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Xia Gu,1,2,* Hui Zhou,1,* Mengyue Miao,1 Daifeng Hu,1 Xinyue Wang,3 Jing Zhou,4 Alexander Tobias Teichmann,1 Youzhe Yang,1,5 Chunyan Wang1 1Sichuan Provincial Center for Gynaecology and Breast Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Department of Gynaecology and Obstetrics, Leshan People’s Hospital, Leshan, 614003, People’s Republic of China; 3The Basic Medical College, Army Medical University, Chongqing, 400038, People’s Republic of China; 4Department of Endocrinology, Chengdu Third People’s Hospital, Chengdu, 610014, People’s Republic of China; 5Academician (Expert) Workstation of Sichuan Province, Luzhou, 646000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Youzhe Yang; Chunyan Wang, The Affiliated Hospital of Southwest Medical University, NO. 25 Taiping Street, Jiangyang District, Luzhou, 646000, People’s Republic of China, Email yangyouzhe@swmu.edu.cn; wangchunyan6813@swmu.edu.cnAbstract: Endometriosis (EMS) is defined as the appearance, growth, infiltration, and repeated bleeding of endometrioid tissue (glands and stroma) outside the uterus cavity, which can form nodules and masses. Endometriosis is a chronic inflammatory estrogen-dependent disease and occurs in women of reproductive age. This disorder may significantly affect the quality of life of patients. The pathogenic processes involved in the development and maintenance of endometriosis remain unclear. Current treatment options for endometriosis mainly include drug therapy and surgery. Drug therapy mainly ties to the use of non-steroidal anti-inflammatory drugs (NSAIDs) and hormonal drugs. However, these drugs may produce adverse effects when used for long-term treatment of endometriosis, such as nausea, vomiting gastrointestinal reactions, abnormal liver and kidney function, gastric ulcers, and thrombosis. Although endometriosis lesions can be surgically removed, the disease has a high recurrence rate after surgical resection, with a recurrence rate of 21.5% within 2 years and 40% to 50% within 5 years. Thus, there is an urgent need to develop alternative or additional therapies for the treatment of endometriosis. In this review, we give a systematic summary of therapeutic multiple component prescriptions (including traditional Chinese medicine and so on), bioactive crude extracts of plants/herbs and purified compounds and their newly found mechanisms reported in literature in recent years against endometriosis.Keywords: endometriosis, treatment, multiple component prescriptions, extracts of plants/herbs, purified compounds, mechanisms

Daifeng Hu,1,* Mengyue Miao,1,* Hui Zhou,1 Xia Gu,1,2 Xuedan Wang,3 Alexander Tobias Teichmann,1 Qin Wang,1 Youzhe Yang1,2 1Sichuan Provincial Center for Gynaecology and Breast Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Academician (Expert) Workstation of Sichuan Province, Luzhou, 646000, People’s Republic of China; 3Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qin Wang; Youzhe Yang, The Affiliated Hospital of Southwest Medical University, NO. 25 Taiping Street, Jiangyang District, Luzhou, 646000, People’s Republic of China, Email wangq@swmu.edu.cn; yangyouzhe@swmu.edu.cnAbstract: Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors originating from perivascular epithelioid cells. In gynecological system, the uterus is one of the most common sites affected by PEComas. Most PEComas are benign, and patients usually have a good prognosis. However, malignant uterus PEComa is rare, and better comprehensive epidemiological investigations are needed. To date, there are a few reported cases of uterus PEComa. We herein report a rare case of malignant PEComa occurred in the uterine corpus and cervix, possibly accompanied by pulmonary lymphangioleiomyomatosis (PLAM). In addition, 55 cases of malignant uterus PEComa were picked out and collected in the data base of PubMed and Medline. On the one hand, the age of onset, population distribution, clinical manifestations, metastatic sites and routes of metastasis were analysed. On the other hand, a summary of the epidemiology, pathogenesis, diagnosis, and treatments of uterus PEComa was given.Keywords: perivascular epithelioid cell tumors, uterus, malignant, rare case, cervix

