republic of China; 2Department of Oncology, Guangyuan Central Hospital, Guangyuan, People’s Republic of China; 3School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of ChinaCorrespondence: Jun Bie, Department of Oncology, Nanchong Central Hospital and The Second Clinical Medical College of North Sichuan Medical College, Hongguang Road, Shunqing District, Nanchong, People’s Republic of China, Email 78593860@qq.comBackground: The neutrophil-to-lymphocyte ratio (NLR) has been shown to have prognostic value in several common cancers. This study aimed to investigate the prognostic value of NLR in patients with advanced oesophageal squamous cell carcinoma (ESCC) after definitive chemoradiotherapy (dCRT).Methods: A retrospective analysis was performed on 158 patients with advanced ESCC who received dCRT from January 2012 to December 2018. The NLR for different treatment stages was calculated based on laboratory test results. The Kaplan–Meier (KM) method and Cox proportional regression model were used to analyse the relationship between NLR and overall survival (OS).Results: The mean NLR of 158 patients with ESCC was 3.403 ± 2.479. The pre-treatment NLR cut-off was 4.839, and patients were divided into the low NLR group (NLR < 4.839) and the high NLR group (NLR ≥ 4.839). NLR in patients with ESCC was related to N stage (P < 0.05). The KM analysis showed that the median OS of all enrolled patients was 29.3 months, the median OS periods of patients in the high and low NLR groups were 15.6 and 35.8 months, respectively, and the OS of the low NLR group was better than that of the high NLR group (P < 0.001). In the multivariate analysis, NLR was an independent prognostic factor that affects the prognosis of patients with ESCC receiving dCRT. Furthermore, patients who maintained a high NLR before and after treatment showed worse clinical outcomes than the other groups.Conclusion: Our findings suggest that NLR can effectively assess the prognosis of patients with advanced ESCC undergoing dCRT.Graphical Abstract: Keywords: oesophageal squamous cell carcinoma, radiochemotherapy, neutrophil-to-lymphocyte ratio

Yu Guo,1,&ast; Qingyu Ma,1,&ast; Xuan Zhou,1 Juan Yang,2 Kejie He,3 Longbin Shen,4 Canghuan Zhao,3 Zhuoming Chen,4 Celia Ia Choo Tan,5 Jiaxu Chen1 1Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Jinan University, Guangzhou City, People’s Republic of China; 2Division of General Internal Medicine, Mayo Clinic, Rochester, MN, USA; 3Department of Acupuncture, First Affiliated Hospital of Jinan University, Guangzhou City, People’s Republic of China; 4Rehabilitation Medicine Center, First Affiliated Hospital of Jinan University, Guangzhou City, People’s Republic of China; 5Department of Physiotherapy, Singapore General Hospital, Singapore, Singapore&ast;These authors contributed equally to this workCorrespondence: Jiaxu Chen, Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Jinan University, No. 601 Huangpu Road West, Tianhe District, Guangzhou City, People’s Republic of China, Email chenjiaxu@hotmail.comPurpose: To evaluate the efficacy of different non-pharmacologic therapies (NPTs) on relieving depressive symptoms and pain intensity in individuals living with chronic low back pain (LBP) and associated depression.Methods: A comprehensive search of seven English databases and two Chinese databases from inception to the search date will be undertaken. The reference lists of previously published relevant reviews and included trials will also be searched. Only peer-reviewed and published moderate-to-high quality randomized controlled trials (RCTs) for chronic LBP and associated depression treated with NPTs will be considered. Two independent reviewers will identify studies, extract data, assess risk of bias, and evaluate the strength of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Meta-analysis will be conducted to estimate the treatment effect of various NPTs. Heterogeneity will be assessed using Cochrane’s Q and the I-squared statistics. Subgroup and sensitivity analyses will be performed to assess the robustness of findings. A funnel plot will be developed to evaluate reporting bias, and Begg’s and Egger’s tests will be used to assess funnel plot symmetries.Results: This protocol outlines the planned scope and methodology for an upcoming systematic review and meta-analysis, which will provide up-to-date evidence on 1) which NPTs are associated with improvements in depressive symptoms and pain intensity and 2) whether the effects of NPTs on chronic LBP and associated depression vary according to clinical condition, participant, and treatment characteristics.Conclusion: Our meta-analyses of moderate-to-high quality RCTs will help to develop specific recommendations on prescribing NPTs in patients with chronic LBP and associated depression.Study Registration: This protocol is registered on the International Platform of Registered Systematic Review and Meta-analysis (INPLASY) protocols platform as record No. INPLASY202260055.Keywords: non-pharmacologic therapies, chronic low back pain and associated depression, meta-analysis, randomized controlled trial, protocol

