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Aili Guan,1 Tao He,1 Xingang Huang,2 Wei Xia,1 Yibing Shao1 1Department of Cardiology, Heart Center, Qingdao Municipal Hospital, Qingdao, Shandong, 266071, People’s Republic of China; 2Department of Pathology, Qingdao Municipal Hospital, Qingdao, Shandong, 266071, People’s Republic of ChinaCorrespondence: Yibing Shao, Email syb2004@yeah.netAbstract: A case of fat liquefaction and fat particles in the pacemaker pocket observed in a female patient 12 years after implantation. The patient had no symptoms and no signs of infection or other discomfort of the heart and pacemaker pocket. The biochemical analysis showed a slight increase in cardiac troponin T, 0.026 ng/mL (reference range, < 0.016 ng/mL), a high increase in total cholesterol, 8.70 mmol/L (reference range, < 5.18 mmol/L), and low density lipoprotein, 5.38 mmol/L (reference range, < 3.37 mmol/L). Thick yellow liquid was seen to flow out of the pacemaker pocket when the pocket was opened, and many fat particles were found adhering to the wall of the pacemaker pocket during the pacemaker replacement procedure. Fat and fibrillar connective tissue with a few inflammatory cells, local tissue degeneration and necrosis were shown on immunohistochemical staining and no bacterial growth including anaerobic bacteria was observed. The aseptic necrosis of post-implantation complications is helpful for differential diagnosis in CIED complication. Moreover, the identification of fat liquefaction has important clinical significance for patient management and surgical decision-making.Keywords: fat liquefaction, fat particles, CIED pocket, CIED complications, CIED replacement

Ling Hou,1,2,&ast; Ke Su,1,&ast; Jinbo Zhao,1 Ting He,2 Yuanhong Li1 1Cardiovascular Disease Center, Central Hospital of Tujia and Miao Autonomous Prefecture, Enshi, Hubei Province, People’s Republic of China; 2Department of Central Hospital of Tujia and Miao Autonomous Prefecture, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanhong Li, Email lyh0101@vip.163.comBackground: Coronary heart disease (CHD) is a leading cause of mortality worldwide, with atrial fibrillation (AF) being a common complication. Chronic inflammatory responses play a significant role in the relationship between coronary artery disease and AF. This study aims to investigate the value of the multi-inflammatory index (MII) in predicting the occurrence of atrial fibrillation in patients with coronary heart disease.Methods: A retrospective analysis was conducted on patients who visited our hospital from January 1, 2020, to December 31, 2023, including a total of 1392 patients. Clinical data and laboratory results were collected. Feature selection was performed using the Boruta algorithm. Five machine learning models were constructed: Logistic Regression, Decision Tree, Elastic Net, Light Gradient Boosting Machine (LightGBM), and Multilayer Perceptron. Model performance was evaluated using five-fold cross-validation. SHAP values were utilized to analyze feature importance and model interpretability.Results: The study included 1302 patients without AF and 90 patients with AF. Patients with AF had significantly higher MII compared to those without AF (10.02 vs 4.79). Thirteen variables most related to AF occurrence were selected using the Boruta algorithm. The LightGBM model outperformed others, showing the highest accuracy and calibration in both training and test sets. In the training set, LightGBM achieved an AUC of 0.958, accuracy of 0.851, and sensitivity of 0.943, while in the testing set, it achieved an AUC of 0.757 and accuracy of 0.821. SHAP analysis indicated that age, heart rate, and MII were the primary predictors of AF occurrence.Conclusion: The LightGBM model demonstrated adequate sensitivity and accuracy. The multi-inflammatory index plays a crucial role in predicting atrial fibrillation in patients with coronary heart disease.Keywords: atrial fibrillation, coronary heart disease, multi-inflammatory index, machine learning models, light gradient boosting machine

Ling Hou,1,2,&ast; Ke Su,1,&ast; Ting He,1 Jinbo Zhao,1 Yuanhong Li1 1Cardiovascular Disease Center, Central Hospital of Tujia and Miao Autonomous Prefecture, Hubei University of Medicine, Enshi, Hubei Province, People’s Republic of China; 2Department of Central Hospital of Tujia and Miao Autonomous Prefecture, Hubei University of Medicine, Shiyan, Hubei Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanhong Li, Email lyh0101@vip.163.comBackground: Percutaneous coronary intervention (PCI) is the primary treatment for acute myocardial infarction (AMI). However, in-stent restenosis (ISR) remains a significant limitation to the efficacy of PCI. The cholesterol-to-lymphocyte ratio (CLR), a novel biomarker associated with inflammation and dyslipidemia, may have predictive value for ISR. Deep learning-based models, such as the multilayer perceptron (MLP), can aid in establishing predictive models for ISR using CLR.Methods: A retrospective analysis was conducted on clinical and laboratory data from 1967 patients. The Boruta algorithm was employed to identify key features associated with ISR. An MLP model was developed and divided into training and validation sets. Model performance was evaluated using ROC curves and calibration plots.Results: Patients in the ISR group exhibited significantly higher levels of CLR and low-density lipoprotein (LDL) compared to the non-ISR group. The Boruta algorithm identified 21 important features for subsequent modeling. The MLP model achieved an AUC of 0.95 on the validation set and 0.63 on the test set, indicating good predictive performance. Calibration plots demonstrated good agreement between predicted and observed outcomes. Feature importance analysis revealed that the number of initial stent implants, hemoglobin levels, Gensini score, CLR, and white blood cell count were significant predictors of ISR. Partial dependence plots (PDP) confirmed CLR as a key predictor for ISR.Conclusion: The CLR, as a biomarker that integrates lipid metabolism and inflammation, shows significant potential in predicting coronary ISR. The MLP model, based on deep learning, demonstrated robust predictive capabilities, offering new insights and strategies for clinical decision-making.Keywords: cholesterol-to-lymphocyte ratio, deep learning, multilayer perceptron, Boruta algorithm, in-stent restenosis

Ling Hou,1,&ast; Ke Su,2,&ast; Ting He,1 Jinbo Zhao,2 Yuanhong Li2 1Central Hospital of Tujia and Miao Autonomous Prefecture, Hubei University of Medicine, Shiyan, Hubei Province, People’s Republic of China; 2Cardiovascular Disease Center, Central Hospital of Tujia and Miao Autonomous Prefecture, Hubei University of Medicine, Enshi, Hubei Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanhong Li, Email lyh0101@vip.163.comObjective: This study aims to investigate their correlation and predictive utility for in-stent restenosis (ISR) in patients with acute coronary syndrome (ACS) following percutaneous coronary intervention (PCI).Methods: We collected medical records of 668 patients who underwent PCI treatment from January 2022 to December 2022. Based on follow-up results (ISR defined as luminal narrowing ≥ 50% on angiography), all participants were divided into ISR and non-ISR groups. The XGBoost machine learning (ML) model was employed to identify the optimal predictive variables from a set of 31 variables. Discriminatory ability was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC), while calibration and performance of the prediction models were assessed using the Hosmer-Lemeshow (HL) test and calibration plots. Clinical utility of each model was evaluated using decision curve analysis (DCA).Results: In the XGBoost importance ranking of predictive factors, LMR and RC ranked first and fourth, respectively. The AUC of the entire XGBoost ML model was 0.8098, whereas the model using traditional stepwise backward regression, comprising five predictive factors, had an AUC of 0.706. The XGBoost model showed superior predictive performance with a higher AUC, indicating better discrimination and predictive accuracy for ISR compared to traditional methods.Conclusion: LMR and RC are identified as cost-effective and reliable biomarkers for predicting ISR risk in ACS patients following drug-eluting stent (DES) implantation. LMR and RC represent cost-effective and reliable biomarkers for predicting ISR risk in ACS patients following drug-eluting stent implantation. Enhances the accuracy and clinical utility of ISR prediction models, offering clinicians a robust tool for risk stratification and personalized patient management.Keywords: Lymphocyte-to-monocyte ratio, residual cholesterol, XGBoost, machine learning, in-stent restenosis, drug-eluting stent

