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Zhiwei Long,1,2,&ast; Qiyuan Zeng,2,&ast; Yonger Ou,1,&ast; Yuelin Liu,2,3 Jieying Hu,1 Ya Wang,1,3 Yan Wang1 1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Department of Clinical Medicine, Guangzhou Medical University, Guangzhou, People’s Republic of China; 3Department of Critical Care Medicine, the First Affiliated Hospital of Guangzhou Medical University; Guangzhou Institute of Respiratory and Health; Medical Center for Respiratory Medicine; State Key Laboratory of Respiratory Disease, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Wang; Ya Wang, Email 345406739@qq.com; wangya811710@163.comPurpose: Elevated red blood cell distribution width (RDW) and decreased hematocrit (HCT) levels are associated with poor prognosis in chronic obstructive pulmonary disease (COPD) patients, but their significance in intensive care unit (ICU) patients with acute exacerbation of COPD (AECOPD) remains uncertain. The RDW/HCT ratio may offer a more comprehensive assessment compared to individual markers, potentially enhancing prognostic accuracy. Furthermore, the utility of RDW/HCT in improving traditional ICU scoring systems remains unexplored.Patients and Methods: The optimal RDW/HCT ratio cutoff was identified via ROC curve analysis, guiding classification into high and low ratio groups. Univariate and multivariate logistic regression analyses, Kaplan-Meier survival curves, and propensity score matching (PSM) were performed to evaluate the association between RDW/HCT ratio and 28-day all-cause mortality. The predictive value of RDW/HCT ratio compared to traditional ICU scoring systems was assessed using the area under the curve (AUC). Additionally, the eICU database was utilized to validate the robustness of the association between RDW/HCT and mortality in patients with AECOPD.Results: 624 patients were included, with 361 in the low RDW/HCT ratio group and 263 in the high ratio group. PSM yielded 145 matched pairs of patients with balanced baseline characteristics. Multivariate logistic regression analysis revealed that patients with RDW/HCT ratio ≥ 0.473 had significantly higher 28-day all-cause mortality compared to those with RDW/HCT ratio < 0.473 (p < 0.001). Combining RDW/HCT ratio with SOFA score improved the diagnostic accuracy significantly (p=0.029).Conclusion: The RDW/HCT ratio is an independent predictor of 28-day all-cause mortality in AECOPD patients in the ICU. It can be used for a preliminary assessment before a systematic evaluation of the patient, indicating its potential value in early assessment of disease severity. In a comprehensive evaluation, combining the RDW/HCT ratio with the SOFA score can further enhance predictive accuracy.Keywords: red blood cell distribution width, hematocrit, chronic obstructive pulmonary disease, intensive care unit, prognosis

Kunzhao Huang,&ast; Xiaoyuan Yi,&ast; Huaying Xie, Jianzhang Luo, Qingyu Zeng, Feifei He, Liyan Wang Digestive Department, The Affiliated Hospital of Guilin Medical College, Guilin, 541001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liyan Wang, Digestive Department, The Affiliated Hospital of Guilin Medical College, Guilin, 541001, People’s Republic of China, Tel +86-15295953938, Email 168wangliyan@163.comPurpose: Ferroptosis is a regulated form of cell death characterized by iron-dependent accumulation of associated lipid peroxides (LPO), which can induce cell death when a certain level is reached. However, the extremely complex tumor microenvironment (TME) has the characteristics of antioxidant, even if it induces ferroptosis of tumor cells, its killing effect on tumor cells is still very limited. To solve this problem, we constructed a novel nanomaterials (GOx/EC@Fe3O4@CCM). We evaluated the anticancer effect of this nanomaterial in inhibiting tumor growth through comprehensive in vitro and in vivo experiments.Methods: We successfully synthesized GOx/EC@Fe3O4 by one-pan synthesis method, then coated the Hepatocellular carcinoma cell membrane on its surface by co-extrusion technology, and finally synthesized the GOx/EC@Fe3O4@CCM nanoplatforms. We characterized the compounds in terms of morphology, particle size, and Zeta potential. In addition, we also studied the anti-tumor effect of GOx/EC@Fe3O4@CCM nanoplatforms from the following aspects, including the performance test of the nanoplatform, the intracellular effect of the nanoplatform, the anti-tumor effect in vitro, the intracellular ROS analysis, the intracellular effect of EC, and the anti-tumor effect in vivo.Results: The iron-based carriers in GOx/EC@Fe3O4@CCM nanoplatforms are released and produce ferrous ions (Fe2+) in an acidic environment. Due to the limitation of the endogenous level of hydrogen peroxide (H2O2), we introduced GOx into the TME or tumor cells. Under the catalysis of GOx, glucose reacted rapidly to produce a large amount of H2O2, which then combined with Fe2+ to produce a large number of Hydroxyl radical (·OH). Its toxicity leads to dysfunction of cell membrane and organelles, and then causes cell damage. EC inhibits Nuclear factor erythroid 2-related factor 2 (Nrf2) in cancer cells, which effectively down-regulates downstream gene products, including NAD(P)H quinone oxidoreductase 1 (NQO1) and heme oxygenase 1 (HMOX1). A series of chain reactions reduce the escape effect of oxidative stress (OS) and effectively maintain a high level of intracellular oxidation. Furthermore, it induces sustained and intense ferroptosis in tumor cells. Finally, the use of cancer cell membrane modified nanoplatforms due to the homology of membrane protein components improves the tumor cell targeting of the nanoplatforms, showing significant tumor cell inhibition and killing effect in vivo.Conclusion: The results showed that the GOx/EC@Fe3O4@CCM nanoplatforms successfully induced significant ferroptosis of Hepatocellular carcinoma cells through a cascade effect, and finally effectively promoted cancer cell regression. Keywords: ferroptosis, mesoporous Fe3O4, glucose oxidase, ethyl carbamate, Nrf2

Abdul Ghafar Sherzad,1 Ahmad Shakib Zalmai,2 Imran Zafarzai,2 Mahmoud Khan Zazai,3 Qingchun Zeng4 1Department of Biochemistry, Faculty of Medicine, Nangarhar University, Nangarhar, Afghanistan; 2Department of Forensic Medicine, Faculty of Medicine, Nangarhar University, Nangarhar, Afghanistan; 3Department of Family Medicine, Beteam International Cure Hospital, Kabul, Afghanistan; 4Department of Cardiology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Abdul Ghafar Sherzad, Department of Biochemistry, Faculty of Medicine, Nangarhar University, Nangarhar, Afghanistan, Tel +93783545284, Email ghafarsherzad15@gmail.comBackground: Congenital heart disease (CHD), characterized by anatomical and functional abnormalities of the heart, can impair an individual’s quality of life and, if not treated with appropriate interventions, it can result in early death. Morbidity and mortality from CHD are greatly reduced by early diagnosis and timely therapy. Therefore, this study aimed to determine the frequency of various forms of CHD among affected children in Eastern Afghanistan considering age, gender, and region of distribution (countryside and city).Patients and Methods: A retrospective hospital-based study was conducted on 1323 patients with a confirmed diagnosis of CHD who were referred for echocardiography to public and private hospitals in Jalalabad City, Afghanistan, from July 2018 to June 2022. Patients from day one of life till 18 years were included. The study participants were chosen using a non-probability convenience sampling technique, and the data were analyzed using the statistical package for social sciences (SPSS) version 27.0.Results: In this study, males comprised 60.4% of the participants, while females made up 39.6%. More than three-quarters (86.4%) of the diagnoses were in children below 1 year of age. 86.5% of them were patients with acyanotic, and 13.5% had cyanotic CHD. The most common acyanotic heart disease was patent ductus arteriosus (PDA; 252.6%), followed by ventricular septal defect (VSD; 18.4%) and atrial septal defect (ASD; 8.5%). The most frequent cyanotic heart disease was Tetralogy of Fallot (TOF). 79.9% of the total cases were patients with simple CDH lesions, and 20.1% had complex CHD lesions. In addition, participants from rural areas had a higher (78.9%) frequency of CHD compared to those from urban areas (21.1%).Conclusion: The study concluded that over 85% of CHD-diagnosed cases were under 1 year of age, with PDA, VSD, ASD, and TOF being the most commonly diagnosed acyanotic and cyanotic lesions. Participants from rural residence had a higher frequency of CHD compared to those from urban residence. Additionally, our study found that more males were affected by CHD compared to females. In order to avoid serious complications, reduce mortality, and improve quality of life, early identification and correction of disease is crucial.Keywords: cyanotic heart disease, acyanotic heart disease, atrial septal defect, ventricular septal defect, patent ductus arteriosus, tetralogy of Fallot

