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Dong Wu,1,&ast; Bingyu Long,1,&ast; Bangxiao Huang,1,&ast; Xiaomei Zhong,1 Xiaoer Chen,1 Xiaoping Shen,1 Qiu Huang,1 Wenchao Zhang,1 Jiayuan Wu,2 Min Chen,1 Dongming Li,1 Bin Wu,1 Dong Lv,3 Dan Huang,1 Xuanna Zhao1 1Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, People’s Republic of China; 2Department of Clinical Research, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, People’s Republic of China; 3Department of Psychiatry, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuanna Zhao; Dan Huang, Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, No. 57, South of Renmin Road, Zhanjiang, Guangdong, 524013, People’s Republic of China, Email 792665234@qq.com; 287538250@qq.comBackground: Education and living environment are related to mental health. But the independent and combined effects of them on mental health among patients with chronic obstructive pulmonary disease (COPD) are uncertain.Methods: The independent and combined effects of education and living environment on mental health were assessed by binary logistic regression in 1064 COPD patients. Additive interaction was assessed with the relative excess risk ratio (RERI), attribution percentage (AP), and synergy index (SI).Results: Our results shown that low education level and urban living environment were independently associated with higher risks for anxiety (odds ratio [OR]: 1.56, 95% confidence interval [CI] 1.06– 2.29 and OR:2.15, 95% CI 1.51– 2.05) or depression (OR:1.62, 95% CI 1.17– 2.27 and OR: 2.01, 95% CI 1.46– 2.75) among COPD patients. The combination effect of them was also associated with higher risks for anxiety (OR: 7.90, 95% CI 3.83– 16.29, P < 0.001) or depression (OR: 11.79, 95% CI 5.77– 24.10, P < 0.001) among these patients. Furthermore, we observed strong synergistic additive interactions between them for anxiety (SI: 11.57, 95% CI 1.41– 95.27; RERI: 6.31, 95% CI 1.60– 11.01; AP: 0.8, 95% CI 0.66– 0.94) and depression (SI: 31.31, 95% CI 1.59– 617.04; RERI: 10.44, 95% CI 2.66– 18.23; AP: 0.89, 95% CI 0.8– 0.97).Conclusion: Low education levels and living in urban areas had an independent and synergistic effects on mental health among COPD patients.Keywords: anxiety, China, COPD, depression, education, living environment

Jiajin Feng,1,&ast; Keming Chen,1,&ast; Haifu Tian,1 Al-qaisi Mohammed Abdulkarem,1 Yunshang Tuo,1 Xuehao Wang,1 Bincheng Huang,1 Yu Gao,1 Zhiyong Lv,1 Rui He,2 Guangyong Li1 1General Hospital of Ningxia Medical University, Yinchuan, 750004, People’s Republic of China; 2Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, 750004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guangyong Li, Email guangyongli1979@hotmail.comObjective: To explore the effectiveness of prostate biopsy density in predicting prostate cancer under cognitive and systematic biopsy mode in multi-parametric magnetic resonance imaging (mpMRI).Methods: A retrospective analysis was conducted on clinical data of 204 patients who were suspected of having prostate cancer with prostate-specific antigen (PSA) levels less than 50 ng mL− 1 and underwent cognitive and systematic biopsy through the perineal approach in our hospital from 2022 to 2023. Univariate and multivariate logistic regression analyses were used to evaluate the odds ratios of prostate biopsy density and relevant clinical indicators. Logistic regression analysis was performed to establish a predictive model combining indicators with predictive value. The predictive value of each indicator and the new model was evaluated using receiver operating characteristic (ROC) curves and the area under the curve (AUC).Results: The detection rate of prostate cancer in the study population was 32.35%. Multivariate analysis showed that age, PSAD, PI-RADS 2.1 score, and prostate biopsy density were independent predictors of prostate cancer. The ROC curve analysis revealed an AUC of 0.707 (95% CI 0.625– 0.790) for biopsy density, with a cutoff value of approximately 0.22 needle mL− 1. The best predictive model consisted of age, PSAD, PI-RADS 2.1 score, and biopsy density, with an AUC of 0.857.Conclusion: Biopsy density is associated with the detection of prostate cancer, with a critical value of 0.22 needle mL− 1. Combining biopsy density with other clinical indicators can significantly improve the ability to predict prostate cancer and avoid unnecessary prostate biopsy cores.Keywords: prostate biopsy, multi-parametric magnetic resonance imaging, biopsy density, cognitive fusion, cancer prediction

Lei Tan,1,2,&ast; Han She,1,2,&ast; Yi Wang,1,2,&ast; Yuanlin Du,1 Jun Zhang,1 Yunxia Du,1 Yinyu Wu,1 Wei Chen,1 Bingqiang Huang,1 Duanyang Long,1 Xiaoyong Peng,2 Qinghui Li,2 Qingxiang Mao,1 Tao Li,2 Yi Hu1 1Department of Anesthesiology, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China; 2State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao Li; Yi Hu, Email lt200132@163.com; huyi921@sina.comBackground: Hemorrhagic shock was a leading cause of death worldwide, with myocardial injury being a primary affected organ. As commonly used solutions in fluid resuscitation, acetated Ringer’s (AR) and Lactate Ringer’s solution (LR) were far from perfect for their adverse reactions such as lactic acidosis and electrolyte imbalances. In previous studies, TPP@PAMAM-MR (TPP-MR), a novel nanocrystal resuscitation fluid has been found to protect against myocardial injury in septic rats. However, its role in myocardial injury in rats with hemorrhagic shock and underlying mechanism is unclear.Methods: The hemorrhagic shock rats and hypoxia-treated cardiomyocytes (H9C2) were utilized to investigate the impact of TPP-MR on cardiac function, mitochondrial function, and lipid peroxidation. The expressions of ferritin-related proteins glutathione peroxidase 4 (GPX4), Acyl CoA Synthase Long Chain Family Member 4 (ACSL4), and Cyclooxygenase-2(COX2) were analyzed through Western blotting to explore the mechanism of TPP-MR on hemorrhagic myocardial injury.Results: TPP-MR, a novel nanocrystalline resuscitation fluid, was synthesized using TPP@PAMAM@MA as a substitute for L-malic acid. We found that TPP-MR resuscitation significantly reduced myocardial injury reflected by enhancing cardiac output, elevating mean arterial pressure (MAP), and improving perfusion. Moreover, TPP-MR substantially prolonged hemorrhagic shock rats’ survival time and survival rate. Further investigations indicated that TPP-MR improved the mitochondrial function of myocardial cells, mitigated the production of oxidative stress agents (ROS) and increased the glutathione (GSH) content. Additionally, TPP-MR inhibited the expression of the ferroptosis-associated GPX4 protein, ACSL4 and COX2, thereby enhancing the antioxidant capacity.Conclusion: The results showed that TPP-MR had a protective effect on myocardial injury in rats with hemorrhagic shock, and its mechanism might be related to improving the mitochondrial function of myocardial cells and inhibiting the process of ferroptosis.Keywords: myocardial injury, hemorrhagic shock, mitochondria, ferroptosis

Zheng Zhang,1,2,&ast; Binbin Shao,3,&ast; Hongzhou Liu,2,4 Ben Huang,2,5 Xuechen Gao,1 Jun Qiu,1 Chen Wang1,2 1Center of Clinical Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, People’s Republic of China; 2Center for Gene Diagnosis, Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, People’s Republic of China; 3Department of Prenatal Diagnosis, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Healthcare Hospital, Nanjing, Jiangsu Province, People’s Republic of China; 4School of Clinical Medicine, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuang Province, People’s Republic of China; 5Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chen Wang; Jun Qiu, Center of Clinical Laboratory, The First Affiliated Hospital of Soochow University, No. 899 Pinghai Road, Suzhou, Jiangsu Province, 215006, People’s Republic of China, Email 1617657224@qq.com; 13606136542@126.comPurpose: Early recognition of coronary artery disease (CAD) could delay its progress and significantly reduce mortality. Sensitive, specific, cost-efficient and non-invasive indicators for assessing individual CAD risk in community population screening are urgently needed.Patients and Methods: 3112 patients with CAD and 3182 controls were recruited from three clinical centers in China, and differences in baseline and clinical characteristics were compared. For the discovery cohort, the least absolute shrinkage and selection operator (LASSO) regression was used to identify significant features and four machine learning algorithms (logistic regression, support vector machine (SVM), random forest (RF) and extreme gradient boosting (XGBoost)) were applied to construct models for CAD risk assessment, the receiver operating characteristics (ROC) curve and precision-recall (PR) curve were conducted to evaluate their predictive accuracy. The optimal model was interpreted by Shapley additive explanations (SHAP) analysis and assessed by the ROC curve, calibration curve, and decision curve analysis (DCA) and validated by two external cohorts.Results: Using LASSO filtration, all included variables were considered to be statistically significant. Four machine learning models were constructed based on these features and the results of ROC and PR curve implied that the XGBoost model exhibited the highest predictive performance, which yielded a high area of ROC curve (AUC) of 0.988 (95% CI: 0.986– 0.991) to distinguish CAD patients from controls with a sensitivity of 94.6% and a specificity of 94.6%. The calibration curve showed that the predicted results were in good agreement with actual observations, and DCA exhibited a better net benefit across a wide range of threshold probabilities. External validation of the model also exhibited favorable discriminatory performance, with an AUC, sensitivity, and specificity of 0.953 (95% CI: 0.945– 0.960), 89.9%, and 87.1% in the validation cohort, and 0.935 (95% CI: 0.915– 0.955), 82.0%, and 90.3% in the replication cohort.Conclusion: Our model is highly informative for clinical practice and will be conducive to primary prevention and tailoring the precise management for CAD patients. Keywords: coronary artery disease, predictive model, machine learning, XGBoost, primary prevention

Bo Huang,&ast; Xin Li,&ast; Xinxin Zhang, Shiwei Li, Yue Liu, Mengjuan Zhang, Jingqiu Cui Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingqiu Cui, Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, 300052, People’s Republic of China, Tel +86 13920765604, Email cuijingqiu@tmu.edu.cnPurpose: People with hyperuricemia (HUA) are often related to metabolic disorders such as diabetes, metabolic syndrome (MetS), and obesity. However, the correlation between excretion of uric acid and these diseases is unclear. Our study aimed to explore the relationship between uric acid excretion and type 2 diabetes (T2D).Methods: A total of 228 HUA patients from Tianjin Medical University General Hospital from 2022 to 2023 were included in this study. We collected demographic, biochemical, and anthropometric data on each subject. Urine uric acid excretion (UUAE) was calculated enzymatically from a single urine collection that lasted 24 hours. And fractional excretion of uric acid (FEUA) was calculated from serum uric acid and creatinine and uric acid and creatinine. Binary logistic regression modeling assessed the association between uric acid excretion and T2D.Results: Of the 228 subjects, 13.4% had T2D and 48.7% had obesity. The obesity group had a lower FEUA (p< 0.05) and a higher UUAE compared to the control group (p< 0.05). And FEUA had a stronger correlation with the risk of T2D (p< 0.001). Also, there was a negative association between BMI and FEUA and a positive link between BMI and UUAE in the outpatients.Conclusion: Increased FEUA levels were significantly associated with T2D in HUA patients. Therefore, routine calculating of FEUA is essential for proper diagnosis and appropriate treatment T2D of in HUA patients. Keywords: urine uric acid excretion, hyperuricemia, obesity, Type 2 diabetes, fractional excretion of urate

Baogen Zhang,1,&ast; Biqing Huang,2,&ast; Fan Yang,3,&ast; Jiandong Yang,1 Man Kong,1 Jing Wang,1 Yaoxian Xiang,1 Kangjie Wang,1 Ruchen Peng,4 Kun Yang,4 Chao An,5 Dong Yan1 1Department of Oncology, Beijing Luhe Hospital Affiliated to Capital Medical University, Beijing, 101149, People’s Republic of China; 2Department of Interventional Radiology and Vascular Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, People’s Republic of China; 3Department of Cardiology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, People’s Republic of China; 4Department of Medical Imaging, Beijing Luhe Hospital Affiliated to Capital Medical University, Beijing, 101149, People’s Republic of China; 5Department of Minimal Invasive Intervention, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative, Innovation Center for Cancer Medicine, Guangzhou, 510060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dong Yan, Department of Oncology, Beijing Luhe Hospital Affiliated to Capital Medical University, Beijing, 101149, People’s Republic of China, Tel/Fax +86-10-69543901, Email dongyan@mail.ccmu.edu.cn Chao An, Department of Minimal invasive intervention, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative, Innovation Center for Cancer Medicine, Guangzhou, 510060, People’s Republic of China, Tel/Fax +86-20-87343272, Email anchao-1983@163.comObjective: To compare the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) with transarterial chemoembolization (TACE) for the treatment of high-risk hepatocellular carcinoma (hHCC) patients.Methods: Between January 2014 and August 2022, a total of 1765 consecutive patients with hHCC who underwent initial intra-arterial therapies were reviewed and divided into a TACE group (n, 507) and a HAIC group (n, 426). The study used propensity score matching (PSM) to reduce selectivity bias. Overall survival (OS) and progression-free survival (PFS) were compared using Kaplan‒Meier curves with the Log rank test. The objective response rate (ORR), conversion surgery rate (CSR) adverse event (AE) comparison and subgroup analysis were performed between the two groups.Results: After PSM 1:1, 444 patients were divided into two groups. The patients with hHCC who received HAIC had higher median PFS (6.1 vs 3.3 months, P < 0.001) and OS (10.3 vs 8.2 months, P=0.303) than TACE. Higher ORR (24.8% vs 11.7%) and CSR (15.5% vs 8.9%) were found in the HAIC group than in the TACE group (both P < 0.05). The incidence of grade 3/4 AE was 23.9% and 8.1% in the TACE and HAIC groups, respectively. The subgroup analysis suggest that HAIC appeared to particularly benefit patients with tumor diameter of more than 10 centimeters (hazard ratio [HR], 0.6; 95% CI, 0.47– 0.77; p, 0.00) and PVTT Vp4 (HR, 0.56; 95% CI, 0.39– 0.8; P, 0.01) for PFS outperforming TACE.Conclusion: HAIC can provide better disease control for hHCC than cTACE, with a comparable long-term OS and safety.Keywords: hepatocellular carcinoma, transarterial chemoembolization, hepatic artery infusion chemotherapy, high risk

