Combined ROS Responsive Polydopamine-Coated Berberine Nanoparticles Effective Against Ulcerative Colitis in Mouse Model.

Introduction: Enhancing the efficacy of berberine (BBR) in the treatment of ulcerative colitis (UC) through the development of dopamine-coated berberine nanoparticles (PDA@BBR NPs) with ROS-responsive and adhesive properties. Methods: Berberine nanoparticles (BBR NPs) were synthesized using the nonsolvent precipitation method, and their surfaces were coated with polydopamine (PDA) through oxidative polymerization. The PDA@BBR NPs were characterized by transmission electron microscopy (TEM), size analysis, and zeta potential analysis. Drug loading and encapsulation efficiency were analyzed using fluorescence spectroscopy. The responsiveness of these nanoparticles to reactive oxygen species (ROS) was assessed in vitro, while their adhesive properties and therapeutic efficacy on UC were evaluated in vivo. Results: Physicochemical property studies showed that PDA coated BBR NPs nanoparticles have good dispersion and stability. In vitro results showed that PDA@BBR NPs could prolong the retention time of the drug at the colonic site and could realize the gradual drug release under ROS environment. In addition, animal studies showed that PDA@BBR NPs exhibited significant anti-inflammatory effects on DSS-induced colitis and effectively reduced intestinal mucosal damage. Conclusion: PDA@BBR NPs are ROS-responsive nanoparticles that adhere well and have a high drug loading capacity. They have shown therapeutic effects in mice with UC, indicating that this formulation may be a promising treatment option.

A study of volatiles of young citrus fruits from four areas based on GC-MS and flash GC e-nose combined with multivariate algorithms.

The present study has successfully established a scientific and precise approach for distinguishing the geographical origins of young citrus fruits (Qingpi) from four primary production regions in China, using gas chromatography-mass spectrometry (GC-MS) and flash gas chromatography electronic nose (flash GC e-nose) to analyze the volatile composition and odor characteristics. Through the application of chemometric analysis, a clear differentiation among Qingpi samples was established using GC-MS. Additionally, the application of flash GC e-nose facilitated the extraction of flavor information, which enabled the discrimination of geographical origins. Several flavor components were identified as significant factors for origin certification. Furthermore, two pattern recognition algorithms were employed to achieve high accuracy in regional identification. The results of this investigation demonstrate that the amalgamation of multivariate chemometrics and algorithms can proficiently discern the sources of those young citrus fruits. The findings of this research can provide a reference for the assessment of quality control in food and other agricultural commodities in the times ahead.

Effect of vinegar steaming on the composition and structure of Schisandra chinensis polysaccharide and its anti-colitis activity.

In this study, infrared spectroscopy, high-performance liquid chromatography, and matrix-assisted laser desorption ionization-time-of-flight-mass spectrometry (MALDI-TOF-MS) technology were applied to systematically explain the Schisandra chinensis's polysaccharide transformation in configuration, molecular weight, monosaccharide composition, and anti-ulcerative colitis (UC) activity after vinegar processing. Scanning electron microscopic results showed that the appearance of S. chinensis polysaccharide changed significantly after steaming with vinegar. The MALDI-TOF-MS results showed that the mass spectra of raw S. chinensis polysaccharides (RSCP) were slightly lower than those of vinegar-processed S. chinensis polysaccharides (VSCP). The RSCP showed higher peaks at m/z 1350.790, 2016.796, and 2665.985, all with left-skewed distribution, and the molecular weights were concentrated in the range of 1300-3100, with no higher peak above m/z 5000. The VSCPs showed a whole band below m/z 3000, with m/z 1021.096 being the highest peak, and the intensity decreased with the increase of m/z. In addition, compared to RSCPs, VSCPs can significantly increase the content of intestinal short-chain fatty acids (SCFAs). This study showed that the apparent morphology and molecular weight of S. chinensis's polysaccharides significantly changed after steaming with vinegar. These changes directly affect its anti-UC effect significantly, and its mechanism is closely related to improving the structure and diversity of gut microbiota and SCFA metabolism.

