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

Zhaoxian Li,1 Wei Bao,1 Yao Wang,1 Shangsong Yan,1 Hong Zheng,2 Junlong Luo1,3 1Psychology College, Shanghai Normal University, Shanghai, People’s Republic of China; 2Changning Mental Health Center Affiliated with East China Normal University, Shanghai, People’s Republic of China; 3Lab for Educational Big Data and Policymaking, Ministry of Education, Shanghai Normal University, Shanghai, People’s Republic of ChinaCorrespondence: Hong Zheng; Junlong Luo, Email zhhmm2@163.com; luo831023@vip.163.comIntroduction: The impact of emotions on intuitive and analytical thinking has been widely studied. Most research suggests that negative emotions enhance analytical processing. However, there are studies indicating that the sense of certainty associated with disgust can stimulate intuitive processing. Despite these findings, the neuroelectrophysiological evidence supporting the role of disgust in promoting intuitive processing remains unexplored.Methods: This study aimed to investigate the neuroelectrophysiological mechanisms by which disgust promotes intuitive processing. A total of 54 participants were recruited and randomly assigned to specific emotion groups. Emotional states were induced by exposing participants to disgust and fear videos designed to evoke specific dimensions of certainty and uncertainty. Event-related potentials (ERP) and the Cognitive Reflection Test (CRT) were utilized as experimental materials to measure participants’ responses.Results: The results demonstrated that disgust facilitated intuitive thinking, as evidenced by the lowest accuracy in behavioral outcomes. ERP findings showed that disgust led to smaller N2 and larger P3b amplitudes under conditions of conflict. These results suggest that disgust reduces individuals’ conflict-detection ability, resulting in a stronger sense of certainty in intuitive but incorrect answers.Conclusion: This study provides neuroelectrophysiological evidence that disgust enhances intuitive thinking. The findings offer a new perspective on the influence of emotions on dual-process thinking, highlighting the role of disgust in shaping intuitive and analytical thought processes.Keywords: certain, uncertain, disgust, fear, dual-process theory, N2, P3b

Jiaxin Luo,1 Qingting Li,1,2 Robin Whittemore,3 Maritta Välimäki,4 Jia Guo1,2 1Xiangya School of Nursing, Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 3School of Nursing, Yale University, New Haven, CT, USA; 4Department of Nursing Science, University of Turku, Turku, FinlandCorrespondence: Jia Guo, Email guojia621@163.comBackground: Positive parent-teen and peer relationships are crucial support resources for adolescents with type 1 diabetes mellitus (T1DM). There is quite a bit of research on parent-teen relationships in Western countries, less so with peer relationships. Additionally, information on these relationships and their influencing factors among adolescents from other regions with different family culture and peer cohesion is limited, which impedes the development of targeted interventions.Methods: This study analyzed baseline data from a randomized controlled trial in China involving 122 adolescents with T1DM aged 12– 18 years. Data were collected using established questionnaires on social-demographic and clinical characteristics, perceived stress, general self-efficacy, coping styles, diabetes self-management, and parent-teen and peer relationships. Multivariate linear regression analysis was conducted to determine the associating factors of parent-teen relationships and peer relationships respectively.Results: The total score of the parent-teen relationships subscale was 11.02 ± 2.77, within a theoretical range of 4– 16. The total score of the peer relationships subscale was 16.51 ± 2.42, within a theoretical range of 5– 20. Positive coping styles, less negative coping styles, and more collaboration with parents in diabetes self-management were associated with better parent-teen relationships. Younger age, positive coping styles, less negative coping styles, and higher goals for diabetes self-management were associated with better peer relationships.Conclusion: There is room to improve parent-teen relationships, maybe via encouraging more collaboration between parents and adolescents for diabetes management. The coping styles training is indicated to improve both relationships.Keywords: type 1 diabetes, adolescents, parent-teen relationships, peer relationships, associating factors

Huaqiong Wu,1,&ast; Guifen Yang,2,&ast; Shaohua Zhang,2 Jinxiang Luo,1 Pei Zhou,1 Yuhua Chen1 1Department of Radiodiagnosis, Central War Zone General Hospital of Wuhan, Wuhan, Hubei, People’s Republic of China; 2Department of Internal Medicine-Cardiovascular, Central War Zone General Hospital of Wuhan, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaohua Zhang, Department of Internal Medicine-Cardiovascular, Central War Zone General Hospital of Wuhan, No. 627, Wuluo Road, Wuchang District, Wuhan, Hubei, 430070, People’s Republic of China, Tel +8618062579072, Email zhangshaohua1258@163.com Jinxiang Luo, Department of Radiodiagnosis, Central War Zone General Hospital of Wuhan, No. 627, Wuluo Road, Wuchang District, Wuhan, Hubei, 430070, People’s Republic of China, Tel +8602750773333, Email luojinxiang2020@21cn.comObjective: To investigate the correlation between risk factors for coronary stenosis and the degree of coronary artery stenosis based on coronary computed tomography angiography (CCTA).Methods: Two hundred seventy-eight patients with coronary artery disease who received treatment in our hospital between January 2020 and January 2021 were selected as the experimental group, and 100 healthy people who received physical examination in our hospital during the same period were selected as the control group (age and gender matched with the study group). The clinical data and CCTA data of the two groups of patients were collected and compared. Computed tomography fractional flow reserve (FFRCT) values were calculated based on the CCTA data of the patients in the study group, risk factors for coronary artery stenosis were analysed and the correlation between the risk factors and CT flow reserve fraction was explored.Results: The serum total bilirubin (BIL), apolipoprotein A (apoA), low-density lipoprotein cholesterol (LDL-C), uric acid, total cholesterol (TC) and mean platelet volume levels were higher in the experimental group than in the control group (P < 0.05). Unconditional logistic regression analysis showed that LDL-C, uric acid, TC, triglyceride, serum total BIL and apoA were independent risk factors for coronary heart disease (P < 0.05). Serum total BIL (r = 0.27), apoA (r = − 0.30), uric acid (r = − 0.48), TC (r = − 0.35), triglyceride (r = − 0.73) and LDL-C (r = − 0.65) showed a negative correlation with FFRCT values (P < 0.05). A positive correlation was detected between high-density lipoprotein cholesterol and FFRCT values (r = 0.37, P < 0.05).Conclusion: Triglycerides, LDL-C, uric acid, TC, serum total BIL and apoA are risk factors for coronary artery stenosis that should be closely monitored and receive active intervention in clinical practice.Keywords: coronary heart disease, coronary artery stenosis, computed tomography angiography, risk factors, computed tomography fractional flow reserve

Yandan Wang,1 Yong Zhang,2 Jincheng Xiao,3 Xiang Geng,3 Lujun Han,4 Junpeng Luo5 1Department of Otorhinolaryngology, Huaihe Hospital of Henan University, Kaifeng, 475000, People’s Republic of China; 2Department of Immunotherapy, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, 450003, People’s Republic of China; 3Department of Minimally Invasive Intervention, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450000, People’s Republic of China; 4Department of Radiology, State Key Laboratory of Oncology in South China, Collaborative Innovation Cancer for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510030, People’s Republic of China; 5Translational Medical Center of Huaihe Hospital, Henan University, Kaifeng, 475000, People’s Republic of ChinaCorrespondence: Junpeng Luo, Translational Medical Center of Huaihe Hospital, Henan University, Kaifeng, 475000, People’s Republic of China, Email hiccp@henu.edu.cnBackground: To develop and validate an innovative predictive model that integrates multisequence magnetic resonance (MR) radiomics, deep learning features, and clinical indicators to accurately predict the recurrence of hepatocellular carcinoma (HCC) after thermal ablation.Methods: This retrospective multicenter cohort study enrolled patients who were diagnosed with HCC and treated via thermal ablation. We extracted radiomic features from multisequence 3T MR images, analyzed these images using a 3D convolutional neural network (3D CNN), and incorporated clinical data into the model. Model performance was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve.Results: The study included 535 patients from three hospitals, comprising 462 males and 43 females. The RDC model, which stands for the Radiomics-Deep Learning-Clinical data model, demonstrated high predictive accuracy, achieving AUCs of 0.794 in the training set, 0.777 in the validation set, and 0.787 in the test set. Statistical analysis confirmed the model’s robustness and the significant contribution of the integrated features to its predictive capabilities.Conclusion: The RDC model effectively predicts HCC recurrence after thermal ablation by synergistically combining advanced imaging analysis and clinical parameters. This study highlights the potential of such integrative approaches to enhance prognostic assessments in HCC patients and offers a promising tool for clinical decision-making.Keywords: hepatocellular carcinoma, thermal ablation, radiomics, deep learning, MRI, prognostic modeling

Xiaoqing Liu,1,2 Qiaoqiao Ma,1 Jianfei Li,1 Zijun Huang,3 Xin Tong,2 Ting Wang,2 Hualong Qin,2 Wenjie Sui,2 Jing Luo2 1School of Nursing, Suzhou Medical College of Soochow University, Suzhou, People’s Republic of China; 2Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 3School of Computer Science and Technology, Soochow University, Suzhou, People’s Republic of ChinaCorrespondence: Jing Luo, Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Gusu District, Suzhou, Jiangsu, 215006, People’s Republic of China, Email luobojenny@163.comBackground: Rapid recovery after lung cancer surgery is challenging. Exercise is a low-cost, effective method to expedite recovery. Despite numerous exercise interventions, many fail to consider patient perspectives, leading to low adherence and short-term effects. Understanding lung cancer patients’ perspectives on postoperative exercise and exploring their exercise-related concerns and needs are crucial for enhancing the effectiveness of exercise-based rehabilitation programs.Objective: This study aims to analyze lung cancer patients’ perspectives on postoperative exercise in their daily lives, exploring their concerns and needs related to postoperative exercise to help healthcare professionals develop personalized exercise plans.Methods: An internet crawling technique collected online inquiries from Baidu webpages about postoperative physical activity in lung cancer patients, using “lung cancer”, “surgery”, and ”exercise” as keywords. The data was encoded, categorized, and analyzed using a large-scale semantic analysis platform in natural language processing and information retrieval to examine term frequency, sentiment tendencies, and attributes in the inquiry texts.Results: Initially, 2727 queries were retrieved; after screening, deduplication, and cleansing, 201 unique queries were identified. Queries related to “modes of exercise” constituted the largest proportion. The most frequently occurring words in the word frequency analysis were “lung”, “ cancer”, “should”, “can”, “long”, “early”, and “surgery”, “exercise”, “respiratory”. Postoperative lung cancer patients demonstrate significant interest in whether they should engage in exercise, as well as in the appropriate types and duration of such activities, indicating a strong need for detailed guidance and knowledge related to exercise. The sentiment analysis showed a positive score of 87.5% and a negative score of 12.5%, indicating that postoperative lung cancer patients view exercise positively and have an enthusiastic attitude towards it. Among the positive sentiment attributes, “good” was the most frequently mentioned term, whereas “bad” and “surprising” were the most prevalent terms within the negative sentiment attributes.Conclusion: Postoperative physical activity receives limited attention from lung cancer patients, who emphasize their preferences for exercise modalities. Their inquiries often reflect psychological concerns, such as fear and helplessness caused by symptoms. Understanding patients’ perspectives on postoperative physical activity within their real-life contexts can help integrate psychological support into exercise plans. This integration could guide healthcare professionals in developing more personalized postoperative exercise regimens for lung cancer patients.Keywords: lung cancer, surgery, exercise, web crawling technology, needs, concern

Chunjiao Lu,&ast; Xuewei Wu,&ast; Xin Meng,&ast; Yi Liu, Ting Yang, Yan Zeng, Yang Chen, Yishan Huang, Zhou Fang, Xiaojun Yang, Juanjuan Luo Engineering Research Center of Key Technique for Biotherapy of Guangdong Province, Shantou University Medical College, Shantou, 515041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaojun Yang; Juanjuan Luo, Shantou University Medical College, 22 Xinling Road, Shantou, 515041, People’s Republic of China, Email yangx@stu.edu.cn; 15jjluo1@stu.edu.cnIntroduction: The potential toxic effects of wastewater discharges containing silver nanoparticles (AgNPs) and their release into aquatic ecosystems on aquatic organisms are becoming a major concern for environmental and human health. However, the potential risks of AgNPs to aquatic organisms, especially for cardiac development by Focal adhesion pathway, are still poorly understood.Methods: The cardiac development of various concentrations of AgNPs in zebrafish were examined using stereoscopic microscope. The expression levels of cardiac development-related genes were analyzed by qRT-PCR and Whole-mount in situ hybridization (WISH). In addition, Illumina high-throughput global transcriptome analysis was performed to explore the potential signaling pathway involved in the treatment of zebrafish embryos by AgNPs after 72 h.Results: We systematically investigated the cardiac developing toxicity of AgNPs on the embryos of zebrafish. The results demonstrated that 2 or 4 mg/L AgNPs exposure induces cardiac developmental malformations, such as the appearance of pericardial edema phenotype. In addition, after 72 h of exposure, the mRNA levels of cardiac development-related genes, such as myh7, myh6, tpm1, nppa, tbx5, tbx20, myl7 and cmlc1, were significantly lower in AgNPs-treated zebrafish embryos than in control zebrafish embryos. Moreover, RNA sequencing, KEGG (Kyoto Encyclopedia of Genes) and Genomes and GSEA (gene set enrichment analysis) of the DEGs (differentially expressed genes) between the AgNPs-exposed and control groups indicated that the downregulated DEGs were mainly enriched in focal adhesion pathways. Further investigations demonstrated that the mRNA levels of focal adhesion pathway-related genes, such as igf1ra, shc3, grb2b, ptk2aa, akt1, itga4, parvaa, akt3b and vcla, were significantly decreased after AgNPs treatment in zebrafish.Conclusion: Thus, our findings illustrated that AgNPs could impair cardiac development by regulating the focal adhesion pathway in zebrafish.Keywords: AgNPs, focal adhesion, cardiac development, zebrafish