Yu Zhang,1– 4 Tingting He,1– 4 Yu Hu,1– 4 Chenlin Gao2– 5 1Graduate School, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2Cardiovascular and Metabolic Diseases Key Laboratory of Luzhou, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 3Sichuan Clinical Research Center for Nephropathy, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 4Metabolic Vascular Disease Key Laboratory of Sichuan Province, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 5Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of ChinaCorrespondence: Chenlin Gao, Department of Endocrinology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China, Tel +86-830-3165361, Email gaochenlin00@swmu.edu.cnPurpose: This manuscript performed a meta-analysis to compare the effects of a low-fat diet (LFD) and a low-carbohydrate diet (LCD) on body weight and lipid levels in adolescents with overweight and obesity.Patients and Methods: PubMed and other databases were searched for the full-text literature comparing LFD and LCD up to November 2023 using a subject plus free word strategy, with search terms such as “low-fat diet”, “low-carbohydrate diet”, “obesity”, “weight”, “adolescents”, “RCT”, and so on. Two independent reviewers selected promising candidate trials, collected the data, and assessed the quality of the trials. RevMan 5.3 software was utilized to conduct a meta-analysis of the randomized controlled trials (RCTs) that were included.Results: 5 RCTs with 192 participants were included in this meta-analysis. Weight (mean difference − 2.81; 95% CI − 5.38 to − 0.25), Body Mass Index (BMI) (− 1.13; 95% CI − 2.14 to − 0.11) and Triglyceride (TG) (− 0.36; 95% CI − 0.46 to − 0.27) of the LCD were significantly lower than that of the LFD. At the same time, the high-density lipoprotein cholesterol (HDL) levels of the LCD were significantly higher than those of the LFD (0.08; 95% CI 0.04 to 0.12) (P < 0.05). However, there was no significant difference in the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), percent body fat, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL) between the two groups (P> 0.05).Conclusion: According to this study, LCD is more helpful in improving weight loss, HDL and TG. Thus, LCD may serve as an effective intervention for weight management in adolescents with overweight and obesity, although further research is needed to determine its long-term effects.Keywords: obesity, diet, weight loss, low-carbohydrate, low-fat

Ling Hou,1,&ast; Jinbo Zhao,2,&ast; Ting He,1,&ast; Yinhua Luo,3 Ke Su,2 Yuanhong Li,2 Ruiyang Zhu3 1Central Hospital of Tujia and Miao Autonomous Prefecture, Hubei University of Medicine, Shiyan, People’s Republic of China; 2Cardiovascular Disease Center, Central Hospital of Tujia and Miao Autonomous Prefecture, Hubei University of Medicine, Enshi, Hubei Province, People’s Republic of China; 3Center for Gene Diagnosis and Department of Clinical Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanhong Li, Cardiovascular Disease Center, Central Hospital of Tujia and Miao Autonomous Prefecture, Hubei University of Medicine, Enshi, 445400, People’s Republic of China, Email lyh0101@vip.163.com Ruiyang Zhu, Center for Gene Diagnosis and Department of Clinical Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People’s Republic of China, Email zhuruiyang@whu.edu.cnAbstract: Granulomatosis with polyangiitis (GPA) is a necrotizing granulomatous vasculitis classified as an autoimmune small-vessel vasculitis. Clinically, approximately 80% of affected organs in GPA involve the upper/lower respiratory tract and kidneys, with cardiovascular system involvement being rare. Here, we report a case of a 50-year-old female patient who presented with sudden-onset chest pain lasting for 1 hour. The patient had normal body temperature, and markers of infection such as C-reactive protein and erythrocyte sedimentation rate were within normal limits. Electrocardiography revealed ST-segment elevation in inferior, precordial, and posterior leads. Emergency coronary angiography showed no significant obstructive disease, prompting consideration of vasospastic angina given the patient’s recurrent chest pain symptoms and findings on laboratory and imaging studies. The patient underwent treatment including coronary vasospasm antagonists and immunomodulation, resulting in clinical improvement and subsequent discharge. During a 7-month follow-up period, the patient did not experience any further adverse cardiovascular events.Keywords: granulomatosis with polyangiitis, vasospastic angina, case report

Tao He,1,2,&ast; Xiao-Yu Sun,1,2,&ast; Meng-Han Tong,1,2 Ming-Jie Zhang,1,2 Zhi-Jun Duan1,2 1Department of Gastroenterology, the First Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China; 2Dalian Central Laboratory of Integrative Neuro-Gastrointestinal Dynamics and Metabolism Related Diseases Prevention and Treatment, Dalian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhi-Jun Duan, Department of Gastroenterology, the First Affiliated Hospital of Dalian Medical University, No. 222 Zhongshan Road, Dalian, 161000, People’s Republic of China, Tel +86 83635963, Email cathydoctor@sina.comBackground and Aim: Obesity is association with elevated risks of erosive esophagitis (EE), and metabolic abnormalities play crucial roles in its development. The aim of the study was to assess the association between metabolic obesity phenotypes and the risk of EE.Methods: This retrospective study enrolled 11,599 subjects who had undergone upper gastrointestinal endoscopy at the First Affiliated Hospital of Dalian Medical University from January 1, 2008, to December 31, 2023. The enrolled individuals were grouped into four cohorts based on their metabolic health and obesity profiles, namely, metabolically healthy non-obesity (MHNO; n=2134, 18.4%), metabolically healthy obesity (MHO; n=1736, 15.0%), metabolically unhealthy non-obesity (MUNO; n=4290, 37.0%), and metabolically unhealthy obesity (MUO; n=3439, 29.6%). The relationships of the different phenotypes of metabolic obesity with the risks of developing EE in the different sexes and age groups were investigated by multivariate logistic regression analysis.Results: The MUNO, MHO, and MUO cohorts exhibited elevated risks of developing EE than the MHNO cohort. The confounding factors were adjusted for, and the findings revealed that the MUO cohort exhibited the greatest risk of EE, with odds ratios (ORs) of 5.473 (95% CI: 4.181– 7.165) and 7.566 (95% CI: 5.718– 10.010) for males and females, respectively. The frequency of occurrence of EE increased following an increase in proportion of metabolic risk factors. Subgroup analyses showed that the individuals under and over 60 years of age in the MHO, MUNO, and MUO cohorts exhibited elevated risks of developing EE. Further analysis suggested that obesity has a stronger influence on the risks of developing EE compared to metabolic disorders.Conclusion: Metabolic disorders and obesity are both related with an elevated risk of EE, in which obesity has a potentially stronger influence. Clinical interventions should target both obesity and metabolic disorders to reduce EE risk. Keywords: metabolic obesity phenotype, erosive esophagitis, metabolic disorders

Ling Hou,1,&ast; Jinbo Zhao,2,&ast; Ting He,2 Ke Su,2 Yuanhong Li2 1Department of Central Hospital of Tujia and Miao Autonomous Prefecture, Hubei University of Medicine, Shiyan, Hubei Province, People’s Republic of China; 2Cardiovascular Disease Center, Central Hospital of Tujia and Miao Autonomous Prefecture, Hubei University of Medicine, Enshi, Hubei Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanhong Li, Email lyh0101@vip.163.comIntroduction: Coronary artery disease (CAD) remains a significant global health challenge, with percutaneous coronary intervention (PCI) being a primary revascularization method. In-stent restenosis (ISR) post-PCI, although reduced, continues to impact patient outcomes. Inflammation and platelet activation play key roles in ISR development, emphasizing the need for accurate risk assessment tools. The systemic inflammation aggregation index (AISI) has shown promise in predicting adverse outcomes in various conditions but has not been studied in relation to ISR.Methods: A retrospective observational study included 1712 patients post-drug-eluting stent (DES) implantation. Data collected encompassed demographics, medical history, medication use, laboratory parameters, and angiographic details. AISI, calculated from specific blood cell counts, was evaluated alongside other variables using machine learning models, including random forest, Xgboost, elastic networks, logistic regression, and multilayer perceptron. The optimal model was selected based on performance metrics and further interpreted using variable importance analysis and the SHAP method.Results: Our study revealed that ISR occurred in 25.8% of patients, with a range of demographic and clinical factors influencing the risk of its development. The random forest model emerged as the most adept in predicting ISR, and AISI featured prominently among the top variables affecting ISR prediction. Notably, higher AISI values were positively correlated with an elevated probability of ISR occurrence. Comparative evaluation and visual analysis of model performance, the random forest model demonstrates high reliability in predicting ISR, with specific metrics including an AUC of 0.9569, accuracy of 0.911, sensitivity of 0.855, PPV of 0.81, and NPV of 0.948.Conclusion: AISI demonstrated itself as a significant independent risk factor for ISR following DES implantation, with an escalation in AISI levels indicating a heightened risk of ISR occurrence.Keywords: coronary artery disease, percutaneous coronary intervention, Systemic inflammation aggregation index, machine learning models, In-stent restenosis