Quality difference analysis of raw and vinegar-processed products of Qingpi based on color and component correlation.

The dried young fruit of Citrus reticulata Blanco, known as Qingpi, is commonly used in clinic both with its raw and vinegar-processed products. However, the distinctions in quality between these two products remain unclear, and the methods for identification are considerably intricate. In this study, an electronic eye technique was applied to assess the overall color of Qingpi products before and after processing. The luminosity (L*) and yellow-blue (b*) values of Qingpi decreased after vinegar processing, while red-green (a*) values increased. The discriminant function models based on color parameters were established to effectively classify the two products. The chemical compositions of different Qingpi products were characterized using ultra-high performance liquid chromatography fingerprint technology, and 10 distinct components were considered as potential chemical markers. The correlation analysis revealed a significant relationship between chromatic values and chemical components. In conclusion, the results of this study suggested that chromaticity can be effectively considered as a valuable instrument for the prediction of component content in both raw and vinegar-processed Qingpi products. This study will provide new ideas and methods for identification and quality evaluation of Qingpi processed products, as well as provide a reference for standardizing traditional Chinese medicine processing techniques.

Ultra-high-performance liquid chromatography-quadrupole-time of flight-mass spectrometry combined with network pharmacology for analysis of potential quality markers of three processed products of Qingpi.

Qingpi, a well-known traditional Chinese medicine for qi-regulating and commonly processed into three types of pieces, has been widely used in the clinical application of liver disease for thousands of years. In this study, an ultra-high-performance liquid chromatography-quadrupole-time of flight-mass spectrometry approach along with multivariate statistical analysis was developed to assess and characterize the differentiations of three processed products and confirm the potential quality markers of Qingpi. In addition, a systematic analysis combined with network pharmacology and molecular docking was performed to clarify the potential mechanism of Qingpi for the treatment of liver disease. As a result, 18 components were identified and an integrated network of Qingpi-Components-Target-Pathway-Liver Disease was constructed. Eight compounds were finally screened out as the potential quality markers acting on ten main targets and pathways of liver disease. Molecular docking analysis results indicated that the quality markers had a good binding activity with the targets. Overall, this work preliminarily identified the potential quality markers of three processed products of Qingpi, and predicted its targets in the prevention and treatment of liver disease, which can provide supporting information for further study of the pharmacodynamic substances and mechanisms of Qingpi.

Challenges for the development of mutant isocitrate dehydrogenases 1 inhibitors to treat glioma.

Glioma is one of the most common types of brain tumors, and its high recurrence and mortality rates threaten human health. In 2008, the frequent isocitrate dehydrogenase 1 (IDH1) mutations in glioma were reported, which brought a new strategy in the treatment of this challenging disease. In this perspective, we first discuss the possible gliomagenesis after IDH1 mutations (mIDH1). Subsequently, we systematically investigate the reported mIDH1 inhibitors and present a comparative analysis of the ligand-binding pocket in mIDH1. Additionally, we also discuss the binding features and physicochemical properties of different mIDH1 inhibitors to facilitate the future development of mIDH1 inhibitors. Finally, we discuss the possible selectivity features of mIDH1 inhibitors against WT-IDH1 and IDH2 by combining protein-based and ligand-based information. We hope that this perspective can inspire the development of mIDH1 inhibitors and bring potent mIDH1 inhibitors for the treatment of glioma.

Biomedical statistics study on the correlation between peripheral blood follicular helper T cell subsets and primary Sjogren's syndrome.

