Re-exposure to iodinated contrast media in two patients with prior severe hypersensitivity reaction.

OBJECTIVE: Most allergic reactions to iodinated contrast media can be managed using a pre-treatment protocol involving corticosteroids and antihistamines. However, under certain circumstances, patients may experience severe allergic symptoms despite pre-treatment. CASE REPORT: Two Chinese men with a history of severe contrast allergy and unstable angina underwent a desensitization protocol that allowed for successful percutaneous coronary intervention. CONCLUSION: Rapid desensitization is an effective and safe strategy that may allow other patients with similar allergies to successfully undergo angiography that requires the use of radiocontrast media.

A review: Pharmacology and pharmacokinetics of Schisandrin A.

Schisandrin A (SA) is a bioactive lignan isolated from the traditional Chinese medicine Fructus schisandrae chinensis. In recent years, it has attracted extensive attention because of its multiple pharmacological activities. This review is the first to provide an overview of SA-related pharmacological effects and pharmacokinetic characteristics. The results showed that SA had many pharmacological effects, such as antiinflammation, anticancer, hepatoprotection, antioxidation, neuroprotection, antidiabetes mellitus, and musculoskeletal protection. Among them, NF-κB, Nrf2, MAPK, NLRP3, PI3K/AKT, Wnt, miRNA, P-gp, CYP450, PXR, and other signal transduction pathways are involved. Pharmacokinetic studies showed that SA had good pharmacokinetic characteristics, but these were affected by other factors, such as drugs or hepatic fibrosis. Thus, SA has a variety of pharmacological effects and good pharmacokinetic characteristics, which is worthy of further research and development in the future.

Diagnostic value of colposcopy in patients with cytology-negative and HR-HPV-positive cervical lesions.

PURPOSE: High-risk human papillomavirus (HR-HPV)-positive but cytology-negative cervical cancer screening results are not uncommon. This study aimed to investigate colposcopy's accuracy and diagnostic value in patients with cytology-negative HR-HPV-positive screening results. METHODS: This retrospective study included patients with HR-HPV-positive cytology-negative screening results who underwent electronic colposcopy with acetic acid and multi-point cervical biopsy, HPV typing (24 HPV subtypes), and quantitative HPV detection. RESULTS: Among 229 patients, 130 had chronic cervicitis, and 99 had cervical lesions (CIN1, n = 37; CIN2/3, n = 55; invasive carcinoma, n = 7). Using colposcopy as a reference, the cervical cytology false-negative rate was 43.2% (99/229). Colposcopy was more accurate in patients with HR-HPV16/18 or high viral loads. Multivariable analyses showed HPV viral load and childbearing history were the independent factors affecting the accuracy of colposcopy (P < 0.05). CONCLUSION: Colposcopy in HR-HPV-positive cytology-negative patients has a moderate diagnostic accuracy. The type of cervical transformation zone and HPV viral load are independent factors affecting the accuracy of colposcopy-based diagnosis.

A review of pharmacological and pharmacokinetic properties of Forsythiaside A.

Traditional Chinese medicine plays a significant role in the treatment of various diseases and has attracted increasing attention for clinical applications. Forsythiae Fructus, the dried fruit of Forsythia suspensa (Thunb.) Vahl, is a widely used Chinese medicinal herb in clinic for its extensive pharmacological activities. Forsythiaside A is the main active index component isolated from Forsythiae Fructus and possesses prominent bioactivities. Modern pharmacological studies have confirmed that Forsythiaside A exhibits significant activities in treating various diseases, including inflammation, virus infection, neurodegeneration, oxidative stress, liver injury, and bacterial infection. In this review, the pharmacological activities of Forsythiaside A have been comprehensively reviewed and summarized. According to the data, Forsythiaside A shows remarkable anti-inflammation, antivirus, neuroprotection, antioxidant, hepatoprotection, and antibacterial activities through regulating multiple signaling transduction pathways such as NF-κB, MAPK, JAK/STAT, Nrf2, RLRs, TRAF, TLR7, and ER stress. In addition, the toxicity and pharmacokinetic properties of Forsythiaside A are also discussed in this review, thus providing a solid foundation and evidence for further studies to explore novel effective drugs from Chinese medicine monomers.

Significance of the viral load of high-risk HPV in the diagnosis and prediction of cervical lesions: a retrospective study.