Xiaochun Chen,1,&ast; Benhong Zhang,2,&ast; Jin He,3,&ast; Xiaohong Rui,4 Tian He,4 Lizhu Zhang,5 Junfeng Bao,6 Yanfei Jing,7 Futao Cao8 1Department of Laboratory Medicine, Taizhou Second People’s Hospital, Taizhou, People’s Republic of China; 2Department of Laboratory Medicine, Hangzhou Gongshu District Integrated Traditional Chinese and Western Medicine Hospital, Hangzhou, People’s Republic of China; 3Department of Laboratory Medicine, Hangzhou Yuhang Jiamu Nursing Home, Hangzhou, People’s Republic of China; 4Department of Laboratory Medicine, Affiliated Wuxi Fifth Hospital of Jiangnan University, Wuxi, People’s Republic of China; 5Department of Research, Nanxin Pharm, Nanjing, People’s Republic of China; 6Department of Laboratory Medicine, Wuxi Maternal and Child Health Care Hospital, Women’s Hospital of Jiangnan University, Wuxi, People’s Republic of China; 7Department of Function, Affiliated Wuxi Fifth Hospital of Jiangnan University, Wuxi, People’s Republic of China; 8Department of Emergency, Jiangnan University Medical Center, Wuxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanfei Jing, Department of Function, Affiliated Wuxi Fifth Hospital of Jiangnan University, Wuxi, Jiangsu, 214005, People’s Republic of China, Email tengfeiba0002@163.com Futao Cao, Department of Emergency, Jiangnan University Medical Center, Wuxi, Jiangsu, 214000, People’s Republic of China, Email caofutao999@163.comIntroduction: The emergence of multidrug-resistant Klebsiella pneumoniae (K. pneumoniae) and the decline of effective antibiotics lead to the urgent need for new antibacterial agents. The aim of this study is to investigate the therapeutic effect of antimicrobial peptides against gentamicin-resistant (RT) K. pneumoniae and to screen effective antimicrobial peptides.Methods: In this study, the RT strains were induced by gradient gentamicin, and the RT strains were selected by detecting the expression levels of efflux pump genes, porin genes, and biofilm formation genes of the strains combined with their effects on the cells. Then the effects of four antimicrobial peptides on the efflux pump activity, biofilm formation level and cell condition after infection were detected to explore the effects of antimicrobial peptides on RT strains. Finally, the RT strain was used to induce a mouse model of pneumonia, and the four antimicrobial peptides were used to treat pneumonia mice for in vivo experiments. The pathological changes in lung tissues in each group were detected to explore the antimicrobial peptide with the most significant effect on the RT strain in vivo.Results: The results showed that the minimal inhibitory concentrations of the RT strains (strain C and strain I) were significantly higher than those of the wild-type strain, and the expression of efflux pump, porin and biofilm formation genes was significantly increased. The antimicrobial peptides could effectively inhibit the biofilm formation and efflux pump protein function of the RT strains. In addition, the antimicrobial peptides showed promising antibacterial effects both in vitro and in vivo.Discussion: Our study provided a theoretical basis for the treatment of gentamicin resistant K. pneumoniae infection with antimicrobial peptides, and found that KLA was significantly superior to LL37, Magainin I, KLA and Dermaseptin (10 μg/mL in cells, 50 μg in mice).Keywords: Klebsiella pneumoniae, K. pneumoniae, antibiotics, antimicrobial peptide, gentamicin-resistant, RT, microenvironment

Lisheng Chen,1,2 Tingting He,3 Ruilin Wang,3 Honghong Liu,4 Xin Wang,1,2 Haotian Li,2 Manyi Jing,2 Xuelin Zhou,5 Shizhang Wei,6 Wenjun Zou,1 Yanling Zhao1,2 1College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Department of Pharmacy Department, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Division of Integrative Medicine, The Fifth Medical Center of General Hospital of PLA, Beijing, People’s Republic of China; 4Integrated TCM & Western Medicine Department, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 5Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing, People’s Republic of China; 6Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University, Beijing, People’s Republic of ChinaCorrespondence: Yanling Zhao, Department of Pharmacy, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China, Email zhaoyl2855@126.com Wenjun Zou, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China, Email zouwenjun@163.comBackground: The Zuojin Pill (ZJP) is widely used for treating chronic atrophic gastritis (CAG) in clinical practice, effectively ameliorating symptoms such as vomiting, pain, and abdominal distension in patients. However, the underlying mechanisms of ZJP in treating CAG has not been fully elucidated.Purpose: This study aimed to clarify the characteristic function of ZJP in the treatment of CAG and its potential mechanism.Methods: The CAG model was established by alternant administrations of ammonia solution and sodium deoxycholate, as well as an irregular diet. Therapeutic effects of ZJP on body weight, serum biochemical indexes and general condition were analyzed. HE staining and AB-PAS staining were analyzed to characterize the mucosal injury and the thickness of gastric mucosa. Furthermore, network pharmacology and molecular docking were used to predict the regulatory mechanism and main active components of ZJP in CAG treatment. RT-PCR, immunohistochemistry, immunofluorescence and Western blotting were used to measure the expression levels of apoptosis-related proteins, gastric mucosal barrier-associated proteins and PI3K/Akt signaling pathway proteins.Results: The results demonstrated that ZJP significantly improved the general state of CAG rats, alleviated weight loss and gastric histological damage and reduced the serum biochemical indicators. Network pharmacology and molecular docking found that ZJP in treating CAG by inhibiting inflammation, suppressing apoptosis, and protecting the gastric mucosal barrier via the PI3K/Akt signaling pathway. Further experiments confirmed that ZJP obviously modulated the expression of key proteins involved in gastric mucosal cell apoptosis, such as Bax, Bad, Apaf-1, cleaved-caspase-3, cleaved-caspase-9, Cytochrome C, Bcl-2, and Bcl-xl. Moreover, ZJP significantly reversed the protein expression of Occludin, ZO-1, Claudin-4 and E-cadherin.Conclusion: Our study revealed that ZJP treats CAG by inhibiting the PI3K/Akt signaling pathway. This research provided a scientific basis for the rational use of ZJP in clinical practice.Keywords: Zuojin Pill, chronic atrophic gastritis, network pharmacology, molecular docking, PI3K/Akt signaling pathway

