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Abstract Tidal marshes are threatened coastal ecosystems known for their capacity to store large amounts of carbon in their water-logged soils. Accurate quantification and mapping of global tidal marshes soil organic carbon (SOC) stocks is of considerable value to conservation efforts. Here, we used training data from 3710 unique locations, landscape-level environmental drivers and a global tidal marsh extent map to produce a global, spatially explicit map of SOC storage in tidal marshes at 30 m resolution. Here we show the total global SOC stock to 1 m to be 1.44 Pg C, with a third of this value stored in the United States of America. On average, SOC in tidal marshes’ 0–30 and 30–100 cm soil layers are estimated at 83.1 Mg C ha−1 (average predicted error 44.8 Mg C ha−1) and 185.3 Mg C ha−1 (average predicted error 105.7 Mg C ha−1), respectively.

Yanping Xiang, Renhua Li, Jia Cai, Qian Jiang Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Renhua Li, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuanjiagang, Yuzhong District, Chongqing, 400016, People’s Republic of China, Email 854561075@qq.comBackground: This study aimed to investigate clinical efficacy, safety and short-term prognosis of plasma exchange (PE), plasma perfusion combining PE (PP+PE), dual-plasma molecular adsorption system combining PE (DPMAS+PE) in treating acute-on-chronic liver failure (ACLF).Methods: Two hundred and fourteen ACLF patients admitted to our hospital were included and divided into PE (n = 72), PP+PE (n = 75), DPMAS+PE group (n = 67). Laboratory indexes and MELD scores were collected, and clinical efficacy was compared. Patients’ adverse reactions during and 24-h after treatment were collected, and safety was compared. Survival status of patients was followed-up within 90 days, and prognosis was analyzed.Results: PE, PP+PE and DPMAS+PE significantly reduce TBiL, DBiL, ALT, AST, SA, PT, INR, PCT and CRP levels, and increase PA and PTA levels, compared with pre-treatments (P < 0.05). WBC and SCR levels in DPMAS+PE group decreased significantly post-treatment (P < 0.05). Na+ and Cl− levels in PE and PP+PE group decreased significantly post-treatment (P < 0.05). Total adverse reaction incidence in PE, PP+PE, DPMAS+PE group were 38.89%, 22.70%, 17.90%, respectively, with significant differences among three groups (P < 0.05). Ninety-day mortality rates of patients in PE, PP+PE, DPMAS+PE group were 41.67%, 34.67%, 20.90%, respectively, with significant differences among three groups (P < 0.05).Conclusion: PE, PP+PE and DPMAS+PE three artificial liver treatment modes can effectively improve liver, kidney and coagulation function of ACLF patients. DPMAS+PE demonstrated better ability to remove endotoxin and inflammatory mediators, showed advantages in reducing ACLF patient mortality within 90 days, and had the least impact on electrolyte post-treatment. Therefore, DPMAS+PE can be used as a better choice for clinical treatment.Keywords: artificial liver treatment mode, acute-on-chronic liver failure, plasma exchange, plasma perfusion, double plasma molecular adsorption system

Jinqi Ding,1,&ast; Yue Wu,1,&ast; Hanxiaoran Li,1 Shengsheng Wang,1 Jia Cai,2 Hong Cheng,3 Sugai Liang1 1Affiliated Mental Health Center & Hangzhou Seventh People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Mental Health Center & Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Hangzhou City University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Sugai Liang, Email liangsugai@zju.edu.cnPurpose: Network modeling has been suggested as an effective method to explore intricate relationships among antecedents, mediators, and symptoms. In this study, we aimed to investigate whether the severity of depressive symptoms in college students affects the multivariate relationships among anhedonia, smartphone addiction, and mediating factors.Methods: A survey was conducted among 1347 Chinese college students (587 female) to assess depressive symptoms, anhedonia, addictive behaviors, anxiety, and insomnia. The participants were categorized the non-depressive symptom (NDS) and depressive symptom (DS) groups based on a cut-off score of 5 on the 9-item Patient Health Questionnaire-9. Network analysis was performed to investigate the symptom-to-symptom influences of symptoms in these two groups.Results: The network of the DS group was more densely connected than that of the NDS group. Social anticipatory anhedonia was a central factor for DS, while withdraw/escape (one factor of smartphone addiction) was a central factor for NDS. The DS group exhibited greater strength between the PHQ9 score and social anticipatory anhedonia, as well as between the PHQ9 score and alcohol misuse score, compared to the NDS group. On the other hand, the NDS group had higher strength between anxiety and feeling lost, as well as between anxiety and withdraw/escape, compared to the DS group.Conclusion: The findings suggest that there is a close relationship between social anhedonia, smartphone addiction, and alcohol consumption in the DS group. Addressing on ameliorating social anhedonia and smartphone addiction may be effective in preventing and managing depression in college students.Keywords: depressive symptoms, anhedonia, smartphone addiction, network analysis, college students

Mi Tang,1,2,&ast; Liling Xiong,3,&ast; Jianghui Cai,2,4,&ast; Xuejia Gong,2 Li Fan,1 Xiaoyu Zhou,1 Shasha Xing,1 Xiao Yang3 1Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 2School of medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 3Obstetrics Department, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 4Department of Pharmacy, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shasha Xing; Xiao Yang, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China, Email xingshasha1230@126.com; wcchgcptg@163.comPurpose: Intrahepatic cholestasis of pregnancy (ICP) is a disorder that characterized by maternal pruritus, abnormal liver function, and an elevation in total bile acid concentrations during pregnancy. Immune factors have been recognized as playing a vital role in the mechanism of ICP. However, the underlying mechanisms regulating dysfunctional immune cells and immune genes remain to be fully elucidated.Patients and Methods: Single-cell RNA sequencing and bulk RNA sequencing data of the placenta were downloaded from the SRA database. The AUCell package, Monocle package and SCENIC package were utilized to explored immune cell activity, cell trajectory and transcription factor, respectively. GO, KEGG, and GSEA were employed to explore potential biological mechanisms. Cell-cell communications were further investigated using the CellChat package. RT-PCR, and Western blot were used to verify the gene expression in placenta.Results: In placenta cells, macrophages were found to be significantly increased in ICP. Additionally, macrophages exhibited the highest immune gene score and were divided into four subclusters (MF1-4). Our analysis revealed significant elevations in MF2, associated with LPS response and antigen presentation, and MF4, associated with TNF and cytokine production. MF3 displayed an anti-inflammatory phenotype. MF1, closely related to ribosomes and proteins, exhibited a sharp decrease. Although ICP maintained an anti-inflammatory state, macrophage trajectories showed a gradual progression toward inflammation. Subsequently, we confirmed that cytokine- and chemokine-related signaling pathways were emphasized in macrophages. Within the CXCL signaling pathway, the increased expression of CXCL1 in macrophages can interact with CXCR2 in neutrophils, potentially inducing macrophage infiltration, stimulating neutrophil chemotaxis, and leading to an inflammatory response and cellular damage.Conclusion: In conclusion, we firstly revealed the transcriptional signatures of macrophages in ICP and discovered a tendency toward an inflammatory state. This study also provides new evidence that the CXCL1-CXCR2 axis may play an important role in the pathogenesis of ICP.Keywords: intrahepatic cholestasis of pregnancy, scRNA-Seq, bulk RNA-Seq, immune gene, macrophage

Taoying Lu,1– 3 Mingyue Fan,1 Jianxiong Cai,4 Aolin Liu,1 Qianwen Xie,2,3 Xiaowen Zhou,1 Bei Chang,1 Lingjia Yin,2,3,5 Guli Jiang,6 Bin Sun,7 Wenyi Tang,7 Darong Wu4 1The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Outcome Assessment Research Team in Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 3Outcome Assessment Research Team in Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China; 4State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 5Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden; 6Department of Scientific Research, Guangzhou Cadre Health Management Center, Guangzhou, People’s Republic of China; 7Department of Traditional Chinese Medicine, Guangzhou Cadre Health Management Center, Guangzhou, People’s Republic of ChinaCorrespondence: Darong Wu, State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, 111 Dade Road, Guangzhou, 510120, People’s Republic of China, Tel +86 13808869436, Email darongwu@gzucm.edu.cnBackground: Dampness syndrome is a basic syndrome of many major and chronic diseases. Early screening and identification of dampness syndrome are important. The Dampness Syndrome Scale of Chinese Medicine (DSSCM) was developed to measure the occurrence and severity of dampness syndrome. The measurement characteristics of the DSSCM should be further validated. The objective of this study is to evaluate the reliability and validity of the DSSCM based on a cross-sectional survey.Methods: The development of DSSCM was based on the traditional Chinese medicine (TCM) theory, expert consensus and clinical investigations. Participants were recruited from Guangdong Provincial Hospital of Chinese Medicine and Guangzhou Cadre Health Management Center in Guangdong Province, China. All participants completed the baseline questionnaire and DSSCM. The reliability of the DSSCM was evaluated by internal consistency reliability and test–retest reliability. The factor structure was tested with confirmatory factor analysis (CFA), while discriminant validity was evaluated by calculating the difference between the total score of the DSSCM and its four dimensions for participants with or without dampness syndrome. We used a clinician’s diagnosis of dampness syndrome as a criterion to evaluate the criterion validity. Multivariate regression analysis was used to analyze the associations among gender, age, height, and weight and dampness syndrome.Results: A total of 880 participants were enrolled for psychometric validation and 869 participants were included in the final analyses after exclusion. The mean age of the participants was 42.62± 12.86 years. The Cronbach’s alpha coefficients for the four dimensions of the DSSCM were 0.809, 0.891, 0.816 and 0.780. The ICCs for the four dimensions of the DSSCM were 0.806, 0.674, 0.780 and 0.760. For validity, the results showed that the DSSCM had good content validity, discriminant validity and criterion validity. For the CFA, the root mean square error of approximation (RMSEA) was 0.091; the standardized root mean square residual (SRMR) was 0.074; the comparative fit index (CFI) was 0.766; and the Tucker–Lewis index (TLI) was 0.745. Weight was found to be associated with the total scores of the DSSCM and its three dimensions.Conclusion: The DSSCM has good reliability and validity to support its use as a tool for assessing the severity of dampness syndrome. This study provides empirical evidence for future updates to the DSSCM.Keywords: dampness syndrome, dampness syndrome scale of Chinese medicine, reliability, validity

Anbang Zhao,1,2,&ast; Bin Hao,1,2,&ast; Simin Liu,3,&ast; Xiaoyu Qiu,1,2,&ast; Xiaoping Ming,1,2 Xiuping Yang,1,2 Jie Cai,1,2 Zhen Li,4,5 Xiong Chen1,2 1Department of Otorhinolaryngology, Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Sleep Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 3Department of Neurosurgery, Union Hospital Tongji Medical College Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 5Bariatric and Metabolic Disease Surgery Center, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiong Chen, Department of Otorhinolaryngology, Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China, Email zn_chenxiong@whu.edu.com Zhen Li, Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China, Email kamel_li@163.comPurpose: The diagnosis of severe OSA still relies on polysomnography, which causes a strong sense of restraint in patients with obesity. However, better prediction tools for severe OSA applicable to patients with obesity have not been developed.Patients and Methods: Relevant clinical data of 1008 patients with OSA who underwent bariatric surgery in our hospital were collected retrospectively. Patients were divided into training and test cohorts by machine learning. Univariate and multivariate logistic regression analysis was used to screen associations, including liver stiff measurement (LSM) and abdominal visceral tissue (aVAT), and to construct a severe OSA risk prediction nomogram. Then, we evaluated the effectiveness of our model and compared our model with the traditional Epworth Sleepiness Scale (ESS) model. Finally, our associations were used to explore the correlation with other indicators of OSA severity.Results: Our study revealed that age, biological sex, BMI, LSM, aVAT, and LDL were independent risk factors for severe OSA in patients with obesity. A severe OSA risk prediction nomogram constructed by six indicators possessed high AUC (0.845), accuracy (77.6%), and relatively balanced specificity and sensitivity (72.4%, 82.8%). The Hosmer-Lemeshow test (P=0.296, 0.785), calibration curves, and DCA of the training and test cohorts suggested better calibration and more net clinical benefit. Compared with the traditional ESS model, our model had higher AUC (0.829 vs 0.545), sensitivity (78.9% vs 12.2%), PPV (77.9% vs 53.3%), and accuracy (75.4% vs 55.2%). In addition, the associations in our model were independently correlated with other indicators reflecting OSA severity.Conclusion: We provided a simple, cheap, and non-invasive nomogram of severe OSA risk prediction for patients with obesity, which would be helpful for preventing further complications associated with severe OSA.Plain Language Summary: Question: Can we predict severe OSA in patients with obesity by their metabolic complications through some non-invasive examinations?Findings: Compared with traditional questionnaires, we developed and validated a new prediction model, including liver stiffness measurement and abdominal visceral adipose tissue, to screen severe OSA in bariatric surgery candidates through non-invasive examinations, which may contribute to perioperative safety and ultimate weight loss outcomes.Meaning: For patients with obesity who are in hospital because of metabolic disorders, it is necessary for them to be screened for possible severe OSA according to our new prediction nomogram, which is helpful for preventing further complications and perioperative risk associated with severe OSA.Keywords: obstructive sleep apnea, obesity, liver stiffness measurement, visceral adipose tissue, nomogram

