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Yuhang Tian,1 Xiang He,1 Yanchi Yuan,1 Shijie Zhang,2 Chunyue Wang,1 Jialin Dong,1 Zhao Liu,1 Hui Jing1 1Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, 150081, People’s Republic of China; 2Department of Radiation Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, People’s Republic of ChinaCorrespondence: Hui Jing, Department of Ultrasound, Harbin Medical University Cancer Hospital, 150 Haping Road, Nangang District, Harbin, 150081, People’s Republic of China, Email jinghuihrb@163.comBackground: Triple negative breast cancer (TNBC) is one of the worst prognosis types of breast cancer that urgently needs effective therapy methods. However, cancer is a complicated disease that usually requires multiple treatment modalities.Methods: A tumor microenvironment (TME)-responsive PFC/TRIM37@Fe-TA@HA (abbreviated as PTFTH) nanoplatform was constructed by coating Fe3+ and tannic acid (TA) on the surface of TRIM37-siRNA loaded phase-transition perfluorocarbon (PFC) nanodroplets and further modifying them with hyaluronic acid (HA) to achieve tumor-specific mild photothermal/gene/ferroptosis synergistic therapy (MPTT/GT/ Ferroptosis) in vitro. Once internalized into tumor cells through CD44 receptor-mediated active targeting, the HA shell of PTFTH would be preliminarily disassembled by hyaluronidase (HAase) to expose the Fe-TA metal-phenolic networks (MPNs), which would further degrade in response to an acidic lysosomal environment, leading to HAase/pH dual-responsive release of Fe3+ and PFC/TRIM37.Results: PTFTH showed good biocompatibility in vitro. On the one hand, the released Fe3+ could deplete the overexpressed glutathione (GSH) through redox reactions and produce Fe2+, which in turn converts endogenous H2O2 into highly cytotoxic hydroxyl radicals (•OH) for chemodynamic therapy (CDT). On the other hand, the local hyperthermia generated by PTFTH under 808 nm laser irradiation could not only improve CDT efficacy through accelerating the Fe2+-mediated Fenton reaction, but also enhance TRIM37-siRNA delivery for gene therapy (GT). The consumption of GSH and accumulation of •OH synergistically augmented intracellular oxidative stress, resulting in substantial tumor cell ferroptosis. Moreover, PTFTH possessed outstanding contrast enhanced ultrasound (CEUS), photoacoustic imaging (PAI) and magnetic resonance imaging (MRI) ability.Conclusion: This PTFTH based multiple-mode therapeutic strategy has successfully achieved a synergistic anticancer effect in vitro and has the potential to be translated into clinical application for tumor therapy in future.Keywords: mild photothermal therapy, gene therapy, ferroptosis, synergistic therapy, multimodal imaging

Junyu Chen,1,* Yupei Yuan,2,* Ying Hu,1 Liang Liang1,3 1Department of Psychology, The Fourth Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 2Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 3Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liang Liang, Department of Psychology, The Fourth Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China, Tel +8609915848029, Email 79023556@qq.comBackground: The adjunctive therapeutic potential of simvastatin in schizophrenia treatment has generated interest due to its anti-inflammatory and neuroprotective properties. This meta-analysis aims to assess the efficacy of simvastatin as an adjunct treatment for schizophrenia, synthesizing results from various controlled trials.Methods: We performed a comprehensive search of databases including PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) evaluating the efficacy of simvastatin as an adjunct therapy in patients with schizophrenia. The primary outcome measures were improvements in the Positive and Negative Syndrome Scale (PANSS) scores. Secondary outcomes included changes in overall clinical condition and level of functioning. Data were pooled using random-effects models, and heterogeneity was assessed through I² statistics.Results: The four RCTs included in the analysis represented 425 participants. The combined results demonstrated no significant advantage of simvastatin over placebo in reducing PANSS total scores with a pooled effect size (Standard Mean Difference, SMD) of − 0.36 (95% Confidence Interval, CI: − 0.82 to 0.11) at 1 month, and − 1.80 (95% Confidence Interval, CI: − 4.82 to 1.21) at 3 months, indicating minimal to no effect. Similarly, analyses of secondary outcomes showed no significant improvements in overall clinical condition and level of functioning. The studies exhibited low heterogeneity (I² = 0%).Conclusion: This meta-analysis provides evidence that simvastatin, used as adjunctive therapy, does not significantly improve the symptomatic outcomes of schizophrenia compared to placebo. Although simvastatin is well-tolerated, its role in enhancing antipsychotic treatment efficacy in patients with schizophrenia appears limited. These findings suggest that simvastatin should not be recommended as an adjunctive treatment in the clinical management of schizophrenia. Further research may explore the potential subgroups that could benefit from such treatment or identify the biological reasons for the lack of efficacy.Keywords: schizophrenia, simvastatin, adjunctive therapy, meta-analysis, randomized controlled trials, efficacy

Jing Yu,1 Yike Zhang,1 Zhixiong Ye,1 Kun Tang,1 Yiming Ma,1 Linlin Fu,1 Tongtong Cui,1 Hening Kang,2 Yadong Yuan,1 Wensen Pan1 1Second Department of Respiratory and Critical Care Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2College of Basic Medicine, Hebei Medical University, Shijiazhuang, People’s Republic of ChinaCorrespondence: Wensen Pan, Email 27400010@hebmu.edu.cnBackground: Despite ongoing interventions, SARS-CoV-2 continues to cause significant global morbidity and mortality. Early diagnosis and intervention are crucial for effective clinical management. However, prognostic features based on transcriptional data have shown limited effectiveness, highlighting the need for more precise biomarkers to improve COVID-19 treatment outcomes.Methods: We retrospectively analyzed 149 clinical features from 189 COVID-19 patients, identifying prognostic features via univariate Cox regression. The cohort was split into training and validation sets, and 77 prognostic models were developed using seven machine learning algorithms. Among these, the least absolute shrinkage and selection operator (Lasso) method was employed to refine the selection of prognostic variables by ten-fold cross-validation strategy, which were then integrated with random survival forests (RSF) to build a robust COVID-19-related prognostic model (CRM). Model accuracy was evaluated across training, validation, and entire cohorts. The diagnostic relevance of interleukin-10 (IL-10) was confirmed in bulk transcriptional data and validated at the single-cell level, where we also examined changes in cellular communication between mononuclear cells with differing IL-10 expression and other immune cells.Results: Univariate Cox regression identified 43 prognostic features. Among the 77 machine learning models, the combination of Lasso and RSF produced the most robust CRM. This model consistently performed well across training, validation, and entire cohorts. IL-10 emerged as a key prognostic feature within the CRM, validated by single-cell transcriptional data. Transcriptome analysis confirmed the stable diagnostic value of IL-10, with mononuclear cells identified as the primary IL-10 source. Moreover, differential IL-10 expression in these cells was linked to altered cellular communication in the COVID-19 immune microenvironment.Conclusion: The CRM provides accurate prognostic predictions for COVID-19 patients. Additionally, the study underscores the importance of early IL-10 level testing upon hospital admission, which could inform therapeutic strategies.Keywords: SARS-CoV-2, machine learning, IL-10, therapeutic guidance, clinical decision making

Xiangdong Gongye,1,2,* Peng Xia,1,2,* Tianyin Ma,1,2,* Yibo Chai,1,2 Zhang Chen,1,2 Yimin Zhu,1,2 Chengming Qu,1,2 Jie Liu,1,2 Wing Wa Guo,1,2 Minghe Zhang,1,2 Yingyi Liu,1,2 Ming Tian,1,2 Yufeng Yuan1– 3 1Department of Hepatobiliary & Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Clinical Medicine Research Center for Minimally Invasive Procedure of Hepatobiliary & Pancreatic Diseases of Hubei Province, Hubei, People’s Republic of China; 3Taikang Center for Life and Medical Sciences of Wuhan University, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ming Tian; Yufeng Yuan, Email dr.med.mingtian@whu.edu.cn; yuanyf1971@whu.edu.cnBackground: The liver’s regenerative capacity allows it to repair itself after injury. Extracellular vesicles and particles (EVPs) in the liver’s interstitial space are crucial for signal transduction, metabolism, and immune regulation. Understanding the role and mechanism of liver-derived EVPs in regeneration is significant, particularly after partial hepatectomy, where the mechanisms remain unclear.Methods: A 70% hepatectomy model was established in mice, and EVPs were isolated and characterized using electron microscopy, nanocharacterization, and Western blot analysis. Combined metabolomic and transcriptomic analyses revealed β-sitosterol enrichment in EVPs and activation of the Hedgehog signaling pathway during regeneration. The role of β-sitosterol in EVPs on the Hedgehog pathway and its targets were identified using qRT-PCR, Western blot analysis. The regulation of carnitine synthesis by this pathway was determined using a dual luciferase assay. The effect of a β-sitosterol diet on liver regeneration was verified in mice.Results: After 70% hepatectomy, the liver successfully regenerated without liver failure or death. At 24 hours post-surgery, tissue staining showed transient regeneration-associated steatosis (TRAS), with increased Ki67 positivity at 48 hours. EVPs displayed a spherical lipid bilayer structure with particle sizes of 70– 130 nm. CD9, CD63, and CD81 in liver-derived EVPs were confirmed. Transcriptomic and metabolomic analyses showed EVPs supplementation significantly promoted carnitine synthesis and fatty acid oxidation. Tissue staining confirmed accelerated TRAS resolution and enhanced liver regeneration with EVP supplementation. Mass spectrometry identified β-sitosterol in EVPs, which binds to Smo protein, activating the Hedgehog pathway. This led to the nuclear transport of Gli3, stimulating Setd5 transcription and inducing carnitine synthesis, thereby accelerating fatty acid oxidation. Mice with increased β-sitosterol intake showed faster TRAS resolution and liver regeneration compared to controls.Conclusion: Liver-derived EVPs promote regeneration after partial hepatectomy. β-sitosterol from EVPs accelerates fatty acid oxidation and promotes liver regeneration by activating Hedgehog signaling pathway. Keywords: liver regeneration, extracellular vesicles and particles, β-sitosterol, carnitine synthesis, hedgehog signaling pathway

Yuan Yuan,1,* Mingyi Hou,2,* Xiaoning Song,1 Xintao Yao,1 Xuerui Wang,1 Xiangjun Chen,2 Shengnan Li1 1School of Chemical Engineering and Technology, Hebei University of Technology, Tianjin, 300401, People’s Republic of China; 2School of Pharmacy, Shandong New Drug Loading & Release Technology and Preparation Engineering Laboratory, Binzhou Medical University, Yantai, 264003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shengnan Li; Xiaoning Song, School of Chemical Engineering and Technology, Hebei University of Technology, Xiping Road, Tianjin, 300401, People’s Republic of China, Email lisn027@hebut.edu.cn; songxn123@hebut.edu.cnBackground: With the rapid development of nanotechnology, constructing a multifunctional nanoplatform that can deliver various therapeutic agents in different departments and respond to endogenous/exogenous stimuli for multimodal synergistic cancer therapy remains a major challenge to address the inherent limitations of chemotherapy.Methods: Herein, we synthesized hollow mesoporous Prussian Blue@zinc phosphate nanoparticles to load glucose oxidase (GOx) and DOX (designed as HMPB-GOx@ZnP-DOX NPs) in the non-identical pore structures of their HMPB core and ZnP shell, respectively, for photothermally augmented chemo-starvation therapy.Results: The ZnP shell coated on the HMPB core, in addition to providing space to load DOX for chemotherapy, could also serve as a gatekeeper to protect GOx from premature leakage and inactivation before reaching the tumor site because of its degradation characteristics under mild acidic conditions. Moreover, the loaded GOx can initiate starvation therapy by catalyzing glucose oxidation while causing an upgradation of acidity and H2O2 levels, which can also be used as forceful endogenous stimuli to trigger smart delivery systems for therapeutic applications. The decrease in pH can improve the pH-sensitivity of drug release, and O2 can be supplied by decomposing H2O2 through the catalase-like activity of HMPBs, which is beneficial for relieving the adverse conditions of anti-tumor activity. In addition, the inner HMPB also acts as a photothermal agent for photothermal therapy and the generated hyperthermia upon laser irradiation can serve as an external stimulus to further promote drug release and enzymatic activities of GOx, thereby enabling a synergetic photothermally enhanced chemo-starvation therapy effect. Importantly, these results indicate that HMPB-GOx@ZnP-DOX NPs can effectively inhibit tumor growth by 80.31% and exhibit no obvious systemic toxicity in mice.Conclusion: HMPB-GOx@ZnP-DOX NPs can be employed as potential theranostic agents that incorporate multiple therapeutic modes to efficiently inhibit tumors. Keywords: Prussian Blue, glucose oxidase, co-delivery system, photothermal therapy, chemotherapy

Chenglin Xu,1,&ast; Song Wen,1,2,&ast; Min Gong,1,&ast; Meiyuan Dong,1,3,&ast; Yue Yuan,1 Yanyan Li,1 Mingyue Zhou,4 Ligang Zhou1,3,5 1Department of Endocrinology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, People’s Republic of China; 2Fudan Zhangjiang Institute, Fudan University, Shanghai, 201203, People’s Republic of China; 3Hebei Medical University, Shijiazhuang, 050013, People’s Republic of China; 4Clinical Research OB/GYN REI Division, University of California, San Francisco, CA, USA; 5Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling, Shanghai Pudong Hospital, Shanghai, 201399, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ligang Zhou, Department of Endocrinology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, People’s Republic of China, Tel +8613611927616, Email zhouligang1n1@163.comObjective: To investigate the implications of elevated myoglobin (MYO) in acute diabetic conditions of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS).Materials and methods: This study integrates in-patient data from Shanghai Pudong Hospital from 2019 to 2023. Laboratory data were compared between stable T2D patients (without acute diabetic complications), DKA, and HHS patients. The multilinear regression explored variables relevant to the elevated MYO in DKA and HHS. The dynamics of MYO, the survival rate, and associated risk factors in HHS were determined.Results: Except for triglyceride, procalcitonin, low-density lipoprotein, islet cell autoimmune antibodies, N-terminal Pro-brain natriuretic peptide (NT-ProBNP), and brain natriuretic peptide (BNP), there were significant differences in age, gender distribution, duration of diabetes, type of diabetes, and other referred laboratory data (p< 0.05). The age, gender, creatine kinase (CK), estimated glomerular filtration rate (eGFR), and free triiodothyronine (FT3) in DKA, whereas osmolar, uric acid (UA), and cardiac troponin I (cTNI) in the HHS, were significant determinants of elevated MYO, respectively (p< 0.05). The dynamic of MYO in HHS was in line with the survival trend, where the percentage of death was 29.73%, and aging with higher procalcitonin levels was a key risk factor. Besides, the cumulative survival rates between patients with or without bone fracture or muscle injury were substantially different.Conclusion: This real-world study demonstrated DKA and HHS potentially have unique causes for increased MYO. By utilizing the appropriate regression parameters, we could forecast the progression of increased MYO in groups of DKA and HHS, while based on risk factors of aging, severity of infection, and different MYO sources, we could predict the prognosis of HHS.Keywords: diabetes mellitus, diabetic ketoacidosis, hyperosmolar hyperglycemic state, myoglobin, survival