Changjin Wang,1,&ast; Bangyuan Yang,1,&ast; Songyuan Luo,1 Shengneng Zheng,2 Yinghao Sun,1 Jiaohua Chen,1 Ruixin Fan,3 Jianfang Luo,1,&ast; Jie Li1,&ast; 1Department of Cardiology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Radiology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 3Department of Cardiac Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Li; Jianfang Luo, Email leomoku1981@163.com; jianfangluo@sina.comBackground: The relationship between pulmonary hypertension (PH) and outcomes after transcatheter aortic valve replacement (TAVR) has been shown to be unfavorable. The impact of gender on TAVR outcomes remains controversial. There have been no studies evaluating the simultaneous effects of both factors on TAVR outcomes.Methods: We retrospectively analyzed a prospective cohort of patients who underwent TAVR between January 2016 and December 2022. The patients were stratified by gender and the presence of PH. The primary outcome of the study was all-cause mortality. Secondary outcome was a composite of all-cause mortality and heart failure hospitalization.Results: We identified a total of 133 female patients without PH, 179 males without PH, 87 females with PH, and 122 males with PH. The median follow-up period was 18 months. Female patients without PH demonstrated a lower cumulative mortality rate compared to those with male gender and/or PH. Adjusted multivariate Cox proportional hazard analyses revealed that male gender and PH status, either individually or in combination, were independently associated with long-term mortality when compared to female patients without PH. Specifically, females with PH (HR 6.80, 95% confidence interval (CI): 1.49– 31.12, P=0.013), males without PH (HR 6.45, 95% CI: 1.47– 28.22, P=0.013), and males with PH (HR 7.2, 95% CI: 1.63– 31.81, P=0.009) demonstrated significantly higher risk for mortality.Conclusion: Patients who were male or had PH status had a higher risk of mortality. However, there was no synergistic effect between being male and having PH on the prognosis after TAVR.Keywords: transcatheter aortic valve replacement, gender, pulmonary hypertension, outcome

Chengfeng Fu,1,&ast; Junwei Shi,2,&ast; Ying Hu,1 Jing Luo1 1Respiratory and Critical Care Medicine, the Second People’s Hospital of Banan District, Chongqing, 400054, People’s Republic of China; 2State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, Jiangsu, 210023, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Luo, Respiratory and Critical Care Medicine, the Second People’s Hospital of Banan District, Chongqing, 400054, People’s Republic of China, Tel +86 15823143609, Email luojing99510@126.comBackground: Chronic obstructive pulmonary disease (COPD) is a widespread respiratory condition characterized by chronic inflammation. Selenium, an essential trace element, possesses anti-inflammatory and antioxidant properties. However, the diet is often complex, and the absence of one nutrient may indicate a concurrent deficiency in others. Therefore, inadequate dietary selenium intake may suggest deficiencies in other elements. Despite its potential benefits, there is a scarcity of evidence regarding the association between dietary selenium intake and COPD.Purpose: This study aims to investigate the potential association between dietary selenium intake and COPD among American adults.Patients and Methods: This cross-sectional study analyzed data from the National Health and Nutrition Examination Survey conducted in the United States from 1999 to 2018. Multivariate logistic regression, restricted cubic spline analyses, subgroup analysis, and sensitivity analysis were conducted to assess the correlation between dietary selenium intake and COPD.Results: A total of 39,654 participants were included in the study. The adjusted odds ratio (OR) for COPD in the highest selenium intake group (T3, > 122.0 μg/day) was 0.80 (95% CI: 0.71– 0.91, p < 0.001) compared to the lowest intake group (T1, < 81.6 μg/day). Dietary selenium intake exhibited a linear negative correlation with COPD. Among participants reporting selenium supplementation, a similar negative association persisted.Conclusion: This study observed a negative correlation between dietary selenium intake and COPD among American adults, indicating a possible association between higher selenium intake and a lower risk of COPD.Keywords: cross-sectional study, chronic obstructive pulmonary disease, COPD, dietary selenium intake, National Health and Nutrition Examination Survey, NHANES

Yufeng Shu,1,&ast; Zhe Chen,2,&ast; Jingshu Chi,1 Sha Cheng,1 Huan Li,1 Peng Liu,3 Ju Luo2 1Department of Gastroenterology, Third Xiangya Hospital, Central South University., Changsha, Hunan, People’s Republic of China; 2Department of Gerontology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China., Changsha, Hunan, People’s Republic of China; 3Department of Gastroenterology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China., Changsha, Hunan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peng Liu, Department of Gastroenterology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, No. 161, South Shaoshan Road, Changsha, Hunan, People’s Republic of China, Email liupeng920416@163.com Ju Luo, Department of Gerontology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, No. 161, South Shaoshan Road, Changsha, Hunan, People’s Republic of China, Email philip841018@sina.comBackground: Whether machine learning (ML) can assist in the diagnosis of Crohn’s disease (CD) and intestinal tuberculosis (ITB) remains to be explored.Methods: We collected clinical data from 241 patients, and 51 parameters were included. Six ML methods were tested, including logistic regression, decision tree, k-nearest neighbor, multinomial NB, multilayer perceptron, and XGBoost. SHAP and LIME were subsequently introduced as interpretability methods. The ML model was tested in a real-world clinical practice and compared with a multidisciplinary team (MDT) meeting.Results: XGBoost displays the best performance among the six ML models. The diagnostic AUROC and the accuracy of XGBoost were 0.946 and 0.884, respectively. The top three clinical features affecting our ML model’s result prediction were T-spot, pulmonary tuberculosis, and onset age. The ML model’s accuracy, sensitivity, and specificity in clinical practice were 0.860, 0.833, and 0.871, respectively. The agreement rate and kappa coefficient of the ML and MDT methods were 90.7% and 0.780, respectively (P< 0.001).Conclusion: We developed an ML model based on XGBoost. The ML model could provide effective and efficient differential diagnoses of ITB and CD with diagnostic bases. The ML model performs well in real-world clinical practice, and the agreement between the ML model and MDT is strong. Keywords: artificial intelligence, machine learning, crohn’s disease, intestinal tuberculosis, multidisciplinary team

Yuxin Wang,1,&ast; Xiaona Wang,1,2,&ast; Jinmei Luo,1 Bintao Qiu,3 Rong Huang,1 Yi Xiao1 1Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Respiratory Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Central Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinmei Luo, Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, People’s Republic of China, Email palmljm@126.comPurpose: There are currently no ideal indicators for predicting the cardiovascular risk of obstructive sleep apnea (OSA). This study aimed to employ urinary metabolomics to detect early cardiovascular risk in patients with moderate-to-severe OSA.Patients and Methods: Male participants who underwent polysomnography from November 2020 to May 2021 were screened. Clinical data, polysomnography data and urine samples were collected. Untargeted metabolomics analyses of urine were performed. Multivariate analyses and receiver operating characteristic (ROC) curve analyses were subsequently performed to identify potential biomarkers. Associations between metabolites and clinical indicators and cardiovascular risk were examined through linear regression analyses with interaction and mediation analyses.Results: Thirty-six male participants were included in the study, comprising 22 males with moderate-to-severe OSA and 14 age-matched controls, with an average age of 39.6 ± 9.2 years. We identified 65 metabolites in the study, involving pathways including pyrimidine, androgen, estrogen, vitamin B6 and sulfate/sulfite metabolism. Among them, epinephrine sulfate was the most significantly altered metabolite. ROC analyses highlighted that epinephrine sulfate had the highest area under the curve (AUC=0.883) for detecting moderate-to-severe OSA. Epinephrine sulfate was statistically correlated with OSA severity, hypoxia-related indicators (apnea-hypopnea index: r=0.685; oxygen desaturation index: r=0.743, p< 0.0001), arterial stiffness (arterial augmentation index: r=0.361, p=0.031) and long-term cardiovascular risk (Framingham cardiovascular risk: r=0.375, p=0.024). Linear regression analysis revealed that epinephrine sulfate was significantly associated with an increased in the Framingham risk (β = 0.004, 95% CI = 0.000– 0.009, p = 0.049), with the effect partly mediated by systolic blood pressure (27.6%) and not moderated by other factors. Additionally, it also significantly associated with the increased in the arterial augmentation index (β = 0.019, 95% CI = 0.000– 0.037, p = 0.046), with the effect fully mediated by blood pressure and not moderated by other indices statistically.Conclusion: There are significant metabolic pathway alterations in moderate-to-severe OSA patients. Urinary epinephrine sulfate markedly predicts early cardiovascular risk in OSA patients.Keywords: metabolomics, Framingham cardiovascular risk score, epinephrine sulfate, obstructive sleep apnea

Huiqian Guo,1,2,&ast; Jing Luo,1,3,&ast; Suming Chen,1 Ting Yu,4 Xiaofei Mu,4 Fangzhou Chen,4 Xiuhui Lu,4 Jiaqi He,4 Yali Zheng,4 Chunmei Bao,2 Peng Wang,4 Zhe Yin,4 Boan Li1– 3 1Department of Clinical Laboratory, the Fifth Medical Center of PLA General Hospital, Beijing, 100039, People’s Republic of China; 2School of Medical Laboratory, Weifang Medical University, Weifang, 261053, People’s Republic of China; 3Medical School of Chinese PLA, Beijing, 100853, People’s Republic of China; 4State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, 100071, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Boan Li, Department of Clinical Laboratory, the Fifth Medical Center of PLA General Hospital, Beijing, 100039, People’s Republic of China, Email lba@263.net Zhe Yin, State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, 100071, People’s Republic of China, Email jerry9yin@163.comPurpose: To investigate the genetic diversity of IncG plasmids, we have proposed a typing scheme based on replicon repA and performed comparative genomic analysis of five IncG plasmids from China.Methods: p30860-KPC, p116965-KPC, pA1705-KPC, pA1706-KPC and pNY5520-KPC total in five IncG plasmids from clinical isolates of Pseudomonas and Enterobacteriaceae, respectively, were fully sequenced and were compared with the previously collected reference plasmid p10265-KPC.Results: Based on phylogeny, IncG-type plasmids are divided into IncG-I to IncG-VIII, the five plasmids belong to IncG-VIII. A detailed sequence comparison was then presented that the IncG plasmid involved accessory region I (Tn 5563a/b/c/d/e), accessory region II (ISpa19), and accessory region III (blaKPC-2-region). Expect for the pNY5520-KPC, the rest of the plasmids had the same backbone structure as the reference one. Within the plasmids, insertion sequences Tn 5563d and Tn 5563e were identified, a novel unknown insertion region was found in Tn 5563b/c/d/e. In addition, Tn 6376b and Tn 6376c were newly designated in the study.Conclusion: The data presented here including a typing scheme and detailed genetic comparison which provide an insight into the diversification and evolution history of IncG plasmids.Keywords: IncG plasmids, blaKPC-2, phylogenetic tree, multidrug resistance, mobile elements

Jing Luo,1,2 Yi Luo,2 Maoru Zhao,3 Yulong Liu,2 Jiayin Liu,2 Zhulin Du,2 Hong Gong,2 Lian Wang,2 Jinghui Zhao,2 Xiaqing Wang,2 Zhanjun Gu,3 Wenhui Zhao,1 Tianyao Liu,2 Xiaotang Fan2 1School of Life Sciences, Chongqing University, Chongqing, 401331, People’s Republic of China; 2Department of Military Cognitive Psychology, School of Psychology, Third Military Medical University (Army Medical University), Chongqing, 400038, People’s Republic of China; 3Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, Institute of High Energy Physics and National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing, 100049, People’s Republic of ChinaCorrespondence: Xiaotang Fan; Tianyao Liu, Email fanxiaotang2005@163.com; squall277@163.comBackground: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition that affects social interaction and communication and can cause stereotypic behavior. Fullerenols, a type of carbon nanomaterial known for its neuroprotective properties, have not yet been studied for their potential in treating ASD. We aimed to investigate its role in improving autistic behaviors in BTBR T+Itpr3tf/J (BTBR) mice and its underlying mechanism, which could provide reliable clues for future ASD treatments.Methods: Our research involved treating C57BL/6J (C57) and BTBR mice with either 0.9% NaCl or fullerenols (10 mg/kg) daily for one week at seven weeks of age. We then conducted ASD-related behavioral tests in the eighth week and used RNA-seq to screen for vital pathways in the mouse hippocampus. Additionally, we used real-time quantitative PCR (RT-qPCR) to verify related pathway genes and evaluated the number of stem cells in the hippocampal dentate gyrus (DG) by Immunofluorescence staining.Results: Our findings revealed that fullerenols treatment significantly improved the related ASD-like behaviors of BTBR mice, manifested by enhanced social ability and improved cognitive deficits. Immunofluorescence results showed that fullerenols treatment increased the number of DCX+ and SOX2+/GFAP+ cells in the DG region of BTBR mice, indicating an expanded neural progenitor cell (NPC) pool of BTBR mice. RNA-seq analysis of the mouse hippocampus showed that VEGFA was involved in the rescued hippocampal neurogenesis by fullerenols treatment.Conclusion: In conclusion, our findings suggest that fullerenols treatment improves ASD-like behavior in BTBR mice by upregulating VEGFA, making nanoparticle- fullerenols a promising drug for ASD treatment. Keywords: fullerenols, BTBR, neurogenesis, autism spectrum disorder, hippocampus