Qian-Qian Liao,1,&ast; Yan-Ju Mo,2,&ast; Ke-Wei Zhu,3,4,&ast; Feng Gao,2 Bin Huang,2 Peng Chen,4 Feng-Tian Jing,5 Xuan Jiang,6 Hong-Zhen Xu,1 Yan-Feng Tang,7 Li-Wei Chu,8 Hai-Ling Huang,1 Wen-Li Wang,8 Fang-Ning Wei,9 Dan-Dan Huang,9 Bin-Jing Zhao,9 Jia Chen,9 Hao Zhang1 1Department of Pharmacy, People’s Hospital of Guilin, Guilin, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, People’s Hospital of Guilin, Guilin, People’s Republic of China; 3GuangZhou BaiYunShan Pharmaceutical Holdings CO.,LTD. BaiYunShan Pharmaceutical General Factory, Guangzhou, People’s Republic of China; 4Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 5Department of Respiratory Medicine, Xing An County People’ Hospital, Guilin, People’s Republic of China; 6Department of Hospital Infection Management, People’s Hospital of Guilin, Guilin, People’s Republic of China; 7Department of Geriatrics, People’s Hospital of Guilin, Guilin, People’s Republic of China; 8Department of Laboratory Medicine, People’s Hospital of Guilin, Guilin, People’s Republic of China; 9School of Clinical Pharmacy, Guilin Medical University, Guilin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ke-Wei Zhu, GuangZhou BaiYunShan Pharmaceutical Holdings CO.,LTD. BaiYunShan Pharmaceutical General Factory, No. 88 Yunxiang Road Tonghe Street, Baiyun District, Guangzhou, Guangdong Province, 510515, People’s Republic of China, Tel +86-020-87062636, Fax +86-020-87095309, Email zhukew2018@outlook.comPurpose: The study comprehensively evaluated the prognostic roles of the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), basophil-to-lymphocyte ratio (BLR), and eosinophil-to-lymphocyte ratio (ELR) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).Patients and Methods: Six hundred and nineteen patients with AECOPD and 300 healthy volunteers were retrospectively included into the study. The clinical characteristics of the patients with AECOPD and the complete blood counts (CBCs) of the healthy volunteers were collected. The associations of PLR, NLR, MLR, BLR, and ELR with airflow limitation, hospital length of stay (LOS), C-reactive protein (CRP), and in-hospital mortality in patients with AECOPD were analyzed.Results: Compared with the healthy volunteers, PLR, NLR, MLR, BLR, and ELR were all elevated in COPD patients under stable condition. PLR, NLR, MLR, and BLR were further elevated while ELR was lowered during exacerbation. In the patients with AECOPD, PLR, NLR, and MLR were positively correlated with hospital LOS as well as CRP. In contrast, ELR was negatively correlated with hospital LOS as well as CRP. Elevated PLR, NLR, and MLR were all associated with more severe airflow limitation in AECOPD. Elevated PLR, NLR, and MLR were all associated with increased in-hospital mortality while elevated ELR was associated with decreased in-hospital mortality. Binary logistic regression analysis showed that smoking history, FEV1% predicted, pneumonia, pulmonary heart disease (PHD), uric acid (UA), albumin, and MLR were significant independent predictors ofin-hospital mortality. These predictors along with ELR were used to construct a nomogram for predicting in-hospital mortality in AECOPD. The nomogram had a C-index of 0.850 (95% CI: 0.799– 0.901), and the calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) further demonstrated its good predictive value and clinical applicability.Conclusion: In summary, PLR, NLR, MLR, and ELR served as useful biomarkers in patients with AECOPD.Keywords: healthy volunteers, in-hospital mortality, length of stay, nomogram, pneumonia, pulmonary heart disease

Xin Li,&ast; Bo Huang,&ast; Yue Liu, Meng Wang, Yi-Xuan Wang, Kai-Lei Feng, Jing-Qiu Cui Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing-Qiu Cui, Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, An Shan Dao 154, Tianjin, 300052, People’s Republic of China, Tel +86-13920765604, Email cuijingqiu@tmu.edu.cnBackground: Hyperuricemia (HUA) is often associated with metabolic syndrome (MetS). However, the role of different metabolic markers in the screening of MetS in out-patients with hyperuricemia is unclear. The study aims to investigate the relationship between different metabolic indexes and MetS.Methods: A total of 399 hyperuricemia patients from Tianjin Medical University General Hospital from 2022 to 2023 were included in this study. We collected demographic, anthropometric, and biochemical data on each subject. And calculate serum uric acid-to-creatinine ratio (SUA/Cr), serum uric acid to high-density lipoprotein cholesterol (UHR), triglyceride to high-density lipoprotein cholesterol (THR), and triglyceride and glucose (TyG) index. Binary logistic regression modeling was performed to explore the association between different metabolic markers and MetS.Results: Out of the 399 subjects, 28.3% had MetS. UHR, THR, and TyG index were significantly higher in the MetS group than those in the control group (p< 0.05), which were associated with an increased risk of MetS. However, SUA/Cr was not associated with MetS (p> 0.05). TyG index had a stronger relationship with the risk of MetS (OR 5.476, 95% CI 2.210– 13.569, p< 0.001). The cut-off with the biggest Youden index of the TyG index was 9.13 and the area under the curve (AUC) was 0.719.Conclusion: A high TyG index is associated with an increased risk of MetS in HUA patients. These findings might help screen MetS in individuals with HUA and could be more standardized management of patients with high uric acid in outpatient clinics.Keywords: metabolic syndrome, serum uric acid-to-creatinine ratio, serum uric acid to high-density lipoprotein cholesterol, triglyceride to high-density lipoprotein cholesterol, TyG index

Qiangjian Mao,1,&ast; Biao Huang,1,&ast; Daocheng Zhu,1 Yuqing Wang,2 Shiqi Xu,2 Desheng Wu,1 Guomin Huang,1 Ziru Li,1 Zhenhai Chi,1 Rixin Chen1 1The Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, People’s Republic of China; 2Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhenhai Chi; Rixin Chen, The Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, People’s Republic of China, Email 348916661@qq.com; chenrixin321@163.comBackground: Acupuncture therapy has been widely used in the treatment of musculoskeletal pain (MP) in many countries around the world. However, there are no bibliometric studies on acupuncture therapy for MP. Therefore, the aim of this study was to analyze the current status, frontiers and hot spots in the use of acupuncture therapy for the treatment of MP.Methods: Literature on acupuncture therapy for MP was extracted from the Web of Science Core Collection database from 2003 to 2022. CiteSpace 6.2.R4 (64-bit) software was used to analyze the number and centrality of journals, countries, institutions, authors, references and keywords, and the functions of co-occurrence and clustering were applied to draw a visual knowledge map.Results: Over the past 20 years, the annual journal publications have been on a steady upward trend, with 438 articles published in 143 journals, including Acupuncture in Medicine Journal published the most (28, 6.39%), JAMA-Journal of the American Medical Association was the journal with the highest impact factor (IF = 120.7003), USA dominated with the most publications (140, 31.96%) among 44 countries, and among 196 research organizations Kyung Hee University was the most prolific (19, 4.34%) and Ha, In-Hyuk was the most published author (9, 2.05%). “Acupuncture” is the most popular and highly sought after keywords. “Low back pain” is the keyword with the highest centrality.Conclusion: This article provides the current situation of the use of acupuncture therapy in the treatment of MP in the past 20 years, and statistical analysis reveals that “low back pain”, “knit osteoporosis” and “break cancer” are new research diseases related to acupuncture therapy for MP, and “myobasic trigger point” is a new research direction of acupuncture therapy for MP. Therefore, this study helps researchers grasp the research hotspots and provide certain references for in-depth research and future topic selection.Keywords: musculoskeletal pain, acupuncture therapy, bibliometrics, CiteSpace

Yuyi Chen,1 Xuemei Zhao,1 Lin Liang,1 Pengchao Tian,1 Jiayu Feng,1 Liyan Huang,1 Boping Huang,1 Yihang Wu,1 Jing Wang,1 Jingyuan Guan,1 Xinqing Li,1 Jian Zhang,1,2 Yuhui Zhang1 1Heart Failure Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2Key Laboratory of Clinical Research for Cardiovascular Medications, National Health Committee, Beijing, People’s Republic of ChinaCorrespondence: Yuhui Zhang, Heart Failure Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China, Tel +8615901314243, Email yuhuizhangjoy@163.com Jian Zhang, Heart Failure Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China, Tel +8613911102015, Email fwzhangjian62@126.comObjective: To identify biomarkers with independent prognostic value and investigate the prognostic value of multiple biomarkers in combination in patients hospitalized with heart failure.Methods: A total of 884 consecutive patients hospitalized with heart failure from 2015 to 2017 were enrolled. Twelve biomarkers were measured on admission, and the relationships between biomarkers and outcomes were assessed.Results: During the median follow-up of 913 days, 291 patients (32.9%) suffered from primary endpoint events. Soluble suppression of tumorigenicity-2 (sST2) (per log [unit] increase, adjusted HR [95% CI]: 1.39 [1.13,1.72], P = 0.002) and big endothelin-1 (big ET-1) (per log [unit] increase, adjusted HR [95% CI]: 1.56 [1.23,1.97], P < 0.001) remained independent predictors of primary endpoint event after adjusting for other predictors including N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT). Both sST2 (C-statistic: 0.810 vs 0.801, P = 0.005, and 0.832 vs 0.826, P = 0.024, respectively) and big ET-1 (C-statistic: 0.829 vs 0.801, P = 0.001, and 0.843 vs 0.826, P < 0.001, respectively) significantly improved the predictive value for primary endpoint event at 1 year and 3 years. However, only big ET-1 (C-statistic: 0.852 vs 0.846, P = 0.014) significantly improved the predictive value at 3 months when added to clinical predictors and known biomarkers. According to the number of elevated biomarkers (including NT-proBNP, hs-cTnT, sST2, and big ET-1), patients with three or more elevated biomarkers had a higher risk of primary endpoint event compared to those with two elevated biomarkers (P = 0.001), as well as in patients with two elevated biomarkers compared to those with one elevated biomarker (P = 0.004). However, the risk of primary endpoint event was comparable between patients with one elevated biomarker and those with no elevated biomarker (P = 0.582).Conclusion: Multiple biomarkers in combination could provide a better prognostic value than a single biomarker. sST2 and big ET-1 could act as alternatives of multi-biomarkers strategies for prognosis evaluation beyond NT-proBNP and hs-cTnT in patients hospitalized with heart failure.Keywords: heart failure, prognostic value, multiple biomarkers, sST2, big ET-1

Jianfeng Hong,1 Xindong Chen,2 Lingli Chen,2 Yigang Wang,2 Biao Huang,2 Hongming Fang1 1Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou, People’s Republic of China; 2Immunological Analysis Laboratory of Academy of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, People’s Republic of ChinaCorrespondence: Hongming Fang, Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou, 310016, People’s Republic of China, Tel + 86 0571-83865858, Email 3295988078@qq.com Biao Huang, Immunological Analysis Laboratory of Academy of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, 310016, People’s Republic of China, Tel +86 0571-86843187, Email jswxhb@163.comPurpose: The present study aimed to evaluate the clinical value of Combined Detection of serum soluble T-cell immunoglobulin 3 (sTim-3) with carcinoembryonic antigen (CEA) or glycotype antigen 19– 9 (CA19-9) for Postoperative Recurrence of Colorectal Cancer (CRC) Diagnosis.Patients and Methods: The serum sTim-3 was measured by highly sensitivity TRFIA, and serum CEA and CA19-9 were obtained through the collection of clinical data. Quantitative detection of serum sTim-3, CEA, CA19-9 in 90 patients after the CRC surgery (52 postoperative recurrence and 38 no-postoperative recurrence), 21 patients with colorectal benign tumors, and 67 healthy controls. To analyze the clinical diagnostic value of combined detection of sTim-3 with CEA or CA19-9 to test whether patients have recurrence after CRC surgery.Results: The sTim-3 (15.94± 11.24ng/mL) in patients after CRC surgery was significantly higher than in healthy controls (8.95± 3.34ng/mL) and colorectal benign tumors (8.39± 2.28ng/mL) (P < 0.05), and sTim-3 (20.33± 13.04ng/mL) in CRC postoperative recurrent group was significantly higher than in the group without recurrence after CRC surgery (9.94± 2.36ng/mL) (P < 0.05). In terms of detecting postoperative recurrence after CRC surgery, combined detection of sTim-3 and CEA (AUC: 0.819, sensitivity: 80.77%, specificity: 65.79%), sTim-3 and CA19-9 test (AUC: 0.813, sensitivity: 69.23%, specificity: 97.30%) was significantly better than the CEA single test (AUC: 0.547, sensitivity: 63.16%, specificity: 48.08%) and CA19-9 single test (AUC: 0.675 sensitivity: 65.38%, specificity: 67.57%), Delong test P < 0.05.Conclusion: The efficacy of CEA and CA19-9 single test was not optimal, and the combination of sTim-3 in serum could significantly improve the sensitivity and specificity of detecting patient recurrence after CRC surgery.Keywords: serum tumor markers, Tim-3, time-resolved fluorescence immunoassay, colorectal cancer recurrence