Ting He,1,&ast; Kangzhi Chen,1,&ast; Yi Li,1 Zhaohui Luo,1 Mengchuan Luo,2 Huan Yang1 1Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China; 2Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huan Yang, Department of Neurology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, People’s Republic of China, Email 403850@csu.edu.cnPurpose: To decipher the discrepancies between muscle-specific kinase antibody-positive myasthenia gravis (MuSK-MG) and double-seropositive myasthenia gravis (DSP-MG), and to determine prognostic factors for minimal manifestation status (MMS) achievement in MG patients with MuSK autoantibodies (MuSK-Ab).Patients and Methods: A total of 34 MG patients seropositive for MuSK-Ab were enrolled in this study. The demographic and clinical features were compared between MuSK-MG (n = 28) and DSP-MG (n = 6) patients, and factors affecting MMS induction in all patients with MuSK-Ab were identified using Cox regression analysis.Results: Compared to MuSK-MG patients, those with DSP-MG had similar clinical characteristics, except that they had a lower frequency of bulbar muscle involvement at nadir (50% vs 92.9%; P = 0.029) and higher proportions of comorbidities with diabetes mellitus (33.3% vs 0%; P = 0.027) and thymic abnormalities (33.3% vs 0%; P = 0.027). Higher MG Activities of Daily Living (MG-ADL) scores (HR = 0.16, 95% CI: 0.037– 0.7, P = 0.015) and axial muscle involvement at nadir (HR = 0.39, 95% CI: 0.16– 0.94, P = 0.035) were negative prognostic factors for MMS achievement in patients with MuSK-Ab regardless of acetylcholine receptor antibody (AChR-Ab) positivity. Multivariable Cox regression analysis further established higher MG-ADL scores at the nadir (HR = 0.19, 95% CI: 0.04– 0.94; P = 0.042) as an independent risk factor for MMS achievement.Conclusion: DSP-MG was comparable to MuSK-MG and could be considered a single entity in our cohort. In all MG patients with MuSK-Ab, a higher MG-ADL score at nadir may herald a lower chance of MMS achievement, with no observed potential effect of AChR-Ab presence.Keywords: double-seropositive myasthenia gravis, muscle-specific kinase antibody, acetylcholine receptor antibody, minimal manifestation status, myasthenia gravis activities of daily living

Qichao Hu,1,2,&ast; Jinhao Zeng,3,4,&ast; Xiaomei Zhang,5 Tingting He,6 Aozhe Zhang,6 Jianyu Li,6 Shizhang Wei,2,7 Manyi Jing,2 Haotian Li,2 Xin Wang,2 Lei Chang,2 Xiao Ma,1,2 Yanling Zhao2 1State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China; 2Department of Pharmacy, Chinese PLA General Hospital, Beijing, People’s Republic of China; 3TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 4Department of Gastroenterology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, People’s Republic of China; 5Institute of Medicinal Chemistry of Chinese Medicine, Chongqing Academy of Chinese Materia Medica, Chongqing, People’s Republic of China; 6Division of Integrative Medicine, The Fifth Medical Center, General Hospital of PLA, Beijing, People’s Republic of China; 7Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao Ma; Yanling Zhao, Email tobymaxiao@163.com; zhaoyl2855@126.comObjective: Chronic non-atrophic gastritis (CNAG) is a common clinical gastrointestinal disease with a long and recurrent course. In China, Wuzhuyu decoction (WZYD) has been used for centuries to treat gastrointestinal disorders. To unravel the efficacy and mechanism of WZYD for CNAG, a clinical study was conducted. And metabolomics was used to explore the mechanism of WZYD for CNAG patients.Methods: Twenty patients in total were recruited in this study (Nos. ChiCTR2200062296) and the protocol was approved by the Ethics Committee (Approval number: KY-2022-2-6-1) and complied with the Declaration of Helsinki. The formula granule of WZYD were assessed by UHPLC-QQQ-TOF to discern the main potential active compounds. The endoscopy evaluation and histopathological changes were detected as effective indicators. Serum samples from patients were used for metabolomics. Inflammatory factors in patients’ serum were determined by ELISA. Metabolomics revealed a series of differential metabolites and signaling pathways.Results: WZYD was capable to prevent CNAG by ameliorating score of endoscopy evaluation including erosion, hemorrhage, as well as chronic inflammation and active chronic inflammation score after treatment were decreased. The results indicated that 10 core metabolic components were associated with the treatment of WZYD. Moreover, these metabolic components proved that pyrimidine metabolism and thiamine metabolism were critically responsible for CNAG. In addition, WZYD treatment effectively reduced serum levels of TNF-α, IL-10, and COX-2.Conclusion: Altogether, WZYD can effectively alleviate CNAG by inhibiting inflammation and regulating related metabolic processes, which might be the molecular mechanism of WZYD treatment of CNAG. More studies are warranted to be conducted in this area.Trial Registration: ChiCTR, ChiCTR2200062296. Registered 1 August 2022, https://www.chictr.org.cn/com/25/showprojen.aspx?proj=174027.Keywords: Wuzhuyu decoction, chronic non-atrophic gastritis, metabolomics, natural product

Xiaohui Liu,1 Tingxin He,2 Siqi Yu,1 Jifang Duan,3 Ruixiang Gao2,4 1School of Music, South China Normal University, Guangzhou, 510006, People’s Republic of China; 2Center for Studies of Psychological Application, Guangdong Key Laboratory of Mental Health and Cognitive Science, and School of Psychology, South China Normal University, Guangzhou, 510631, People’s Republic of China; 3School of Chinese Language and Literature, South China Normal University, Guangzhou, 510006, People’s Republic of China; 4Empirical Research Center for Aesthetics and Aesthetic Education, South China Normal University, Guangzhou, 510631, People’s Republic of ChinaCorrespondence: Jifang Duan, School of Chinese Language and Literature, South China Normal University, No. 378, Waihuan West Road, University Town, Panyu District, Guangzhou, Guangdong Province, 510006, People’s Republic of China, Email duanjifang@163.com Ruixiang Gao, Empirical Research Center for Aesthetics and Aesthetic Education, South China Normal University, No. 55, West of Zhongshan Avenue, Tianhe District, Guangzhou, Guangdong Province, 510631, People’s Republic of China, Email ruixianggao@m.scnu.edu.cnIntroduction: Emotional labor is an important research area, but four key gaps remain regarding outcomes of nonwork strains, explanatory frameworks beyond the conservation of resources theory, adoption of person-centered approaches, and subjects of performers.Methods: By surveying 183 Chinese dance students, we employed cluster analysis to examine the adoption of emotional labor strategies (ie, surface acting, deep acting, and expression of naturally felt emotions) and to explore the outcomes on work strain (ie, emotional exhaustion and reduced flow experience) and nonwork strain (ie, depression and anxiety) with introducing the allostatic load theory as an analytical basis.Results: Four types of emotional workers were identified, namely, flexible regulators (33.33%), authentic regulators (15.85%), display rules compliers (39.34%), and non-regulators (11.48%). Authentic regulators had the lowest emotional exhaustion. Non-regulators had the lowest flow. No differences emerged in depression or anxiety across clusters.Discussion: Findings partially align with past research showing risks of surface acting in terms of emotional exhaustion. However, all three strategies enhanced flow states. Moreover, dancers’ work strains did not extend to psychological problems, unlike other professions. Possible explanations include training in emotional regulation and flow states in performing. Practical implications exist for training emotional regulation and fostering flow at work.Keywords: dancer, emotional labor, strain, emotional exhaustion, flow experience, depression, anxiety, allostatic load theory