Chunmei Liu,1 Yuzheng He,2 Jianmin Luo3 1Department of Radiation Oncology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, People’s Republic of China; 2Department of Thoracic Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, People’s Republic of China; 3Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, People’s Republic of ChinaCorrespondence: Jianmin Luo, Department of Hematology, The Second Hospital of Hebei Medical University, 215 West Heping Road, Shijiazhuang, Hebei Province, People’s Republic of China, Tel +86 1348368527, Email luojm31555@163.comPurpose: In situations where pathological acquisition is difficult, there is a lack of consensus on distinguishing between adenocarcinoma and squamous cell carcinoma from imaging images, and each doctor can only make judgments based on their own experience. This study aims to extract imaging features of chest CT, extract sensitive factors through logistic univariate and multivariate analysis, and model to distinguish between lung squamous cell carcinoma and lung adenocarcinoma.Methods: We downloaded chest CT scans with clear diagnosis of adenocarcinoma and squamous cell carcinoma from The Cancer Imaging Archive (TCIA), extracted 19 imaging features by a radiologist and a thoracic surgeon, including location, spicule, lobulation, cavity, vacuolar sign, necrosis, pleural traction sign, vascular bundle sign, air bronchogram sign, calcification, enhancement degree, distance from pulmonary hilum, atelectasis, pulmonary hilum and bronchial lymph nodes, mediastinal lymph nodes, interlobular septal thickening, pulmonary metastasis, adjacent structures invasion, pleural effusion. Firstly, we apply the glm function of R language to perform logistic univariate analysis on all variables to select variables with P < 0.1. Then, perform logistic multivariate analysis on the selected variables to obtain a predictive model. Next, use the roc function in R language to calculate the AUC value and draw the ROC curve, use the val.prob function in R language to draw the Calibrat curve, and use the rmda package in R language to draw the DCA curve and clinical impact curve. At the same time, 45 patients diagnosed with lung squamous cell carcinoma and lung adenocarcinoma through surgery or biopsy in the Radiotherapy Department and Thoracic Surgery Department of our hospital from 2023 to 2024 were included in the validation group. The chest CT features were jointly determined and recorded by the two doctors mentioned above and included in the validation group. The included image feature data are complete and does not require preprocessing, so directly entering statistical calculations. Perform ROC curves, calibration curves, DCA, and clinical impact curves in the validation group to further validate the predictive model. If the predictive model performs well in the validation group, further draw a nomogram to demonstrate.Results: This study extracted 19 imaging features from the chest CT scans of 75 patients downloaded from TCIA and finally selected 18 complete data for analysis. First, univariate analysis and multivariate analysis were performed, and a total of 5 variables were obtained: spicule, necrosis, air bronchogram Sign, atelectasis, pulmonary hilum and bronchial lymph nodes. After conducting modeling analysis with AUC = 0.887, a validation group was established using clinical cases from our hospital, Draw ROC curve with AUC = 0.865 in the validation group, evaluate the accuracy of the model through Calibrate calibration curve, evaluate the reliability of the model in clinical practice through DCA curve, and further evaluate the practicality of the model in clinical practice through clinical impact curve.Conclusion: It is possible to extract influential features from ordinary chest CT scans to determine lung adenocarcinoma and squamous cell carcinoma. The model we have set up performs well in terms of discrimination, accuracy, reliability, and practicality.Keywords: lung cancer, LUAD, LSCC, image features, predict

Jiaqi He,1,&ast; Xiuhui Lu,2,&ast; Chenchen Yuan,1 Yali Zheng,2 Fangzhou Chen,2 Jing Luo,2 Kejiao Ma,2 Fan Yang,2 Peng Wang,2 Dongsheng Zhou,2 Li Wang,1 Zhe Yin2 1Department of Clinical Laboratory, The First Affiliated Hospital of Henan University, Kaifeng, 475000, People’s Republic of China; 2State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, 100071, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Wang, Department of Clinical Laboratory, The First Affiliated Hospital of Henan University, Kaifeng, 475000, People’s Republic of China, Email wangli851217@163.com Zhe Yin, State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, 100071, People’s Republic of China, Email jerry9yin@163.comPurpose: Pseudomonas aeruginosa is a common causative bacteria in nosocomial infections. This study aims to describe the structure and evolutionary characteristics of mobile genetic elements (MGEs) carrying antibiotic resistance genes (ARGs) from P. aeruginosa and to conduct bioinformatics and comparative genomic analysis to provide a deeper understanding of the genetic characteristics and diversity of MGEs in P. aeruginosa.Methods: Fifteen clinical isolates of P. aeruginosa from China were collected and sequenced in this study, and 15 novel MGEs were identified. Together with four MGEs from GenBank, a total of 19 MGEs were used to perform detailed modular structure dissection and sequence comparison. Then, the biological experiments were carried out to verify the biological characteristics of these isolates and MEGs.Results: The novel MGEs identified in this study displayed diversification in modular structures, which showed complex mosaic natures. The seven types of 19 MGEs included in this study were divided into three groups: i) novel MGEs (firstly identified in this study): four IncpSE5381-aadB plasmids and three Tn 7495-related integrative and mobilizable elements (IMEs); ii) newly defined MGEs (firstly designated in this study, but with previously determined sequences): four Tn 7665-related IMEs; iii) novel transposons with reference prototypes identified in this study: two Tn 6417-related integrative and conjugative elements (ICEs), two IS-based transposition units, two Tn 501-related unit transposons, two Tn 1403-related unit transposons. At least 36 ARGs involved in resistance to 11 different classes of antimicrobials and heavy metals were identified. Additionally, three novel blaOXA variants were identified. Antimicrobial susceptibility testing showed that these variants were resistant to some β-lactamase antibiotics and blaOXA-1204 was additionally resistant to cephalosporins.Conclusion: The continuous evolution of ARG-carrying MGEs during transmission, leading to the emergence of novel MGEs or ARGs, which facilitates the spread of antibiotic resistance in P. aeruginosa and enhances the diversity of transmission modes of bacterial resistance.Keywords: Pseudomonas aeruginosa, genome sequencing, mobile genetic elements, antimicrobial resistance, OXA

Yiyu Chen,1 Chuxuan Fang,1 Jun Luo,1 Xueling Pan,2 Zongyan Gao,3 Shuangyi Tang,1 Meng Li4– 6 1Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Newborn ICU, Guigang Maternal and Child Health Care Hospital, Guigang City, Guangxi, People’s Republic of China; 3Newborn ICU, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 4Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 5Key Laboratory of Clinical Laboratory Medicine, Guangxi Department of Education, Nanning, Guangxi, People’s Republic of China; 6Key Laboratory of Fungi and Mycosis Research and Prevention, Guangxi Health Commission, Nanning, Guangxi, People’s Republic of ChinaCorrespondence: Meng Li, Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China, Tel/Fax +8613367809642, Email gxmulimeng@foxmail.comAbstract: The prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) has been increasing in recent years. Chinese Infectious Disease Surveillance of Pediatrics (ISPED) showed that in 2022, its resistance rate to meropenem was 18.5%. However, there is limited data available on the treatment of CRKP infection in neonates. In this study, we present a case involving a premature infant infected with OXA-48-producing Klebsiella pneumoniae. The combined susceptibility test revealed a significant synergistic effect between ceftazidime–avibactam(CAZ-AVI), and aztreonam(ATM). The infection was successfully treated with a combination of CAZ-AVI, ATM, and fosfomycin. This case represents the first reported instance of sepsis in a premature infant caused by OXA-48-producing Klebsiella pneumoniae in China. The objective of our study is to evaluate the effectiveness and safety of combination therapy in treating CRKP infections in premature infants. We hope that the findings of this study will provide valuable insights for clinicians in their treatment approach.Keywords: OXA-48, Klebsiella pneumoniae, premature infant, ceftazidime–avibactam, aztreonam

Weiwei Xie,1,&ast; Junqi Luo,1,&ast; Ruowei Tang,2,&ast; Xuan Zhou,3 Xiaohong Wang,4,5 Guojie Wang,1,5 Yaqin Zhang1 1Department of Radiology, the Fifth Hospital of Sun Yat-sen University, Zhuhai, Guangdong Province, People’s Republic of China; 2Department of Radiology, Beijing Friendship Hospital, Beijing, People’s Republic of China; 3Departments of Pathology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong Province, People’s Republic of China; 4Department of Radiology, the Third Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, People’s Republic of China; 5Department of Radiology, The First People’s Hospital of Kashi Prefecture, Kashi Prefecture, Xinjiang Uygur Autonomous Region, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yaqin Zhang; Guojie Wang, Department of Radiology, the Fifth Hospital of Sun Yat-sen University, 52 East Meihua Road, Xiangzhou District, Zhuhai, Guangdong Province, People’s Republic of China, Email zhyaqin@mail.sysu.edu.cn; wanggj5@mail.sysu.edu.cnPurpose: To explore the clinical and imaging features of rare site Kimura’s disease (KD).Methods: Retrospective analysis was conducted on the clinical manifestations, laboratory examinations, and imaging features of five patients with rare site KD. All imaging data, including the location, quantity, size, uniformity, boundary, and enhanced appearance of the lesion were evaluated by two independent radiologists.Results: Of the five patients, four were asymptomatic, and one experienced localized skin itching. Four cases involved subcutaneous nodules in the upper arm, while one was in the inguinal region. The main manifestations were single (three cases) or multiple (two cases) subcutaneous nodules/masses, with three patients accompanied by local lymph node enlargement. Four patients exhibited elevated eosinophil counts in their peripheral blood. Four patients had lesions with vascular flow voids; in three of these, the lesions also showed prominent enhancement. Notably, the lesion in a 5-year-old did not show vascular flow voids but displayed significant enhancement. Additionally, two patients showed edema around the lesions.Conclusion: The presence of solitary or multiple subcutaneous nodules/masses in the upper arm or inguinal area, accompanied by lymph node enlargement, elevated eosinophils in the peripheral blood, and the observation of internal vascular within the lesion, can aid in the diagnosis of KD occurring in uncommon anatomical locations.Keywords: Kimura disease, increased eosinophils, image, uncommon anatomical locations

Changjin Wang,1,&ast; Xiaolu Hu,1,2,&ast; Songyuan Luo,1,&ast; Yinghao Sun,1 Bangyuan Yang,1 Shengneng Zheng,3 Jiaohua Chen,1 Ming Fu,1 Ruixin Fan,4 Jie Li,1 Jianfang Luo1,2 1Department of Cardiology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 2School of Medicine South China University of Technology, Guangzhou, People’s Republic of China; 3Department of Radiology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 4Department of Cardiac Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Li; Jianfang Luo, Department of Cardiology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, &num;96 Dongchuan Road, Yuexiu District, Guangzhou, Guangdong, 510080, People’s Republic of China, Tel +86-20-83827812, Fax +86-20-83875453, Email leomoku1981@163.com; jianfangluo@sina.comPurpose: In mixed aortic valve disease (MAVD), the results of transcatheter aortic valve replacement (TAVR) are conflicting. There is limited data on the outcomes of TAVR in patients with bicuspid aortic valve (BAV) and MAVD. The objective of this study is to compare outcomes after TAVR in BAV patients with MAVD and predominant aortic stenosis (PAS).Patients and Methods: Patients with BAV who underwent TAVR between January 2016 and April 2023 were included. The primary outcome was device success. The secondary endpoints were periprocedural mortality and other complications as defined by the Valve Academic Research Consortium-3 (VARC-3). Propensity score matching was used to minimize potential confounding.Results: A total of 262 patients were included in this study, 83 of whom had MAVD. The median age was 72 years, and 55.7% were male. The baseline comorbidity risk files were comparable between the two groups. Patients with MAVD had more mitral regurgitation, tricuspid regurgitation and pulmonary hypertension, larger annular and left ventricular outflow tract dimensions, and more severe calcification than PAS. In the unmatched population, MAVD patients had similar device success rate (69.9% vs 79.9%, P=0.075) and 30-day mortality (3.6% vs 3.4%, P=1) compared to PAS. Propensity score matching resulted in 66 patient pairs. Device success rate were still comparable in the matched population. Other clinical outcomes, including stroke, bleeding (type 2– 4), major vascular complications, acute kidney injury (stage 2– 4) and permanent pacemaker implantation, were comparable between the two groups. Multivariable logistic regression analysis did not show MAVD to be an independent negative predictor of device success. At one year, survival was similar between patients with MAVD and those with PAS.Conclusion: For the bicuspid valve, patients with MAVD had a more challenging anatomy. MAVD patients associated with comparable 30-day clinical outcomes after TAVR compared to PAS patients in patients with BAV.Keywords: transcatheter aortic valve replacement, mixed aortic valve disease, bicuspid aortic valve, device success, propensity score match

Chen Yang,1,2,&ast; Wangjun Dong,2,&ast; Jianbo Luo,2 Mengzhao Ma,2 Yeyue Gao,2 Lijie Ni,2 Huixing Liu,2 Chengjun Cha,2 Yangli Xiao,2 Shaoqiang Huang1 1Department of Anesthesia, Obstetrics & Gynecology Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Anesthesia, Yongping County People’s Hospital, Yunnan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaoqiang Huang, Department of Anesthesia, Obstetrics & Gynecology Hospital, Fudan University, 128&num; Shenyang Road, Shanghai, 200090, People’s Republic of China, Email Drhuangsq@163.comObjective: Alterations in altitude can lead to an augmented requirement for local anesthesia among patients. Nevertheless, the necessity for an elevated dosage of local anesthetic for parturients at moderately high altitudes during spinal anesthesia for cesarean section remains uninvestigated. This up-down sequential study endeavors to determine the ED50 dose of bupivacaine required for spinal anesthesia during cesarean sections at moderately high-altitude.Methods: Thirty singleton parturients at moderately high altitude underwent elective cesarean section under combined spinal-epidural anesthesia. The up-and-down sequential method was employed, starting with an initial dose of 12mg (1.6mL) of 0.75% hyperbaric bupivacaine for the first participant. The dose for the next case was adjusted up or down by 0.75mg based on the effectiveness of the previous participant. Effectiveness was defined as the bilateral sensory block reaching T6 within 15 minutes after spinal anesthesia injection, without the need for additional epidural anesthesia before fetal delivery. The ED50 dose and 95% confidence interval were calculated using the Dixon sequential method and isotonic regression, respectively. The incidence of maternal hypotension, nausea, and vomiting during the study period was also recorded.Results: The ED50 of hyperbaric bupivacaine for spinal anesthesia in cesarean section was calculated as 8.23 mg (95% CI, 6.52– 9.32 mg) using the Dixon up-and-down method. Further validation using isotonic regression yielded a value of 8.39 mg (95% CI, 7.48– 9.30 mg), confirming the accuracy and sensitivity of the conclusion. During the operation, only 6 parturients experienced hypotension, and no adverse reactions such as nausea, vomiting, and shivering were observed.Conclusion: The ED50 dose of 0.75% hyperbaric bupivacaine for spinal anesthesia during cesarean section at moderately high altitude is 8.23 mg, which exceeds the ED50 dose typically required by parturients at low altitude. Comprehensive investigations are warranted to ascertain the ED90 or ED95 dose of local anesthetics for cesarean section at moderately high altitudes, thereby offering enhanced guidance for clinical practice.Keywords: bupivacaine, high altitude, spinal anesthesia, ED50 dose