To study the expressions of follicular helper T cell (Tfh) subsets--Tfh1, Tfh2, and Tfh17, in peripheral blood (PB) of primary Sjogren's syndrome (PSS) patients in the active phase and remission period after treatment, and to analyze the pathogenic effects of Tfh subsets in PSS patients. The proportions of Tfh1, Tfh2, and Tfh17 were measured by flow cytometry in the healthy group, PSS patients group, active phase group, and remission phase group. Enzyme-linked immunosorbent assay was used to detect IL-21 expression in SS patients in active and remission stages. Biomedical statistics was used to analyze the correlation between Tfh subsets and SS disease activity index; and analyze the correlation between the proportions of Tfh subsets in the healthy group, primary group, active stage, and remission stage In contrast with the healthy group, the levels of Tfh1, Tfh2, and Tfh17 in CD4+ T cells of PSS patients were prominently reduced. PSS patients in the active phase had significantly lower Tfh1, Tfh2, and Tfh17 levels but remarkably higher IL-21 levels than in the remission phase. The contents of Tfh1, Tfh2, and Tfh17 are negatively correlated with the severity of PSS.

UTP11 deficiency suppresses cancer development via nucleolar stress and ferroptosis.

The eukaryotic ribosome is essential for cancer cell survival. Perturbation of ribosome biogenesis induces nucleolar stress or ribosomal stress, which restrains cancer growth, as rapidly proliferating cancer cells need more active ribosome biogenesis. In this study, we found that UTP11 plays an important role in the biosynthesis of 18S ribosomal RNAs (rRNA) by binding to the pre-rRNA processing factor, MPP10. UTP11 is overexpressed in human cancers and associated with poor prognoses. Interestingly, depletion of UTP11 inhibits cancer cell growth in vitro and in vivo through p53-depedednt and -independent mechanisms, whereas UTP11 overexpression promotes cancer cell growth and progression. On the one hand, the ablation of UTP11 impedes 18S rRNA biosynthesis to trigger nucleolar stress, thereby preventing MDM2-mediated p53 ubiquitination and degradation through ribosomal proteins, RPL5 and RPL11. On the other hand, UTP11 deficiency represses the expression of SLC7A11 by promoting the decay of NRF2 mRNA, resulting in reduced levels of glutathione (GSH) and enhanced ferroptosis. Altogether, our study uncovers a critical role for UTP11 in maintaining cancer cell survival and growth, as depleting UTP11 leads to p53-dependent cancer cell growth arrest and p53-independent ferroptosis.

The optimal diagnosis and treatment of intravenous leimyomatosis.

Intravenous leiomyomatosis (IVL) is a rare form of gynaecological- uterine leiomyoma. Clinically, the diagnosis and treatment are more difficult and challenging due to occult symptoms and clinical presentations, which can be similar to other common diseases. In this report, comprehensive management of a case of IVL is reported and discussed, with the aim of sharing our academic and clinical experience to improve the medical management of IVL.

Short-Term Results on Leaflet Mobility in Patients Undergoing Rheumatic Mitral Valve Repair With an Efficient 4-Step Commissuroplasty Technique.

BACKGROUND: Mitral valve stenosis (MS) is the primary pathologic feature of rheumatic mitral valve disease, and the complex repair affects its clinical outcome. This study aimed to examine the efficacy of the 4-step commisuroplasty "SCORe" procedure by assessing changes in the mobility of mitral valve leaflets and its clinical effects. METHODS: From September 1, 2018, to January 13, 2019, patients with MS who underwent mitral valve repair with the SCORe procedure in the study center were analyzed in this prospective study. Mitral valve structure was assessed by transthoracic echocardiography pre- and postoperatively as well as during follow-up. RESULTS: In total, 60 consecutive patients were examined. In 56 patients (93.3%), mitral valve orifice area (MVOA) was less than 1.5 cm2, and mean (SD) MVOA for the whole cohort was 1.20 (0.34) cm2. The mobility of the anterior leaflet was improved (P < .001) during the cardiac cycle postsurgery, but that of the posterior leaflet was not (P = .591). The mean (SD) coaptation length was increased significantly from 6.69 (1.32) mm to 7.92 (1.24) mm (P < .001) postoperatively. Mean (SD) MVOAs increased to 2.24 (0.38) cm2 postoperatively (P < .001). During the 1-year follow-up, there were no deaths or reoperations. Follow-up echocardiography revealed minor or mild regurgitation in 98.3% of patients. CONCLUSION: These findings demonstrated that the SCORe procedure can effectively improve the mobility of mitral leaflets and enlarge the valve orifice area in patients with rheumatic MS in China, with minimal complications and promising results.