Qi Lou,1,&ast; Lu Pan,1,&ast; Shengjin Xiang,1,2,&ast; Yueting Li,1 Jiahui Jin,1 Jingyang Tan,1 Baoshan Huang,1,2 Kaihui Nan,1,2 Sen Lin1,2 1National Engineering Research Center of Ophthalmology and Optometry, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, 325027, People’s Republic of China; 2State Key Laboratory of Ophthalmology, Optometry and Vision Science, School of Ophthalmology & Optometry, Wenzhou Medical University, Wenzhou, 325027, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kaihui Nan; Sen Lin, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, People’s Republic of China, Tel +86-577-88067962, Email lin_sen@wmu.edu.cn; nankh@l63.comIntroduction: Benzalkonium chloride (BAC) is widely employed as a preservative in eye drops, which will cause the death of corneal epithelial cells due to ROS production, DNA strand breakage, and mitochondrial dysfunction, resulting in dry eye disease (DED)-like changes in ocular surface tissues. In this study, Melatonin (MT) liposomes (TAT-MT-LIPs) designed by loading MT into TAT-modified liposomes have been developed, characterized, and used for inhibiting BAC-induced DED (BAC-DED).Methods: The TAT was chemically grafted onto the Mal-PEG2000-DSPE by Michael’s addition between the sulfhydryl group in TAT and the maleimide group in Mal-PEG2000-DSPE. TAT-MT-LIPs were prepared using film dispersion followed by the extrusion method and topically treated in rats once a day. BAC-DED was induced in rats by topical administration with 0.2% BAC twice daily. Defects, edema, and inflammation of the corneas, as well as IOP, were examined. Histologic analyses of corneas were performed to assess the change of mitochondrial DNA oxidation and NLRP3/Caspase-1/GSDMD signaling transduction.Results: After topical administration, TAT-MT-LIPs significantly alleviated DED-clinical symptoms of experimental animals by inhibiting tissue inflammation and preventing the loss of the corneal epithelium and conjunctival goblet cells. Our data suggested continuous ocular surface exposure of BAC-induced NLRP3/Caspase-1/GSDMD mediated corneal epithelium pyroptosis, which was not reported before. BAC caused substantial mt-DNA oxidation, which promoted the transduction of NLRP3/Caspase-1/GSDMD and consequent corneal epithelium pyroptosis. TAT-MT-LIPs could efficiently suppress the BAC-induced corneal epithelium pyroptosis and inflammation by inhibiting mt-DNA oxidation and the subsequent signal transmission.Conclusion: NLRP3/Caspase-1/GSDMD mediated corneal epithelium pyroptosis is involved in the development of BAC-DED. The present study provided new insights into the adverse effects of BAC, which can serve as a new target for protecting corneal epithelium when applying BAC as a preservative in eye drops. The developed TAT-MT-LIPs can efficiently inhibit BAC-DED and give great potential to be developed as a new DED treatment.Keywords: melatonin liposome, dry eye disease, benzalkonium chloride, pyroptosis, NLRP3/Caspase-1/GSDMD signaling axis

Baozi Huang,1,2 Jianle Li,1 Pingping Li,1,2 Chunyong Chen,1,2 Suhan Cao,1 Zimu Jiang,1 Jinsheng Zeng1 1Department of Neurology and Stroke Center, Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital, Sun Yat-sen University, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, People’s Republic of China; 2Department of Neurology of the First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of ChinaCorrespondence: Jinsheng Zeng, Department of Neurology and Stroke Center, Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital, Sun Yat-sen University, National Key Clinical Department and Key Discipline of Neurology, No. 58 Zhongshan Road 2, Guangzhou, 510080, People’s Republic of China, Tel +86-20-87755766-8253, Fax +86-20-87335935, Email zengjsh@mail.sysu.edu.cnObjective: We aimed to assess the prevalence and risk factors of new-onset paroxysmal atrial fibrillation (PAF) in patients hospitalized with ICH and determine whether the new-onset PAF had influenced functional outcomes.Methods: We analyzed a database of all consecutive patients with ICH from October 2013 to May 2022. Univariate and multivariable regression analyses were performed to identify risk factors for new-onset PAF in patients with ICH. Multivariate models were also constructed to assess whether the new-onset PAF was an independent predictor of poor functional outcome, as measured using the modified Rankin scale.Results: This study included 650 patients with ICH, among whom 24 patients had new-onset PAF. In the multivariable model, older age (OR per 10-y increase, 2.26 [95% CI, 1.52– 3.35]; P< 0.001), hematoma volume (OR per 10-mL increase, 1.80 [95% CI, 1.26– 2.57]; P=0.001), and heart failure (OR, 21.77 [95% CI, 5.52– 85.91]; P< 0.001) were independent risk factors for new-onset PAF. In a sensitivity analysis restricted to 428 patients with N-terminal pro-B-type natriuretic peptide (NT-proBNP), older age, larger hematoma volume, heart failure, and increased NT-proBNP were associated with new-onset PAF. After adjusting for baseline variables, new-onset PAF was an independent predictor of poor functional outcome (OR, 10.35 [95% CI, 1.08– 98.80]; P=0.042).Conclusion: Older age, larger hematoma volume, and heart failure were independent risk factors for new-onset PAF after ICH. Increased NT-proBNP is correlated with higher risks for new-onset PAF when their information is available at admission. Furthermore, new-onset PAF is a significant predictor of poor functional outcome.Keywords: intracerebral hemorrhage, paroxysmal atrial fibrillation, prognostic implication, risk factors

Lina Wang, Xiaolin Zhang, Bo Huang, Yue Hou, Xinmin Liu, Hongmei Jiao Department of Geriatrics, Peking University First Hospital, Beijing, People’s Republic of ChinaCorrespondence: Hongmei Jiao, Department of Geriatrics, Peking University First Hospital, Beijing, 100034, People’s Republic of China, Email jiaohm@139.comBackground: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome. SARS-CoV-2 infection can induce secondary HLH, as described in previous case reports, but diagnosis and treatment are challenging.Case Study: We described an older male patient diagnosed with HLH related to previous SARS-CoV-2 infection. Fever was the only clinical manifestation initially but deterioration in clinical condition and laboratory parameters was observed during hospitalization. He responded poorly to classical therapy but was successfully treated with ruxolitinib.Conclusion: Clinicians should be aware of the possibility of HLH secondary to mild SARS-CoV-2 infection and take timely therapeutic measures to inhibit an inflammatory factor storm. Ruxolitinib is a potential choice for COVID-19 related HLH.Keywords: hemophagocytic lymphohistiocytosis, COVID-19, ruxolitinib, case report

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

Ling Ma,1,&ast; Yi Wang,2,&ast; Ming Yao,1 Bing Huang,1 Jiajia Deng,1 Huaichang Wen2 1Department of Anesthesiology and Pain Research Center, The Affiliated Hospital of Jiaxing University, Jiaxing, People’s Republic of China; 2Department of Anesthesiology, First Affiliated Hospital of Wannan Medical College, Wuhu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huaichang Wen, No. 2 Zhe shan Street, Wuhu, People’s Republic of China, Email wenhc19851207@163.comObjective: To verify the injectate dispersal patterns (IDP) and therapeutic outcome of ultrasound-guided cervical selective nerve root block (UG-SCNRB) in treating cervical radiculopathy (CR).Methods: Overall, 18 CR patients were recruited to undergo UG-SCNRB in the CT room. Following placement of the puncture needle tip between the target nerve root and posterior tubercle, 3 mL of the drug was administered per root (0.33% lidocaine 0.5 mL + Compound betamethasone injection 0.5mL + methylcobalamin injection 1mL + iohexol 1mL). Subsequently, the IDP was assessed on postintervention CT scan images.Results: In all, 18 participants were analyzed. We injected 21 target cervical nerve roots, namely, 1 C4 nerve, 9 C5 nerves, and 11 C6 nerves. Among the IDPs on postintervention CT scan images, two IDPs were most prevalent, namely, the contrast spread into the extraforaminal spaces (Zone I, the interscalene) in 100% (21/21) of cases, and the foraminal space spread (Zone II) in 61.90% (13/21) of cases. The injectate spread into the epidural spaces (Zone III) in only 2 out of 21 cases (9.52%). The pain relief was significantly improved two hours after surgery, compared to the preoperative VAS pain scores (2 hours, 1.39± 0.50 vs VAS at baseline, P< 0.01). The VAS pain scores during follow-up were significantly lower than preoperation (1 weeks, 1.94± 0.54 vs VAS at baseline; 2 weeks, 2.61± 0.70, P< 0.01 vs VAS at baseline; 4 weeks, 2.67± 0.59, P< 0.01 vs VAS at baseline).Conclusion: We verified, via CT imaging, that the UG-SCNRB drug diffusion was within safe range (the injectate mainly spread to the extraforaminal spaces), and without any serious complications, such as, intravascular drug injection, extensive diffusion of the epidural space, and general spinal anesthesia.Keywords: ultrasound-guided, cervical radiculopathy, selective nerve root block, efficacy, tomography

Bingyue Xin, Keyue Xie, Bing Huang, Ming Yao Department of Anesthesiology and Pain Research Center, The First Hospital of Jiaxing or The Affiliated Hospital of Jiaxing University, Jiaxing, People’s Republic of ChinaCorrespondence: Ming Yao, Department of Anesthesiology and Pain Research Center, The First Hospital of Jiaxing or The Affiliated Hospital of Jiaxing University, No. 1882 South Zhonghuan Road, Nanhu District, Jiaxing, Zhejiang Province, People’s Republic of China, Email jxyaoming666@163.comObjective: To investigate the effectiveness and safety of computed tomography (CT)-guided radiofrequency thermocoagulation (RFTC) of the thoracic sympathetic nerve versus chemical resection (CTS) for the treatment of pain caused by Raynaud’s disease.Methods: Patients who underwent CTS or thoracic sympathetic nerve RFTC between March 2012 and March 2021 were enrolled in this retrospective study. There were 28 cases in the alcohol group (Group A) and 44 in the radiofrequency group (Group R). Visual analog scores (VAS) were collected from patients at different time points, as well as preoperative and postoperative finger end perfusion index (PI) and hand temperature (T). The efficiency, postoperative recurrence rate, complications, and improvement in postoperative quality of life were observed in both groups.Results: Pain scores at different follow-up times after surgery decreased in both groups compared to the preoperative period (P < 0.05). Postoperative T and PI were higher in both groups than preoperatively all (P < 0.05). The recurrence rate was higher in the R group than in the A group. Postoperative complications were observed in 13.6% and 25% of patients in groups R and A, respectively. Meanwhile, the postoperative quality of life improved in both groups, but the radiofrequency (RF) group was better than the alcohol group in terms of improvement in quality of life (P < 0.05).Conclusion: Both CT-guided CTS and RFTC of the thoracic sympathetic nerve provided good treatment outcomes. However, the RF group was superior to the alcohol group in terms of complication rate and quality of life improvement.Keywords: Raynaud’s disease, sympathetic nerve, radiofrequency thermocoagulation, chemical thoracic sympathectomy, CT guidance

Wenjie Wen,1,2,&ast; Bin Huang,1,2,&ast; Shandong Ye1,2 1Department of Endocrinology and Laboratory for Diabetes, The First Affiliated Hospital of University of Science and Technology of China (USTC), Department of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China; 2Department of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shandong Ye, University of Science and Technology of China, No. 96 Jinzhai Road, Hefei, Anhui Province, 230026, People’s Republic of China, Email ysd196406@163.comBackground: Metformin is used as a first-line drug for the treatment of type 2 diabetes. Epithelial–mesenchymal transition (EMT) plays a significant role in the development of renal tubular damage in diabetic kidney disease. However, the underlying mechanisms of EMT in diabetic kidney disease are unclear and how to inhibit this process remains to be explored.Methods: C57 mice were randomly divided into four groups, including the normal control group (NC group), the Type 2 diabetes group (T2DM group), the metformin group (MET group), and glibenclamide group (GLIB). Fasting blood glucose (FBG), glycated hemoglobin (HbA1c), urinary albumin, RBP, PCX, and creatinine were measured. Renal pathology was observed with HE staining. Molecular mechanism of VDR expression are regulated by metformin through wound healing assay, and Western blot analysis of VDR, Ecad, and SMA in HK2 cells.Results: In animal experiments, compared with the NC group, the T2DM group showed decreased body weight, increased levels of FBG, HbA1c, UAlb/UCR, URBP/UCR, and UPCX/UCR, decreased levels of VDR protein and mRNA expression in renal tissues (P < 0.05), and significantly increased renal pathological damage in mice in the T2DM group. Compared with the T2DM group, mice in the GLIB and MET groups had higher body weight and lower FBG, HbA1c, UAlb/UCR, URBP/UCR, and UPCX/UCR (P < 0.05). In addition, renal pathological damage was significantly reduced in the MET group compared to the GLIB group. In HK2 cells, high glucose promoted the reduction of VDR and the development of EMT compared to the NC group. In addition, we found that Metformin can up-regulate VDR and inhibit EMT.Conclusion: Our study shows that the renoprotective effect of metformin is independent of glycemic control and metformin is involved in the progression of EMT by regulating VDR expression.Keywords: type 2 diabetes, diabetic kidney disease, metformin, VDR, EMT