BACKGROUND: The significance of HPV viral load in the detection of cervical lesions is still controversial. This study analyzed the correlation between the high-risk HPV viral load and different cervical lesion degrees. METHODS: This retrospective study included women positive for high-risk HPV DNA and screened for cervical lesions between 01/2015 and 06/2018. The high-risk HPV DNA load was measured by the second-generation Hybrid Capture technology and classified as low, moderate, and high. Colposcopy and biopsy were performed in all patients. The patients were grouped as normal, cervical intraepithelial neoplasia (CIN) grade 1, CIN grade 2, CIN grade 3, and cervical cancer. Multivariable logistic regression was performed to explore the association between high-risk HPV DNA load and cervical lesions. The odds ratios (ORs) represent the odds for increasing from low to high viral load. RESULTS: Finally, 265 patients were grouped as normal (n = 125), CIN 1 (n = 51), CIN 2 (n = 23), CIN 3 (n = 46), and cervical cancer (n = 20). Among them, 139 (52.5%) had a low viral load, 90 (34.0) had a moderate viral load, and 36 (13.4%) had a high viral load. Taking the normal control group as a reference, a high viral load was an independent factor for CIN 1 (OR = 3.568, 95% CI: 1.164-10.941, P = 0.026), CIN 2 (OR = 6.939, 95% CI: 1.793-26.852, P = 0.005), CIN 3 (OR = 7.052, 95% CI: 2.304-21.586, P = 0.001), and cervical cancer (OR = 8.266, 95% CI: 2.120-32.233, P = 0.002). CONCLUSIONS: Among women who underwent cervical biopsy, higher high-risk HPV viral load in cervical lesions was associated with a higher risk of high-grade cervical lesions.

Reciprocal regulation of Akt and Oct4 promotes the self-renewal and survival of embryonal carcinoma cells.

Signaling via the Akt serine/threonine protein kinase plays critical roles in the self-renewal of embryonic stem cells and their malignant counterpart, embryonal carcinoma cells (ECCs). Here we show that in ECCs, Akt phosphorylated the master pluripotency factor Oct4 at threonine 235, and that the levels of phosphorylated Oct4 in ECCs correlated with resistance to apoptosis and tumorigenic potential. Phosphorylation of Oct4 increased its stability and facilitated its nuclear localization and its interaction with Sox2, which promoted the transcription of the core stemness genes POU5F1 and NANOG. Furthermore, in ECCs, unphosphorylated Oct4 bound to the AKT1 promoter and repressed its transcription. Phosphorylation of Oct4 by Akt resulted in dissociation of Oct4 from the AKT1 promoter, which activated AKT1 transcription and promoted cell survival. Therefore, a site-specific, posttranslational modification of the Oct4 protein orchestrates the regulation of its stability, subcellular localization, and transcriptional activities, which collectively promotes the survival and tumorigenicity of ECCs.

MicroRNA-214 Suppresses Ovarian Cancer by Targeting ß-Catenin.

BACKGROUND/AIMS: Ovarian cancer is one of the most common malignancies with a high rate of mortality in women. However, current therapies for ovarian cancer treatment are ineffective. Therefore, novel target identification is an urgent requisite. The present study aimed to investigate the role of microRNA-214 (miR-214) in ovarian cancer. METHODS: The expression of miR-214, ß-catenin, cyclin D1, c-myc, and TCF-1 at the transcriptional level was measured by real-time PCR, while that of ß-catenin, Cyclin D1, and c-Myc at the protein level were detected by western blot. Colony formation assay and transwell assay were used to explore the invasion ability of the cancer cells. Cell cycle was measured by flow cytometry. RESULTS: Real-time PCR showed that miR-214 expression in ovarian cancer cell lines was lower than that in the human normal ovarian epithelial cells, IOSE80. Furthermore, the low expression of miR-214 was correlated with high pathological grade. The rate of colony formation and invasion of miR-214 overexpression in SKOV-3 cells were weaker than that in control cells. Moreover, miR-214 overexpression led to the G0/G1 phase arrest. The expression of ß-catenin, Cyclin D1, and c-Myc was suppressed by the overexpression of miR-214. CONCLUSION: These results suggested that miR-214 may serve as a tumor suppressor of ovarian cancer by targeting the ß-catenin pathway.

MiR-214 suppressed ovarian cancer and negatively regulated semaphorin 4D.

