The key pathogenesis of coronary heart disease （CHD） is spleen deficiency and phlegm stasis， and dysfunctional high-density lipoprotein （dys-HDL） may be the biological basis for the occurrence of CHD due to spleen deficiency and phlegm stasis. Considering the biological properties and effects of high-density lipoprotein （HDL）， it is believed that the structure and components of HDL are abnormal in the state of spleen deficiency which led to dys-HDL； and dys-HDL contributes to the formation of atherosclerotic plaques through two major pathways， namely， mediating the dysfunction of endothelial cells and mediating the foaminess of macrophages and smooth muscle cells， thus triggering the development of CHD. It is also believed that dys-HDL is a microcosmic manifestation and a pathological product of spleen deficiency， and spleen deficiency makes foundation for the production of dys-HDL； dys-HDL is also an important biological basis for the phlegm-stasis interactions in CHD. The method of fortifying spleen， resolving phlegm， and dispelling stasis， is proposed as an important principle in the treatment of CHD by traditional Chinese medicine， which can achieve the therapeutic purpose by affecting the changes in the structure and components of dys-HDL， thus revealing the scientific connotation of this method， and providing ideas for the diagnosis and treatment of CHD by traditional Chinese medicine.

The second plenary session of the 20th Central Commission for Discipline Inspection proposed the"develop-ment of a five-year plan for information technology construction to establish a digital disciplinary inspection and supervision system that covers the entire process and all elements."This provides guidance and momentum for disciplinary inspection agencies at all levels to implement the strategic deployment of the Party's 20th National Congress regarding comprehensive and strict governance of the Party.In this context,utilizing information technology to enhance the efficiency of supervision,discipline enforcement,and accountability while ensuring the high-quality development of public hospitals has become a key task for their disciplinary inspec-tion departments.The Disciplinary Inspection Commission of a public hospital has explored the establishment of a disciplinary in-spection management platform to achieve modular management of inspection tasks.By utilizing functions such as task allocation,statistical analysis,data migration,and early warning reminders,the platform aims to improve the efficiency of disciplinary in-spection work.This approach helps address the challenges of heavy workloads and limited inspection resources in hospitals,enab-ling real-time supervision,early warning correction,and time-bound oversight,thereby providing strong support for the construc-tion of integrity in the hospital.

Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory therapy.However,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified.Deoxynyboquinone(DNQ)is a natural small molecule discovered from marine actinomycetes.The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1.DNQ exhibited signif-icant anti-inflammatory properties both in vitro and in vivo.The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α,β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine.DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway.Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation.The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry.DNQ triggered the ubiquitination and subsequent degra-dation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of Nrf2.Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

The current study explored the hepatotoxicity among closed-ring genipin, open-ring tautomer of genipin and gardenia blue that generated from genipin and amino acid reaction using HepaRG cells to identify the material basis of genipin-induced hepatotoxicity in vitro. The effects of temperature, pH value and different kinds of amino acids on the chemical structure tautomerism between closed-ring and open-ring tautomer of genipin and the production of gardenia blue were investigated firstly, which aimed to explicit the conditions that could distinguish the closed-ring genipin and its open-ring tautomer, and the conditions generating gardenia blue, which were applied to prepare different kinds of gardenia blue; the CCK-8 kit was employed to analyze the hepatotoxicity of closed-ring genipin, open-ring tautomer of genipin and gardenia blue. From the results, it was found that, the structure transformation from close-ring to open-ring of genipin could be inhibited under the condition with acid environment; being essential groups to generate gardenia blue, the primary amino group and the open-ring tautomer of genipin reacting to generate the dihydropyridine ring was probably the key structure of gardenia blue; the structure characteristics existed apparent distinction at the reactive temperature of 37 ℃ and 80 ℃; compared to the culture condition with pH = 7.4, the concentration of genipin with close-ring in culture medium was significantly increased at pH = 5, but the cell viability did not decreased; the cell toxicity of gardenia blue was apparently lower than open-ring tautomer of genipin, and even some kinds of gardenia blue showed growth promoting effect on HepaRG cells. Here, it was suggested potentially that open-ring tautomer of genipin be the important material basis to induce hepatotoxicity, which could provide a cue and lay a foundation for the elucidation of the underlying mechanism of genipin-induced hepatotoxicity.

Background: Xylazole (Xyl) is a veterinary anesthetic that is structurally and functionally similar to xylazine. However, the effects of Xyl in vitro remain unknown. Objectives: This study aimed to investigate the anesthetic mechanism of Xyl using fetal rat nerve cells treated with Xyl. Methods: Fetal rat nerve cells cultured for seven days were treated with 10, 20, 30, and 40 μg/ mL Xyl for 0, 5, 10, 15, 20, 25, 30, 45, 60, 90, and 120 min. Variations of amino acid neurotransmitters (AANTs), Nitric oxide-Cyclic GMP (NO-cGMP) signaling pathway, and ATPase were evaluated. Results: Xyl decreased the levels of cGMP and NO in nerve cells. Furthermore, Xyl affected the AANT content and Na+ -K+ -ATPase and Ca2+ -Mg2+ -ATPase activity in nerve cells. These findings suggested that Xyl inhibited the NO-cGMP signaling pathway in nerve cells in vitro. Conclusions This study provided new evidence that the anesthetic and analgesic effects of Xyl are related to the inhibition of the NO-cGMP signaling pathway.