Yaning Li,1 Junfang Nie,1 Jie Dai,1 Jun Yin,1 Binbin Huang,1 Jia Liu,1 Guoguang Chen,1 Lili Ren1,2 1School of Pharmacy, Nanjing Tech University, Nanjing, People’s Republic of China; 2Department of Microbiology and Immunology, Stanford University, Stanford, CA, USACorrespondence: Guoguang Chen; Lili Ren, School of Pharmacy, Nanjing Tech University, Nanjing, People’s Republic of China, Tel +86-2558-139-416, Email ggchen@njtech.edu.cn; renlili@njtech.edu.cnPurpose: Nanotechnology has been widely used in antitumor research. The complex physiological environment has brought significant challenges to the field of antitumor micelles. The ideal micelles must not only have an invisible surface to extend the circulation time but must also enhance the retention of drugs and cellular internalization at the tumor.Methods: A graded response micelle (RPPssD@IR780/DOC) was designed to self-assemble by cRGD-poly(β-amino esters)-polyethylene glycol-ss-distearoyl phosphatidylethanolamine (cRGD-PBAE-PEG-ss-DSPE) loaded with docetaxel (DOC) and IR-780 iodide (IR780). The micelles were designed to allow the PEG shell to prolong the blood circulation time in the body and effectively accumulate in the tumor. Subsequently, the acidic microenvironment of the tumor could transform the PBAE to hydrophilic, thereby increasing the size of micelles and exposing cyclic Arg-Gly-Asp (cRGD) peptides to increase the retention and cellular internalization of micelles in the tumor. After tumor cells had captured micelles, the high expression of glutathione in the cells prompted the release of DOC and IR780. Subsequently, the IR780 was stimulated by an 808-nm laser to generate local heat and reactive oxygen species (ROS) to synergize with DOC to treat the tumor.Results: In vitro and in vivo experimental results suggested that RPPssD@IR780/DOC was a potential photochemical effective for the treatment of tumors with non-negligible antitumor activity and good biocompatibility.Conclusion: A dual-response pH/redox delivery system with on-demand RGD exposure was designed to achieve photochemotherapy of tumors with good biosafety and antitumor effects.Graphical Abstract: Keywords: micelles, drug delivery, ligand hidden, size variable, photo-chemotherapy

Zhang S, Wang Q, Li D, et al. Cancer Manag Res. 2020;12:10389–10396. We, the Editors and Publisher of Cancer Management and Research, have retracted the following article. Since publication, concerns have been raised about the integrity of the data in the article. When approached for an explanation, the authors did not respond to our queries, nor did they provide original data for their study. As verifying the validity of the 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”.

Bin Huang,1,2,&ast; Shengju Yang,1,&ast; Shandong Ye1 1Department of Endocrinology, The First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China; 2Research Institution of Diabetes, University of Science and Technology of China, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shandong Ye, Department of Endocrinology, The First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China, Email 981257013@qq.comIntroduction: Early detection of bacterial infections associated with adequate antibiotic treatment is key to improving diabetic ketoacidosis (DKA) outcomes. Our study aimed to investigate the different sepsis markers (including procalcitonin to lactic acid ratio, PLR) to diagnose bacterial infection in patients with DKA within one hour after admission.Methods: A total of 165 patients diagnosed with DKA were enrolled between July 2014 and July 2018 and divided into an infection group (N =62) and a non-infection group (N=103) based on the positive aetiological tests such as blood culture, sputum culture, urine culture, or definite focus of pulmonary, soft tissue, kidney, etc.Results: Our findings suggest the following: 1) leucocytes (threshold above 10× 109 /L) and PLR (threshold above 0.438) within one hour after admission can help to identify patients with infection in the context of DKA. 2) A subgroup analysis demonstrated that PLR also has a high diagnostic efficacy for infection in patients with DKA, regardless of the type of diabetes.Conclusion: This study concludes that leucocyte count (threshold > 10× 109/L) and PLR (threshold above 0.438) show a diagnostic value to help distinguish DKA patients with infection. By combining these two markers, the reduction of antibiotic misuse may be possible.Keywords: diabetic ketoacidosis, infections, procalcitonin to lactic acid ratio, diagnostic value

Jian Zhu,1,&ast; Chuan-Yang Jiang,2,&ast; Bin Huang,3,&ast; Ji-Min Hu,4 Si-Zhen Fang,5 Ke Huang,1 Yan-Hong Gao,6 Jiao Yu7 1Department of Thoracic Cardiovascular Surgery, General Hospital of Central Theater Command of People’s Liberation Army, Wuhan, 430070, People’s Republic of China; 2College of Mechanical Engineering, Liaoning Petrochemical University, Fushun, 113001, People’s Republic of China; 3The First School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 4Science Technology and Standards Center, Jiangsu Testing and Inspection Institute for Medical Devices, Nanjing, 210019, People’s Republic of China; 5Spectris Instrumentation & Systems Shanghai Ltd. Guangzhou Branch, Guangzhou, 510620, People’s Republic of China; 6Department of Ultrasound, General Hospital of Central Theater Command of People’s Liberation Army, Wuhan, 430070, People’s Republic of China; 7College of Science, Liaoning Petrochemical University, Fushun, 113001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiao Yu, College of Science, Liaoning Petrochemical University, Fushun, 113001, People’s Republic of China, Email yujiaojoy@hotmail.com Yan-Hong Gao, Department of Ultrasound, General Hospital of Central Theater Command of People’s Liberation Army, Wuhan, 430070, People’s Republic of China, Email gaoyh200509@163.comBackground: The COVID-19 pandemic has continued for more than two years since its outbreak. Due to the clinical auscultation needs of doctors when wearing airtight protective clothing, a cylindrical tube stethoscope was proposed to address this problem. However, the idea has been questioned by some experts.Methods: To address these questions, we performed three-part experiments using cylindrical tube stethoscopes. First, we performed laboratory tests to detect the sound intensity from a cylindrical tube stethoscope. Second, we improved the cylindrical tube stethoscope to achieve better results. Third, we revealed the difference in the auscultation effects of the cylindrical tube stethoscope and a conventional professional 3 M stethoscope.Results: From these experiments, we found that a narrow cylindrical tube with a diameter of 4.2 cm and a length of 20 cm equipped with a silicone gasket better auscultation of heart sounds. A cylindrical tube stethoscope and a 3 M stethoscope were used to perform stethoscope tests on 10 volunteers. The alveolar lung sounds were 44.478 decibels vs 49.529 decibels, the heart sounds were 46.631 decibels vs 41.109 decibels, and the intestinal sounds were 40.132 decibels vs 43.787 decibels, respectively.Conclusion: This improved cylindrical tube stethoscope can meet the auscultation requirements for cardiorespiratory and abdominal diagnosis during infectious disease pandemics.Keywords: stethoscope, auscultation, COVID-19, SARS-CoV-2, acoustic optimization

Bing Huang,1– 4 Hui Yan,2 Limei Hu,1,3,4 Guiqiu Cao,2 Guipeng Wang,2 Jing Meng,2 Wanting Li,5 Gang Liu,2 Juan Wang,2 Wenqing Le,5 Hong Jiang1,3,4 1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Department of Cardiology, Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 3Cardiovascular Research Institute, Wuhan University, Wuhan, Hubei, People’s Republic of China; 4Hubei Key Laboratory of Cardiology, Wuhan, Hubei, People’s Republic of China; 5Department of Critical Care, Wuhan Hankou Hospital, Wuhan, Hubei, People’s Republic of ChinaCorrespondence: Hong JiangDepartment of Cardiology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuchang District, Wuhan City, Hubei Province, 430060, People’s Republic of ChinaTel +86 2788041911Fax +86 2788042292Email hong-jiang@whu.edu.cnGuiqiu CaoDepartment of Cardiology, Fifth Affiliated Hospital of Xinjiang Medical University, No. 118 Henan Road, Xinshi District, Urumqi, Xinjiang, 830000, People’s Republic of ChinaTel/Fax +86 09917598403Email 809624056@qq.comBackground: Increasing numbers of patients have recovered from severe coronavirus disease 2019 (COVID-19) in Wuhan, China. This study aimed to evaluate the association of psychological distress with resting palpitations in recovered patients.Methods: In this prospective cohort study, consecutive patients who recovered from severe COVID-19 and complained of resting palpitations were included. Dynamic electrocardiogram (ECG) was continuously monitored for 2 hours while patients were at rest. A survey using a palpitation frequency scale and the Hospital Anxiety and Depression Scale (HADS) was administered to all participants.Results: Of the 289 consecutive patients who recovered from severe COVID-19, 24 patients (8.3%) suffered resting palpitation symptoms, and 22 patients were finally included. Two-hour Holter monitoring showed that 18 (81.8%) patients had tachyarrhythmias, of which the most common was sinus tachycardia (17/22, 77.3%). However, patients with sinus tachycardia showed a similar frequency of palpitation episodes compared to those without sinus tachycardia. Anxiety (68.2%) and depression (59.1%) were prevalent among these recovered patients. Patients with anxiety or depression symptoms had a higher frequency of palpitation episodes than those without anxiety or depression symptoms. In addition, both the HADS-anxiety score (r =0.609, P< 0.01) and HADS-depression score (r =0.516, P=0.01) were positively related to the frequency of palpitation episodes.Conclusion: Symptoms of resting palpitations, manifested mainly by sinus tachycardia, are not uncommon in patients who recovered from severe COVID-19. Psychological distress (anxiety and depression) may be responsible, at least in part, for resting palpitation symptoms.Keywords: coronavirus disease 2019, palpitations, sinus tachycardia, anxiety, depression

Weisheng Chen,1 Mengjing Wang,1,2 Minmin Zhang,1 Weichen Zhang,1 Jun Shi,1 Jiamin Weng,1 Bihong Huang,1 Kamyar Kalantar-Zadeh,3– 5 Jing Chen1,2 1Division of Nephrology, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 2National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine Medical Center, Orange, CA, USA; 4Fielding School of Public Health at UCLA, Los Angeles, CA, USA; 5Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA, USACorrespondence: Mengjing Wang; Jing ChenDivision of Nephrology, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai, People’s Republic of ChinaTel +86 21 52889393; +86 21 52889387Fax +86 21 52889325; +86 21 52888304Email fiyona27@126.com; chenjing1998@fudan.edu.cnPurpose: Previous research on incremental hemodialysis transition has mainly focused on one or two benefits or prognoses. We aimed to conduct a comprehensive analysis by investigating whether incremental hemodialysis was simultaneously associated with adequate dialysis therapy, stable complication indicators, long-lasting arteriovenous vascular access, and long-lasting preservation of residual kidney function (RKF) without increasing mortality or hospitalization.Patients and Methods: Incident hemodialysis patients from Huashan Hospital in Shanghai, China, over the period of 2012 to 2019, were enrolled and followed every three months until death or the time of censoring. Changes in complication indicators from baseline to all post-baseline visits were analyzed by mixed-effects models. The outcomes of RKF loss, arteriovenous vascular access complications, and the composite of all-cause mortality and cardiovascular events were compared between incremental and conventional hemodialysis by Cox proportional hazards model.Results: Of the 113 patients enrolled in the study, 45 underwent incremental and 68 conventional hemodialysis. There were no significant differences in the changes from baseline to post-baseline visits in complication indicators between the two groups. Incremental hemodialysis reduced the risks of RKF loss (HR, 0.33; 95% CI, 0.14– 0.82), de novo arteriovenous access complication (HR, 0.26; 95% CI, 0.08– 0.82), and recurrent arteriovenous access complications under the Andersen–Gill (AG) model (HR, 0.27; 95% CI, 0.10– 0.74) and the Prentice, Williams and Peterson Total Time (PWP-TT) model (HR, 0.31; 95% CI, 0.12– 0.80). There were no significant differences in all-cause hospitalization or the composite outcome between groups.Conclusion: Incremental hemodialysis is an effective dialysis transition strategy that preserves RKF and arteriovenous access without affecting dialysis adequacy, patient stability, hospitalization risk and mortality risk. Randomized controlled trials are warranted.Keywords: incremental hemodialysis, arteriovenous vascular access, residual kidney function, hospitalization, mortality