Qian Zeng,1 Lu Liu,1 Ying Chen,1 Daohong Chen,1 Ziyang Zhou,1 Wenjiao Hu,1 Siyao Gong,1 Bin He,1 Wenchuan Qi,1,2 Chao Wang,1,3 Zuoqin Yang,4 Shuguang Yu,1,2 Ling Zhao1,2 1Department of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Key Laboratory of Acupuncture for Senile Disease, Chengdu University of Traditional Chinese Medicine, Ministry of Education, Chengdu, People’s Republic of China; 3Sub-health Management Center, Sichuan Integrative Medicine Hospital, Chengdu, People’s Republic of China; 4Department of Acupuncture and Tuina, Chengdu Pidu District Hospital of Traditional Chinese Medicine, Sichuan, People’s Republic of ChinaCorrespondence: Ling Zhao, Department of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, 1166 Liutai Avenue, Wenjiang District, Chengdu City, Sichuan Province, 611137, People’s Republic of China, Tel +86 28 6180 0000, Email zhaoling@cdutcm.edu.cnBackground: Acupuncture has been used as an adjuvant therapy for Chronic obstructive pulmonary disease (COPD). However, systematic reviews (SRs) and meta-analyses (MAs) have reported inconsistent results and unknown quality. This overview aimed to summarize the current SRs/MAs to provide evidence for the effectiveness and safety of acupuncture in the treatment of COPD.Methods: SRs/MAs were searched via eight databases from their establishment to December 31, 2023. The methodological quality was assessed by A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2). The risk of bias was assessed using the Risk of Bias in Systematic Review (ROBIS) tool. The Preferred Reporting Items for Systematic Reviews and Meta-analyses for Acupuncture (PRISMA-A) to evaluate the reporting quality. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to determine the strength of evidence. In addition, we also conducted an analysis of the acupuncture points used in the primary RCTs.Results: Twenty-two SRs/MAs were included in this overview. Based on the assessment using AMSTAR 2, nineteen SRs/MAs were “critically low”. Eight SRs/MAs had a low risk of bias. Based on PRISMA-A, the reporting completeness of eighteen SRs/MAs were more than 70%. As for GRADE assessment, only three outcome measures were of high quality. COPD patients can benefit from moxibustion, acupoint application, acupoint catgut embedding, manual acupuncture, and electroacupuncture, as indicated by effectiveness in measures including lung function, 6MWD, mMRC, CAT, and acute exacerbation. In addition, the efficacy of TENS needed to be further demonstrated. The commonly used acupuncture points in the RCTs include BL13, BL23, and EX-B1.Conclusion: Evidence from SRs showed that acupuncture is beneficial to lung function, acute exacerbation, 6MWD, mMRC and CAT. For SGRQ and brog scale, acupuncture should be used selectively, but this finding should still be taken with caution.Keywords: acupuncture, COPD, systematic reviews, overview

Qiying Zeng,1,&ast; Wenjun Xue,2,&ast; Zhicheng Wei,1 Hangdong Shen,1 Huajun Xu,1 Huaming Zhu,1 Jian Guan,1 Hongliang Yi,1 Yunhai Feng,2 Xinyi Li,1 Haibo Ye1 1Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Sleep Disordered Breathing, Otorhinolaryngology Institute of Shanghai Jiao Tong University, Shanghai, 200233, People’s Republic of China; 2Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Eighth People’s Hospital Affiliated to Jiangsu University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinyi Li; Haibo Ye, Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Sleep Disordered Breathing, Otorhinolaryngology Institute of Shanghai JiaoTong University, Shanghai, 200233, People’s Republic of China, Tel/Fax +86-2164834143, Email lixinyilixinyi123@163.com; yehaibo_2012@163.comBackground: Sleep-disordered breathing is more prevalent in individuals with allergic rhinitis (AR) than in those without AR. In addition to increased risk for sleep-disordered breathing, AR is associated with greater severity of obstructive sleep apnea (OSA) symptoms. The aim of this research study was to evaluate the association of multiple single nucleotide polymorphism (SNP) variations in AR with sleep- and breathing-related parameters in men with OSA.Methods: Men who had complained of snoring were consecutively enrolled in the Shanghai Sleep Health Study of Shanghai Sixth People’s Hospital from 2007 to 2018. After rigorous screening, 5322 men were included in the analysis. Anthropometric, fasting biochemical, and polysomnographic parameters, along with 27 AR-associated SNPs were analyzed. The associations between AR-related genetic polymorphisms and OSA were determined via linear, binary, and multinomial logistic regression analyses.Results: Rs12509403 had significantly positive associations with most sleep-breathing parameters. While the risk for OSA was increased by rs12509403, it was decreased by rs7717955 [odds ratio (OR) = 1.341, 95% confidence interval [CI] = 1.039– 1.732, P = 0.024; OR = 0.829, 95% CI = 0.715– 0.961, P = 0.013, respectively]. A graded increase in the risk of being in the highest quartile (Q4) vs the reference category (Q1) for sleep breathing indicators, especially REM-AHI and NREM-AHI, was identified by rs12509403 (OR = 1.496, 95% CI = 1.175– 1.904, P = 0.001; OR = 1.471, 95% CI = 1.151– 1.879, P < 0.001, respectively).Conclusion: The association of multiple AR SNPs with OSA-related hypoxia and sleep indices provides a genetic explanation for the higher AR susceptibility of OSA patients. Understanding the AR-related genetic underpinnings of OSA may lead to more personalized treatment approaches.Keywords: allergic rhinitis, obstructive sleep apnea, single nucleotide polymorphism, polysomnography

Wanjun Gu, Qi Zeng, Xin Wang, Huthaifa Jasem, Ling Ma Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Ling Ma, No. 36 Sanhao Street, Heping District, Shenyang, 110004, People’s Republic of China, Tel +86-18940256927, Email mal@cmu.edu.cnAbstract: Acute lung injury (ALI) manifests through harm to the capillary endothelium and alveolar epithelial cells, arising from a multitude of factors, leading to scattered interstitial alterations, pulmonary edema, and subsequent acute hypoxic respiratory insufficiency. Acute lung injury (ALI), along with its more serious counterpart, acute respiratory distress syndrome (ARDS), carry a fatality rate that hovers around 30– 40%. Its principal pathological characteristic lies in the unchecked inflammatory reaction. Currently, the main strategies for treating ALI are alleviation of inflammation and prevention of respiratory failure. Concerning the etiology of ALI, NLRP3 Inflammasome is essential to the body’s innate immune response. The composition of this inflammasome complex includes NLRP3, the pyroptosis mediator ASC, and pro-caspase-1. Recent research has reported that the inflammatory response centered on NLRP3 inflammasomes plays a key part in inflammation in ALI, and may hence be a prospective candidate for therapeutic intervention. In the review, we present an overview of the ailment characteristics of acute lung injury along with the constitution and operation of the NLRP3 inflammasome within this framework. We also explore therapeutic strategies targeting the NLRP3 inflammasome to combat acute lung injury.Keywords: acute lung injury, NLRP3 inflammasome, caspase-1, IL-1β, IL-18