Ischemic heart diseases are one of the major causes of death worldwide. Effective restoration of blood flow can significantly improve patients’ quality of life and reduce mortality. However, reperfusion injury cannot be ignored. Flavonoids possess well-established antioxidant properties; They also have other benefits that may be relevant for ameliorating myocardial ischemia-reperfusion injury (MIRI). In this review, we focus on flavonoids with cardiovascular-protection function and emphasize their pharmacological effects. The main mechanisms of flavonoid pharmacological activities against MIRI involve the following aspects: a) antioxidant, b) anti-inflammatory, c) anti-platelet aggregation, d) anti-apoptosis, and e) myocardial-function regulation activities. We also summarized the effectiveness of flavonoids for MIRI.

Purpose: The aim of this study was to compare the efficacy of liver transplantation (LT) and liver resection (LR) for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) and to investigate risk factors affecting prognosis. Materials and Methods: A total of 94 HCC patients with PVTT type I (segmental PVTT) and PVTT type II (lobar PVTT) were involved and divided into LR (n=47) and LT groups (n=47). Recurrence-free survival (RFS) and overall survival (OS) were compared before and after inverse probability of treatment weighting (IPTW). Prognostic factors for RFS and OS were explored. Results: Two treatment groups were well-balanced using IPTW. In the entire cohort, LT provided a better prognosis than LR. Among patients with PVTT type I, RFS was better with LT (p=0.039); OS was not different significantly between LT and LR (p=0.093). In subgroup analysis of PVTT type I patients with α-fetoprotein (AFP) levels >200 ng/mL, LT elicited significantly longer median RFS (18.0 months vs. 2.1 months, p=0.022) and relatively longer median OS time (23.6 months vs. 9.8 months, p=0.065). Among patients with PVTT type II, no significant differences in RFS and OS were found between LT and LR (p=0.115 and 0.335, respectively). Multivariate analyses showed treatment allocation (LR), tumor size (>5 cm), AFP and aspartate aminotransferase (AST) levels to be risk factors of RFS and treatment allocation (LR), AFP and AST as risk factors for OS. Conclusion LT appeared to afford a better prognosis for HCC with PVTT type I than LR, especially in patients with AFP levels >200 ng/mL.

CRISP R/Cas9 is an emerging gene editing technique, which plays an important role in life science research.It is of great significance to introduce this cutting-edge scientific technique into the experimental teaching for undergraduates.Therefore, we established an undergraduate experiment system based on CRISPR/Cas9 technology.This experiment system focuses on the application of CRISPR/Cas9- mediating gene editing in mammalian cells.An engineered mouse embryonic fibroblast which genome were inserted with fluorescein mCherry gene was selected as the experimental model, and called STO-82.Firstly, sgRNAs targeting mCherry gene were designed to construct CRISPR-Cas9/sgRNA co-expression plasmids.After being confirmed by sequencing, they were transfected into STO-82 cells.Two groups of cells with mCherry negative and positive signals were detected by fluorescence-activated cell sorting.Single cells with negative fluorescence were separated and then cultivated to become monoclonal cells.The mutation status of mCherry gene in monoclonal cell lines was detected by sequence analysis.The result showed that there were mutations of insertion or deletion at target sites, indicating that the experimental system was successfully established.Therefore, this comprehensive experiment is comprised of sgRNA design, construction of CRISPR-Cas9/sgRNA co-expression plasmids, cell transfection, cell sorting, monoclonal cell cultivation and sequence analysis.This experiment system is used for experimental teaching for senior undergraduates.Teaching practice can either be decomposed into content modules or be taken as a whole program in light of actual situation.In the teaching practice at 3 classes (13 groups in total, two students every group), which adopted the model of small-class teaching (about 10 students per class), the majority completed the content modules and the expected outcomes were achieved.Through the design and teaching practice of this experiment system, the students acquire a deeper understanding for the principle and experimental procedure of CRISPR/Cas9 technology, an enhanced experimental ability and rigorous scientific thinking and also some knowledge in the risk of its medical application.

【Objective】 To analyze the cause of single-ELISA reactive of four blood screening items in 18 blood stations in Henan, so as to provide the basis for improving the quality of blood screening. 【Methods】 The single-ELISA reactive rate of HBsAg, anti-HCV, HIV Ag/Ab and anti-TP of 18 blood station laboratories in Henan throughout 2019 was calculated, and the causes were analyzed according to different ELISA reagent combinations and gray area settings in each laboratory. 【Results】 The overall single-ELISA reactive rates of HBsAg, anti-HCV, HIV Ag/Ab and anti-TP were 1.740(2 154/1 237 789), 0.564‰(698/1 237 789), 1.421‰(1 759/1 237 789) and 1.561‰(1 932/1 237 789), respectively, showing significant differences by detection items (P <0.05). Person correlation analysis showed that the single-ELISA reactive rate was independent of the gray area settings.but dependent on laboratories and reagent combinations. The single-ELISA reactive rate of HBsAg, anti-HCV, HIV Ag/Ab and anti-TP in D laboratory was the highest and higher than that in other labs using the same reagent.The laboratories with high HBsAg single-ELISA reactive rate were mostly those using a combination of imported reagents and domestic reagents, including the top 6 laboratories. The laboratories with high anti-HCV single-ELISA reactive rate were mostly those using certain domestic reagents. No obvious rules was noticed by single-ELISA reactive for anti-HIV. Laboratories with high anti-TP single-ELISA reactive rate were mostly those using combination 4. 【Conclusion】 The HBsAg single-ELISA reactive rate was the highest in the four blood screening items of blood station laboratories in Henan. The single-ELISA reactive rate is related to the laboratory itself and the reagent manufacturer, suggesting that laboratory quality control should be strengthened and proper reagent combination should be selected to reduce the waste of blood.