Chunxia Yin,1,&ast; Taohua Lan,2,3,&ast; Yunshan Wu,4,5 Jing Cai,1 Haoxiang Li,1 Xiaolan Kuang,1 Lin Jiao,1 Xiaomin Ou,1 Hua Yang,2 Bo Liu,3– 5 Weihui Lu2,6,7 1The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Department of Cardiology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China; 3State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 4Guangzhou Key Laboratory of Chirality Research on Active Components of Traditional Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China; 5Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 6State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 7Chinese Medicine Guangdong Laboratory, Guangdong Hengqin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weihui Lu, Bo Liu, The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Email weihui.lu@gzucm.edu.cn; doctliu@gzucm.edu.cnPurpose: This study was designed to evaluate the effect and mechanism of the Qushi Huatan (QSHT) decoction against coronary heart disease (CHD) through network pharmacology and experimental verification.Methods: In the present study, the active ingredients of the QSHT decoction were identified by ultra performance liquid chromatography/tandem mass spectrometry (UPLC/MS), then the potential ingredients and coronary heart disease targets were predicted using the SwissTarget Prediction database and the database of Genecards and OMIM database, respectively. A herb-compound-target network was constructed using Cytoscape. GO and KEGG enrichment analysis were performed using the ClusterProfiler data package of R software. Molecular docking was used to predict the core targets of QSHT against CHD. In addition, we used a myocardial infarction (MI) and high-fat diet ApoE−/− mice model to investigate the cardioprotective effects of QSHT. Western blotting and immunochemistry were used to verify the core targets and the signaling pathway.Results: A total of 68 active ingredients were found in the QSHT decoction. Network pharmacology indicated 28 targets and 147 signal pathways, including AKT1, HIF-1α, GSK-3β, TLR4 and NF-κB, those key targets were also verified by molecular docking. The results of GO and KEGG enrichment analysis showed that the targets of QSHT against CHD were largely associated with inflammatory and oxidative stress, and AKT/HIF-1α and TLR4/NF-κB pathways might be key functional pathways. In vivo, QSHT significantly improved cardiac function and attenuated fibrosis and inflammation. Furthermore, QSHT could significantly inhibit the expression of HIF-1α, TLR4, phosphorylation of AKT1, GSK-3β and NF-κB after MI in ApoE−/− mice.Conclusion: Based on network pharmacology, molecular docking and experimental verification, this study demonstrated that QSHT could improve cardiac function and attenuate cardiac fibrosis by regulating TLR4/NF-κB and AKT/HIF-1α signaling pathway in post- MI and high-fat diet ApoE−/− mice.Keywords: network pharmacology, molecular docking, Qushi Huatan decoction, coronary heart disease

Jiaying Cai,1,&ast; Xiyue Tan,2,&ast; Qichao Hu,2,&ast; Huafeng Pan,3 Maoyuan Zhao,4 Cui Guo,4 Jinhao Zeng,1,4,5 Xiao Ma,2 Yanling Zhao6 1School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 3Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 4TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 5Department of Gastroenterology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 6Department of Pharmacy, Chinese PLA General Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinhao Zeng; Yanling Zhao, Email zengjinhao@cdutcm.edu.cn; zhaoyl2855@126.comAbstract: Gastric cancer (GC) is a prevalent gastrointestinal tumor characterized by high mortality and recurrence rates. Current treatments often have limitations, prompting researchers to explore novel anti-tumor substances and develop new drugs. Flavonoids, natural compounds with diverse biological activities, are gaining increasing attention in this regard. We searched from PubMed, Web of Science, SpringerLink and other databases to find the relevant literature in the last two decades. Using “gastric cancer”, “stomach cancers”, “flavonoid”, “bioflavonoid”, “ 2-Phenyl-Chromene” as keywords, were searched, then analyzed and summarized the mechanism of flavonoids in the treatment of GC. It was revealed that the anti-tumor mechanism of flavonoids involves inhibiting tumor growth, proliferation, invasion, and metastasis, as well as inducing cell death through various processes such as apoptosis, autophagy, ferroptosis, and pyroptosis. Additionally, combining flavonoids with other chemotherapeutic agents like 5-FU and platinum compounds can potentially reduce chemoresistance. Flavonoids have also demonstrated enhanced biological activity when used in combination with other natural products. Consequently, this review proposes innovative perspectives for the development of flavonoids as new anti-GC agents.Keywords: flavonoid, gastric cancer, apoptosis, angiogenesis

Longyin Zhu,&ast; Juan Cai,&ast; Jia Fang, Lingyu Ran, Huan Chang, Huhai Zhang, Jiamin Zeng, Qin Yang, Chunxiao Fu, Qingping Li, Qianguang Pan, Hongwen Zhao Department of Nephrology, the First Hospital Affiliated to Army Military Medical University (Southwest Hospital), Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongwen Zhao; Qianguang Pan, Email zhaohw212@126.com; panqianguang@163.comObjective: Analyze risk factors for cardiac surgery-associated acute kidney injury (CSA-AKI) in adults and establish a nomogram model for CSA-AKI based on plasma soluble urokinase-type plasminogen activator receptor (suPAR) and clinical characteristics.Methods: In a study of 170 patients undergoing cardiac surgery with cardiopulmonary bypass, enzyme-linked immunosorbent assay (ELISA) measured plasma suPAR levels. Multivariable logistic regression analysis identified risk factors associated with CSA-AKI. Subsequently, the CSA-AKI nomogram model was developed using R software. Predictive performance was evaluated using a receiver operating characteristic (ROC) curve and the area under the curve (AUC). Internal validation was performed through the Bootstrap method with 1000 repeated samples. Additionally, decision curve analysis (DCA) assessed the clinical applicability of the model.Results: Multivariable logistic regression analysis revealed that being male, age ≥ 50 years, operation time ≥ 290 minutes, postoperative plasma suPAR at 2 hours, and preoperative left ventricular ejection fraction (LVEF) were independent risk factors for CSA-AKI. Employing these variables as predictive factors, a nomogram model was constructed, an ROC curve was generated, and the AUC was computed as 0.817 (95% CI 0.726– 0.907). The calibration curve indicated the accuracy of the model, and the results of DCA demonstrated that the model could benefit the majority of patients.Conclusion: Being male, age ≥ 50 years, operation time ≥ 290 minutes, low preoperative LVEF, and elevated plasma suPAR at 2 hours are independent risk factors for CSA-AKI. The nomogram model established based on these risk factors has high accuracy and clinical value, serving as a predictive tool for assessing the risk of CSA-AKI.Keywords: nomogram, acute kidney injury, prediction model, risk factors, cardiac surgery

Zhenghuan Song,1,&ast; Jiaqin Cai,2,&ast; Yihu Zhou,3 Yueyi Jiang,3 Shiyi Huang,2 Lianbing Gu,1,2 Jing Tan1,2 1Department of Anesthesiology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 21009, People’s Republic of China; 2Xuzhou Medical University, Xuzhou, 21009, People’s Republic of China; 3Nanjing Medical University, Nanjing, 21009, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Tan; Lianbing Gu, Department of Anesthesiology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 21009, People’s Republic of China, Tel +86-13813967939; +86-13951947684, Email tanjing@njmu.edu.cn; 13951947684@163.comPurpose: Artificial intelligence (AI) is increasingly influencing various medical fields, including anesthesiology. The Introduction of artificial intelligent patient-controlled analgesia (Ai-PCA) has been seen as a significant advancement in pain management. However, the adoption and practical application of Ai-PCA by medical staff, particularly in anesthesia and thoracic surgery, have not been extensively studied. This study aimed to investigate the knowledge, attitudes and practices (KAP) among anesthesia and thoracic surgery medical staff toward artificial intelligent patient-controlled analgesia (Ai-PCA).Participants and Methods: This web-based cross-sectional study was conducted between November 1, 2023 and November 15, 2023 at Jiangsu Cancer Hospital. A self-designed questionnaire was developed to collect demographic information of anesthesia and thoracic surgery medical staff, and to assess their knowledge, attitudes and practices toward Ai-PCA.Results: A total of 519 valid questionnaires were collected. Among the participants, 278 (53.56%) were female, 497 (95.76%) were employed in the field of anesthesiology, and 188 (36.22%) had participated in Ai-PCA training. The mean knowledge, attitude, and practice scores were 7.8± 1.75 (possible range: 0– 10), 37.43± 4.16 (possible range: 9– 45), and 28.38± 9.27 (possible range: 9– 45), respectively.Conclusion: The findings revealed that anesthesia and thoracic surgery medical staff have sufficient knowledge, active attitudes, but poor practices toward the Ai-PCA. Comprehensive training programs are needed to improve anesthesia and thoracic surgery medical staff’s practices in this area.Keywords: knowledge, attitudes, practices, Ai-PCA, cross-sectional study

Jiachen Ge,1,&ast; Ming Tao,2,&ast; Gaolei Zhang,1 Jianping Cai,1 Deyu Li,1 Lianyuan Tao1 1Department of Hepatobiliary Surgery, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of General Surgery, Peking University Third Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Deyu Li; Lianyuan Tao, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, No. 7 Weiwu Road, Zhengzhou City, Henan Province, People’s Republic of China, Email lideyu19@hotmail.com; tly2007tly@hotmail.comPurpose: Hepatocellular carcinoma has become one of the severe diseases threatening human health. T cell exhaustion is deemed as a reason for immunotherapy resistance. However, little is known about the roles of CD8 Tex-related lncRNAs in HCC.Materials and Methods: We processed single-cell RNA sequencing to identify CD8 Tex-related genes. CD8 Tex-related lncRNAs were identified based on their correlations with mRNAs. Unsupervised clustering approach was used to identify molecular clusters of CD8 Tex-related lncRNAs. Differences in prognosis and immune infiltration between the clusters were explored. Machine learning algorithms were used to construct a prognostic signature. Samples were classified as low- and high-risk groups based on their risk scores. We identified prognosis-related lncRNAs and constructed a ceRNA network. In vitro experiments were conducted to investigate the impacts of CD8 Tex-related lncRNAs on proliferation and apoptosis of HCC cells.Results: We clarified cell types within two HCC single-cell datasets. We identified specific markers of CD8 Tex cells and analyzed their potential functions. Twenty-eight lncRNAs were identified as CD8 Tex-related. Based on CD8 Tex-related lncRNAs, samples were categorized into two distinct clusters, which exhibited significant differences in survival rates and immune infiltration. Ninety-six algorithm combinations were employed to establish a prognostic signature. RSF emerged as the one with the highest C-index. Patients in high- and low-risk groups exhibited marked differences in prognosis, enriched pathways, mutations and drug sensitivities. MCM3AP-AS1, MAPKAPK5-AS1 and PART1 were regarded as prognosis-related lncRNAs. A ceRNA network was constructed based on CD8 Tex-related lncRNAs and mRNAs. Experiments on cell lines and organoids indicated that downregulation of MCM3AP-AS1, MAPKAPK5-AS1 and PART1 suppressed cell proliferation and induced apoptosis.Conclusion: CD8 Tex-related lncRNAs played crucial roles in HCC progression. Our findings provided new insights into the regulatory mechanisms of CD8 Tex-related lncRNAs in HCC.Keywords: hepatocellular carcinoma, lncRNA, T cell exhaustion, single-cell RNA-seq, machine learning, prognostic signature

Xiaoqing Wei,1,&ast; Junying Zhang,2,&ast; Youwen Mei,3 Eqiong Li,4 Qianling Dai,1 Xiaoli Yang,1 Dan Luo,5 Biao Li,6 Ping Hua,7 Jian Cai,7 Hua Lai,8 Dongfeng Qi,9 Sha Lai,10 Mi Qin,11 Yonghong Lin4 1Department of Cervical Disease and Cervical Cancer Prevention and Treatment, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 2Clinical Laboratory Department, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 3Department of Reproduction and Infertility, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 4Department of Gynecology, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 5Department of Obstetrics, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 6Department of Neonatal Intensive Care Unit, Chengdu Women’ and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 7Department of Pathology, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 8Department of Radiation and Interventional Therapy, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 9Department of Ultrasonics, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 10Dermatology Department, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 11Department of Pediatric Surgery, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yonghong Lin; Xiaoqing Wei, Email linyhcd2011@163.com; xqcherry@163.comObjective: We report a case of Carmi Syndrome in a neonate.Aim: To share our lessons in diagnosis of the case of Carmi Syndrome.Case Report: Carmi Syndrome is an extremely rare autosomal recessive genetic disorder characterized the coexistence of pyloric atresia and junctional epidermolysis bullosa, and with aplasia cutis congenita in approximately 28% patients. In this case, a full-term male neonate was born to a G4P2+1L1 multipara through cesarean section delivery in hospital in a non-consanguineous marriage with 4000mL of II°meconium-stained amniotic fluid. He was found extensive skin loss over lower legs and other parts, with scattered blisters and bilateral microtia. Plain abdominal X-ray revealed a large gastric air bubble with no gas distally. The mother had an intrauterine fetal loss previously for reasons unknown. The dermatologist diagnosed the newborn with Bart Syndrome, while the pediatric surgeon diagnosed congenital pyloric atresia(CPA). The parents refused further treatment and the neonate passed away about 30 hours after birth.Outcome: The neonate passed away about 30 hours after birth.Conclusion: Lessons from this case:①.Rule out Carmi Syndrome in patients with PA, and differentiate Bart syndrome and Carmi Syndrome in patients with abnormal skin manifestations. ②. For rare and/or severe diseases, multidisciplinary teams(MDTs) should be establish. ③. Genetic counseling and prenatal diagnosis are necessary prior to subsequent childbearings. ④.Termination of pregnancy might be contemplated if certain indicators are revealed.Keywords: Carmi syndrome, bart syndrome, epidermolysis bullosa, EB, junctional epidermolysis bullosa, JEB, congenital pyloric atresia, CPA, aplasia cutis congenita, ACC, congenital localized absence of skin, CLAS, pyloric atresia, PA, epidermolysis bullosa with pyloric atresia, EB-PA, multidisciplinary teams, MDT