Zhichao Xing,1,&ast; Anping Su,1,&ast; Li Mi,1 Yujie Zhang,1 Ting He,1 Yuxuan Qiu,2 Tao Wei,1 Zhihui Li,1 Jingqiang Zhu,1 Wenshuang Wu1 1Division of Thyroid Surgery, Department of General Surgery and Laboratory of Thyroid and Parathyroid Disease, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Ultrasound, West China Hospital, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingqiang Zhu; Wenshuang Wu, Division of Thyroid Surgery, Department of General Surgery and Laboratory of Thyroid and Parathyroid Disease, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, People’s Republic of China, Email zhujingqiang@scu.edu.cn; wenshuang_wu@163.comAbstract: Cancer, as the leading cause of death worldwide, poses a serious threat to human health, making the development of effective tumor treatments a significant challenge. Natural products continue to serve as crucial resources for drug discovery. Among them, Withaferin A (WA), the most active phytocompound extracted from the renowned dietary supplement Withania somnifera (L.) Dunal, exhibits remarkable anti-tumor efficacy. In this manuscript, we aim to comprehensively summarize the pharmacological characteristics of WA as a potential anti-tumor drug candidate, with the objective of contributing to its further development and the discovery of prospective drugs. Through an extensive review of literature from PubMed, Science Direct, and Web of Science, we have gathered substantial evidence showcasing WA’s significant anti-tumor effects against a wide range of cancers in both in vitro and in vivo studies. Mechanistically, WA exerts its anti-tumor influence by inducing cell cycle arrest, apoptosis, autophagy, and ferroptosis. Additionally, it inhibits cell proliferation, cancer stem cells, tumor metastasis, and also suppresses epithelial-mesenchymal transition (EMT) and angiogenesis. Several studies have identified direct target proteins of WA, such as vimentin, Hsp90, annexin II and mFAM72A, while BCR-ABL, Mortalin (mtHsp70), Nrf2, and c-MYB are potential targets of WA. Notwithstanding its remarkable anti-tumor efficacy, there are some limitations associated with WA, including potential toxicity and poor oral bioavailability, which need to be addressed when considering it as an anti-tumor candidate agent. Nevertheless, I given its promising anti-tumor attributes, WA remains an encouraging candidate for future drug development. Unveiling the exact target and comprehensive mechanism of WA’s action represents a crucial research direction to pursue in the future.Graphical Abstract: Keywords: Withaferin A, Withania somnifera, dietary supplement, anti-cancer activity, pharmacological mechanism, direct target

Tianwen He,1,2,&ast; Muheremu Muhetaer,1,2,&ast; Jiahe Wu,1,2 Jingjing Wan,1,2 Yushuang Hu,1,2 Tong Zhang,1,2 Yunxiang Wang,1,2 Qiongxin Wang,1,2 Huanhuan Cai,1,2 Zhibing Lu1,2 1Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Institute of Myocardial Injury and Repair, Wuhan University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhibing Lu; Huanhuan Cai, Department of Cardiology, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Wuhan, 430071, People’s Republic of China, Email luzhibing222@163.com; caihuanhuan@whu.edu.cnBackground: Coronary artery disease (CAD) is a multifactorial immune disease, but research into the specific immune mechanism is still needed. The present study aimed to identify novel immune-related markers of CAD.Methods: Three CAD-related datasets (GSE12288, GSE98583, GSE113079) were downloaded from the Gene Expression Integrated Database. Gene ontology annotation, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis and weighted gene co-expression network analysis were performed on the common significantly differentially expressed genes (DEGs) of these three data sets, and the most relevant module genes for CAD obtained. The immune cell infiltration of module genes was evaluated with the CIBERSORT algorithm, and characteristic genes accompanied by their diagnostic effectiveness were screened by the machine-learning algorithm least absolute shrinkage and selection operator (LASSO) regression analysis. The expression levels of characteristic genes were evaluated in the peripheral blood mononuclear cells of CAD patients and healthy controls for verification.Results: A total of 204 upregulated and 339 downregulated DEGs were identified, which were mainly enriched in the following pathways: “Apoptosis”, “Th17 cell differentiation”, “Th1 and Th2 cell differentiation”, “Glycerolipid metabolism”, and “Fat digestion and absorption”. Five characteristic genes, LMAN1L, DOK4, CHFR, CEL and CCDC28A, were identified by LASSO analysis, and the results of the immune cell infiltration analysis indicated that the proportion of immune infiltrating cells (activated CD8 T cells and CD56 DIM natural killer cells) in the CAD group was lower than that in the control group. The expressions of CHFR, CEL and CCDC28A in the peripheral blood of the healthy controls and CAD patients were significantly different.Conclusion: We identified CHFR, CEL and CCDC28A as potential biomarkers related to immune infiltration in CAD based on public data sets and clinical samples. This finding will contribute to providing a potential target for early noninvasive diagnosis and immunotherapy of CAD.Keywords: biomarkers, coronary artery disease, CAD, immune infiltration, inflammation, machine learning

Collecting and analyzing the vast amount of information available in the solid-state chemistry literature may accelerate our understanding of materials synthesis. However, one major problem is the difficulty of identifying which materials from a synthesis paragraph are precursors or are target materials. In this study, we developed a two-step chemical named entity recognition model to identify precursors and targets, based on information from the context around material entities. Using the extracted data, we conducted a meta-analysis to study the similarities and differences between precursors in the context of solid-state synthesis. To quantify precursor similarity, we built a substitution model to calculate the viability of substituting one precursor with another while retaining the target. From a hierarchical clustering of the precursors, we demonstrate that the "chemical similarity"of precursors can be extracted from text data. Quantifying the similarity of precursors helps provide a foundation for suggesting candidate reactants in a predictive synthesis model.

The domain of allowed von Neumann entropies of a holographic field theory carves out a polyhedral cone — the holographic entropy cone — in entropy space. Such polyhedral cones are characterized by their extreme rays. For an arbitrary number of parties, it is known that the so-called perfect tensors are extreme rays. In this work, we constrain the form of the remaining extreme rays by showing that they correspond to geometries with vanishing mutual information between any two parties, ensuring the absence of Bell pair type entanglement between them. This is tantamount to proving that besides subadditivity, all non-redundant holographic entropy inequalities are superbalanced, i.e. not only do UV divergences cancel in the inequality itself (assuming smooth entangling surfaces), but also in the purification thereof.

Digitizing large collections of scientific literature can enable new informatics approaches for scientific analysis and meta-analysis. However, most content in the scientific literature is locked-up in written natural language, which is difficult to parse into databases using explicitly hard-coded classification rules. In this work, we demonstrate a semi-supervised machine-learning method to classify inorganic materials synthesis procedures from written natural language. Without any human input, latent Dirichlet allocation can cluster keywords into topics corresponding to specific experimental materials synthesis steps, such as “grinding” and “heating”, “dissolving” and “centrifuging”, etc. Guided by a modest amount of annotation, a random forest classifier can then associate these steps with different categories of materials synthesis, such as solid-state or hydrothermal synthesis. Finally, we show that a Markov chain representation of the order of experimental steps accurately reconstructs a flowchart of possible synthesis procedures. Our machine-learning approach enables a scalable approach to unlock the large amount of inorganic materials synthesis information from the literature and to process it into a standardized, machine-readable database.

Yao Wang,1,2 Yujie He,1,2 Yanyan Zhu,1,2 Ting He,1,2 Jie Xu,1,2 Qinmei Kuang,1,2 Yuqi Ji,1,2 Renshi Xu,3 Fangjun Li,4 Fuqing Zhou1,2 1Department of Radiology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China; 2Neuroimaging Lab, Jiangxi Province Medical Imaging Research Institute, Nanchang, 330006, People’s Republic of China; 3Department of Neurology, Jiangxi Provincial People’s Hospital Affiliated to Nanchang University, Nanchang, 330006, People’s Republic of China; 4Department of Neurology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of ChinaCorrespondence: Fuqing Zhou, Department of Radiology, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Nanchang, 330006, People’s Republic of China, Tel +86- 13694881033, Email fq.chou@yahoo.com; ndyfy02301@ncu.edu.cn Fangjun Li, Department of Neurology, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Nanchang, 330006, People’s Republic of China, Tel +86- 13576937919, Email fishmonger@126.comObjective: Clinical symptoms such as major defects in energy metabolism may involve the hypothalamus in amyotrophic lateral sclerosis (ALS) patients. Our recent study discovered that the single-nucleotide polymorphisms (SNPs) of rs2619566, rs79609816 and rs10260404 are associated with sporadic ALS (sALS). Thus, this study aims to investigate the hypothalamic functional reorganization and its association with the above polymorphisms risk alleles in sALS patients of Chinese Han ancestry.Methods: Forty-four sALS patients (28 males/16 females) and 40 healthy subjects (HS; 28 males/12 females) underwent resting-state functional MRI, genotyping and clinical assessments. A two-sample t test (P < 0.01, GRF correction at P < 0.05) was performed to compare hypothalamic connectivity for group-level analysis in disease diagnosis and genotype, and then the genotype-diagnosis interaction effect was assessed. Finally, Spearman correlation analyses were performed to assess the relationship between the altered functional connectivity and their clinical characteristics.Results: The sALS patients showed a short disease duration (median = 12 months). Regarding the diagnosis effect, the sALS patients showed widespread hypothalamic hyperconnectivity with the left superior temporal gyrus/middle temporal gyrus, right inferior frontal gyrus, and left precuneus/posterior cingulate gyrus. For the genotype effect of SNPs, hyperconnectivity was observed in only the medial hypothalamus when the sALS patients harboring the minor C allele of rs2619566 in contactin-4 (CNTN4), while the sALS patients with the TT allele showed a hyperconnectivity network in the right lateral hypothalamus. This connectivity pattern was not observed in other SNPs. No significant genotype-diagnosis interaction was found. Moreover, altered functional connectivity was not significantly correlated with clinical characteristics (P : 0.11– 0.90).Conclusion: These results demonstrated widespread hypothalamic hyperconnectivity in sALS. The risk allele C of the CNTN4 gene may therefore influence functional reorganization of the medial hypothalamus. The effects of the CNTN4 rs2619566 polymorphism may exist in the hypothalamic functional connectivity of patients with sALS.Keywords: sporadic amyotrophic lateral sclerosis, hypothalamus, lateral hypothalamus, medial hypothalamus, resting-state functional connectivity