Junjie Cheng,1,&ast; Yuan Yuan,1,&ast; Jinmeng Li,1 Ruoying Zhang,1 Xudong Fan,1 Zhirou Xu,2 Huirong Lin,3 Xinjun Cai,1 Mingfeng Zheng4 1Department of Pharmacy, Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, People’s Republic of China; 2Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, People’s Republic of China; 3Department of Pharmacy, Taizhou Cancer Hospital, Taizhou, People’s Republic of China; 4Department of Orthopaedics, Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingfeng Zheng; Xinjun Cai, Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, Zhejiang Province, 310003, People’s Republic of China, Email zmfyxz3@163.com; zjtcmcxj@zcmu.edu.cnPurpose: Previous studies have indicated that the development of severe adverse events is associated with linezolid peak concentration (Cmax), but the factors affecting linezolid Cmax and evidences on therapeutic drug monitoring to anticipate toxicity in drug-resistant tuberculosis (DR-TB) patients have not been clarified clearly. This study aimed to explore the factors influencing linezolid Cmax and investigate the association between linezolid concentration and hematological toxicity.Patients and Methods: This study included patients with drug-resistant tuberculosis treated with linezolid from January 2022 to September 2023. We analyzed the factors affecting linezolid Cmax using chi-squared and binary logistic regression. The diagnostic utility of linezolid Cmax in predicting hematological toxicity was evaluated using receiver operating characteristic (ROC) analysis.Results: A total of 76 patients were enrolled in the study. 63.20% met the standard rates for linezolid Cmax. Age (P=0.036), weight (P=0.0016), and creatinine clearance (P=0.0223) significantly correlated with the Cmax. Hematological toxicity was observed in 46.05% (35/76) of patients, characterized by thrombocytopenia (31.58%, 24/76), anemia (6.58%, 5/76), and leukopenia (21.05%, 16/76). ROC curve analysis confirmed the predictive value of linezolid Cmax for thrombocytopenia with an area under curve of 0.728.Conclusion: Suboptimal linezolid Cmax was prevalent among patients with DR-TB, with age, weight, and renal function emerging as influential factors. Elevated linezolid Cmax increases the risk of thrombocytopenia. Meticulous monitoring of linezolid Cmax is imperative during anti-DR-TB therapy to tailor treatment and mitigate hematological toxicity.Keywords: linezolid, therapeutic drug monitoring, influencing factors, hematological toxicity

Jiping Zhang,&ast; Xianan Sang,&ast; Yichao Yuan, Jiawei Shen, Yuanyuan Fang, Minjing Qin, Hangsheng Zheng, Zhihong Zhu College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, 311402, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hangsheng Zheng; Zhihong Zhu, College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China, Email hs-zheng@163.com; zzhjanny@163.comBackground: Anthraquinone drugs are widely used in the treatment of tumors. However, multidrug resistance and severe cardiac toxicity limit its use, which have led to the discovery of new analogues. In this paper, 4-Deoxy-&epsiv;-pyrromycinone (4-Deo), belonging to anthraquinone compounds, was first been studied with the anti-tumor effects and the safety in vitro and in vivo as a new anti-tumor drug or lead compound.Methods: The quantitative analysis of 4-Deo was established by UV methodology. The anti-cancer effect of 4-Deo in vitro was evaluated by cytotoxicity experiments of H22, HepG2 and Caco2, and the anti-cancer mechanism was explored by cell apoptosis and cycle. The tumor-bearing mouse model was established by subcutaneous inoculation of H22 cells to evaluate the anti-tumor effect of 4-Deo in vivo. The safety of 4-Deo was verified by the in vitro safety experiments of healthy cells and the in vivo safety experiments of H22 tumor-bearing mice. Tumor tissue sections were labeled with CRT, HMGB1, IL-6 and CD115 to explore the preliminary anti-cancer mechanism by immunohistochemistry.Results: In vitro experiments demonstrated that 4-Deo could inhibit the growth of H22 by inducing cell necrosis and blocking cells in S phase, and 4-Deo has less damage to healthy cells. In vivo experiments showed that 4-Deo increased the positive area of CRT and HMGB1, which may inhibit tumor growth by triggering immunogenic cell death (ICD). In addition, 4-Deo reduced the positive area of CSF1R, and the anti-tumor effect may be achieved by blocking the transformation of tumor-associated macrophages (TAMs) to M2 phenotype.Conclusion: In summary, this paper demonstrated the promise of 4-Deo for cancer treatment in vitro and in vivo. This paper lays the foundation for the study of 4-Deo, which is beneficial for the further development anti-tumor drugs based on the lead compound of 4-Deo. Keywords: 4-deoxy-&epsiv;-pyrromycinone, lead compound, drug safety, drug efficacy, anti-tumor drug

Mingyue Fu,1,2,&ast; Diliaremu Aihemaiti,1,2,&ast; Haowen Fu,1,2,&ast; Na Li,1,2 Yifan Yuan,3 Mei Ye1,2 1Department of Gastroenterology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Hubei Clinical Centre and Key Laboratory of Intestinal and Colorectal Diseases, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, People’s Republic of China; 3Center of Gerontology and Geriatrics, West China Hospital, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yifan Yuan; Mei Ye, Email yifanyuan95@163.com; wumeiye08@163.comBackground: Crohn’s disease (CD) is a persistent inflammatory condition that impacts the gastrointestinal system and is characterized by a multifaceted pathogenesis involving genetic, immune, and environmental components. This study primarily investigates the relationship between gene expression and immune cell infiltration in CD, focusing on disulfidptosis—a novel form of cell death caused by abnormal disulfide accumulation—and its impact on various immune cell populations. By identifying key disulfidptosis-related genes (DRGs) and exploring their association with distinct gene expression subtypes, this research aims to enhance our understanding of CD and potentially other autoimmune diseases.Methods: Gene expression data from intestinal biopsy samples were collected from both individuals with CD and healthy controls, and these data were retrieved from the GEO database. Through gene expression level comparisons, various differentially expressed genes (DEGs) were identified. Subsequently, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to reveal the biological processes and pathways linked to these DEGs. Later, immune cell infiltration was evaluated. Hub candidate DRGs were identified using machine learning algorithms. Validation of the expression of hub DRGs was carried out using quantitative real-time polymerase chain reaction. The hub DRGs were subjected to unsupervised hierarchical clustering to classify CD patients into subtypes. The characteristics of each subtype were then analyzed.Results: Two hub DRGs (NDUFA11 and LRPPRC) were identified. NDUFA11 showed a significantly positive association with the abundance of Th17 cells. Conversely, higher expression levels of LRPPRC were associated with a reduced abundance of various immune cells, particularly monocytes. CD patients were classified into two disulfidptosis-related subtypes. Cluster B patients exhibited lower immune infiltration and milder clinical presentation.Conclusion: LRPPRC and NDUFA11 are identified as hub DRGs in CD, with potential roles in disulfidptosis and immune regulation. The disulfidptosis subtypes provide new insights into disease progression.Keywords: Crohn’s disease, disulfidptosis, machine learning, expression pattern, immune cell infiltration

Wen-Juan Yi,1,&ast; Yifan Yuan,2,&ast; Qionglin Bao,3 Zhuowei Zhao,4 Hua-Sheng Ding,5 Jiquan Song1 1Department of Dermatology, Zhongnan hospital of Wuhan University, Wuhan, People’s Republic of China; 2Center of Gerontology and Geriatrics, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 3Wound Repair Center, Chronic Wound and Diabetic Foot Clinical Medical Research Center, Liyuan Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, People’s Republic of China; 5Department of Emergency, Shenzhen Hospital, Southern Medical University, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hua-Sheng Ding; Jiquan Song, Email hsding2019@126.com; songjiq@126.comBackground: Diabetes impairs wound healing, notably in diabetic foot ulcers (DFU). Stress, marked by the accumulation of lipoylated mitochondrial enzymes and the depletion of Fe–S cluster proteins, triggers cuproptosis—a distinct form of cell death. The involvement of copper in the pathophysiology of DFU has been recognized, and currently, a copper-based therapeutic strategy is emerging as a viable option for enhancing ulcer healing. This study investigates genes linked to copper metabolism in DFU, aiming to uncover potential targets for therapeutic intervention.Methods: Two diabetic wound Gene Expression Omnibus (GEO) datasets were analyzed to study immune cell dysregulation in diabetic wounds. Differentially expressed genes related to copper metabolism were identified and analyzed using machine learning methods. Gene ontology, pathway enrichment, and immune infiltration analyses were performed using DFU samples. The expression of identified genes was validated using qRT-PCR and single-cell RNA sequencing.Results: Ten genes associated with copper metabolism were identified. Among these, SLC31A1 and ADNP were found to be significantly differentially expressed in DFU. Notably, SLC31A1 exhibited higher expression in macrophages, whereas ADNP was found to be highly expressed in fibroblasts and chondrocytes.Conclusion: The study indicates a close link between copper metabolism, the infiltration of immune cells, and DFU. It proposes that copper metabolism could influence the progression of DFU through the activation of immune responses. These observations offer fresh perspectives on the underlying mechanisms of DFU and identify potential targets for therapeutic intervention.Keywords: diabetic foot ulcers, copper metabolism, immune infiltration, single-cell RNA analysis, differentially expressed genes

Tianwen Lai,1,&ast; Chaole Luo,1,&ast; Yalian Yuan,2,&ast; Jia Fang,1,&ast; Yun Wang,1 Xiantong Tang,1 Lihuan Ouyang,1 Keyan Lin,1 Bin Wu,2 Weimin Yao,1 Ruina Huang1 1Department of Respiratory and Critical Care Medicine, the First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, 523121, People’s Republic of China; 2Respiratory Diseases Research Institute, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ruina Huang; Weimin Yao, Email wolidedd@163.com; yaoweimin@gdmu.edu.cnIntroduction: Chronic obstructive pulmonary disease (COPD), an incurable chronic respiratory disease, has become a major public health problem. The relationship between the composition of intestinal microbiota and the important clinical factors affecting COPD remains unclear. This study aimed to identify specific intestinal microbiota with high clinical diagnostic value for COPD.Methods: The fecal microbiota of patients with COPD and healthy individuals were analyzed by 16S rDNA sequencing. Random forest classification was performed to analyze the different intestinal microbiota. Spearman correlation was conducted to analyze the correlation between different intestinal microbiota and clinical characteristics. A microbiota-disease network diagram was constructed using the gut MDisorder database to identify the possible pathogenesis of intestinal microorganisms affecting COPD, screen for potential treatment, and guide future research.Results: No significant difference in biodiversity was shown between the two groups but significant differences in microbial community structure. Fifteen genera of bacteria with large abundance differences were identified, including Bacteroides, Prevotella, Lachnospira, and Parabacteroides. Among them, the relative abundance of Lachnospira and Coprococcus was negatively related to the smoking index and positively related to lung function results. By contrast, the relative abundance of Parabacteroides was positively correlated with the smoking index and negatively correlated with lung function findings. Random forest classification showed that Lachnospira was the genus most capable of distinguishing between patients with COPD and healthy individuals suggesting it may be a potential biomarker of COPD. A Lachnospira disease network diagram suggested that Lachnospira decreased in some diseases, such as asthma, diabetes mellitus, and coronavirus disease 2019 (COVID-19), and increased in other diseases, such as irritable bowel syndrome, hypertension, and bovine lichen.Conclusion: The dominant intestinal microbiota with significant differences is related to the clinical characteristics of COPD, and the Lachnospira has the potential value to identify COPD.Keywords: chronic obstructive pulmonary disease, intestinal microbiota, 16S rDNA sequencing, Lachnospira, gut-lung axis

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

Da Ke,1 Jian Ni,1 Yuan Yuan,1 Mingzhen Cao,1 Si Chen,2 Heng Zhou1 1Department of Cardiology, Renmin Hospital of Wuhan University, Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, 430060, People’s Republic of China; 2Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, 430060, People’s Republic of ChinaCorrespondence: Heng Zhou, Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China, Email hengzhou@whu.edu.cnPurpose: Studies have shown that neutrophil-mediated formation of neutrophil extracellular traps (NETs) leads to increased inflammatory response and cellular tissue damage during myocardial infarction (MI). We aimed to identify and validate possible hub genes in the process of NETs-mediated cell damage.Methods: We performed an immune cell infiltration analysis of the MI transcriptome dataset based on CIBERSORT and ssGSEA algorithms. Gene expression profiles of NETs formation (GSE178883) were used to analyze the physiological processes of peripheral blood neutrophils after phorbol myristate acetate (PMA) stimulation. Bioinformatics and machine learning algorithms were utilized to find candidate hub genes based on NETs-related genes and transcriptome datasets (GSE66360 and GSE179828). We generated the receiver operating curve (ROC) to evaluate the diagnostic value of hub genes. Next, the correlation between hub genes and immune cells was analyzed using CIBERSORT, ssGSEA and xCell algorithms. Finally, we used quantitative real-time PCR (qRT-PCR) and immunohistochemistry to verify gene expression.Results: Immune cell infiltration analysis revealed that inflammatory cells such as neutrophils were highly expressed in the peripheral blood of patients with MI. Functional analysis of differentially expressed genes (DEGs) in GSE178883 indicated that the potential pathogenesis lies in immune terms. Using weighted gene co-expression network analysis (WGCNA) and machine learning algorithms, we finally identified the seven hub genes (FCAR, IL1B, MMP9, NFIL3, CXCL2, ICAM1, and ZFP36). The qRT-PCR results showed that IL-1B, MMP9, and NFIL3 mRNA expression was up-regulated in the MI group compared to the control. Immunohistochemical results showed high MMP9, IL-1B, and NFIL3 expression in the infarcted area compared to the non-infarcted area and sham-operated groups.Conclusion: We identified seven hub genes associated with NETs-mediated cellular damage during MI. Our results may provide insights into the mechanisms of neutrophil-mediated cell injury during MI. Keywords: myocardial infarction, neutrophils, cell damage, neutrophil extracellular traps, bioinformatics, endothelial cells