Yuanfeng Wang,1,&ast; Xu Qiu,1,&ast; Jiao Liu,1,&ast; Xuanyi Liu,1 Jialu Pan,2 Jiayi Cai,2 Xiaodong Liu,1,3 Shugen Qu1,3 1College of Public Health and Management, Zhejiang Provincial Key Laboratory of Watershed Science and Health, Wenzhou Medical University, Wenzhou, People’s Republic of China; 2The First Clinical Medical College, Wenzhou Medical University, Wenzhou, People’s Republic of China; 3South Zhejiang Institute of Radiation Medicine and Nuclear Technology, Wenzhou, People’s Republic of China&ast;These authors contributed equally to this work.These authors contributed equally to this workCorrespondence: Xiaodong Liu; Shugen Qu, Email forget45@wmu.edu.cn; shugenju@wmu.edu.cnIntroduction: Sepsis is a worldwide epidemic, with high morbidity and mortality. Cuproptosis is a form of cell death that is associated with a wide range of diseases. This study aimed to explore genes associated with cuproptosis in sepsis, construct predictive models and screen for potential targets.Methods: The LASSO algorithm and SVM-RFE model has been analysed the expression of cuproptosis-related genes in sepsis and immune infiltration characteristics and identified the marker genes under a diagnostic model. Gene-drug networks, mRNA-miRNA networks and PPI networks were constructed to screen for potential biological targets. The expression of marker genes was validated based on the GSE57065 dataset. Consensus clustering method was used to classify sepsis samples.Results: We found 381 genes associated with the development of sepsis and discovered significantly differentially expressed cuproptosis-related genes of 16 cell types in sepsis and immune infiltration with CD8/CD4 T cells being lower. NFE2L2, NLRP3, SLC31A1, DLD, DLAT, PDHB, MTF1, CDKN2A and DLST were identified as marker genes by the LASSO algorithm and the SVM-RFE model. AUC > 0.9 was constructed for PDHB and MTF1 alone respectively. The validation group data for PDHB (P=0.00099) and MTF1 (P=7.2e-14) were statistically significant. Consistent clustering analysis confirmed two subtypes. The C1 subtype may be more relevant to cellular metabolism and the C2 subtype has some relevance to immune molecules.The results of animal experiments showed that the gene expression was consistent with the bioinformatics analysis.Discussion: Our study systematically explored the relationship between sepsis and cuproptosis and constructed a diagnostic model. And, several cuproptosis-related genes may interfere with the progression of sepsis through immune cell infiltration.Keywords: machine learning, cuproptosis, immune infiltration, sepsis, diagnostic model

Bo-Lun Zhang,1 Jia Liu,2 Guanghao Diao,2 Jianping Chang,1 Junshuai Xue,1 Zhen Huang,1 Hong Zhao,1 Lingxiang Yu,2 Jianqiang Cai1 1Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Hepatobiliary Surgery, the Fifth Medical Center of the PLA General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Jianqiang Cai, Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, People’s Republic of China, Tel +86-10-87787100, Fax +86-10-67709698, Email caijianqiang@cicams.ac.cnPurpose: We developed a nomogram based on the liver function, nutrition, inflammation, and immunity (LFNII) score to predict recurrence-free survival (RFS) post-resection in patients with hepatocellular carcinoma (HCC) exhibiting alpha-fetoprotein (AFP) negativity (AFP ≤ 20 ng/mL).Patients and Methods: Clinical data of 661 patients diagnosed with alpha-fetoprotein-negative hepatocellular carcinoma (AFP-NHCC) who underwent surgical resection at two medical centers between 2012 and 2021 were collected. A total of 462 and 199 patients served as the training and validation sets, respectively. Pre-operative blood markers were collected and analyzed for LFNII. The LFNII score was formulated using the least absolute shrinkage and selection operator Cox regression model. A nomogram model was developed using the training set to incorporate other relevant clinicopathological indicators and predict postoperative recurrence. Model discrimination was assessed using the receiver operating characteristic curve, calibration was evaluated using a calibration curve, and clinical applicability was assessed using clinical decision curve analysis. A comparison with liver cancer staging was performed using the nomogram model. Finally, a cohort study was conducted to validate our findings.Results: We derived the LFNII scores from nine indicators. Elevated LFNII scores correlated with unfavorable clinicopathological features. The LFNII score area under the curve revealed superior predictive efficacy at 1-, 2-, and 5-year RFS intervals, with values of 0.675, 0.658, and 0.633, respectively. Multivariate Cox analysis revealed that a high LFNII score independently increased RFS risk in patients with AFP-NHCC. The C-index of the LFNII-nomogram model was 0.686 (95% confidence interval [CI], 0.651– 0.721). The nomogram model’s clinical application value surpassed that of standard HCC staging systems.Conclusion: The LFNII score-derived nomogram effectively predicted the RFS of patients with AFP-NHCC after curative resection.Keywords: hepatocellular carcinoma, alpha-fetoprotein-negative, immunity, inflammation, nutrition, recurrence-free survival

Mi Qi, Yajuan Cheng, Ke Liu, Jingxing Cai, Tianyu Liu, Xiaoying Wu, Huili Tang, He Huang, Qinbiao Chen, Xiaoguang Zhou The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Mi Qi; Xiaoguang Zhou, Tel +86-13510794978 ; +86-18818780760, Email qimi@mail.sysu.edu.cn; gzzhouxg@163.comPurpose: Ischemic stroke is a high-incidence disease that threatens human well-being. The potent neuroprotective effects render reactive oxygen species (ROS) scavengers potential agents for acute ischemic stroke therapy. Challenges such as inadequate permeability across the blood-brain barrier (BBB), limited half-life, and adverse effects hinder the widespread utilization of small molecule and inorganic ROS scavengers. Thus, there is an urgent demand for efficacious neuroprotective agents targeting ischemic stroke. Our study discovered the superoxide dismutase (SOD)-mimetic activity of recombinant human heavy chain ferritin (rHF) nanoparticles expressed from Escherichia coli (E. coli). Subsequent investigations delved into the ROS-scavenging proficiency of rHF within neural cells, its therapeutic efficacy against ischemic stroke, and the elucidation of its neuroprotective mechanisms.Methods: rHF protein nanoparticles were expressed in E. coli and purified via size-exclusion chromatography. The superoxide anion (•O2−) scavenging SOD-mimetic activity of rHF nanoparticles was measured using a SOD detection kit. The ROS scavenging ability and protection effects against oxidative damage of rHF nanoparticles were studied in H2O2-induced PC12 cells. Therapeutic effects and neuroprotective mechanisms of rHF against ischemic stroke were investigated with transient middle cerebral artery occlusion (MCAO) reperfusion mice model.Results: rHF nanoparticles can eliminate excessive ROS in nerve cells and alleviate oxidative damage. The results of animal experiments demonstrated that rHF nanoparticles passed across BBB, reduced infarct areas in brain tissue, and lowered the neurological deficit score of ischemia-reperfusion model mice. Additionally, rHF nanoparticles mitigated neuronal apoptosis and ferroptosis, suppressed microglial activation, maintained oxygen homeostasis, and exhibited negligible organ toxicity.Conclusion: rHF nanoparticle could be developed as a new ROS scavenger for nerve cells and has therapeutic potential as a drug for cerebral ischemia-reperfusion injury. Keywords: human heavy chain ferritin, ROS scavenger, ischemic stroke, SOD-mimetic, neuroprotection

Xi Wu, Mingxing Wu, Haobo Huang, Lei Wang, Zhe Liu, Jie Cai, He Huang Department of Cardiology, Xiangtan Central Hospital, Xiangtan, Hunan, 411100, People’s Republic of ChinaCorrespondence: He Huang, Department of Cardiology, Xiangtan Central Hospital, Xiangtan, Hunan, 411100, People’s Republic of China, Email 1764200045@e.gzhu.edu.cnPurpose: The prognostic implications of calcified versus non-calcified tissue protrusions (TPs) following stent implantation remain undetermined. This study aimed to evaluate the differential clinical outcomes associated with calcified and non-calcified TP morphologies.Patients and Methods: Employing intravascular ultrasound (IVUS), we identified calcified TPs as calcium fragment extrusions permeating the stent struts, while non-calcified TPs were characterized as plaque and/or thrombus extensions through the stent into the arterial lumen. The primary endpoint encompassed target lesion failure (TLF), comprising cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization (TLR), or stent thrombosis, assessed in patients with a follow-up period exceeding one year.Results: Of 1033 patients subjected to pre- and post-intervention IVUS, 62 exhibited calcified TPs (6.0%), and 279 presented non-calcified TPs (27.0%), forming the basis of this analysis. Multivariable linear regression indicated calcified nodules as a significant predictor of calcified TP [Odds Ratio (OR) 2.47; 95% Confidence Interval (CI) 2.33 to 2.62; P < 0.001], with ST-segment elevation myocardial infarction emerging as an inverse correlate [OR 0.82; 95% CI 0.73 to 0.93; P = 0.004]. Two-year data revealed a higher incidence of TLF in patients with calcified TPs versus their non-calcified counterparts (11.3% vs 2.2%, P < 0.001), and a marked increase in clinically driven TLR (9.7% vs 1.4%, P < 0.001). Calcified TPs were independently correlated with increased TLF risk in the adjusted model [Hazard Ratio (HR) 2.47; 95% CI 1.17 to 5.16; P = 0.027].Conclusion: After drug-eluting stent implantation, IVUS-identified calcified TPs correlate with adverse clinical outcomes compared to non-calcified TP formations.Keywords: percutaneous coronary intervention, intravascular ultrasound, tissue protrusion, prognosis

Xiaofeng Sun,1 Junhong Cai,1 Hongkui Yu,1 Ting Zhang,1 Lanlang Zhang2 1Department of Ultrasound, Shenzhen Baoan Women’s and Children’s Hospital, Shenzhen, Guangdong Province, 518102, People’s Republic of China; 2Department of Hemodialysis, Fuyong People’s Hospital of Baoan District, Shenzhen, Guangdong Province, 518103, People’s Republic of ChinaCorrespondence: Lanlang Zhang, Department of Hemodialysis, Fuyong People’s Hospital of Baoan District, Shenzhen, Guangdong Province, 518103, People’s Republic of China, Tel +86-13603098960, Email 710394655@qq.comBackground: Transvaginal four-dimensional hysterosalpingo-contrast sonography (TVS 4D-HyCoSy) is a pivotal diagnostic tool in the assessment and management of infertility. Conventionally, a 20mL syringe is employed for contrast agent injection, either at a constant or pulsatile pressure. However, in cases of bilateral fallopian tube obstruction, continued injection can lead to discomfort and excessive pressure within the uterine cavity, necessitating discontinuation of the examination.Case Presentation: In this illuminating case study, a patient underwent TVS 4D-HyCoSy due to infertility concerns. Initial contrast agent injection failed to visualize both fallopian tubes, accompanied by acute pain. Bilateral tubal obstruction was diagnosed, prompting an innovative approach. A 2.5mL syringe was chosen for pulsed injection, leading to successful visualization of patency in one fallopian tube. Remarkably, the patient achieved natural pregnancy within three months of the examination.Conclusion: Pulsed injection using a small-volume syringe emerges as a promising technique in cases of fallopian tube obstruction during TVS 4D-HyCoSy. This method not only enhances patient comfort but also improves the likelihood of visualizing fallopian tube patency, contributing to accurate infertility assessments. As a supplementary technique, it addresses limitations associated with constant pressure injection and offers a novel approach to enhance diagnostic success.Keywords: hysterosalpingography, tubal obstruction, contrast agent, pulsed injection, small-volume syringe

Jingjing Du,1 Yiqing Tao,2 Jiaxing Yang,1 Jiachang Cai,1 Hongwei Zhou,1 Rong Zhang,1 Yanyan Hu1 1Department of Clinical Laboratory, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, People’s Republic of China; 2Department of Orthopedics, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Rong Zhang; Yanyan Hu, Department of Clinical Laboratory, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, 310009, People’s Republic of China, Email zhang-rong@zju.edu.cn; yanyanhu@zju.edu.cnAbstract: Brucellosis is a zoonotic disease caused by Brucella spp., with the highest prevalence found in the northern cities of China. In this case report, we present an occurrence of spinal infection caused by B. melitensis in a 67-year-old man residing in a non-endemic area of southern China. The patient initially presented with chest and back pain, which was not accurately diagnosed and treated at a local hospital. Subsequently, due to worsening pain, he was admitted to our hospital. To determine the cause of the infection, we performed CT-guided aspiration biopsy and collected biopsy tissue for metagenomic next-generation sequencing (mNGS) on the second day of hospitalization. Imaging investigations revealed involvement of the thoracic vertebrae, specifically thoracic 4– 7 with the main focus on 5– 6, accompanied by stenosis of the intervertebral space. The mNGS results indicated that the spine infection was caused by B. melitensis. The patient’s history as a shepherd and a positive Rose Bengal plate test (RBPT) further supported the diagnosis of brucella spondylitis. In order to alleviate pain and restore spinal function, the patient underwent posterior internal fixation of the thoracic spine. Treatment was initiated with cefoperazone/sulbactam, followed by doxycycline. Subsequently, the patient was switched to a combination therapy of rifampicin and doxycycline for a duration of six weeks. The patient responded well to treatment, and his condition remained stable. In conclusion, brucellosis is a common disease that can be easily misdiagnosed. This case report highlights the potential value of mNGS in early and rapid diagnosis. We believe that mNGS can serve as an effective tool to improve the diagnosis of spine infections caused by this pathogen.Keywords: spine infection, Brucella melitensis, metagenomic next-generation sequencing, Rose Bengal plate test

