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Pei Zhang,1,* Tian-Yu Wang,2,* Zi-Yue Luo,2 Jun-Can Ding,2 Qiang Yang,2 Peng-Fei Hu3 1Department of Cardiology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou, Zhejiang Province, 310018, People’s Republic of China; 2Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310053, People’s Republic of China; 3Department of Cardiology, the Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310005, People’s Republic of China*These authors contributed equally to this workCorrespondence: Peng-Fei Hu, Department of Cardiology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310005, People’s Republic of China, Tel +86 15267037741, Email 20064012@zcmu.edu.cnPurpose: Heart failure is a serious complication after acute myocardial infarction (AMI). It is crucial to investigate the mechanism of action of empagliflozin in the treatment of heart failure.Methods: A total of 20 wild type (WT) male C57BL6/J mice were used to establish a model of heart failure after myocardial infarction and randomly divided into 2 groups: treatment group and control group. The treatment group was treated with empagliflozin, and the control group was treated with placebo. After 8 weeks of treatment, mouse heart tissues were collected for next generation sequencing. Bioinformatics methods were used to screen the key genes. Finally, the correlation between clinical data and gene expression was analyzed. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the expression of key genes.Results: A mouse model of heart failure was successfully constructed. By DEG analysis, a total of 740 DEGs in the treatment group vs the control group were obtained. Dendritic cells, granulocytes, follicular B, plasma cell, cDC1, cDC2, pDC and neutrophils were 8 different immune cells identified by immunoinfiltration analysis. Through WGCNA, the turquoise module with the highest correlation with the above differential immune cells was selected. One hundred and forty-two immune-related DEGs were obtained by taking intersection of the DEGs and the genes of the turquoise module. Col17a1 and Gria4 were finally screened out as key immune-related genes via PPI analysis and machine learning. Col17a1 was significantly up-regulated, while Gria4 was significantly down-regulated in the treatment group. At the same time, the expression level of Col17a1 was significantly correlated with left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS) and left ventricular internal dimension systole (LVIDs).Conclusion: Col17a1 and Gria4 are key immune-related genes of empagliflozin in the treatment of heart failure after myocardial infarction. This study provides a scientific basis for elucidating the mechanism of action of empagliflozin in treating heart failure after myocardial infarction.Keywords: heart failure after myocardial infarction, empagliflozin, immunology, RNA-seq

Ting Xia,1– 3 Xiao Liang,4 Chang-Shun Liu,1– 3 Yan-Nan Hu,1– 3 Zhen-Ye Luo,1– 3 Xiao-Mei Tan1– 3 1School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 3Guangdong Provincial Engineering Laboratory of Chinese Medicine Preparation Technology, Guangzhou, 510515, People’s Republic of China; 4School of Pharmaceutical Sciences, Guilin Medical University, Guilin, 541199, People’s Republic of ChinaCorrespondence: Xiao-Mei Tan, Tel/Fax + 86-020-61648265, Email tanxm_smu@163.comBackground: Ermiao Wan (EMW) is commonly used to treat atopic dermatitis (AD) in China. However, the pharmacological mechanisms underlying the action of EMW against AD remain unclear.Purpose: We aimed to determine the mechanisms underlying the effectiveness of EMW in the treatment of AD.Methods: We evaluated the effect of EMW on AD induced by dinitrochlorobenzene (DNCB) in BALB/C mice. To clarify the key components of EMW in AD treatment, the main components of EMW were identified using HPLC. Serum pharmacochemistry was used to analyze the absorbed ingredients from blood. Based on the phytochemical results, network pharmacology and molecular docking were used to predict the action of EMW. Skin transcriptomic analysis was used to validate the network pharmacology results. RT-qPCR,ELISA, and immunohistochemical were performed to validate the results of skin transcriptomics.Results: EMW improved the symptoms of AD, with less rashes, less spontaneous scratching, less inflammatory cell infiltration, and fewer allergic reactions. The established HPLC method is simple and reliable. Chlorogenic acid, phellodendrine, magnoflorine, jatrorrhizine, palmatine, berberine, and atractylodin were the key effective ingredients with a high blood concentration. Fifty-seven primary causal targets of EMW against AD were identified. These targets are mainly involved in ErbB signaling pathways including EGFR, AKT1, MAPK8, JUN, MAPK1. Molecular docking showed that EGFR, AKT1, MAPK8, JUN, MAPK1 had good binding force with EMW. In AD mice, EMW regulated the EGFR/AKT signaling through upregulation of Grb2, GAB1, Raf-1, EGFR, and AKT, and downregulation of MAPK1 and JUN, compared to that in the MD group.Conclusion: EMW could alleviate AD through activating EGFR/AKT signaling and suppressing MAPK. This study provides a theoretical basis for the clinical use of EMW.Keywords: Ermiao Wan, atopic dermatitis, network pharmacology, serum pharmacochemistry, skin transcriptome, EGFR/AKT signaling