Shuo Tian,1,2 Lin Guo,3 Yagang Song,1,2 Huiyan Yang,1 Jia Wang,3 Jingyi Qiao,1,2 Xiangxiang Wu,1,2 Ming Bai,1,2 Mingsan Miao1,2 1Academy of Traditional Chinese Medicine, Henan University of Chinese Medicine, Zhengzhou, Henan, 450046, People’s Republic of China; 2Henan Collaborative Innovation Center for Research and Development on the Whole Industry Chain of Yu-Yao, Henan University of Chinese Medicine, Zhengzhou, Henan, 450046, People’s Republic of China; 3Department of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, Henan, 450046, People’s Republic of ChinaCorrespondence: Mingsan Miao, Henan Collaborative Innovation Center for Research and Development on the Whole Industry Chain of Yu-Yao, Henan University of Chinese Medicine, Zhengzhou, Henan, 450046, People’s Republic of China, Tel/Fax +86 371 65962546, Email miaomingsan@hactcm.edu.cnPurpose: Radix Salvia miltiorrhiza (RSM), a commonly used medicinal plant, has been reported to have anti-inflammatory effects, but relevant studies on burn injuries are lacking. We investigated the anti-inflammation and wound healing (WH) effects of an aqueous extract of RSM on a burn model in rats.Methods: The effects of RSM were studied by heat-induced burns in rats, treatment with vehicle, Jinwanhong ointment, and RSM (1.5 or 0.75 g/mL). Indicators of burn tissue (BT) were photographed by digital machines and analyzed. The microcirculation in BT was detected by scattered full-frame real-time imaging. Levels of inflammatory mediators and growth factors were measured by enzyme-linked immunosorbent assay (ELISA) and immunohistochemical staining. Local pathologic changes in BT were observed by hematoxylin-and-eosin (HE) staining. Ultrahigh pressure liquid chromatography–linear ion trap–Orbitrap mass spectrometry (UHPLC–LTQ–Orbitrap-MS) was used to explore the absorption of RSM in local skin, subcutaneous tissue, muscle tissue, serum, liver tissue, and kidney tissue.Results: RSM treatment could reduce the wound area, increase percent WH, increase blood perfusion in BT, reduce serum levels of interleukin (IL)-6, IL-1, tumor necrosis factor-α (TNF-α), increase levels of epidermal growth factor (EGF), transforming growth factor (TGF)-β, and hydroxyproline (Hyp) in serum, and increase protein expression of basic fibroblast growth factor (bFGF), TGF-β 1, EGF, and insulin-like growth factor-1 (IGF)-1 in skin tissues. RSM treatment led to micro-absorption in the skin, subcutaneous tissues, and muscle, but not in the blood, liver, or kidney.Conclusion: RSM may promote WH by exerting anti-inflammatory effects, improving local-wound microcirculation, and accelerating the metabolism at the wound surface.Keywords: Radix Salvia miltiorrhiza, burns, anti-inflammatory, wound healing

Meng Miao,1 Mingyang Lyu,2 Chi Zhong,1 Ying Liu3 1Department of Neurology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, People’s Republic of China; 2Haihe Laboratory of Cell Ecosystem, Tianjin, People’s Republic of China; 3Department of Neurology, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Ying Liu, Department of Neurology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of China, Tel +8618005316460, Email liuyingql@163.com Chi Zhong, Department of Neurology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, 758 Hefei Road, Qingdao, Shandong, 266035, People’s Republic of China, Tel +8618561817360, Email zhong7376_cn@sina.comBackground/Objective: Dyskinesia caused by transient ischemic attack (TIA) and mild ischemic stroke (MIS) is mild and short-lived; however, cognitive impairment (CI) can occur in the acute phase and be easily overlooked. DNA methylation is an epigenetic phenomenon that can affect gene expression through gene silencing. Blood levels of matrix metalloproteinase (MMP) 9 are elevated in ischemic stroke patients and is associated with the destruction of the blood-brain barrier and the occurrence of CI. No studies have investigated the relationship between MMP9 gene methylation and TIA/MIS with early cognitive impairment (ECI). As such, the purpose of the present study was to investigate the correlation between MMP9 gene methylation and TIA/MIS with ECI.Methods: Data from 112 subjects were collected, including 84 with TIA/MIS (National Institutes of Health Stroke