Danyu Zhang,1 Shoujie Li,1 Mohan Fan,2 Changqi Zhao1 1Gene Engineering and Biotechnology Beijing Key Laboratory, College of Life Science, Beijing Normal University, Beijing, People’s Republic of China; 2Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of ChinaCorrespondence: Changqi Zhao, Tel +86-5880-5046, Email 04020@bnu.edu.cnAbstract: The secondary metabolites isolated from soil fungi have received more and more attention, especially new compounds that exhibited good biological activities. In this review, a total of 546 new compounds are included in the relevant literature since 2011. The new compounds are isolated from soil fungi, We divided these compounds into seven categories, including alkaloids, terpenoids, steroids, ketones, phenylpropanoids, quinones, esters, lactones, etc. In addition, the biological activities and structure–activity relationships of these compounds have also been fully discussed. The activities of these compounds are roughly divided into eight categories, including anticancer activity, antimicrobial activity, anti-inflammatory activity, antioxidant activity, antiviral activity, antimalarial activity, immunosuppressive activity and other activities. Since natural products are an important source of new drugs, this review may have a positive guiding effect on drug screening.Keywords: soil fungi, new compounds, chemical structure, biological activity

Jie Wang, Yao Zhang, Changsong Zhao, Qiang Zhang Department of Orthopedics, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of ChinaCorrespondence: Qiang Zhang, Email zhangqianggk@sina.comIntroduction: The causes of femoral head necrosis mainly include trauma, corticosteroid, and alcohol, among which Brucella is highly unusual.Patients and Methods: This paper reported three rare cases of femoral head necrosis due to Brucella, summarizing and analyzing the epidemiological history, clinical manifestations, laboratory examinations, imaging findings, individualized therapy, and biopsy results of patients with this disease. A literature review related to brucellosis and femoral head necrosis was conducted.Results: All three patients had an epidemic history of brucellosis. They suffered from hip pain and limitation of movement for months, and femoral head necrosis was confirmed by magnetic resonance imaging (MRI). Pathological Giemsa staining or real-time polymerase chain reaction (real-time PCR) confirmed Brucella melitensis (B. melitensis) as the cause of osteonecrosis. Each patient received individualized therapy according to the degree of osteonecrosis, which was based on anti-brucellosis medications and hip puncture and irrigation decompression. They were followed up for more than two years and rehabilitated well.Conclusion: Brucella infection should always be considered the cause of femoral head necrosis for patients with hip pain, especially for those with an epidemic history; early diagnosis and individual stepwise therapy can prevent the progression of osteonecrosis.Keywords: Brucella, femoral head necrosis, core decompression, total hip arthroplasty, case series

Haiyan Zhang,1 Shuwei Sun,2 Han Xu,1 Chuyu Zhao1 1Business School, Jiangsu Normal University, Xuzhou, People’s Republic of China; 2School of Mathematics and Statistics, Xuzhou University of Technology, Xuzhou, People’s Republic of ChinaCorrespondence: Shuwei Sun, School of Mathematics and Statistics, Xuzhou University of Technology, No. 2 Lishui Road, Yunlong, Xuzhou, 221111, People’s Republic of China, Tel +86 15996963525, Fax +86 051683105396, Email ssw@xzit.edu.cnPurpose: Pay for employee characteristic human capital inputs, which results in part of horizontal pay dispersion (HPD) and is well acknowledged by organizations and employees, has been greatly ignored by scholars. This study proposes “the characteristic-human-capital-inputs-based HPD” and explores what impact it tends to exert on team member work role performance (TMWRP), why, and when. Drawing on social comparison theory, goal-setting theory, and self-regulatory depletion theory, we develop a dual-mediation model elaborating the detrimental effect of this type of HPD on TMWRP from the perspective of employee benign and malicious envy and test it using objective and subjective data of 364 members coming from 65 Chinese ordinary employee teams.Methods: We on-site collected objective data including each member’s pay level, outcome performance, and characteristic human capital inputs. Using five-point Likert rating method, team supervisors were requested to evaluate each member’s TMWRP and members were asked to self-rate benign and malicious envy. Hierarchical regression analysis, simple slope analysis, and bootstrapping approach were employed to verify the model.Results: The characteristic-human-capital-inputs-based HPD adversely affects TMWRP by reducing employee benign envy (the mediating effect=− 0.053, 95% CI=[− 0.111, − 0.002], excluding 0) and enhancing employee malicious envy (the mediating effect=− 0.025, 95% CI=[− 0.059, − 0.004], excluding 0). The positive linkage between employee benign envy and TMWRP is only observed in lower-paid employees (the simple slope=0.145, p< 0.05). Employee pay level does not moderate the relationship between malicious envy and TMWRP (β=− 0.033, p> 0.10).Conclusion: The characteristic-human-capital-inputs-based HPD, which involves the HPD part mainly resulting from employee differences in characteristic human capital inputs, tends to impair TMWRP through inhibiting employee benign envy and promoting employee malicious envy. Employee pay level is an important boundary condition constraining the positive effect of benign envy on TMWRP.Keywords: the characteristic-human-capital-inputs-based HPD, team member work role performance, employee benign envy, employee malicious envy, employee pay level