Chun-Yang Wang,1,2 Shu Liu,1,2 Xiao-Nv Xie,1,2 Zhi-Ying Luo,1,2 Li Yang,1,2 Zhi-Rong Tan1,2 1Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, People’s Republic of China; 2Department of Clinical Pharmacology, Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, People’s Republic of China Introduction: The small peptide transporter 1 (PepT-1) and adipose phospholipase A2 (AdPLA) play a key role in the development of obesity. However, there are no data assessing the impact of PepT-1 (SLC15A1) and AdPLA (PLA2G16) variants on obesity susceptibility. Therefore, we assessed the contribution of 9 single-nucleotide polymorphisms (SNPs) between these two genes on obesity susceptibility in Chinese subjects.Materials and methods: A total of 611 participants were enrolled in the study, and 9 SNPs in the SLC15A1 and PLA2G16 genes were selected. Blood samples were collected for genotyping. Overweight and obesity were established by body mass index. Regression analyses were performed to test for any association of genetic polymorphisms with weight abnormality.Results: The genotype frequencies (P=0.04 for rs9557029, P=0.027 for rs1289389) were significantly different between obese or overweight subjects and healthy controls. However, no significant difference in allele was found between these three groups (P>0.05). Further logistic regression analyses adjusted for age and sex also failed to reveal significant associations between overweight, obesity, and the selected SNPs (P>0.05).Conclusion: Data indicate that the selected 9 SNPs in SLC15A1 and PLA2G16 genes were not related to obesity susceptibility in the Han Chinese population. Keywords: obesity, BMI, Chinese subjects, genotyping, SNPs

Hai-Fei Chen,1,2 Li-Ping Xu,1 Zhi-Yong Luo,1 Zi-Qiang Yu,2 Zheng-Yang Li,1 Qing-Ya Cui,1 Long-Mei Qin,1 Yong-Ya Ren,1 Hong-Shi Shen,1 Jie-Qing Tang,1 Ling-Juan Jin,1 Jing-Jing Zhu,1 Jing Wang,1 Ke-Yuan Wang,1 Tian-Qin Wu,1 Zhao-Yue Wang21Department of Hematology, 100th Hospital of People's Liberation Army, 2Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, People's Republic of ChinaAbstract: A 41-year-old male had suffered from gradual hearing loss in his right ear for 2 years. Head computed tomography and magnetic resonance imaging scans showed a neoplasm in the cerebellopontine angle region, which was confirmed by the diagnosis of acoustic neurilemmoma by pathological findings after surgery. Following surgery, he routinely received valproic acid (VPA) to prevent seizures. However, the patient presented with hypofibrinogenemia and cerebral hemorrhage after taking VPA for 12 days. The hypofibrinogenemia recurred when VPA was re-administered. After withdrawal of VPA, his fibrinogen concentration rose to normal within several days. As far as we are aware, this is the first case of cerebral hemorrhage due to VPA to have been reported. Herein, as well as reporting on this case, a mini review of the relevant literature is also presented.Keywords: side effect, hypofibrinogenemia, cerebral hemorrhage, cerebellopontine angle, neoplasm

Overexpression of RhoC in breast cancer cells indicates poor prognosis. In the present study, we aim to investigate the possible antitumor effects of anti-RhoC small-interfering RNA (siRNA) in inflammatory breast cancer cells. In this study, a specific anti-RhoC siRNA was used to inhibit RhoC synthesis. Transfection of anti-RhoC siRNA into two IBC cells SUM149 and SUM190 induced extensive degradation of target mRNA and led to significant decrease in the synthesis of protein. Anti-RhoC siRNA inhibited cell proliferation and invasion, increased cell apoptosis, and induced cell cycle arrest in vitro. Moreover, the transfection of siRNA increased the expression of KAI1 and decreased the expression of MMP9 and CXCR4 in both mRNA and protein levels. Furthermore, transplantation tumor experiments in BALB/c-nu mice showed that intratumoral injection of anti-RhoC siRNA inhibited tumor growth and increased survival rate. Our results suggested that RhoC gene silencing with specific anti-RhoC siRNA would be a potential therapeutic method for metastatic breast cancer., Competing Interests: Disclosure The authors report no conflicts of interest in this work.