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Hua Fan,* Ruile Shen,* Junqiang Yan,* Yongjie Bai, Qizhi Fu, Xiaofei Shi, Ganqin Du, Dongmei Wang The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, 471003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ganqin Du; Dongmei Wang, Email dgq99@163.com; wdmzgadyx@163.comAbstract: This review elucidates the pivotal role of pyroptosis, triggered by gut microbiota, in the development of multiple sclerosis (MS), emphasizing its significance within the gut-brain axis. Our comprehensive analysis of recent literature reveals how dysbiosis in the gut microbiota of MS patients—characterized by reduced microbial diversity and shifts in bacterial populations—profoundly impacts immune regulation and the integrity of the central nervous system (CNS). Pyroptosis, an inflammatory form of programmed cell death, significantly exacerbates MS by promoting the release of inflammatory cytokines and causing substantial damage to CNS tissues. The gut microbiota facilitates this detrimental process through metabolites such as short-chain fatty acids and neuroactive compounds, or self-structural products like lipopolysaccharides (LPS), which modulate immune responses and influence neuronal survival. This review highlights the potential of modulating gut microbiota to regulate pyroptosis, thereby suggesting that targeting this pathway could be a promising therapeutic strategy to mitigate inflammatory responses and preserve neuronal integrity in patients with MS.Keywords: multiple sclerosis, gut microbiota, pyroptosis, gut-brain axis, neuroinflammation, therapeutic targets

Rong Huang,1,* Jun Zeng,1,* Xiaoze Yu,1 Yunke Shi,2 Na Song,1 Jie Zhang,1 Peng Wang,1 Min Luo,1 Yiming Ma,2 Chuang Xiao,1 Lueli Wang,1 Guanhua Du,3 Hongyan Cai,4 Weimin Yang1 1School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 2The First Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 3Key Laboratory of Drug Target Research and Drug Screen, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China; 4The Second Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weimin Yang, School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunnan, 650500, People’s Republic of China, Email ywmbessie@yeah.net Hongyan Cai, The Second Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, People’s Republic of China, Email caihy@ydyy.cnPurpose: Luteolin is a promising candidate for diabetic nephropathy due to its potential anti-inflammatory and anti-fibrotic properties. This study explored the molecular mechanisms through which luteolin combats fibrosis in DN.Methods: Potential targets affected by luteolin and genes associated with DN were collected from databases. Overlapping targets between luteolin and diabetic nephropathy were identified through Venn analysis. A protein-protein interaction network was constructed using these common targets, and critical pathways and targets were elucidated through GO and KEGG analysis. These pathways and targets were confirmed using a streptozotocin-induced mouse model. Luteolin was administered at 45 mg/kg and 90 mg/kg. Various parameters were evaluated, including body weight, blood glucose levels, and histopathological examinations. Protein levels related to energy metabolism, inflammation, and fibrosis were quantified.Results: Fifty-three targets associated with luteolin and 36 genes related to diabetic nephropathy were extracted. The AGE-RAGE signaling pathway was the key pathway impacted by luteolin in diabetic nephropathy. Key molecular targets include TGF-β, IL-1β, and PPARG. Luteolin reduced body weight and blood glucose levels, lowered the left kidney index, and improved insulin and glucose tolerance. Furthermore, luteolin mitigated inflammatory cell infiltration, basement membrane thickening, and collagen deposition in the kidney. Luteolin up-regulated the protein expression of p-AMPKα (Th172) while simultaneously down-regulated the protein expression of p-NF-ĸB (p65), NLRP3, TGF-β 1, α-SMA, and Collagen I.Conclusion: Luteolin mitigated renal fibrosis by alleviating energy metabolism disruptions and inflammation by modulating the AMPK/NLRP3/TGF-β signaling pathway.Keywords: diabetic nephropathy, network pharmacology, inflammation, TGF-β, fibrosis