Weijie Chen,1,2,&ast; Simin Deng,3,&ast; Huali Jiang,2,&ast; Heng Li,2 Yu Zhao,2 Yiqiang Yuan4 1Department of Cardiology, The Second School of Clinical Medicine, Southern Medical University, Guangdong, People’s Republic of China; 2Department of Cardiology, Dongguan Tung Wah Hospital, Guangdong, People’s Republic of China; 3Research Center, Dongguan Eighth People’s Hospital, Guangdong, People’s Republic of China; 4Department of Cardiology, The Second School of Clinical Medicine, Southern Medical University, The Seventh People’s Hospital of Zhengzhou, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yiqiang Yuan, Department of Cardiology, The Second School of Clinical Medicine, Southern Medical University, The Seventh People’s Hospital of Zhengzhou, No. 17 Jingnan 5th Road, Zhengzhou Economic and Technological Development Zone, Zhengzhou, Henan, People’s Republic of China, Tel +86-0371-61205666, Email zzqyyuanyiqiang@126.comPurpose: To explore the topology of the white matter network in individuals with essential hypertension by graph theory.Patients and Methods: T1-weighted image and diffusion tensor imaging (DTI) data from 43 patients diagnosed with essential hypertension (EHT) and 33 individuals with normotension (healthy controls, HCs) were incorporated in this cross-sectional study. Furthermore, structural networks were constructed by graph theory to calculate whole brain network characteristics and intracerebral node characteristics.Results: Both EHT and HC groups displayed small-worldness in their structural networks. The area under the curve (AUC) of the small-worldness coefficient (σ) was higher in the EHT group compared to the HC group, whereas the AUC of assortativity was lower in the EHT group in contrast to the HC group. The nodal clustering coefficient (CP) and local efficiency (Eloc) of the EHT group decreased in the right dorsolateral superior frontal gyrus and the left medial superior frontal gyrus. These values increased in the left anterior cingulate and paracingulate gyrus. Furthermore, weight and body mass index (BMI) were positively correlated with σ.Conclusion: The EHT group showed brain network separation and integration dysfunction. Weight and BMI were positively correlated with σ. The data acquired in this investigation implied that altered structural connectivity in the prefrontal region may be a potential neuroimaging marker in EHT patients.Keywords: DTI, EHT, graph theory, whole brain network characteristics, intracerebral node characteristics

Huanhuan Zhu, Chen Chen, Luhan Geng, Qing Li, Chengning Zhang, Lin Wu, Bo Zhang, Suyan Duan,&ast; Changying Xing,&ast; Yanggang Yuan&ast; Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanggang Yuan, Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, 210029, People’s Republic of China, Tel/Fax +86-25-6813-6462, Email ygyuan@njmu.edu.cnBackground: Mounting evidence suggests that mitochondrial dysfunction contributes to lupus nephritis (LN) pathogenesis. Mitochondrial pyruvate carrier 1 (MPC1) and mitochondrial pyruvate carrier 2 (MPC2) mediating pyruvate transport from the cytoplasm to the mitochondrial matrix, determines the cell survival and cellular energy supply. Here, we aimed to investigate the association of mitochondrial pyruvate carrier expression with the clinical and histological features in LN.Methods: Patients with biopsy-proven proliferative LN (class III and class IV, n=18) and membranous LN (class V, n=18) were included. Expression of MPC1 and MPC2 were examined by immunohistochemistry. MPC protein levels in the two groups were evaluated by the Student’s t-test. Correlation analysis between MPC levels and clinicopathological features was performed by Spearman’s rank correlation.Results: Both MPC1 and MPC2 were exclusively expressed in renal tubules of enrolled LN. Significantly lower MPC1 and MPC2 were observed in patients with proliferative LN compared to membranous LN. In addition, the MPC1 and MPC2 were negatively correlated with SLEDAI-2K score, renal function, and renal pathology activity index.Conclusion: Both MPC1 and MPC2 were localized in renal tubules, and decreased MPC content was more pronounced in proliferative LN than membranous LN. MPC levels were significantly correlated with renal functions and renal pathology activity.Keywords: lupus nephritis, mitochondrial pyruvate carrier, proliferative, membranous, tubulointerstitial lesions

Yuyi Yuan,1,&ast; Fang Wang,2,&ast; Xingxing Liu,1,&ast; Bo Shuai,1 Heng Fan1 1Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China; 2Department of Rehabilitation Medicine, Jingshan Union Hospital, Union Hospital, Huazhong University of Science and Technology, Jingshan, Hubei, 431800, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo Shuai; Heng Fan, Email bo_shuai@hust.edu.cn; fanheng009@aliyun.comAbstract: Ulcerative colitis (UC) is a chronic non-specific inflammatory bowel disease characterized by inflammation and ulcer formation of the intestinal mucosa. Due to its high recurrence rate, prolonged course, limited curative options, and significant impact on patients’ quality of life, along with a notable potential for malignant transformation, UC is designated as a refractory global health challenge by the World Health Organization (WHO). The elucidation of the pathogenesis and therapeutic strategies for UC requires further in-depth investigation. AMP-activated protein kinase (AMPK) serves as a central regulator of cellular energy metabolic homeostasis. Emerging evidence indicates that interventions involving traditional Chinese medicine (TCM) components, as well as other pharmacological measures, exert beneficial effects on the intestinal mucosal inflammation and epithelial barrier dysfunction in UC by modulating AMPK signaling, thereby influencing biological processes such as cellular autophagy, apoptosis, inflammatory responses, macrophage polarization, and NLRP3 inflammasome-mediated pyroptosis. The role of AMPK in UC is of significant importance. This manuscript provides a comprehensive overview of the mechanisms through which AMPK is involved in UC, as well as a compilation of pharmacological agents capable of activating the AMPK signaling pathway within the context of UC. The primary objective is to facilitate a deeper comprehension of the pivotal role of AMPK in UC among researchers and clinical practitioners, thereby advancing the identification of novel therapeutic targets for interventions in UC.Keywords: ulcerative colitis, AMPK, colitis-associated biological processes, traditional Chinese medicine monomers

Wenjuan Yan,1,&ast; Jiaojiao Wu,2,&ast; Shanmei Wang,1 Qi Zhang,1 Youhua Yuan,1 Nan Jing,1 Jiangfeng Zhang,1 Hangchan He,3 Yi Li1 1Department of Clinical Microbiology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou, Henan, People’s Republic of China; 2Department of Clinical Microbiology, Xiayi People’s Hospital, Shangqiu, Henan, People’s Republic of China; 3Department of Clinical Laboratory, Baofeng Traditional Chinese Medicine Hospital, Pingdingshan, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Li, Department of Clinical Microbiology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou, Henan, People’s Republic of China, Tel +8615939039006, Email liyilabmed@henu.edu.cnPurpose: To analyze the risk factors and clinical outcomes of patients isolated with polymyxin B-resistant (PR) Enterobacterales from various clinical specimens to prevent and control the spread of these strains.Methods: This retrospective case-control study included 72 PR Enterobacterales-positive cases and 144 polymyxin B-susceptible (PS) Enterobacterales controls from 2018 to 2022. Patients with PR Enterobacterales isolated in various clinical cultures were defined as cases. Patients with PS Enterobacterales cultures at similar anatomic sites during the same period were randomly selected as controls. Data were collected from clinical and laboratory test records. Bivariable logistic regression and Pearson’s chi-square tests were used to assess risk factors.Results: PR strains were predominantly Klebsiella pneumoniae (72.2%) and Salmonella enteritidis (8.3%). Of the patients, 66.04% were admitted to an intensive care unit (ICU). Risk factors for isolation with PR strains included chronic heart disease (P = 0.012; odds ratio [OR] 1.15; 95% confidence interval [CI] 1.03– 1.28), immunosuppressant use (P = 0.016; OR 1.04 [1.0– 1.07), drainage tube [head] (P = 0.006; OR 1.1 [1.0– 1.1]), and polymyxin B exposure (P = 0.007; OR 1.03 [1.0– 1.06]. With respect to outcomes, admission to an ICU (P = 0.003; OR 7.1 [1.9– 25.4]), hypertension (P = 0.035; OR 1.4 [1.02– 1.83]), and drainage tube [head] (P = 0.044; OR 1.1 [1.0– 1.15]) were associated with treatment failure. Additionally, treatment failure was more frequent in patients (45.83%) than in controls (14.58%).Conclusion: The major risk factors for isolation with PR strains were chronic heart disease, exposure to immunosuppressants, use of drainage tubes, and polymyxin B exposure. The isolation of PR strains in patients was a predictor of unfavorable outcomes. These findings provide a basis for monitoring the spread of PR Enterobacterales.Keywords: polymyxin B resistance, treatment failure, Klebsiella pneumoniae, Salmonella enteritidis

Gang Chen,1– 3 Lei Li,2,4 Taipeng Sun,1– 3 Chenguang Jiang,1,2 Wei Xu,1,2 Suzhen Chen,1,2 Changchun Hu,1 Yingying Yue,1,2 Tianyu Wang,1,2 Wenhao Jiang,1,2 Yonggui Yuan1,2 1Department of Psychosomatics and Psychiatry, ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China; 2Institute of Psychosomatics, School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China; 3Department of Medical Psychology, Huai’an NO 3 People’s Hospital, Huaian, People’s Republic of China; 4Department of Sleep Medicine, The Fourth People’s Hospital of Lianyungang, Lianyungang, People’s Republic of ChinaCorrespondence: Wenhao Jiang; Yonggui Yuan, Department of Psychosomatics and Psychiatry, ZhongDa Hospital, School of Medicine, Southeast University, No. 87 Dingjiaqiao, Gulou District, Nanjing, Jiangsu, 210009, People’s Republic of China, Tel +86-25-83285124, Email wjiang43@outlook.com; yygylh2000@sina.comBackground: Depression is a heritable brain disorder. Laminin genes were recently identified to affect the brain’s overall thickness through neurogenesis, differentiation, and migration in depression. This study aims to explore the effects of the LAMA2’s single nucleotide polymorphisms (SNP), a subunit gene of laminin, on the detected brain regions of patients with major depressive disorder (MDD).Methods: The study included 89 patients with MDD and 60 healthy controls with T1-weighted structural magnetic resonance imaging and blood samples for genotyping. The interactions between LAMA2 gene SNPs and diagnosis as well as duration of illness (DOI) were explored on brain measures controlled for age, gender, and site.Results: The right transverse temporal gyrus and right parahippocampal gyrus showed reduced thickness in MDD. Almost all seven LAMA2 SNPs showed significant interactions with diagnosis on both gyrus (corrected p < 0.05 or trending). In MDD, rs6569604, rs2229848, rs2229849, rs2229850, and rs2784895 interacted with DOI on the right transverse temporal gyrus (corrected p < 0.05), but not the right parahippocampal gyrus.Conclusion: The thickness of the right transverse temporal gyrus in patients with MDD may be affected by LAMA2 gene and DOI.Keywords: major depressive disorder, right transverse temporal gyrus, LAMA2, interaction

Yu Pan,&ast; Zhu Qing Feng,&ast; Yan Yuan,&ast; Gui Ming Hu, Yi Jiang, Jiang Chuan Dong Department of Geriatrics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China&ast;This authors Contributed equally to this workCorrespondence: Jiang Chuan Dong, Department of Geriatrics, The Second Affiliated Hospital of Chongqing Medical University, No. 74 Linjiang Road, Yuzhong District, Chongqing, 400010, People’s Republic of China, Email dongjiangchuan2023@163.comAbstract: Coupled with the ageing population, frailty, characterized by high prevalence and difficult treatment, has progressively evolved into a significant public health concern. Frail individuals can often observe serious metabolic disorders and sleep-wake cycle disruption, which may be caused by the decline in physiological reserve and increased vulnerability. Moreover, sleep-wake cycle disruptions and metabolic dysfunctions associated with circadian rhythm disorders are considered to be a central part of the disorder. Previous studies have documented a correlation between frailty and sleep-wake disruptions; nevertheless, the association between circadian rhythm disorders and frailty has not yet been definitively established. Hence, we hypothesize a bidirectional link between circadian rhythm disorders and frailty, with each condition exerting a significant influence on the progression of the other’s disease trajectory.Keywords: circadian rhythm, frailty, metabolism, neuropathy, insulin resistance

Xiucai Li,1,&ast; Song Wen,1,&ast; Meiyuan Dong,1,2 Yue Yuan,1 Min Gong,1 Congcong Wang,1 Xinlu Yuan,1 Jianlan Jin,1 Mingyue Zhou,3 Ligang Zhou1,2,4 1Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, People’s Republic of China; 2Hebei Medical University, Shijiazhuang, 050013, People’s Republic of China; 3Clinical Research OB/GYN REI Division, University of California, San Francisco, CA, USA; 4Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling, Shanghai Pudong Hospital, Shanghai, 201399, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ligang Zhou, Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, People’s Republic of China, Tel +8613611927616, Email zhouligang@yahoo.comBackgrounds and Objective: Diabetic foot is a relatively severe complication in patients with type 2 diabetes (T2D), with peripheral neuropathy and angiopathy frequently serving as risk factors. However, it is unknown how the other major systemic metabolic factors impacted the profile of these patients, besides glucose management. Thus, we investigated the distinct characteristics of patients with diabetic foot ulcers and their relationships with angiopathy.Materials and Methods: We obtained the laboratory data of 334 diabetic patients at Shanghai Pudong Hospital from 2020 to 2023. The comparisons were performed between the groups with or without diabetic foot, including glucose metabolism, lipids profile, liver and kidney function, thyroid function, and serum iron. The association between metabolic factors and lower extremity computed tomography angiography (CTA) was analyzed.Results: We found significant disparities between groups in relation to age, serum protein content, liver transferase, serum creatinine, estimated glomerular filtration rate (eGFR), serum uric acid (UA), small dense low-density lipoprotein (sdLDL), lipoprotein A (LP(a)), apolipoprotein A1 (APOA1), thyroid function, serum iron, and hemoglobin (Hb) (p< 0.05). The Spearman correlational analyses showed that the severity of CTA, categorized by the unilateral or bilateral plaque or occlusion, was positively significantly correlated with UA (r=0.499), triglyceride (TG) (r=0.751), whereas inversely correlated with serum albumin (r=− 0.510), alanine aminotransferase (r=− 0.523), direct bilirubin (DBil) (r=− 0.494), total bilirubin (TBil) (r=− 0.550), Hb (r=− 0.646).Conclusion: This cross-section investigation showed that compared to T2D only, the patients with diabetic foot ulcer (DFU) might display similar glucose metabolic control context but adverse metabolic profiles, and this profile is associated with macrovascular angiopathy characteristics and their severity.Keywords: diabetic foot, macrovascular angiopathy, CTA, thyroid function, serum iron, serum bilirubin