Jun Liu,1,&ast; Yi Zhang,2,&ast; Jianpeng Cai,2,&ast; Lingyun Shao,2 Xiufeng Jiang,3 Xiaohong Yin,4 Xinguo Zhao,4 Sen Wang2,5 1Department of Laboratory medicine, Wuxi Fifth People’s Hospital Affiliated to Nanjing Medical University, Wuxi, People’s Republic of China; 2Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Wuxi Fifth People’s Hospital Affiliated to Nanjing Medical University, Wuxi, People’s Republic of China; 4Department of Tuberculosis, Wuxi Fifth People’s Hospital Affiliated to Nanjing Medical University, Wuxi, People’s Republic of China; 5Huashen Institute of Microbes and Infections, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Sen Wang; Xinguo Zhao, Email wangsen329@126.com; zhaoxg0469@sina.comBackground: Klebsiella pneumoniae (K. pneumoniae) is one of the most common pathogens leading to pulmonary tuberculosis (PTB) co-infection, but the data of co-infections is scarce. This research aimed to study the clinical and microbiological characteristics of K. pneumoniae co-infections in pulmonary tuberculosis cases.Methods: Clinical manifestations and examination results of PTB cases co-infected by K. pneumoniae were retrospectively collected from the medical record database of a tertiary teaching hospital in China between November 2019 and October 2021. The K. pneumoniae strains isolated from the patients were sent for whole-genome sequencing. Statistical analyses were conducted using Stata v.14.0.Results: A total of 80 strains were collected from 76 PTB patients with K. pneumoniae co-infections (two strains were isolated from each of the four patients at different time points), including 37 primary and 39 retreated TB cases. Among these, 29 (36.3%) of the K. pneumoniae isolates were extended-spectrum β-lactamase (ESBL)-producing strains, and seven (8.8%) were determined as carbapenem-resistant Enterobacteriaceae (CRE) strains. We found that patients in the multidrug resistance (MDR)-group received more respiratory support than the non-MDR group (40.6% vs 18.2%, P= 0.031) and possessed higher elevated C-reactive protein (62.6% vs 41.8%, P=0.008) and lower haemoglobin (87.5% vs 47.7%, P=0.001). We found that 80.3% (61/76) patients had lung lesions and 57.8% (44/76) patients were immunocompromised within one month. The most common K. pneumoniae strain sequence type was ST23 (15%), followed by ST15 (12.5%) and ST273 (7.5%). Among the strains, 26.25% were classically hypervirulent K1/K2 K. pneumoniae, and all carried salmochelin and rmpA.Conclusion: This study demonstrated the important clinical features, phenotypic and genomic characteristics of isolated strains of PTB patients with K. pneumoniae co-infection. These data suggested a special attention for multidrug resistant K. pneumoniae infections with more obvious inflammatory responses which calls for more respiratory support and timely clinical management.Keywords: Klebsiella pneumoniae, tuberculosis, co-infection, manifestation, multidrug resistant

Jiexiong Li,1,&ast; Jiachun Cai,2,&ast; Jianjin Li,1 Zhitao Li1 1Department of Anesthesiology, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China; 2Department of Fundus Disease, Shenzhen Eye Hospital, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhitao Li, Email lytow@qq.comBackground: Worrying about increasing the use of instrument-assisted delivery and prolonging the process, midwives in our institution tended to persuade the parturients who had entered the second stage of labor, to give up neuraxial analgesia. Remifentanil seemed to be suitable for this situation due to its advantages of fast onset and metabolism. We designed a single arm and prospective study to explore the analgesic effect and safety of remifentanil intravenous patient-controlled analgesia (PCA) in singleton parturients during the second stage of labor.Methods: Ten pregnancies were included, whose cervical dilation had exceeded 8 cm when they arrived into the delivery room. The patient was given 40 μg remifentanil intravenously as soon as she felt the contraction with a lockout time of 2 minutes. The maternal heart rate (MHR), mean arterial pressure (MAP), SpO2, fetal heart rate (FHR), OAA/S score, and VAS analgesia score were recorded before and at 5, 10, 20, 30, and 60 minutes after administration. An umbilical artery blood gas analysis and Apgar scores at 1 and 5 minutes were also recorded after the delivery of the newborn. The incidence of adverse events and overall satisfaction with analgesia were recorded.Results: The VAS score decreased from 9.2 to 4.6 after remifentanil administration. All umbilical artery PH values were beyond 7.20. All 1-minute newborns’ Apgar scores were 8 points or greater, and 9 points or greater in the 5th minute. Adverse events included 3 cases of dizziness, 3 cases of nausea, 1 case of vomiting, and 1 case of parturients had a transient FHR drop at the 10th minute, accompanied by hypoxemia and hypersomnia. The overall satisfaction rate was 70%.Conclusion: Remifentanil PCA could effectively relieve the severe uterine contraction pain suffered by the parturients in the second stage of labor with safety.Keywords: labor, analgesia, remifentanil

Xi Wu,&ast; Mingxing Wu,&ast; Haobo Huang,&ast; Zhe Liu, Jie Cai, Qizhou Zhang, He Huang Department of Cardiology, Xiangtan Central Hospital, Xiangtan, Hunan, 411100, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: He Huang, Department of Cardiology, Xiangtan Central Hospital, Xiangtan, Hunan, 411100, People’s Republic of China, Email 1764200045@e.gzhu.edu.cnPurpose: This research aimed to evaluate the procedural and in-hospital clinical outcomes of percutaneous coronary intervention (PCI) for ostial or stumpless chronic total occlusion (CTO) utilizing both the antegrade-only and retrograde approaches.Methods: A comprehensive retrospective examination was conducted on the procedural and in-hospital clinical outcomes of 89 consecutive patients subjected to ostial or stumpless CTO PCI at our institution between April 2015 and October 2022.Results: The antegrade-only technique demonstrated a superior technical success rate (92.0% vs 71.9%, p = 0.041) and procedural success rate (92.0% vs 68.8%, p = 0.022) in comparison to the retrograde approach (RA). The RA group presented a notably elevated Japanese-CTO (J-CTO) score relative to the antegrade-only approach group (2.45± 0.73 vs 1.64± 0.70, p < 0.001). The antegrade-only approach group manifested an increased frequency of microchannels at the proximal stump relative to the RA group (56.0% vs 10.9%, p < 0.001). In-hospital major adverse cardiac events (MACE) and in-hospital myocardial infarction (MI) were observed more prevalently in the RA group (18.8% vs 0, p = 0.003; 15.6% vs 0, p = 0.008; respectively). A J-CTO score below 2 and the manifestation of microchannels at the proximal stump were identified as predictors for successful antegrade-only approach PCI for ostial or stumpless CTO (OR: 2.79 [95% CI: 1.92– 5.03, P =0.003]; OR: 2.89 [95% CI: 1.32– 6.03, P =0.001]; respectively).Conclusion: Relative to RA PCI for ostial or stumpless CTO, the antegrade-only approach is utilized for less complex CTO lesions and is associated with a diminished probability of in-hospital MACE.Keywords: chronic total occlusion, percutaneous coronary intervention, intravascular ultrasound

Jiawei Cai,1– 3,&ast; Chao He,4,&ast; Jiaheng Xu,1– 3,&ast; Qiu He,1– 3 Jinye Su,1– 3 Zanyi Wu,1– 3 Yawen Xu1– 3 1Department of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, People’s Republic of China; 2Department of Neurosurgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, People’s Republic of China; 3Fujian Provincial Institutes of Brain Disorders and Brain Sciences, First Affiliated Hospital, Fujian Medical University, Fuzhou, People’s Republic of China; 4Department of Neurosurgery, Zhuji Affiliated Hospital of Wenzhou Medical University, Zhuji, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yawen Xu; Zanyi Wu, Department of Neurosurgery, The First Affiliated Hospital, Fujian Medical University, No. 20 Chazhong Road, Taijiang District, Fuzhou, Fujian, 350005, People’s Republic of China, Email xuyawen121314@163.com; kirby98@126.comObjective: To identify whether intracranial hematoma (ICH) evacuation improves the prognosis of patients with ruptured anterior communicating artery (AcomA) aneurysms concomitant with small ICHs (≥ 10 mL and < 25 mL).Methods: Data on patients diagnosed with small ICHs secondary to ruptured AcomA aneurysms who underwent surgery in our department between January 2010 and February 2018 was retrospectively analyzed. The patients were divided into two groups based on whether the hematoma was evacuated. The modified Rankin Scale (mRS) was used to assess prognosis six months after onset.Results: The study recruited 58 patients, 19 of whom underwent aneurysm clipping and ICH evacuation. While 33 patients underwent aneurysm clipping, 6 patients underwent coiling embolism without ICH evacuation. The average ICH volume was 15.27± 4.07 mL. In the hematoma-evacuated group, 13 (68.4%) patients had unfavorable outcomes (mRS scores of 4 to 6). In the non-evacuated hematoma group, 13 (33.3%) patients had unfavorable outcomes (P = 0.001), postoperative infarction occurred in 11 (57.9%) patients in the hematoma evacuation group and 9 (23.1%) patients in the other group (P = 0.009).Conclusion: ICH evacuation was associated with unfavorable outcomes and postoperative infarction in ruptured AcomA aneurysms with concomitant small hematomas (< 25 mL). Aneurysm clipping or coiling without ICH evacuation may be a safe and effective choice; however, further investigation is needed.Keywords: AcomA aneurysms, intracranial hematoma, infarction, prognosis, ICH evacuation

Weibo Zhang,1,2,&ast; Siyuan He,1,&ast; Liam Wilson,3 Astrid Foix-Colonier,4 Maud Pacou,4 Youwei Zhu,1 Yi Zhu,1 Lili Xue,1 Yanfeng Wang,1 Junmei Li,1 Yanli Liu,1 Jun Cai1,2 1Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Mental Health Branch, China Hospital Development Institute, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Amaris Consulting, Shanghai, People’s Republic of China; 4Amaris Consulting, Paris, France&ast;These authors contributed equally to this workCorrespondence: Jun Cai, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai, 200030, People’s Republic of China, Email caijun533@163.comPurpose: This study aimed to quantify the preferences of Chinese patients with schizophrenia and their caregivers for antipsychotic treatment.Patients and Methods: Patients with schizophrenia (aged 18– 35) and their caregivers were recruited via six outpatient mental health clinics in Shanghai, People’s Republic of China. In a discrete choice experiment (DCE), participants chose between two hypothetical treatment scenarios that varied regarding the type of treatment, rate of hospitalization, severity of positive symptoms, treatment cost and rates of improvement in daily and social functioning. Data for each group were analyzed using the modelling approach that yielded the lower deviance information criterion. The relative importance score (RIS) for each treatment attribute was also determined.Results: A total of 162 patients and 167 caregivers participated. Frequency of hospital admission was the most important treatment attribute for patients (average scaled RIS=27%), followed by mode and frequency of treatment administration (24%). Improvement in ability to carry out daily activities (8%) and improvement in social functioning (8%) were least important. Patients in full-time employment placed more importance on the frequency of hospital admission than unemployed patients (p< 0.01). Frequency of hospital admission was also the most important attribute for caregivers (RIS=33%), followed by improvement in positive symptoms (20%), while improvement in daily activities (7%) was the least important.Conclusion: Patients with Schizophrenia in China prefer treatments that help reduce the number of times they are admitted to hospital, as do their caregivers. These results may bring insight for physicians and health authorities in China regarding the treatment characteristics that patients value the most.Keywords: conjoint analysis, discrete choice experiment, schizophrenia, preference study, patients, caregivers

Chunjiao Lu,&ast; Yi Liu,&ast; Yao Liu, Guanhua Kou, Yang Chen, Xuewei Wu, Yuhang Lv, Jiahao Cai, Renyuan Chen, Juanjuan Luo, Xiaojun Yang Guangdong Provincial Key Laboratory of Infectious Disease and Molecular Immunopathology, Shantou University Medical College, Shantou, 515041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Juanjuan Luo; Xiaojun Yang, Guangdong Provincial Key Laboratory of Infectious Disease and Molecular Immunopathology, Shantou University Medical College, Shantou, 515041, People’s Republic of China, Tel +86-754-88900236, Fax +86-754-88900276, Email lujj770@163.com; yangx@stu.edu.cnIntroduction: Silver nanoparticles (AgNP) are widely used as coating materials. However, the potential risks of AgNP to human health, especially for neural and vascular systems, are still poorly understood.Methods: The vascular and neurotoxicity of various concentrations of AgNP in zebrafish were examined using fluorescence microscopy. In addition, Illumina high-throughput global transcriptome analysis was performed to explore the transcriptome profiles of zebrafish embryos after exposure to AgNP. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to elucidate the top 3000 differentially expressed genes (DEGs) between AgNP-exposed and control groups.Results: We systematically investigated the neural and vascular developmental toxicities of AgNP exposure in zebrafish. The results demonstrated that AgNP exposure could cause neurodevelopmental anomalies, including a small-eye phenotype, neuronal morphology defects, and inhibition of athletic abilities. In addition, we found that AgNP exposure induces angiogenesis malformation in zebrafish embryos. Further RNA-seq revealed that DEGs were mainly enriched in the neuroactive ligand-receptor interaction and vascular endothelial growth factor (Vegf) signaling pathways in AgNP-treated zebrafish embryos. Specifically, the mRNA levels of the neuroactive ligand-receptor interaction pathway and Vegf signaling pathway-related genes, including si:ch73-55i23.1, nfatc2a, prkcg, si:ch211-132p1.2, lepa, mchr1b, pla2g4aa, rac1b, p2ry6, adrb2, chrnb1, and chrm1b, were significantly regulated in AgNP-treated zebrafish embryos.Conclusion: Our findings indicate that AgNP exposure transcriptionally induces developmental toxicity in neural and vascular development by disturbing neuroactive ligand-receptor interactions and the Vegf signaling pathway in zebrafish embryos.Keywords: silver nanoparticles, neurological development, vascular development, developmental toxicity, zebrafish