Novel recombinant human thyroid-stimulating hormone in aiding postoperative assessment of patients with differentiated thyroid cancer-phase I/II study.

PURPOSE: Thyroid hormone withdrawal (THW) inevitably induced hypothyroidism in patients with differentiated thyroid cancer (DTC), and we aimed to evaluate the safety and efficacy of a novel recombinant human thyroid-stimulating hormone (rhTSH, ZGrhTSH) as an alternative of THW in China. METHODS: Totally, 64 DTC patients were enrolled with 24 in the dose-escalation cohort equally grouped into 0.9 mg × 1 day, 0.9 mg × 2 day, 1.8 mg × 1 day, and 1.8 mg × 2 day dosage, and 40 further enrolled into 0.9 mg × 2 day dose-expansion cohort. All patients underwent both ZGrhTSH phase and levothyroxine (L-T4) withdrawal phase for self-comparison in terms of TSH levels, the radioactive iodine (RAI) uptake, stimulated thyroglobulin level, and the quality of life (QoL). RESULTS: In ZGrhTSH phase, no major serious adverse events were observed, and mild symptoms of headache were observed in 6.3%, lethargy in 4.7%, and asthenia in 3.1% of the patients, and mostly resolved spontaneously within 2 days. Concordant RAI uptake was noticed in 89.1% (57/64) of the patients between ZGrhTSH and L-T4 withdrawal phases. The concordant thyroglobulin level with a cut-off of 1 µg/L was noticed in 84.7% (50/59) of the patients without the interference of anti-thyroglobulin antibody. The QoL was far better during ZGrhTSH phase than L-T4 withdrawal phase, with lower Billewicz (- 51.30 ± 4.70 vs. - 39.10 ± 16.61, P < 0.001) and POMS (91.70 ± 16.70 vs. 100.40 ± 22.11, P = 0.011) scores which indicate the lower the better. Serum TSH level rose from basal 0.11 ± 0.12 mU/L to a peak of 122.11 ± 42.44 mU/L 24 h after the last dose of ZGrhTSH. In L-T4 withdrawal phase, a median of 23 days after L-T4 withdrawal was needed, with the mean TSH level of 82.20 ± 31.37 mU/L. The half-life for ZGrhTSH clearance was about 20 h. CONCLUSION: The ZGrhTSH held the promise to be a safe and effective modality in facilitating RAI uptake and serum thyroglobulin stimulation, with better QoL of patients with DTC compared with L-T4 withdrawal.

[Quality evaluation of Ginseng Radix et Rhizoma based on UPLC characteristic chromatogram and quantitative analysis of multi-components by single marker (QAMS)].

Based on UPLC characteristic chromatogram and quantitative analysis of multi-components by single marker(QAMS), the content of seven types of ginsenosides in Ginseng Radix et Rhizoma was simultaneously determined, and the quality of Ginseng Radix et Rhizoma was evaluated by the principal component analysis(PCA). The chromatographic separation was performed on the Acquity UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 µm) with the mobile phase of acetonitrile-water for gradient elution at the flow rate of 0.3 mL·min~(-1), the column temperature of 30 ℃, the detection wavelength of 203 nm, and the injection volume of 2 µL. The UPLC chromatogram was established with 19 batches of Ginseng Radix et Rhizoma samples from three producing areas by Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(version 2012). Thirteen characteristic peaks were determined and seven components were identified. SPSS 26.0 was used to conduct PCA on the characteristic peak areas. With the peak of ginsenoside Rb_1 as reference peak S, ginsenoside Rb_1 showed good durability of relative correction factor as compared with other ginsenosides. The QAMS method for the determination of seven ginsenosides in Ginseng Radix et Rhizoma was established. There was no significant difference in results between the QAMS method and the external standard method. As revealed by the results of PCA and the determination of the total content of seven ginsenosides, the four batches of Ginseng Radix et Rhizoma numbered S19, S18, S1, and S2 were of superior quality. The characteristic chromatogram and QAMS method for the determination of seven ginsenosides in this study were convenient and accurate, which greatly shortened the analysis time and improved the analysis efficiency. The findings of this study are expected to provide a basis for the overall quality evaluation of Ginseng Radix et Rhizoma.