Peng J, Chen W, Chen J, Yuan Y, Zhang J, He Y. Cancer Manag Res. 2018;10:1163-1175. We, the Editor and Publisher of the journal Cancer Management and Research, have retracted the following article. Following publication of the article, concerns were raised about the duplication of images from Figure 3 with images from an unrelated article. Specifically, Images for Figure 3C and 3D have been duplicated with images for Figure 2c, 2d and 2h from Cao Q, Liu F, Ji K, et al. MicroRNA-381 inhibits the metastasis of gastric cancer by targeting TMEM16A expression. J Exp Clin Cancer Res. 2017;36:29. https://doi.org/10.1186/s13046-017-0499-z. The authors responded to our queries but were unable to provide a satisfactory explanation for the duplicated images or provide satisfactory data for the study. As verifying the validity of published work is core to the integrity of the scholarly record, the Publisher and Editor requested to retract the article and the authors agree with this decision. The authors wish to apologize for any inconvenience caused to the journal and readers. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Fangfang Liu, Yinghan Dong, Yuan Yuan, Yingjie Jiang School of Psychology, Northeast Normal University, Changchun, Jilin, People’s Republic of ChinaCorrespondence: Yingjie Jiang, School of Psychology, Northeast Normal University, No. 5268, Renmin Street, Changchun, Jilin Province, People’s Republic of China, Email jiangyj993@nenu.edu.cnIntroduction: Interpersonal relationship serve as crucial of social support and a sense of security for left-behind children, playing a compensatory role in mitigating the absence of familial affection. Interpersonal distress can significantly impact their mental well-being. Although previous research has established a connection between empathy and interpersonal distress, the mechanisms by which empathy triggers interpersonal distress, as well as potential gender-based variations in this relationship, remain elusive. To bridge this gap in knowledge, this study investigates the mediating influence of emotion regulation and the moderating impact of gender in the relationship between empathy and interpersonal distress.Methods: A total of 713 rural left-behind children completed the Interpersonal Reactivity Index scale, Emotion Regulation Competence Scale, and Interpersonal Relationship Assessment Scale.Results: Pearson correlation analyses suggested strong significant correlations among empathy, emotion regulation ability, and interpersonal distress. Path analyses indicated that emotion regulation ability mediated the relationship between empathy and interpersonal distress. Furthermore, hierarchical regression analyses suggest a moderating effect of gender in the relationship between empathy and emotion regulation ability.Discussion: The present study reveals the role of emotion regulation ability and gender in the relationship between empathy and interpersonal distress, which has important theoretical and practical implications for the prevention and intervention of interpersonal distress in left-behind children. Moreover, it may strengthen the relationship between peer and teacher at school, and improve the quality of parent-child communication at home.Keywords: empathy, interpersonal distress, emotion regulation ability, gender, left-behind children

Jinzhu Huang,&ast; Jinxin Zhao,&ast; Miao Yi, Yaling Yuan, Peiwen Xia, Bingxue Yang, Jiajia Liao, Zijun Dang, Yun Xia&ast; Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yun Xia, Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel +86-13668043942, Fax +86-23-89012513, Email xiayun12cn@aliyun.comPurpose: This research aims to profile ten novel strains of carbapenem-resistant Enterobacteriaceae (CRE) co-carrying blaKPC and blaNDM.Methods: Clinical CRE strains, along with corresponding medical records, were gathered. To ascertain the susceptibility of the strains to antibiotics, antimicrobial susceptibility tests were conducted. To validate the transferability and cost of fitness of plasmids, conjugation experiments and growth curves were employed. For determining the similarity between different strains, ERIC-PCR was utilised. Meanwhile, whole genome sequencing (WGS) was performed to characterise the features of plasmids and their evolutionary characteristics.Results: During the course of this research, ten clinical CRE strains co-carrying blaKPC and blaNDM were gathered. It was discovered that five out of these ten strains exhibited resistance to tigecycline. A closer examination of the mechanisms underlying tigecycline resistance revealed that tmexCD 1-toprJ 1, blaKPC-2, and blaNDM-1 existed concurrently within a single Citrobacter freundii strain (CF10). This strain, with a minimum inhibitory concentration (MIC) of 32 mg/L to tigecycline, was obtained from a sepsis patient. Furthermore, an investigation of genome evolution implied that CF10 belonged to a novel ST type 696, which lacked analogous strains. Aligning plasmids exposed that similar plasmids all had less than 70% coverage when compared to pCF10-tmexCD1, pCF10-KPC, and pCF10-NDM. It was also found that tmexCD 1-toprJ 1, blaKPC-2, and blaNDM-1 were transferred by Tn 5393, IS 5, and Tn 6296, respectively.Conclusion: This research presents the first report of coexistence of tmexCD 1-toprJ 1, blaKPC-2, and blaNDM-1 in a carbapenem and tigecycline-resistant C. freundii strain, CF10.Importance: Tigecycline is considered a “last resort” antibiotic for treating CRE infections. The ongoing evolution of resistance mechanisms to both carbapenem and tigecycline presents an alarming situation. Moreover, the repeated reporting of both these resistance mechanisms within a single strain poses a significant risk to public health. The research revealed that the genes tmexCD 1-toprJ 1, blaKPC-2, and blaNDM-1, which cause carbapenem and tigecycline-resistance in the same strain, were located on mobile elements, suggesting a potential for horizontal transmission to other Gram-negative bacteria. The emergence of such a multi-resistant strain within hospitals should raise significant concern due to the scarcity of effective antimicrobial treatments for these “superbugs”.Keywords: blaKPC, blaNDM, carbapenem-resistantEnterobacteriaceae, tigecycline-resistance, tmexCD 1-toprJ 1

Xiaxia Jin,1,&ast; Haideng Yang,2,&ast; Weiwei Ma,1,&ast; Yuan Yuan,1 Tao Li3 1Department of Clinical Laboratory, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, People’s Republic of China; 2Department of Gastroenterology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, People’s Republic of China; 3Department of Cardiovascular Medicine, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuan Yuan, Department of Clinical Laboratory, Taizhou Hospital of Zhejiang Province, 150 Ximen Road, Linhai, Zhejiang Province, People’s Republic of China, Email yuany@enzemed.com Tao Li, Department of Cardiovascular Medicine, Taizhou Hospital of Zhejiang Province, 150 Ximen Road, Linhai, Zhejiang Province, People’s Republic of China, Email litao@enzemed.comObjective: To evaluate the relationship between high-sensitivity cardiac troponin T (hs-cTnT) and prognosis in elderly patients with coronavirus disease 2019 (COVID-19).Methods: This study recruited 1399 COVID-19 patients aged 65 years or older admitted to Taizhou Hospital or Enze Hospital in Zhejiang Province from December 15, 2022, to January 4, 2023. The Cox regression model was used to evaluate the relationship between hs-cTnT level and in-hospital death. The logistic regression model was used to evaluate the relationship between hs-cTnT level and major adverse events. The restricted cubic spline (RCS) model is used for nonlinear analysis.Results: The increase of peak hs-cTnT was associated with the increased risk of death (HR 9.49; 95% CI 1.19– 75.48; trend p = 0.012) and major adverse events (OR 20.59; 95% CI 10.41– 40.71; trend p < 0.001). RCS model showed the association between peak hs-cTnT and death and major adverse events were nonlinear (P for non-line < 0.001). Starting from the limit of quantification of hs-cTnT (3ng/L), the risk of death and major adverse events had a steep S-shaped increase until hs-cTnT reached the 90th percentile point (hs-cTnT = 131 ng/L), followed by a plateau period. Peak hs-cTnT has good predictive value for death and major adverse events, with AUC of 0.834 and 0.804, respectively.Conclusion: Peak hs-cTnT has high predictive value for the risk of in-hospital death and major adverse events in elderly patients with COVID-19. The association between peak hs-cTnT and death and major adverse events were nonlinear.Keywords: high-sensitivity cardiac troponin T, elderly, COVID-19, nonlinearly, prognosis

Xun Lu,1– 3 Yue Yuan,4 Ning Cai,1– 3 Dean Rao,1– 3 Min Chen,4 Xiaoping Chen,1– 3 Bixiang Zhang,1– 3 Huifang Liang,1– 3 Lei Zhang3,5 1Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Clinical Medical Research Center of Hepatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4Division of Gastroenterology, Department of Internal Medicine at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 5Key Laboratory of Hepatobiliary and Pancreatic Diseases of Shanxi Province (Preparatory), Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Shanxi Medical University; Shanxi Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Taiyuan, People’s Republic of ChinaCorrespondence: Lei Zhang, Key Laboratory of Hepatobiliary and Pancreatic Diseases of Shanxi Province (Preparatory), Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Shanxi Medical University; Shanxi Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Taiyuan, 030032, People’s Republic of China, Email zhangl@tjh.tjmu.edu.cn Huifang Liang, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, People’s Republic of China, Email lianghuifang1997@126.comPurpose: Tripartite motif containing 55 (TRIM55) is a member of the TRIM family and functions as an E3 ubiquitin ligase. It acts as a cancer promoter or suppressor in the malignant processes of multiple cancers. However, its proliferative function in hepatocellular carcinoma (HCC) has been poorly studied, and its underlying molecular mechanism remains unclear. In the present study, we investigated the role of TRIM55 in HCC and its mechanism of promoting HCC proliferation.Materials and Methods: Protein expression levels of TRIM55 were measured in paired HCC and normal tissue samples using immunohistochemical (IHC) staining. The correlation between TRIM55 and clinical features was evaluated by statistical analysis. At the same time, overexpression and knockdown experiments, cycloheximide (CHX) interference experiments, ubiquitination, co-immunoprecipitation and immunofluorescence staining experiments, as well as animal experiments were used to evaluate the potential mechanism that TRIM55 promotes proliferation of hepatocellular carcinoma in vitro and in vivo.Results: TRIM55 expression in HCC specimens was higher compared with the corresponding non-tumor tissues. The overall survival and disease-free survival time of patients with high TRIM55 expression were shorter than those with low expression of TRIM55. Functionally, TRIM55 promoted the proliferation of HCC cells and accelerated the growth of HCC xenografts. Mechanistically, TRIM55 interacted with thyroid receptor interacting protein 6 (TRIP6) and regulate its stability by influencing the ubiquitination process, thereby affecting the Wnt signaling pathway.Conclusion: Our results indicate that TRIM55 promotes HCC proliferation by activating Wnt signaling pathways by stabilizing TRIP6. Therefore, targeting TRIM55 may be an effective therapeutic strategy to inhibit HCC growth.Keywords: TRIM55, TRIP6, hepatocellular carcinoma, proliferation

Jingliang Ran,1 Huiyue Liu,2 Yue Yuan,3 Xuan Yu,4 Tiantian Dong5 1School of Business Administration, Chongqing Technology and Business University, Chongqing, People’s Republic of China; 2Department of Psychology, Hunan Normal University, Changsha, People’s Republic of China; 3College of State Governance, Southwest University, Chongqing, People’s Republic of China; 4School of Economics and Management, Southwest Petroleum University, Chengdu, People’s Republic of China; 5Hilton School of Hospitality Management, Sichuan Tourism University, Chengdu, People’s Republic of ChinaCorrespondence: Yue Yuan, College of State Governance, Southwest University, No. 2 Tiansheng Road, Beibei District, Chongqing, 400715, People’s Republic of China, Tel +86 15736077200, Email yuanyue_xue@163.com Xuan Yu, School of Economics and Management, Southwest Petroleum University, No. 8 Xindu Avenue Xindu District, Chengdu, Sichuan Province, 637001, People’s Republic of China, Tel +86 15213202551, Email yuxuan_0917@aliyun.comIntroduction: In the post-pandemic era, the cultivation of vocational adaptability among college students holds equal significance to fostering subjective well-being in the face of an increasingly daunting professional landscape. This intricate process can be influenced by exploratory expeditions into potential career paths, sincere introspection, and a profound sense of vocation.Methods: Drawing upon Bandura’s self-regulation theory, this research project employed structural equation modeling (SEM) to scrutinize the interconnectedness between career exploration, self-reflection, vocational calling, vocational adaptability, and subjective well-being within a sample of 1077 Chinese undergraduates.Results: The findings demonstrated that career exploration and self-reflection positively predicted career adaptability and subjective well-being. In addition, career calling had a significant mediating effect in this model.Conclusion: The findings of this study shed light on the significance of career exploration and self-reflection in fostering both adolescent career adaptability and subjective well-being. And are expected to provide a reference for the career construction and development of college students and career education in colleges and universities.Keywords: career exploration, self-reflection, career calling, career adaptability, subjective well-being