Jiasheng Cai,1,&ast; Mingxuan Li,2,&ast; Wei Wang,1,&ast; Rong Luo,1 Zheng Zhang,1 Haibo Liu1 1Department of Cardiology, QingPu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, 201700, People’s Republic of China; 2Department of Cardiology, Shanghai Medical College Fudan University, Huadong Hospital, Shanghai, 200040, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haibo Liu; Zheng Zhang, Department of Cardiology, QingPu Branch of Zhongshan Hospital Affiliated to Fudan University, 1158 Park, Shanghai, 201700, People’s Republic of China, Email haiboliu13@fudan.edu.cn; zhangzheng@qphospital.comBackgrounds and Aims: Atrial fibrillation (AF) is the most common cardiac arrhythmia among the older patients (≥ 80 years) in clinical practice. The index of neutrophil percentage-to-albumin ratio (NPAR) is a reliable predictor of adverse outcomes in cardiovascular diseases. There is scarce evidence regarding the association between NPAR and mortality among the older patients with AF.Methods: The research was conducted among 1141 patients with AF between January 2015 and June 2020, hospitalized at Huadong Hospital affiliated with Fudan University. The primary outcome were 28-day all-cause and cardiovascular mortality. Cox regression analysis and Kaplan-Meier survival curves were used to explore the correlation between NPAR and 28-day all-cause or cardiovascular mortality. Receiver operating characteristic (ROC) curve and the area under the curve (AUC) were performed for the predictive values of NPAR on prognosis.Results: The 28-day death rate from cardiovascular disease and all-causes were 3.3% and 8.7%, respectively. Continuous NPAR levels were positively associated with all-cause (HR 1.13, 95% CI 1.09, 1.16) and cardiovascular (HR 1.16, 95% CI 1.10, 1.23) mortality after adjustment for confounding variables. Relative to patients in the T1 group, those in higher NPAR tertiles also exhibit elevated risks of all-cause (P < 0.001) and cardiovascular mortality (P < 0.001). Furthermore, both all-cause and cardiovascular mortality rates rose with increasing NPAR in all analyzed subgroups.Conclusion: NPAR values are consistently positively related to 28-day all-cause and cardiovascular mortality rates in patients ≥ 80 years of age with AF.Keywords: cardiovascular disease, neutrophil, atrial fibrillation, mortality, older

Changzhi Chen,1 Jieyun Cai,2 Ling Li1 1The Second Nanning People’s Hospital Department of Hepatobiliary and Pancreatic, Nanning, People’s Republic of China; 2The Second Affiliated Hospital of Guang Xi Medical University, Nanning, People’s Republic of ChinaCorrespondence: Ling Li, The Second Nanning People’s Hospital Hepatobiliary and Pancreatic, No. 13, Dancun Ave, Nanning, 530000, People’s Republic of China, Tel +8613977125942, Email chenchangzhi1@163.com

Coastal wetlands, such as saltmarshes, are globally widespread and highly effective at capturing and storing ‘blue carbon’ and have the potential to regulate climate over varying timescales. Yet only Australia and the United States of America have national inventories of organic carbon held within saltmarsh habitats, hindering the development of policies and management strategies to protect and preserve these organic carbon stores. Here we couple a new observational dataset with 4,797 samples from 26 saltmarshes across Great Britain to spatially model organic carbon stored in the soil and the above and belowground biomass of Great British saltmarshes. Using average values derived from the 26 marshes, we deliver first-order estimates of organic carbon stocks across Great Britain’s 448 saltmarshes (451.66 km2). The saltmarshes of Great Britain contain 5.20 ± 0.65 Mt of organic carbon, 93% of which is in the soil. On average, the saltmarshes store 11.55 ± 1.56 kg C m-2 with values ranging between 2.24 kg C m-2 and 40.51 kg C m-2 depending on interlinked factors such as geomorphology, organic carbon source, sediment type (mud vs sand), sediment supply, and relative sea level history. These findings affirm that saltmarshes represent the largest intertidal blue carbon store in Great Britain, yet remain an unaccounted for component of the United Kingdom’s natural carbon stores.

Yuzhao Liu,1,&ast; Jingru Cai,2,&ast; Yangang Wang,1 Xiangli Zhao,3 Yun Qiao,4 Chuan-Ju Liu3 1Department of Endocrinology, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 2Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 3Department of Orthopaedic Surgery, New York University Grossman School of Medicine, New York, NY, USA; 4Department of Traditional Chinese Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yun Qiao; Chuan-Ju Liu, Email qlyyqy@163.com; Chuanju.Liu@nyulangone.orgObjective: This study is aimed to determine the metabolomic effects of the hybrid medicine formula Yi-Qi-Bu-Shen (YQBS) on the neurotransmitter aspects of cognitive impairment in diabetic rats.Methods: In the current study, streptozotocin (STZ) was used to induce diabetic animal model in male Sprague Dawley (SD) rats. After successful establishment of diabetic SD rats’ model, age-matched healthy SD rats and diabetic SD rats were treated with low and high doses of YQBS, and then tested for learning memory ability and analyzed for pathological changes. In addition, neurotransmitter metabolic changes in hippocampal subdivisions of rats from different treated groups were analyzed using liquid chromatography-mass spectrometry (LC-MS) technique.Results: YQBS could significantly improve memory-cognitive impairment in diabetic rats as evidenced by the shortening of latency to target and the reduction of latency first entrance to target. Moreover, YQBS also improved the pathological alterations in the hippocampal region in the brains of diabetic rats. Metabolomic analysis showed that the expression of noradrenaline hydrochloride was down-regulated and the expressions of levodopa and 5-hydroxytryptophan were up-regulated in the hippocampal tissues of diabetic rats treated with YQBS.Conclusion: These findings demonstrate that YQBS has protective effects against diabetic cognitive dysfunction, which might act through alteration in tyrosine and tryptophan metabolism.Keywords: diabetes mellitus, cognitive dysfunction, Yi-Qi-Bu-Shen, hippocampus, metabolomics

Changqiang Chen,1,&ast; Pu Li,1,&ast; Jiuming Chen,1,&ast; Chunxiao Liu,2 Xiaodan Wang,3 Jialin Cai,4 Enfei Xiang,4 Zhidong Gu,1,5 Peizhan Chen4 1Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Neurology & Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Clinical Research Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 5Department of Laboratory Medicine, Ruijin-Hainan Hospital, Shanghai Jiao Tong University School of Medicine (Hainan Boao Research Hospital), Hainan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peizhan Chen, Clinical Research Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201821, People’s Republic of China, Tel +86 13918550745, Email pzchen@me.com Zhidong Gu, Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201821, People’s Republic of China, Tel +86 13801653534, Email guzhidongruijin@163.comPurpose: Vitamin D, an essential nutrient and a pleiotropic steroid hormone, has been reported to be associated with the risk and severity in patients infected with Coronavirus Disease-2019 (COVID-19). The role of vitamin D in predicting clinical outcome for COVID-19 patients is unknown. Here, we aimed to determine the prognostic value of plasma 25(OH)D level in COVID-19 patients.Patients and Methods: A total of 158 patients infected with novel COVID-19 Omicron variants in Shanghai were recruited in this study and were categorized into three groups by the tertile levels of plasma 25(OH)D. Plasma 25(OH)D level was determined along with routine blood tests related to liver and renal functions in newly diagnosed COVID-19 patients at admission. The nucleic acid negative conversion time of throat swab samples was evaluated as the primary clinical outcome. The prognostic value of clinical characteristics and plasma 25(OH)D level was assessed using the Kaplan–Meier plot and Cox proportional hazards regression tests.Results: Higher level of plasma 25(OH)D level in COVID-19 patients was independently associated with shorter nucleic acid negative conversion time from COVID-19 infection (multivariate adjusted HR: 0.54, 95%CI: 0.35– 0.82, P=0.004, tertile 2 vs 1; multivariate adjusted HR: 0.60, 95%CI: 0.39– 0.90, P=0.014, tertile 3 vs 1).Conclusion: Plasma 25(OH)D level may serve as an independent prognostic factor in COVID-19 patient. Our findings indicate the protective roles of vitamin D supplementation in the regiment of patients with COVID-19.Keywords: SARS-CoV-2, COVID-19, plasma 25(OH)D level, nucleic acid negative conversion time

Xiao-Hui Song,1,&ast; Bo Liu,2,3,&ast; Fang Lei,2,4 Ye-Mao Liu,2,5,6 Xingyuan Zhang,2,4 Ze Chen,7 Peng Zhang,2,4 Xiao-Jing Zhang,2,4 Zhi-Gang She,1,2 Jingjing Cai,2,8 Jin-Hua Wang,9 Hongliang Li1– 3,6 1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Institute of Model Animal, Wuhan University, Wuhan, People’s Republic of China; 3Medical Science Research Center, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 4School of Basic Medical Science, Wuhan University, Wuhan, People’s Republic of China; 5Department of Cardiology, Huanggang Central Hospital of Yangtze University, Huanggang, People’s Republic of China; 6Huanggang Institute of Translational Medicine, Huanggang Central Hospital of Yangtze University, Huanggang, People’s Republic of China; 7Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 8Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 9Department of Neurology, Huanggang Central Hospital of Yangtze University, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongliang Li, Department of Cardiology, Renmin Hospital of Wuhan University, Luojia Mount Wuchang, Wuhan, 430072, People’s Republic of China, Tel/Fax +86-27-68759302, Email lihl@whu.edu.cn Jin-Hua Wang, Department of Neurology, Huanggang Central Hospital of Yangtze University, Hubei, 438000, People’s Republic of China, Email wangjinhua1985@qq.comPurpose: Emerging evidence suggested that metabolic dysfunction-associated fatty liver disease (MAFLD) was significantly associated with atherosclerotic diseases. Atherosclerosis in the peripheral arteries is the most common cause of peripheral arterial disease (PAD), which has not been substantially controlled in the past. We aimed to investigate the association between MAFLD and PAD in the Chinese population.Patients and Methods: This observational study covered 102,115 participants who underwent health checkups with detailed examinations for PAD and MAFLD. PAD was measured by ankle-brachial index, and MAFLD was diagnosed by abdominal ultrasound. The generalized linear mixed models and random-effects Cox proportional hazards models were used to analyze the relationship between MAFLD and PAD.Results: The baseline characteristics showed that patients with MAFLD had higher prevalence of PAD compared with those without MAFLD (2.7% vs 2.2%). Compared to non-MAFLD, the individuals with MAFLD were associated with a higher risk of the presence of PAD (adjusted odds ratio: 1.30, 95% confidence interval (CI): 1.19– 1.42, P < 0.001). In the prospective cohort study, 6833 participants underwent a follow-up of 2.76 (standard deviation: 1.36) years, and MAFLD at baseline was a higher risk of associated with incident PAD (adjusted hazards ratio: 1.67, 95% CI: 1.17– 2.38, P = 0.005). Moreover, with the accumulation of metabolic abnormalities, the risk of the PAD was increased in the individuals with MAFLD. Furthermore, MAFLD attributed risk of PAD was more evident in participants without metabolic comorbidities.Conclusion: MAFLD was associated with a significantly higher risk for the prevalence and incidence of PAD in the Chinese population. The finding suggested that individuals with MAFLD are not only have a higher risk of coronary heart diseases but also have an increased risk of atherosclerosis in peripheral arteries.Keywords: chronic liver disease, metabolic disorder, arteriosclerosis, cross-sectional study, prospective cohort study

Chen Huang,1,&ast; Chunbin Li,2,3,&ast; Jiaxuan Cai,1,4,&ast; Jie Chen,1 Baobei Wang,1 Mengxia Li,1 Wei Zhou,5 Jianguo Wang,3 Pengfei Zhang,2 Jian V Zhang1 1Center for Energy Metabolism and Reproduction, Shenzhen Key Laboratory of Metabolic Health, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People’s Republic of China; 2Guangdong Key Laboratory of Nanomedicine, CAS Key Laboratory of Health Informatics, Shenzhen Bioactive Materials Engineering Laboratory for Medicine, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People’s Republic of China; 3College of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot, People’s Republic of China; 4Shenzhen College of Advanced Technology, University of Chinese Academy of Sciences, Shenzhen, People’s Republic of China; 5Gynecology Department, Huazhong University of Science and Technology Union, Shenzhen Hospital, Shenzhen, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian V Zhang; Pengfei Zhang, Shenzhen Institute of Advance Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, 518055, People’s Republic of China, Tel +86 0755-86392591, Fax +86 0755-86585222, Email jian.zhang@siat.ac.cn; pf.zhang@siat.ac.cnIntroduction: Lack of highly expressed tumor target and ligands limits application of nano-medicine against triple-negative breast cancer (TNBC). Previous study reported that placenta-derived oncofetal chondroitin sulfate glycosaminoglycan chain (CSA) expressed on 90% of stage I–III invasive ductal breast carcinomas. Our study found the CSA anchor protein VAR2CSA derived small peptide plCSA had strong binding activity with TNBC cell lines and tumor tissue. Here, we combined the AIEgens TBZ-DPNA and therapy drug paclitaxel (PTX) to fabricate near-infrared fluorescence-guided nanodrug (plCSA-NP) to investigate its targeting and anti-tumor effect on TNBC.Methods: We synthesized and purified TBZ-DPNA with one step, measured optical properties and photoluminescence (PL) spectra. We prepared nanodrug plCSA-NP by encapsulating TBZ-DPNA and PTX and conjugating them with peptide plCSA. We evaluated plCSA-NP targeting activity by examining AIEdots fluorescence signal on TNBC cell lines and subcutaneous and lung metastatic mouse model. We assessed PTX delivery effect by cytotoxicity assay on TNBC line and tumor growth of subcutaneous and lung metastatic mouse models.Results: PL spectra and TEM imaging results showed plCSA-NP had maximum emission feature at 718 nm and nearly monodispersed nanosphere with an average diameter of 70 nm. In vitro studies showed plCSA-NPs had high affinity and cytotoxicity with TNBC cell lines. In vivo subcutaneous and lung metastasis mouse studies showed plCSA-NPs accumulated on TNBC tumor tissue, and significantly prevented TNBC subcutaneous and lung metastasis tumor growth.Conclusion: In conclusion, we provide solid evidence for chondroitin sulfate targeting peptide plCSA guided nanodrug, exhibit good targeting efficiency and therapeutic effect against TNBC primary and lung metastatic tumor growth.Keywords: triple-negative breast cancer, lung metastasis, chemotherapy, aggregation-induced emission, drug delivery system, plCSA