Yishan Niu,1 Xiaoye Yuan,2 Fansheng Guo,1 Jinglin Cao,1 Yang Wang,1 Xin Zhao,1 Jian Dou,1 Qiang Zeng1 1Department of Hepatobiliary Surgery, Hebei Medical University Third Hospital, Shijiazhuang, Hebei, 050051, People’s Republic of China; 2Department of Gerontology, Hebei General Hospital, Shijiazhuang, Hebei, 050051, People’s Republic of ChinaCorrespondence: Qiang Zeng, Department of Hepatobiliary Surgery, Hebei Medical University Third Hospital, No. 139 Ziqiang Road, Shijiazhuang, Hebei, 050051, People’s Republic of China, Email zengqiang457@hebmu.edu.cnBackground: This investigation evaluated the prognostic significance of the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR), and introduced a combined NLR-PLR score to evaluate the correlation between NLR-PLR score and hepatocellular carcinoma (HCC) recurrence.Material/Methods: We enrolled 110 patients who underwent orthotopic liver transplantation (LT) for HCC. The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were assessed, and appropriate cut-off values were established. The NLR-PLR score ranged from 0 to 2 as follows: score of 2, high NLR (≥ 3.37) and high PLR (≥ 105.96); score of 1, either high NLR or high PLR; score of 0, neither high NLR nor high PLR.Results: The median overall survival (OS) of patients with NLR-PLR score of 0, 1 and 2 was 27, 26.5, and 6 months, respectively. The median OS of patients with NLR-PLR score of 2 was shorter than those with 0 (P < 0.001) and 1 (P < 0.001). The median disease-free survival (DFS) time of patients with NLR-PLR score of 0, 1 and 2 was 24.5, 24, and 6 months, The median DFS of patients with NLR-PLR score of 2 was shorter than those with 0 (P = 0.001) and 1 (P = 0.015). Multivariate analysis showed that NLR-PLR score was an independent risk factor for prognosis and survival.Conclusion: NLR, PLR and NLR-PLR score can predict the long-term survival of patients, and NLR-PLR score, having more predictive value than NLR and PLR alone is an independent risk factor for patient survival. more predictive value than NLR and PLR alone.Keywords: hepatocellular carcinoma, liver transplantation, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, NLR-PLR score, prognosis

Lu Liu,1,&ast; Zili Tang,1,&ast; Qian Zeng,1,&ast; Wenchuan Qi,1 Ziyang Zhou,1 Daohong Chen,1 Dingjun Cai,1– 3 Ying Chen,1 Shiqi Sun,1 Siyao Gong,1 Bin He,1 Shuguang Yu,1– 3 Ling Zhao1– 3 1Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu City, Sichuan Province, People’s Republic of China; 2Acupuncture and Chronobiology Key Laboratory of Sichuan Province, Chengdu, Sichuan, People’s Republic of China; 3Key Laboratory of Acupuncture for Senile Disease (Chengdu University of Traditional Chinese Medicine), Ministry of Education, Chengdu City, Sichuan Province, China&ast;These authors contributed equally to this workCorrespondence: Ling Zhao; Shuguang Yu, College of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, 1166 Liutai Avenue, Wenjiang District, Chengdu City, Sichuan Province, 611137, People’s Republic of China, Tel +86 28 6180 0000, Email zhaoling@cdutcm.edu.cn; ysg28588@126.comBackground: Electroacupuncture (EA), with varying stimulation intensities, has demonstrated therapeutic potentials in both animal and clinical studies for the treatment of chronic obstructive pulmonary disease (COPD). However, a comprehensive investigation of the intensity-related effects, particularly 1mA and 3mA of EA, and the underlying mechanisms remains lacking.Methods: A COPD rat model was established by prolonged exposure to cigarette smoke and intermittent intratracheal instillation of lipopolysaccharide. EA treatment was administered at acupoints BL13 (Feishu) and ST36 (Zusanli), 20 minutes daily for 2 weeks, with intensities of 1mA and 3mA. EA effectiveness was evaluated by pulmonary function, histopathological change, serum level of inflammatory cytokines, and level of oxidative stress markers in serum and lung tissues. Transcriptome profiling and weighted gene co-expression network analysis (WGCNA) were performed to reveal gene expression patterns and identify hub genes. Real-time quantitative PCR (RT-qPCR) and Western blot (WB) were performed to detect the mRNA and protein expression levels, respectively.Results: EA at both 1mA and 3mA exerted differing therapeutic effects by improving lung function and reducing inflammation and oxidative stress in COPD rats. Transcriptome analysis revealed distinct expression patterns between the two groups, functionally corresponding to shared and intensity-specific (1mA and 3mA) enriched pathways. Eight candidate genes were identified, including Aqp9, Trem1, Mrc1, and Gpnmb that were downregulated by EA and upregulated in COPD. Notably, Msr1 and Slc26a4 exclusively downregulated in EA-1mA, while Pde3a and Bmp6 upregulated solely in EA-3mA. WGCNA constructed 5 key modules and elucidated the module–trait relationship, with the aforementioned 8 genes being highlighted. Additionally, their mRNA and protein levels were validated by RT-qPCR and WB.Conclusion: Our results demonstrated that 1mA and 3mA intensities induce distinct gene expression patterns at the transcriptional level, associated with shared and 1mA vs 3mA-specific enriched pathways. Genes Mrc1, Gpnmb, Trem1, and Aqp9 emerge as promising targets, and further studies are needed to elucidate their functional consequences in COPD.Keywords: chronic obstructive pulmonary disease, electroacupuncture, intensity, transcriptome profiling, weighted gene co-expression network analysis

Ziyan Wang,1,2,&ast; Chengxin Liu,1,2,&ast; Jiaming Wei,2,3 Hui Yuan,1,2 Min Shi,2,3 Fei Zhang,2,3 Qinghua Zeng,2,3 Aisi Huang,2,3 Lixin Du,4 Ya Li,4 Zhihua Guo2,3 1First Clinical College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208, People’s Republic of China; 2Hunan Key Laboratory of Colleges and Universities of Intelligent Traditional Chinese Medicine Diagnosis and Preventive Treatment of Chronic Diseases of Hunan Universities of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208, People’s Republic of China; 3School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208, People’s Republic of China; 4School of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ya Li; Zhihua Guo, Email 003872@hnucm.edu.cn; 004294@hnucm.edu.cnObjective: This study aims to explore the mechanism of action of Yixintai in treating chronic ischemic heart failure by combining bioinformatics and experimental validation.Materials and Methods: Five potential drugs for treating heart failure were obtained from Yixintai (YXT) through early mass spectrometry detection. The targets of YXT for treating heart failure were obtained by a search of online databases. Gene ontology (GO) functional enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were conducted on the common targets using the DAVID database. A rat heart failure model was established by ligating the anterior descending branch of the left coronary artery. A small animal color Doppler ultrasound imaging system detected cardiac function indicators. Hematoxylin-eosin (HE), Masson’s, and electron microscopy were used to observe the pathological morphology of the myocardium in rats with heart failure. The network pharmacology analysis results were validated by ELISA, qPCR, and Western blotting.Results: A total of 107 effective targets were obtained by combining compound targets and eliminating duplicate values. PPI analysis showed that inflammation-related proteins (TNF and IL1B) were key targets for treating heart failure, and KEGG enrichment suggested that NF-κB signaling pathway was a key pathway for YXT treatment of heart failure. Animal model validation results indicated the following: YXT can significantly reduce the content of intestinal microbiota metabolites such as trimethylamine oxide (TMAO) and improve heart failure by improving the EF and FS values of heart ultrasound in rats and reducing the levels of serum NT-proBNP, ANP, and BNP to improve heart failure. Together, YXT can inhibit cardiac muscle hypertrophy and fibrosis in rats and improve myocardial ultrastructure and serum IL-1β, IL-6, and TNF-α levels. These effects are achieved by inhibiting the expressions of NF-κB and PKC.Conclusion: YXT regulates the TMAO/PKC/NF-κB signaling pathway in heart failure.Keywords: heart failure, yixintai, TMAO, PKC/NF-κB pathway, traditional Chinese medicine, network pharmacology