Yanting Ma,1 Yongyuan Li,2 Zhanfeng Zhang,3 Guomei Du,4 Ting Huang,1 Zhi Zhong Zhao,5 Shou Liu,1 Zhancui Dang1 1Department of Public Health, Medical College, Qinghai University, Xining, Qinghai, People’s Republic of China; 2Disease Control department, Huangzhong District health Bureau, Xining, Qinghai, People’s Republic of China; 3Huangzhong District, Duoba County Health Services Center, Xining, Qinghai, People’s Republic of China; 4Clinical Laboratory, Qinghai Red Cross Hospital, Xining, Qinghai, People’s Republic of China; 5Disease Control Department, Qinghai Provincial Center for Endemic Disease Control and Prevention, Xining, Qinghai, People’s Republic of ChinaCorrespondence: Shou Liu; Zhancui Dang, Email liushou2004@aliyun.com; yxyyy2019@163.comPurpose: The prevalence of metabolic syndrome (MetS) is increasing worldwide, and early prediction of MetS risk is highly beneficial for health outcomes. This study aimed to develop and validate a nomogram to predict MetS risk in Qinghai Province, China, and it provides a methodological reference for MetS prevention and control in Qinghai Province, China.Patients and Methods: A total of 3073 participants living between 1900 and 3710 meters above sea level in Qinghai Province participated in this study between March 2014 and March 2016. We omitted 12 subjects who were missing diagnostic component data for MetS, ultimately resulting in 3061 research subjects, 70% of the subjects were assigned randomly to the training set, and the remaining subjects were assigned to the validation set. The least absolute shrinkage and selection operator (LASSO) regression analysis method was used for variable selection via running cyclic coordinate descent with 10-fold cross-validation. Multivariable logistic regression was then performed to develop a predictive model and nomogram. The receiver operating characteristic (ROC) curves was used for model evaluation, and calibration plot and decision curve analysis (DCA) were used for model validation.Results: Of 24 variables studied, 6 risk predictors were identified by LASSO regression analysis: hyperlipidaemia, hyperglycemia, abdominal obesity, systolic blood pressure (SBP), diastolic blood pressure (DBP), and body mass index (BMI). A prediction model including these 6 risk factors was constructed and displayed good predictability with an area under the ROC curve of 0.914 for the training set and 0.930 for the validation set. DCA revealed that if the threshold probability of MetS is less than 82%, the application of this nomogram is more beneficial than both the treat-all or treat-none strategies.Conclusion: The nomogram developed in our study demonstrated strong discriminative power and clinical applicability, making it a valuable reference for meets prevention and control in the plateau areas of Qinghai Province.Keywords: metabolic syndrome, nomogram, prediction model, plateau section

Wenying Jiang,1 Yunxing Wang,1 Changtao Yu,1 Deling Sui,1 Gang Du,2 Youchun Li1 1Department of General Surgery, The Second People’s Hospital of Liaocheng Affiliated to Shandong First Medical University, Liaocheng, Shandong, People’s Republic of China; 2Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Youchun Li, Department of General Surgery, The Second People’s Hospital of Liaocheng Affiliated to Shandong First Medical University, No. 306, Health Street, Linqing, Shandong, 252600, People’s Republic of China, Email lyc19820102@163.comBackground: Hepatocellular carcinoma (HCC) is a major cause of cancer death in the world. The aim of this study was to establish a new model to predict the prognosis of HCC.Materials and Methods: The mRNA, miRNA and lncRNA expression profiles of early (stage I–II) and late (stage III–IV) stage HCC patients were acquired from The Cancer Genome Atlas (TCGA) database. The differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs) and lncRNAs (DElncRNAs) were identified between early and late stage HCC. Key molecules associated with the prognosis, and important immune cell types in HCC were identified. The nomogram based on incorporating age, gender, stage, and all important factors was constructed to predict the survival of HCC.Results: A total of 1516 DEmRNAs, 97 DEmiRNAs and 87 DElncRNAs were identified. A DElncRNA-DEmiRNA-DEmRNA regulatory network including 78 mRNAs, 50 miRNAs and 1 lncRNA was established. Among the regulatory network, 11 molecules were significantly correlated with the prognosis of HCC based on Lasso regression analysis. Then, Preadipocytes and 3 survival-associated DEmRNAs were identified as crucial biomarkers. Subsequently, a nomogram with a differentiation degree of 0.758, including 1 immune cell, 11 mRNAs and 3 miRNAs, was generated.Conclusion: Our study constructed a model by incorporating clinical information, significant biomarkers and immune cells to predict the survival of HCC, which achieved a good performance.Keywords: hepatocellular carcinoma, stage, nomogram, TCGA

Qi Meng,1,2,* Jing Yang,1,2 Fei Wang,1,2 Cheng Li,3 Guoyao Sang,4 Hua Liu,1,2 Di Shen,1,2 Jinxia Zhang,1,2 Sheng Jiang,1,2,* Aibibai Yusufu,1,2,* Guoli Du1,2,* 1State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Urumqi, People’s Republic of China; 2Department of Endocrinology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 3Laboratory Medicine Diagnostic Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 4Data Statistics and Analysis Center of Operation Management Department, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guoli Du; Aibibai Yusufu, Department of Endocrinology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830000, People’s Republic of China, Email genemagic@126.com; hebibe@163.comPurpose: Cardiovascular disease is the leading cause of mortality in patients with type 2 diabetes mellitus (T2DM). This study aimed to develop and validate a nomogram for predicting the risk factors for coronary heart disease (CHD) in T2DM in the population of northwestern China.Patients and Methods: The records of 2357 T2DM patients who were treated in the First Affiliated Hospital of Xinjiang Medical University from July 2021 to July 2022 were reviewed. After some data (n =239) were excluded, 2118 participants were included in the study and randomly divided into a training set (n =1483) and a validation set (n = 635) at a ratio of 3:1. Univariate and stepwise regression analysis was performed to screen risk factors and develop predictive models. The results of logistic regression are presented through a nomogram. The C-index, receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis (DCA) were employed to verify the distinction, calibration, and clinical practicality of the model.Results: The stepwise logistic regression analysis suggested that independent factors in patients with T2DM combined with CHD were age, gender, hypertension (HTN), glycated hemoglobin (HbA1c), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and Uygur, which were associated with the occurrence of CHD. The nomogram demonstrated good discrimination with a C-index of 0.771 (95% CI, 0.741, 0.800) in the training set and 0.785 (95% CI, 0.743, 0.828) in the validation set. The area under curve (AUC) of the ROC curves were 0.771 (95% CI, 0.741, 0.800) and 0.785 (95% CI, 0.743, 0.828) in the training and validation sets, respectively. The nomogram was well-calibrated. The DCA revealed that the nomogram was clinically valuable.Conclusion: A nomogram based on 7 clinical characteristics was developed to predict CHD in patients with T2DM.Keywords: nomogram, coronary heart disease, type 2 diabetes mellitus, ethnicity, risk factor