Tao He,1,&ast; Gang Li,2,&ast; Shoujia Xu,1 Leyun Guo,1 Bing Tang1 1Department of Orthopedics, Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Shiyan, Hubei, 442008, People’s Republic of China; 2Department of Sports Medicine, Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Shiyan, Hubei, 442008, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Leyun Guo; Bing TangDepartment of Orthopedics, Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Daling Road 16#, Shiyan, Hubei, 442008, People’s Republic of China, Tel +86 0719-8210666, Email guoleyun@sohu.com; tangbingsy@163.comBackground: We hypothesized that the blood urea nitrogen (BUN) to serum albumin ratio (BAR) could serve as an independent predictor for incident acute kidney injury (AKI) in intensive care unit (ICU) patients with rib fracture.Methods: Rib fracture patients in ICU were extracted from Medical Information Mart for Intensive Care IV (MIMIC-IV v1.0) database. The primary outcome in this study was the incidence of AKI. Univariate and multivariate logistic regression analyses were used to determine the relationship between BAR and AKI and propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were also applied to assure the robustness of our results.Results: The optimal cut-off value for BAR was 5.26 based on receiver operator characteristic curve. Among the 953 patients who diagnosed with rib fracture, 197 high-BAR group (≥ 5.26) patients and 197 low-BAR group (< 5.26) patients who had similar propensity scores were finally included in the matched cohort. High-BAR group patients had a significantly higher incidence of AKI (odds ratio, OR, 3.85, 95% confidence index, 95% CI, 2.58– 5.79, P< 0.001) in the original cohort, in the matched cohort (OR, 4.47, 95% CI 2.71– 7.53, P< 0.001), and in the weighted cohort (OR, 4.28, 95% CI 2.80– 6.53, P< 0.001). Furthermore, BAR was superior to that of acute physiology score III for predicting AKI and could add more net benefit for incident AKI in critical care patients with rib fracture.Conclusion: As an easily access and cost-effective parameter, BAR could serve as a good diagnostic predictor for AKI in ICU patients with rib fracture.Keywords: blood urea nitrogen to serum albumin ratio, rib fracture, intensive care unit, acute kidney injury, medical information mart for intensive care

Jiaqi Xu, Kun Cheng, Hai Lin, Wei Han, Tieying He, Xiaohan Nie, Yonghui Sun, Sulidankazha Qiuman, Yilidan Reheman, Qilong Chen Department of Pancreatic Surgery, Centre of Digestive and Vascular Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, People’s Republic of ChinaCorrespondence: Qilong Chen Email chenqilong651003@sohu.comBackground: Pancreatic cancer (PC) presents a phenomenal disease burden worldwide. The GATA transcription factor family is associated with a variety of human malignancies. However, the relation between GATA family members (GATAs) and PC has not been elucidated.Methods: This study integrates large-scale bioinformatics database resources to analyze the expression patterns of GATAs in PC patients and explore their underlying function mechanism and relevance to immune infiltration and other different cell types in the tumor microenvironment in pancreatic cancer. First, the expression pattern of GATAs in pancreatic cancer was detected by the Oncomine database and the Gene Expression Profile Interaction Analysis (GEPIA2) database and verified through other datasets in the R2 platform. Then, we used the cBioPortal database and the Human Protein Atlas to assess the correlation between GATAs and clinicopathological features of PC. Then, survival analyses were performed to identify candidate prognostic factors in the GATA family in PC patients. Further, we performed gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, protein-protein interaction (PPI) network, immune-infiltration correlation analysis, and cell type analysis of the tumor microenvironment at the single-cell level to explain the function of GATAs in pancreatic cancer.Results: We found that GATA3 and GATA6 were highly expressed in pancreatic cancer, and the expression levels of GATA4 and GATA6 correlated with the pathological stage, differentiation grade, and molecular subtype of pancreatic cancer. The survival analysis revealed that lower GATA4 of PC patients was associated with better outcomes, and higher GATA6 might be associated with longer OS. In addition, GATA3 was associated with immune cell infiltration of PC, and GATA6 was mainly distributed in the epithelial cells with ductal phenotype.Conclusion: This work tentatively identified GATA3, GATA4, and GATA6 in the GATA family associated with pancreatic cancer. GATA4 may serve as a prognostic factor for PC patients, and GATA6 may act as a subtype marker for PC. In addition, GATA3 may reflect the immune-infiltration status of PC.Keywords: pancreatic cancer, GATA transcriptional factor, prognosis, tumor microenvironment, bioinformatics analysis

Yuanming Jiang,&ast; Ting He,&ast; Wei Liu Department of Otolaryngology, Wuhan No. 1 Hospital, Wuhan, Hubei, 430022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanming JiangDepartment of Otolaryngology, Wuhan No. 1 Hospital, Wuhan, Hubei, 430022, People’s Republic of ChinaTel +86-27-85332681Email jiangmingent@126.comPurpose: Evaluating the treatment of infected preauricular fistulas by resecting the lesion combining with local flap repairing.Patients and Methods: This clinical study was implemented in Ningbo No. 1 Hospital and Wuhan No. 1 Hospital of China. We included 100 cases who were diagnosed with infected preauricular fistulas and needed further surgery treatment. Among them, 50 patients experienced the conventional treatment including a fully infection control following with a surgery to remove preauricular fistulas (conventional treatment group). Other 50 patients only took some simple pre-operation treatment for about 1– 7 days, and then preauricular fistulas resection combining local flap repairing were performed regardless of the infection (local flap repairing group). The duration of total treatment procedure, healing index, and total cost were observed.Results: All patients were discharged at about 7 days after surgery, the duration of the post-operative period had no significant difference between groups. The total duration of treatment (from any first treatment time point to patient discharge) was only 13.98± 2.14 days in the local flap treatment group compared with that of 43.06± 8.24 days in the conventional treatment group. Further, the total cost of treatment per patient in the local flap repairing treatment group was about 47.1% of that in the conventional treatment group.Conclusion: For the treatment of infected preauricular fistula, performing a lesion removing surgery combining a local flap repairing can shorten the total treatment course, relieve patient’s suffering, reduce treatment cost, and achieve a better clinical prognosis.Keywords: preauricular fistula, local flap, infection, surgery, treatment