Jianxia Ma,&ast; Ke Wang,&ast; Jun Wang, Qinlian Zeng, Kangwei Liu, Songbai Zheng, Yuanwen Chen, Jianfeng Yao Department of Gastroenterology, Hua Dong Hospital of Fu Dan University, Shanghai, 200040, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianfeng Yao, Department of Gastroenterology, HuaDong Hospital of Fu Dan University, No. 221. Road West Yanan, Shanghai, 200040, People’s Republic of China, Tel +8602162483180, Email yjf1966@126.comObjective: The fecal microbiota was studied in patients with inflammatory bowel disease (IBD), and the characteristics of gut microbiota were compared among patients with different subtypes and stages of IBD, aiming to identify the gut microbiota associated with IBD.Methods: Fecal samples were collected from 41 IBD patients (18 patients with ulcerative colitis [UC] and 23 patients with Crohn’s disease [CD]) in the Department of Gastroenterology of East China Hospital, Fudan University between January 2021 and January 2022. In addition, fecal samples were collected from 20 healthy volunteers. The fecal microbiota was subjected to 16S rRNA gene sequencing, followed by bioinformatics analysis.Results: There was significant difference in the fecal microbiota between IBD patients and controls. The abundance and diversity of fecal microbiota in the IBD patients were significantly lower than in controls. The relative abundance of Subdoligranulum, Ruminococcus, Anaerostipes and Lachnospira was reduced markedly in the IBD patients. As compared to controls, the relative abundance of Streptococcus increased dramatically in the UC patients. The relative abundance of Lachnoclostridium, Fusobacterium, Cloacibacillus and Erysipelatoclostridium significantly increased in the CD patients. As compared to CD patients, the relative abundance of Alistipes was reduced markedly in the UC patients; the relative abundance of Faecalibacterium, Roseburia and Haemophilus was reduced dramatically in the CD patients. In addition, significant difference was also noted in the fecal microflora between patients with active IBD and those with IBD in remission period. In active IBD patients, the relative abundance of Roseburia, Coprococcus and Ruminiclostridium was reduced significantly.Conclusion: There is intestinal microbiota imbalance in IBD patients, and the abundance of Roseburia, Coprococcus and Ruminiclostridium is reduced significantly in the active period of IBD, which may be related to the active IBD.Keywords: inflammatory bowel disease, ulcerative colitis, Crohn’s disease, gut microbiota, 16S rRNA gene sequencing

Yinhui Zeng,1,&ast; Jinyuan Li,1,&ast; Yueqiang Wen,2,&ast; Haiqing Xiao,1 Chao Yang,1 Qingxiang Zeng,1 Wenlong Liu1 1Department of Otolaryngology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510623, People’s Republic of China; 2Department of Nephrology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenlong Liu, Department of Otolaryngology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510623, People’s Republic of China, Email lwl20103@163.comPurpose: Eosinophils have pivotal roles in the development of allergic rhinitis (AR) through the release of cytotoxic substances. Apolipoprotein A-I (Apo-AI) exhibits a strong inhibitory effect on eosinophil infiltration in allergic diseases. Nevertheless, the precise impact of Apolipoprotein A-I on eosinophils remains uncertain.Methods: Our study recruited a total of 15 AR children and 15 controls. The correlation between Apo-AI expression and the counts of blood eosinophils was examined. Flow cytometry was employed to assess the role of Apo-AI in eosinophil apoptosis and adhesion. The Transwell system was performed to conduct the migration assay. An animal model using AR mice was established to test the effect of Apo-AI on eosinophils.Results: Serum Apo-AI were negatively related to eosinophils counts and eosinophil chemotactic protein levels in AR. Apo-AI exerts a pro-apoptotic effect while also impeding the processes of adhesion, migration, and activation of eosinophils. The apoptosis triggered by Apo-AI was facilitated through the phosphoinositide 3-kinase (PI3K) pathway. The chemotaxis and activation of eosinophils, which are influenced by Apolipoprotein A-I, are regulated through the PI3K and MAPK signaling pathways. Apo-AI treated mice presented with decreased blood and nasal eosinophilic inflammation as well as down-regulated eosinophil related cytokines.Conclusion: Our findings provide confirmation that Apo-AI exhibits inhibitory effects on the function of eosinophils in allergic rhinitis. This suggests that Apo-AI holds potential as a therapeutic target for future treatment strategies.Keywords: apolipoprotein A-I, eosinophils, allergic rhinitis, apoptosis, adhesion, migration, activation

Qiu Zeng, Xiaoyi Liu, Lina Li, Qin Zhang, Chengping Luo, Shu Yang, Shuqiang Wu, An Yang, Jie Li Department of Rehabilitation Medicine, The Sixth People’s Hospital of Yibin, Yibin, Sichuan, People’s Republic of ChinaCorrespondence: An Yang; Jie Li, Email yangan19661063@163.com; lijieyibin@163.comBackground: Osteoarthritis (OA) is a common disease in geriatric rehabilitation medicine caused by the progressive destruction of articular cartilage. Traditional Chinese exercise (TCE) is an important component of traditional sports in China and aims to stretch the musculoskeletal tract and relieve joint pain. Bibliometrics can help researchers find suitable partners and understand the research hotspots and trends in a certain field. However, there is still a lack of bibliometric analysis in the field of TCE and OA.Methods: All the literature was obtained from the Web of Science Core Collection database. The last search was performed on July 28, 2023. The bibliometric indicators, such as publications, citations, and H-index, were recorded. Bibliometrix and CiteSpace were used for visualization analysis. In addition, randomized controlled trials were included to summarize the exercise prescription of TCE for OA.Results: A total of 170 articles were included. The field of OA with TCE had great development potential and was in the rising period. The countries, institutions, and authors with the most publications were the United States, Tufts Medical Center, and Harvey WF, respectively. The most popular journal was Osteoarthritis and Cartilage. The recent burst keywords in this field were mainly “hip”, “pilot”, and “risk”. Tai Chi was the most studied TCE with the most detailed content of exercise prescription, followed by Baduanjin and Wuqinxi.Conclusion: Our study provides a basis for researchers in this field to choose appropriate partner and academic journals. Moreover, pain, muscle strength, and quality of life management of elderly OA patients are research hotspots in this field. The intervention of hip OA risk through TCE is expected to become a research direction for emerging teams. The TCE prescription we summarized can better provide researchers with more treatment details.Keywords: osteoarthritis, traditional Chinese exercise, traditional Chinese medicine, rehabilitation, bibliometrics