Jiaxin Luo,1,2,&ast; Hanchi Wang,1,2,&ast; Jingxia Chen,1,2 Xuyan Wei,1,2 Jian Feng,1,2 Yidi Zhang,1,2 Yanmin Zhou1,2 1Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, Changchun, 130021, People’s Republic of China; 2Department of Oral Implantology, Hospital of Stomatology, Jilin University, Changchun, 130021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yidi Zhang; Yanmin Zhou, Department of Oral Implantology, Hospital of Stomatology, Jilin University, Changchun, 130021, People’s Republic of China, Email zhangyidi@jlu.edu.cn; zhouym@jlu.edu.cnAbstract: Immune cells are pivotal in the dynamic interplay between hypoxia and inflammation. During hypoxic conditions, HIF-1α, a crucial transcription factor, facilitates the adaptation of immune cells to the hypoxic micro-environment. This adaptation includes regulating immune cell metabolism, significantly impacting inflammation development. Strategies for anti-inflammatory and hypoxic relief have been proposed, aiming to disrupt the hypoxia-inflammation nexus. Research extensively focuses on anti-inflammatory agents and materials that target immune cells. These primarily mitigate hypoxic inflammation by encouraging M2-macrophage polarization, restraining neutrophil proliferation and infiltration, and maintaining Treg/TH17 balance. Additionally, oxygen-releasing nano-materials play a significant role. By alleviating hypoxia and clearing reactive oxygen species (ROS), these nano-materials indirectly influence immune cell functions. This paper delves into the response of immune cells under hypoxic conditions and the resultant effects on inflammation. It provides a comprehensive overview of various therapies targeting specific immune cells for anti-inflammatory purposes and explores nano-materials that either carry or generate oxygen to alleviate anoxic micro-environments.Keywords: hypoxia, inflammation, immunometabolism, immunotherapy, nanotherapy

Liyang Dong,1,&ast; Yafang Zhao,1,&ast; Juan Luo,1,2 Xiaopeng Li,1 Shuxian Wang,1 Menghan Li,1 Peng Zou,1 Hui Kong,1 Qingguo Wang,1 Yan Zhao,1 Huihua Qu1 1School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Institute of Precision Medicine, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingguo Wang; Yan Zhao, Email wangqg8558@sina.com; zhaoyandr@163.comBackground: Acute myocardial infarction (AMI) is a common cardiovascular disease in clinic. Currently, there is no specific treatment for AMI. Carbon dots (CDs) have been reported to show excellent biological activities, which hold promise for the development of novel nanomedicines for the treatment of cardiovascular diseases.Methods: In this study, we firstly prepared CDs from the natural herb Curcumae Radix Carbonisata (CRC-CDs) by a green, simple calcination method. The aim of this study is to investigate the cardioprotective effect and mechanism of CRC-CDs on isoproterenol (ISO) -induced myocardial infarction (MI) in rats.Results: The results showed that pretreatment with CRC-CDs significantly reduced serum levels of cardiac enzymes (CK-MB, LDH, AST) and lipids (TC, TG, LDL) and reduced st-segment elevation and myocardial infarct size on the ECG in AMI rats. Importantly, cardiac ejection fraction (EF) and shortening fraction (FS) were markedly elevated, as was ATPase activity. In addition, CRC-CDs could significantly increase the levels of superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), and reduce the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) in myocardial tissue, thereby exerting cardioprotective effect by enhancing the antioxidant capacity of myocardial tissue. Moreover, the TUNEL staining image showed that positive apoptotic cells were markedly declined after CRC-CDs treatment, which indicate that CRC-CDs could inhibit cardiomyocyte apoptosis. Importantly, The protective effect of CRC-CDs on H2O2 -pretreated H9c2 cells was also verified in vitro.Conclusion: Taken together, CRC-CDs has the potential for clinical application as an anti-myocardial ischemia drug candidate, which not only provides evidence for further broadening the biological application of cardiovascular diseases, but also offers potential hope for the application of nanomedicine to treat intractable diseases. Keywords: acute myocardial infarction, Curcumae Radix Carbonisata, carbon dots, oxidative stress

Xingping Zhou,1,&ast; Jinjin Luo,1,&ast; Xi Liang,1,2 Peng Li,1 Keke Ren,1 Dongyan Shi,1,2 Jiaojiao Xin,1,2 Jing Jiang,1,2 Jiaxian Chen,1 Lulu He,1 Hui Yang,1 Shiwen Ma,1 Bingqi Li,1 Jun Li1,2 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of China; 2Precision Medicine Center, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Li, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, People’s Republic of China, Tel/Fax +86-571-87236425, Email lijun2009@zju.edu.cnBackground and Aim: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a complicated syndrome with high short-term mortality. Effective biomarkers are required for its early diagnosis and prognosis. This study aimed to determine the diagnostic and prognostic value of thrombomodulin (TM) in patients with HBV-ACLF.Methods: The expression of TM during disease progression was evaluated through transcriptomics analysis. The plasma TM concentrations of 393 subjects with HBV-ACLF (n=213), acute-on-chronic hepatic dysfunction (ACHD, n=50), liver cirrhosis (LC, n=50) or chronic hepatitis B (CHB, n=50), and normal controls (NC, n=30) from a prospective multicenter cohort, were measured to verify the diagnostic and prognostic significance of plasma TM for HBV-ACLF patients by enzyme-linked immunosorbent assay (ELISA).Results: TM mRNA was highly expressed in the HBV-ACLF group compared with the ACHD group (AUROC=0.710). High expression of TM predicted poor prognosis for HBV-ACLF patients at 28/90 days (AUROCs=0.823/0.788). Functional analysis showed that TM was significantly associated with complement activation and the inflammatory signaling pathway. External validation confirmed its high diagnostic accuracy for HBV-ACLF patients (AUROC=0.796). Plasma TM concentrations were correlated with organ failure, including coagulation and kidney failure. Plasma TM concentrations showed a potential prognostic value for 28-day mortality rates (AUROC=0.702). Risk stratification specifically identified HBV-ACLF patients with a high risk of death as having a plasma TM concentration of ≥ 8.4 ng/mL.Conclusion: This study reveals that the plasma TM can be a candidate biomarker for early diagnosis and prognosis of HBV-ACLF, and might play a vital role in coagulation and inflammation.Keywords: thrombomodulin, HBV-ACLF, biomarker, organ failure

Qiong Luo,1,&ast; Jing Luo,1,&ast; Xixi Wang,2 Sifei Gan3 1Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 3Department of Anesthesiology, The First Hospital of Nanchang, Nanchang, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Sifei Gan, Department of Anesthesiology, The First Hospital of Nanchang, Nanchang, Jiangxi, People’s Republic of China, Email sifei1632023@163.comPurpose: Functional connectivity between the prelimbic medial prefrontal cortex (PL-mPFC) and the core of the nucleus accumbens (NAc core) predicts pain chronification. Inhibiting the apoptosis of oligodendrocytes in the PL-mPFC prevents fentanyl-induced hyperalgesia in rats. However, the role of prefrontal cortex (PFC)-NAc projections in opioid-induced hyperalgesia (OIH) remains unclear. Herein, we explored the role of the PL-NAc core circuit in fentanyl-induced hyperalgesia.Methods: An OIH rat model was established, and patch-clamp recording, immunofluorescence, optogenetics, and chemogenetic methods were employed for neuron excitability detection and nociceptive behavioral assessment.Results: Our results showed decreased activity of the right PL-mPFC layer V output neurons in rats with OIH. Similarly, the excitability of the NAc core neurons receiving glutamatergic projections from the PL-mPFC decreased in OIH rats, observed by the light-evoked excitatory postsynaptic currents/light-excited inhibitory postsynaptic currents ratio (eEPSC/eIPSC ratio). Fentanyl-induced hyperalgesia was reversed by optogenetic activation of the PL-NAc core pathway, and chemogenetic suppression of this pathway induced hyperalgesia in control (saline-treated) rats. However, behavioral hyperalgesia was not aggravated by this chemogenetic suppression in OIH (fentanyl-treated) rats.Conclusion: Our findings indicate that inactivation of the PL-NAc core pathway may be a cause of OIH and restoring the activity of this pathway may provide a strategy for OIH treatment.Keywords: fentanyl-induced hyperalgesia, prelimbic medial prefrontal cortex, nucleus accumbens core, circuit

Pengzhi Bu,1 Ruqian Duan,1 Ji Luo,1 Tao Yang,1 Ning Liu,2 Chuanbiao Wen1 1Institute of Intelligent Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, People’s Republic of China; 2College of Acupuncture and Massage, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, People’s Republic of ChinaCorrespondence: Chuanbiao Wen, Institute of Intelligent Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, Sichuan, People’s Republic of China, Email 553276475@qq.comBackground: Home beauty devices for facial rejuvenation utilizing technologies such as radiofrequency, microcurrent, and light emitting diode have gained widespread attention due to their claimed ability to improve skin tightness and elasticity, making them popular among consumers. However, there is controversy within the industry regarding the effectiveness and safety of these devices.Objective: This study aims to verify the safety and effectiveness of these home beauty devices in treating skin aging based on relevant efficacy evaluation indicators.Methods: A systematic search of PubMed and web of science was conducted to include original research literature on the efficacy of home beauty devices for facial rejuvenation over the past two decades. The selected literature was processed and analyzed based on efficacy evaluation indicators such as sample size, follow-up period, experimental results, adverse reactions, and others.Results: After screening, a total of 18 clinical studies were included. A comprehensive analysis of the experimental results and adverse reaction indicators from existing literature revealed that home beauty devices for facial rejuvenation can improve skin aging to a certain extent. Apart from transient redness and swelling, no other adverse reactions were observed.Conclusion: Despite the variety of home beauty devices for facial rejuvenation available in the market, corresponding research reports are limited. Existing studies suffer from issues such as small sample sizes and short follow-up periods, highlighting the need for a more comprehensive efficacy evaluation system. Furthermore, the physical stimulation of meridian acupoints by home beauty devices for facial rejuvenation may meet the multi-dimensional anti-aging needs of patients, suggesting a potential direction for future research.Keywords: facial rejuvenation, home beauty devices, radiofrequency, LED, microcurrent, Meridian acupoints

Jingsong Luo,1,2 Yuxin Chen,2 Yanmin Tao,1 Yaxin Xu,3 Kexin Yu,2 Ranran Liu,2 Yuchen Jiang,2 Cichong Cai,2 Yiyang Mao,2 Jingyi Li,2 Ziyi Yang,2 Tingting Deng1 1School of Nursing, The Chengdu University of Traditional Chinese Medicine, Sichuan, 610000, People’s Republic of China; 2Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China; 3School of Nursing, Tongji University, Shanghai, 200000, People’s Republic of ChinaCorrespondence: Tingting Deng, School of Nursing, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China, Email dengtingting999@163.comBackground: There is substantial evidence from previous studies that abnormalities in sleep parameters associated with depression are demonstrated in almost all stages of sleep architecture. Patients with symptoms of sleep-wake disorders have a much higher risk of developing major depressive disorders (MDD) compared to those without.Objective: The aim of the present study is to establish and compare the performance of different machine learning models based on sleep-wake disorder symptoms data and to select the optimal model to interpret the importance of sleep-wake disorder symptoms to predict MDD occurrence in adolescents.Methods: We derived data for this work from 2020 to 2021 Assessing Nocturnal Sleep/Wake Effects on Risk of Suicide Phase I Study from National Sleep Research Resource. Using demographic and sleep-wake disorder symptoms data as predictors and the occurrence of MDD measured base on the center for epidemiologic studies depression scale as an outcome, the following six machine learning predictive models were developed: eXtreme Gradient Boosting model (XGBoost), Light Gradient Boosting mode, AdaBoost, Gaussian Naïve Bayes, Complement Naïve Bayes, and multilayer perceptron. The models’ performance was assessed using the AUC and other metrics, and the final model’s predictor importance ranking was explained.Results: XGBoost is the optimal predictive model in comprehensive performance with the AUC of 0.804 in the test set. All sleep-wake disorder symptoms were significantly positively correlated with the occurrence of adolescent MDD. The insomnia severity was the most important predictor compared with the other predictors in this study.Conclusion: This machine learning predictive model based on sleep-wake disorder symptoms can help to raise the awareness of risk of symptoms between sleep-wake disorders and MDD in adolescents and improve primary care and prevention.Keywords: adolescent major depressive disorder, sleep-wake disorders symptom, insomnia, obstruct sleep apnea, machine learning prediction model, xgboost