Meng Zhou,&ast; Fang Lu,&ast; Ling Jiang, Chen Chen, Si Chen, Luhan Geng, Rui Sun, Qing Li, Suyan Duan, Bo Zhang, Huijuan Mao, Changying Xing, Yanggang Yuan Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanggang Yuan; Changying Xing, Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, 300 Guangzhou Road, Nanjing, Jiangsu Province, 210029, Tel/Fax +86-25-6830-6462, Email ygyuan@njmu.edu.cn; cyxing62@126.comAim: Diabetic kidney disease (DKD) continues to be devastating complication of diabetes mellitus. Immune response and inflammatory reaction play essential roles in the progression of DKD. But the specific mechanism of immune cells, and their act on renal innate cells remains unclear. This article focused on immune cells and their communication with renal innate cells to provide bioinformatic evidence for further understanding the immune mechanism in DKD.Methods: Data were analyzed to evaluate the differentially expressed genes (DEGs) and their pathways in DKD patients and mice. Gene set enrichment analysis (GSEA) was used to explore the immune inflammation-related pathways. CIBERSORT was applied to evaluate the distribution of inflammatory cells in different states. Cell-type DEGs and their enrichment pathways were further explored in podocytes, proximal tubule cells and injured tubule cells. Cellchat was used to reveal the cellular communication between immune cells and renal innate cells in DKD.Results: GO and KEGG analysis showed that DEGs were mainly enriched in immune inflammation-related pathways. Monocytes, M2 macrophages and T cells were significantly increased in DKD samples, especially in renal tubule. ScRNA datasets showed that the immune cells number in DKD were significantly increased. Cell-type DEGs were involved in kidney growth and development. In DKD, the interaction numbers and strength between immune cells and innate cells were significantly increased. VISTANT, SPP1 and IGF signal flow were increased in DKD. SPP1-CD44, NRG1-ERBB4, NAMPT-INSR, and Igf1-Igf1r receptor ligand pairs were enhanced in DKD, which mediated the communication between immune-inflammatory cells and innate cells.Conclusion: Our study explored the pathogenesis of renal injury promoted by immunoinflammatory in DKD. VISTANT, SPP1, and IGF signaling pathways and SPP1-CD44, NRG1-ERBB4, NAMPT-INSR, and Igf1- Igf1r receptor ligand pairs might occupy essential place in the occurrence and progress of DKD.Keywords: diabetic kidney disease, immune cells, renal innate cells, bioinformatics

Yi Liang,1,2 Xiaohong Li,1 Fang Wang,2 Zongting Yan,2 Yuhuan Sang,2 Yuan Yuan,2 Yun Qin,1 Xuefei Zhang,1 Mei Ju2 1Health Management Center, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 2Nursing College, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of ChinaCorrespondence: Mei Ju; Xiaohong Li, Email 593576753@qq.com; 1848922774@qq.comBackground: Thyroid nodules (TNs) are among the most common thyroid lesions, and rates of these nodules have risen over the past three decades. As the majority of TN patients remain asymptomatic when these nodules are in the early stages of development, malignant nodules may continue to develop into thyroid cancer when not detected. As such, early screening and diagnosis-based strategies represent the most promising means of preventing or treating TNs and associated cancers. The present study was thus developed to explore TN prevalence among individuals in Luzhou, China.Methods: Here, thyroid ultrasonography and metabolic-related indicators from 45,023 adults undergoing routine physical examinations in the Health Management Center of a large Grade A hospital in Luzhou over the last three years were retrospectively reviewed in an effort to identify factors associated with TN risk and the detection of these nodules through univariate and multivariate logistic regression analyses.Results: In total, 13,437 TNs were detected in these 45,023 healthy adults for an overall 29.8% detection rate. This TN detection rate rose with age, and multivariate logistic regression analyses revealed that independent risk factors associated with TNs included greater age (≥ 31 years old), female (OR = 2.283, 95% CI: 2.177– 2.393), central obesity (OR = 1.115, 95% CI: 1.051– 1.183), impaired fasting glucose (OR = 1.203, 95% CI: 1.063– 1.360), overweight status (OR = 1.085, 95% CI: 1.026– 1.147), and obesity (OR = 1.156, 95% CI: 1.054– 1.268), while low BMI was a protective factor associated with lower rates of TN incidence (OR = 0.789, 95% CI: 0.706– 0.882). When results were stratified by gender, impaired fasting glucose was not an independent predictor of TN risk among males, while high LDL levels were an independent predictor of TNs among females, and other risk factors were not significantly changed.Conclusion: TN detection rates were high among adults in Southwestern China. Female, elderly individuals, individuals exhibiting central obesity, and those with high levels of fasting plasma glucose are more likely to develop TN.Keywords: thyroid nodules, detection rate, influence factors

Dong Zhang,1 Yan Qu,2 Changlin Sui,2 Meiling Li,1 Yanmei Yuan,1 Ningning Wang,1 Weiyuan Ma1 1Department of Dermatology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, People’s Republic of China; 2Department of Dermatology, Yantai Yuhuangding Hospital, Yantai, Shandong, People’s Republic of ChinaCorrespondence: Weiyuan Ma, Department of Dermatology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, People’s Republic of China, Email fymaweiyuan@wfmc.edu.cnBackground: Condyloma cuminata (CA) is a sexually transmitted disease caused by human papillomavirus (HPV) infection, which is prone to recurrence and difficult to cure in the short term. CD207 is a C-type lectin receptor that is specifically expressed on the surface of Langerhans cells (LCs) and is considered as an LC-specific immunohistochemical marker. The main purpose of this study is to explore the correlation between the expression of CD207 in CA skin lesions and the duration of CA disease course and frequency of recurrence, in order to provide new prognostic markers for CA to clinicians.Materials and Methods: A total of 40 male patients with CA and their skin lesions were collected, as well as 40 healthy male penile tissue samples. The skin lesions of CA were clinically and histologically confirmed by acetic acid test. The expression of CD207 in epidermal tissues was detected using immunohistochemistry. The difference in the number of CD207 positive cells between CA skin lesions and healthy skin controls was compared, and the association between the number of CD207 positive cells in CA skin lesions and the duration of disease course and the frequency of recurrence was determined through Spearman correlation analysis.Conclusion: In CA skin lesions, CD207 positive cells were found to have morphological abnormalities and the number of cells was significantly reduced compared to healthy skin, suggesting that there may be antigen presentation dysfunction in CA skin lesions, which may be the reason for the prolonged and unresolved condition of the disease. The fewer CD207 positive cells in CA skin lesions, the longer the disease course and the more frequent the recurrence, therefore, the expression level of CD207 can be used as a new prognostic marker for predicting the outcome of CA.Keywords: condyloma acuminata, CD207, langerhans cells, prognosis, biomarker

Junhong Xu,1 Youhua Yuan,1 Baoya Wang,1 Qi Zhang,1 Jing Wang,2 Shanmei Wang,1 Yi Li,1 Wenjuan Yan1 1Department of Clinical Laboratory, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, and People’s Hospital of Henan University, Zhengzhou, Henan, 450003, People’s Republic of China; 2Xinyang Third People’s Hospital, Xinyang, Henan, 464000, People’s Republic of ChinaCorrespondence: Yi Li; Wenjuan Yan, Department of Clinical Laboratory, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, and People’s Hospital of Henan University, Zhengzhou, Henan, 450000, People’s Republic of China, Tel +86-371-65580484, Fax +86-371-87160318, Email liyilabmed@henu.edu.cn; yanwenjuan2008@126.comPurpose: To study the etiological characteristics and risk factors affecting the prognosis of patients with polymicrobial bloodstream infections.Patients and Methods: Overall, 141 patients with polymicrobial bloodstream infections in Henan Provincial People’s Hospital during 2021 were included. Laboratory test indexes, department of admission, sex, age, intensive care unit (ICU) admission, surgical history, and central venous catheter placement were collected. Patients were divided into surviving and deceased groups based on outcomes at discharge. Mortality risk factors were identified by univariate and multivariable analyses.Results: Seventy-two of 141 patients survived. Patients were mainly from the ICU and the Departments of Hepatobiliary Surgery and Hematology. Overall, 312 microbial strains were detected: 119 gram-positive, 152 gram-negative, and 13 anaerobic bacteria and 28 fungi. Among the gram-positive bacteria, coagulase-negative staphylococci were most frequent (44/119, 37%), followed by enterococci (35/119, 29.4%). Among coagulase-negative staphylococci, methicillin-resistant coagulase-negative staphylococci incidence was 75% (33/44). Among gram-negative bacteria, Klebsiella pneumoniae was most common (45/152, 29.6%), followed by Escherichia coli (25/152, 16.4%) and Pseudomonas aeruginosa (13/152, 8.6%). Among K. pneumoniae, the incidence of carbapenem-resistant (CR) K. pneumoniae was 45.7% (21/45). On univariate analysis, mortality risk factors included increased white blood cells and C-reactive protein, decreased total protein and albumin, CR strains, ICU admission, central venous catheter, multiple organ failure, sepsis, shock, pulmonary diseases, respiratory failure, central nervous system diseases, cardiovascular diseases, hypoproteinemia, and electrolyte disturbances (P < 0.05). Multivariable analysis showed that ICU admission, shock, electrolyte disorders, and central nervous system diseases were independent mortality risk factors. The survival curve shows that the survival rate of patients with polymicrobial CR bloodstream infections was lower than that of patients with polymicrobial non-CR bloodstream infections (P=0.029).Conclusion: Patients with polymicrobial bloodstream infections are typically critically ill and harbor multidrug-resistant bacteria. Thus, to minimize mortality rate in critically ill patients, changes in infectious flora should be monitored, antibiotics selected reasonably, and invasive procedures reduced.Keywords: clinical characteristic, etiology, intensive care unit, polymicrobial bloodstream infections, risk factors

Yun Wang,1 Zhongfeng Huang,2 Huijuan Chen,3 Ye Yuan,2 Edward B McNeil,4 Xiaolong Lu,5 Aihua Zhang1 1Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 2Department of Tuberculosis, Guiyang Public Health Clinical Center, Guiyang, Guizhou, People’s Republic of China; 3Department of Tuberculosis Prevention and Control, Guizhou Center for Disease Prevention and Control, Guiyang, Guizhou, People’s Republic of China; 4Department of Infectious Diseases, School of Public Health and Primary Care, Chinese University of Hong Kong, Hong Kong, People’s Republic of China; 5School of Medicine and Health Management, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of ChinaCorrespondence: Aihua Zhang, Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China, Tel +86 851 88416187, Fax +86 851 88416187, Email 97349238@qq.comPurpose: We aimed to assess the household financial burden due to multidrug-resistant tuberculosis (MDR-TB) treatment and its predictors, examine its association with patient mobility, and test their impact on patient loss to follow-up (LTFU).Methods: A cross-sectional study combining follow-up data collection was conducted at the largest designated MDR-TB hospital in Guizhou. Data were collected from medical records and questionnaires. Household financial burden was measured by the incidence of 2 indicators: catastrophic total costs (CTC) and catastrophic health expenditure (CHE). Mobility was classified as mover or non-mover after the patient’s address was verified twice. A multivariate logistic regression model was used to identify associations between variables. Model I and Model II were separated by CHE and CTC.Results: Out of 180 households, the incidence of CHE and CTC was 51.7% and 80.6%, respectively. Families with low income and patients who were primary income earners were significantly associated with catastrophic costs. 42.8% of patients were movers. Patients from households with CHE (ORadj=2.2, 95% CI: 1.1– 4.1) or with CTC (ORadj=2.6, 95% CI: 1.1– 6.3) were more likely to move. Finding a job against financial difficulty (58.4%) was the top reason for movers. 20.0% of patients experienced LTFU. Patients from households with catastrophic payments (CHE: ORadj=4.1, 95% CI 1.6– 10.5 in Model I; CTC: ORadj=4.8, 95% CI 1.0– 22.9 in Model II), patients who were movers (ORadj=6.1, 95% CI 2.5– 14.8 in Model I; ORadj=7.4, 95% CI 3.0– 18.7 in Model II) and primary income earners (ORadj=2.5, 95% CI: 1.0– 5.9 in Model I; ORadj=2.7, 95% CI 1.1– 6.6 in Model II) had an increased risk of LTFU.Conclusion: There is a significant association between household financial burden due to MDR-TB treatment and patient mobility in Guizhou. They impact patients’ treatment adherence and cause LTFU. Being a primary breadwinner increases the risk for catastrophic household payments and LTFU.Keywords: household catastrophic costs, migration, loss to follow-up, Guizhou, MDR-TB

Xia Liu,1,2,&ast; Xiaojing Jiao,1,&ast; Xiaowei Gong,3 Qingrong Nie,4 Yang Li,2 Guohua Zhen,5 Mengyu Cheng,6 Jianguo He,7 Yadong Yuan,3 Yuanhua Yang1 1Department of Respiratory and Critical Care Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Capital Medical University Daxing Teaching Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Beijing Fangshan District Liangxiang Hospital, Beijing, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 7Department of Cardiovascular Medicine, Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanhua Yang, Department of Respiratory and Critical Care Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China, Email yyh1031@sina.com Yadong Yuan, The Second Hospital of Hebei Medical University, Hebei, 050004, People’s Republic of China, Email yyd1108@163.comBackground and Objective: The prevalence of venous thrombus embolism (VTE) in patients with chronic obstructive pulmonary disease (COPD) is higher than in patients without COPD. Owing to the similarity of clinical symptoms between PE and acute exacerbation COPD (AECOPD), PE is likely to be overlooked or underdiagnosed in patients with AECOPD. The aim of the study was to investigate the prevalence, risk factor, clinical characteristics, and prognostic impact of VTE in patients with AECOPD.Methods: This multicenter, prospective, cohort study was conducted in 11 research centers of China. Data on the baseline characteristics, VTE-related risk factors, clinical symptoms, laboratory examination results, computed tomography pulmonary angiography (CTPA) and lower limb venous ultrasound of AECOPD patients were collected. Patients were followed up for 1 year.Results: A total of 1580 AECOPD patients were included in the study. The mean (SD) age was 70.4 (9.9) years and 195 (26%) patients were women. The prevalence of VTE was 24.5% (387/1580) and PE was 16.8% (266/1580). VTE patients were older; had higher BMI; and longer course of COPD than non-VTE patients. The history of VTE, cor pulmonale, less purulent sputum, increased respiratory rate, higher D-dimer, and higher NT-proBNP/BNP were independently associated with VTE in hospitalized patients with AECOPD. The mortality at 1-year was higher in patients with VTE than patients without VTE (12.9% vs 4.5%, p< 0.01). There was no significant difference in the prognosis of patients with PE in segmental or subsegmental arteries and in main pulmonary arteries or lobar arteries (P> 0.05).Conclusion: VTE is common in COPD patients and is associated with poor prognosis. Patients with PE at different locations had poorer prognosis than patients without PE. It is necessary to perform active screening strategy for VTE in AECOPD patients with risk factors.Keywords: chronic obstructive pulmonary disease, venous thromboembolism, computed tomography pulmonary angiography, prognosis