Jian Li,1– 3 Qing Zhang,1– 3 Jiahui Cai,1– 3 Yibo Yang,1– 3 Jia Zhang,1– 3 Yanting Gao,1– 3 Shihe Liu,1– 3 Kun Li,1– 3 Ming Shi,1– 3 Zhiwei Liu,1– 3 Liming Gao4 1College of Environmental & Chemical Engineering, Yanshan University, Qinhuangdao, People’s Republic of China; 2Applied Chemistry Key Laboratory of Hebei Province, Yanshan University, Qinhuangdao, People’s Republic of China; 3Key Laboratory of Nanobiotechnology of Hebei Province, Yanshan University, Qinhuangdao, People’s Republic of China; 4Oncology Department, the First Hospital of Qinhuangdao, Qinhuangdao, People’s Republic of ChinaCorrespondence: Jian Li, College of Environment & Chemical Engineering, Yanshan University, No. 438 Hebei Street, Qinhuangdao, 066004, People’s Republic of China, Tel +86-335-8061569, Fax +86-335-8061569, Email Lijianbio@ysu.edu.cnIntroduction: During the combined treatment of tumors, the non-interfering transportation of drugs with different solubilities and the controllable sequential release are the main challenges. Here, we reported a double-chamber “Dandelion” -like sequential drug delivery system to realize the sequential release of different drugs for treating malignant tumors synergistically.Methods: After synthesizing mesoporous silica nanoparticles (MSN) by template method, a hydrophilic chemotherapy drug doxorubicin (DOX) was loaded into the channels of mesoporous silica (MSN) and locked with polydopamine (PDA) coating. Next, β-cyclodextrin (β-CDs) was decorated on PDA by Michael addition reaction, and the hydrophobic photosensitizer chlorin e6 (Ce6) was encapsulated into the hydrophobic chambers of β-CDs. Finally, AS1411 was modified on the surface of PDA and obtained DOX@MSN@PDA-β-CD/Ce6-AS1411 nanoparticles (DMPCCA) through which orthogonal loading and effective controlled release of different drugs were realized.Results: Under the sequential irradiations of 808 nm and 660 nm near-infrared (NIR) laser, PDA promoted the extensive release of Ce6 firstly while playing the effect of photothermal therapy (PTT), further to achieve the effect of photodynamic therapy (PDT) of Ce6. Meanwhile, the rapid release of DOX loaded in MSN channels showed a time lag of about 5 h after Ce6 release, through which it maximized the chemotherapeutic effect. Besides, the present drug loading nano-platform combined passive tumor-targeting effect given by EPR and active tumor-targeting effect endowed by AS1411 realized PTT-PDT-chemotherapy triple mode synergistic combination.Conclusion: We offer a general solution to address the key limitations for the delivery and sequential release of different drugs with different solubilities.Graphical Abstract: Keywords: sequential release, mesoporous silica, chemotherapy, tumor-targeting, PTT-PDT-chemotherapy combination

Taoying Lu,1– 3 Jingwen Yan,4 Jianfang Chang,5 Jianxiong Cai,1– 3 Lingjia Yin,1,3,6 Jiamin Yuan,1,7 Li Huang,1,7 Yingshuai Li,8 Minghua Bai,9 Kit-Tai Hau,5 Darong Wu,1– 3 Zhimin Yang1,7 1State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 3Program for Outcome Assessment in TCM, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China; 4The Second Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 5Department of Education Psychology, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China; 6Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden; 7Health Construction Administration Center, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China; 8National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 9School of Traditional Chinese Medicine/National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of ChinaCorrespondence: Darong Wu; Zhimin Yang, State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, 111 Dade Road, Guangzhou, 510120, People’s Republic of China, Tel +86 13808869436 ; +86 13822296363, Email darongwu@gzucm.edu.cn; yangyo@vip.tom.comBackground: Body constitution is a fundamental concept in traditional Chinese medicine (TCM) for clinical diagnosis, treatment of illness, and community-based health promotion. Clinical assessment of patients’ body constitutions, however, has never been easy and consistent, even by well-trained clinicians and TCM practitioners. Therefore, questionnaires such as the popular Constitution in Chinese Medicine Questionnaire (CCMQ) can be an appealing and convenient assessment alternative. The present research borrowed advanced methodologies for questionnaire development in psychology and other social sciences to examine the performance of the CCMQ in terms of (i) the strength of relations of each item with its designated constitution, (ii) the reliabilities of each constitution, and (iii) the overall 9-constitution structure. This research provided empirical evidence to support the use of the CCMQ and proposed directions for refinement in future revisions of the CCMQ or similar measures.Methods: A total of 1571 volunteers from three villages in southern China participated in the CCMQ survey. The item characteristics, reliabilities, interconstitution correlations, and confirmatory factor analysis of the 9-body-constitution structure were examined.Results: The results generally supported the appropriateness of the clinical observations (the questionnaire items) and the CCMQ 9-constitution classification structure. Nevertheless, some relatively weaker items, item pairs with similar meanings, and highly overlapping constitutions were identified for future CCMQ revisions.Conclusion: The CCMQ measured the 9 constitutions efficiently and with reasonably good reliability and construct validity. Given the various challenges to assessing TCM body constitutions even by experienced clinicians, the CCMQ provides an appealing alternative to measure the Chinese body constitutions of healthy participants in large-scale research or community health promotion programs. The present study also demonstrated how advanced methodologies in social sciences can help validate and refine the CCMQ and similar complementary medicine measures.Keywords: Chinese constitution, body constitution, CCMQ, Constitution in Chinese Medicine Questionnaire, reliability, construct validity

Huan Tang, Wenjuan Di, Hanmei Qi, Juan Liu, Jing Yu, Jinmei Cai, Bing Lai, Guoxian Ding, Peng Cheng Department of Gerontology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Peng Cheng, Department of Gerontology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, Jiangsu, People’s Republic of China, Tel +86-25-68305171, Fax +86-25-83724440, Email cphh@sohu.comPurpose: This study was designed to explore age-related changes in trabecular bone score (TBS) and bone mineral density (BMD) in Chinese men through cross-sectional and longitudinal studies.Patients and Methods: We included adult men who had at least twice TBS and BMD examinations in our hospital between January 2013 and December 2020. All men were divided into an age subgroup per 10 years, comparing differences in baseline lumbar spine (LS) TBS and BMD at various parts between each age group and analyzing age-related changes in TBS and BMD during follow-up.Results: Baseline data showed that in men aged 36 to 85 years, BMD in the hip region showed a decreasing trend with age (P for trend < 0.01). However, TBS reached a high value around the age of 50, after which it decreased with age (P for trend = 0.03). During a mean follow-up of 3 years, the average annual change rate at TBS was − 0.17% in men aged 36 to 85 years, with the fastest decrease rate − 1.08% at 66 to 75 years (P < 0.05). The mean annual rate of change in LS BMD in different age subgroups increased with age (P for trend = 0.001). There was no significant decrease in mean annual change in BMD in hip regions.Conclusion: In men aged 36∼ 85 years, the trend of TBS was inconsistent with BMD. Men experience a high value of LS TBS around age 50, later than the commonly believed age of peak BMD, which may reflect developmental differences between bone microstructure and bone minerals. The TBS may be used as a better indicator of changes in bone strength than BMD in adult men at short-term follow-up. The rapid loss of TBS at age 66 to 75 may have implications for the prevention and medication of osteoporosis in men.Keywords: age-related, bone loss, bone mineral density, men, osteoporosis, trabecular bone score

Junhong Cai,1 Siyuan Peng,2 Haibo Wang,2 Shan Bao2 1Medical Laboratory Center, Hainan General Hospital/Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570311, People’s Republic of China; 2Department of Gynaecology and Obstetrics, Hainan General Hospital/Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570311, People’s Republic of ChinaCorrespondence: Shan Bao, Tel/Fax +86-0898-68642629, Email baoshan3@126.comBackground: Endometrial carcinoma (EC) is one of the most common malignant gynecological malignancies. BCL11A gene may have a tumor-suppressor role in EC. Until now, no studies have reported the effect of BCL11A variants on EC predisposition in Chinese population.Methods: Six BCL11A polymorphisms were genotyped using Agena MassARRAY system among 509 EC patients and 506 matched healthy women. Risk assessment of the BCL11A polymorphisms for EC risk was performed by calculating odds ratios (OR) with 95% confidence intervals (CI) through logistic regression models.Results: We found that rs7581162 (OR = 1.29, p = 0.012), rs10189857 (OR = 1.26, p = 0.028), rs1427407 (OR = 1.30, p = 0.015), rs766432 (OR = 1.27, p = 0.025), and rs6729815 (OR = 1.32, p = 0.008) in BCL11A were associated with higher susceptibility to EC in Chinese Han women. Age and BMI stratified analysis displayed that the risk association between BCL11A variants and EC predisposition might be age- and BMI-dependent. Haplotype analysis revealed that Ars10189857Trs1427407 and Grs10189857Grs1427407 haplotypes were related to an increased risk of EC. MDR analysis indicated that rs1427407 was the most influential attributor on EC risk in the single-locus model, and the best combination was the two-locus model containing rs7581162 and rs766432.Conclusion: Our study provided the first evidence that rs7581162, rs10189857, rs1427407, rs766432, and rs6729815 in BCL11A were risk factors for EC in Chinese Han women. These findings add our understanding of the role of BCL11A gene in EC pathogenesis.Keywords: endometrial carcinoma, BCL11A variants, susceptibility, haplotype analysis, MDR analysis

Wei Tang,1,&ast; Qian Lv,1,&ast; Xiao Huang,2,&ast; Yuzhen Li,2 JunJie Zou,1 Jiaoyang Zheng,1 Liangliang Sun,1 Yi Bao,1 Haiyan Chen,1 Tuo Li,1 Bei Zhang,1 Song Xue,1 Yan Song,1 Xingxing Zhang,1 Xiangfang Chen,1 Jiping Cai,2 Yongquan Shi1 1Department of Endocrinology, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, People’s Republic of China; 2Department of Ophthalmology, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangfang Chen; Yongquan Shi, Department of Endocrinology, Second Affiliated Hospital of Naval Medical University, No. 415 Fengyang Road, Huangpu District, Shanghai, 200003, People’s Republic of China, Email chenxiangfang@smmu.edu.cn; young.stone@smmu.edu.cnObjective: Thyroid-associated ophthalmopathy (TAO) is an autoimmune disease that involves the remodeling of orbit and periorbital tissues. Thyroid-stimulating hormone receptor (TSHR) and insulin-like growth factor 1 receptor (IGF-1R) may stimulate the activation of autoimmunity in TAO, but the exact mechanism is unclear. We investigated whether IGF-1R/TSHR modulation in TAO may involve microRNA regulation.Methods: We conducted microarray analysis using RNA from the orbital connective tissue samples of 3 healthy and 3 patients with TAO. The involvement of differentially regulated microRNA in IGF-1R/TSHR modulation in TAO was evaluated in orbital fibroblasts (OFs) and female BALB/c mice.Results: Using hierarchical cluster analysis, we identified that miR-143 was downregulated in TAO. The expression levels of miR-143 in OFs were significantly reduced under IL-1B stimulation. However, OF proliferation and inflammatory responses decreased when miR-143 is overexpressed. In contrast, the suppression of miR-143 increased levels of inflammatory markers (IL-6, IL-8, MCP1) and hyaluronan accumulation. Moreover, overexpression of miR-143 significantly lowers levels of IGF-1R and TSHR. A luciferase assay indicated that miR-143 targets the 3′-UTR of IGF-1R. Increases in the expression of IGF-1R increased the expression of the inflammasome marker NLRP3 and apoptotic marker cleaved caspase-1; however, miR-143 overexpression decreased levels of IGF-1R, TSHR, NLRP3, cleaved caspase 1, IL-1B, and IL-18. In a mouse model of TAO, overexpression of miR-143 significantly reduced levels of IGF-1R and attenuated the adipogenesis associated with TAO.Conclusion: We found that miR-143 directly targets IGF-1R to alleviate the inflammatory response in TAO by indirectly decreasing levels of TSHR and inactivating NLRP3.Keywords: thyroid-associated ophthalmopathy, miR-143, thyroid-stimulating hormone receptor, insulin-like growth factor 1 receptor, NLRP3