Shuaijun Cao,1,&ast; Xiaoying Jiang,2,&ast; Jinshan Suo,3 Yanyan Lu,2 Mohan Ju,2 Qixiang Zeng,1 Qingru Zheng,1 Zuoyan Zhang,1 Wenqi Tang1 1Department of Critical Care Medicine, Shanghai Sixth People’s Hospital, Shanghai, People’s Republic of China; 2Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Department of Ophthalmology, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zuoyan Zhang; Wenqi Tang, Department of Critical Care Medicine, Shanghai Sixth People’s Hospital, No. 600 Yishan Road, Shanghai, 200000, People’s Republic of China, Tel +86 021-24058331, Email 18930177049@189.cn; zhang_zy1969@163.comIntroduction: Carbapenem-Resistant Enterobacteriaceae (CRE) has posed a significant threat to humans.The aim of this study was to investigate the molecular characteristics of blaKPC-producing Escherichia coli in a university-affiliated tertiary hospital.Methods: Polymerase chain reaction (PCR) and BLAST+ software were used to detect the prevalence of blaKPC in E. coli and Klebsiella pneumoniae. Whole-genome sequencing was performed for the blaKPC-harboring clinical E. coli isolates. Antimicrobial resistance genes, MLSTs, KPC-carrying plasmid typing and genetic environment of blaKPC were analyzed. A maximum likelihood core single nucleotide polymorphism (SNP)-based phylogeny tree was constructed to determine the evolutionary relationships within this ST131 collection. Conjugation experiments were performed to determine the mobilization of blaKPC. The minimal inhibitory concentrations of the common antimicrobial agents were determined using the broth microdilution method.Results: The prevalence of blaKPC in 424 clinical E. coli isolates and 1636 E. coli strains from GenBank database were 2.2% (45/2060) whereas the detection rate of blaKPC in K. pneumoniae from the GenBank database was 29.8% (415/1394). The blaKPC-harboring conjugants exhibited resistance to multiple β-lactams, except for cefepime-zidebactam and ceftazidime-avibactam. All blaKPC-carring E. coli isolates were susceptible to tigecycline and polymyxin B. ST131 was the dominant sequence type of blaKPC-carring E. coli, accounting for 40.0% (18/45). Most of the blaKPC-producing ST131 E. coli (89.5%,17/19) belonged to clade C ST131 lineage. Genetic environment analysis revealed that 57.8% (26/45) of blaKPC gene was linked to Tn 4401-associated structure ISKpn6-blaKPC-ISKpn7. IncN was the most common plasmid type in KPC-producing E. coli whereas IncFII was the dominant plasmid type in KPC-producing K. pneumoniae.Conclusion: The detection rate of blaKPC was lower in E. coli compared with K. pneumoniae. The dominant sequence and plasmid types of blaKPC-harboring isolates differed between E. coli and K. pneumoniae. Further studies about the role of the defense system in acquisition of KPC-plasmids in E. coli will be performed to provide new insights into the low prevalence of blaKPC.Keywords: Escherichia coli, blaKPC, carbapenemases, plasmids typing

Luyang Gao,&ast; Sicheng Zhang,&ast; Zhihui Zhao, Qing Zhao, Tao Yang, Qixian Zeng, Yi Zhang, Xin Li, Zhihua Huang, Anqi Duan, Qin Luo, Zhihong Liu Center for Respiratory and Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, National Clinical Research Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhihong Liu; Qin Luo, Center for Respiratory and Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, National Clinical Research Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Xicheng District, Beijing, 100037, People’s Republic of China, Tel/Fax +86-010-88396589, Email zhihongliufuwai@163.com; luoqin2009@163.comIntroduction: Mounting evidence indicates a possible connection between the systemic inflammatory response index (SIRI) and the prognosis of heart failure, but its role in idiopathic pulmonary arterial hypertension (IPAH) is not well understood. This study aimed to investigate the relationship between SIRI and variables such as functional ability, echocardiography results, hemodynamic measurements, and long-term outcomes in patients with IPAH.Methods: The study included 426 consecutive IPAH patients who underwent right heart catheterization at Fuwai Hospital from January 2013 to December 2020. SIRI was calculated using composite inflammation indicators from routine blood tests. The main outcome measure was clinical deterioration. Spearman correlation coefficients were used to assess associations between SIRI and indicators of IPAH severity. Receiver operating characteristic (ROC) curve analysis was conducted to determine the optimal SIRI threshold and predictive ability. Kaplan-Meier analysis and Cox proportional hazard models were used to examine the relationship between SIRI and clinical deterioration.Results: SIRI showed positive associations with indicators such as N-terminal pro-brain natriuretic peptide, right ventricular end-diastolic diameter, pericardial effusion, mean pulmonary arterial pressure, and pulmonary vascular resistance. Conversely, SIRI had inverse relationships with 6-minute walking distance and left ventricular end-diastolic diameter. Kaplan-Meier curves revealed a significantly higher rate of clinical deterioration in individuals with SIRI > 0.741 compared to those with SIRI ≤ 0.741 (P < 0.001). Adjusted Cox analysis showed SIRI remained an independent predictor of clinical worsening (hazard ratio 1.366, 95% confidence interval 1.073– 1.738, P = 0.011). ROC analysis demonstrated SIRI provided additional predictive value beyond the risk assessment score of the European Society of Cardiology/European Respiratory Society.Discussion: In summary, SIRI could predict the severity and prognosis of IPAH independently. It was associated with various indicators of IPAH severity and was a significant predictor of clinical deterioration. SIRI also offered additional predictive value beyond existing risk assessment scores.Keywords: prognosis, pulmonary arterial hypertension, risk factor, systemic inflammatory response index

Han Chen,1,2 Dan Cao,1,2 Ning Han,1,2 Mingming Zhang,1,2 Wei Jiang,1,2 Xin Wang,1,2 Qinmin Zeng,1,2 Hong Tang1,2 1Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, 610041, People’s Republic of ChinaCorrespondence: Hong Tang, Email tanghong6198@wchscu.cnIntroduction: Hepatocellular carcinoma (HCC) is a solid tumor with a rich blood supply, and anti-angiogenesis has important clinical significance. Hepatitis B Virus-Encoded MicroRNA 3 (HBV-miR-3) has recently been reported to be involved in HCC development. In this study, we aim to elucidate the role of HBV-miR-3 in promoting HBV-related HCC angiogenesis through Factor Inhibiting Hypoxia-inducible factor 1 (FIH-1).Results: By analyzing HBV-related HCC tissue samples, we found that high expression of HBV-miR-3 was associated with poor overall survival and HBV-miR-3 expression was significantly correlated with VEGFR2 and FIH-1 expressions. In vitro, HBV-miR-3 agomir repressed FIH-1 expression and promoted HIF-1α/VEGFA signaling activation in HepG2 cells, resulting in increased HUVEC lumen formation in HepG2-HUVEC co-culture model. Conversely, HBV-miR-3 antagomir induced FIH-1 expression and inhibited HIF-1α/VEGFA signaling activation in HepG2.2.15 cells, resulting in decreased HUVEC lumen formation in HepG2.2.15-HUVEC co-culture model. The effect of HBV-miR-3 to HCC angiogenesis was also confirmed by a mouse tumor bearing model. We also confirmed that HBV-miR-3 repressed FIH-1 expression via targeting the 3’-UTR of FIH-1 mRNA by luciferase activity assay.Conclusion: HBV-miR-3 was related to HCC patients’ overall survival and it promoted angiogenesis by repressing FIH-1 expression. HBV-miR-3 may be a new marker for predicting prognosis and a novel target for anti-angiogenic treatment of HBV-related HCC. Keywords: HBV-miR-3, FIH-1, HBV-related HCC, angiogenesis