Ge Du, Fangfang Liu, Xiaomin Ma, Shanshan Chen, Min Dai, Li Wei,&ast; Zishuang Liu&ast; Department of Rehabilitation Center for Elderly, Beijing Rehabilitation Hospital Affiliated to Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Wei; Zishuang Liu, Department of Rehabilitation Center for Elderly, Beijing Rehabilitation Hospital Affiliated to Capital Medical University, Beijing, 100144, People’s Republic of China, Tel/Fax + 86-010-56981582, Email weili2014@sina.com; 1774332663@qq.comPurpose: We retrospectively compared the complications, blood biochemical indexes and outcomes in patients with swallowing disturbances receiving nasogastric tube (NGT) feeding and percutaneous endoscopy gastrostomy (PEG).Methods: Among 160 patients, 72 cases received PEG and 88 cases received NGT. All patients were followed up for two years. We collected their clinical data from the medical records. Indicators, such as body mass index (BMI), white blood cell (WBC), hemoglobin (HGB), complications, including recurrent aspiration pneumonia, gastrointestinal bleeding, reflux esophagitis, and outcomes (survival or death) were compared between the two groups semi-annually.Results: SAt both six months and one year after receiving treatment, there was no statistical difference between the two groups in indicators, complications and outcomes, with all P > 0.05. It can be seen that, when the patients were followed up for one and a half years18 months, ALB was lower in the NGT group (33.81± 0.46) compared with the PEG group (36.14± 0.50) (P < 0.05). After two years of follow-up, differences between the NGT and PEG group could be seen in a variety of indicators, including BMI (20.08± 0.27 vs 21.03± 0.25), WBC (9.12± 0.56 vs 7.08± 0.29), ALB (33.11± 0.43 vs 35.75± 0.49), creatinine (55.07± 1.83 vs 63.21± 2.94), and the complications, such as aspiration pneumonia, gastrointestinal bleeding, reflux esophagitis, and electrolyte disorder, in the PEG group were significantly reduced compared to the NGT groupthan that in its counterpart, P < 0.05. In the two-year follow-up period, there were 13 and 22 patients died in the PEG group and NGT group, respectively.Conclusion: Both techniques are safe and effective in the short term. However, on a longer-term basis, PEG is shown to be superior to NGT feeding in improving nutrition and preventing common complications for patients with swallowing disturbances.Keywords: percutaneous endoscopy gastrostomy, nasogastric tube feeding, swallowing disturbances, two-year, follow-up

Fulai Tu,1,&ast; Ruizhe Yang,2,&ast; Weixiang Wang,3,&ast; Rui Li,1,&ast; Guoping Du,4 Yangyang Liu,1 Wei Li,5 Pingmin Wei1 1Key Laboratory of Environmental Medicine Engineering, Department of Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing, 210009, People’s Republic of China; 2Department of Prevention and Health Care, Children’s Hospital of Nanjing Medical University, Nanjing, 210008, People’s Republic of China; 3Department of Acute Infectious Disease Control, Nanjing Municipal Center for Disease Control and Prevention, Nanjing, 210003, People’s Republic of China; 4Department of General Practice, Southeast University Hospital, Nanjing, 210018, People’s Republic of China; 5Department of Quality Management, Children’s Hospital of Nanjing Medical University, Nanjing, 210009, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pingmin Wei, Key Laboratory of Environmental Medicine Engineering, Department of Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing, 210009, People’s Republic of China, Tel/Fax +86 025 87232481, Email mpw1963@126.com Wei Li, Department of Quality Management, Children’s Hospital of Nanjing Medical University, Nanjing, 210009, People’s Republic of China, Tel/Fax +86 025 52862911, Email weili126@126.comObjective: We aimed to describe the knowledge, attitude and practice (KAP) status of hepatitis B virus (HBV) among freshmen who were in the class of 2020 and from Jiangsu Province.Methods: A random multistage sampling had been used to screen freshmen to conduct online questionnaire. The chi-square test was applied for pairwise comparison between sub-groups. Lasso regression and logistic regression were used to analyze the influencing factors of KAP about HBV. A structural equation model was established to explore the relationships among KAP of HBV.Results: The total awareness rate of HBV among freshmen was 63.1%. More than 50% of freshmen reported that they were not willing to live with hepatitis B carriers. Only 51.0% of students had been immunized against HBV. The knowledge of HBV among students whose fathers had college/bachelor degree or above was 1.464 times higher than those whose fathers’ education level was junior high school or below (95% CI = 1.277∼ 1.677). Both of positive attitude and behavior among female students were 1.424 times (95% CI = 1.329∼ 1.525) and 1.468 times (95% CI = 1.291∼ 1.669) than that within male students, respectively. The positive behaviors of students whose mothers had college education or above were 1.347 times higher than those whose mothers had the degree of junior high or below (95% CI = 1.147∼ 1.582). Students who living with their parents were 1.167 times likely to have positive behaviors than those who living in other methods (95% CI = 1.020∼ 1.334). The structural equation model had shown that the direct effect of knowledge on preventive motivation, attitude and behavior was 0.28, 0.53 and 0.10, respectively.Conclusion: The population of freshmen still was far from a comprehensive understanding of HBV prevention and treatment. It is suggested that administrators of colleges and universities should pay more attentions to education of HBV knowledge as well as take multi-channel measures for prevention and management.Keywords: hepatitis B virus, knowledge attitude and practice, freshmen, Lasso-logistic regression, structural equation model