Scale < 5 points) and 28 non-stroke control subjects. Patients were evaluated within 7 days of TIA/MIS onset according to four single-domain cognitive scales. Whole blood DNA methylation was detected using MethylTarget sequencing technology. Comparison of MMP9 gene methylation levels among subgroups was performed using statistical methods.Results: The site S33-79 in the TIA/MIS group was hypomethylated compared with the control group, and sites S33-25 and S33-30 in TIA/MIS with ECI was hypomethylated compared with TIA/MIS without ECI. Compared with the small artery occlusion group, MMP9 gene, S33-25, 30, 39, 53, 58, 73, 79, 113 and 131 sites in the large artery atherosclerosis group were hypomethylated.Conclusion: MMP9 gene hypomethylation sites were associated with TIA/MIS and TIA/MIS with ECI, and there was a strong correlation between MMP9 gene hypomethylation and atherosclerotic TIA/MIS. MMP9 gene methylation can reflect the severity of TIA/MIS. MMP9 gene hypomethylation sites may be used as potential biomarkers and therapeutic targets for TIA/MIS and TIA/MIS with ECI.Keywords: early cognitive impairment, hypomethylation, amyloid β-protein, blood-brain barrier, MMP9 gene

Sizhe Liu, Le Kang, Yagang Song, Mingsan Miao School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, People’s Republic of ChinaCorrespondence: Mingsan Miao, School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, People’s Republic of China, Tel/Fax +86-371-65962546, Email miaomingsan@163.comAbstract: Recurrence of hepatocellular carcinoma (HCC) negatively affects the quality of life of patients and leads to death. Studies have shown that recurrent hepatocellular carcinoma (RHCC) is closely related to tissue hypoxia and autophagy. It has been shown that hypoxia-inducible factor-1α (HIF-1α) and its downstream factor BCL-2 19 kDa-interacting protein 3 (BNIP3) promote cellular autophagy under hypoxic conditions, resulting in metastasis and RHCC. In this article, the molecular structures of HIF-1α and BNIP3 are described, and the significance of the HIF-1α/BNIP3 signaling pathway in RHCC is explained. Moreover, the role and mechanism of traditional Chinese medicine (TCM) in treating RHCC by modulating the HIF-1α/BNIP3 signaling pathway is discussed. Studies have shown that the HIF-1α/BNIP3 signaling pathway is a potential target of TCM in the treatment of RHCC. The mechanism of the HIF-1α/BNIP3 signaling pathway in RHCC and the progress achieved in TCM research on targeting and regulating this pathway are also reviewed in this article. The objective was to provide a theoretical basis for the prevention and treatment of RHCC, as well as further drug development.Keywords: recurrent hepatocellular carcinoma, HIF-1α/BNIP3 signaling pathway, traditional Chinese medicine, hypoxia, autophagy

Tao Jiang,1,&ast; Yuan Chen,1,&ast; Xia Gu,1,2 Mengyue Miao,1 Daifeng Hu,1 Hui Zhou,1 Jing Chen,3 Alexander Tobias Teichmann,1 Youzhe Yang1,2 1Sichuan Provincial Center for Gynaecology and Breast Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Academician (Expert) Workstation of Sichuan Province, Luzhou, 646000, People’s Republic of China; 3Reproductive Medicine Center, The Second People’s Hospital of Yibin, Yibin, 644000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Alexander Tobias Teichmann; Youzhe Yang, The Affiliated Hospital of Southwest Medical University, No. 25 Taiping Street, Jiangyang District, Luzhou, 646000, People’s Republic of China, Email alexandertobiasteichmann@swmu.edu.cn; yangyouzhe@swmu.edu.cnAbstract: Endometriosis is a hormone-dependent inflammatory disease characterized by the existence of endometrial tissues outside the uterine cavity. Pharmacotherapy and surgery are the current dominant management options for endometriosis. The greater incidence of recurrence and reoperation after surgical treatment as well as the adverse effects of medical approaches predispose patients to potential limitations for their long-term usage. Consequently, it is essential to explore novel supplementary and alternative drugs to ameliorate the therapeutic outcomes of endometriotic patients. Resveratrol is a phenolic compound that has attracted increasing interest from many researchers due to its pleiotropic biological activities. Here, we