Ting Sun,1 Tao Wang,1 Yiwen Qiu,1 Shu Shen,1 Xianwei Yang,1 Yi Yang,1 Bin Huang,2 Wentao Wang1 1Department of Liver Surgery & Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, People’s Republic of China; 2Department of Vascular Surgery, West China Hospital of Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Wentao Wang Email wwtdoctor02@163.comBackground: Sarcopenia and visceral adiposity have been shown to be associated with postoperative complications in numerous diseases. However, their effects on the postoperative complications of end-stage hepatic alveolar echinococcosis (HAE) patients undergoing ex vivo liver resection and autotransplantation (ELRA) remain unclear.Methods: This retrospective study included 101 end-stage HAE patients who underwent ELRA from January 2014 to August 2020. We measured the skeletal muscle and adipose tissue of all patients at the level of the third lumbar vertebra on plain abdominal computed tomography (CT) images and subsequently derived an equation via least absolute shrinkage and selection operator (LASSO) regression analysis to calculate the sarcopenia score. Univariate and multivariate regression were performed to reveal the relationship between major postoperative complications and perioperative clinical data, and the obtained nomogram was validated with the bootstrapping method.Results: The sarcopenia score was constructed as a personalized indicator to evaluate sarcopenia and visceral adiposity in each patient. Logistic regression analysis finally selected duration from primary diagnosis to obvious symptoms (OR=1.024, 95% CI, 1.007– 1.042), surgical time (OR=1.003, 95% CI, 0.999– 1.007) and sarcopenia score (OR=4.283, 95% CI, 1.739– 10.551) as independent risk factors for predicting major postoperative complications following ELRA for end-stage HAE patients. The area under the receiver operating characteristic curve (AUROC) of 0.807 (95% CI, 0.720– 0.895) and the calibration curve for this prediction model were satisfactory.Conclusion: The sarcopenia score, which systematically evaluates the skeletal muscle and adipose tissue of end-stage HAE patients, was a significant predictive factor for major postoperative complications of ELRA. Relevant interventions should be conducted for those who have a high risk of postoperative complications according to the nomogram.Keywords: hepatic alveolar echinococcosis, liver transplantation, hepatectomy, sarcopenia, postoperative complications

Zhou X, Liu Z, Huang B, et al. Drug Des Devel Ther. 2019;13:2703–2713. The Editor and Publisher of Drug Design, Development and Therapy wish to retract the published article. Concerns were raised regarding the alleged duplication of Oil Red O images in Figures 4 and Figure 6. Specifically, Figure 4C, Oil Red O, Ctrl, appears to have been duplicated with the same image for Figure 6D, Oil Red O, OG+ICG-001. The authors cooperated with the investigation and provided data associated with the study. However, despite the authors’ assistance, it was still not clear how the images came to be duplicated, and, as we cannot verify the validity of the published work, we are therefore retracting the article and the authors agree with this decision. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Lingli Chen,1,&ast; Jianfeng Hong,2,&ast; Renjing Hu,3,&ast; Xiaomei Yu,1 Xindong Chen,1 Shaoxiong Zheng,1 Yuan Qin,1 Xiumei Zhou,1 Yigang Wang,1 Liping Zheng,2 Hongming Fang,2 Pengfei Liu,4 Biao Huang1 1Department of Immunoassay Laboratory, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, People’s Republic of China; 2Department of Laboratory, Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou, People’s Republic of China; 3Department of Laboratory, The Affiliated Wuxi No.2 People’s Hospital of Nanjing Medical University, Wuxi, People’s Republic of China; 4Department of Gastroenterology, The Jiangyin Clinical College of Xuzhou Medical University, Wuxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Biao HuangImmunoassay Laboratory, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, 310016, People’s Republic of ChinaTel +86 571-86843187Email jswxhb@163.comHongming FangDepartment of Laboratory, Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou, 310016, People’s Republic of ChinaTel +86 571 83865858Email 3295988078@qq.comPurpose: The present study aimed to evaluate the clinical value of the combined detection of soluble T cell immunoglobulinand mucin domain molecule 3 (sTim-3) and pepsinogen (PG) in sera for gastric cancer (GC) diagnosis.Patients and Methods: The double antibody sandwich method was used to establish a highly sensitive time-resolved fluorescence immunoassay for the detection of sTim-3. Serum sTim-3, PGI, and PGII levels in 149 GC patients (123 first-diagnosis GC patients and 26 post-GC patients), 81 patients with benign gastric disease (BGD), and 73 healthy controls were quantitatively detected. The clinical diagnostic value of the combined detection of sTim-3 and PG in GC was analyzed.Results: Serum sTim-3 levels in GC (20.41 ± 9.55 ng/mL) and BGD (16.50 ± 9.76 ng/mL) patients were significantly higher (P < 0.001) than those in healthy controls (9.22 ± 3.40 ng/mL). Combined detection of sTim-3 and PGI/PGII (AUC: 0.9330, sensitivity: 86.44%, and specificity: 91.78%) showed a high diagnostic value for GC. When the level of PGI/PGII was less than 12.11 and that of sTim-3 was greater than 14.30 ng/mL, the positive rate of the control group was reduced to 0%, and the positive detection rate of GC was 54.47%. In addition, in post-operative patients, serum sTim-3 levels in the recurrence group (33.56 ± 4.91 ng/mL) were significantly higher than those in the no recurrence group (11.95 ± 5.16 ng/mL).Conclusion: sTim-3 levels in BGD and GC sera were significantly higher than those in the control group sera. Additionally, sTim-3 serum levels can predict recurrence in post-operative patients. Compared with PG alone, the combined detection of serum PG and sTim-3 can significantly improve the detection sensitivity and specificity of BGD and GC.Keywords: T cell immunoglobulin and mucin domain molecule 3, time-resolved fluorescence immunoassay, biomarker, gastric cancer

Tianyan Ding1,2 &ast;, Cantong Liu1,2 &ast;, Binliang Huang,1,2 Lingyu Chu,1,2 Laifeng Wei,1,2 Yiwei Lin,1,2 Yun Luo,1,2 Biao Zhang,1,2 Chaoqun Hong,3 Yiwei Xu,1,2 Yuhui Peng1,2 1Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou, People’s Republic of China; 2Precision Medicine Research Center, Shantou University Medical College, Shantou, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Breast Cancer Diagnosis and Treatment, Cancer Hospital of Shantou University Medical College, Shantou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yiwei XuDepartment of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, 7 Raoping Road, Shantou, 515041, Guangdong, People’s Republic of ChinaFax +86-754-8856-0352Email yiwei512@126.comYuhui Peng Email pengyuhui666@163.comBackground: Neoadjuvant chemoradiotherapy (NCRT) followed by surgery is a component of the standard treatment for resectable locally advanced esophageal squamous cell carcinoma (ESCC), and the parameters for survival prediction are not clear yet. Our study aimed to construct a survival prediction nomogram for ESCC with NCRT followed by surgery.Methods: We analyzed hematological parameters and related-derivative indexes from 122 ESCC patients treated with NCRT followed by surgery. Univariate and multivariate Cox survival analyses were performed to identify independent prognostic factors to establish a nomogram and predict overall survival (OS). The predictive value of the nomogram for OS was evaluated by the concordance index (C-index), decision curve analysis (DCA), the clinical impact curve (CIC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI).Results: The pretreatment nutritional candidate, prognostic nutrition index, inflammation-related absolute monocyte count and TNM staging were entered into the nomogram for ESCC with NCRT followed by surgery. The C-index of the nomogram for OS was 0.790 (95% CI = 0.688– 0.893), which was higher than that of TNM staging (0.681; 95% CI = 0.565– 0.798, P = 0.026). The DCA, CIC, NRI, and IDI of the nomogram showed moderate improvement in predicting survival. Based on the cut point calculated according to the constructed nomogram, the high-risk group had poorer OS than that of the low-risk group (P < 0.05).Conclusion: A novel nomogram based on nutrition- and inflammation-related indicators might help predict the survival of ESCC treated with NCRT followed by surgery.Keywords: esophageal squamous cell carcinoma, neoadjuvant chemoradiotherapy, surgery, nomogram, survival, prognosis

Zuyi Ma,1,2,&ast; Zhenchong Li,1,3,&ast; Shujie Wang,1,4,&ast; Qi Zhou,5,6,&ast; Zuguang Ma,7 Chunsheng Liu,1,2 Bowen Huang,8 Zehao Zheng,1,2 LinLing Yang,9 Yiping Zou,1,2 Chuanzhao Zhang,1,3,4 Shanzhou Huang,1,3,4 Baohua Hou1,3,4 1Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 2Shantou University of Medical College, Shantou, 515000, People’s Republic of China; 3South China University of Technology School of Medicine, Guangzhou, 51000, People’s Republic of China; 4The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 5Department of General Surgery, Hui Ya Hospital of the First Affiliated Hospital, Sun Yat-Sen University, Huizhou, 516081, People’s Republic of China; 6Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510000, People’s Republic of China; 7Sanshui Disease Prevention Cure Station, Foshan, 528100, People’s Republic of China; 8Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China; 9Guangzhou Medical University, Guangzhou, 511436, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shanzhou Huang; Baohua Hou Tel +86 13928842869; +86 13609006510Email hshanzh@163.com; hbh1000@126.comBackground: Recent evidence has shown that Solute Carrier Family 39 Member 10 (SLC39A10) promoted tumor progression in several cancer types. The study intended to explore the expression and function of SLC39A10 in hepatocellular carcinoma (HCC).Methods: Multiple bioinformatics analyses were used to evaluate SLC39A10 expression and potential role in HCC. Quantitative real-time polymerase chain reaction and immunohistochemistry were used to confirm SLC39A10 expression. Intro studies were performed to assess the effects of SLC39A10 on HCC cells proliferation and migration. Furthermore, flow cytometry was conducted to identify its specific function in apoptosis of HCC.Results: SLC39A10 was significantly over-expressed in HCC samples from both bioinformatic databases and our cohort. Survival analyses suggested patients with high expression of SLC39A10 had poor overall survival and disease-free survival (P-value < 0.01). Further, the expression of SLC39A10 was positively correlated with tumor-infiltrating lymphocytes and some immune checkpoints like CTLA4, TIM3 and TGFB1. In HCC cell lines, SLC39A10 knockdown inhibited cells proliferation and migration, but promoted apoptosis.Conclusion: An increased SLC39A10 expression was found and served as an unfavorable indicator of survival in HCC. Further studies suggested SLC39A10 promotes tumor aggressiveness and may provide a novel target for HCC therapy.Keywords: Solute Carrier Family 39 Member 10, hepatocellular carcinoma, immune infiltration, prognosis, cancer aggressiveness

Yuying Chen,1,&ast; Jia Chen,2,&ast; Yu Zhang,3,&ast; Zhi Lin,1 Meng Wang,1 Lifei Huang,2 Mengqi Huang,1 Mimi Tang,1 Xiaoqi Zhou,1 Zhenpeng Peng,1 Bingsheng Huang,2 Shi-Ting Feng1 1Department of Radiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 2Medical AI Lab, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, Guangdong, People’s Republic of China; 3Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bingsheng HuangMedical AI Lab, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, Guangdong, People’s Republic of ChinaTel +86 755-86172208Fax +86 755-86171820Email huangb@szu.edu.cnShi-Ting FengDepartment of Radiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of ChinaTel +86 20-87755766 Ext 8471Fax +86 20-87615805Email fengsht@mail.sysu.edu.cnPurpose: Cytokeratin 19 (CK19) expression is a proven independent prognostic predictor of hepatocellular carcinoma (HCC). This study aimed to develop and validate the performance of a deep learning radiomics (DLR) model for CK19 identification in HCC based on preoperative gadoxetic acid-enhanced magnetic resonance imaging (MRI).Patients and Methods: A total of 141 surgically confirmed HCCs with preoperative gadoxetic acid-enhanced MRI from two institutions were included. Prediction models were established based on hepatobiliary phase (HBP) images using a training set (n=102) and validated using time-independent (n=19) and external (n=20) test sets. A receiver operating characteristic curve was used to evaluate the performance for CK19 prediction. Recurrence-free survival (RFS) was also analyzed by incorporating the CK19 expression and other factors.Results: For predicting CK19 expression, the area under the curve (AUC) of the DLR model was 0.820 (95% confidence interval [CI]: 0.732– 0.907, P< 0.001) with sensitivity, specificity, accuracy of 0.800, 0.766, and 0.775, respectively, and reached 0.781 in the external test set. Combined with alpha fetoprotein, the AUC increased to 0.833 (95% CI: 0.753– 0.912, P

Kun Li,1,&ast; Bin Huang,2,&ast; Tao Ji,3 Shao-Gan Xu,3 Wen Jiang4 1Department of Anesthesiology, General hospital of central theater command of the People’s Liberation Army, Wuhan, Hubei Province, 430070, People’s Republic of China; 2The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong Province, 510515, People’s Republic of China; 3Department of Thoracic Cardiovascular Surgery, General Hospital of Central Theater Command of People’s Liberation Army, Wuhan, Hubei Province, 430070, People’s Republic of China; 4Department of Health Medicine, General hospital of central theater command of the People’s Liberation Army, Wuhan, Hubei Province, 430070, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wen Jiang; Shao-Gan XuGeneral hospital of central theater command of the People’s Liberation Army, 627#, Wuluo Road, Wuchangqu, Wuhan, Hubei, 430070, People’s Republic of ChinaTel +86 17720529297Fax +86 27-50772388Email zbzqzyyjw@163.com; whzyyxsg@163.comAbstract: At the moment, the SARS-CoV-19 pandemic is still attacking the health of humanity, and vaccines are the primary health strategy to eradicate this global challenge. So, with the exception of the SARS-CoV-2 vaccine, no vaccine for any disease has been brought to clinical use so quickly. Therefore, even with strict management, it can still bring some special adverse effects. One of the most notable is the adverse cardiovascular reactions to SARS-CoV-2 vaccines. No case reports of individuals with irreversible arrhythmia complications following the SARS-CoV-2 vaccine have been found in the available literature. We report the first case of a postoperative man with Marfan syndrome with atrial fibrillation after receiving the SARS-CoV-2 vaccine.Keywords: SARS-CoV-2, vaccine, adverse reactions, arrhythmology