Min Zhang,1,&ast; Gang Du,2,&ast; Zhengtian Li,2 Dehui Li,3 Weichao Li,2 Hening Li,4 Xingxin Gao,3 Zhanhong Tang1 1Department of Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China; 2Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China; 3Department of Burns and Plastic, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China; 4Guangxi Medical University, Nanning, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhanhong Tang; Xingxin Gao, Email 18777008107@163.com; gao11500315@163.comBackground: Oxidative stress (OS) responses have been linked to oncogenesis and tumor progression and have recently been regarded as a potential strategy for tumor therapy. However, OS-related therapeutic targets have not been identified to date in the bladder cancer (BC).Methods: The mRNA expression and clinical data of BC were downloaded from the public database. Prognostic risk score signature was constructed using LASSO Cox regression analysis. External validation was performed in GSE15307 cohort. ESTIMATE, CIBERSORT, and ssGSEA algorithm were used to analyze immune cell infiltration and immune microenvironment. Next, functional enrichment analysis was performed to elucidate the mechanism underlying the signature. Additionally, we performed a nomogram to forecast the survival rate of individual BC patients.Results: An OS-related genes (OSRGs) signature was constructed. Overall survival was lower in the high-risk group than in the low-risk group, according to survival analyses. The area under the curve (AUC) of ROC curves further validated the prognostic signature’s strong prediction performance in these two cohorts. The risk score was verified as an independent risk factor for BC by independent prognostic analysis. Moreover, as compared to TNM stage alone, a nomogram that integrated the risk score with TNM stage showed a much superior predictive value. Immune infiltration and tumor microenvironment studies indicated that immune cells and functions may play a significant role in carcinogenesis and development. The levels of expression of prognostic genes were shown to be substantially linked with drug sensitivity.Conclusion: We developed a novel OSRGs signature for predicting overall survival and impacting the immune status in patients with BC. New nomogram can help clinicians predict the survival rate of BC patients. These findings shed new light on the potential usage of OSRGs signature in BC patients.Keywords: bladder cancer, oxidative stress, prognosis, risk signature, immune cell infiltration, drug sensitivity

Guoping Du,1,&ast; Chao Li,2,&ast; Yangyang Liu,3,&ast; Fulai Tu,3 Ruizhe Yang,4 Rui Li,3 Hongbing Shen,2 Wei Li5 1Department of General Practice, Southeast University Hospital, Nanjing, Jiangsu, People’s Republic of China; 2Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 3Key Laboratory of Environmental Medicine Engineering, Department of Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing, Jiangsu, People’s Republic of China; 4Department of Prevention and Health Care, Children’s Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 5Department of Quality Management, Children’s Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Li, Department of Quality Management, Children’s Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China, Tel/Fax +86 025 52862911, Email weili126@126.com Hongbing Shen, Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China, Tel/Fax +86 025 86868409, Email hbshen@njmu.edu.cnBackground: Adolescents aged from 19 to 22 are the main high-risk population of pulmonary tuberculosis (PTB). This study aimed to understand the current status of knowledge, attitudes and practices (KAP) about TB among freshmen from Jiangsu colleges and universities. Analyze its influencing factors and explore the interrelationships of KAP. This provides a basis for building a reversing mechanism for health education on tuberculosis prevention and treatment in middle and high schools.Methods: A multistage randomly was used to select freshmen to conduct this online survey. The χ2 test was used to compare the rates. Construct linear regression model, logistic regression model, decision tree model and random forest model, use grid search to adjust the parameters of the model, and use multiple models to explore the influencing factors of the overall awareness rate of students’ core knowledge of tuberculosis.Results: A total of 6980 freshmen in colleges and universities were investigated. The total awareness rate was 89.02%, and the awareness rate of all core knowledge about TB was 58.94%. It is characterized by general demographic data, and all core knowledge is known as a label to establish a model, based on the f1- of the four models The score believes that the random forest model has the best fitting effect, and the ranking of the influencing factors included in the model is school type (0.72) >father’s education (0.15) >family monthly income (0.03) >mother’s education, gender, region (0.02); a structural equation model is established, and the modified knowledge and attitude path coefficient is 0.29 (P< 0.05); the attitude and behavior path coefficient is 0.64 (P< 0.05).Conclusion: The total awareness rate of core knowledge of Jiangsu college freshmen reaches the national requirements, but the overall awareness rate is low. It is necessary to strengthen the health education of tuberculosis for those with identified risk factors.Keywords: knowledge, attitudes and practices, tuberculosis, freshmen