Jia-Xin Cai,1– 3,&ast; Ji-Hua Liu,1– 3,&ast; Jun-Yong Wu,1– 3 Yong-Jiang Li,1– 3 Xiao-Han Qiu,1– 3 Wen-Jie Xu,1– 3 Ping Xu,1,2 Da-Xiong Xiang1– 3 1Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People’s Republic of China; 2Institute of Clinical Pharmacy, Central South University, Changsha, 410011, Hunan, People’s Republic of China; 3Hunan Provincial Engineering Research Center of Translational Medicine and Innovative Drug, Changsha, Hunan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ping Xu; Da-Xiong Xiang, Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People’s Republic of China, Email xuping1109@csu.edu.cn; xiangdaxiong@csu.edu.cnPurpose: In order to prepare a biomimetic nano-carrier which has inflammatory chemotaxis, homologous targeting and reduce immune clearance, for targeted chemotherapy of osteosarcoma, we fabricated the paclitaxel-loaded poly(lactic-co-glycolic) acid (PLGA) nanoparticles coated with 143B-RAW hybrid membrane (PTX-PLGA@[143B-RAW] NPs) and evaluate its anti-cancer efficacy in vitro and vivo.Methods: PTX-PLGA@[143B-RAW] NPs were prepared by the ultrasonic method and were characterized by size, zeta potential, polymer dispersion index (PDI), Coomassie bright blue staining, transmission electron microscopy (TEM) and high performance liquid chromatography (HPLC). Cellular uptake, cell viability assay, flow cytometry and chemotactic effect of PTX-PLGA@[143B-RAW] NPs were evaluated in vitro. Biodistribution, anti-cancer therapeutic efficacy and safety of PTX-PLGA@[143B-RAW] NPs were evaluated in 143B osteosarcoma xenograft mice.Results: The hybrid membrane successfully coated onto the surface of PLGA nanoparticles. PTX-PLGA@[143B-RAW] NPs had a drug loading capacity of 4.24 ± 0.02% and showed targeting ability to osteosarcoma. PTX-PLGA@[143B-RAW] NPs showed high cellular uptake and improved anti-cancer efficacy against 143B cells. More importantly, PTX-PLGA@[143B-RAW] NPs treatment suppressed tumor growth in tumor-bearing mice with minimal damage to normal tissues.Conclusion: PTX-PLGA@[143B-RAW] NPs could be used for targeted drug delivery and osteosarcoma therapy.Keywords: biomimetic nano-drug delivery system, osteosarcoma, paclitaxel, targeted therapy

Political discourse around coastal wetland restoration and blue carbon management strategies has increased in the past decade, yet carbon storage has neither been a reason for restoration, nor a criterion to measure the success of current saltmarsh restoration schemes in the UK. To maximise climate change mitigation through saltmarsh restoration, knowledge on the key drivers of carbon stock variability is required. We use restored saltmarshes of similar age, paired with adjacent natural marshes as references, to identify drivers of carbon stocks following managed realignment within an estuary in southeastern England. From surficial soil cores (top 30 cm), we measured carbon stock alongside environmental characteristics. Carbon stock between natural and restored sites were similar after ~ 30 years when restored sites were above mean high water neap (MHWN) tidal levels. Elevated marsh platforms likely provide suitable conditions for the development of mature plant communities associated with greater capture and production of organic carbon. The restored site at Tollesbury (Essex, UK) had a 2-fold lower carbon stock than other restored sites in the estuary. We attribute this to the site’s low position in the tidal frame, below MHWN tidal levels, coupled with low sediment supply and the dominance of pioneer plant communities. As blue carbon is anticipated to become an important facet of saltmarsh restoration, we recommend that sites above MHWN tidal levels are selected for managed realignment or that preference is given to coastlines with a high sediment supply that may rapidly elevate realignment sites above MHWN. Alternatively, elevation could be artificially raised prior to realignment. Restoration schemes aiming to maximise climate change mitigation should also encourage the establishment of key plant species (e.g., Atriplex portulacoides in our study) to enhance carbon stocks. However, the overall goal of restoration ought to be carefully considered as trade-offs in ecosystem services may ensue if restoration for climate change mitigation alone is pursued.

Weikang Chen,1,&ast; Wenhao Zhang,2,3,&ast; Tao Zhou,1,&ast; Jian Cai,1 Zhixian Yu,1 Zhigang Wu1 1Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China; 2The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 325000, People’s Republic of China; 3Department of Urology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 325000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhixian Yu; Zhigang WuDepartment of Urology, The First Affiliated Hospital of Wenzhou Medical University, No. 2, Fuxue Road Lucheng District, Wenzhou, Zhejiang, 325000, People’s Republic of ChinaEmail yuzx515@163.com; andrologywzg@wmu.edu.cnBackground: Bladder cancer (BC), as the most common urinary system tumor type and the main cause of tumor-related death, has an unsatisfactory prognosis. In recent years, related literature has proposed that cell pyroptosis is an inflammatory form of programmed cell death. However, in BC, the relationship between the expression of pyroptosis-related genes and the prognosis has not been elucidated.Methods: We got the RNA sequencing data from TCGA and GEO datasets. Fifty-two pyroptosis-related genes were extracted for further explore. Then, we compared the gene expression levels between the normal bladder and BC tissues. After that, we develop and validate a pyroptosis-related gene prognostic model and made following functional enrichment analysis and single-sample gene set enrichment analysis of the differentially expressed genes between the high- and low-risk groups.Results: Twenty-nine differentially expressed genes (DEGs) were found between normal and tumor tissues. Based on the median score calculated by the risk score formula from 8 pyroptosis-related genes, 414 patients were equally divided into low- and high-risk subgroups. The survival probability of BC patients in the high-risk group was significantly lower than that in the low-risk group (P < 0.001). Through multivariate analysis, our risk score is an independent factor predicting OS in BC patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis show that high-risk populations are rich in immune-related genes and have a decreased immune status. All the above results have been externally verified from GEO cohort.Conclusion: Pyroptosis-related genes are closely related to tumor immunity and are a potential prognostic tool for predicting BCs.Keywords: pyroptosis, bladder cancer, immune, prognosis, TCGA

Lijin Lin,1– 4,&ast; Ze Chen,4,5,&ast; Ting Ding,1,2,&ast; Hui Liu,4,6,&ast; Feng Zhou,4,7 Xuewei Huang,3,4 Xingyuan Zhang,4,8 Weifang Liu,4,8 Bing-Hong Zhang,9 Yufeng Yuan,10 Peng Zhang,4,8 Xiao-Jing Zhang,4,8 Zhi-Gang She,3,4 Jingjing Cai,4,11 Wenping Chen,1,2 Hongliang Li2– 4,7 1Department of Endocrinology, Huanggang Central Hospital, Huanggang, People’s Republic of China; 2Huanggang Institute of Translational Medicine, Huanggang, People’s Republic of China; 3Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 4Institute of Model Animal of Wuhan University, Wuhan, People’s Republic of China; 5Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 6Neonatology of Gastroenterology, Tongren Hospital of Wuhan University & Wuhan Third Hospital, Wuhan, People’s Republic of China; 7Medical Science Research Center, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 8Basic Medical School of Wuhan University, Wuhan, People’s Republic of China; 9Neonatology Department, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 10Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 11Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongliang Li; Wenping Chen Email lihl@whu.edu.cn; chenwenping@hgyy.org.cnPurpose: To analyze the impact of hyperglycemia on the clinical outcome of COVID-19 in patients with newly diagnosed diabetes (NDD).Patients and Methods: We performed a retrospective study of 3114 cases of COVID-19 without pre-existing diabetes, 351 of which had NDD, in Hubei Province, China. The Cox regression model was used to calculate the risk of adverse clinical outcomes comparing the NDD vs non-NDD group before and after propensity score-matched (PSM) analysis. Patients with NDD were further divided into a sustained hyperglycemia group, a fluctuating group, and a remitted group based on their blood glucose levels during hospitalization as well as into hypoglycemic agent users and nonusers.Results: Compared to the non-NDD individuals, individuals with NDD had a significantly increased risk of all-cause mortality (adjusted HR after PSM, 2.65; 95% CI, 1.49– 4.72; P = 0.001) and secondary outcomes involving organ damage during the 28-day follow-up period. Subgroup analyses indicated that among individuals with NDD, the individuals with remitted hyperglycemia had the lowest 28-day mortality, whereas those with sustained hyperglycemia had the highest (IRR 24.27; 95% CI, 3.21– 183.36; P < 0.001). Moreover, individuals treated with hypoglycemic agents had significantly lower all-cause mortality than those not treated with hypoglycemic agents (IRR 0.08; 95% CI, 0.01– 0.56; P < 0.001).Conclusion: Our study reinforces the clinical message that NDD is strongly associated with poor outcomes in COVID-19 patients. Furthermore, resolved hyperglycemia in the later phase of the disease and the use of hypoglycemic agents were associated with improved prognosis in patients with NDD.Keywords: COVID-19, newly diagnosed diabetes, hyperglycemia, prognosis, blood glucose

Yanwu Jin,1 Shanshan Zhao,1 Jiahui Cai,2 Marcelle Blessing,3 Xin Zhao,1 Haizhu Tan,2 Jinlei Li3 1Department of Anesthesiology, Second Hospital of Shandong University, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Preventive Medicine, Shantou University Medical College, Shantou, Guangdong, People’s Republic of China; 3Department of Anesthesiology, Yale University School of Medicine, New Haven, CT, USACorrespondence: Jinlei Li; Haizhu TanDepartment of Anesthesiology, Yale University School of Medicine, 333 Cedar Street, TMP 3, New Haven, CT, 06520-8051, USATel +1 203 785-2802Fax +1 203 785-6664Email jinlei.li@yale.edu; linnanqia@126.comBackground: Spine surgery causes severe pain and can be associated with significant opioid utilization; however, the evidence for opioid-sparing analgesic techniques such as erector spinae plane (ESP) block from controlled studies is limited. We aimed to investigate the analgesic effects of ESP block in lumbar laminoplasty.Methods: In this prospective, double-blind, controlled single-center trial, 62 consecutive elective lumbar laminoplasty patients were randomized into either a control group (Group G, N=32) or a treatment group (Group E, N=30). Group G received general anesthesia and multimodal analgesia, similar to group E, while Group E received additional bilateral ESP block after induction of general anesthesia. The primary outcome was postoperative pain scores for the first 48 h after surgery, and the secondary outcomes analyzed included intraoperative anesthetic usage, perioperative analgesic consumption, return of bowel function and satisfaction for acute pain management indicated by overall benefit of analgesia score (OBAS).Results: Significant differences in pain scores over time were found between the two groups (P=0.010), with Group E patients having significantly lower pain scores than Group G during the first six hours (P=0.000). The opioid consumption in Group G was significantly higher than in Group E both intraoperatively (P=0.000) and postoperatively (P=0.0005). Group E patients had lower intraoperative sevoflurane requirement, improved satisfaction with pain management, and earlier return of bowel function than Group G patients.Conclusion: ESP block is effective in reducing postoperative pain scores and lowering opioid utilization (both intraoperatively and postoperatively), resulting in improved patient satisfaction for pain management in lumbar laminoplasty.Keywords: erector spinae plane block, laminoplasty, spine, perioperative pain, opioid, short-term outcome

Shutian Zhang,1,2,&ast; Yufeng Yan,3,&ast; Yongze Wang,1,2 Zhaodong Sun,1,2 Chengzhi Han,1,2 Xinyi Qian,1,2 Xiaorong Ren,1,2 Yi Feng,4 Jian Cai,5 Chunmei Xia1 1Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, People’s Republic of China; 2Department of Clinical Medicine, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of China; 3Experimental Teaching Center of Basic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, People’s Republic of China; 4Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, People’s Republic of China; 5Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200240, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunmei XiaDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, People’s Republic of ChinaTel +86 21 54237612-805Email cmxia@fudan.edu.cnJian CaiDepartment of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200240, People’s Republic of ChinaEmail feele@sina.comPurpose: Glial activation and the disorders of cytokine secretion induced by endoplasmic reticulum stress (ERS) are crucial pathogenic processes in establishing ischemia/reperfusion (I/R) injury of the brain and spinal cord. This present study aimed to investigate the effects of mucous-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) on spinal cord ischemia/reperfusion (SCI/R) injury via regulating glial ERS.Methods: SCI/R was induced by thoracic aorta occlusion-reperfusion in rats. The MALT1-specific inhibitor MI-2 or human recombinant MALT1 protein (hrMALT1) was administrated for three consecutive days after the surgery. Immunofluorescent staining was used to detect the localization of MALT1 and ERS profiles in activated astrocyte and microglia of spinal cord. The ultrastructure of endoplasmic reticulum (ER) was examined by transmission electron microscopy. Blood-spinal cord barrier (BSCB) disruption and noninflammatory status were assessed. The neuron loss and demyelination in the spinal cord were monitored, and the hindlimb motor function was evaluated in SCI/R rats.Results: Intraperitoneally postoperative MI-2 treatment down-regulated phos-NF-κB (p65) and Bip (ERS marker protein) expression in the spinal cord after SCI/R in rats. Intraperitoneal injection MI-2 attenuated the swelling/dilation of ER of the glia in SCI/R rats. Furthermore, MI-2 attenuated I/R-induced Evans blue (EB) leakage and microglia M1 polarization in spinal cord, implying a role for MALT1 in the BSCB destruction and neuroinflammation after SCI/R in rats. Furthermore, intrathecal injection of hrMALT1 aggravated the fragmentation of neuron, loss of neurofibrils and demyelination caused by I/R, while 4-PBA, an ERS inhibitor, co-treatment with hrMALT1 reversed these effects in SCI/R rats. hrMALT1 administration aggravated the motor deficit index (MDI) scoring, while 4-PBA co-treatment improved SCI/R-induced motor deficits in rats.Conclusion: Inhibition of MALT1 alleviates SCI/R injury-induced neuroinflammation by modulating glial endoplasmic reticulum stress in rats.Keywords: MALT1, blood-spinal cord barrier, astrocytes, microglia, endoplasmic reticulum stress, spinal cord ischemia/reperfusion injury