Ovarian cancer is one of the most common human malignancies in women. MiR-214 and semaphorin 4D (sema 4D) were found to be abhorrently expressed and involved in the progress of several kinds of malignant cancers. This study is aimed to investigate the cellular role of miR-214 and demonstrate that miR-214 negatively regulated sema 4D in ovarian cancer cells. The data showed that miR-214 expression was consistently lower in ovarian cancer tissues and cells than those in the normal controls. Over-expression of miR-214 in ovarian cancer SKOV-3 cells inhibited cell proliferation and induced apoptosis. It was suggested that miR-214 functioned as the tumor suppressor in ovarian cancer. Bioinformatic analysis indicated that miR-214 possibly regulated sema 4D by binding the sema 4D messenger RNA (mRNA) 3'-untranslated region (UTR). Sema 4D mRNA and protein levels were up-regulated in ovarian cancer tissues and SKOV-3 cells. Up-regulation of miR-214 in SKOV-3 cell line suppressed the sema 4D expression in both protein and nucleic acid levels. While, down-regulation of miR-214 in SKOV-3 cells would increase sema 4D protein and nucleic acid expression levels. The effects of miR-214 up- and down-regulation on luciferase activities of wild-type (WT) sema 4D 3'-UTR were completely removed upon introduction of mutation in 3'-UTR of WT sema 4D. Therefore, the data also demonstrated that sema 4D was the direct target of miR-214 and was negatively regulated by miR-214 in ovarian cancer cells.

Correlation Between SNPs in Candidate Genes and VerifyNow-Detected Platelet Responsiveness to Aspirin and Clopidogrel Treatment.

PURPOSE: Patients with high on-treatment platelet reactivity (HPR) against aspirin or clopidogrel are at increased risk for adverse cardiovascular events. In this study, we explored the predictive value of common SNPs for the on-treatment platelet reactivity (OPR) against aspirin and clopidogrel assessed by VerifyNow assays. METHODS: This study recruited 286 Han Chinese individuals undergoing antiplatelet treatment, including 159 cases with aspirin only (100 mg/day) and 127 cases with dual therapy (aspirin 100 mg/day plus clopidogrel 75 mg/day) for at least 2 weeks. The OPR against aspirin and clopidogrel were assessed by VerifyNow Aspirin (ARU) and P2Y12 assays (PRU), respectively. Genotyping for the selected 25 SNPs within 11 genes and 2 GWAS loci was carried out by ABI multiplex SNaPshot method. RESULTS: The results indicated that rs4244285 (CYP2C19) and rs342293 (7q22.3) were significantly associated with PRU value (both P < 0.01). As for the OPR to aspirin, a weak statistical significance was observed in rs5445 (GNB3) (P = 0.049) and rs5758 (TBXA2R) (P = 0.045). After adjusting for the covariates including gender, age and smoking, carriers of allele A of rs4244285 remained as a strong predictor for HPR against clopidogrel. CONCLUSION: The current study suggests that common SNPs may predict OPR against clopidogrel as assessed by VerifyNow P2Y12, but are less likely to respond against aspirin as assessed by VerifyNow Aspirin.

Possible quantum-spin-liquid state in van der Waals cluster magnet Nb3Cl8.

The cluster magnet Nb3Cl8consists of Nb3trimmers that form an emergentS= 1/2 two-dimensional triangular layers, which are bonded by weak van der Waals interactions. Recent studies show that its room-temperature electronic state can be well described as a single-band Mott insulator. However, the magnetic ground state is non-magnetic due to a structural transition below about 100 K. Here we show that there exists a thickness threshold below which the structural transition will not happen. For a bulk crystal, a small fraction of the sample maintains the high-temperature structure at low temperatures and such remnant gives rise to linear-temperature dependence of the specific heat at very low temperatures. This is further confirmed by the measurements on ground powder sample orc-axis pressed single crystals, which prohibits the formation of the non-magnetic state. Moreover, the intrinsic magnetic susceptibility also tends to be constant with decreasing temperature. Our results suggest that Nb3Cl8with the high-temperature structure may host a quantum-spin-liquid ground state with spinon Fermi surfaces, which can be achieved by making the thickness of a sample smaller than a certain threshold.

Constitutive NF-kappaB activation by the t(11;18)(q21;q21) product in MALT lymphoma is linked to deregulated ubiquitin ligase activity.