Yi Zhong,1,2,* Guoyong Du,1,2,* Jie Liu,1,2,* Shaohua Li,1 Junhua Lin,1 Guoxiong Deng,1,2 Jinru Wei,1,2 Jun Huang1,2 1Department of Cardiology, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530022, People’s Republic of China; 2Department of Cardiology, The First People’s Hospital of Nanning, Nanning, Guangxi, 530022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jinru Wei; Jun Huang, Tel +867712636193, Email weijinru@stu.gxmu.edu.cn; huangjijun1981@163.comBackground: Cardiovascular complications are a major cause of death and disability in patients with diabetes mellitus, but how such complications arise is unclear.Methods: Weighted gene correlation network analysis (WGCNA) was performed on gene expression profiles from healthy controls, individuals with diabetes mellitus, and individuals with diabetes mellitus-associated coronary artery disease (DMCAD). Phenotypically related module genes were analyzed for enrichment in Gene Ontology (GO) terms and Kyoto Gene and Genome Encyclopedia (KEGG) pathways. Predicted biological functions were validated using gene set enrichment analysis (GSEA) and ClueGo analysis. Based on the TRRUST v2 database and hypergeometric tests, a global network was built to identify transcription factors (TFs) and downstream target genes potentially involved in DMCAD.Results: WGCNA identified three modules associated with progression from diabetes mellitus to DMCAD. The module genes were significantly involved in biological processes related to interferon and viral infection, while GSEA of DMCAD samples suggested involvement in viral myocarditis, chemokine signaling and phagosomes. RUNX1 was identified as a potential TF regulating these module genes. Analysis of the global regulatory network of TFs and their targets suggested that CCL3 may be a key regulator in DMCAD.Conclusion: We found bioinformatic evidence that CCL3 may be a key regulator and RUNX1 a key TF in DMCAD.Keywords: diabetes mellitus, coronary artery disease, transcription factors

Xiaojie Bai, Yuanfei Cao, Xin Yan, Kurerban Tuoheti, Guowei Du, Zhao Chen, Huahui Wu, Linfa Guo, Tongzu Liu Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of ChinaCorrespondence: Tongzu LiuDepartment of Urology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, 430071, People’s Republic of ChinaTel +86-27-67813104Fax +86-27-67812667Email liutongzu@163.comPurpose: This study aims to carry out a pan-cancer analysis of kinesin family member 23 (KIF23) and construct a predictive model for the prognosis of clear cell renal cell carcinoma (ccRCC) patients.Methods: We evaluated the differential expression of KIF23 in pan-cancer by The Cancer Genome Atlas (TCGA) and Oncomine database. Then, the correlation between KIF23 with prognosis, clinical grade, stage, immune subtype, tumor mutation burden (TMB), microsatellite instability (MSI) and immune microenvironment was explored by TCGA, an integrated repository portal for tumor-immune system interactions (TISIDB) and cBioPortal. Subsequently, we screened out ferroptosis-related genes (FRGs) related to KIF23 and constructed a risk score model. Univariate Cox analysis was used to determine independent prognostic factors for ccRCC overall survival (OS), and a nomogram was established. Furthermore, gene set enrichment analysis (GSEA) was applied to study the biological functions and pathways of KIF23. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to evaluate the expression of KIF23.Results: KIF23 was highly expressed in most tumors. Further, KIF23 was strongly correlated with prognosis, clinical grade, stage, immune subtype, TMB, MSI and immune microenvironment in different tumors. We found that KIF23 was significantly associated with all aspects of ccRCC. Then, 8 FRGs were identified to construct a risk score model together with KIF23. And a prognostic nomogram prediction model of OS was established. After GSEA analysis, cell cycle, condensed chromosome and other physiological processes were screened out. Finally, qRT-PCR verified the high expression of KIF23 in ccRCC cell lines than normal kidney cell line.Conclusion: KIF23 may act as a pivotal part in occurrence and progression of different tumors. In ccRCC, KIF23 can be a great prognostic biomarker, and the nomogram based on KIF23 may contribute to better treatment plans for ccRCC patients.Keywords: clear cell renal cell carcinoma, ferroptosis, nomogram