Kaiao Zou,1,2,&ast; Jun Ying,3,&ast; Huihui Xu,1,2 Qinghe Zeng,1,2 Haipeng Huang,1,2 Wenzhe Chen,1,2 Xuefeng Li,1,2 Pinger Wang,1 Hongting Jin,1 Ju Li,3 Yungang Wu4 1Institute of Orthopaedics and Traumatology of Zhejiang Province, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310006, People’s Republic of China; 2The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3Department of Orthopaedics, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, People’s Republic of China; 4Department of the Orthopedics of TCM, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325000, People’s Republic of China&ast;These authors have contributed equally to this workCorrespondence: Yungang Wu; Ju Li, Email zjwyg@126.com; juli@zcmu.edu.cnBackground: Intervertebral disc degeneration (IDD) is a prevalent degenerative disease and often recognized as the primary cause of lower back pain (LBP). Aucubin (Au) is a natural compound with anti-inflammatory properties in various diseases. The present study aimed to confirm the therapeutic effect of Au on IDD and explore its potential mechanism in vivo and in vitro.Methods: The process of IDD was simulated using the lumbar spine instability (LSI) model. In vivo, the therapeutic effect of Au on LSI-induced mice was evaluated by micro-CT and histomorphometry. Additionally, immunohistochemistry was applied to detect the cartilage metabolism and inflammasome activation in endplate. In vitro, the cytotoxicity of Au on ATDC5 cells was detected by Cell Counting Kit-8 (CCK-8), and the biological effects of Au were evaluated by Quantitative Real-time PCR (qRT-PCR) and Western blotting.Results: Micro-CT analysis showed that Au administration significantly alleviated LSI-induced disc volume narrowing and endplate cartilage degeneration, which was further supported by Alcian Blue Hematoxylin/Orange G (ABH/OG) staining. Immunohistochemistry results verified that Au could increase the expression of Col2α 1 and Aggrecan, reduce the expression of Mmp-13, and attenuate the degradation of the endplate extracellular matrix (ECM). Mechanistically, we found that Au treatment, both in vivo and in vitro, significantly inhibited NF-κB-NLRP3 inflammasome activation in chondrocytes as determined by the decreased expression of p-P65, NLRP3, and Caspase-1.Discussion: Taken together, our findings have demonstrated for the first time that Au treatment ameliorated the degeneration of cartilage endplates in IDD may by inhibiting NF-κB-NLRP3 inflammasome activation in chondrocytes and provided a potential candidate for the treatment of IDD.Keywords: Aucubin, cartilage endplate, intervertebral disc degeneration, NF-κB-NLRP3, inflammasome

Fansheng Guo,1 Xiaoye Yuan,2 Jinglin Cao,1 Xin Zhao,1 Yang Wang,1 Wenpeng Liu,1 Baowang Liu,1 Qiang Zeng1 1Department of Hepatobiliary Surgery, the Third Hospital of Hebei Medical University, Shijiazhuang, 050000, People’s Republic of China; 2Department of Gerontology, Hebei General Hospital, Shijiazhuang, 050000, People’s Republic of ChinaCorrespondence: Qiang Zeng, Department of Hepatobiliary Surgery, the Third Hospital of Hebei Medical University, No. 139, Ziqiang Road, Shijiazhuang, 050051, People’s Republic of China, Tel +86-15511308373, Email zengqiangtg@163.comBackground: Hepatocellular carcinoma (HCC) relapse is the main reason for the poor prognosis of HCC after Liver transplantation (LT). This study aimed to explore the molecular mechanisms and immune repertoire profiles of HCC relapse.Material and Methods: RNA-seq of blood samples from patients with normal (n=12) and HCC relapse (n=6) after LT was performed to identify differentially expressed genes (DEGs) and key signalling pathways. The DEGs and immune genes were further analyzed by bioinformatics. TRUST4 was used to analyze the differences in the immune repertoire between the two groups. Another 11 blood samples from patients with HCC who had received LT were collected for RT-qPCR verification of key genes.Results: A total of 131 upregulated and 157 downregulated genes were identified using RNA-seq, and GO enrichment analysis revealed that the top 15 pathways were immune-related. The PPI network identified 10 key genes. Immune infiltration analysis revealed a significant difference in the five immune cell types between the two groups. A total of 83 intersecting genes were obtained by intersecting DEGs and immune genes. 6 key genes, including MX1, ISG15, OAS1, PRF1, SPP1, and THBS1 were obtained according to the intersection of DEGs, PPI network top 10 genes and immune intersecting genes. Immune repertoire analysis showed that the usage frequency of variable (V) and joining (J) genes in the normal group was higher than that in the relapse group. RT-qPCR validation showed that the expression levels of key genes were consistent with the RNA-seq results.Conclusion: Our study identified key pathways and genes that could help determine whether transplant recipients are more prone to HCC relapse. Immune repertoire analysis revealed a difference in the usage frequency of VJ genes between the normal and relapse groups, providing a research direction for immunotherapy in patients with HCC relapse after liver transplantation.Keywords: liver transplantation, hepatocellular carcinoma relapse, RNA-sequencing, immune repertoire, variable and joining genes, V and J genes

Zeng Q, Sun Q, Xu H, et al. J Inflamm Res. 2023;16:3455-3468 The authors have advised there is an error in the author list and affiliations on page 3455. Minwei Jin’s affiliation should read “Department of Orthopaedic Surgery, the First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou, People’s Republic of China” The corrected author list and affiliations is: Qinghe Zeng 1,2,*, Qi Sun3,*, Huihui Xu 1,2,*, Jiali Chen1, Houfu Ling4, Qinwen Ge1,2, Kaiao Zou1,2, Xu Wang1,2, Hongting Jin1, Ju Li4,*, Minwei Jin5,* 1Institute of Orthopedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Chinese Medicine, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3Department of Orthopaedic Surgery, Fuyang Orthopaedics and Traumatology Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 4Department of Orthopaedics, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 5Department of Orthopaedic Surgery, the First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou, People’s Republic of China *These authors contributed equally to this work

Qinghe Zeng,1,2,&ast; Qi Sun,3,&ast; Huihui Xu,1,2,&ast; Jiali Chen,1 Houfu Ling,4 Qinwen Ge,1,2 Kaiao Zou,1,2 Xu Wang,1,2 Hongting Jin,1 Ju Li,4,&ast; Minwei Jin4,&ast; 1Institute of Orthopedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Chinese Medicine, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3Department of Orthopaedic Surgery, Fuyang Orthopaedics and Traumatology Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 4Department of Orthopaedics, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Minwei Jin; Ju Li, Email jin872@zcmu.edu.cn; juli@zcmu.edu.cnBackground: Intervertebral disc degeneration (IDD) is a major cause of lower back pain (LBP), in which inflammatory is frequently involved. Amygdalin (AMD) is a naturally occurring compound that exerts anti-fibrotic, anti-inflammatory, analgesic, and immunomodulatory effects in various diseases. The purpose of this study was to investigate the therapeutic effects and molecular mechanisms of AMD on Lumbar spine instability (LSI)-induced IDD in mice.Methods: In this study, we first explored the effects of AMD in vivo, and then further explored the mechanism of its effects both in vivo and in vitro. Ten-week-old male C57BL/6J mice were administrated with AMD. At 10 weeks after LSI, spinal were collected for tissue analyses, including histology, micro-CT, and immunohistochemistry for Col2, Mmp-13, TNF-α, and p-P65. Additionally, we also evaluated the mRNA and protein expression level of p-P65 and p-IKBα after being treated with AMD in vitro.Results: Histological staining, micro-CT and immunohistochemical analysis showed that AMD treatment significantly inhibited the expression of TNF-α and Mmp-13, increased the expression of Col2 as well as attenuated the calcification of cartilage endplates, eventually to delayed the progression of IDD. Meanwhile, in vivo and in vitro fluorescence imaging revealed that AMD markedly inhibited the AMD significantly inhibited the LSI-induced increase in TNF-α expression and P65and IKBα phosphorylation.Discussion: Our findings suggest that AMD partly inhibits the activation of NF-κB signaling pathway to reduce the release of inflammatory mediators and delay the degeneration of cartilage endplate in IDD model mice. Therefore, AMD may be a potential candidate for the treatment of IDD.Keywords: intervertebral disc degeneration, amygdalin, cartilage endplate, inflammatory processes, NF-κB pathway