review the possible therapeutic efficacies and molecular mechanisms of resveratrol against endometriosis based on in vitro, animal, and clinical studies. The potential mechanisms of resveratrol include anti-proliferative, pro-apoptotic, anti-angiogenic, anti-oxidative stress, anti-invasive and anti-adhesive effects, thereby suggesting that resveratrol is a promising candidate for endometriosis. Because most studies have investigated the effectiveness of resveratrol on endometriosis via in vitro trials and/or experimental animal models, further high-quality clinical trials should be undertaken to comprehensively estimate the clinical application feasibility of resveratrol on endometriosis.Keywords: endometriosis, resveratrol, therapeutic efficacies, molecular mechanisms, clinical application

Ying Song,1,2,&ast; Zhen-Zhen Wang,1,3,&ast; Lixin Wang,4,&ast; Paul Faybusovich,2 Kamal Srivastava,3,5 Changda Liu,1,2 Jody Tversky,6 David Dunkin,7 Paula Busse,8 Xianqing Ren,9 Rachel Miller,8 Mingsan Miao,1 Xiu-Min Li3,10 1Academy of Chinese Medicine, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 2Department of Pediatrics, Division of Allergy and Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 3Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY, USA; 4Integrated TCM & Western Medicine Department, Shanghai Pulmonary Hospital Affiliated to Tongji University, Shanghai, People’s Republic of China; 5General Nutraceutical Technology LLC, Elmsford, NY, USA; 6The Department of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland, USA; 7Department of Pediatrics, Division of Gastroenterology and Nutrition, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 8Division of Clinical Immunology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 9The First Affiliated Hospital of Henan University of TCM, Zhengzhou, People’s Republic of China; 10Department of Otolaryngology, New York Medical College, Ardsley, NY, USA&ast;These authors contributed equally to this workCorrespondence: Xiu-Min LiProfessor of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY Email XiuMin_Li@NYMC.eduBackground: It has been demonstrated that ASHMI (antiasthma-simplified herbal medicine intervention) can improve airway function and reduce inflammation in human asthmatic patients with high safety and tolerability. In addition, ASHMI significantly suppresses Th2 cytokine production and increases Th1 cytokine production in treating asthma.Objective: Allergic asthma is associated with dysregulation of cytokines. We focused on IL-5 and IL-10 as signature Th2 and Treg cytokines to characterize ASHMI immunomodulatory components.Methods: The effects of ASHMI and individual herbal constituents on IL-5 and IL-10 production by PBMCs from asthmatic subjects were determined ex vivo. Sophora flavescens (SF)-F2, containing alkaloid compounds, effects on PBMC IL-10 and IL-5 production in the presence or absence of dexamethasone (Dex), and on DNA methylation levels at the foxp3 gene promoter were determined.Results: The ratio of anti-CD3/CD28 stimulated IL-10/IL-5 production by PBMCs from asthmatic subjects was significantly reduced compared to healthy subjects. In PBMCs from asthmatic subjects, ASHMI significantly reduced IL-5 production and increased IL-10 secretion in a dose-dependent manner (p < 0.05– 0.01). SF-F2 was most effective in increasing IL-10, whereas SF-F4 (flavonoid compounds) was most effective in suppressing IL-5 production. Dex-treated PBMCs from asthma subjects showed a trend of increasing ratio of IL-10/IL-5 while demonstrating reduced levels in both IL-5 and IL-10 (p < 0.05). Co-culture with Dex and SF-F2 significantly prevented Dex suppression of IL-10, while retained Dex-suppression of IL-5 production, and increased IL-10/IL-5 ratio by Dex. Co-culture with SF-F2 and Dex significantly reduced DNA methylation levels at the foxp3 gene promoter at CpG− 126.Conclusion: The SF alkaloid-rich fraction may be responsible for ASHMI induction of IL-10 production by PBMCs and plays a synergistic effect with Dex for augmenting IL-10/IL-5 ratio.Keywords: Sophora flavescens, IL-10/IL-5 ratio, asthma, foxp3 methylation, synergistic effect