Hongbiao Luo,1,2,&ast; Ji Luo,3,&ast; Ning Ding,1 Tao Zhang,1 Yongheng He1,4 1Graduate School, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China; 2Department of Anorectal Surgery, Chenzhou NO. 1 People’s Hospital, Chenzhou, Hunan, 423000, People’s Republic of China; 3Hunan Key Laboratory of Chinese Medicine on Oncology, Affiliated Hospital of Hunan Academy of Chinese Medicine, Changsha, Hunan, 410006, People’s Republic of China; 4Department of Anorectal Surgery, Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine, Changsha, Hunan, 410006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongheng He, Department of Anorectal Surgery, Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine, 58 Lushan Road, Yuelu District, Changsha, Hunan, 410006, People’s Republic of China, Tel +86-13517401858, Email 2320990685@qq.comBackground: Bicaudal-D (BICD) Family Like Cargo Adaptor 1 (BICDL1) is an essential component of the molecular mechanism during neuronal development. However, BICDL1 has not been reported in cancer. Using bioinformatics analysis, we systematically evaluated the potential role of BICDL1 in CRC.Methods: Colorectal cancer (CRC) and normal tissue samples were retrieved from the Gene Expression Omnibus (GEO), Genotype-Tissue Expression (GTEx), and Cancer Genome Atlas (TCGA) databases. Kaplan–Meier (K-M) analysis, nomogram, COX analysis, and receiver operating characteristic (ROC) curves were used to evaluate the prognostic power. Correlation analysis was also conducted to explore the correlation between mRNA expression and the methylation level of BICDL1 using cBioPortal, and the correlation between immune infiltration and BICDL1. RT-qPCR and Western blot assays were performed to analyze BICDL1 expression level between human colorectal cancer cell lines and normal colonic epithelial cells.Results: BICDL1 had a higher expression in CRC tissues than in normal tissues (p < 0.001) in TCGA and GES 74602 datasets. Kaplan-Meier survival analysis revealed that patients with high BICDL1 expression had lower overall survival (OS) (1.53, 95% confidence interval: 1.07– 2.17, p=0.019). The ROC curves demonstrated that BICDL1 has high specificity and efficiency in diagnosis (AUC=0.919, CI: 0.895– 0.943). The expression level of BICDL1 was significantly correlated with the infiltrating levels of Treg (R=0.146, p < 0.001), TFH (R=0.080, p=0.043), NK CD56bright cells (R=0.149, p < 0.001), aDC (R=0.095, p=0.016), and T helper cell infiltration (R=− 0.084, p=0.034). The correlation between BICDL1 expression and methylation levels was negative (R2=0.134, p < 0.001), and CRC patients had lower methylation levels than normal people (p=0.036). BICDL1 mRNA and its protein expression levels in CRC cell lines (SW620) was markedly increased compared with that of normal colonic epithelial cells (NCM460) (p < 0.001).Conclusion: BICDL1 may be a potential biomarker for evaluating immune infiltration levels and prognosis of CRC.Keywords: colorectal cancer, BICDL1, prognosis, biomarker, immune infiltration, methylation

Wenjun Liang,1 Angela TH Kwan,2 Huifang Ye,3 Mohammad Mofatteh,4 Mingzhu Feng,1 Jack Wellington,5 Pingzhong Fu,6 Wenlong Wei,1 Yu Sun,1 Jianhui Huang,7 Jie Luo,7 Yimin Chen,1 Shuiquan Yang,1 Sijie Zhou7 1Department of Neurology and Advanced National Stroke Center, Foshan Sanshui District People’s Hospital, Foshan, People’s Republic of China; 2Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada; 3Department of Pharmacy, Foshan Sanshui District People’s Hospital, Foshan, People’s Republic of China; 4School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, United Kingdom; 5School of Medicine, Cardiff University, Cardiff, United Kingdom; 6Department of Radiology, Foshan Sanshui District People’s Hospital, Foshan, Guangdong Province, People’s Republic of China; 7Department of Surgery of Cerebrovascular Diseases, First People’s Hospital of Foshan, Foshan, Guangdong Province, People’s Republic of ChinaCorrespondence: Shuiquan Yang, Department of Neurology and Advanced National Stroke Center, Foshan Sanshui District People’s Hospital, Foshan, Guangdong Province, 528100, People’s Republic of China, Email yangshuiquan1969@126.com Sijie Zhou, Department of Neurosurgery, First People’s Hospital of Foshan, Foshan, Guangdong Province, 528000, People’s Republic of China, Email zhousijie91@163.comPurpose: In this study, we aimed to determine whether post-Alberta Stroke Project Early CT Changes Score (post-ASPECTS) in anterior stroke and post-(posterior circulation) PC-ASPECTS in posterior stroke on CT can predict post-endovascular thrombectomy (EVT) functional outcomes among patients with acute ischemic stroke (AIS) after EVT.Patients and Methods: A total of 247 consecutive patients aged 18 and over receiving EVT for LVO-related AIS were recruited into a prospective database. The data was retrospectively analyzed between March 2019 and February 2022 from two comprehensive tertiary care stroke centers: Foshan Sanshui District People’s Hospital and First People’s Hospital of Foshan in China. Patient parameters included EVT within 24 hr of symptom onset, premorbid modified Rankin scale (mRS) ≤ 2, presence of distal and terminal cerebral blood vessel occlusion, and subsequent 24– 72-hr post-stroke onset CT scan. Univariate comparisons were performed using the Fisher’s exact test or χ2 test for categorical variables and the Mann–Whitney U-test for continuous variables. Logistic regression analysis was performed to further analyze for adjusting for confounding factors. A p-value of ≤ 0.05 was statistically significant.Results: Overall, 236 individuals with 196 anterior circulation ischemic strokes and 40 posterior strokes of basilar artery occlusion were examined. Post-ASPECTS in anterior stroke and post-pc-ASPECTS as strong positive markers of favorable outcome at 90 days post-EVT; and lower rates of inpatient mortality/hospice discharge, 90-day mortality, and 90-day poor outcome were observed. Moreover, patients in the post-ASPECTS ≥ 7 cohort experienced shorter door-to-recanalization time (DRT), puncture-to-recanalization time (PRT), and last known normal-to-puncture time (LKNPT).Conclusion: Post-ASPECTS ≥ 7 in anterior circulation AIS and post-pc-ASPECTS ≥ 7 in posterior circulation can serve as strong prognostic markers of functional outcome after EVT.Keywords: endovascular therapy, thrombectomy, large vessel occlusion, cerebral ischemic stroke, ASPECTS

Wenyu Hu,1,&ast; Lei Wang,1,&ast; JiaLing Luo,1 Jian Zhang,2 Nanlin Li1 1Department of Thyroid, Breast and Vascular Surgery, Xijing Hospital, Air Force Military Medical University, Xi’an, Shaanxi, People’s Republic of China; 2The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Air Force Military Medical University, Xi’an, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nanlin Li; Jian Zhang, Email nanlin-74@163.com; biozhangj@fmmu.edu.cnPurpose: Inhibition of the cyclin-dependent kinase (CDK) 4/6-retinoblastoma (RB) pathway exerts a considerable inhibitory effect, preventing the spread and metastasis of breast cancer cells and promoting tumor regression. In this study, we examined the antitumor activity of TQB3616, a novel inhibitor of CDK4/6 activity, which showed a greater efficacy improvement in antitumor effects.Methods: TQB3616 group, abemaciclib group and endocrine or HER-2 targeted combination therapy group were set up respectively. The effects of drugs on cell proliferation activity, cell cycle, apoptosis, downstream protein expression and gene expression of HR positive (T47D, MCF-7) and HER-2 positive (BT474, MDA-MB-361) breast cancer cell lines were studied. The antiproliferative effect of TQB3616 was also measured in vivo.Results: TQB3616 showed a remarkable inhibitory effect on the proliferation of hormone receptor-positive breast cancer cells in vitro. In addition, TQB3616 combined with endocrine therapy or Human Epidermal Growth Factor Receptor 2 (HER2) targeted therapy showed significant synergistic antitumor activity in estrogen receptor (ER)-positive/HER2-negative or HER2-positive breast cancer. In contrast to abemaciclib, which targets the CDK4/6 pathway with proven efficacy, the oral agent TQB3616 not only induced G1 stalling, leading to a profound reduction in the level of RB protein phosphorylated at Ser807/811, but also showed enhanced tumor killing effects by promoting cell apoptosis. Oral administration of TQB3616 showed more potent antitumor activity than abemaciclib in an in vitro breast cancer xenograft model, causing significant tumor regression associated with sustained target inhibition in tumor tissue and manageable in vivo toxicity.Conclusion: The results of this study indicate that TQB3616 is a novel CDK4/6 inhibitor, and its highly effective antitumor activity against breast cancer is expected to yield promising therapeutic effects in clinical studies.Keywords: breast cancer, endocrine therapy, CDK inhibitors, apoptosis, abemaciclib

Jian Yang,1,&ast; Jing Zhang,1,&ast; Jiayan Luo,2 Jie Ouyang,1 Qicai Qu,1 Qitao Wang,1 Yongyu Si1 1Department of Anesthesiology, Second Affiliated Hospital of Kunming Medical University, Kunming, 650101, People’s Republic of China; 2Department of Anesthesiology, People’s Hospital of Yanting, Sichuan, 621600, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongyu Si, Department of Anesthesiology, Second Affiliated Hospital of Kunming Medical University, No. 374 of Dianmian Road, Wuhua District, Kunming, 650101, People’s Republic of China, Tel +86 10 65333681, Fax +86 10 65334416, Email siyongyyu@126.comObjective: In this study, we evaluated the efficacy of tranexamic acid (TXA) and acute normovolemic hemodilution (ANH) with 6% hydroxyethyl starch (130/0.4) in minimizing blood loss during open partial liver resection. Coagulation function was assessed using thromboelastography (TEG) and hemostasis tests, while renal function changes were tracked through serum creatinine values post-surgery.Methods: Thirty patients undergoing open partial liver resection were allocated to two groups: Group T received TXA + ANH, and Group A received ANH alone. Blood was drawn from the radial artery under general anesthesia. Both groups received peripheral vein injections of 6% hydroxyethyl starch 130/0.4. Group T additionally received intravenous TXA. Primary outcomes included blood loss and allogeneic blood transfusions. TEG assessed coagulation status and renal function was monitored.Results: Group T demonstrated superior outcomes compared to Group A. Group T had significantly lower intraoperative blood loss (700 mL vs 1200 mL) and a lower bleeding rate per kilogram of body weight (13.3 mL/kg vs 20.4 mL/kg). Coagulation parameters favored Group T, with higher TEG maximum amplitude (55.91 mm vs 45.88 mm) and lower activated partial thromboplastin time (38.04 seconds vs 41.49 seconds). Neither group experienced acute renal injury or kidney function deficiency during hospitalization.Conclusion: TXA and ANH in a small dose during liver resection stabilize clotting, reduce blood loss by 6% compared to hydroxyethyl starch 130/0.4, and do not affect renal function.Keywords: acute normovolemic hemodilution, coagulation function, liver resection, thromboelastography, tranexamic acid

Zhaojun Liang,1,2 Nan Wang,1,2 Chunxue Fan,1,2 Lili Shang,1,2 Yaping Zhang,1,2 Chong Gao,3 Jing Luo1,2 1Division of Rheumatology, Department of Medicine, the Second Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Shanxi Key Laboratory for Immunomicroecology, the Second Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 3Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USACorrespondence: Jing Luo, Email ljty966@hotmail.comIntroduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to disorders of immune function and a decrease in the diversity of intestinal flora. We aimed to explore the changes of circulating immune cell subsets and the plasma level of intestinal short-chain fatty acids (SCFAs) in patients with Coronavirus disease 2019 (COVID-19), further understanding the pathogenesis of COVID-19.Methods: The study included 83 newly diagnosed COVID-19 patients and 39 non-COVID-19 controls. All have completed a full course of vaccination against SARS-CoV-2. The levels of peripheral lymphocyte subsets and plasma cytokines were detected by flow cytometry. Targeted metabolomics was used to explore the level of SCFAs in plasma.Results: Compared with the non-COVID-19 group, COVID-19 patients showed a decrease in CD19+B cells, CD4+T cells, CD8+T cells, NK cells, CD4+CD8+T cells and CD4–CD8–T cells (all p< 0.001) and concomitantly an increase in sIL-2R, IL-6 and IL-10 (all p< 0.005). These alterations were more pronounced in those critical patients. In addition, COVID-19 patients had lower levels of propanoic acid (PA), butyric acid (BA), isobutyric acid (IBA) and isohexanoic acid (ICA) (all p< 0.01). Among them, the level of ICA is positively correlated with the absolute number of immune cells.Conclusion: Our study suggests the immune cell subsets in COVID-19 patients who had completed vaccination were still severely disturbed and concomitantly lower SCFAs, especially in severe patients with poor prognosis. Lower levels of plasma SCFAs may contribute to lymphopenia in COVID-19. The potential relationship between plasma SCFAs and immune cell reduction provides a new direction for the treatment of COVID-19.Keywords: coronavirus disease 2019, severe acute respiratory syndrome coronavirus 2, adaptive immunity, short-chain fatty acids

