Drug metabolism will change significantly during inflammation, including the reduction of expression and activity of many drug metabolizing enzymes and transporters. Body would release a series of inflammatory cytokines which can regulate drug metabolizing enzymes. Recent studies have revealed that drug transporters are also regulated by the cytokines with obvious species difference. Mechanism studies show that several transcription factors play important roles during the signal pathways of regulation. This review focuses on the progress in the regulation of drug transporters during inflammation.

Objective　To investigate the role of suramin in inhibiting the angiogenesis of lung cancer. Methods　The protei n expression of VEGF and its receptor fms-like tyrosine kinase(Flt), kinase ins ert domain-containing receptor(KDR) in lung cancer cell A549 and ECV-304 was studied with immunohistochemical technique. The anti-angiogenesis effect of su ramin was evaluated with immunohistochemical technique and cell culture. Results　Suramin showed no effect on the production of lung cancer cel ls and their secretion of VEGF. No possitive expression of Flt, KDR in A549 was found in the suramin interfered group and non-interfered group, but VEGF w as e xpressed in both groups. The Flt and KDR expressions in ECV-304 cells were decr eased significantly after the treatment of suramin at 0.25 ng/ml and 2.5 ng/ml r espectively. There was no effect on proliferetion of A549 and ECV-304 after sur amin in terference. Conclusion　The mechanism of inhibiting-angiogenes is of suramin is pro bably due to reducing the VEGF receptor expression in vascular endothelial cells and inhibiting the binding of VEGF and its receptors.

Objective To summarize and report the experiences of surgical treatment of infective endocarditis. Methods From March 1995 to March 2004, surgical operations were performed in 25 patients with infective endocarditis, 9 of who received emergency surgery and 16 received selective operation. Replacement of mitral valve was performed in 3, aortic valve replacement in 13, mitral and aortic valve replacement in 8, Bentall procedure in 1.Associated cardiac lesions included patent ductus arterioles in 1, ventricular septal defect in 2, rupture of Valsalvaps sinus in 1. Results There was one postoperative death, which gave an overall hospital mortality of 4%. Twenty-four patients were cured and improved. Conclusion Surgical operation should be the preferred mode of surgical correction for infective endocarditis. The timing of surgery and proper perioperative management are key factors for the successful treatment of infective endocarditis.

Objective　Coronary artery bypass grafting (CABG)i n 13 patients was analyzed. Methods　9 patients were performed C ABG with cardiopulmonary bypass, 4 patients undergone off-pump coronary artery bypass(OPCAB). Among the 4 patients, 3 undergone transmyocardial laser revascula rization concomitantly. 2 patients with single-vessel disease, 3 with double-v essel disease, 7 with triple-vessel disease and 1 with left main coronary arter y disease. The average bypass per patient was 2.3. Results　All patients survived, 11 patients were angina free, 2 were angina relief. C onclusion　CABG is a safe operation, OPCAB may reduce blood transfusion and complication, patients recover more quickly after OPCAB compared with those with CABG.

Aim To develop an in vitro high throughput drug screening system based on reporter gene assay for identification of novel compounds with PXR, FXR and LXRα agonist activity. Methods The expressions of exogenous PXR, FXR and LXRαgene in HEK293, HepG2 and LS174T cells were examined by Real-Time quantity PCR. pSG5-hPXR and pGL3-XREM-CYP3A4, pEGFP-N3-hFXR and EcRE-TK-Luc, pCMX-FLAG-hLXRα and pGL3-XREM-CYP3A4 were cotransfected into cells and the optimal ratio of three plasmids was determined. The dose-response relationship between the positive drug and the fold induction was determined. The specificity of the model was ex-amined, and the repeatability was also determined by Z′ value. Results ① The PXR, FXR and LXRα mRNA expression in HEK293 cell is low among three different cells. ②reporter gene vector and expression plasmid ratio of 1∶ 1, 2∶ 1 and 2∶ 1 were proved to be suitable for highest relative luciferase activity for PXR, FXR or LXRα agonist screening model. ③ The relative luciferase activity was induced by Rif, CDCA or T0901317 in a dose-dependent manner. ④Only Rif, CDCA or T0901317 could significantly increase the relative luciferase activity in PXR,FXR or LXRα agonist screening model, no effect of other nuclear re-ceptors agonist was observed, and the values of Z′-factor for PXR, FXR and LXRαagonist screening model were 0. 58, 0. 66 and 0. 63, respectively. Conclusion An in vitro PXR, FXR and LXRα agonist high-throughput screening models are devel-oped with acceptable specificity and repeatability, and the mod-els can be used to screen PXR, FXR and LXRα agonist.