Yunjia Yang,1,* Hairong Huang,1,* Zeying Cui,2 Jun Chu,3 Guankui Du2,4,5 1School of Public Health, Hainan Medical University, Haikou, People’s Republic of China; 2Key Laboratory of Molecular Biology, Hainan Medical University, Haikou, People’s Republic of China; 3Key Laboratory of Xin’an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, Anhui, People’s Republic of China; 4Department of Biochemistry and Molecular Biology, Hainan Medical University, Haikou, People’s Republic of China; 5Biotechnology and Biochemisty Laboratory, Hainan Medical University, Haikou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guankui DuDepartment of Biochemistry and Molecular Biology, Hainan Medical University, Haikou, 571101, People’s Republic of ChinaTel +86-898-66893779Fax +86-898-66893600Email duguankui@163.comJun ChuKey Laboratory of Xin’an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, 230038, Anhui, People’s Republic of ChinaEmail chuj@ahtcm.edu.cnBackground: Betel nuts have long been used in traditional Chinese medicine. In our study, the bioactive components of betel nut were systematically investigated, and the main components and their target genes in the treatment of depression were predicted.Methods: The metabolites of the kernels and peels were analyzed with a UPLC–MS/MS system. Mass spectrometry outcomes were annotated by MULTIAQUANT. “Compound‐disease targets” were utilized to construct a pharmacology network.Results: A total of 873 metabolites were identified, with a high abundance of flavonoids, alkaloids, and phenols. Moreover, the abundance of flavonoids, alkaloids, and phenols in the kernel was significantly higher than that in the peel. A high abundance of catechin, arginine, and phenylalanine was detected in the kernel, while a high abundance of arginine, arecoline, and aminobutyric acid was detected in the peel. Catechins and cyanoside were the most abundant flavonoids in the kernel and peel, respectively. Arecoline was the most abundant alkaloid. A total of 111 metabolites showed a significant difference between the kernels and peels. The relative abundance of 40 differential metabolites was higher than 100,000, including 14 primary metabolites, 12 flavonoids, 4 phenols, and 4 alkaloids. Among the 40 high abundance metabolites, 20 were higher in the kernel and 20 in the peel. In addition, the enrichment of metabolic pathways found that the kernel and peel of the fruit adopted different metabolic pathways for the synthesis of flavonoids and alkaloids. Network pharmacology prediction showed that 93 metabolites could target 141 depression-related genes. The main components of betel nut intervention in depression were predicted to include L-phenylalanine, protocatechuic acid, okanin, nicotinic acid, L-tyrosine, benzocaine, syringic acid, benzocaine, phloretic acid, cynaroside, and 3,4-dihydroxybenzaldehyde.Conclusion: Betel nuts are rich in natural metabolites, and some of these metabolites can participate in the intervention of depression. In addition, the metabolites showed distinct characteristics between the kernel and peel. Therefore, it is necessary to comprehensively and rationally use betel nuts.Keywords: betel nut, metabolites, flavonoid, alkaloids, phenols

Guangbin Zhu,1,&ast; Jinwen Luo,1,&ast; Zhongmin Ouyang,1 Zenglan Cheng,1 Yi Deng,1 Yubao Guan,1 Guoxin Du,1 Fengjin Zhao2 1Guangzhou Key Laboratory of Enhanced Recovery after Abdominal Surgery, Department of Radiology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510799, People’s Republic of China; 2Department of Urology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510799, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhongmin OuyangGuangzhou Key Laboratory of Enhanced Recovery after Abdominal Surgery, Department of Radiology, The Fifth Affiliated Hospital of Guangzhou Medical University, No. 621 of Gangwan Road, Huangpu District, Guangzhou, 510799, People’s Republic of ChinaTel +86-20-85959142Email ouyangzm2021@aliyun.comObjective: To explore the value of combining dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) quantitative parameters with apparent diffusion coefficient (ADC) values in the diagnosis of prostate cancer.Methods: The clinical data of 146 patients with prostate lesions, including 87 patients with prostate cancer (PCa) and 59 with benign prostatic hyperplasia (BPH), were collected. After DCE-MRI and diffusion-weighted imaging (DWI) prostate scans, the magnitude of the DCE-MRI transfer constant (Ktrans), rate constant (kep), the volume of the extravascular extracellular space (ve), and the ADC between the groups were compared, and the correlations between the DCE-MRI parameters and Gleason scores were analyzed. The diagnostic efficacy of these quantitative parameters was assessed by the area under the receiver operating characteristic (ROC) curve.Results: The DCE-MRI parameters Ktrans and kep were significantly greater in the PCa group than in the BPH group (p < 0.05). The ROC curve showed the area under the Ktrans, kep, and ADC curves to be 0.665, 0.658, and 0.782, respectively. When all three quantitative indicators were combined, the area under the ROC curve was 0.904, with sensitivity and specificity rates of 83.6% and 93.7%, respectively. The Gleason scores were positively correlated with the Ktrans, kep, and ve (r = 0.39, 0.572, 0.30, respectively; p < 0.05) and negatively correlated with the ADC (r = – 0.525; p < 0.05).Conclusion: The DCE-MRI quantitative parameters Ktrans and kep, as well as the ADC value, provided effective references for the differential diagnosis of PCa and BPH, as well as more precise and reliable quantitative parameters for grading the aggressiveness of PCa.Keywords: quantitative DWI, dynamic contrast-enhanced MRI, ADC value, Ktrans, kep, benign prostatic hyperplasia, prostate cancer