Jincheng Xiao,1,&ast; Jing Wang,2,&ast; Chaoqun Zhou,3 Junpeng Luo4,5 1Department of Radiology, Zhengzhou University Affiliated Cancer Hospital, Zhengzhou, 450008, People’s Republic of China; 2Department of General Medicine, the First Medical Center, Department of Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Department of Pathology, Huaihe Hospital, Henan University, Henan University, Kaifeng, 475000, People’s Republic of China; 4Translational Medical Center of Huaihe Hospital, Henan University, Kaifeng, 475000, People’s Republic of China; 5Academy for Advanced Interdisciplinary Studies, Henan University, Zhengzhou, 450046, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junpeng Luo, Translational Medical Center of Huaihe Hospital, Henan University, 115 West Gate Street, Kaifeng, 475000, People’s Republic of China, Tel/Fax +86 371 23999999, Email hiccp@henu.edu.cnBackground: Studies have demonstrated that propionate metabolism-related genes (PMRGs) are associated with cancer progression. PMRGs are not known to be involved in Hepatocellular carcinoma (HCC).Methods: In this study, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were accessed for HCC-related transcriptome data and clinical information. First, DE-PMRGs were derived by intersecting PMRGs and DEGs between HCC tissues and normal controls. The clusterProfiler R package was then used to enrich DE-PMRGs. In addition, biomarkers of HCC were identified, and a prognostic model was developed. Using functional analysis and tumor microenvironment analysis, new insights were obtained into HCC. The expression of biomarkers was validated using quantitative real-time polymerase chain reaction (qRT-PCR).Results: 132 DE-PMRGs were obtained by intersecting 3690 DEGs and 291 PMRGs. Steroid and organic acid metabolism were associated with these genes. For the construction of the risk model for HCC samples, five biomarkers were identified, including Acyl-CoA dehydrogenase short chain (ACADS), CYP19A1, formiminotransferase cyclodeaminase (FTCD), glucose-6-phosphate dehydrogenase (G6PD), and glutamic-oxaloacetic transaminase (GOT2). ACADS, FTCD, and GOT2 were positive factors, whereas CYP19A1 and G6PD were negative. HCC patients with AUC greater than 0.6 were predicted to survive 1/2/3/4/5 years, indicating decent efficiency of the model. The probability of 1/3/5-survival for HCC was also predicted by the nomogram using the risk score, pathologic T stage, and cancer status. Moreover, functional enrichment analysis revealed the high-risk genes were associated with invasion and epithelial-mesenchymal transition. Significantly, immune cell infiltration and immune checkpoint expression were linked to HCC development.Conclusion: This study identified five biomarkers of propionate metabolism that can predict HCC prognosis. This finding may provide a deeper understanding of PMRG function in HCC.Keywords: Hepatocellular carcinoma, propionate metabolism-related genes, prognosis, biomarkers, tumor microenvironment

Guang-Yao Chen,1,2,&ast; Xiao-Yu Liu,3,&ast; Xue-Er Yan,4,&ast; XinBo Yu,1,2 Yi Liu,5 Jing Luo,1,2 Qing-Wen Tao1,2 1Department of TCM Rheumatology, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 2Beijing Key Laboratory for Immune-Mediated Inflammatory Diseases, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 3School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 5Humanities School, Beijing University of Chinese Medicine, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qing-Wen Tao, Email taoqg1@outlook.comObjective: Previous clinical studies have found that total flavonoids of Rhizoma Drynariae (TFRD) have a good therapeutic effect on osteoarthritis (OA), but its therapeutic mechanism needs further research.Methods: OA rat model was established by Hulth method and was intervened by TFRD. Pathological assessments were conducted to assess the protective effect of TFRD on cartilage. Serum metabolomics and network pharmacology were detected to predict the mechanism of TFRD treating OA. In further experiments, molecular biology experiment was carried out to confirm the predicted mechanisms in vivo and in vitro.Results: TFRD can effectively reduce chondrocyte apoptosis and cartilage degeneration in OA model rats. Serum metabolomics revealed that the intervention effect may be closely related to arachidonic acid metabolism pathway. Network pharmacologic prediction showed that COX-2 was the key target of TFRD in treating OA, and its mechanism might be related with NFκB, apoptosis, AMPK and arachidonic acid metabolism pathway. In vivo experiments indicated that TFRD can inhibit the abnormal expression of COX-2 mRNA in OA model rats. In the in vitro studies, the expression of COX-2 mRNA and protein increased, AMPK phosphorylation was inhibited, and NFκB signaling pathway was activated in IL-1β-induced chondrocytes, and these changes can be reversed by TFRD. After the activation of AMPK signaling pathway or the block-down of NFκB signaling pathway, the effect of TFRD on COX-2 mRNA expression was significantly weakened.Conclusion: TFRD can inhibit COX-2-mediated arachidonic acid metabolites, and its mechanism is closely related to AMPK/NFκB pathway, which may be a key mechanism in the treatment of OA.Keywords: total flavonoids of Rhizoma Drynariae, osteoarthritis, network pharmacology, serum metabolomics, cyclooxygenase-2, AMPK/NFκB pathway

Xiaogang Zhang,&ast; Zhongying Xing,&ast; Chao Fang, Meiling Yang, Jun Luo, Zhongping Ning Department of Cardiology, Shanghai Pudong New Area Zhoupu Hospital (Shanghai Health Medical College Affiliated Zhoupu Hospital), Shanghai, 201318, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhongping Ning, Department of Cardiology, Shanghai Pudong New Area Zhoupu Hospital (Shanghai Health Medical College Affiliated Zhoupu Hospital), No. 1500 Zhouyuan Road, Pudong New District, Shanghai, 201318, People’s Republic of China, Tel +86-021-68135590, Email ningzpsh@163.comBackground: To investigate the safety and effectiveness of cryo-balloon pulmonary vein isolation (PVI) and left atrial appendage closure (LAAC) combined procedure and half-dose rivaroxaban after operation in elderly patients with atrial fibrillation (AF).Patients and Methods: A total of 203 AF patients presented for cryo-balloon PVI, and LAAC combined procedure was included from 2019 to 2021. Postoperative patients were anticoagulated with rivaroxaban with/without clopidogrel for 60 days, with oral rivaroxaban of 10 mg in the elderly group and 20 mg in the non-elderly group. Patients with AF ≥ 80 and < 80 years were considered elderly and non-elderly groups, respectively. Scheduled follow-ups and transesophageal echocardiography were used to assess peri- and post-procedural safety and effectiveness.Results: A total of 203 patients underwent the combined procedure, 83 in the elderly and 120 in the non-elderly groups. All patients successfully obtained PVI and satisfactory LAAC. During the perioperative period, one patient had puncture complications in the elderly group and one with thrombosis in the non-elderly group. Oral rivaroxaban was administered to 83.2% and 75% of patients in the elderly and non-elderly groups, respectively, and rivaroxaban was combined with clopidogrel anticoagulation in the remaining patients. The annual rates of composite clinical events were 8.4% and 9.2% in the elderly and non-elderly groups, respectively, with no statistically significant difference. Patients in both groups had complete sealing, and there was no displacement of devices, death and peripheral arterial thrombosis. Recurrence of AF occurred in 25 and 32 patients in the elderly and non-elderly groups, respectively, with no statistically significant difference. Besides, the two groups had no statistically significant difference in cerebral infarction/transient ischemic attack and device-related thrombosis (p > 0.05).Conclusion: This study suggests that cryo-balloon PVI and LAAC combined procedure and half-dose rivaroxaban after the operation is safe and effective in treating elderly patients with AF.Keywords: pulmonary vein isolation, left atrial appendage closure, cryo-balloon, rivaroxaban, atrial fibrillation, elderly patients

Huang Y, Chen J, Yang S, et al. Drug Des Devel Ther. 2020;14:4625–4637. We, the Editor and Publisher of the journal Drug Design, Development and Therapy, have retracted the following article. Following publication of the article, concerns were raised about the duplication of images from Figures 4 and 6. Specifically, Images for Figure 4F, MG63, control and 80 µM, have been duplicated. Images for Figure 4J, MG63, 12H, control and 100 µM, have been duplicated. Images for Figure 6D, Osteosarcoma, Blank (x 200) and 75 mg/kg (x 200) have been duplicated. Images for Figure 6E, p-Akt (Ser473), 50 mg/kg (x 400) and 75 mg/kg (x 400) have been duplicated. 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, we are therefore retracting the article and the authors were notified of this. 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”.

Chunyun Fu,1,&ast; Jingsi Luo,2,&ast; Jiasun Su,2 Shujie Zhang,2 Qi Yang,2 Yue Zhang2 1Medical Science Laboratory, Children’s Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530003, People’s Republic of China; 2Department of Genetic Metabolism, Children’s Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunyun Fu, Email fuchunyun2008@sina.comObjective: Congenital central hypothyroidism (CCH) is a rare disorder poorly described in childhood and adolescence. The current knowledge on the genetic bases of CCH is scarce. The purpose of this study was to analyze the clinical characteristics and molecular genetic basis of CCH in children.Methods: We conducted a thorough evaluation of the clinical features in children diagnosed with CCH. Genomic DNA was extracted from peripheral blood of both children and their parents, and chromosomal microarray analysis and whole-exome sequencing were performed. Candidates for single nucleotide variants were validated using Sanger sequencing and were classified according to the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) guidelines.Results: Two cases with likely pathogenic variants were detected by whole-exome sequencing. Individual 1 carried a novel homozygous ATP6V0A4 c.1418C>T (p.Ser473Phe) variant and a novel heterozygous POU1F1 c.416G>A. (p.Arg139Gln) variant. Individual 2 had a novel homozygous POU1F1 c.212C>T (p.Ala71Val) variant. The chromosomal microarray detected the presence of a 24 Mb heterozygous deletion (LOH: loss of heterozygosity) in the p12.1p13.13 region of chromosome 2 in individual 3, and the copy number variant was unknown of clinical significance.Conclusion: Our study employed chromosomal microarray and whole-exome sequencing to investigate central hypothyroidism in seven children, leading to the detection of genetic anomalies in three individuals. The identification of novel variants has contributed to the expanded genetic spectrum of POU1F1 and ATP6V0A4 associated with pediatric central hypothyroidism.Keywords: congenital central hypothyroidism, genetic, chromosomal microarray, whole-exome sequencing, pathogenic variants

Yunli Xing, Ying Sun, Mei Tang, Wei Huang, Jia Luo, Qing Ma Department of Geriatrics, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Qing Ma, Department of Geriatrics, Beijing Friendship Hospital, Capital Medical University, No. 95, Yongan Road, Xicheng District, Beijing, 100050, People’s Republic of China, Tel +86 13801019331, Fax +86 10 6313 8040, Email maqing3@163.comBackground: Advanced age increases the risk for severe COVID-19. However, the risk factors for mortality from COVID-19 in very elderly patients (≥ 80-years-old) are unknown.Objective: Investigate the relationship of mortality with the clinical characteristics of very elderly COVID-19 patients.Materials and Methods: Very elderly patients who were hospitalized with COVID-19 from December 3, 2022 to January 1, 2023 were retrospectively examined. Sociodemographic and clinical variables were recorded and survival was recorded after 30 days.Results: We examined 181 patients (median age: 90.84 years; 114 older than 90 years). The median Barthel index was 30.69, and 55.8% of patients had severe or critical COVID-19 pneumonia. Forty-two patients (33.2%) received a high-flow nasal cannula or non-invasive ventilation, and only 4.4% received mechanical ventilation. The overall mortality was 35.9%, and there was no significant difference in mortality for the 80 to 90-year-old group and the over 90-year-old group (37.7% vs 32.8%, P=0.508). A multivariate analysis showed that the Barthel index (OR, 0.975; 95% CI, 0.962– 0.989), serum creatinine (SCr) level (OR, 1.003; 95% CI, 1.000– 1.006), white blood cell (WBC) count (OR, 1.160; 95% CI, 1.056– 1.276), D-dimer level (OR, 1.060; 95% CI, 1.009– 1.113), and corticosteroid use (OR, 0.268; 95% CI, 0.124– 0.582) were significantly and independently related to 30-day mortality. A binary classification model based on the multivariate analysis had good predictive value (area under the curve, 0.794).Conclusion: Very elderly COVID-19 patients have a high risk for mortality. The Barthel index, SCr, WBC count, D-dimer level, and corticosteroid use were independently associated with mortality.Keywords: COVID-19, over-80-year-old, characteristic, mortality

Hui Zhu,1,2 Ke Yang,3 Huan Yao,1 Xueying Chen,1 Shujin Yan,1,2 Yiman He,1,2 Yang Cao,2 Jie Luo,1 Dong Wang1 1Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Key Laboratory of Ultrasound Molecular Imaging, Chongqing Medical University, Chongqing, People’s Republic of China; 3Pediatric Research Institute, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Jie Luo; Dong Wang, Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400042, People’s Republic of China, Email luojie1983@cqmu.edu.cn; wangdong4429@cqmu.edu.cnBackground: Breast cancer has become the most common cancer in women. Compare with other subtypes of breast cancer, triple-negative breast cancer (TNBC) is more likely to relapse and metastasize. Highly effective therapeutic strategies are desperately needed to be explored. In this study, a multifunctional nanoplatform is expected to mediate chemo-photothermal therapy, which can combine immunogenic cell death with checkpoint blockade to combat TNBC and distant metastasis.Methods: Poly (lactic acid-glycolic acid)-Poly (ethylene glycol) (PLGA-PEG) nanoparticles (NPs), a type of polymeric NPs, loaded with IR780, a near-infrared (NIR) dye, and doxorubicin (DOX) as the chemotherapeutic drug, were assembled by an improved double emulsification method (designated as IDNPs). The characterization, intracellular uptake, biosafety, photoacoustic (PA) imaging performance, and biodistribution of IDNPs were studied. Chemo-photothermal therapeutic effect and immunogenic cell death (ICD) were evaluated both in vitro and in vivo. The potency of chemo-photothermal therapy-triggered ICD in combination with anti-PD-1 immune checkpoint blockade (ICB) immunotherapy in eliciting immune response and treating distant tumors was further investigated.Results: IR780 and DOX were successfully loaded into PLGA-PEG to form the IDNPs, with size of 243.87nm and Zeta potential of − 6.25mV. The encapsulation efficiency of IR780 and DOX was 83.44% and 5.98%, respectively. IDNPs demonstrated remarkable on-site accumulation and PA imaging capability toward 4T1 TNBC models. Chemo-photothermal therapy demonstrated satisfactory therapeutic effects both in vitro and in vivo, and triggered ICD efficiently. ICD, in combination with anti-PD-1, provoked a systemic antitumor immune response against distant tumors.Conclusion: Multifunctional IDNPs were successfully synthesized to mediate chemo-photothermal therapy, which combines immunogenic cell death with checkpoint blockade to combat TNBC and distant metastasis, showing great promise preclinically and clinically.Keywords: immunogenic cell death, immunotherapy, checkpoint blockade, chemo-photothermal therapy, triple-negative breast cancer