Zhongyuan Lin,&ast; Changliang Luo,&ast; Yulin Yuan Department of Clinical Laboratory, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yulin Yuan, Department of Clinical Laboratory, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, (No. 6 Tao Yuan Road), Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China, Email yiran2020221007@126.comObjective: To explore the predictive value of the ratio of monocyte to apolipoprotein A1 (MAR) (a new index related to inflammation and lipid in breast cancer (BC)) and its relationship with clinicopathological staging.Methods: The hematological test results of 394 patients with breast diseases, including 276 cases of BC, 118 cases of benign breast disease (BBD), and 219 healthy volunteers (HV), were retrospectively collected. The clinical value of MAR was analyzed with binary logistic regression.Results: Using statistical software analysis, the results showed that MAR level (P< 0.001) was the largest in the BC group, followed by BBD, and the lowest in the HV group, and it was found to be an indicator to distinguish BC from BBD, also an independent risk factor for BC. The increase in MAR level showed that the risk of BC was 3.733 times higher than that of HV (P< 0.001). In addition, there was a notable difference in MAR between early, middle and late stages of BC patients (P=0.047), with the highest MAR level in late stage (0.510± 0.078) and the lowest MAR level in early stage (0.392± 0.011); the MAR level of those with tumor invasion depth of Phase 4 was the highest (0.484± 0.072), and that of Phase 1/2 was the lowest (0.379± 0.010), with a statistically significant difference (P< 0.001). MAR was positively correlated with tumor invasion depth (P< 0.001, r=0.210), that’s, the size of MAR increased when there was more deeper tumor invasion.Conclusion: MAR is a new indicator for the auxiliary differential diagnosis of benign and malignant breast diseases, and is also an independent risk factor for BC. High-level MAR is closely related to late staging and tumor invasion depth of BC. It can be seen that MAR is a potentially valuable predictor of BC, and this is the first study to explore the clinical value of MAR in BC.Keywords: breast cancer, breast benign disease, the ratio of monocyte to apolipoprotein A1, Monocyte, Apolipoprotein A1

Yifan Yuan,1,2,&ast; Na Li,1,2,&ast; Mingyue Fu,1,2,&ast; Mei Ye1,2 1Department of Gastroenterology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, 430071, China; 2Hubei Clinical Centre and Key Laboratory of Intestinal and Colorectal Diseases, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, 430071, China&ast;These authors contributed equally to this workCorrespondence: Mei Ye, Email wumeiye08@163.comBackground: Ulcerative colitis (UC) is a chronic inflammatory disease of the colon and rectum that has no exact cause and is characterized by relapsing and remitting episodes. We aimed to find biomarkers of UC and its causes.Methods: We got GSE73661 from the GEO database and used WGCNA to find DEGs that were expressed in the same way in both normal and UC samples. To identify the co-expression modules, we used Weighted Gene Co-Expression Network Analysis. Next, we selected genes that were both DEGs and parts of main modules. Later, three datasets were used to find the hub genes, and qRT-PCR was utilized to confirm the in-silico findings. Additionally, we analyzed the connection between the hub genes and the filtration of immune cells in UC. Using the databases, we made predictions about the miRNAs and lncRNAs that regulate the hub genes and predicted possible therapeutic drugs.Results: We found 822 DEGs and three main modules related to immunity, endoplasmic reticulum, and metabolism. Using another three datasets and human samples to confirm the mRNA expression of these genes in UC patients, XBP1 and PLPP1 were selected as hub genes, and had excellent diagnostic potential. According to the findings of the immune infiltration, patients with UC exhibited a larger proportion of immune cells. And hub genes, particularly XBP1, were closely linked to a number of immune cell infiltrations. Based on the databases and hub genes, a lncRNA-miRNA-mRNA network, including two miRNAs (miR-214-3p and miR-93-5p), two hub genes, and 124 lncRNAs, and potential therapeutic medicine were identified.Conclusion: We found two new genes, XBP1 and PLPP1, that are involved in UC and can help diagnose and measure the disease. XBP1 also relates to clinical scores and immune cells. We suggested a gene network and possible drugs based on them.Keywords: ulcerative colitis, hub genes, biomarkers, bioinformatics analysis, ceRNA regulatory network

Chao Han,1,2 Haiyan Ji,1 Yaxin Guo,1 Yuanhui Fei,1 Chunhui Wang,1 Yanbo Yuan,1 Zhihui Ruan,1 Tieliang Ma1,2 1Department of Anesthesiology, The Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu, 214200, People’s Republic of China; 2Yixing Clinical College, Medical College of Yangzhou University, Yixing, Jiangsu, 214200, People’s Republic of ChinaCorrespondence: Chao Han, Department of Anesthesiology, The Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu, 214200, People’s Republic of China, Tel +86 13961568178, Fax +86 051087921010, Email staff940@yxph.comBackground: Perioperative neurocognitive disorders (PND), including delayed neurocognitive recovery (dNCR) and postoperative cognitive dysfunction (POCD), are common postoperative complications in elderly patients and adversely affect their prognosis. The study was designed to explore the effects of esketamine on postoperative cognitive function in elderly patients who underwent gastrointestinal surgery under general anesthesia and its potential mechanism.Methods: Eighty-four patients aged 65 and above undergoing gastrointestinal surgery were randomly divided into 2 groups: the esketamine group (group S) and the control group (group C). Group S received intravenous sub-anesthetic doses of esketamine (0.15 mg/kg) 5 minutes before the initiation of surgery, while group C received the same volume of saline. A battery of neuropsychological tests was used to assess cognitive function before surgery, 7 days, and 3 months after surgery. The primary outcome was the incidence of dNCR at 7 days postoperatively and POCD at 3 months postoperatively in both groups. The secondary outcome measures included changes in the levels of serum interleukin-6 (IL-6) and calcium-binding protein β (S100β) before and 1 day after surgery.Results: The incidence of dNCR in group S was lower than that of group C (18.15% vs 38.24% P=0.033). Contrarily, there was no difference in both groups regarding POCD 3 months postoperatively (6.06% vs 14.37% P=0.247). Plasma IL-6 and S100β levels were significantly elevated in both groups on postoperative day 1 (p< 0.05), but esketamine pretreatment reduced these levels to some extent compared with group C (p< 0.05).Conclusion: Sub-anesthetic doses of esketamine might reduce the incidence of dNCR and improve early postoperative cognitive function in elderly patients undergoing gastrointestinal surgery, which might be related to the anti-neuroinflammation effects of esketamine.Keywords: esketamine, perioperative neurocognitive disorders, gastrointestinal surgery, elderly, neuroinflammatory

Rongcheng An,1 Yingwei Ou,1 Lingxiao Pang,1 Yongsheng Yuan,1 Qian Li,1 Hao Xu,2 Bin Sheng1 1Emergency and Critical Care Center, Department of Emergency Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, People’s Republic of China; 2Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of ChinaCorrespondence: Bin Sheng, Emergency and Critical Care Center, Department of Emergency Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, People’s Republic of China, Tel +86 571 85893793, Email shengbin@hmc.edu.cnPurpose: Community-associated bloodstream infection (CA-BSI) is increasing in many community settings. However, the clinical significance and epidemiology of CA-BSI present in hospital admissions in China are not well established. In this work, we identified the risk factors in outpatients presenting with CA-BSI, and investigate the role of procalcitonin (PCT) and hypersensitive C-reactive protein (CRP) in diagnosing different types of the pathogen in patients with acute CA-BSI.Methods: A retrospective study enrolling 219 outpatients with CA-BSI from The Zhejiang People’s Hospital from January 2017 to December 2020 was performed. Susceptibility of the isolates obtained from these patients was examined. Subjecting receiver operating characteristic curves (ROC) were constructed to analyze the specificity and sensitivity of PCT, CRP, and WBC in determining infections caused by different bacterial genera. Risk factors for CA-BSI in the emergency setting were analyzed using essential information and simple identification of other pathogenic bacterial species through rapidly tested biomarkers.Results: A total of 219 patients were included in the selection criteria, of which 103 were infected with Gram-positive bacteria (G+) and 116 with Gram-negative bacteria (G-). The PCT was significantly higher in the GN-BSI group than in the GP-BSI group, while no significant difference was observed between the two groups for CRP. Subjecting ROC curves were constructed to analyze WBC, CRP, and PCT, and the area under the curve (AUC) of the PCT in this model was 0.6661, with sensitivity = 0.798 and specificity = 0.489.Conclusion: The PCT between the GP-BSI group and the GN-BSI group was significantly different. By combining the knowledge of clinicians and the clinical signs of patients, PCT should be utilized as a supplementary approach to initially determine pathogens and direct medication in the early stages of clinical practice.Keywords: community-associated bloodstream infections, PCT, gram-negative, gram-positive, diagnostic predictions

Zheng Liu,1 Qian Wang,1 Hui Wang,1 Jing Li,1 Ying Yuan,2 Guo-zhen Yi1 1Department of Respiratory Medicine, the Petroleum Clinical Medical College of Hebei Medical University, Langfang, People’s Republic of China; 2Department of Respiratory Medicine, the Langfang Third Hospital, Langfang, People’s Republic of ChinaCorrespondence: Zheng Liu, Department of Respiratory Medicine, the Petroleum Clinical Medical, College of Hebei Medical University, No. 51 of Xinkai Road, Guangyang District, Langfang, Hebei, 065000, People’s Republic of China, Tel +863162077814, Email zhengl06drsun@163.comBackground: To look at the differences and similarities in albumin and lipid metabolism in non-severe COVID-19 infection, non-severe community-acquired pneumonia, and severe community pneumonia with underlying diseases, as well as the relationship between albumin and lipid metabolism and inflammatory mediators.Methods: This retrospective analysis comprised 253 individuals with bacterial pneumonia and COVID-19 infection (1 May 2021– 1 May 2022). Routine blood examination, blood lipid levels, albumin level, C-reactive protein (CRP) levels, coagulation function, cardiac enzymes, liver function, renal function, immunological function, and bacterial culture were also collected. Correlation analysis was performed using Spearman’s test for lipid parameter and Inflammatory factors in the blood. Furthermore, the multiple linear regression (MLR) analysis was employed to analyze the multicollinearity in lipidomics data. The statistical analysis was performed using SPSS statistic version 19.0.Results: There were 63 (24.90%) non-severe community-acquired pneumonia patients (NSCAP), 48 (18.97%) severe community-acquired pneumonia patients (SCAP), 112 (44.27%) non-severe COVID-19 infection patients (NSCOV), and 30 (11.86%) healthy volunteers (HV). In all, 45.59% (116/253) of the patients had underlying diseases. Patients with community-acquired pneumonia had lower albumin and cholesterol levels than those with non-severe COVID-19 infection and healthy controls (t = − 3.81, − 2.09, P = 0.00, 0.04). Albumin, triglyceride, cholesterol, and LDL-C levels in peripheral blood were considerably lower in the SCAP group than in the NSCAP group. Albumin, cholesterol, HDL-C, LDL-C, and aop-A were all inversely connected with CRP in the SCAP with underlying illness group, but cholesterol level was favorably correlated with lymphocyte count (R = 0.36, P = 0.01). Hypoproteinemia, hypotriglyceridemia, and an elevated neutrophil-to-lymphocyte count ratio are all risk factors for severe community-acquired pneumonia.Conclusion: Hypoalbuminemia and abnormal lipid metabolism are important indicators of bacterial infection, especially severe bacterial pneumonia.Keywords: bacterial pneumonia, COVID-19, hypoproteinemia, lipids

Yiran Chen,1,2,&ast; Xiaoling Wu,3,&ast; Xi Chen,1,2 Deliang Guo,1,2 Weijie Ma,1,2 Yonghua Guo,1,2 Kequan Xu,1,2 Shuxian Ma,1,2 Yufeng Yuan,1,2,4 Qian Zhu1,2 1Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China; 2Clinical Medicine Research Center for Minimally Invasive Procedure of Hepatobiliary & Pancreatic Diseases of Hubei Province, Wuhan, Hubei, 430071, People’s Republic of China; 3Department of Liver Surgery, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 4TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430071, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yufeng Yuan; Qian Zhu, Email yuanyf1971@whu.edu.cn; zhuqian@whu.edu.cnIntroduction: Hepatocellular carcinoma (HCC) was the sixth most prevalent cancer worldwide. Long non-coding RNA TGFB2-OT1 has been proven to mediate inflammation and autophagy in vascular endothelial cells. However, its function in HCC is still unknown.Methods: We analyzed the relationship between TGFB2-OT1 expression and the clinicopathological features of 202 HCC patients. RT-qPCR was used to analyze the TGFB2-OT1 expression in HCC cell lines and tissues. In vitro and in vivo assays were conducted to verify the effect of TGFB2-OT1 on the phenotype of HCC. RNA pull-down assays were applied to reveal the proteins binding to the TGFB2-OT1. Western-blot assays were conducted to analyze the protein expression in HCC cell lines.Results: TGFB2-OT1 was found to be highly expressed in HCC samples and hepatoma cells. TGFB2-OT1 expression was significantly associated with age (P = 0.001), cirrhosis (P = 0.003), tumor size (P < 0.001), tumor encapsulation (P = 0.029), tumor protruding from the liver surface (P = 0.040), and alpha fetoprotein (AFP, P < 0.001) levels. TGFB2-OT1 promoted proliferation, migration, invasion, and angiogenesis in HCC cells, both in vitro and in vivo. TGFB2-OT1 binds to β-catenin and competitively impaired the binding of β-catenin to GSK3β, thus suppressing the phosphorylation of β-catenin at Ser33, Ser37, and Thr41.Conclusion: TGFB2-OT1 is overexpressed in HCC and predicts the poor prognosis of HCC patients. TGFB2-OT1 impedes the phosphorylation of β-catenin and acts as an alternative activator of the Wnt/β-catenin pathway to promote the progression and angiogenesis of HCC.Keywords: TGFB2-OT1, HCC, β-catenin, angiogenesis, phosphorylation