Mucosa-associated lymphoid tissue (MALT) lymphoma is a common type of lymphoma in extranodal sites. The most frequent chromosome translocation associated with MALT lymphoma is t(11;18)(q21;q21), which generates a chimeric protein of c-IAP2 and MALT1/paracaspase. The c-IAP2/MALT1 fusion protein activates the NF-kappaB pathway, which is considered critical to malignant B cell transformation and lymphoma progression. The mechanism by which this fusion protein activates NF-kappaB, however, remains unclear. Here we show that self-oligomerization of the c-IAP2/MALT1 protein causes deregulated ubiquitin ligase activity of MALT1/paracaspase. The chimeric protein targets NEMO for polyubiquitination and thereby activates NF-kappaB. Consistent with this finding, NEMO ubiquitination is increased in t(11;18)(q21;q21)-positive MALT lymphoma samples. Thus, t(11;18)(q21;q21) deregulates MALT1/paracaspase ubiquitin ligase activity, causing constitutive NF-kappaB activation and promoting tumorigenesis.

[Evaluation of myocardial perfusion in patients with coronary slow flow by myocardial contrast echocardiography].

OBJECTIVE: To explore myocardial perfusion of patients with coronary slow flow (CSF) using myocardial contrast echocardiography. METHODS: Myocardial contrast echocardiography was performed in coronary artery angiography diagnosed CSF patients (n = 20) and control patients (n = 20). The images at baseline and after low dose dobutamine stress test were analyzed by automatic tracking software and the maximal amplitude score A, the mean ascending slope of the curve ß and the product of A×ß were measured. The reserve of A×ß was also calculated. Electrocardiogram at rest and at each stage of dobutamine stress test was obtained simultaneously. RESULTS: At baseline, the A [(6.85 ± 2.99) dB vs. (7.01 ± 3.49) dB], ß[(0.59 ± 0.33)/s vs. (0.61 ± 0.38)/s] and A×ß [(3.48 ± 1.46) dB/s vs. (3.31 ± 0.96) dB/s] values were similar between CSF group and control group (all P > 0.05). After dobutamine stress test, both ß and A×ß were significantly increased in two groups. The ß [(0.89 ± 0.42)/s vs. (1.31 ± 0.54)/s, P < 0.01] and A×ß [(5.82 ± 2.69) dB/s vs. (8.07 ± 2.76)dB/s, P < 0.05] in CSF group were significantly lower than in control group. Electrocardiogram of all the subjects was normal at rest, but the electrocardiogram positive rate was significantly higher in CSF group than in control group after dobutamine stress test (12% vs. 2%, 60% vs. 10%, P < 0.01). CONCLUSIONS: Dobutamine stress test could induce myocardial perfusion abnormalities in patients with coronary slow flow phenomenon.

Phillygenin inhibited M1 macrophage polarization and reduced hepatic stellate cell activation by inhibiting macrophage exosomal miR-125b-5p.

Liver fibrosis (LF) is an important stage in chronic liver disease development, characterized by hepatic stellate cell (HSC) activation and excessive extracellular matrix deposition. Phillygenin (PHI), an active component in the traditional Chinese medicine Forsythiae Fructus with a significant anti-inflammatory effect, has been proved to inhibit HSC activation. Macrophages can polarize to pro-inflammatory M1 phenotype and anti-inflammatory M2 phenotype, participating in LF development. Currently, Forsythiae Fructus and its many components have been proved to inhibit the inflammatory activation of macrophages. However, there is no direct evidence that PHI can regulate macrophage polarization, and the relationship between macrophage polarization and the anti-LF effect of PHI has not been studied. In this study, we found that PHI inhibited the co-expression of CD80 and CD86, and inhibited the mRNA expression and protein secretion of related inflammatory cytokines in RAW264.7 cells. For mechanism, PHI was found to inhibit the JAK1/JAK2-STAT1 and Notch1 signaling pathways. Subsequently, mHSCs were co-cultured with the conditioned media or exosomes from macrophages with different treatments. It was found that the conditioned media and exosomes from PHI-treated macrophages inhibited the expression of MMP2, TIMP1, TGF-ß, α-SMA, COL1 and NF-κB in mHSCs. Moreover, through bioinformatic analysis and cell transfection, we confirmed that PHI reduced HSC activation by inhibiting the overexpression of miR-125b-5p in M1 macrophage-derived exosomes and restoring Stard13 expression in mHSCs. On the whole, PHI could inhibit M1 macrophage polarization by suppressing the JAK1/JAK2-STAT1 and Notch1 signaling pathways, and reduce HSC activation by inhibiting macrophage exosomal miR-125b-5p targeting Stard13. DATA AVAILABILITY: The raw data supporting the conclusions of this study are available in the article/Supplementary figures, and can be obtained from the first or corresponding author.