Meng Miao,1 Fang Yuan,2 Xiaotian Ma,3 Haiming Yang,1 Xiang Gao,1 Zhengyu Zhu,4 Jianzhong Bi4 1Department of Neurology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, 266035, People’s Republic of China; 2Department of Health Care, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, 266035, People’s Republic of China; 3Department of Medicine Experimental Center, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, 266035, People’s Republic of China; 4Department of Neurology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250033, People’s Republic of ChinaCorrespondence: Zhengyu Zhu; Jianzhong BiDepartment of Neurology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250033, People’s Republic of ChinaTel +8617660083488; +8615153178111Email zhuzhengyu_1@hotmail.com; bjz@sdu.edu.cnBackground: Early cognitive impairment after transient ischemic stroke (TIA)/mild ischemic stroke (MIS) is common but easily overlooked. It has been demonstrated that DNA methylation plays a significant role in cognitive impairment and ischemic stroke. Furthermore, it has been reported that the RIN3 gene influences transportation of the amyloid β-protein. However, to our knowledge, there has been no research related to correlations between RIN3 methylation and early-onset cognitive impairment after TIA/MIS. Therefore, this study aimed to investigate this relationship in TIA/MIS patients.Methods: This study include 28 control subjects and 84 patients with TIA/MIS who were evaluated within 7 days of TIA/MIS onset using four single-domain cognitive scales. In addition, DNA methylation of whole blood was tested. RIN3 methylation was compared between TIA/MIS and control groups and between TIA/MIS patients with early cognitive impairment and those without early cognitive impairment. Clinical variables and RIN3 methylation sites with statistical differences were then used to construct a predictive model.Results: Hypomethylation of the RIN3 gene was observed in the whole blood of TIA/MIS patients relative to healthy controls. Furthermore, patients with early cognitive impairment after TIA/MIS had hypomethylation of RIN3 relative to those without early cognitive impairment.Conclusion: RIN3 methylation is strongly associated with TIA/MIS and TIA/MIS with early cognitive impairment. It is possible to influence the disease process by methylation via appropriate lifestyle and clinical interventions, and methylation of RIN3 gene sites may predict the occurrence of TIA/MIS with early cognitive impairment.Keywords: amyloid &Bgr;-protein, cognitive impairment, hypomethylation, ischemic stroke, transportation

Mingzhuo Cao,1 Mengling Zhan,1,2 Zheng Wang,1,2 Zeqian Wang,1,2 Xiu-Min Li,3 Mingsan Miao1 1Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou 450058, People’s Republic of China; 2College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450058, People’s Republic of China; 3Department of Microbiology and Immunology, and Otolaryngology, New York Medical College, Valhalla, NY 10595, USACorrespondence: Xiu-Min LiDepartment of Microbiology and Immunology, and Otolaryngology, New York Medical College, Valhalla, NY 10595, USAEmail XiuMin_Li@NYMC.eduMingsan MiaoAcademy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou 450058, People’s Republic of ChinaEmail miaomingsan@126.comPurpose: Isoliquiritigenin (ILQ), an important component of Anti-Asthma Herbal Medicine Intervention (ASHMI), had shown potent anti-asthma effect in vitro in our previous study. However, poor solubility and low bioavailability hindered in vivo application to treat asthma. This study was to develop a novel ILQ loaded self-nanoemulsifying drug delivery system (ILQ-SMEDDS) with enhanced bioavailability.Methods: The optimized SMEDDS formulation was composed of ethyl oleate (oil phase), Tween 80 (surfactant) and PEG400 (co-surfactant) at a mass ratio of 3:6:1. The physiochemical properties of ILQ-SMEDDS, including drug content, globule size, zeta potential, scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, were characterized. And the in vitro release profile, in situ intestinal absorption, in vivo pharmacokinetic parameters and the anti-asthma effect of ILQ suspension and ILQ-SMEDDS were evaluated.Results: The ILQ-SMEDDS had an average globule size of 20.63 ± 1.95 nm with a polydispersity index (PDI) of 0.11 ± 0.03, and its zeta potential