Qi Zhang,1,&ast; Wenjuan Yan,1,&ast; Yingjie Zhu,2,&ast; Nan Jing,1 Shanmei Wang,1 Youhua Yuan,1 Bing Ma,1 Junhong Xu,1 Yafei Chu,1 Jiangfeng Zhang,1 Qiong Ma,1 Baoya Wang,1 Wenbo Xu,1 Liqiang Zhu,3 Ying Sun,2 Caiqin Shi,4 Juan Fang,5 Yi Li,1 Shengqun Liu6 1Department of Clinical Microbiology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, and People’s Hospital of Henan University, Zhengzhou, People’s Republic of China; 2Department of Clinical Microbiology, Henan No.3 Provincial People’s Hospital, Zhengzhou, People’s Republic of China; 3Department of Clinical Microbiology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 4Department of Microbiology Laboratory, KingMed Diagnostics Group Co., Ltd, Zhengzhou, People’s Republic of China; 5Department of Research and Development, Autobio Diagnostics Co., Ltd, Zhengzhou, People’s Republic of China; 6Department of Anesthesia and Perioperative Medicine, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, and People’s Hospital of Henan University, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Li; Shengqun Liu, Department of Anesthesia and Perioperative Medicine, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, and People’s Hospital of Henan University, Weiwu Road 7, Zhengzhou, Henan, 450003, People’s Republic of China, Tel +8613526882118, Fax +8637187160318, Email liyilabmed@henu.edu.cn; tim2002627@163.comPurpose: To evaluate the performance of five widespread commercial products for colistin and polymyxin B susceptibility testing in China for mcr-positive and -negative Escherichia coli and Klebsiella pneumoniae.Methods: A total of 132 E. coli and 83 K. pneumoniae strains (including 68 mcr-1-positive E. coli and 28 mcr-8-positive K. pneumoniae) were collected. We analysed the performance of colistin susceptibility (with Vitek 2 and Phoenix M50) and the performance of polymyxin B susceptibility (with DL-96II, MA120, and a Polymyxin B Susceptibility Test strip; POL E-strip). Broth microdilution was used as the gold standard. Categorical agreement (CA), essential agreement (EA), major error (ME), and very major error (VME) were calculated for comparisons.Results: For E. coli, the total CA, EA, ME, and VME to colistin were as follows: Vitek 2, 98.5%/98.5%/0%/2.9%; and Phoenix M50, 98.5%/97.7%/0%/2.9%. The total CA, EA, ME, and VME to polymyxin B were as follows: POL E-strip, 99.2%/63.6%/1.6%/0%; MA120, 70.0%/-/0%/58.8%; and DL-96II, 80.2%/-/1.6%/36.8%. Only Vitek 2 and Phoenix M50 presented satisfactory performances for mcr-1-positive E. coli. For K. pneumoniae, the total CA, EA, ME, and VME to colistin were as follows: Vitek 2, 73.2%/72.0%/0%/61.6%; and Phoenix M50, 74.7%/74.7%/0%/58.3%. The total CA, EA, ME, and VME to polymyxin B were as follows: POL E-strip, 91.6%/74.7%/2.1%/16.7%; MA120, 92.8%/-/2.1%/13.9%; and DL-96II, 92.2%/-/2.1%/8.3%. All systems were unsatisfactory for mcr-8-positive K. pneumoniae. When the susceptibility of mcr-negative strains was tested, all systems presented excellent performance.Conclusion: Vitek 2 and Phoenix M50 with colistin for E. coli showed acceptable performance regardless of mcr-1 expression, while DL-96II, MA120, and the POL E-strip performed worse for mcr-1-positive strains. Furthermore, mcr-8 greatly affected the performance of all systems with both colistin and polymyxin B for K. pneumoniae isolates.Keywords: polymyxin B, colistin, mobilised colistin resistance, broth microdilution, susceptibility testing, semi-automated systems

Meiyuan Dong,1,2 Huiling Chen,2 Song Wen,2 Yue Yuan,2 Liling Yang,2 Yanyan Li,2 Xinlu Yuan,2 Dongxiang Xu,2 Ligang Zhou1– 3 1Graduate School of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, People’s Republic of China; 3Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling, Shanghai Pudong Hospital, Shanghai, People’s Republic of ChinaCorrespondence: Ligang Zhou, Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, People’s Republic of China, Tel +8613611927616, Email zhouligang@yahoo.comAbstract: With the emergence of sodium-glucose cotransporter 2 inhibitors (SGLT2i), the treatment of type 2 diabetes mellitus (T2DM) has achieved a new milestone, of which the insulin-independent mechanism could produce weight loss, improve insulin resistance (IR) and exert other protective effects. Besides the well-acknowledged biochemical processes, the dysregulated balance between sympathetic and parasympathetic activity may play a significant role in IR and obesity. Weight loss caused by SGLT-2i could be achieved via activating the liver–brain–adipose neural axis in adipocytes. We previously demonstrated that SGLT-2 are widely expressed in central nervous system (CNS) tissues, and SGLT-2i could inhibit central areas associated with autonomic control through unidentified pathways, indicating that the role of the central sympathetic inhibition of SGLT-2i on blood pressure and weight loss. However, the exact pathway of SGLT2i related to these effects and to what extent it depends on the neural system are not fully understood. The evidence of how SGLT-2i interacts with the nervous system is worth exploring. Therefore, in this review, we will illustrate the potential neurological processes by which SGLT2i improves IR in skeletal muscle, liver, adipose tissue, and other insulin-target organs via the CNS and sympathetic nervous system/parasympathetic nervous system (SNS/PNS).Keywords: sodium-glucose cotransporter 2 inhibitors, central nervous system, autonomic nervous system, insulin resistance, weight loss

Meiyuan Dong,1,2 Huiling Chen,2 Song Wen,2 Yue Yuan,2 Liling Yang,2 Dongxiang Xu,2 Ligang Zhou1– 3 1Graduate School of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, People’s Republic of China; 3Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling, Shanghai Pudong Hospital, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Ligang Zhou, Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, People’s Republic of China, Tel +8613611927616, Email zhouligang@yahoo.comAbstract: Hyperuricemia is a common comorbidity in patients with type 2 diabetes mellitus (T2DM), as insulin resistance (IR) or hyperinsulinemia is associated with higher serum uric acid (SUA) levels due to decreased uric acid (UA) secretion, and SUA vice versa is an important risk factor that promotes the occurrence and progression of T2DM and its complications. Growing evidence suggests that sodium-glucose cotransporter 2 inhibitors (SGLT-2i), a novel anti-diabetic drug initially developed to treat T2DM, may exert favorable effects in reducing SUA. Currently, one of the possible mechanisms is that SGLT2i increases urinary glucose excretion, probably inhibiting glucose transport 9 (GLUT9)-mediated uric acid reabsorption in the collecting duct, resulting in increased uric acid excretion in exchange for glucose reabsorption. Regardless of this possible mechanism, the underlying comprehensive mechanisms remain poorly elucidated. Therefore, in the present review, a variety of other potential mechanisms will be covered to identify the therapeutic role of SGLT-2i in hyperuricemia.Keywords: hyperuricemia, uric acid, type 2 diabetes mellitus, sodium-glucose cotransporter 2 inhibitors

Yuan Yuan, Peng Yu, Huihua Shen, Guozhu Xing, Wu Li Department of Cardiothoracic Surgery, Xinjiang Military Region General Hospital, Urumqi, People’s Republic of ChinaCorrespondence: Yuan Yuan; Wu Li, Department of Cardiothoracic Surgery, Xinjiang Military Region General Hospital, No. 359, Youhao North Road, Urumqi, 830000, Xinjiang, People’s Republic of China, Tel +86-13899886276 ; +86-991-4992101, Email doctor_yyuan@163.com; doctorli_xxwk@163.comBackground: Long non-coding RNA FOXD2 antisense RNA 1 (FOXD2-AS1) has been reported in many malignancies. However, the molecular mechanism of many actions is not clarified. This study was conducted to investigate the function of FOXD2-AS1 in lung adenocarcinoma and its molecular mechanism.Methods: Bioinformatics and in vitro analysis including RT-qPCR, CFU, CCK8, Transwell, Cell Apoptosis and Cell Cycle Assay were used for the analysis of gene expression and related effects.Results: It revealed increased expression of lncRNA FOXD2-AS1 in lung adenocarcinoma cell lines (A549 cells), and abundant expression of lncRNA FOXD2-AS1 was also observed in the acquired lung adenocarcinoma tissues. In vitro results showed that knockdown of lncRNA FOXD2-AS1 in A549 cells weakened cell proliferation, invasion and increased apoptosis. At the same time, we found that reducing the expression of lncRNA FOXD2-AS1 caused cell cycle arrest in the G1/S phase. Differential gene analysis of lung adenocarcinoma and adjacent normal tissues showed that the cell cycle and its related process regulation were significantly enriched. Gene Set Enrichment Analysis (GSEA) analysis showed that miR-206, miR-143, lL6-JAK-STAT3 signalling pathway, STAT3, E2F targets, EZH2, P53 signalling pathway and E2F3 targets interacting with lncRNA FOXD2-AS1 were also enriched.Conclusion: This study demonstrates the role and mechanism of the lncRNA FOXD2-AS1 in lung adenocarcinoma and provides a better understanding for the treatment of lung adenocarcinoma, which indicates that interfering with lncRNA FOXD2-AS1 expression may be a novel strategy.Keywords: lncRNA FOXD2-AS1, lung adenocarcinoma, non-small cell lung cancer, cell cycle, proliferation

Zili Hu,1,2,&ast; Yu Yuan,3,&ast; Zhiwen Hu,1,2,&ast; Qingbo Liu,4 Yizhen Fu,1,2 Jingyu Hou,1,2 Xuqi Sun,5 Shaoqiang Li,6 Wenbin Duan,7 Minshan Chen1,2 1Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 2Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 3Department of Respiratory Medicine, the Second Xiangya Hospital, Central South University, Changsha, 510235, People’s Republic of China; 4Department of Hepatobiliary Surgery, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, 528308, People’s Republic of China; 5Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of China; 6Hepatic Pancreatobiliary Surgery Center, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 7Department of Hepatobiliary Surgery, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, 410005, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Minshan Chen; Wenbin Duan, Fax ++86-20-87343117 ; +86-20-877557668214, Email chenmsh@sysucc.org; cnduanwenbin0222@163.comBackground: The value of lactate dehydrogenase (LDH) compared with other inflammation-based scores in predicting the outcomes of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients after curative resection remains unknown. This study aims to evaluate the predictive value of LDH and develop novel nomograms to predict postoperative recurrence and survival in these patients.Methods: This study retrospectively collected 1560 patients with HBV-related HCC who underwent curative resection from four institutions in China. In total, 924 patients were recruited from our center and randomly divided into the training cohort (n = 616) and internal validation (n = 308) cohorts. Additionally, 636 patients were selected from three other centers as the external validation cohort. The C index of inflammation-based scores was calculated and compared in the training cohort. Novel models were developed according to multivariable Cox regression analysis in the training cohort and validated in the internal and external validation cohorts.Results: LDH showed a higher C-index than other inflammation-based scores for recurrence survival (RFS, 0.60, 95% CI, 0.58– 0.61) and overall survival (OS, 0.65, 95% CI, 0.63– 0.68). The nomograms of RFS and OS were developed based on tumor diameter, macrovascular invasion, AFP, operative hemorrhage, tumor differentiation, tumor number and LDH and achieved a high C-index (0.78, 95% CI, 0.76– 0.79 and 0.81, 95% CI, 0.79– 0.83), which were remarkably higher than the C-indexes of the five conventional HCC staging systems (0.52– 0.62 for RFS and 0.53– 0.67 for OS). The nomograms were validated in the internal validation cohort (0.77 for RFS, 0.78 for OS) and external validation cohort (0.80 for RFS, 0.81 for OS) and performed well-fitted calibration curves.Conclusion: The two nomograms based on inflammatory markers achieved optimal prediction for RFS and OS of patients with HBV-related HCC after hepatectomy.Keywords: hepatocellular carcinoma, hepatectomy, inflammation-based scores, lactate dehydrogenase, nomogram

Shaoqin Zheng1,2 &ast;, Yuan Liang2 &ast;, Zhaojia Wang,1 Min Liu,1 Yingyi Chen,1 Ying Ai,1 Wenfeng Guo,1,3 Guoming Li,1 Yueming Yuan,1,2 Zhiyong Xu,2 Wanting Wu,1 Xinan Huang,1,3 Zhibing Wu,3 Qin Xu,1,3 Jianping Song,1,3 Changsheng Deng1,3 1Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Science and Technology Institute, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 3The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianping Song; Changsheng Deng, Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, People’s Republic of China, Tel +86-20-3658 5633 ; +86-20-8746 1723, Email songjp@gzucm.edu.cn; dcs19811202@163.comIntroduction: Artemisinin-based combination therapies (ACTs) act as first-line antimalarial drugs and play a crucial role in the successful control of falciparum malaria. However, the recent emergence of resistance of Plasmodium falciparum to ACTs in South East Asia is of particular concern. Hence, there is an urgent need to identify the genetic determinants of and understand the molecular mechanisms underpinning such resistance. Artemisinin resistance (AR) is primarily driven by the mutations in the P. falciparum K13 protein, which is widely recognized as the major molecular marker of AR. However, association of K13 mutations with in vivo AR has been ambiguous due to the absence of a tractable model.Methods: In this study, we have successfully produced artemisinin- and piperaquine-resistant P. berghei K173 following drug administrations. Prolonged parasite clearance and early recrudescence were found following daily exposure to high doses of artemisinin and piperaquine. We have also sequenced the DNA of artemisinin-resistant strains and piperaquine-resistant strains of P. berghei K173 to explore the relationship between PfK13 and AR.Results: The resistance index of P. berghei K173 reached 12.4 after 30 artemisinin-resistant generations, but AR declined gradually after 30 generations. On the 50th generation, the resistance index of artemisinin-resistant strains was only 5.0 compared with the severe drug resistance of piperaquine-resistant strains (I90=148.8). DNA sequencing of artemisinin-resistant strains showed that there were 9 meaningful mutations at P. berghei K13-propeller domain, but the above mutations did not include common clinical point mutations.Conclusion: Our data show that artemisinin is less susceptible to severe resistance compared with other antimalarial drugs. In addition, mutation on P. berghei K13 has a multi-drug-resistant phenotype and may be used as a biomarker to monitor its resistance. More studies need to be conducted on the new mutations detected so as to understand their association, if any, with ACT resistance.Keywords: malaria, Plasmodium berghei, P. berghei K13 gene, artemisinin resistance