Preparation of Phillygenin-Hyaluronic acid composite milk-derived exosomes and its anti-hepatic fibrosis effect.

Liver fibrosis remains a serious problem affecting the health of millions of people worldwide. Hepatic stellate cells (HSCs) are the main effector cells in liver fibrosis and their activation could lead to extracellular matrix deposition, which may aggravate the development of liver fibrosis and inflammation. Previous studies have reported the potential of Phillygenin (PHI) as a hepatoprotective agent to inhibit HSCs activation and fibrosis development. However, the poor water solubility of PHI hinders its clinical application as a potential anti-liver fibrosis therapy. Milk-derived exosomes (mEXO) serve as scalable nanocarriers for delivering chemotherapeutic agents due to their excellent biocompatibility. Here, we developed a PHI-Hyaluronic acid (HA) composite mEXO (PHI-HA-mEXO) drug delivery system, in which DSPE-PEG2000-HA was conjugated to the surface of mEXO to prepare HA-mEXO, and PHI was encapsulated into HA-mEXO to form PHI-HA-mEXO. As a specific receptor for HA, CD44 is frequently over-expressed during liver fibrosis and highly expressed on the surface of activated HSCs (aHSCs). PHI-HA-mEXO can bind to CD44 and enter aHSCs through endocytosis and release PHI. PHI-HA-mEXO drug delivery system can significantly induce aHSCs death without affecting quiescent HSCs (qHSCs) and hepatocytes. Furthermore, we carried out in vitro and in vivo experiments and found that PHI-HA-mEXO could alleviate liver fibrosis through aHSCs-targeted mechanism. In conclusion, the favorable biosafety and superior anti-hepatic fibrosis effects suggest a promising potential of PHI-HA-mEXO in the treatment of hepatic fibrosis. However, detailed pharmokinetics and dose-responsive experiments of PHI-HA-mEXO and the mechanism of mEXO loading drugs are still required before PHI-HA-mEXO can be applied clinically.

CD44-Targeting Drug Delivery System of Exosomes Loading Forsythiaside A Combats Liver Fibrosis via Regulating NLRP3-Mediated Pyroptosis.

Liver fibrosis is a progressive pathological process induced by various stimuli and may progress to liver cirrhosis and cancer. Forsythiaside A (FA) is an active ingredient extracted from traditional Chinese medicine Forsythiae Fructus and has prominent hepatoprotective activities. However, the unsatisfactory pharmacokinetic properties restrict its clinical application. In this study, the nanocarrier of CD44-specific ligand Hyaluronic acid (HA)-modified milk-derived exosomes (mExo) encapsulated with FA (HA-mExo-FA) is developed. As a result, HA modification could deliver drug-loaded exosomes to the target cells and form a specific ligand-receptor interaction with CD44, thus improving the anti-liver fibrosis effect of FA. In vitro findings indicate that HA-mExo-FA could inhibit TGF-ß1-induced LX2 cell proliferation, reduce α-SMA and collagen gene and protein levels, and promote the apoptosis of activated LX2 cells. In vivo results demonstrate that HA-mExo-FA could improve liver morphology and function changes in zebrafish larvae. The anti-liver fibrosis mechanism of HA-mExo-FA may be attributed to the inhibition of NLRP3-mediated pyroptosis. In addition, the effect of HA-mExo-FA on TAA-induced increase in NLRP3 production is attenuated by NLRP3 inhibitor MCC950. Collectively, this study demonstrates the promising application of HA-mExo-FA in drug delivery with high specificity and provides a powerful and novel delivery platform for liver fibrosis therapy.

The protective effect of forsythiaside A on 3,5-diethoxycarbonyl-1,4-dihydrocollidine-induced cholestatic liver injury in mice: Based on targeted metabolomics and molecular biology technology.