Xueying Bai, Ji Luo Department of Thoracic Surgery, The First Hospital of China Medical University, Shenyang, 110001, People’s Republic of ChinaCorrespondence: Xueying Bai, Email baixueying9914@163.comBackground: Invasive candidiasis (ICs) is one of the common causes of death in patients with solid tumors. However, studies on the clinical characteristics of ICs with solid tumors are limited.Methods: The purpose of this study was to retrospectively analyse the clinical characteristics, laboratory results and risk factor prediction of inpatients with ICs and solid tumors. We reviewed the clinical data and candida specimen information of hospitalized patients diagnosed with solid tumors combined with ICs at the First Hospital of China Medical University from January 2016 to December 2020. Multivariate logistic regression analysis was used to assess the prognostic factors associated with mortality in these patients.Results: A total of 243 ICs patients with solid tumors were included in this study. The average ± SD age was 62.8 ± 11.7 (range: 27– 93 years old), of which nearly 41% were ≥ 65 years old (99/243, 40.7%), and most were male (162/243, 66.6%). Most patients had malignant tumors of the digestive system. The most common candida was Candida parapsilosis (101/243, 41.5%), followed by Candida guilliermondii (83/243, 34.1%), Candida albicans (32/243, 13.1%), Candida glabrata (17/243, 6.9%), Candida tropicalis (7/243, 2.8%) and Candida krusei (3/243, 1.2%). Multivariate logistic regression analysis showed that the length of stay in the ICU, urinary catheter, total parenteral nutrition, stay in the ICU, renal failure and neutrophil count were prognostic factors related to death.Conclusion: In this study, based on the clinical data of solid tumor patients with ICs in the past 5 years, the results showed that the length of stay in the ICU, urinary catheter, total parenteral nutrition, stay in the ICU, renal failure and neutrophil count were identified as the main prognostic factors. This study can be used to help clinicians carry out early intervention for high-risk patients.Keywords: invasive candidiasis, solid tumors, epidemic, single center, prognosis

Yong Li,1,2,&ast; Senbo Zhu,2,&ast; Junchao Luo,2 Yu Tong,2 Yixuan Zheng,1 Lichen Ji,2 Zeju He,2 Qiangan Jing,1 Jiaqing Huang,2 Yinjun Zhang,1 Qing Bi2 1College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, Zhejiang, 310014, People’s Republic of China; 2Laboratory Medicine Center, Department of Laboratory Medicine, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yinjun Zhang, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, Zhejiang, 310014, People’s Republic of China, Tel +86-13735494556, Email zhangyj@zjut.edu.cn Qing Bi, Laboratory Medicine Center, Department of Laboratory Medicine, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China, Tel +86-13588302991, Email bqzjsrmyy@163.comIntroduction: Osteoarthritis (OA) is a common chronic joint disease characterized by articular cartilage degeneration. OA usually manifests as joint pain, limited mobility, and joint effusion. Currently, the primary OA treatment is non-steroidal anti-inflammatory drugs (NSAIDs). Although they can alleviate the disease’s clinical symptoms and signs, the drugs have some side effects. Selenium nanoparticles (SeNPs) may be an alternative to relieve OA symptoms.Materials and Results: We confirmed the anti-inflammatory effect of selenium nanoparticles (SeNPs) in vitro and in vivo experiments for OA disease in this study. In vitro experiments, we found that SeNPs could significantly reduce the expression of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), the major inflammatory factors, and had significant anti-inflammatory and anti-arthritic effects. SeNPs can inhibit reactive oxygen species (ROS) production and increased glutathione peroxidase (GPx) activity in interleukin-1beta (IL-1β)-stimulated cells. Additionally, SeNPs down-regulated matrix metalloproteinase-13 (MMP-13) and thrombospondin motifs 5 (ADAMTS-5) expressions, while up-regulated type II collagen (COL-2) and aggrecan (ACAN) expressions stimulated by IL-1β. The findings also indicated that SeNPs may exert their effects through suppressing the NF-κB p65 and p38/MAPK pathways. In vivo experiments, the prevention of OA development brought on by SeNPs was demonstrated using a DMM model.Discussion: Our results suggest that SeNPs may be a potential anti-inflammatory agent for treating OA.Keywords: osteoarthritis, NF-κB p65 signaling pathway, p38/MAPK signaling pathway, selenium nanoparticles

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

Xuehe Zhang,1 Fen Liu,1 Wenling Li,1 Jixin Zhang,1 Tong Zhang,1 Xiaolin Yu,2 Junyi Luo,1 Qian Zhao,1 Jinyu Zhang,1 Binbin Fang,1 Yining Yang,2 Xiaomei Li1 1Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 2Department of Cardiology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, People’s Republic of ChinaCorrespondence: Yining Yang, Department of Cardiology, People’s Hospital of Xinjiang Uygur Autonomous Region, 91 Tianchi Road, Urumqi, 830054, People’s Republic of China, Tel +86-991-4361690, Email yangyn5126@163.com Xiaomei Li, Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, 137 Liyushan South Road, Urumqi, 830054, People’s Republic of China, Tel +86-991-4362611, Email lixm505@163.comPurpose: This study aimed to evaluate the association between metabolic score for insulin resistance (METS-IR) and adverse cardiovascular events in patients with ischemic cardiomyopathy (ICM) and type 2 diabetes mellitus (T2DM).Methods: METS-IR was calculated using the following formula: ln[(2 × fasting plasma glucose (mg/dL) + fasting triglyceride (mg/dL)] × body mass index (kg/m2)/(ln[high-density lipoprotein cholesterol (mg/dL)]). Major adverse cardiovascular events (MACEs) were defined as the composite outcome of nonfatal myocardial infarction, cardiac death, and rehospitalization for heart failure. Cox proportional hazards regression analysis was used to evaluate the association between METS-IR and adverse outcomes. The predictive value of METS-IR was evaluated by the area under the curve (AUC), continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI).Results: The incidence of MACEs increased with METS-IR tertiles at a 3‑year follow‑up. Kaplan‒Meier curves showed a significant difference in event-free survival probability between METS-IR tertiles (P< 0.05). Multivariate Cox hazard regression analysis adjusting for multiple confounding factors showed that when comparing the highest and lowest METS-IR tertiles, the hazard ratio was 1.886 (95% CI:1.613– 2.204; P< 0.001). Adding METS-IR to the established risk model had an incremental effect on the predicted value of MACEs (AUC=0.637, 95% CI:0.605– 0.670, P< 0.001; NRI=0.191, P< 0.001; IDI=0.028, P< 0.001).Conclusion: METS-IR, a simple score of insulin resistance, predicts the occurrence of MACEs in patients with ICM and T2DM, independent of known cardiovascular risk factors. These results suggest that METS-IR may be a useful marker for risk stratification and prognosis in patients with ICM and T2DM.Keywords: metabolic score for insulin resistance, ischemic cardiomyopathy, type 2 diabetes mellitus, major adverse cardiac events, prognosis

Wusheng Deng,1,&ast; Yun Jiang,2,&ast; Jiaoxia Qin,1,&ast; Gang Chen,3,&ast; Yongjie Lv,1 Yanmei Lei,1 Jing Luo,1 Kangkang Hong,1 Bing Huang,1 Luhai Qin,4 Xiujia Tang,1 Liumei Ye,1 Yuhai Dang,1 Chao Wang,1 Feiyang Long,1 Ke Wang,1 Jinliang Kong1 1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Shaoyang University, Shaoyang, Hunan, People’s Republic of China; 3Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 4Department of Pulmonology, Hechi Traditional Chinese Medicine Hospital, Hechi, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinliang Kong; Ke Wang, Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, People’s Republic of China, Email kjl071@163.com; keewang@hotmail.comBackground: Aspergillus fumigatus is an opportunistic fungal pathogen, which is commonly found in lungs and rarely causes infections in mediastinum. Mediastinal Aspergillus abscess is a serious infectious condition, and is characterized by difficult diagnosis due to its clinical manifestations being nonspecific.Case Presentation: Here, we report a case of a mediastinal Aspergillus fumigatus abscess in an immunocompetent patient. The patient was a 45-year-old woman who presented with a 20-day history of sore throat without any underlying diseases. Chest computed tomography (CT) showed a mass in the anterior superior mediastinum. Metagenomic next-generation sequencing (mNGS) identified Aspergillus fumigatus sequences in endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) tissue, indicating the mediastinal Aspergillus fumigatus infection of this patient. The following mediastinal biopsy histological analysis and tissue fungi culture also suggested Aspergillus fumigatus infection, confirming the mNGS detection. The patient was diagnosed with mediastinal aspergillosis caused by Aspergillus fumigatus. After timely voriconazole treatment, the patient was discharged with good condition.Conclusion: Our study presented a rare case with mediastinal Aspergillus fumigatus abscess in an immunocompetent patient. As a new clinical diagnostic method, mNGS could assist timely diagnosis and precise treatment of Aspergillus infection.Keywords: mediastinal abscess, Aspergillus fumigatus, metagenomic next-generation sequencing, diagnosis, case report

Xinwei Zhou,1,&ast; Ke Lin,2,&ast; Liangmin Fu,1,&ast; Fei Liu,3,&ast; Hansen Lin,1 Yuhang Chen,1 Bowen Zhuang,2 Hui Liang,4 Qiong Deng,4 Zhu Wang,4 Wei Chen,1 Junhang Luo,1,5 Jiazheng Cao,6 Pengju Li1 1Department of Urology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Department of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 4Department of Urology, Affiliated Longhua People’s Hospital, Southern Medical University, Shenzhen, People’s Republic of China; 5Institute of Precision Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 6Department of Urology, Jiangmen Central Hospital, Jiangmen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pengju Li, Department of Urology, The First Affiliated Hospital of Sun Yat-sen University, No. 58, Zhongshan Road II, Guangzhou, 510080, People’s Republic of China, Tel +86-20-87618227, Email lipj25@mail.sysu.edu.cn Jiazheng Cao, Department of Urology, Jiangmen Central Hospital, Haibang Street 23, Jiangmen, 529030, People’s Republic of China, Tel +86-750-3165500, Email spotatos@163.comBackground: Triggering receptors expressed by myeloid cells-1 (TREM1) is a receptor belonging to the immunoglobulin superfamily and plays an important role in pro-inflammation in acute and chronic inflammatory disorders. However, the understanding of the immunomodulatory roles of TREM1 in the tumor microenvironment remains incomplete.Methods: The expression patterns of TREM1 mRNA in tumors and adjacent normal tissues were compared by analyzing data obtained from the Genotype-Tissue Expression and The Cancer Genome Atlas datasets. Survival analysis was performed to determine the prognostic value of TREM1. Functional enrichment analysis was applied to decipher the discrepancy in biological processes between high- and low-TREM1 groups across various cancers. The correlation between TREM1 and immune cell infiltration determined by using multiple algorithms was evaluated with the Pearson method. Four independent immunotherapy cohorts were adopted to validate the role of TREM1 as a biomarker.Results: TREM1 was elevated in most cancers as verified with clinical samples. Overexpression of TREM1 was linked with undesirable prognosis in patients. Further analysis revealed that TREM1 was positively correlated with immune response, pro-tumor pathways, and myeloid cell infiltration, while being negatively correlated with CD8+ T cell (including infiltration level and biological processes). Concordantly, tumors with high TREM1 levels were more resistant to immunotherapy. Through connective map analysis, therapeutically potential compounds like tozasertib and TPCA-1 were identified, which can be used synergistically with immunotherapy to improve the poor prognosis of patients with high TREM1 levels.Conclusion: Through a systematic and comprehensive pan-cancer analysis, we demonstrated that overexpression of TREM1 in tumors correlated closely with unfavorable outcome, infiltration of immune-suppressive cells, and immune regulation, which highlights its potential use as a tumor prognostic biomarker and a novel target for immunotherapy.Keywords: triggering receptors expressed by myeloid cells-1, pan-cancer, prognostic biomarker, tumor microenvironment, clear cell renal cell carcinoma, immunotherapy

Jun Luo,1 Qing Liu,2 Zhujizhaba Gama,3 Deji Gesang,3 Ying Zhu,2 Lining Yang,2 Dingqun Bai,2 Qinghua Zhao,4 Mingzhao Xiao1 1Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Rehabilitation Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Rehabilitation Medicine, Tibet Autonomous Region People’s Hospital, Tibet, People’s Republic of China; 4Department of Nursing, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Mingzhao Xiao, 1st Youyi Road, Chongqing, 400016, People’s Republic of China, Tel +86 13608399433, Email xmz.2004@163.comPurpose: To investigate the current situation of assistive device (AD) usage among seniors in Tibet, China, and explore its influencing factors.Methods: A mixed-methods design was used. Cognition, attitude, behavior, and preference toward ADs were assessed by a self-designed questionnaire. Additionally, participants responded to the open-ended questions. Anderson’s behavior model analyzed the impacts of the prerequisite factors, enabling factors, and demand factors influencing the utilization of ADs by Tibetan seniors.Results: Of the 211 Tibetan seniors, 149 (70.6%) Tibetan seniors expressed the willingness to utilize ADs. Binary Logistic regression analysis showed that one prerequisite factor: age; one enabling factor: care situation, and one demand factor: dysfunctional condition were factors influencing the utilization of ADs. Qualitative comments described: psychological, physical environment, and social support factors were the main influencing factors.Conclusion: This study presents the current situation to utilize ADs by Tibetan seniors on the Qinghai-Tibet Plateau, incorporates Anderson’s behavioral model for quantitative analysis, and combines qualitative research to explore the facilitating and hindering factors, to provide reference and basis for the development of ADs for seniors and policy formulation. The sample size of this study is relatively small and limited to ethnic groups, and we plan to increase the sample size and include more ethnic groups in the future study.Keywords: assistive devices, seniors, Qinghai-Tibet Plateau, mixed-methods research