Background The traumatic dislocation of the radial head in children is commonly treated by closed reduction. Sometimes, however, this strategy of treatment may not be effective due to the location of soft tissues in the radio‐shoulder joint. The literature presents a few cases of the irreducible radial head dislocation with ulnar plastic deformation. Because it is a relatively rare condition, such a traumatic dislocation can be easily missed. Neglected injuries can lead to unwanted complications and unpredictable surgical outcomes. Case presentation This study presents a relatively rare case of traumatic radial head dislocation with ulnar plastic deformation in a 3‐year‐old child, which was successfully treated by open reduction. The examined case did not require osteotomy and ligamentous reconstruction. The initial attempt of closed reduction failed due to annular ligament interposition, which has been detected on MRI. After 3 months of treatment, the range of motion of the operated arm gradually improved. At the 6‐month follow‐up, the Mayo elbow‐performance score indicated an excellent treatment outcome. Conclusions The delayed treatment of radial head dislocation with ulnar plastic deformation can hinder the supination and pronation of the forearm, resulting in elbow/forearm deformity. The earlier this condition is detected, the easier it will be to treat it and the better the treatment outcome will be. The examined case of irreversible traumatic dislocation, successfully treated by open reduction, may help to treat radial head dislocation better.

Guangrui Chai,1 Shu Liu,2 Hongwei Yang,1 Guoqiang Du,3 Xiaolong Chen1 1Department of Ophthalmology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China; 2Department of Geratology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China; 3Department of Otolaryngology, Qingdao Municipal Hospital, Qingdao, Shandong, People’s Republic of ChinaCorrespondence: Xiaolong Chen Email chenxl@sj-hospital.orgBackground: Inflammation and angiogenesis are the two dominant mechanisms of diabetic retinopathy (DR), which act more as mutual pathways rather than individual processes. However, the underlying mechanism of their interactions is still unclear. Here, we explored the potential crossing points between these pathways and the targeted therapeutic method in rats with DR.Materials and Methods: Sprague–Dawley rats were randomly assigned to four groups: normal control group, streptozocin (STZ)-induced diabetes mellitus (DM) group, DM+shNC (non-specific negative control shRNA) group, and DM+shNLRP3 group. Silencing the NLR family pyrin domain containing 3 (NLRP3) protein was performed by intravitreal injections of NLRP3-targeted shRNA (shNLRP3) for rats in the DM+shNLRP3 group. All the rats’ retinas were collected for further morphological examination and pro-inflammatory and pro-angiogenic cytokine detection. Human retinal endothelial cells (HRECs) were also employed to explore the underlying mechanism.Results: NLRP3-targeted shRNA given by intravitreal injection effectively alleviated the retinal histopathological changes in STZ-induced diabetic rats, which reduced the activation of the NLRP3 inflammasome and suppressed the expressions of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and inflammatory cytokines in diabetic rats’ retinas. In HRECs, NLRP3 over-expressing plasmid evoked an increase in pro-inflammatory cytokines and VEGF. In addition, YC-1, a HIF-1α inhibitor, could reverse the NLRP3 over-expression-induced VEGF production but not the pro-inflammatory cytokine expressions.Conclusion: Our results suggest NLRP3 inflammasome as the potential cross-point between inflammation and pro-angiogenesis in DR and support the effectiveness of NLRP3-targeted shRNA administrated by intravitreal injection in animal models of DR. The protective effect of NLRP3-targeted shRNA may stem from the inhibition of both pro-inflammatory cytokines and HIF-1α/VEGF axis.Keywords: NLRP3 inflammasome, inflammation, angiogenesis, VEGF, diabetic retinopathy