Cholestasis is a disorder of bile secretion and excretion caused by a variety of etiologies. At present, there is a lack of functional foods or drugs that can be used for intervention. Forsythiaside A (FTA) is a natural phytochemical component isolated from the medicinal plant Forsythia suspensa (Thunb.) Vahl, which has a significant hepatoprotective effect. In this study, we investigated whether FTA could alleviate liver injury induced by cholestasis. In vitro, FTA reversed the decrease in viability of human intrahepatic bile duct epithelial cells, the decrease in antioxidant enzymes (SOD1, CAT and GSH-Px), and cell apoptosis induced by lithocholic acid. In vivo, FTA protected mice from 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced liver injury, abnormal serum biochemical indexes, abnormal bile duct hyperplasia, and inflammatory infiltration. Furthermore, FTA treatment alleviated liver fibrosis by inhibiting collagen deposition and HSC activation. The metabonomic results showed that DDC-induced bile acid disorders in the liver and serum were reversed after FTA treatment, which may benefit from the activation of the FXR/BSEP axis. In addition, FTA treatment increased the levels of antioxidant enzymes in the serum and liver. Meanwhile, FTA treatment inhibited ROS and MDA levels and cleaved caspase 3 protein expression, thereby reducing DDC-induced hepatic oxidative stress and apoptosis. Further studies showed that the antioxidant effects of FTA were dependent on the activation of the BRG1/NRF2/HO-1 axis. In a word, FTA has a significant hepatoprotective effect on cholestatic liver injury, and can be further developed as a functional food or drug to prevent and treat cholestatic liver injury.

Mesenchymal stem cell-derived exosomes and non-coding RNAs: Regulatory and therapeutic role in liver diseases.

Liver disease has become a major health problem worldwide due to its high morbidity and mortality. In recent years, a large body of literature has shown that mesenchymal stem cell-derived exosomes (MSC-Exo) are able to play similar physiological roles as mesenchymal stem cells (MSCs). More importantly, there is no immune rejection caused by transplanted cells and the risk of tumor formation, which has become a new strategy for the treatment of various liver diseases. Moreover, accumulating evidence suggests that non-coding RNAs (ncRNAs) are the main effectors by which they exert hepatoprotective effects. Therefore, by searching the databases of Web of Science, PubMed, ScienceDirect, Google Scholar and CNKI, this review comprehensively reviewed the therapeutic effects of MSC-Exo and ncRNAs in liver diseases, including liver injury, liver fibrosis, and hepatocellular carcinoma. According to the data, the therapeutic effects of MSC-Exo and ncRNAs on liver diseases are closely related to a variety of molecular mechanisms, including inhibition of inflammatory response, alleviation of liver oxidative stress, inhibition of apoptosis of hepatocytes and endothelial cells, promotion of angiogenesis, blocking the cell cycle of hepatocellular carcinoma, and inhibition of activation and proliferation of hepatic stellate cells. These important findings will provide a direction and basis for us to explore the potential of MSC-Exo and ncRNAs in the clinical treatment of liver diseases in the future.

Protective effects of dietary quercetin on cerebral ischemic injury: pharmacology, pharmacokinetics and bioavailability-enhancing nanoformulations.

Cerebral ischemia, as an ischemic stroke-like disease, has become a health problem of global concern. Studies have found that oxidative stress, inflammation, apoptosis, and impaired blood-brain barrier (BBB) and ion channel regulation are the basis for the development of cerebral ischemia pathology. Quercetin, a flavonoid compound, commonly found in the daily diet and in some Chinese herbal medicines, including vegetables, fruits, and tea, is one of the most prominent dietary antioxidants. Modern pharmacological studies have shown that quercetin can effectively protect against cerebral ischemic injury, and its mechanisms may involve antioxidant, anti-inflammatory, anti-apoptotic, BBB protection, ion channel regulation, cell excitatory glutamate toxicity alleviation and cognitive impairment recovery activities. However, the low bioavailability of quercetin and the presence of the BBB structure limit the therapeutic efficacy. There have been studies targeting the delivery of quercetin to the injury site through nanotechnology to enhance the therapeutic effect of quercetin. This review discusses and reviews the pharmacological activity, pharmacokinetic characteristics, and targeted delivery nanosystems of quercetin in protecting against cerebral ischemic injury, and provides information on various downstream signaling pathways regulated by quercetin, such as PI3k/Akt, MAPK, and Sirt1. We hope to provide a scientific basis for the development and application of quercetin in the field of cerebral ischemia.