Bo Huang,&ast; Yating Zhao,&ast; Lin Zhou,&ast; Tingyu Gong, Jiawen Feng, Peilin Han, Jianhua Qian Department of Gynecology and Obstetrics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, 310003, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianhua QianDepartment of Gynecology and Obstetrics, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Shangcheng District, Hangzhou City, 310003, Zhejiang Province, People’s Republic of ChinaTel +8613858028056Email qianjianhua@zju.edu.cnPurpose: Peptidyl arginine deiminase, type VI (PADI6), a member of the subcortical maternal complex, plays an important role in oocyte growth and the development of fertilized oocytes. Human patients with PADI6 mutations can suffer from multiple reproductive deficiencies including hydatidiform moles and miscarriages. Recent studies have demonstrated that the Hippo signaling pathway plays a central role in the specification of the first cell fates and the maintenance of the human placental trophoblast epithelium. The present study aimed to verify the hypothesis that PADI6 regulates the biological functions of trophoblast cells by targeting YAP1 and to explore the mechanism by which PADI6 accomplishes this in trophoblast cells.Methods: Villi from HMs and human trophoblast cell lines were used to identify the localization of PADI6 and YAP1 by immunohistochemistry and immunocytochemistry. PADI6 overexpression and knockdown were induced in human trophoblast cells. Co-immunoprecipitation was used to explore the interaction between PADI6 and YAP1. Wound healing, Transwell and EdU staining assays were used to detect migration, invasion and proliferation. Flow cytometric analysis was used to analyze the cell cycle and apoptosis. β-Tubulin and F-actin levels were determined by Western blot, quantitative real-time PCR and phalloidin staining.Results: The results showed that PADI6 and YAP1 had the same expression pattern in villi and colocalized in the cytotrophoblast. An interaction between PADI6 and YAP1 was also confirmed in human trophoblast cell lines. We found that PADI6 positively regulated the expression of YAP1. Functionally, overexpression of PADI6 promoted cell cycle progression and enhanced migration, invasion, proliferation and apoptosis, whereas downregulation of PADI6 showed the opposite effects.Conclusion: This study demonstrates that YAP1 is a novel target of PADI6 that serves as an important regulator of trophoblast dysfunction. The crosstalk between the Hippo/YAP1 pathway and the SCMC might be a new topic to explore to uncover the pathological mechanisms of HMs.Keywords: PADI6, yes-associated protein, trophoblast cell, hydatidiform moles

Chunmei Wang,1,2,* Jun Liu,3,* Xiaoye Shi,1 Shaoze Ma,1 Guangqin Xu,1 Tingwei Liu,1 Tingting Xu,3 Bo Huang,3 Ying Qu,4 Xiaozhong Guo,1 Xingshun Qi1 1Department of Gastroenterology, General Hospital of Northern Theater Command (Formerly General Hospital of Shenyang Military Area), Shenyang, People’s Republic of China; 2Graduate School, Jinzhou Medical University, Jinzhou, People’s Republic of China; 3Military Joint Teaching and Research Office, The 32684 Troop of Chinese PLA, Shenyang, People’s Republic of China; 4Department of Health Care, General Hospital of Northern Theater Command (Formerly General Hospital of Shenyang Military Area), Shenyang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xingshun Qi; Xiaozhong GuoDepartment of Gastroenterology, General Hospital of Northern Theater Command (Formerly General Hospital of Shenyang Military Area), No. 83 Wenhua Road, Shenyang, Liaoning Province, 110840, People’s Republic of ChinaTel +86-24-28897603Fax +86-24-28851113Email xingshunqi@126.com; guo_xiao_zhong@126.comPurpose: Helicobacter pylori infection is an important cause of peptic ulcer disease and gastric cancer. Current knowledge regarding epidemiology of H. pylori infection in military personnel has insufficiently been updated. This cross-sectional study aimed to estimate the prevalence of H. pylori infection in military personnel and to compare the prevalences in military and civilian groups.Patients and Methods: We retrospectively enrolled the subjects who underwent 14C-urea breath tests at the Department of Gastroenterology of the General Hospital of Northern Theater Command between January 2017 and July 2020. Subjects were divided into military and civilian groups. H. pylori infection and major endoscopic findings were reviewed.Results: Overall, 23,496 subjects were eligible, including 2282 subjects in the military group and 21,214 subjects in the civilian group. In the overall analysis, the prevalence of H. pylori infection was not significantly different between military and civilian groups (33.9% versus 34.4%, P=0.592). In the population aged 17– 25 years, the prevalence of H. pylori infection was significantly higher in the military group than in the civilian group (35.6% versus 25.9%, P=0.001). Both 14C-UBT and endoscopy were performed in 547 inpatients, including 83 military inpatients and 464 civilian inpatients. There was a significantly higher prevalence of H. pylori in inpatients with peptic ulcer and/or gastric cancer than in those without (65.5% versus 41.4%, P=0.001).Conclusion: Among the adolescent population, H. pylori infection may be more common in military personnel as compared to the civilians. Well-designed prospective studies should be required to validate such a high prevalence and to explain its potential causes.Keywords: Helicobacter pylori, prevalence, military, epidemiology, endoscopy

Yong Fei, Bing Huang, Jiajia Deng, Longsheng Xu, Ming Yao Department of Anesthesiology and Pain Medicine, Affiliated Hospital of Jiaxing University, Jiaxing, 314001, People’s Republic of ChinaCorrespondence: Longsheng Xu; Ming YaoDepartment of Anesthesiology and Pain Medicine, Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, 314001, People’s Republic of ChinaEmail xlsh2468@163.com; jxyaoming666@163.comObjective: The purpose of this study was to investigate the clinical efficacy of dorsal root ganglion (DRG) pulsed radiofrequency combined with paravertebral injection of recombinant human interferon-α 2b in the treatment of patients with acute herpes zoster neuralgia and its preventive effectiveness on postherpetic neuralgia (PHN).Methods: A retrospective analysis of 62 patients with acute herpes zoster neuralgia was implemented. All patients were divided into two groups: pulsed radiofrequency paraspinal injection of recombinant human interferon-α 2b (group P); pulsed radiofrequency combined with paravertebral injection of saline (group C). The numerical rating scales (NRS) scores were used for pain assessment, and the dose of the analgesic drug was recorded. Gal-3 and IL-6 levels in blood were compared between the two groups before treatment and at 1 week, 2, and 4 weeks after treatment. The incidence of PHN was recorded in both groups.Results: The pain intensity, the levels of Gal-3 and IL-6 in blood and the dose of oral administration of gabapentin capsules and morphine were reduced in all patients after treatment. Compared with group C, patients in group P had lower NRS scores, blood levels of Gal-3 and IL-6, and dosages of oral gabapentin capsules and morphine hydrochloride immediate-release tablets after treatment. The incidence of PHN was significantly lower at 8 and 12 weeks.Conclusion: DRG pulsed radiofrequency combined with paravertebral injection of recombinant human interferon-α 2b for acute stage herpes zoster neuralgia is a more effective treatment, and can effectively prevent the incidence rate of PHN.Keywords: pulsed radiofrequency, dorsal root ganglion, recombinant human interferon-α 2b, herpes zoster, postherpetic neuralgia

Zhenhua Li,1,2,* Bin Huang,2,* Wenfeng Yi,2,* Fei Wang,1 Shizhuang Wei,1 Huaixing Yan,1 Pan Qin,1 Donghua Zou,1 Rongguo Wei,3 Nian Chen4 1Department of Emergency Medicine, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, 530022, People’s Republic of China; 2Intensive Care Unit, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, 530022, People’s Republic of China; 3Department of Clinical Laboratory, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, 530022, People’s Republic of China; 4Department of Infectious Diseases, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, 530022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rongguo Wei; Nian Chen Email unwrong@126.com; chennian1111@163.comObjective: The goal of this article was to identify potential biomarkers for early diagnosis of sepsis in order to improve their survival.Methods: We analyzed differential gene expression between adult sepsis patients and controls in the GSE54514 dataset. Coexpression analysis was used to cluster coexpression modules, and enrichment analysis was performed on module genes. We also analyzed differential gene expression between neonatal sepsis patients and controls in the GSE25504 dataset, and we identified the subset of differentially expressed genes (DEGs) common to neonates and adults. All samples in the GSE54514 dataset were randomly divided into training and validation sets, and diagnostic signatures were constructed using least absolute shrink and selection operator (LASSO) regression. The key gene signature was screened for diagnostic value based on area under the receiver operating characteristic curve (AUC). STEM software identified dysregulated genes associated with sepsis-associated mortality. The ssGSEA method was used to quantify differences in immune cell infiltration between sepsis and control samples.Results: A total of 6316 DEGs in GSE54514 were obtained spanning 10 modules. Module genes were mainly enriched in immune and metabolic responses. Screening 51 genes from among common genes based on AUC > 0.7 led to a LASSO model for the training set. We obtained a 25-gene signature, which we validated in the validation set and in the GSE25504 dataset. Among the signature genes, SLC2A6, C1ORF55, DUSP5 and RHOB were recognized as key genes (AUC > 0.75) in both the GSE54514 and GSE25504 datasets. SLC2A6 was identified by STEM as associated with sepsis-associated mortality and showed the strongest positive correlation with infiltration levels of Th1 cells.Conclusion: In summary, our four key genes may have important implications for the early diagnosis of sepsis patients. In particular, SLC2A6 may be a critical biomarker for predicting survival in sepsis.Keywords: sepsis, early diagnosis, LASSO model, SLC2A6, WGCNA, diagnostic biomarker

Ping-Xin Qi,1,2,* Jia-Ni Zou,3,* Jian Zhu,2 Bin Huang,4 Er-Ping Xi,2 Xu-Hui Gao2 1School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, People’s Republic of China; 2Department of Thoracic Cardiovascular Surgery, General Hospital of Central Theater Command of the People’s Liberation Army, Wuhan 430070, People’s Republic of China; 3Department of Radiology, General Hospital of Central Theater Command of the People’s Liberation Army, Wuhan 430070, People’s Republic of China; 4The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xu-Hui Gao; Er-Ping XiDepartment of Thoracic Cardiovascular Surgery, General Hospital of Central Theater Command of the People’s Liberation Army, 627#, Wuluo Road, Wuchang District, Wuhan, Hubei 430070, People’s Republic of ChinaTel +86-13307195757Fax +86-27-50772388Email whzyygxh@126.com; wo5351@126.comAbstract: A 55-year-old man was treated at the village hospital with six months medical history of recurrent chills and fever. Due to the lack of imaging examination, antipyretic and anti-infective medications were given. Although symptomatic treatment can relieve fever symptoms, symptoms easily flare up again two to three days after taking the drug. Later, the patient suffered from fever again during the COVID-19 epidemic and was sent to our hospital for isolation and treatment. During this hospitalization, chest CT examination is mandatory for all patients in order to meet the requirements of epidemic prevention and control. This led to the inadvertent discovery of a large cystic solid mass in the right thoracic cavity communicating with the esophageal lumen. The patient was preliminarily diagnosed as giant midesophageal diverticulum after three-dimensional CT image reconstruction of the chest was reviewed. Considering the patient’s persistent fever with poor nutritional status, we decided to temporarily place two gastric tubes (diverticulum decompression and gastrointestinal nutrition), and antibiotics were used at the same time as another main treatment. However, after the symptoms eased and nutritional status improved, he refused all further treatment. We believe that this patient’s diverticulum is very classic, and the treatment plan is highly integrated with the needs of epidemic prevention and control and achieves a satisfactory therapeutic effect, so we hope to provide colleagues with new diagnosis and treatment enlightenment through this case.Keywords: giant midesophageal diverticulum, symptom, treatment, imaging

Lingdun Zhuge,1,2,* Binhao Huang,1,2,* Juntao Xie,1,2 Zhendong Gao,1,2 Difan Zheng,1,2 Shanbo Zheng,1,2 Jiaqing Xiang,1,2 Jie Zhang3 1Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 3Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jie ZhangDepartment of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of ChinaTel +86 189 30598097Email zhangjie2289@hotmail.comObjective: The aim of this study was to construct the immunoscore (IS) to facilitate the prediction of postoperative survival and benefit from adjuvant chemotherapy (ACT) in esophageal squamous cell carcinoma (ESCC).Methods: A total of 249 patients who received radical esophagectomy at Fudan University Shanghai Cancer Center were divided into training set and testing set. Eighty-nine patients with ESCC from TCGA database were enrolled into the validation set. Myeloid cells in tumor microenvironment were evaluated by immunohistochemistry or CIBERSORT, and then were included into a LASSO Cox regression model to construct the immunoscore. The predictive value of the immunoscore for prognosis after surgery or ACT was analyzed.Results: The immunoscore was constructed by four types of myeloid cells including macrophages, neutrophils, mast cells, and dendritic cells and was demonstrated as IS=2^(0.527719*M&phis; − 0.2604269*MC-0.4812935*DC-0.4519706*Neu). The overall survival was significantly different between two immunotypes, which were divided according to the immunoscore, in all sets (P< 0.001, P=0.005, and P=0.002, respectively). Immunotype A was identified as an independent predictor for survival benefit in all three sets (HR=2.068, P=0.005; HR=2.028, P=0.007; HR=6.474, P=0.007; respectively). In patients who received ACT, immunotype A was significantly related to longer overall survival both in the training set (P< 0.001) and in the testing set (P=0.011). The nomogram based on immunotype and other clinicopathological factors showed good efficiency of predicting response to ACT. Finally, several important cytokines and pathways were highly enriched in immunoscore A subgroup.Conclusion: The immunoscore was an effective prognostic predictor in ESCC for patients undergoing surgical resection and receiving ACT.Keywords: adjuvant chemotherapy, prognosis, immunoscore, esophageal squamous cell carcinoma