[Rapid identification of raw and sulfur-fumigated Paeoniae Radix Alba based on Heracles NEO ultra-fast gas phase electronic nose].

Since the current identification method for Paeoniae Radix Alba is complex in operation and long time-consuming with high requirements for technicians, the present study employed Heracles NEO ultra-fast gas phase electronic nose(E-nose) technology to identify raw and sulfur-fumigated Paeoniae Radix Alba decoction pieces in order to establish a rapid identification method for sulfur-fumigated Paeoniae Radix Alba. The odors of raw Paeoniae Radix Alba and its sulfur-fumigated products were analyzed by Heracles NEO ultra-fast gas phase E-nose to obtain the odor chromatographic information. The chemometric model was established, and the data were processed by principal component analysis(PCA), discriminant function analysis(DFA), soft independent modeling of class analogy(SIMCA), and partial least squares discriminant analysis(PLS-DA). The differential compounds of raw and sulfur-fumigated samples were qualitatively analyzed based on the Kovats retention index and Arochembase. As revealed by the comparison of gas chromatograms of raw and sulfur-fumigated Paeoniae Radix Alba, the heights of several peaks in the chromatograms before and after sulfur fumigation changed significantly. The peak(No.8) produced by ethylbenzene disappeared completely due to sulfonation reaction in the process of sulfur fumigation, indicating that ethylbenzene may be the key component in the identification of Paeoniae Radix Alba and its sulfur-fumigated products. In PCA, DFA, SIMCA, and PLS-DA models, the two types of samples were separated into two different regions, indicating that the established models can clearly distinguish between raw and sulfur-fumigated Paeoniae Radix Alba. The results showed that Heracles NEO ultra-fast gas phase E-nose technology could realize the rapid identification of raw and sulfur-fumigated Paeoniae Radix Alba, which provides a new method and idea for the rapid identification of sulfur-fumigated Chinese medicine.

[Characteristic chromatogram and index components content of substance benchmark of Xuanfu Daizhe Decoction].

The methods for determining the characteristic chromatogram and index components content of Xuanfu Daizhe Decoction were established to provide a scientific basis for the quality evaluation of substance benchmarks and preparations. Eighteen batches of Xuanfu Daizhe Decoction were prepared with the decoction pieces of different batches and of the same batch were prepared respectively, and the HPLC characteristic chromatograms of these samples were established. The similarities of the chromatographic fingerprints were analyzed. With liquiritin, glycyrrhizic acid, 6-gingerol, ginsenoside Rg_1, and ginsenoside Re as index components, the high performance liquid chromatography was established for content determination with no more than 70%-130% of the mass average as the limit. The results showed that there were 19 characteristic peaks corresponding to the characteristic chromatograms of 18 batches of Xuanfu Daizhe Decoction, including 8 peaks representing liquiritin, 1,5-O-dicaffeoylqunic acid, ginsenoside Rg_1, ginsenoside Re, 1-O-acetyl britannilactone, ginsenoside Rb_1, glycyrrhizic acid, and 6-gingerol, and the fingerprint similarity was greater than 0.97. The contents of liquiritin, glycyrrhizic acid, 6-gingerol, and ginsenosides Rg_1 + Re in the prepared Xuanfu Daizhe Decoction samples were 0.53%-0.86%, 0.61%-1.2%, 0.023%-0.068%, and 0.33%-0.66%, respectively. Except for several batches, most batches of Xuanfu Daizhe Decoction showed stable contents of index components, with no discrete values. The characteristic chromatograms and index components content characterized the information of Inulae Flos, Ginseng Radix et Rhizoma, Glycyrrhizae Radix et Rhizoma, and Zingiberis Rhizoma Recens in Xuanfu Daizhe Decoction. This study provides a scientific basis for the further research on the key chemical properties of substance benchmark and preparations of Xuanfu Daizhe Decoction.