Zipu Jia,1 Jinyong Yu,2 Chunmei Zhao,2 Hao Ren,2 Fang Luo2 1Department of Day Surgery Center; Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Pain Management; Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Fang Luo, Department of Anesthesiology and Pain Management, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, People’s Republic of China, Tel +86 13611326978, Email luofangwt@yahoo.comBackground: Duloxetine has been reported to significantly relieve the pain of persistent idiopathic dentoalveolar pain (PIDP); however, the number of studies available is scarce and no study has identified the predictors of response of duloxetine for the treatment of PIDP.Objective: To report the efficacy, safety, and identification of positive predictors of duloxetine for PIDP patients through a retrospective multicenter observational study.Methods: We retrospectively reviewed the clinical database of PIDP patients who were prescribed duloxetine at 3 hospitals between January 2018 and November 2021. Demographic and pain-related baseline data, efficacy of patients after 3 months of medication by visual analog scale (VAS) scores for pain and adverse events were extracted and analyzed. The predictors of pain-relieving effect of duloxetine were identified by logistic regression analysis.Results: A total of 135 patients were included in this study. Side effects occurred immediately after taking duloxetine in 24 (17.8%) patients, and the treatment with duloxetine was discontinued on 13 of them because they could not tolerate the side effects. Other 11 (8.1%) patients gradually tolerated the side effects within 2 weeks. Ninety-four out of 122 (77.0%) patients obtained pain relief with VAS significantly decreased (p < 0.01) and the other 28 (23.0%) patients stopped taking the drug because of weak efficacy. Binary logistic regression analysis showed that short disease duration (OR = 1.017, 95% CI = 1.004– 1.030, P = 0.012) was an independent predictor of the positive response of duloxetine.Conclusion: This study confirmed that duloxetine can significantly improve chronic pain of PIDP patients, and the safety was tolerable. Patients with shorter disease duration had more benefit from duloxetine.Limitations: This is a retrospective observational study. Long-term efficacy and safety of duloxetine in the treatment of PIDP patients were not evaluated.Keywords: persistent idiopathic dentoalveolar pain, efficacy, safety, predictor of response, duloxetine

Yuan Zhang,1,&ast; Hongli Yue,1,&ast; Yirui Qin,1 Jiajing Wang,1 Chenyang Zhao,1 Miao Cheng,1 Bo Han,2 Ruquan Han,1 Weihua Cui1,&ast; 1Department of Anesthesiology, Beijing Tian Tan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ruquan Han; Weihua Cui, Department of Anesthesiology, Beijing Tian Tan Hospital, Capital Medical University, No. 119, Nan Si Huan Xi Lu, Fengtai District, Beijing, 100070, People’s Republic of China, Tel +8613701285393 ; Tel +8613701285393, Fax +861059976658, Email ruquan.han@ccmu.edu.cn; weihuacui@ccmu.edu.cnPurpose: Patients undergoing intraspinal tumor resection usually experience severe postoperative pain. Inadequate postoperative analgesia usually leads to severe postsurgical pain, which could cause patients to suffer from many other related complications. Recently, an increasing number of studies have found that gabapentin can relieve hyperalgesia, postoperative pain, and postoperative inflammation. However, there have been no reports on the use of gabapentin combined with sufentanil preoperatively for acute pain following intraspinal tumor resection.Study Design and Methods: This is a protocol for a randomized, placebo-controlled, and double-blinded trial. One-hundred and sixty-eight participants with chronic pain related to the intraspinal tumor will be randomized into the gabapentin and placebo groups in a 1:1 ratio. In the gabapentin group, patients will be given 300 mg gabapentin orally 36 h, 24 h, and 12 h before surgery; the placebo group will receive a placebo orally at the same time points preoperatively. To estimate the efficacy and safety endpoints, all the researchers and patients will be blinded until the completion of this study. The primary outcome will be the consumption of sufentanil within 48 h postoperatively. The secondary outcomes include the visual analog scale pain score and Von Frey mechanical pain threshold 36 h and 24 h before and 24 h and 48 h after surgery, the incidence of postoperative nausea, vomiting, and drowsiness, the length of hospital stay and medical expenses.Discussion: This trial is to evaluate the efficacy and safety of gabapentin combined with sufentanil for postoperative analgesia in patients who complain of pain before intraspinal tumor resection. The findings will provide a new strategy for multimode perioperative analgesia management in these patients.Keywords: gabapentin, intraspinal tumor resection, multimode perioperative analgesia, opiates