Chengcheng Pu,1,* Bingjie Huang,1,* Tianhang Zhou,1 Zhang Cheng,1 Yi Wang,2 Chuan Shi,1 Xin Yu1 1Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, People’s Republic of China; 2Neuropsychology and Applied Cognitive Neuroscience Laboratory, CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Department of Psychology, University of Chinese Academy of Sciences, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xin Yu; Chuan ShiPeking University Sixth Hospital, 51 Huayuan North Road, Beijing 100089, People’s Republic of ChinaEmail yuxin@bjmu.edu.cn; shichuan@bjmu.edu.cnObjective: To investigate the gender differences in the efficacy and side effects of three frequently used antipsychotic medicines (risperidone, olanzapine, aripiprazole) for patients with first-episode schizophrenia during the first year of treatment.Methods: A total of 569 patients with first-episode schizophrenia were randomly assigned to risperidone, olanzapine, and aripiprazole groups. All patients were treated according to their actual clinical needs. Clinical efficacies were assessed by the Positive and Negative Symptom Scale (PANSS) and side effects were assessed by the Udvalg for Kliniske Undersogelser Side-Effect scale (UKU). All assessments were completed at baseline and at 1, 2, 3, 6, 9, and 12 months.Results: Males had higher baseline PANSS total scores and PANSS negative and general pathological scores. No significant interactions were found between treatment time and gender in psychopathology improvements in all three groups. In the end of the first year, female patients receiving risperidone reported more dermatological symptoms (rashes) than males, female patients receiving olanzapine reported more autonomic side effects and dermatological symptoms than males, and female patients receiving aripiprazole reported more psychotic side effects than males.Conclusion: Gender differences exhibited in response to antipsychotic treatments for Chinese patients with first-episode schizophrenia. After the first year of antipsychotic treatment, drug-related side effects were more likely presented in female patients than male patients.Keywords: first-episode schizophrenia, gender difference, antipsychotic treatment, treatment response, side effects

Wenjing Pei,1,2 Biying Huang,1,2 Sijie Chen,1,2 Long Wang,3 Yan Xu,1,2 Chengcheng Niu1,2 1Department of Ultrasound Diagnosis, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of China; 2Research Center of Ultrasonography, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of China; 3Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People’s Republic of ChinaCorrespondence: Chengcheng NiuDepartment of Ultrasound Diagnosis, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of ChinaEmail niuchengcheng@csu.edu.cnBackground: Traditional nanoparticle-based drug delivery systems suffer from several limitations, such as easy clearance from blood and inaccurate targeting.Materials and Methods: Here, we developed platelet membrane-coated nanoparticles (PM-NPs) to improve the precise delivery of drugs to tumor sites and enable a more efficient photothermal therapy (PTT) treatment.Results: Mimicking the natural platelet membrane, nanoparticles containing drugs and photothermal agents were not recognized and cleared by the immune system; they could circulate in the blood for a long time and accumulate more efficiently at the tumor site, thus releasing more antitumor drugs and achieving better PTT effects. It is worth mentioning that, in this study, we found that tumors in mice treated with the platelet-mimicking nanoparticles were completely eliminated without recurrence during the observation period (up to 18 days).Conclusion: This study provides a new strategy to design delivery systems of drugs or photothermal agents, whether in biotherapy or other fields.Keywords: platelet-mimicking, drug delivery, IR780, doxorubicin, chemo-photothermal therapy

Shuwen Yue,1,* Ning Xue,2,* Honglei Li,3 Zhen Chen,1 Baosheng Huang,4 Xing Wang1 1Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China; 2Department of Acupuncture, Jurong Hospital Affiliated to Jiangsu University, Zhenjiang, People’s Republic of China; 3Department of Pharmacy, Kangda College of Nanjing Medical University, Lianyungang, People’s Republic of China; 4Department of Neurosurgery, Sir Run Run Hospital, Nanjing Medical University, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xing WangChina Pharmaceutical University, Nanjing, Jiangsu 211199, People’s Republic of ChinaEmail star10000@sina.comBaosheng HuangSir Run Run Hospital, Nanjing Medical University, No. 101, Longmiandadao, Jiangning District, Nanjing, Jiangsu 211166, People’s Republic of ChinaEmail labskcpu@sina.comAim: Renal injury induced by diabetes is reported to be associated with inflammation. Isomangiferin (ISO), a xanthone C-glucoside from the Cyclopia subfamily, exhibits many pharmacological properties. This study aimed to evaluate the protection of ISO against renal damage in diabetic mice.Methods: Serum glucose, insulin, uric acid, creatinine, total cholesterol (TC), triglyceride (TG), and inflammatory cytokines in serum and the kidney of db/db diabetes model mice were detected. The components of high mobility group protein B1 (HMGB1)/NACHT leucine-rich repeat- and PYD-containing 3 (NLRP3)/nuclear factor kappa-B (NF-κB) pathway in the kidney were detected by Western blot and immunohistochemical analysis.Results: ISO improved lipid profile and glucose tolerance, and inhibited the production of inflammatory cytokines in a db/db model mice. Moreover, ISO decreased biochemical indexes in the serum and inhibited the activation of HMGB1/NLRP3/NF-κB signaling in the kidney of db/db model mice.Conclusion: ISO provides protection against renal injury via inhibiting HMGB1/NLRP3/NF-κB signaling in a diabetic mouse model.Keywords: isomangiferin, renal injury, inflammation, HMGB1/NLRP3/NF-κB, diabetics

Baozhen Huang,1 Yanlin Niu,2 Weiguo Zhao,3 Pengtao Bao,4 Diangeng Li1,5 1Nanlou Respiratory Diseases Department, 2nd Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Beijing Center for Disease Prevention and Control, Institute for Nutrition and Food Hygiene, Beijing, People’s Republic of China; 3Department of Respiratory Medicine, The Eighth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, The Eighth Medical Center of Chinese, Beijing, People’s Republic of China; 5Department of Nephrology, Chinese PLA General Hospital, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, People’s Republic of ChinaCorrespondence: Diangeng LiNanlou Respiratory Diseases Department, 2nd Medical Center of Chinese PLA General Hospital, 28th Fuxing Road, Beijing 100853, People’s Republic of ChinaEmail lidiangeng@126.comPengtao BaoDepartment of Pulmonary and Critical Care Medicine, The Eighth Medical Center of Chinese PLA General Hospital, 17th Heishanhu Road, Beijing 100093, People’s Republic of ChinaEmail bao03@163.comBackground: The rapid outbreak of coronavirus disease 2019 (COVID-19) is a major health concern, in response to which widespread risk factor research is being carried out.Objective: To discover how physical activity and lifestyle affect the epidemic as well as the disease severity and prognosis of COVID-19 patients.Methods: This multicenter, retrospective cohort study included 203 adults infected with COVID-19 and 228 uninfected adults in three Chinese provinces, with 164 (80.7%) of the infected participants and 188 (82.5%) of the uninfected participants answering a doctor-administered telephone questionnaire on lifestyle. The binary logistic regression model and the ordinal logit model were used to observe relevance.Results: Comparing sick and non-sick patients, we found that irregular exercise (P=0.004), sedentary lifestyle (P=0.010), and overexertion (P< 0.001) may be associated with the susceptibility to COVID-19. In symptomatic patients, using the recommended status as a reference, risk of severe infection increased with decreased sleep status, being 6.729 (95% CI=2.138– 21.181) times higher for potentially appropriate sleep (P=0.001) and peaking at 8.612 (95% CI=1.913– 38.760) times higher for lack of sleep (P=0.005). Reduction in average daily sleep time significantly increased the likely severity (P=0.002).Discussion: Through further examination of damage of external lung organs, we found that lack of sleep affected not only disease severity but also prognosis. Based on these findings, the public should prioritize a healthy lifestyle and get adequate sleep in response to the outbreak. The study of life habits may bring new ideas for the prevention and treatment of COVID-19.Keywords: COVID-19, disease severity, sleep status, damage of external lung organs

Sijie Chen,1– 3 Biying Huang,1,2 Wenjing Pei,1,2 Long Wang,4 Yan Xu,1,2 Chengcheng Niu1,2 1Department of Ultrasound Diagnosis, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of China; 2Research Center of Ultrasonography, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of China; 3Department of Ultrasound Diagnosis, Changsha Central Hospital, Nanhua University, Changsha, Hunan 410014, People’s Republic of China; 4Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People’s Republic of ChinaCorrespondence: Chengcheng NiuDepartment of Ultrasound Diagnosis, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of ChinaEmail niuchengcheng@csu.edu.cnBackground: Although photothermal therapy (PTT) and photodynamics therapy (PDT) have both made excellent progress in tumor therapy, the effectiveness of using PTT or PDT alone is dissatisfactory due to the limitations of the penetration depth in PTT and the hypoxic microenvironment of tumors for PDT. Combination phototherapy has currently become a burgeoning cancer treatment.Methods and Materials: In this work, a mitochondria-targeting liquid perfluorocarbon (PFC)-based oxygen delivery system was developed for the synergistic PDT/photothermal therapy (PTT) of cancer through image guiding.Results: Importantly, these nanoparticles (NPs) can effectively and accurately accumulate in the target tumor via the enhanced permeability and retention (EPR) effect.Conclusion: This approach offers a novel technique to achieve outstanding antitumor efficacy by an unprecedented design with tumor mitochondria targeting, oxygen delivery, and synergistic PDT/PTT with dual-imaging guidance.Keywords: IR780, mitochondria-targeting, perfluorocarbon, photodynamic therapy, photothermal therapy

Banggao Huang,1 Danhong Zhou,2 Xinmian Huang,1 Xiaobo Xu,1 Zhihui Xu1 1Department of Urology, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang Province, People’s Republic of China; 2Department of Surgery, The Third People’s Hospital of Hangzhou, Hangzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Zhihui XuDepartment of Urology, Zhejiang Provincial People’s Hospital, No. 158, Shangtang Road, Hangzhou 310014, People’s Republic of ChinaTel +86-571-87666666Fax +86-571-85335800Email xuzhihui_xzh1@163.comBackground: Emerging evidence indicates that circular RNAs (circRNAs), which form as covalently closed loops, play a regulatory role in various types of cancer, including prostate cancer (PCa). CircSLC19A1, one kind of circRNA, was subjected to the study and its role in PCa was explored.Methods: Expressions of circSLC19A1, miR-326 and MAPK1 in PCa tissues and cells were assessed by qRT-PCR. CircSLC19A1 was identified by RNase R treatment. The binding relations between circSLC19A1 and miR-326 and between miR-326 and MAPK1 were predicted by RegRNA2.0 or Targetscan7.2 and further confirmed by dual-luciferase reporter assay. Pearson correlation analysis of the correlation among circSLC19A1, miR-326 and MAPK1 was performed. CCK-8, cell colony formation, wound healing and Transwell assays were used to assess PCa cell viability, proliferation, migration and invasion, respectively.Results: CircSLC19A1 expression was up-regulated in PCa tissue and cell cytoplasm. Silencing circSLC19A1 inhibited PCa cell viability, proliferation, migration, invasion and miR-326 expression. MiR-326 inhibitor promoted the luciferase activities of circSLC19A1 and MAPK1, increased MAPK1 expression and facilitated PCa cell progression. MiR-326 expression was down-regulated in PCa tissue and there was a negative correlation between miR-326 and circSLC19A1 expressions. MAPK1 expression was up-regulated in PCa tissue. There was a negative correlation between MAPK1 and miR-326 expressions as well as a positive correlation between MAPK1 and circSLC19A1 expressions. Silencing MAPK1 promoted the viability, proliferation, migration, and invasion of PCa cells co-transfected with siRNA-circSLC19A1a and miR-326 inhibitor.Conclusion: CircSLC19A1 silencing inhibited PCa cell proliferation, migration and invasion through regulating miR-326/MAPK1 axis.Keywords: circSLC19A1, miR-326, MAPK1, prostate cancer, proliferation, migration, invasion