Risk factors for postoperative recurrent tricuspid regurgitation after concomitant tricuspid annuloplasty during left heart surgery and the association between tricuspid annular circumference and secondary tricuspid regurgitation.

BACKGROUND: To identify the association between tricuspid annular circumference and secondary tricuspid regurgitation and analyze the risk factors of recurrent tricuspid regurgitation after concomitant tricuspid annuloplasty during left heart surgery. METHODS: From October 2018 to June 2019, a total of 117 patients receiving concomitant tricuspid annuloplasty within left heart surgery were enrolled. Severity of tricuspid regurgitation was classified as 4 subtypes: normal, mild, moderate and severe. Perioperative data and mid-term outcome were collected. Tricuspid annular circumference (TAC) was measured under cardiac arrest during surgery procedure by cardioplegia. Optimal TAC and TAC index (TAC/body surface area, BSA) cutoffs of significant tricuspid annulus dilatation (moderate and severe) were obtained. Univariable and multivariable logistic regression analyses were performed to identify the risk factors of postoperative recurrent tricuspid regurgitation. The follow up period is 13-19 months (mean 15.5 ± 3.2 months). RESULTS: There was 1 patient was excluded who died after surgery. A total of 116 patients receiving tricuspid annuloplasty were included. Optimal cutoffs of significant tricuspid annulus dilatation were recommended (TAC 11.45 cm, Sensitivity 82.89%, Specificity 73.68%, AUC 0.915; TAC index 7.09 cm/m2, Sensitivity 73.68%, Specificity 85%, AUC 0.825, respectively). Based on findings of multivariable logistic regression, it has been showed that TAC index and postoperative atrial fibrillation were the independent risk factors of recurrent regurgitation after surgery. Optimal TAC index cutoff to predict recurrent tricuspid regurgitation was 7.86 cm/m2 CONCLUSIONS: The severity of secondary tricuspid regurgitation is associated with the tricuspid annular circumference. The cut-offs of significant tricuspid regurgitation (more than moderate) were TAC 11.45 cm and TAC index 7.09 cm/m2, respectively. Clinically, concomitant tricuspid annuloplasty is relative safe and effective. TAC index ≥ 7.86 cm/m2 and postoperative atrial fibrillation are the risk factors of recurrent significant tricuspid regurgitation after concomitant tricuspid annuloplasty during left heart surgery.

Surgical rheumatic mitral valve repair compared with percutaneous balloon mitral valvuloplasty in mitral stenosis in current era: a propensity score matching study.