Weipu Mao,1– 3,&ast; Si Sun,1,&ast; Ting He,1,&ast; Xin Jin,4,&ast; Jianping Wu,1 Bin Xu,1 Guangyuan Zhang,1 Keyi Wang,5,&ast; Ming Chen1– 3 1Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, 210009, People’s Republic of China; 2Surgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, 210009, People’s Republic of China; 3Department of Urology, Nanjing Lishui District People’s Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing, 211200, People’s Republic of China; 4Department of Urology, Taizhou People’s Hospital, Taizhou, 225700, People’s Republic of China; 5Department of Urology, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ming Chen; Guangyuan ZhangDepartment of Urology, Affiliated Zhongda Hospital of Southeast University, No. 87 Dingjiaqiao, Hunan Road, Gulou District, Nanjing, 210009, People’s Republic of ChinaTel +86-13913009977; +86-13951658634Fax +86-13913009977; +86-13770334095Email mingchenseu@126.com; zgy0879@qq.comBackground: We conducted a multicenter clinical study to examine the prognostic value of the systemic inflammation response index (SIRI) in renal cell carcinoma (RCC) patients.Methods: We collected patients who underwent nephrectomy from 2014 to 2019 at three centers (343 in the training group and 100 in the validation group). SIRI was created based on hemoglobin and lymphocyte to monocyte ratio (LMR). Kaplan–Meier curves and receiver operating characteristic (ROC) curves were used to analyze the effect of LMR, hemoglobin and SIRI on overall survival (OS) and cancer-specific survival (CSS) effects.Results: In both the training and validation groups, SIRI was a better predictor of OS and CSS than LMR and hemoglobin. A total of 192 (56.0%) patients were included in grade 1, 108 (31.5%) in grade 2, and 43 (12.5%) in grade 3 based on SIRI in the training group. Higher SIRI was associated with worse prognosis. Multivariate cox regression analysis showed that SIRI was an independent prognostic risk factor for OS (grade 3 vs grade 1: HR=4.93; 95% CI 2.21– 11.00, p < 0.001) and CSS (grade 3 vs grade 1: HR=6.29; 95% CI 2.28– 17.39, p < 0.001) in patients with RCC. In addition, SIRI-based prognostic nomograms were able to better predict OS and CSS in RCC patients.Conclusion: SIRI is an independent prognostic factor for patients undergoing laparoscopic nephrectomy for RCC, and a prognostic nomogram covering SIRI can better predict survival of RCC patients.Keywords: renal cell carcinoma, systemic inflammation response index, nomogram, prognostic indicator

Jihui Yue,1,2,&ast; Shuming Zhong,1,&ast; Aimin Luo,3 Shunkai Lai,1 Tingting He,4 Yuchong Luo,2 Ying Wang,5 Yiliang Zhang,1 Shiyi Shen,4 Hui Huang,4 Shenglin Wen,2 Yanbin Jia1 1Department of Psychiatry, First Affiliated Hospital, Jinan University, Guangzhou, Guangdong Province, People’s Republic of China; 2Department of Psychiatry, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong Province, People’s Republic of China; 3Department of Psychology, Guangdong Sanjiu Brain Hospital, Guangzhou, Guangdong Province, People’s Republic of China; 4School of Management, Jinan University, Guangzhou, Guangdong Province, People’s Republic of China; 5Medical Imaging Center, First Affiliated Hospital, Jinan University, Guangzhou, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanbin JiaDepartment of Psychiatry, First Affiliated Hospital, Jinan University, Guangzhou, People’s Republic of ChinaTel +86 13392489168Fax +86 020-38688888Email Yanbinjia2006@163.comPurpose: This study aimed to investigate the mechanism of working memory (WM) impairment in drug-naive obsessive-compulsive disorder (OCD) by using neuropsychological tests and proton magnetic resonance spectroscopy (1H-MRS).Patients and Methods: A total of 55 patients with drug-naive OCD and 55 healthy controls (HCs) were recruited for this study. The working memory (WM) was evaluated using the digit span test (DST), visual space memory test (VSMT), and the 2-back task and stroop color word test (SCWT). The bilateral metabolite levels of the prefrontal cortex (PFC) were evaluated by 1H-MRS, then determined the ratios of N-acetyl aspartate (NAA), choline-containing compounds (Cho), and myo-inositol (MI) to creatine (Cr). The independent sample t-test was used to analyse the differences in WM performance and neurometabolite ratios. Multivariate linear regression analysis was performed to screen the influential factors of WM, with an introduction level of 0.05 and a rejection level of 0.10.Results: 1) Patients with OCD performed significantly worse on DST (score), VSMT (score), 2-back task (accuracy rate), SCWT (execution time) when compared with HCs. 2) NAA/Cr and Cho/Cr in the left PFC (lPFC) and MI/Cr ratios in the bilateral PFC of OCD patients were significantly lower when compared to HCs. 3) For OCD patients, the NAA/Cr ratio in the lPFC was negatively correlated with the score of DST (forwards), the Cho/Cr ratio in the lPFC was positively correlated with the accuracy rate of 2-back task, and the MI/Cr ratio in the right PFC (rPFC) was positively correlated with the score of DST (forwards) and the accuracy rate of VSMT. We also found that the compulsive symptoms showed a positive correlation with MI/Cr ratio of the rPFC.Conclusion: Drug-naive OCD patients have demonstrated WM impairments, including phonological loop, visual-spatial sketchpad and central executive system, and the WM impairments might be associated with hypometabolism in the PFC, especially the lPFC.Keywords: obsessive compulsive disorder, prefrontal cortex, working memory, neurometabolites, proton magnetic resonance spectroscopy

Chunliang Shang,1 Yuan Li,1 Zhangxin Wu,1 Qin Han,1 Yuan Zhu,2 Tianhui He,1 Hongyan Guo1,3 1Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, People’s Republic of China; 2Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 3National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing 100191, People’s Republic of ChinaCorrespondence: Hongyan GuoDepartment of Obstetrics and Gynecology, Peking University Third Hospital, No. 49 Huayuan North Road, Haidian District, Beijing 100191, People’s Republic of ChinaTel +86-17301281996Fax +86 1082267842Email bysyghy@163.comBackground: To depict the prognostic landscape of gynecological cancers from the perspective of DNA methylation, alternative splicing (AS) and polyadenylation (APA) events and investigate their correlation with immune infiltrates.Methods: Methylation and RNA-seq data and corresponding clinical information regarding gynecologic cancers were used to explore the relationships between changes in DNA methylation, AS and APA events and gynecologic cancer prognosis. QRT-PCR and multiple bioinformatics tools were employed to construct a gene interaction network and explore immune infiltrates.Results: Only the mRNA levels of CIRBP and INPP5K were simultaneously significantly decreased in gynecologic cancers and negatively associated with overall survival, which verified by qrt-PCR. We also identified that CIRBP or INPP5K DNA methylation, AS and APA events are prognostic indicators of gynecologic cancers. The activation of T cells might be the main signaling pathway by which these genes modulate cancer progression. CIRBP/INPP5K expression is positively associated with immune infiltration and is a major risk factor of survival, especially among uterine corpus endometrial carcinoma (UCEC) patients.Conclusion: According to these findings, the DNA methylation, AS and APA events of CIRBP and INPP5K may serve as important prognostic biomarkers and targets in gynecological cancers by modulating T cell infiltration.Keywords: DNA methylation, alternative splicing, alternative polyadenylation, activation of T cells, immune infiltration

The addition of Biochar (BC) into the soil is expected to improve soil physicochemical properties and plant growth. However, few studies have verified such an effect on the growth and physiological characteristics of conifers. The current study aims to assess the efficacy of novel physiological parameters as an indicator for assessing the impact of hardwood biochar (BH) on the development of Fokienia hodginsii seedlings to strengthen our understanding of the impacts of the BH on soil to optimize the achievement of BC-based restoration projects. The BH was applied to the soil under four different levels (0, 5, 20, and 80 g Kg-1 of soil) to assess their influence on the leave’s photosynthetic pigments, photosynthesis (Pn), and biochemical traits of F. hodginsii seedlings in four different seasons, and on biomass and soil physicochemical properties at final harvest under greenhouse conditions for one year. In the first two seasons, BH20 and BH80 amended seedlings responded with an improved photosynthetic rate with more production of photosynthetic pigments and biochemical attributes. However, none of the BC doses increased the Pn of seedlings in the final season. Nonetheless, after one year a rise in soil pH as well as P and K availability resulted in a maximum 25% increase in biomass of F. hodginsii under BH80 amendments. Our findings reveal that the incorporation of BH (20 and 80 g kg-1 of soil) has a substantial positive effect on seedling biomass and soil fertility. However, the application of BH into acidic soils may be effective in restoring degraded soils if initially combined with fertilizers. We recommend a careful approach to the selection of BC because its influence may vary between different soil types, plant species, and BC feedstocks.