Fengqi Liu,1,2,&ast; Li Zhong,1,2,&ast; Feifei Zhou,3,&ast; Cheng Zheng,1,4 Kai Zhang,1 Jiachang Cai,5 Hongwei Zhou,5 Kankai Tang,2 Zhaohui Dong,2 Wei Cui,1 Gensheng Zhang1 1Department of Critical Care Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, People’s Republic of China; 2Department of Critical Care Medicine, First Affiliated Hospital, Huzhou Teachers College, The First People’s Hospital of Huzhou, Huzhou, 313000, Zhejiang, People’s Republic of China; 3Department of Critical Care Medicine, Ningbo Medical Center, Li Huili Hospital, Ningbo, Zhejiang, 315040, People’s Republic of China; 4Department of Critical Care Medicine, Taizhou Municipal Hospital, Taizhou, Zhejiang, 318000, People’s Republic of China; 5Department of Clinical Microbiology Laboratory, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gensheng Zhang; Wei CuiDepartment of Critical Care Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, cc88 Jiefang Road, Hangzhou, 310009, People’s Republic of ChinaTel +86-571-8778-3636; +86-571-8778-3551Fax +86-571- 87022776Email genshengzhang@zju.edu.cn; zricu@zju.edu.cnPurpose: Candida albicans (C. albicans) candidemia has been well reported in previous studies, while research on non-albicans Candida (NAC) bloodstream infections remains poorly explored. Therefore, the present study aimed to investigate the clinical characteristics and outcomes of patients with NAC candidemia.Patients and Methods: We recruited inpatients with candidemia from January 2013 to June 2020 in a tertiary hospital for this retrospective observational study.Results: A total of 301 patients with candidemia were recruited in the current study, including 161 (53.5%) patients with NAC candidemia. The main pathogens in NAC candidemia were Candida tropicalis (C. tropicalis) (23.9%), Candida parapsilosis (15.6%) and Candida glabrata (10.3%). Patients with NAC candidemia had more medical admissions (P=0.034), a higher percentage of hematological malignancies (P=0.007), a higher frequency of antifungal exposure (P=0.012), and more indwelling peripherally inserted central catheters (P=0.002) than those with C. albicans candidemia. In a multivariable analysis, prior antifungal exposure was independently related to NAC candidemia (adjusted odds ratio [aOR], 0.312; 95% confidence interval [CI], 0.113– 0.859). Additionally, NAC was obviously resistant to azoles, especially C. tropicalis had a high cross-resistance to azoles. However, no significant differences were noted in the mortality rates at 14 days, 28 days and 60 days between these two groups.Conclusion: NAC is dominant in candidemia, and prior antifungal exposure is an independent risk factor. Of note, although the outcomes of NAC and C. albicans candidemia are similar, drug resistance to specific azoles as well as cross-resistance frequently occurs in patients with NAC candidemia, and this drug resistance deserves attention in clinical practice and further in-depth investigation.Keywords: non-albicans candidemia, clinical features, risk factor, cross-resistance

Jiarong Cai,1,&ast; Fei Yang,1,&ast; Xuelian Chen,1 He Huang,2 Bin Miao3 1Department of Urology, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510630, People’s Republic of China; 2General Surgery Department, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510630, People’s Republic of China; 3Department of Organ Transplantation, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510630, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: He HuangGeneral Surgery Department, the Third Affiliated Hospital of Sun Yat-sen University, No. 600, Tianhe Road, Guangzhou, Guangdong, 510630, People’s Republic of ChinaEmail huangh85@mail.sysu.edu.cnBin MiaoDepartment of Organ Transplantation, the Third Affiliated Hospital of Sun Yat-Sen University, No. 600, Tianhe Road, Guangzhou, Guangdong, 510630, People’s Republic of ChinaTel +86-20-82179517Fax +86-20-82179517Email miaobin@mail.sysu.edu.cnBackground: Radical prostatectomy is the main treatment for prostate cancer (PCa), a common cancer type among men. Recurrence frequently occurs in a proportion of patients. Therefore, there is a great need to early screen those patients to specifically schedule adjuvant therapy to improve the recurrence-free survival (RFS) rate. This study aims to develop a biomarker to predict RFS for patients with PCa based on the data of methylation, an important heritable contributor to carcinogenesis.Methods: Methylation expression data of PCa patients were downloaded from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus database (GSE26126), and the European Bioinformatics Institute (E-MTAB-6131). The stable co-methylation modules were identified by weighted gene co-expression network analysis. The genes in modules were overlapped with differentially methylated RNAs (DMRs) screened by MetaDE package in three datasets, which were used to screen the prognostic genes using least absolute shrinkage and selection operator analyses. The prognostic performance of the prognostic signature was assessed by survival curve analysis.Results: Five co-methylation modules were considered preserved in three datasets. A total of 192 genes in these 5 modules were overlapped with 985 DMRs, from which a signature panel of 11 methylated messenger RNAs and 3 methylated long non-coding RNAs was identified. This signature panel could independently predict the 5-year RFS of PCa patients, with an area under the receiver operating characteristic curve (AUC) of 0.969 for the training TCGA dataset and 0.811 for the testing E-MTAB-6131 dataset, both of which were higher than the predictive accuracy of Gleason score (AUC = 0.689). Also, the patients with the same Gleason score (6– 7 or 8– 10) could be further divided into the high-risk group and the low-risk group.Conclusion: These results suggest that our prognostic model may be a promising biomarker for clinical prediction of RFS in PCa patients.Keywords: prostate cancer, recurrence-free survival, methylation, prognostic signature

Yangnan Hu,1,&ast; Dan Li,2,&ast; Hao Wei,3,&ast; Shan Zhou,1 Wei Chen,1 Xiaoqian Yan,1 Jaiying Cai,1 Xiaoyan Chen,1 Bo Chen,4 Menghui Liao,1 Renjie Chai,1,5 Mingliang Tang1,5,6 1State Key Laboratory of Bioelectronics, School of Life Sciences and Technology, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing, 210096, People’s Republic of China; 2School of Biology, Food and Environment, Hefei University, Hefei, 230601, People’s Republic of China; 3Department of Otorhinolaryngology Head and Neck Surgery, Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, 210000, People’s Republic of China; 4Materials Science and Devices Institute, Suzhou University of Science and Technology, Suzhou, 215009, People’s Republic of China; 5Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, People’s Republic of China; 6Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Medical College, Soochow University, Suzhou, 215000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Renjie Chai; Mingliang Tang Email renjiec@seu.edu.cn; mltang@suda.edu.cnIntroduction: Neuroregeneration is a major challenge in neuroscience for treating degenerative diseases and for repairing injured nerves. Numerous studies have shown the importance of physical stimulation for neuronal growth and development, and here we report an approach for the physical guidance of neuron orientation and neurite growth using superparamagnetic iron oxide (SPIO) nanoparticles and magnetic fields (MFs).Methods: SPIO nanoparticles were synthesized by classic chemical co-precipitation methods and then characterized by transmission electron microscope, dynamic light scattering, and vibrating sample magnetometer. The cytotoxicity of the prepared SPIO nanoparticles and MF was determined using CCK-8 assay and LIVE/DEAD assay. The immunofluorescence images were captured by a laser scanning confocal microscopy. Cell migration was evaluated using the wound healing assay.Results: The prepared SPIO nanoparticles showed a narrow size distribution, low cytotoxicity, and superparamagnetism. SPIO nanoparticles coated with poly-L-lysine could be internalized by spiral ganglion neurons (SGNs) and showed no cytotoxicity at concentrations less than 300 μg/mL. The neurite extension of SGNs was promoted after internalizing SPIO nanoparticles with or without an external MF, and this might be due to the promotion of growth cone development. It was also confirmed that SPIO can regulate cell migration and can direct neurite outgrowth in SGNs preferentially along the direction imposed by an external MF.Conclusion: Our results provide a fundamental understanding of the regulation of cell behaviors under physical cues and suggest alternative treatments for sensorineural hearing loss caused by the degeneration of SGNs.Keywords: physical cues, neurites orientation, hearing loss, cochlear implants, migration

Jiansheng Cai,1,2,&ast; Shuzhen Liu,1,&ast; You Li,3,&ast; Qiumei Liu,1 Min Xu,1 Chunbao Mo,3 Tingyu Mai,3 Xia Xu,1 Xu Tang,1 Quanhui Chen,1 Chuntao Nong,1 Huaxiang Lu,1,3 Haoyu He,1,4 Jiexia Tang,5 Junling Zhang,1 Chunmei Wei,1 Dechan Tan,3 Jian Qin,1 Zhiyong Zhang1,3 1Department of Environmental and Occupational Health, School of Public Health, Guangxi Medical University, Nanning, 530021, Guangxi Province, People’s Republic of China; 2Guangxi Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, People’s Republic of China; 3Department of Environmental Health and Occupational Medicine, School of Public Health, Guilin Medical University, Guilin, People’s Republic of China; 4Quality Management Department, the Affiliated Hospital of Stomatology, Guangxi Medical University, Nanning, People’s Republic of China; 5Guangxi Center for Disease Prevention and Control, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Qin; Zhiyong ZhangDepartment of Environmental and Occupational Health, School of Public Health, Guangxi Medical University, Shuangyong Road No. 22, Nanning, 530021, Guangxi Province, People’s Republic of ChinaTel +86-771-5358124Fax +86-771-5358124Email qinjian@gxmu.edu.cn; rpazz@163.comBackground: Animal experiments have found that oil tea reduces body weight and improves blood lipid levels. However, the effect of oil tea on human health has not been confirmed yet. This study aims to explore the relationship between oil tea consumption and obesity and dyslipidemia.Methods: In a cross-sectional population study in Guangxi, China, a semi-quantitative questionnaire was used to investigate the oil tea consumed and food consumption frequency in adults aged 30 years and over. Anthropometric variables and serum biochemical indicators were measured. A total of 2001 adults were divided into five groups based on their non-consumption status and quartile of consumption (groups non-drink oil tea, Q1–Q4).Results: The risk of abdominal obesity tended to decrease significantly with increasing consumption of oil tea (P for trend< 0.05) in the overall participants (Q3 group, OR = 0.545, 95% CI = 0.336– 0.884; Q4 group, OR = 0.520, 95% CI = 0.311– 0.871) and in women (Q2 group, OR = 0.502, 95% CI = 0.274– 0.920; Q3 group, OR = 0.397, 95% CI = 0.213– 0.740; Q4 group, OR = 0.421, 95% CI = 0.228– 0.780). Oil tea consumption Q1, Q2, Q3 and Q4 group significantly reduced the risk of abnormal HDL-cholesterol (P < 0.05). Oil tea consumption Q2 group significantly increased the risk of abnormal LDL-cholesterol (OR = 2.600, 95% CI = 1.033– 6.546) in women. Oil tea consumption Q1 (OR = 0.081, 95% CI =0.008– 0.864) and Q3 (OR = 0.057, 95% CI = 0.004– 0.913) groups significantly reduced the risk of abnormal HDL-cholesterol in women.Conclusion: Oil tea consumption may be associated with a low risk of abdominal obesity. High-dose oil tea consumption may be associated with a low risk of abnormal HDL-cholesterol. Prospective studies with large sample sizes would be required to further investigate this association.Keywords: abdominal obesity, blood lipid, HDL-C

A new saltmarsh soil dataset comprising of geochemical and physical property data from 752 soil samples collected through a sampling program supported by citizen scientists has been brought together with existing data to make the first national estimates of the surficial (top 10 cm) soil OC stock for Great British (GB) saltmarshes. To allow the inclusion of secondary data in the soil stock estimate a new bespoke organic matter to organic carbon conversion for GB saltmarsh soil was developed allowing organic matter data measured using loss-on-ignition to be convert to organic carbon content. The total GB surficial soil OC stock is 2.320 ± 0.470 Mt; English saltmarshes hold 1.601 ± 0.426 Mt OC, Scottish saltmarshes hold 0.368 ± 0.091 Mt OC, and Welsh saltmarshes hold 0.351 ± 0.082 Mt OC. The stocks were calculated within a Markov Chain Monte Carlo framework allowing robust uncertainty estimates to be derived for the first time. Spatial mapping tools are available to accompany these stock estimates at individual saltmarsh habitats throughout GB. This data will aid in the protection and management of saltmarshes and represents the first steps towards the inclusion of saltmarsh OC in the national inventory accounting of blue carbon ecosystems.

Qi Qi,* Xuemeng Qian,* Xinfang Zhu, Jiajing Cai, Rong Xia, Qi Zhang Department of Transfusion Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rong Xia; Qi ZhangDepartment of Transfusion Medicine, Huashan Hospital, Fudan University, 12 Urumqi Middle Road, Shanghai, 200040, People’s Republic of ChinaEmail xiarongcn@126.com; friday0451@163.comPurpose: Blood loss may be corrected with red blood cell transfusion, but may ultimately contribute to negative impacts. This study was a retrospective analysis to assess the impact of perioperative blood transfusion on hospital stay days in liver cancer patients.Methods: We retrospectively examined data from patients with primary liver cancer who underwent curative resection. Patients were divided into perioperative blood transfusion (PBT) and non-PBT groups. Data were given as means and SDs for continuous variables and as counts and percentage for categorical variables. The correlation between blood transfusion and hospital stay days was analyzed by Fisher’s exact test. Multivariable logistic regression analyses were used to identify independent predictors of length of hospital stays.Results: Totally 206/1031 patients (20.3%) were given perioperative transfusion. The mean length of hospital stay was 17.8 days in PBT and 13.9 days in non-PBT groups. Our multivariable logistic regression showed transfusion, total bilirubin, indirect bilirubin, and the ratio of albumin to bilirubin were all indicators of the length of hospital stay days. Perioperative transfusion was also associated with prolonged length of hospital stays (95% CI: 0.395– 0.811, p = 0.002). Transfusion also affected intrinsic coagulation factors (activated partial thromboplastin time, fibrinogen, platelet), inflammatory index (neutrocyte to lymphocyte ratio, monocyte), albumin and bilirubin levels.Conclusion: Perioperative transfusion of blood was associated with a significantly increased length of hospital stays probably via changing intrinsic coagulation and inflammatory factors and bilirubin levels in plasma.Keywords: primary liver cancer, transfusion, length of hospital stays, bilirubin, coagulation factor, inflammatory factor