This study aims to investigate the function of two SNPs (rs8904C > T and rs696G >A) in 3' untranslated region (3'UTR) of NFKBIA gene by constructing luciferase reporter gene. A patient's genomic DNA with rs8904 CC and rs696 GA genotype was used as the PCR template. Full-length 3'UTR of NFKBIA gene was amplified by different primers. After sequencing validation, these fragments were inserted to the luciferase reporter vector, pGL3-promoter to construct recombinant plasmids containing four kinds of haplotypes, pGL3-rs8904C/rs696G, pGL3-rs8904C/rs696A, pGL3-rs8904T/rs696G and pGL3-rs8904T/rs696A. Then these plasmids were transfected into LS174T cells and the luciferase activity was detected. Compared with pGL3-vector transfected cells (negative control), the luciferase activity of the four kinds of recombinant plasmids was significantly decreased (P < 0.001). For rs696G > A, the luciferase activity of the recombinant plasmids containing A allele (pGL3-rs8904C/rs696A and pGL3-rs8904T/rs696A) was about 45.1% (P < 0.05) and 56.1% (P < 0.001) lower than those containing G allele (pGL3-rs8904C/rs696G and pGL3-rs8904T/rs696G), respectively. For rs8904C > T, there were no significant differences in the luciferase activity between the recombinant plasmids containing T allele and those with C allele. Together, the luciferase reporter gene vectors containing SNPs in NFKBIA gene 3'UTR were constructed successfully and rs696G > A could decrease the luciferase activity while rs8904C >T didn't have much effect on the luciferase activity.

Objective To summarize the experience of surgical treatment of ascending aortic aneurysms and aortic dissections. Methods From February 2001 to October 2005, 31 patients including 26 male, 5 female, aged 41.3 years old (range 14-72) received surgical management. Twenty cases were diagnosed as ascending aortic aneurysm and aortic root aneurysm, 8 as Standford A dissection, 3 as Stanford B dissection. Twenty-one patients underwent classic Bentall procedure in which VSD repair was carried out in 1 case, mitral valvoplasty in 2 and mitral valve replacement in 2; Four patients underwent modified Bentall procedure (coronary button technique); Three patients underwent Wheat procedure; The remaining 3 patients with Stanford B dissection underwent graft replacement of descending aorta. Results There was no death during hospital stay that lasted 13-46 d with an average of 16.4 d after operation. The mean clinical follow-up was (21?18.5) months (range 1-63 months). One patient died without describable cause two years later. One patient had ascending aorta-pulmonary artery fistula at color Doppler examination half a year later. One patient was detected rupture of distal anastomoses half a year after operation and underwent stent-graft, SG. Conclusion The surgical treatment of aortic aneurysms and aortic dissections could be carried out safely based on the accurate diagnosis, specific surgical strategy and fine technique.

Alcohol abuse leads to alcoholic liver disease and no effective therapy is currently available. Wuzhi Tablet (WZ), a preparation of extract fromthat is a traditional hepato-protective herb, exerted a significant protective effect against acetaminophen-induced liver injury in our recent studies, but whether WZ can alleviate alcohol-induced toxicity remains unclear. This study aimed to investigate the contribution of WZ to alcohol-induced liver injury by using chronic-binge and acute models of alcohol feeding. The activities of ALT and AST in serum were assessed as well as the level of GSH and the activity of SOD in the liver. The expression of CYP2E1 and proteins in the NRF2-ARE signaling pathway including NRF2, GCLC, GCLM, HO-1 were measured, and the effect of WZ on NRF2 transcriptional activity was determined. We found that both models resulted in liver steatosis accompanied by increased transaminase activities, but that liver injury was significantly attenuated by WZ. WZ administration also inhibited CYP2E1 expression induced by alcohol, and elevated the level of GSH and the activity of SOD in the liver. Moreover, the NRF2-ARE signaling pathway was activated by WZ and the target genes were all upregulated. Furthermore, WZ significantly activated NRF2 transcriptional activity. Collectively, our study demonstrates that WZ protected against alcohol-induced liver injury by reducing oxidative stress and improving antioxidant defense, possibly by activating the NRF2-ARE pathway.

Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over the past few decades, significant progress has been made in the development of targeted epigenetic modulators (e.g., inhibitors). However, epigenetic inhibitors have faced multiple challenges, including limited clinical efficacy, toxicities, lack of subtype selectivity, and drug resistance. As a result, the design of new epigenetic modulators (e.g., degraders) such as PROTACs, molecular glue, and hydrophobic tagging (HyT) degraders has garnered significant attention from both academia and pharmaceutical industry, and numerous epigenetic degraders have been discovered in the past decade. In this review, we aim to provide an in-depth illustration of new degrading strategies (2017-2023) targeting epigenetic proteins for cancer therapy, focusing on the rational design, pharmacodynamics, pharmacokinetics, clinical status, and crystal structure information of these degraders. Importantly, we also provide deep insights into the potential challenges and corresponding remedies of this approach to drug design and development. Overall, we hope this review will offer a better mechanistic understanding and serve as a useful guide for the development of emerging epigenetic-targeting degraders.