was − 12.64 ± 2.12 mV. The cumulative release rate of ILQ from ILQ-SMEDDS to the simulated gastrointestinal tract was significantly higher than that of free ILQ suspension. And area under curve with ILQ-SMEDDS was found to be 3.95 times higher than that of ILQ suspension indicating improved bioavailability by SMEDDS. Although ILQ-SMEDDS showed a slight less effective inhibitory effect on eotaxin-1 in human lung fibroblast (HFL-1) cells than free ILQ, in an ovalbumin-induced asthma model, ILQ-SMEDDS exhibited more efficacy than ILQ suspension in improving asthma-associated inflammation, including eosinophil production, ovalbumin-specific immunoglobulin E (OVA-sIgE), interleukin 4 (IL 4), interleukin 5 (IL 5) and interferon-γ (IFN-γ). Even the low dose of ILQ-SMEDDS group (10 mg/kg) showed better anti-asthma effect than that of the ILQ suspension group (20 mg/kg).Conclusion: Compared with ILQ suspension, ILQ-SMEDDS showed significantly improved bioavailability and anti-asthma effect, revealing its potential as a favorable pharmaceutical agent for treating asthma.Keywords: isoliquiritigenin, self-nanoemulsifying drug delivery system, SMEDDS, ovalbumin-induced asthma, eotaxin-1, increased bioavailability

Miao Miao,1 Xixi Jing,1 Erik De Clercq,2 Guangdi Li1 1Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha 410078, People’s Republic of China; 2Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, Leuven 3000, BelgiumCorrespondence: Guangdi Li Email liguangdi.research@gmail.comAbstract: On June 8, 2018, an NS3/4A protease inhibitor called danoprevir was approved in China to treat the infections of HCV genotype (GT) 1b – the most common HCV genotype worldwide. Based on phase 2 and 3 clinical trials, the 12-week regimen of ritonavir-boosted danoprevir (danoprevir/r) plus peginterferon alpha-2a and ribavirin offered 97.1% (200/206) of sustained virologic response at post-treatment week 12 (SVR12) in treatment-naïve non-cirrhotic patients infected with HCV genotype 1b. Adverse events such as anemia, fatigue, fever, and headache were associated with the inclusion of peginterferon alpha-2a and ribavirin in the danoprevir-based regimen. Moreover, drug resistance to danoprevir could be traced to amino acid substitutions (Q80K/R, R155K, D168A/E/H/N/T/V) near the drug-binding pocket of HCV NS3 protease. Despite its approval, the clinical use of danoprevir is currently limited to its combination with peginterferon alpha-2a and ribavirin, thereby driving its development towards interferon-free, ribavirin-free regimens with improved tolerability and adherence. In the foreseeable future, pan-genotypic direct-acting antivirals with better clinical efficacy and less adverse events will be available to treat HCV infections worldwide.Keywords: danoprevir, ITMN-191, R7227, HCV NS3/4A inhibitor, HCV genotype

In this work, a mechanical degradation of weathering steel and carbon steel caused by strong acid corrosion has been studied in order to clarify the threat of industrial acid vehicle leakage to steel structure bridge. Twenty-seven specimens of Q345 weathering steel plates and Q345 carbon steel plates were immersed in a 36% hydrochloric acid solution at room temperature, with the corrosion time being 0 h, 1 h, 2 h, 4 h, 8 h, 12 h, 24 h, 48 h, and 72 h, respectively. Subsequently, the obtained specimens were subjected to a uniaxial tensile test to determine the stress-strain curves. The surface morphology was studied by the noncontact surface topography instrument DSX500. By analyzing the degree of mechanical degradation, the constitutive models of test steels under strong acid corrosion were established. The analysis of results shows that the corrosion rate of carbon steel is higher than that of weathering steel. After 72 hours of corrosion, the mass loss rate of carbon steel and weathering steel was 4.77% and 4.30%, respectively. The maximum corrosion pit depth of carbon steel was 25.52 μm higher than that of weathering steel. The constitutive models were in good agreement with the test results, and the resistance to corrosion degradation and deformation of the weathering steel was higher compared to the carbon steel. The results can serve as a guideline for designing steel constructions of improved durability.