Yuhong Gan,1 Xiaobin Meng,1 Nanfeng Lei,1 Hong Yu,1 Qingkao Zeng,2 Qingyan Huang3,4 1Department of Clinical Pharmacy, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 2Department of Intensive Care Unit, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 3Center for Precision Medicine, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 4Guangdong Provincial Engineering and Technology Research Center for Clinical Molecular Diagnostics and Antibody Therapeutics, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of ChinaCorrespondence: Qingyan Huang, Center for Precision Medicine, Guangdong Provincial Engineering and Technology Research Center for Clinical Molecular Diagnostics and Antibody Therapeutics, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, No. 63 Huangtang Road, Meijiang District, Meizhou, 514031, People’s Republic of China, Tel +86 753 2131 591, Email Huangqingyan03@163.comPurpose: This study aimed to investigate the pharmacokinetics and target attainment of meropenem and compare the effect of meropenem dosing regimens in critically ill patients.Patients and Methods: Thirty-seven critically ill patients who were administered meropenem in intensive care units were analyzed. Patients were classified according to their renal function. Pharmacokinetic parameters were assessed based on Bayesian estimation. The target attainment of 40%fT > MIC (fraction time that the free concentration exceeds the minimum inhibitory concentration) and 100%fT > MIC with the pathogen MIC of 2 mg/L and 8 mg/L were specially focused. Furthermore, the effects of standard dosing (1g meropenem, 30 min intravenous infusion every 8h) and non-standard dosing (dosage regimens except standard dosing) were compared.Results: The results showed that the values of meropenem clearance (CL), central volume of distribution (V1), intercompartmental clearance (Q), and peripheral volume of distribution (V2) were 3.3 L/h, 9.2 L, 20.1 L/h and 12.8 L, respectively. The CL of the patients among renal function groups was significantly different (p < 0.001). The tow targets attainment for the pathogen MIC of 2 mg/L and 8 mg/L were 89%, 73%, 49% and 27%, respectively. The severe renal impairment group has higher fraction of target attainment than the other group. The standard dosing achieved the target of 40%fT > 2/8 mg/L (85.7% and 81%, respectively) and patients with severe renal impairment achieved the target fraction of 100% for 40%fT > MIC. Additionally, there was no significant difference between standard and non-standard dosing group in target attainment.Conclusion: Our findings indicate that renal function is an important covariate for both meropenem pharmacokinetics parameters and target attainment. The target attainment between standard and non-standard dosing group was not comparable. Therefore, therapeutic drug monitoring is indispensable in the dosing adjustment for critically ill patients if it is available.Keywords: meropenem, critically ill patients, pharmacokinetics, therapeutic drug monitoring

Yingshi He,1,&ast; Qing Zeng,1,&ast; Minqiang Zhang1– 4 1School of Psychology, South China Normal University, Guangzhou, People’s Republic of China; 2Key Laboratory of Brain, Cognition and Education Sciences, Ministry of Education, Guangzhou, People’s Republic of China; 3Center for Studies of Psychological Application, School of Psychology, Guangzhou, People’s Republic of China; 4Guangdong Key Laboratory of Mental Health and Cognitive Science, South China Normal University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Minqiang Zhang, School of Psychology, South China Normal University, No. 55, West of Zhongshan Avenue, Tianhe District, Guangzhou, 510631, People’s Republic of China, Email 2640726401@qq.comPurpose: Depressive symptoms are serious mental health problems, which are harmful for adolescents’ physical and psychological development. Limited studies have focused on depressive symptoms of vocational high school students, who are more susceptible to mental health problems than high school students. Based on the main effect model of social support and self-regulation theory, the current study aims at exploring two potential mediating roles of hope and future work self on the relationship between perceived social support and depressive symptoms among vocational high school students by a cross-sectional study.Participants and Methods: A total of 521 vocational high school students aged 14– 21 (M= 16.45; SD= 0.91) participated in the survey. There were 266 males (51.1%) and 255 females (48.9%). The multidimensional scale of perceived social support, the future work self scale, the children’s hope scale, and the center for epidemiologic studies depression scale were applied in the study.Results: The results revealed that: (1) perceived social support, future work self, and hope were negatively related to depressive symptoms (r = − 0.25 to − 0.35, p < 0.001); (2) students who perceived more social support have fewer depressive symptoms (β = − 0.22, p < 0.001); (3) perceived social support predicted a more salient future work self and then was associated with higher levels of hope, which in turn, was related to lower levels of depressive symptoms (β = − 0.02, and 95% CI = [− 0.035, − 0.005]).Conclusion: Perceived social support was the protective factor against vocational school students’ depressive symptoms. More specifically, stronger perceived social support predicted a more salient future work self, which promoted high level of hope, and ultimately decreased vocational school students’ depressive symptoms. The findings provide enlighten implications for interventions on depressive symptoms among vocational high school students.Keywords: perceived social support, future work self, hope, depressive symptoms, vocational high school students

Daohong Chen, Qian Zeng, Lu Liu, Ziyang Zhou, Wenchuan Qi, Shuguang Yu, Ling Zhao Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of ChinaCorrespondence: Ling Zhao; Shuguang Yu, Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, No. 37, Twelve Bridge Road, Chengdu, Sichuan Province, People’s Republic of China, Email zhaoling@cdutcm.edu.cn; ysg@cdutcm.edu.cnBackground: The pathogenesis of chronic obstructive pulmonary disease (COPD) has been studied in relation to the microbiome, providing space for more targeted interventions and new treatments. Numerous papers on the COPD microbiome have been reported in the last 10 years, yet few publications have used bibliometric methods to evaluate this area.Methods: We searched the Web of Science Core Collection for all original research articles in the field of COPD microbiome from January 2011 to August 2022 and used CiteSpace for visual analysis.Results: A total of 505 relevant publications were obtained, and the number of global publications in this field is steadily increasing every year, with China and the USA occupying the first two spots in international publications. Imperial College London and the University of Leicester produced the most publications. Brightling C from the UK was the most prolific writer, while Huang Y and Sze M from the USA were first and second among the authors cited. The American Journal of Respiratory and Critical Care Medicine had the highest frequency of citations. The top 10 institutions, cited authors and journals are mostly from the UK and the US. In the ranking of citations, the first article was a paper published by Sze M on changes in the lung tissue’s microbiota in COPD patients. The keywords “exacerbation”, “gut microbiota”, “lung microbiome”, “airway microbiome”, “bacterial colonization”, and “inflammation” were identified as cutting-edge research projects for 2011– 2022.Conclusion: Based on the visualization results, in the future, we can use the gut–lung axis as the starting point to explore the immunoinflammatory mechanism of COPD, and study how to predict the effects of different treatments of COPD by identifying the microbiota, and how to achieve the optimal enrichment of beneficial bacteria and the optimal consumption of harmful bacteria to improve COPD.Keywords: COPD, microbiome, bibliometric analysis, CiteSpace, gut microbiome, respiratory microbiome, bacterial colonization