[Diagnostic value of 320-slice computed tomography coronary angiography to assess in-stent restenosis].

OBJECTIVE: To evaluate the diagnostic accuracy of 320-slice CT coronary angiography (CTA) in the evaluation of in-stent restenosis (ISR, ≥50% luminal narrowing) in comparison with quantitative coronary angiography (CAG). METHODS: A total of 69 patients with previous stent implantation who underwent both CTA and CAG were prospectively included. We assessed diagnostic valve for ISR with CTA in comparison with CAG. RESULTS: A total of 110 stents were implanted in these patients.CAG identified 14 ISR. CTA correctly identified 13 ISR and misdiagnosed 5 ISR in stents without ISR. Besides, 6 stents could not be evaluated by CTA due to unsatisfied image quality. Accordingly, sensitivity, specificity, positive and negative predictive value of CTA for diagnosing ISR were 93%, 89%, 54% and 99%, respectively. The image quality of CTA was significantly better in larger stents (percentages of good and moderate stent image of ≥3.0 mm and <3.0 mm: 56% vs. 27%, 25% vs. 49%) and which was linked with better diagnostic coincidence rate (95% vs. 78%) for larger stents. The image quality of CTA was significantly better in stents with thinner stent strut thickness (percentages of poor CTA stent image quality of stent strut thickness<140 µm and ≥140 µm: 12% vs. 45%, P<0.01) and which was associated with better diagnostic coincidence rate for stents with thinner stent strut thickness (94% vs. 76%, P<0.05). The image quality of CTA was also significantly better in single stent (percentages of poor CTA stent image quality of single stent vs. overlap and dedicated stent: 17% vs. 36%, P<0.05). However, heart rate (≥65 beats/min vs. <65 beats/min) during CTA acquisition was not associated with image quality and the diagnostic coincidence rate (all P>0.05). CONCLUSIONS: Our results indicate that 320-slice CTA allows accurate noninvasive assessment of significant in-stent restenosis in selected patients. Stents with a large diameter and thin struts are associated with better image quality and higher diagnostic accuracy.

[Clinical application of VerifyNow-P2Y12 assay in evaluation of platelet inhibition efficacy of clopidogrel].

OBJECTIVE: To evaluate the platelet inhibition efficacy in patients under regular maintenance dose of clopidogrel by VerifyNow-P2Y12 assay and explore the clinical characteristics of clopidogrel non-responders and related predicting factors. METHODS: A total of 99 patients underwent percutaneous coronary intervention procedure and receiving clopidogrel in regular maintenance dose for at least 1 week were enrolled. Platelet reactivity, including baseline, P2Y12 reaction unit (PRU), and platelet inhibition rate were measured with VeifyNow-P2Y12 assay. The dosage of anti-platelet drugs, combination with any other drugs, clinical characters in baseline of all enrolled patients were analyzed. PRU ≤ 240 was used as cut-off to identify clopidogrel responder and clopidogrel non-responder. In the non-responder group, patients were further separated into 3 sub-groups (types) according to the baseline and platelet inhibition rate: type I with high baseline, high inhibition rate, representing false non-responder; type II with low inhibition rate, representing true non-responder and type III mixed type. RESULTS: In this study, 48 of 99 patients were found to be clopidogrel non-responder (48.5%). The ratio of type I, type II and type III in the non-responder group was 9.1% (n = 9), 27.3% (n = 27), and 12.1% (n = 12), respectively. Baseline platelet value in female patients was significantly higher than in males (P < 0.01), number of females with high PRU also is higher than males (P < 0.01), female gender was a predict factor for type I non-responder (OR = 6.5, 95%CI 2.295 - 18.407, P < 0.01). BMI > 24 kg/m(2) was a risk factor for clopidogrel non-responder (P < 0.05), and may be regarded as a predict factor for type II non-responder (OR = 3.207, 95%CI 1.375 - 7.485, P < 0.01). Age, hypertension, diabetics, smoking, hyperlipidemia, CRP and pantoprazole use do not show significant correlation with baseline and platelet inhibition rate. CONCLUSIONS: Clopidogrel responses could be reliably detected by VerifyNow-P2Y12 assay. Female gender and high body weight are independent risk factors for clopidogrel non-responses.