Jianjun Zhu,1 Lihong Shi,2 Genlai Du,1 Li Li,1 Ming Liu1 1Department of Medical Cellular Biology and Genetics, Shanxi Medical University, Taiyuan 030001, People’s Republic of China; 2Department of Human Anatomy, School of Basic Medicine, Shanxi Medical University, Taiyuan 030001, People’s Republic of ChinaCorrespondence: Lihong ShiDepartment of Human Anatomy, School of Basic Medicine, Shanxi Medical University, 56 Xinjian South Road, Taiyuan 030001, People’s Republic of ChinaTel/ Fax +86-351-3985176Email czxy12@163.comPurpose: SET has been proven to be an oncogene, which promotes the initiation and progression in several kinds of malignant carcinomas. However, the expression and its functional roles in colorectal carcinoma (CRC) remained unknown.Materials and Methods: CRC tissues samples, CRC cell lines and xenograft mouse tumors were used in this study. The mRNA and protein expressions were detected by quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC), and Western blot (WB), respectively. siRNAs were used to silence the gene expression. Cell viability, cell proliferation, colony formation, and apoptosis were measured by MTS assay, EdU incorporation assay, plated colony formation assay, and flow cytometry, respectively. Western blot was applied to evaluate the levels of Akt, p-Akt, c-Myc and cyclin D1. Xenograft mouse model was performed to observe the role of SET in vivo.Results: Our results revealed that SET was up-regulated in CRC, and the expression of SET was increased with the development of CRC. SET knockdown in vitro attenuated cell proliferation activity, and increased cell apoptosis in CRC cells. Moreover, the knockdown of SET reduces tumorigenic potential in nude mice. For the mechanism, knockdown of SET promoted the dephosphorylation of Akt, followed by suppressing the translocation of NF-κB to nucleus. In addition, SET knockdown-mediated dephosphorylation of Akt downregulated the expression of c-Myc and Cyclin D1, which inhibited the cell survival in CRC.Conclusion: Our results indicated that SET promoted cell survival via activating Akt/NF-κB signaling pathway in CRC, which strongly suggested that SET might be a potential therapeutic target in the colorectal carcinoma treatment.Keywords: SET, colorectal adenocarcinoma, PP2A, Akt, NF-κB

Asthma is a complex genetic disease caused by a combination of genetic and environmental risk factors. We sought to test classes of genetic variants largely missed by genome-wide association studies (GWAS), including copy number variants (CNVs) and low-fre

Tianfeng Yang,1,* Guowen Du,2,* Yuxin Cui,1 Runze Yu,1 Chen Hua,2 Wei Tian,2,3 Yanmin Zhang1 1School of Pharmacy, Health Science Center, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China; 2The Key Laboratory of Space Applied Physics and Chemistry Ministry of Education and Shanxi Key Laboratory of Macromolecular Science and Technology, School of Science, Northwestern Polytechnical University, Xi’an 710072, China; 3Xi’an Institute for Biomedical Materials and Engineering, Northwestern Polytechnical University, Xi’an 710072, China *These authors contributed equally to this work Background: Doxorubicin (DOX) is one of the most effective treatments for hepatocellular carcinoma (HCC), but is restricted by its poor pharmacokinetics. Herein, we exploited efficient targeted drug delivery systems and they have been found to be a worthy strategy for liver cancer therapy. Materials and methods: We investigated polymeric nanoparticles which were synthesized based on host–guest interaction between β-cyclodextrin and benzimidazole. The properties of nanoparticles with regard to size/shape, encapsulation efficiency, and drug release were investigated using conventional experiments. Cell proliferation assay in vitro, cell uptake assay, and cell apoptosis analysis were used to investigate cytotoxicity, uptake, and mechanism of targeted supramolecular prodrug complexes (TSPCs)-based self-assemblies and supramolecular prodrug complexes (SPCs)-based self-assemblies. Results: The pH-sensitive lactobionic acid (LA)-modified pH-sensitive self-assemblies were synthesized successfully. The results of in vitro released assay showed that the accelerated released of DOX from TSPCs-based self-assemblies with the decrease of pH value. When TSPCs-based self-assemblies were taken up by HepG2 cells, they demonstrated a faster release rate under acidic conditions and proved to have higher cytotoxicity than in the presence of LA. A mechanistic study revealed that TSPCs-based self-assemblies inhibited liver cell proliferation by inducing cell apoptosis. Conclusion: The pH-sensitive nanocomplex, as liver-targeted nanoparticles, facilitated the efficacy of DOX in HepG2 cells, offering an appealing strategy for the treatment of HCC. Keywords: pH-sensitive, hepatocellular carcinoma, doxorubicin, drug delivery

An updated accumulation map for Greenland is presented on the basis of 39 new ice core estimates of accumulation, 256 ice sheet estimates from ice cores and snow pits used in previous maps, and reanalysis of time series data from 20 coastal weather stations. The period 1950-2000 is better represented by the data than are earlier periods. Ice-sheetwide accumulation was estimated based on kriging. The average accumulation (95% confidence interval, or ±2 times standard error) over the Greenland ice sheet is 30.0 ± 2.4 g cm -2 a-1, with the average accumulation above 2000-m elevation being essentially the same, 29.9 ± 2.2 g cm-2 a -1. At higher elevations the new accumulation map maintains the main features shown in previous maps. However, there are five coastal areas with obvious differences: southwest, northwest, and eastern regions, where the accumulation values are 20-50% lower than previously estimated, and southeast and northeast regions, where the accumulation values are 20-50% higher than previously estimated. These differences are almost entirely due to new coastal data. The much lower accumulation in the southwest and the much higher accumulation in the southeast indicated by the current map mean that long-term mass balance in both catchments is closer to steady state than previously estimated. However, uncertainty in these areas remains high owing to strong gradients in precipitation from the coast inland. A significant and sustained precipitation measurement program will be needed to resolve this uncertainty. Copyright 2009 by the American Geophysical Union.