Zhaohua Xiao,1 Xumei Feng,2 Yongjia Zhou,1 Peiwei Li,3 Junwen Luo,1 Wenhao Zhang,1 Jie Zhou,1 Jiangfeng Zhao,1 Dong Wang,4 Yongjie Wang,5 Zhongxian Tian,1,6 Xiaogang Zhao1,6 1Department of Thoracic Surgery, The Second Hospital of Shandong University, Jinan, 250033, People’s Republic of China; 2Health Management Center, The Second Hospital of Shandong University, Jinan, People’s Republic of China; 3Institute of Medical Sciences, The Second Hospital of Shandong University, Jinan, People’s Republic of China; 4Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, People’s Republic of China; 5Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266000, People’s Republic of China; 6Key Laboratory of Chest Cancer, Shandong University, The Second Hospital of Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Zhongxian Tian; Xiaogang Zhao, Department of Thoracic Surgery, The Second Hospital of Shandong University, Jinan, 250033, People’s Republic of China, Tel +86-17660082365 ; +86-053185875009, Email tianzhongxian@email.sdu.edu.cn; zhaoxiaogang@sdu.edu.cnBackground: Cancer cell-derived exosomal microRNAs (miRNAs) play critical role in orchestrating intercellular communication between tumor cells and tumor microenvironmental factors, including lymphatic endothelial cells (LECs). Nevertheless, the functions and underlying mechanisms of exosomal miRNAs in lymphatic metastasis and lymphangiogenesis in esophageal squamous cell carcinoma (ESCC) remain unclear.Methods: Small RNA sequencing, Gene Expression Omnibus (GEO) analysis and qRT‒PCR were performed to identify the candidate exosomal miRNAs involved in ESCC metastasis. Receiver operating characteristic curve analysis was conducted to evaluate the diagnostic potential of exosomal miR-10527-5p in predicting lymph node metastasis (LNM) status. An in vitro coculture system was used to investigate the effects of exosomal miR-10527-5p on ESCC cells and human LECs (HLECs), followed by a popliteal LNM assay in vivo. The relationship between miR-10527-5p and Rab10 was identified by dual-luciferase reporter, fluorescence in situ hybridization and qRT‒PCR assays. Then, a series of rescue assays were performed to further investigate whether Rab10 is involved in exosomal miR-10527-5p mediated ESCC metastasis.Results: MiR-10527-5p was found to be notably reduced in both the plasma exosomes and tumor tissues of ESCC patients with LNM, and plasma exosomal miR-10527-5p had a high sensitivity and specificity for discrimination of LNM status. Moreover, exosome-shuttled miR-10527-5p suppressed the migration, invasion and epithelial-to-mesenchymal transition (EMT) of ESCC cells as well as the migration and tube formation of HLECs via Wnt/β-catenin signaling in vitro and in vivo. Further investigation revealed that Rab10 was a direct target of miR-10527-5p, and re-expression of Rab10 neutralized the inhibitory effects of exosomal miR-10527-5p.Conclusion: Our study demonstrated that exosomal miR-10527-5p had a strong capability to predict preoperative LNM status and anti-lymphangiogenic effect. Exosomal miR-10527-5p inhibited lymphangiogenesis and lymphatic metastasis of ESCC in a vascular endothelial growth factor-C (VEGF-C)-independent manner, showing potential as a therapeutic target for ESCC patients.Keywords: esophageal squamous cell carcinoma, exosomes, miR-10527-5p, biomarker, lymphangiogenesis

Rui Song,1,2,&ast; Hanghang Ni,1,&ast; Juntao Huang,1,&ast; Chenglei Yang,1 Shangdong Qin,1,3 Huaning Wei,1 Jiefu Luo,1 Yuxiang Huang,1 Bangde Xiang1– 3 1Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 2Key Laboratory of Early Prevention and Treatment for Regional High-Frequency Tumors, Ministry of Education, Nanning, People’s Republic of China; 3Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bangde Xiang, Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, 71 Hedi Road, Qingxiu District, Nanning, Guangxi, 530021, People’s Republic of China, Tel +86-7715301253, Email xiangbangde@gxmu.edu.cnPurpose: The study aimed to investigate the ability of inflammation-immunity-nutrition score (IINS) and inflammatory burden index (IBI), individually or in combination, to predict prognosis of hepatocellular carcinoma (HCC) patients after hepatectomy.Methods: A total of 701 patients who underwent HCC resection at Guangxi Medical University Cancer Hospital were enrolled in the study. An IINS ranging from 0 to 3 was defined based on preoperative C-reactive protein (CRP), lymphocyte count, and serum albumin level, while an IBI was based on CRP and neutrophil-to-lymphocyte ratio. The prognostic value of IINS and IBI was assessed using univariate and multivariate Cox regression and Kaplan–Meier survival curves. The concordance index and calibration curve were used for internal validation of models. Decision curve analysis, net reclassification index and integrated discrimination improvement were used to compare the predictive performance of the models with traditional staging systems.Results: IINS and IBI were able to predict poor prognosis in HCC patients after hepatectomy, and a nomogram based on the IINS predicted survival at 1, 3, and 5 years better than other models or traditional staging systems.Conclusion: IINS may be accurate predictors of survival in HCC patients after hepatectomy, with potentially greater prognostic value than conventional markers.Keywords: hepatocellular carcinoma, inflammation-immunity-nutrition score, inflammatory burden index, prognosis, hepatectomy

Jingya Li,1,2,&ast; Junqun Fang,3,&ast; Jiayou Luo,1 Yamei Duan,1 Xiang Xiao,1 Yamei Li,4 Miyang Luo5 1Department of Women and Children Health, Xiangya School of Public Health, Central South University, Changsha, People’s Republic of China; 2Department of Social Medicine and Health Management, Xiangya School of Public Health, Central South University, Changsha, People’s Republic of China; 3Department of Child Health Care, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, People’s Republic of China; 4Department of Women Health Care, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, People’s Republic of China; 5Department of Epidemiology and Biostatistics, Xiangya School of Public Health, Central South University, Changsha, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Miyang Luo, Department of Epidemiology and Biostatistics, Xiangya School of Public Health, Central South University, No. 238 Shang Ma Yuan Ling Road, Changsha, 410078, People’s Republic of China, Tel +86 731-84805465, Email miyangluo@csu.edu.cnPurpose: Anemia is a worldwide common condition during pregnancy, conferring a number of health risks to mothers. However, very little is known about the association between severity of anemia and severe maternal outcomes. This study aimed to assess the association between severity of anemia during pregnancy and the risk of severe maternal outcomes.Patients and Methods: This retrospective cohort study was based on data from China’s National Maternal Near Miss Surveillance System for the period 2017– 2018, which included 18 hospitals in southern China. Pregnant women admitted for delivery were divided into 4 groups based on severity of anemia during pregnancy: no anemia, mild anemia, moderate anemia, and severe anemia groups. Severe maternal outcomes were a composite of life-threatening conditions (ie, organ dysfunction) as defined by the WHO criteria, occurring at any time after admission until discharge or death. Modified Poisson regression analyses and propensity score-weighted regression analyses were used to estimate the relative risks (RRs) and 95% confidence intervals (CIs) of severe maternal outcomes among women with anemia of varying severity during pregnancy.Results: The incidence of severe maternal outcomes was 0.3% (417/138,556) in total, and the rates were 0.1% (85/99,755), 0.2% (30/18,502), 1.2% (234/19,697) and 11.3% (68/602) in no anemia, mild anemia, moderate anemia and severe anemia group, respectively. Compared with no anemia, the adjusted RR for severe maternal outcomes was 4.19 (95% CI, 3.20– 5.50) in moderate anemia group and 22.12 (95% CI, 15.43– 31.69) in severe anemia group; the weighted RR was 1.01 (95% CI, 1.01– 1.01) in moderate anemia group and 1.11 (95% CI, 1.07– 1.14) in severe anemia group.Conclusion: Moderate to severe anemia during pregnancy was independently associated with an increased risk of severe maternal outcomes. Maternal health care providers and pregnant women themselves should give more attention to the prevention and treatment of anemia during pregnancy, especially moderate to severe anemia.Keywords: anemia, severity, severe maternal outcome, retrospective cohort, propensity score weighting

Yujie Huang,1 You Zhai,1 Meijia Wu,1 Chengdong Chang,2 Jindan Luo,3 Dongsheng Hong,1 Qingwei Zhao,1 Yao Dai,4 Jian Liu1 1Research Center for Clinical Pharmacy, Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4Department of Radiation Oncology, College of Medicine, University of Florida, Gainesville, FL, USACorrespondence: Jian Liu, Research Center for Clinical Pharmacy, Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China, Tel +86-571-87236560, Fax +86-571-87236531, Email lindaliu87@zju.edu.cn Yao Dai, Department of Radiation Oncology, College of Medicine, University of Florida, Gainesville, FL, USA, Tel +1-352-273-8237, Fax +1-352-273-8252, Email yaodai1111@hotmail.comPurpose: Mammalian Target of rapamycin (mTOR) plays a central role in regulating cell growth, proliferation, and cell cycle. The key component of mTORC2 is highly expressed in docetaxel-resistant prostate cells. However, the underlying molecular effects on prostate cells remain unclear.Methods: A docetaxel-resistant human prostate cell line (PC-3/DTX) was constructed to investigate the role of mTORC2 in docetaxel resistance. The lentivirus was transfected into cells to knock down the expression of Rictor, and cell viability was measured by Cell Counting Kit 8 (CCK-8). Flow cytometry was used to analyze the cell cycle, and the changes in related signal cascades were assessed by immunohistochemistry (IHC) staining and Western blot.Results: Docetaxel showed the lowest IC50 (50% inhibitory concentration) in PC-3/DTX cells with sh-RNA. Decreased Rictor expression resulted in a larger proportion of arrested cells in the G0/G1 phase in PC-3/DTX cells. The IC50 values of the AZD8055 group were lower than in the Rapamycin group when treated with docetaxel again. Furthermore, a larger proportion of PC-3/DTX cells were arrested in the G0/G1 phase in the AZD8055 group compared to the Rapamycin group. The IHC results of the prostate cancer tissues from a CRPC patient revealed the over expression of Rictor only, while Raptor expression was unaffected.Conclusion: We investigated the role of mTORC2 signaling on the acquired docetaxel -resistant PC-3 cells to identify potential methods for clinical treatment. MTORC2 expression is essential for docetaxel drug resistance of PC-3 cells. The mTORC1/2 inhibitor AZD8055 caused more significant disruption of mTORC2 kinase activity than the mTORC1 inhibitor Rapamycin, which lead to decreased docetaxel-mediated resistance. Therefore, reversing docetaxel resistance, may become a therapeutic option in the treatment of mCRPC patients.Keywords: prostate cancer cell, docetaxel, drug resistance, mTORC2, reverse

Jinyan Lin,&ast; Yu Zhang,&ast; Chongxi Bao, Huasong Lu, Yun Zhong, Chuanfeng Huang, Qiuping Huang, Dezhen Wang, Jing Luo, Ke Wang, Jinliang Kong Pulmonary and Critical Care Medicine Ward, Guangxi Medical University First Affiliated Hospital, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinliang Kong; Ke Wang, Pulmonary and Critical Care Medicine Ward, Guangxi Medical University First Affiliated Hospital, No. 6 Shuangyong Road, Nanning, 530021, People’s Republic of China, Email kjl071@126.com; 497256113@qq.comBackground: Streptococcus constellatus, a commensal, plays an important role in purulent infections. It has been reported as aggressive pathogen causing pleural empyema. But the role of S. constellatus in empyema has not been taken seriously. There are no studies about clinical characteristics of empyema caused by S. constellatus domestically and abroad. This study aimed to explore the clinical features and management of empyema caused by S. constellatus.Methods: A retrospective review of 9 patients diagnosed with empyema caused by S. constellatus in a hospital between January 2010 and August 2021 was performed.Results: S. constellatus empyema were mostly seen in old males (66.7%) with comorbid diseases. The high-risk factors include diabetes mellitus, oral infection, and oral surgery. All were unilateral encapsulated empyema (right-side, 55.6%), diagnosed with pneumonia (bilateral pneumonia, 88.9%; ipsilateral lung abscess, 44.4%). 33.3% of patients had S. constellatus and anaerobes co-isolated. S. constellatus were sensitive to penicillin G, linezolid, levofloxacin, vancomycin, ceftriaxone, and chloramphenicol, resistant to erythromycin, tetracycline, and clindamycin. 33.3% of the patients needed ventilator support. The primary treatment to S. constellatus empyema was timely pus drainage, intravenous antibiotics, and enough nutrition support, intrapleural fibrinolytics and surgery (VAST recommended first) in necessity.Conclusion: S. constellatus may cause pneumonia and lung abscess first and then spread to cause empyema mainly in old males with comorbid diseases. S. constellatus often co-isolated with anaerobes in empyema. Antibiotics should cover simultaneously both S. constellatus and anaerobes.Keywords: S. constellatus, empyema, clinical features, anaerobes

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