Liping Luo,1,2,&ast; Ronghua Yan,3,4,&ast; Qingjing Zeng,2 Yinglin Long,2 Xuqi He,2 Kai Li,2 Erjiao Xu1 1Department of Medical Ultrasonics, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, People’s Republic of China; 2Department of Medical Ultrasonics, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Department of Radiology, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China; 4Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Erjiao Xu, Department of Medical Ultrasonics, The Eighth Affiliated Hospital of Sun Yat-sen University, No. 3025, Shennanzhong Road, Shenzhen, 518033, People’s Republic of China, Email xuerjiao@mail.sysu.edu.cn Kai Li, Department of Ultrasound, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, People’s Republic of China, Email likai@mail.sysu.edu.cnObjective: This study intends to compare the efficacy and safety between patients undergoing invasive isolation or monitoring measures and patients undergoing intra-operative contrast-enhanced ultrasound (CEUS) monitoring who underwent radiofrequency ablation (RFA) of hepatocellular carcinomas (HCC) adjacent to the gallbladder (GB).Methods: We retrospectively assessed patients with HCC adjacent to the GB who underwent ultrasound-guided RFA. They were divided into two groups: group A was monitored under intra-operative CEUS, while group B was assisted by invasive auxiliary means. The efficacy, complications and survival were followed up and compared.Results: Thirty-eight patients with 39 HCCs were enrolled into group A and 31 patients with 35 HCCs were enrolled into group B. The technique efficacy rates were both 100% in the two groups. There were no significant differences of the cumulative 1-, 3-, and 5-year local tumor progression, tumor-free survival and overall survival between the two groups (P = 0.851, 0.081 and 0.700, respectively). There were no significant differences of major and minor complications rates between the two groups (P = 1.000, 0.994, respectively). More importantly, no GB related complications occurred in group A.Conclusion: Intra-operative CEUS monitoring without protective isolation of the GB might be also a potentially safe and effective method for the RFA of HCC adjacent to the GB, when compared with those assisted with invasive auxiliary means.Keywords: hepatocellular carcinoma, gallbladder, contrast-enhanced ultrasound, thermal ablation, monitoring

Pinger Wang,1– 3,&ast; Jianbo Xu,1,&ast; Qi Sun,4,&ast; Qinwen Ge,2,3 Min Qiu,1 Kaiao Zou,2,3 Jun Ying,3,5 Wenhua Yuan,2,3 Jiali Chen,2,3 Qinghe Zeng,2,3 Qi Cui,1 Hongting Jin,2,3 Chunchun Zhang,1 Fanzhu Li1 1College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 4Department of Orthopedic Joint Surgery, Hangzhou Fuyang Hospital of TCM Orthopaedics and Traumatology, Hangzhou, People’s Republic of China; 5Department of Orthopedic Surgery, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunchun Zhang, College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China, Tel/Fax +86 571-86613684, Email 20081026@zcmu.edu.cn Fanzhu Li, College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China, Tel/Fax +86 571-86613684, Email lifanzhu@zcmu.edu.cnBackground: Knee osteoarthritis (KOA) is the primary prevalent disabling joint disorder among osteoarthritis (OA), and there is no particularly effective treatment at the clinic. Traditional Chinese medicine (TCM) herbs, such as Eucommia ulmoides Oliv. and Glycyrrhiza uralensis Fisch. (E.G.) couplet medicines, have been reported to exhibit beneficial health effects on KOA, exact mechanism of E.G. nevertheless is not fully elucidated.Purpose: We assess the therapeutic effects of E.G. on KOA and explore its underlying molecular mechanism.Methods: UPLC-Q-TOF/MS technique was used to analyze the active chemical constituents of E.G. The destabilization of the medial meniscus model (DMM) was employed to evaluate the chondroprotective action of E.G. in KOA mice using histomorphometry, μCT, behavioral testing and immunohistochemical staining. Additionally, network pharmacology and molecular docking were used to predict potential targets for anti-KOA activities of E.G., which was further verified through in vitro experiments.Results: In vivo studies have shown that E.G. could significantly ameliorate DMM-induced KOA phenotypes including subchondral bone sclerosis, cartilage degradation, gait abnormality and thermal pain reaction sensibility. E.G. treatment could also promote extracellular matrix synthesis to protect articular chondrocytes, which was indicated by Col2 and Aggrecan expressions, as well as reducing matrix degradation by inhibiting MMP13 expression. Interestingly, network pharmacologic analysis showed that PPARG might be a therapeutic center. Further study proved that E.G.-containing serum (EGS) could up-regulate PPARG mRNA level in IL-1β-induced chondrocytes. Notably, significant effects of EGS on the increment of anabolic gene expressions (Col2, Aggrecan) and the decrement of catabolic gene expressions (MMP13, Adamts5) in KOA chondrocytes were abolished due to the silence of PPARG.Conclusion: E.G. played a chondroprotective role in anti-KOA by inhibiting extracellular matrix degradation, which might be related to PPARG.Graphical Abstract: Keywords: couplet medicines, UPLC-Q-TOF/MS, network pharmacology, cartilage degeneration, knee osteoarthritis, PPARG

Zhaolin Li,1,&ast; Qiaojun Zeng,1,&ast; Shuwan Xu,2,&ast; Yuewei Li,1 Tiantian Tang,1 Jianting Shi,1 Xueming Song,1 Wenman He,1 Liang Chen,1 Guirong Liu,1 Boying Gao,3 Jianming Zheng,4 Linjie Huang,1 Ming Chen,1 Shanping Jiang1 1Department of Pulmonary and Critical Care Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Cardiology, the Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, People’s Republic of China; 3Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 4Cardiovascular Medicine Department, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shanping Jiang; Ming Chen, Department of Pulmonary and Critical Care Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Yan-jiang Xi Road 107, Guangzhou, 510120, People’s Republic of China, Tel +86-20-81332441, Email jiangshp@mail.sysu.edu.cn; chenm69@mail.sysu.edu.cnBackground: Although tigecycline is an effective drug against drug-resistant bacteria, it demonstrated a higher all-cause mortality than comparator antibiotics and a high incidence of coagulation disorders which can be accompanied by severe bleeding. At present, a predictive model for tigecycline-related coagulopathy is not readily available, and the prognostic value of coagulopathy in tigecycline-administered patients has not been elucidated. In this paper, we investigate the association between tigecycline-related coagulopathy and in-hospital mortality to develop a nomogram for the prediction of tigecycline-related coagulopathy.Methods: This retrospective cohort study includes 311 adults prescribed with tigecycline from 2018 to 2020. The primary cohort and validation cohort were constructed by dividing the participants in a ratio of 7:3. The endpoint is tigecycline-related coagulopathy, defined as a condition with no abnormality in coagulation prior to tigecycline application but developed the following symptoms upon prescription: activated partial thromboplastin time (APTT) extended by > 10 s than the upper limit of normal (ULN), prothrombin time (PT) prolonged for > 3 s than the ULN or reduced serum level of fibrinogen to < 2.0 g/L. A predictive nomogram based on logistic regression was subsequently constructed.Results: Tigecycline intake for over 7 days, combined other antibiotics, initial PT, initial fibrinogen and estimated glomerular filtration rate (eGFR), are independent prognostic factors of tigecycline-related coagulopathy. The primary and validation cohort each has an area under the receiver operating characteristic curve (AUC) of 0.792 (0.732– 0.851) and 0.730 (0.629– 0.832) for nomogram, respectively. Furthermore, the fitted calibration curve illustrated adequate fit of the model, while the decision curve analysis demonstrated good clinical value. Survival curves showed a high mortality rate among patients with tigecycline-related coagulopathy.Conclusion: This nomogram exhibited helpful clinical value in predicting tigecycline-related coagulopathy that could reduce the high mortality rate of patients prescribed with tigecycline.Keywords: tigecycline, drug-resistant bacteria, coagulopathy, nomogram