Neng Wang,&ast; Conglin Zhao,&ast; Congchen Tang, Lichun Wang Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lichun Wang, Center of Infectious Diseases, West China Hospital of Sichuan University, 37 Guoxue Lane, Chengdu, 610041, People’s Republic of China, Tel +86 288 542 2859, Fax +86 288 542 3052, Email mindywang0218@163.comBackground: Histoplasmosis is a deep fungal infection caused by Histoplasma capsulatum and can be classified as pulmonary, disseminated or central. Disseminated histoplasmosis is the most dangerous of all clinical types and is characterized by rapid onset, rapid progression, high mortality, and difficulty in diagnosis and treatment.Case Presentation: This report describes a 31-year-old female who presented with fever, with a maximum temperature of 39.8 °C. There were no concomitant symptoms, such as cough, sputum, abdominal pain and diarrhoea, before the onset of fever, and the illness lasted for more than 20 days. On examination, the liver and spleen were enlarged, and laboratory tests showed a significant decrease in CD4 cell count, suggesting immune deficiency. Broad-spectrum antibiotic treatment was ineffective, and specific infectious diseases and haematological neoplasms were considered likely. She was finally diagnosed with disseminated histoplasmosis after undergoing bone marrow aspiration and metagenomic next-generation sequencing (mNGS) and was treated with amphotericin B, fluorouracil and itraconazole, with good results.Conclusion: This case demonstrates that disseminated histoplasmosis infection can present with unexplained fever and that mNGS can be an important complement to bone marrow aspiration for the diagnosis of this disease.Keywords: disseminated histoplasmosis, immune deficiency, metagenomic next-generation sequencing, amphotericin B, case report

Chun Zhao1 &ast;, Yan Huang2 &ast;, Lei Chen,1 Sheng Ye,1 Xiao-Qiang Liu1 &#x002A1Department of Ophthalmology, Tenth People’s Hospital Affiliated to Shanghai Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China; 2Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, People’s Republic of China&ast; These authors contributed equally to this workCorrespondence: Xiao-Qiang Liu, Email liuxiaoqiang@hotmail.comBackground: Central serous chorioretinopathy (CSC) is preferential cocurated in males, however the associations between sex hormones and CSC incidence or progression remains unclear. The sex hormone concentration assessments in CSC cases and healthy controls will update the knowledge in CSC management.Methods: This case-control study included 59 CSC cases and 30 healthy controls, from January 2019 to December 2020. The CSC cases would be defined as spontaneous resolved if the subretinal fluid were absorbed within three months. The concentrations of total testosterone (TT), free testosterone (FT), estradiol (E2), sex hormone-binding globulin (SHBG), progesterone, leuteinizing hormone (LH) and dehydroepiandrosterone sulfate (DHEA-S) were detected in all the participants. The relationships between sex hormone concentrations and CSC-related characteristics were analyzed with Pearson correlation analyses.Results: Significantly increased TT, FT, FT/E2 ratio, SHBG concentrations as well as decreased DHEA-S level were detected in non-resolved CSC group compared with the control group. Comparing with the resolved ones, it was found that TT, FT and SHBG concentrations were increased in the non-resolved CSC. A significant positive correlation between TT concentrations and CMT (R2=0.168, P=0.031) as well as SRF height (R2=0.146, P=0.045) were detected in the non-solved CSC group.Conclusion: Different concentrations of TT, FT, FT/E2 ratio, DHEA-S and SHBG were detected in resolved and non-resolved CSC cases. Sex hormones were related to CSC symptom durations and related parameters.Keywords: central serous chorioretinopathy, sex hormones, cortisol, testosterone, case-control study