Lifang Ma,1,* Youyuan Yuan,2,* Xiumei Wang3 1Department of Hospital Infection Management Office, Shanxi Bethune Hospital, Taiyuan, People’s Republic of China; 2Department of Interventional Therapy for Tumor and Vascular Disease, Shanxi Bethune Hospital, Taiyuan, People’s Republic of China; 3Department of Central Operating Room, Shanxi Bethune Hospital, Taiyuan, Shanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Youyuan Yuan, Department of Interventional Therapy for Tumor and Vascular Disease, Shanxi Bethune Hospital, No. 99, Longcheng Street, Taiyuan City, Shanxi, 030032, People’s Republic of China, Tel +86 13934554638, Fax +86 10 48993553, Email youyuanyuan1504@163.comObjective: To evaluate the effect of a feedforward control model on nursing error behaviour and nursing attitudes in the operating room.Methods: A total of 216 patients admitted to our hospital from January 2018 to December 2020 were randomly selected as the research subjects and divided into a control group and a research group, with 108 cases in each. The control group received routine surgical nursing management, while the research group received surgical nursing management with a feedforward control model. Nursing quality, error behaviour, and work attitude score, as well as the occurrence of safety hazards and patient satisfaction, were compared between the two groups of patients.Results: Compared with the control group, the nursing quality score, including nursing document quality (72.0 ± 1.8 vs 97.2 ± 2.0), quality control inspection (75.4 ± 1.9 vs 95.5 ± 1.2), disinfection and isolation (73.4 ± 2.4 vs 96.6 ± 2.0) and nursing safety management (71.1 ± 2.2 vs 98.0 ± 1.8), were higher in the research group (P < 0.05); the scores for nursing error behaviour (13.2 ± 1.0 vs 19.4 ± 1.8) and work attitudes of the research group (14.0 ± 1.2 vs 19.0 ± 2.0) were higher (P < 0.05); and the research group had a lower incidence of safety hazards (11.1% vs 0.9%, P < 0.05); finally, the research group had higher patient satisfaction (71.3% vs 93.5%, P < 0.05).Conclusion: The application of a feedforward control model for nursing management in the operating room can significantly reduce nurses’ errors and improve their attitudes, continuously reduce the incidence of safety incidents, improve the quality of operating room nursing and increase the satisfaction of patients and their families with the nursing care they received.Keywords: operating room nursing management, feedforward control model, nurse nursing error behaviour, nursing attitude, impact

Yanxuan Xie,1 Xiaoyang Jiao,2 Mi Zeng,2 Zhiqiang Fan,2 Xin Li,2 Yumeng Yuan,2 Qiaoxin Zhang,1,&ast; Yong Xia1,&ast; 1The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, 515041, People’s Republic of China; 2Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, 515041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiaoxin Zhang; Yong Xia, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, People’s Republic of China, Tel: +86138 2968 2808 ; +86137 1590 8963, Email qiaoxinzhang@126.com; yxia@stu.edu.cnObjective: Both genetic and microbial factors play important roles in colorectal cancer (CRC) development. The effects of Fusobacterium nucleatum (F. nucleatum) and microsatellite instability (MSI) on CRC prognosis require more clinical evidence. We aimed to investigate the role of F. nucleatum and MSI as biomarkers in predicting the prognosis of CRC.Methods: CRC patients in various TNM stages were enrolled. MSI status and F. nucleatum were detected by immunohistochemical staining of formalin-fixed paraffin-embedded (FFPE) specimens. The associations between MSI status and F. nucleatum and clinical parameters were analyzed.Results: MSI tumors were more frequently observed in the colon than in the rectum. Cancerous tissues had higher levels of F. nucleatum than adjacent noncancerous tissues. There were no significant differences in F. nucleatum abundance in different age, sex, tumor stage, location, and tumor marker groups. MSI status was associated with tumor location and stage. Survival analyses revealed that disease-free survival (DFS) was significantly longer in the F. nucleatum-negative, younger age, and TNM stage I–II groups (p< 0.05), and age, advanced TNM stage (III and IV), and F. nucleatum status were independent factors for poor prognosis. Multivariate Cox regression and receiver operating characteristic (ROC) curve analyses showed that conventional tumor biomarkers of CRC had more prognostic value than F. nucleatum and MSI.Conclusion: Age, advanced TNM stage, and F. nucleatum positivity were independent factors of poor prognosis, suggesting that F. nucleatum and MSI may contribute to the identification of new strategies for the prevention and treatment of CRC.Keywords: colorectal cancer, microsatellite instability, Fusobacterium nucleatum, prognostic, factors

Jing Luo,1 Nuoyan Wang,1 Ling Hua,1 Fei Deng,1 Dan Liu,1 Jun Zhou,1 Yue Yuan,1 Fumin Ouyang,1 Xuemin Chen,1 Shujuan Long,1 Yasi Huang,1 Zhanxing Hu,2,3 Hong Zhou1 1Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, People’s Republic of China; 2State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, People’s Republic of China; 3The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang, People’s Republic of ChinaCorrespondence: Hong Zhou, Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, People’s Republic of China, Tel +86-085128643451, Fax +86-085128642303, Email zhouh64@163.com Zhanxing Hu, State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, People’s Republic of China, Email huzhxi88@163.comBackground: The anti-inflammatory application of Guizhou ethnic medicine in the Karst area of China is mainly based on folk medicine experience, and there has been a lack of systematic research, leading to limited application of Guizhou ethnic medicine.Purpose: To evaluate the anti-inflammatory effects of compounds extracted from Guizhou ethnic medicine in the Karst area and investigate their molecular mechanisms.Methods and Results: Preliminarily, the anti-inflammatory effects of 181 compounds extracted from Guizhou ethnic medicine were screened in lipopolysaccharide (LPS)-stimulated peritoneal macrophages and the 41 compounds with anti-inflammatory effects were selected. Then, these 41 compounds with anti-inflammatory effects were investigated for their druggability and 18 compounds were selected. Thirdly, compound Hx-150, named isocorydine, was selected as the candidate compound. In vitro and in vivo, isocorydine inhibited LPS-induced TNF-α and IL-6 release from LPS-treated mouse peritoneal macrophages. Isocorydine decreased TNF-α, IL-6, and IL-1β levels in the blood, lung, and spleen, and ameliorated lung tissue damage. Mechanistically, isocorydine had no effect on the mRNA expressions and protein levels of Tlr4, Myd88, and Traf6. Isocorydine also had no effect on the expression of RelA (encoding NFκB p65) mRNA, but inhibited phosphorylation of IκBα and NFκB p65 in the TLR4-mediated signaling pathway. Furthermore, isocorydine increased the cytoplasmic level of NFκB p65 and decreased its nuclear level in LPS-treated macrophages. Importantly, isocorydine upregulated Vdr mRNA (encoding the vitamin D receptor) expression and increased the nuclear VDR protein level.Conclusion: Many compounds from Guizhou ethnic medicine had potential anti-inflammatory activities. Among them, isocorydine has a strong anti-sepsis effect, which is tightly related to its upregulation of VDR expression and inhibition of NFκB p65 translocation into the nucleus, leading to reduced pro-inflammatory cytokines release and protection for LPS-challenged mice.Keywords: Guizhou ethnic medicine, LPS, Sepsis, Pro-inflammatory cytokines, NFκB, VDR

Yingying Yin,1,2 Chunming Xie,3 Haisan Zhang,4 Hongxing Zhang,5 Zhijun Zhang,3 Yonggui Yuan1,2 1Department of Psychosomatics and Psychiatry, ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, 210009, People’s Republic of China; 2Institute of Psychosomatics, Medical School of Southeast University, Nanjing, 210009, People’s Republic of China; 3Department of Neurology, ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, People’s Republic of China; 4Departments of Clinical Magnetic Resonance Imaging, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453002, People’s Republic of China; 5Departments of Psychiatry, the Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453002, People’s Republic of ChinaCorrespondence: Yonggui Yuan; Yingying Yin, Department of Psychosomatics and Psychiatry, ZhongDa Hospital, School of Medicine, Southeast University, No. 87 Dingjiaqiao Road, Nanjing, 210009, People’s Republic of China, Email yygylh2000@sina.com; 348281107@qq.comBackground: Previous studies revealed different cerebral blood flow (CBF) changes of major depressive disorder (MDD) patients with psychomotor retardation (PMR). These different changes might result from the modulation of other factors, such as genes. This study aimed to investigate the influence of COMT Val158Met polymorphism on the CBF alterations in MDD patients with PMR.Methods: COMT Val158Met genotypes and arterial spin labeling-magnetic resonance imaging (ASL-MRI) data of 103 Chinese Han participants (63 MDD, 40 NCs) were collected in this study. MDD patients were divided into PMR group (N = 23) and NPMR group (N = 40) according to the Salpetriere Retardation Rating Scale score. PMR, NPMR and NCs groups were further divided into two subgroups, respectively, based on the COMT Val158Met genotype. CBF throughout the whole brain was calculated based on the ASL-MRI data. A two-way factorial analysis of covariance was used to investigate the main effects of PMR, COMT Met allele, as well as the interactions between COMT genotype and PMR on the CBF in a voxel-wise manner. Partial correlation analyses were also applied to evaluate the association between the CBF of significant brain regions and the PMR severity.Results: Main effect of PMR mainly influenced the CBF of the prefrontal cortex (PFC). Main effect of COMT Met allele mainly influenced the CBF of the thalamus. The interaction between PMR and COMT Met allele primarily influenced the CBF of left precuneus and right caudate. The CBF of PFC was positively correlated with the PMR severity.Conclusion: Our findings indicate that the COMT Met allele could modulate the CBF changes of the left precuneus and right caudate in MDD patients with PMR, providing additional layer of information regarding earlier reports for different CBF changes of MDD patients with psychomotor retardation in the literature, which were assessed irrespective of polymorphisms among patients.Keywords: major depressive disorder, psychomotor retardation, ASL, cerebral blood flow, COMT Val158Met polymorphism

Miaomiao Li,1,&ast; Yue Yuan,1,&ast; Xue Han,2 Xinjuan Liu,1 Weizhen Zhang,2 Jianyu Hao1 1Department of Gastroenterology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianyu Hao, Department of Gastroenterology, Beijing Chao-Yang Hospital, Capital Medical University, No. 8, South Road of Workers Stadium, Chaoyang District, Beijing, 100020, Email haojianyu@ccmu.edu.cn Weizhen Zhang, Department of Physiology and Pathophysiology, Peking University Health Science Center, No. 38, Xueyuan Road, Haidian District, Beijing, 100191, Email weizhenzhang@bjmu.edu.cnBackground: Chronic pancreatitis (CP) is a long-term inflammatory disease of the pancreas that can be caused by various pathogenic factors. Oxidative stress (OS), which is associated with several pancreatic diseases, can induce pancreatic stellate cell (PSC) activation, leading to pancreatic fibrosis. Given the inefficacy of existing treatments for CP, in this study, our objective was to evaluate the therapeutic effect of the antioxidant, mitoquinone (MitoQ).Methods: First, in vivo, we established a CP mouse model via the repeated injection of cerulein. Mice in the MitoQ group simultaneously received MitoQ daily. After 4 weeks of cerulein injection, pancreatic tissues from mice were evaluated by morphological changes and the expression of fibrosis markers. Further, OS in the collected pancreatic tissue samples was evaluated by determining the level of malondialdehyde (MDA) as well as the expression levels and activities of antioxidants. Furthermore, in vitro, the effect of MitoQ on human PSCs (hPSCs) was evaluated based on PSC activation markers and fibrotic phenotypes, and OS in these treated hPSCs was evaluated by measuring reactive oxygen species (ROS), MDA, and antioxidant levels.Results: In vivo, MitoQ alleviated pancreatic fibrosis and inhibited OS in the cerulein-induced murine CP model. In vitro, it inhibited PSC activation as well as the subsequent development of the profibrogenic phenotypes by balancing out the levels of free radicals and the intracellular antioxidant system.Conclusion: MitoQ is a potential candidate for CP treatment.Keywords: chronic pancreatitis, pancreatic stellate cells, pancreatic fibrosis, oxidative stress, mitochondria-specific antioxidant, MitoQ, superoxide dismutase

Siyang Lin,1,2,&ast; Fang Wang,2– 4,&ast; Jiaxin Zheng,1,2 Yin Yuan,1,2,5,6 Feng Huang,1,2,5,6 Pengli Zhu1,2,5,6 1Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 2Department of Geriatric Medicine, Fujian Provincial Hospital, Fuzhou, Fujian, People’s Republic of China; 3Fujian Health College, Fuzhou, Fujian, People’s Republic of China; 4Nursing School of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 5Fujian Provincial Center for Geriatrics, Fuzhou, Fujian, People’s Republic of China; 6Fujian Provincial Key Laboratory of Geriatrics, Fuzhou, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Huang; Pengli Zhu, Shengli Clinical Medical College of Fujian Medical University, No. 134 Dongjie Road, Gulou District, Fuzhou, 350001, Fujian, People’s Republic of China, Tel/Fax +86-591-88216023, Email wmhf0327@126.com; zpl7755@hotmail.comPurpose: Intrinsic capacity (IC) reflects the overall health status of older adults and has great public health significance. But few studies described the related biomarkers for IC. The aim of this study was to investigate the association between homocysteine (Hcy) and IC in older adults.Participants and Methods: This cross-sectional study included 1927 community-dwelling Chinese older adults aged 60– 98 years from May 2020 to December 2020. Data were collected through interviews, physical examinations, and laboratory tests. IC involved five domains of cognition, locomotion, sensory, vitality, and psychology evaluated by the Mini-cog scale, 4-m walk test, self-reported visual and hearing conditions, MNA-SF scale, and GDS-4 scale, respectively. The score of each domain dichotomized as 0 (normal) and 1 (impaired) was added together to an IC total score. Low IC was defined as a score of 3– 5, and high IC as 0– 2. Hcy was measured by a two-reagent enzymatic assay. A restricted cubic spline regression model was used to explore the non-linear relationship between Hcy and low IC.Results: Hcy was higher in the low IC group than in the high IC group. Restricted cubic spline analysis revealed a J-shaped nonlinear association between Hcy and low IC. The risk of IC decline was slowly decreased until 8.53 μmol/L of Hcy (OR=0.753, 95% CI=0.520– 1.091, P=0.132), and increased with elevations of per 5 μmol/L Hcy afterwards (OR=1.176, 95% CI=1.059– 1.327, P=0.005). Among the five domains of IC, Hcy had ORs of 1.116 (1.009– 1.247) for cognition impairment, 1.167 (1.055– 1.305) for vitality, and 1.160 (1.034– 1.303) for psychology per 5 μmol/L increase in Hcy above the change point. Additional sensitivity analysis also demonstrated the nonlinear association between Hcy and low IC.Conclusion: Hcy had a J-shaped association with low IC. Higher Hcy (Hcy ≥ 8.53μmol/L) might provide clinical implications for early identifying the risk of low IC.Keywords: homocysteine, intrinsic capacity, older adults, frailty