BACKGROUND: Many comparative studies of percutaneous balloon mitral valvuloplasty (PBMV) and surgical mitral commissurotomy (SMC) in rheumatic mitral stenosis (MS) were done in the last few decades. With the development of valve repair techniques, various surgical rheumatic valve repair techniques have been applied in clinic, but there is a lack of comparison with PBMV. Our study was designed to compare the perioperative and mid-term outcomes of PBMV and mitral valve repair with "four-step" procedure in the treatment of rheumatic MS. METHODS: Patients with MS were treated with PBMV or rheumatic mitral valve repair (rMVP) at Beijing Anzhen Hospital between January 1, 2013 and September 30, 2018 were selected. By using propensity score matching (PSM) method, we compared the changes in post-operation clinical outcomes between the two matched groups. Kaplan-Meier analyses was used for survival analysis and drawing the curve, and log-rank test were used to compare intergroup differences. RESULTS: A total of 252 cases were enrolled after selection, 74 cases in PBMV and 178 cases in rMVP. Seventy-four pairs were matched successfully after PSM. There were 53 females in PBMV and 54 in rMVP. The mean age of two groups was 46.95±12.50 and 47.55±11.91 years respectively. There was no significantly differences in mitral valve orifice area (MVOA) (1.05±0.32 vs. 0.97±0.24 cm2, P=0.12) and left ventricular ejection fraction (EF) (62.36%±5.17% vs. 62.52%±4.94%, P=0.76) between two groups preoperatively. Baseline characteristics were basically balanced after PSM. In each group, there was one case transferred to surgical mitral valve replacement due to the failure of valvuloplasty before discharge. All patients survived the interventions and no severe complications were found. MVOA were significantly increased in rMVP compared with PBMV postoperatively, as well as grading of MS and tricuspid regurgitation (TR) were significantly improved in rMVP. Three cases in PBMV were lost during the follow-up. Mitral replacement was performed in 11 patients and one of them died in PBMV, while none of patients underwent re-intervention in rMVP, but one patient died of pneumonia. CONCLUSIONS: For selected patients with rheumatic MS in China, our study shows that there are comparable clinical outcomes in terms of operative, mid-term mortality and complications between PBMV and surgical rMVP with "four-step" procedure. Surgical rMVP shows more advantageous in the correction of valve stenosis and the management of concomitant tricuspid valve lesions and atrial fibrillation (AF).

LncRNA ANRIL acts as a modular scaffold of WDR5 and HDAC3 complexes and promotes alteration of the vascular smooth muscle cell phenotype.

Many studies have shown that long-noncoding RNA (lncRNA) is associated with cardiovascular disease, but its molecular mechanism is still unclear. In this study, we explored the role of lncRNA ANRIL in ox-LDL-induced phenotypic transition of human aortic smooth muscle cells (HASMC). The results of quantitative fluorescence PCR showed that the expression of ANRIL in patients with coronary atherosclerotic heart disease (CAD) was significantly higher than that in normal subjects. RNA-FISH detection showed that the ANRIL expression increased in HASMC treated by ox-LDL. Ox-LDL could upregulate the expression of ANRIL and ROS and promote the phenotypic transition of HASMC. After downregulation of ANRIL by siRNA, ROS level decreased and HASMC phenotypic transition alleviated. ANRIL could act as a molecular scaffold to promote the binding of WDR5 and HDAC3 to form WDR5 and HDAC3 complexes, they regulated target genes such as NOX1 expression by histone modification, upregulated ROS level and promote HASMC phenotype transition. Therefore, we found a new epigenetic regulatory mechanism for phenotype transition of VSMC, ANRIL was a treatment target of occlusive vascular diseases.

[Studies on fingerprints and efficacy-related substance of classical prescription Zhuru Decoction].

Based on fingerprint and network pharmacology,the whole process quality control of Zhuru Decoction was conducted and efficacy-related substances were predicted.The fingerprints of raw materials,decoction pieces and Zhuru Decoction were established,and 25 common peaks were identified,including 9 common chromatographic peaks of 3'-hydroxy puerarin,puerarin,3'-methoxy puerarin,puerarin,aperioside,daidzin,daidzein,liquiritin,glycyrrhizic acid and 6-gingerol, with similarity all greater than 0.95.The main groups of pharmacodynamic substances can be transferred from raw materials,decoction pieces to Zhuru Decoction step by step,with a clear affiliation relationship.Based on the testability and traceability,the active ingredients were screened,and the network relationship of "component-target-pathway" was constructed and analyzed for the nine chemical components screened by network pharmacology.The enriched pathways included energy metabolism,alcoholism,and smooth muscle contraction and relaxation-related pathways.The nine active components of Zhuru Decoction may achieve the effects of clearing heat, alleviating a hangover, harmonizing stomach and stopping vomiting through these signaling pathways.Based on transitive and traceable properties of the above 9 components as well as their close relationship to the efficacy of Zhuru Decoction,these 9 components can be identified as potential efficacy-related substances and provide basis for the overall quality control of Zhuru Decoction.