Pengcheng Liu,1,* Jie Tan,2,* Qiuwen Tan,1 Li Xu,1 Tao He,1 Qing Lv1 1Department of Breast Surgery, Clinical Research Center for Breast, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China; 2Department of Orthopaedic Surgery & Orthopaedic Institute, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qing LvDepartment of Breast Surgery, Clinical Research Center for Breast, West China Hospital, Sichuan University, No. 37 Guoxuexiang, Chengdu 610041, Sichuan, People’s Republic of ChinaEmail lvqingwestchina@163.comBackground: Accurate lymph node (LN) staging has considerably prognostic and therapeutic value in patients with colorectal cancer (CRC). The purpose of this study is to evaluate the feasibility of applying carbon nanoparticles (CNPs) to track LN metastases in CRC.Methods: Two researchers independently screened publications in PubMed, EMBASE, Cochrane and Ovid MEDLINE databases. The keywords were (carbon nanoparticles OR activated carbon nanoparticles) AND (colon cancer OR rectal cancer OR colorectal cancer). Titles and abstracts of the articles were meticulously read to rule out potential publications. Next, full texts of the ultimately obtained eligible publications were retrieved and analyzed in detail.Results: The search produced 268 publications, and 140 abstracts were identified after a bibliographic review. Finally, 20 studies relevant to our subject were obtained; however, only 14 papers met our inclusion criteria and were included for final review. All studies included have compared the control group with carbon nanoparticles group (control group, defined as nontattooed group; and carbon nanoparticles group, defined as administering carbon nanoparticles during surgery) for their efficacy in intraoperative detecting and positioning. After analysis, appreciably less amount of bleeding (3/5 trials), shorter operation time (2/4 trials), and shorter time to detect lesions and dissect LNs (2/2 trials) were revealed in CNPs group compared to control group. Thirteen studies have recorded the numbers of the harvested LNs in both groups; meanwhile, CNPs group shows superiority to control group in LN retrieval as well (11/13 trials), which also could effectively aid in locating and harvesting more LNs with diameter below 5 mm.Conclusion: The tracing technique for CNPs is a safe and useful strategy both in localizing tumor and tracing LNs in CRC surgery. But there is still a need for more randomized controlled trials to further establish its contribution to patient survival.Keywords: carbon nanoparticles, colorectal cancer, lymph nodes, trace, tumor location

Shanhong Fang,1,* Tianmin He,2,* Jiarun Jiang,3 Yongfeng Li,1 Peng Chen1 1Department of Orthopedics, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, People’s Republic of China; 2Department of Vascular Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, People’s Republic of China; 3Department of Orthopedics, The Hospital of Changle District, Fuzhou 350005, People’s Republic of China*These authors contributed equally to this workCorrespondence: Peng ChenDepartment of Orthopedics, The First Affiliated Hospital of Fujian Medical University, Taijiang District, Fuzhou 350005, People’s Republic of ChinaEmail 290633950@qq.comPurpose: Steroids are known to inhibit osteogenic differentiation and subsequent bone formation in bone mesenchymal stem cells (BMSCs). However, little is known about the role of BMSC exosomes (Exos) and tRNA-derived small RNAs (tsRNAs) in steroid-induced osteonecrosis of the femoral head (SONFH). The objective of this study was to characterize the tsRNA expression profiles of plasma Exos collected from SONFH patients and healthy individuals using small RNA sequencing and further explore the effect of BMSC Exos carrying specific tsRNAs on osteogenic differentiation.Materials and Methods: Based on insights from small RNA sequencing, five differentially expressed (DE) tsRNAs were selected for quantitative real-time polymerase chain reaction (qRT-PCR). The regulatory networks associated with interactions of the tsRNAs-mRNA-pathways were reconstructed. The osteogenesis and adipogenesis in BMSCs were detected via ALP and oil red O staining methods, respectively.Results: A total of 345 DE small RNAs were screened, including 223 DE tsRNAs. The DE tsRNAs were enriched in Wnt signaling pathway and osteogenic differentiation. We identified five DE tsRNAs, among which tsRNA-10277 was significantly downregulated in plasma Exos of SONFH patients compared to that in healthy individuals. Dexamethasone-induced BMSCs were associated with an increased fraction of lipid droplets and decreased osteogenic differentiation, whereas BMSC Exos restored the osteogenic differentiation of that. After treatment of tsRNA-10277-loaded BMSC Exos, the lipid droplets and osteogenic differentiation ability were found to be decreased and enhanced in dexamethasone-induced BMSCs, respectively.Conclusion: An altered tsRNA profile might be involved in the pathophysiology of SONFH. tsRNA-10277-loaded BMSC Exos enhanced osteogenic differentiation ability of dexamethasone-induced BMSCs. Our results provide novel insights into the osteogenic effect of BMSC Exos carrying specific tsRNAs on SONFH.Keywords: steroid-induced femoral head necrosis, small RNA sequencing, tsRNA-10277, BMSC exosomes, osteogenic differentiation

Dan Lin,1 Xiaoyang Lin,2 Tianlin He,1 Guoqun Xie1 1Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Integrated TCM and Western Medicine, The First People’s Hospital of Wenling, Wenling, Zhejiang, People’s Republic of ChinaCorrespondence: Dan Lin Department of OncologyYueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No. 128 Henggao Road, Gaojing Town, Baoshan District, Shanghai 200439, People’s Republic of ChinaTel +86 15801988721Fax +86 21-65161782-1663Email coddef@163.comBackground: Gastric cancer (GC) is a major cancer-related mortality disease. Gambogic acid (GA) has been investigated to inhibit cancer progression. In the present study, the molecular mechanism of GA in regulating GC progression was studied.Methods: The expression levels of circular RNA ASAP2 (circ_ASAP2), miR-33a-5p and cyclin-dependent kinases 7 (CDK7) were detected by quantitative real-time polymerase reaction (qRT-PCR). CDK7 protein level was evaluated by Western blot. Cell colony formation assay, 3-(4,5-Dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, transwell assay and flow cytometry analysis were employed to reveal the functional effects among circ_ASAP2, miR-33a-5p and CDK7 on GA-induced GC progression. Mechanistically, the binding relationship between miR-33a-5p and circ_ASAP2 or CDK7 was predicted with starBase v3.0 online database and verified by dual-luciferase reporter assay. In vivo tumor formation assay was used to explain the impacts of GA treatment on GC growth in vivo.Results: Circ_ASAP2 and CDK7 expression were downregulated in GA-induced GC cells compared with GC cells. MiR-33a-5p expression was upregulated in GA-induced GC cells relative to GC cells. The protein expression level of CDK7 was lower in GA-induced GC cells than that in GC cells. Further, circ_ASAP2 overexpression decreased GA-induced inhibition effects on cell proliferation, migration and invasion and GA-induced promotion effect on cell apoptosis in both AGS and HGC-27 cells, whereas this phenomenon was reversed by miR-33a-5p. In addition, circ_ASAP2 functioned as a sponge of miR-33a-5p and miR-33a-5p was associated with CDK7. Furthermore, GA treatment inhibited GC growth in vivo.Conclusion: Circ_ASAP2 overexpression promoted cell proliferation, migration and invasion, whereas inhibited cell apoptosis by upregulating CDK7 expression through binding to miR-33a-5p in GA-induced GC cells. This study provided a theoretical basis in GC treatment with GA.Keywords: gambogic acid, circ_ASAP2, miR-33a-5p, CDK7, gastric cancer