Shuilong Zhang,1 Qiang Wang,1 Dewei Li,1 Bo Huang,2 Xia Hou,3 Dongliang Wang,1 Zhifu Xiao,1 Hongjing Meng,1 Yuhang Zhang,1 Lingxiang Dong1 1Department of Thyroid Surgery, Shanxi Provincial People’s Hospital, Taiyuan, People’s Republic of China; 2Department of Gastrointestinal Pancreas, Hernia and Abdominal Wall Surgery, Shanxi Provincial People’s Hospital, Taiyuan, People’s Republic of China; 3Department of Chest Radiotherapy, Tumor Hospital of Shanxi Province, Taiyuan, People’s Republic of ChinaCorrespondence: Shuilong ZhangDepartment of Thyroid Surgery, Shanxi Provincial People’s Hospital, No. 29 Shuangtasi Street, Taiyuan, Shanxi 030012, People’s Republic of ChinaTel +86-0351-4960327Email slzhang_shanxi@126.comBackground: Papillary thyroid carcinoma (PTC) is the most common type of thyroid malignancy, and cases have been rising steadily worldwide in the past few decades. Despite great progress having been made in surgery and chemotherapy for PTC, the survival rate of PTC patients has not increased significantly. Therefore, there is an urgent need to explore novel treatment strategies.Materials and Methods: The levels of circRNA_103598, miR-23a-3p and IL-6 mRNA in PTC tissues and cells were examined by qRT-PCR assay. Cell proliferation and IC50 values of oncolytic vaccinia virus (OVV) were detected by CCK-8 assay. A dual-luciferase reporter assay was performed to detect the relationships among circRNA_103598, miR-23a-3p and IL-6. ELISA was carried out to detect the expression of IL-6.Results: We found that circRNA_103598 was increased in PTC tissues and cell lines and acted as a sponge for miR-23a-3p. Moreover, knockdown of miR-23a-3p suppressed the OVV-mediated antitumor effect and cell proliferation in PTC. In addition, we revealed that circRNA_103598 bound to miR-23a-3p as a sponge to promote IL-6 expression.Conclusion: Our study first revealed the high expression and oncogenic function of circRNA_103598 in PTC cells. Then, circRNA_103598 sponged miR-23a-3p to upregulate IL-6 expression, with the resulted that cell proliferation was promoted and the OVV-mediated antitumor effect was enhanced by strengthening the viral replication, providing new insights into future therapy for PTC.Keywords: OVV, cell proliferation, circRNA_103598, miR-23a-3p, IL-6, PTC

Jianjun Zhu,1,2,* Yong Fei,2,* Jiajia Deng,2 Bin Huang,2 Ming Yao2 1The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2Department of Anesthesiology and Pain Research Center, The First Hospital of Jiaxing or The Affiliated Hospital of Jiaxing University, Jiaxing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ming YaoDepartment of Anesthesiology and Pain Research Center, The First Hospital of Jiaxing or The Affiliated Hospital of Jiaxing University, No. 1882 South Zhonghuan Road, Nanhu District, Jiaxing City, Zhejiang Province, People’s Republic of ChinaTel +86 573 13456218632Email jxyaoming666@163.comPurpose: In CT-guided dorsal root ganglion puncture, especially T1–T3, it is often difficult to reach the target due to obstruction of the lamina, transverse process, and ribs. Therefore, a safe and effective puncture method with high success rate is urgently needed to guide us in our clinical work.Patients and Methods: A total of 44 patients with dorsal root ganglion underwent pulsed radiofrequency therapy for pain T1–T3 herpes zoster neuralgia at the pain department of Affiliated Hospital of Jiaxing University from January 2019 to February 2020 were retrospectively reviewed. Each patient underwent the same surgical method. The patient’s operation time, CT filming times, nerve electrophysiological tests, the NRS scores before and after operation at one, four, eight, and 12 weeks, Pittsburgh Sleep Disorder Index (PSQI), dosage of gabapentin capsules and tramadol hydrochloride sustained-release tablets, surgical complications and incidence of postherpetic neuralgia (PHN) were recorded.Results: The success rate of 44 patients who underwent puncturing of the costal transverse process to T1 target was 88.46%, to T2 target was 90.68%, and to T3 target was 90.68%, respectively. The NRS score of patients before surgery was 5.48± 0.59, and those at one, four, eight, and 12 weeks after surgery were 3 (3,3), 1 (1,2), 0 (0, 1), and 0 (0, 0). The difference of NRS score between preoperation and postoperation is statistically significant. No intraoperative and postoperative complications occurred. Two patients developed PHN after standard treatment, and the incidence of it was 4.55%.Conclusion: CT-guided puncturing of the costal transverse process in the dorsal root ganglion of patients who underwent pulsed radiofrequency treatment of T1–T3 herpes zoster neuralgia showed a high success rate and is considered to be safe and effective.Keywords: costotransverse joint, pulsed radiofrequency, dorsal root ganglion, herpes zoster neuralgia

Jing-Yi Ye,1 Zhong-Yun Chen,1 Chuan-Li Huang,1 Bei Huang,2 Yu-Rong Zheng,2 Ying-Feng Zhang,1 Ban-Yi Lu,2 Lin He,2 Chang-Shun Liu3 ,* Xiao-Ying Long1,4, * 1School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, People’s Republic of China; 2School of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, People’s Republic of China; 3School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 4Guangdong Engineering & Technology Research Center of Topical Precise Drug Delivery System, Guangdong Pharmaceutical University, Guangzhou 510006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chang-Shun LiuSouthern Medical University, No. 1023-1063 of Shatai South Road, Guangzhou, Guangdong 510515, People’s Republic of ChinaTel +86 13430301554Email lcshun1225@163.comXiao-Ying LongGuangdong Pharmaceutical University, No. 280 of Waihuan East Road, Guangzhou, Guangdong 510006, People’s Republic of ChinaTel +86 13798171092Fax +86 2039352174Email longxy3156@163.comObjective: A non-lipolysis nanoemulsion (NNE) was designed to reduce the first-pass metabolism of raloxifene (RAL) by intestinal UDP-glucuronosyltransferases (UGTs) for increasing the oral absorption of RAL, coupled with in vitro and in vivo studies.Methods: In vitro stability of NNE was evaluated by lipolysis and the UGT metabolism system. The oral bioavailability of NNE was studied in rats and pigs. Finally, the absorption mechanisms of NNE were investigated by in situ single-pass intestinal perfusion (SPIP) in rats, Madin-Darby canine kidney (MDCK) cells model, and lymphatic blocking model.Results: The pre-NNE consisted of isopropyl palmitate, linoleic acid, Cremophor RH40, and ethanol in a weight ratio of 3.33:1.67:3:2. Compared to lipolysis nanoemulsion of RAL (RAL-LNE), the RAL-NNE was more stable in in vitro gastrointestinal buffers, lipolysis, and UGT metabolism system (p < 0.05). The oral bioavailability was significantly improved by the NNE (203.30%) and the LNE (205.89%) relative to the suspension group in rats. However, 541.28% relative bioavailability was achieved in pigs after oral NNE intake compared to the suspension and had two-fold greater bioavailability than the LNE (p < 0.05). The RAL-NNE was mainly absorbed in the jejunum and had high permeability at the intestine of rats. The results of both SPIP and MDCK cell models demonstrated that the RAL-NNE was absorbed via endocytosis mediated by caveolin and clathrin. The other absorption route, the lymphatic transport (cycloheximide as blocking agent), was significantly improved by the NNE compared with the LNE (p < 0.05).Conclusion: A NNE was successfully developed to reduce the first-pass metabolism of RAL in the intestine and enhance its lymphatic transport, thereby improving the oral bioavailability. Altogether, NNE is a promising carrier for the oral delivery of drugs with significant first-pass metabolism.Keywords: non-lipolysis nanoemulsion, raloxifene, first-pass metabolism, stability, bioavailability, endocytosis

Sijia Guo1,2 ,* Jing Lu,1– 3,* Yufang Wang,2 Yuqin Li,2 Binxin Huang,2 Yuxin Zhang,2 Wenhui Gong,2 Dezhong Yao,1– 3 Yin Yuan,1 Yang Xia1– 3 1The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2Center for Information in BioMedicine, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 3Research Unit of NeuroInformation, Chinese Academy of Medical Sciences, 2019RU035, Chengdu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yin Yuan; Yang Xia Email 1140587540@qq.com; xiayang@uestc.edu.cnBackground: Music has shown positive effects on pain management in previous studies. However, the relationship between musical emotional types and therapeutic effects remains unclear. To investigate this issue, this study tested three typical emotional types of music and discussed their neural mechanisms in relation to pain modulation.Subjects and Methods: In this experiment, 40 participants were exposed to cold pain under four conditions: listening to happy music, listening to neutral music, listening to sad music and no sound. EEG and pain thresholds were recorded. The participants were divided into the remission group and the nonremission group for analysis. Differences among conditions were quantified by the duration of exposure to the pain-inducing stimulus in the remission group. EEG data were obtained using a fast Fourier transform (FFT) and then correlated with the behavioral data.Results: We found that sad music had a significantly better effect on alleviating pain, as a result of brain oscillations in a higher beta band and the gamma band at the O2 and P4 electrodes. The comparison between the remission group and the nonremission group suggested that personality may affect music-induced analgesia, and dominance, liveliness and introvert and extrovert personality traits were associated with pain modulation by sad music. Additionally, in the network analysis, we compared brain networks under the three conditions and discussed the possible mechanisms underlying the better analgesic effect of sad music.Conclusion: Sad music may have a better effect on alleviating pain, and its neural mechanisms are also discussed. This work may help understand the effects of music on pain modulation, which also has potential value for clinical use.Keywords: pain, music-induced analgesia, personality, EEG, brain network

Zezheng Liu,1,* Wenquan Liang,1,* Dawei Kang,1 Qingjing Chen,1 Zhicong Ouyang,1 Huibo Yan,1 Bin Huang,1 Dadi Jin,1 Yinkui Chen,2 Qingchu Li1 1Academy of Orthopedics, Guangdong Province, Department of Spine Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Oncology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qingchu LiDepartment of Spine Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, People’s Republic of ChinaEmail lqc16@263.netYinkui ChenDepartment of Oncology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, People’s Republic of ChinaEmail clytze2@126.comIntroduction: Estrogen deficiency leads to bone loss in postmenopausal osteoporosis, because bone formation, albeit enhanced, fails to keep pace with the stimulated osteoclastic bone resorption. The mechanism driving this uncoupling is central to the pathogenesis of postmenopausal osteoporosis, which, however, remains poorly understood. We previously found that Cxcl9 secreted by osteoblasts inhibited osteogenesis in bone, while the roles of Cxcl9 on osteoclastic bone resorption and osteoporosis are unclear.Materials and Methods: Postmenopausal osteoporosis mouse model was established by bilateral surgical ovariectomy (OVX). In situ hybridization was performed to detect Cxcl9 mRNA expression in bone. ELISA assay was conducted to assess Cxcl9 concentrations in bone and serum. Cxcl9 activity was blocked by its neutralizing antibody. Micro-CT was performed to determine the effects of Cxcl9 neutralization on bone structure. Cell Migration and adhesion assay were conducted to evaluate the effects of Cxcl9 on osteoclast activity. TRAP staining and Western blot were performed to assess osteoclast differentiation. CXCR3 antagonist NBI-74,330 or ERK antagonist SCH772984 was administered to osteoclast to study the effects of Cxcl9 on CXCR3/ERK signaling.Results: Cxcl9 was expressed and secreted increasingly in OVX mice bone. Neutralizing Cxcl9 in bone marrow prevented bone loss in the mice by facilitating bone formation as well as inhibiting bone resorption. In vitro, Cxcl9 secreted from osteoblasts facilitated osteoclast precursors adhesion, migration and their differentiation into mature osteoclasts. The positive role of osteoblastic Cxcl9 on osteoclasts was eliminated by blocking CXCR3/ERK signaling in osteoclasts. Estrogen negatively regulated Cxcl9 expression and secretion in osteoblasts, explaining the increased Cxcl9 concentration in OVX mice bone.Conclusion: Our study illustrates the roles of Cxcl9 in inhibiting bone formation and stimulating bone resorption in osteoporotic bone, therefore providing a possible therapeutic target to the treatment of postmenopausal osteoporosis.Keywords: postmenopausal osteoporosis, bone resorption, osteoclast, Cxcl9

Anyang Li,1,2 Luhui Wang,2 Qi Jiang,2 Wenlie Wu,2 Baoyou Huang,2 Haiyan Zhu1,2 1Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200126, People’s Republic of China; 2Department of Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, People’s Republic of ChinaCorrespondence: Haiyan ZhuDepartment of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200126, People’s Republic of ChinaTel +86 57755069162Email zhuhaiyandoc@sina.comPurpose: Stage IIIC1 cervical cancer showed heterogeneous in oncologic outcomes with highly variable survival rates. Our objective was to determine the prognostic significance of removed and metastatic pelvic lymph node status and further perform risk stratification in patients with stage IIIC1p cervical cancer.Patients and Methods: Patients with stage IIIC1p cervical cancer and undergoing radical hysterectomy with lymphadenectomy in 2008– 2018 were retrospectively analyzed. Patients’ stage was classified using the revised 2018 International Federation of Gynecology and Obstetrics (FIGO) staging schema. Univariate and multivariable models were used to examine the association between removed and metastatic lymph node status and recurrence-free survival/overall survival.Results: During a median follow-up of 34 months, 73 relapses and 44 deaths were observed among 273 patients with stage IIIC1p cervical cancer. Parametrial involvement and metastatic lymph node ratio (mLNR) were identified as independent predictors for recurrence-free survival. Parametrial involvement and mLNR were independent predictors for overall survival. A stratification system was then created based on parametrial involvement and mLNR. A total of 123 (45.1%), 127 (46.5%) and 23 (8.4%) patients were classified into the low-risk, intermediate-risk, and high-risk groups, with as a 5-year recurrence-free survival of 81.7%, 51.1%, 38%, respectively. Compared to the low-risk group, the intermediate- and high-risk groups had a significantly greater risk of recurrence and death.Conclusion: The prognosis of stage IIIC1p patients varied significantly. A risk stratification system based on parametrial involvement and mLNR successfully separated patients into low, intermediate, and high-risk group. Our findings could facilitate the practical use of further stratification in Stage IIIC1p cervical cancer.Keywords: cervical cancer, stage IIIC1p, pelvic lymph node, prognosis