A cross-sectional study of appropriateness evaluation of anticoagulation therapy for inpatients with nonvalvular atrial fibrillation.

Background: Oral anticoagulants (OACs) are essential for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). However, the appropriateness of anticoagulation treatment in locally practice remains unclear. This study evaluated compliance with anticoagulation therapy concerning the guidelines and drug labels in patients with NVAF. Methods: Hospitalized patients diagnosed with NVAF between 1 November 2020, and 31 December 2021, were retrospectively enrolled. The appropriateness of anticoagulation regimens at discharge was evaluated based on a flowchart designed according to atrial fibrillation (AF) guidelines and medication labels. Furthermore, we explored factors potentially influencing the "no-use of OACs" using binary logistic regression and verified anticoagulation-related issues through a physician questionnaire. Results: A total of 536 patients were enrolled in this study, including 254 patients (47.4%) with inappropriate anticoagulation regimens. 112 patients (20.9%) were categorized as "underdosing-use of OACs," 134 (25%) who needed anticoagulation therapy were "no-use of OACs" and eight (1.5%) were "over-use of OACs." The results of a binary logistic regression analysis showed that paroxysmal AF (odds ratio [OR], 7.74; 95% confidence interval [CI], 4.57-13.10), increased blood creatinine levels (OR, 1.88; 95% CI, 1.11-3.16), hospitalized pacemaker implantation (OR, 6.76; 95% CI, 2.67-17.11), percutaneous coronary intervention (OR, 3.35; 95% CI, 1.44-7.80), and an increased HAS-BLED score (OR, 1.62; 95% CI, 1.11-2.35) were associated with "no-use of OACs" in patients with NVAF who had indications for anticoagulation therapy. Conclusion: For patients with NVAF with severe renal dysfunction and paroxysmal AF, anticoagulation therapy was inadequate. The underdosing-use of OACs in patients with NVAF was frequently observed. We recommend an anticoagulation management team to tailor anticoagulation regimens to suit each patient's needs.

Pien Tze Huang Inhibits Migration and Invasion of Hepatocellular Carcinoma Cells by Repressing PDGFRB/YAP/CCN2 Axis Activity.

OBJECTIVE: To investigate the effects of Pien Tze Huang (PZH) on the migration and invasion of HCC cells and underlying molecular mechanism. METHODS: Cell counting kit-8 (CCK-8) was applied to evaluate the cell viabilities of SMMC-7721, SK-Hep-1, C3A and HL-7702 (6 × 103 cells/well) co-incubated with different concentrations of PZH (0, 0.2, 0.4, 0.6, 0.8 mg/mL) for 24 h. Transwell, wound healing assay, CCK-8 and Annexin V-FITC/PI staining were conducted to investigate the effects of PZH on the migration, invasion, proliferation and apoptosis of SK-Hep-1 and SMMC-7721 cells (650 µ g/mL for SK-Hep-1 cells and 330 µ g/mL for SMMC-7721 cells), respectively. In vivo, lung metastasis mouse model constructed by tail vein injection of HCC cells was used for evaluating the anti-metastasis function of PZH. SK-Hep-1 cells (106 cells/200 µ L per mice) were injected into B-NDG mice via tail vein. Totally 8 mice were randomly divided into PZH and control groups, 4 mice in each group. After 2-d inoculation, mice in the PZH group were administered with PZH (250 mg/kg, daily) and mice in the control group received only vehicle (PBS) from the 2nd day after xenograft to day 17. Transcriptome analysis based on RNA-seq was subsequently used for deciphering anti-tumor mechanism of PZH. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were applied to verify RNA-seq results. Luciferase reporter assay was performed to examine the transcriptional activity of yes-associated protein (YAP). RESULTS: PZH treatment significantly inhibited the migration, invasion, proliferation and promoted the apoptosis of HCC cells in vitro and in vivo (P<0.01). Transcriptome analysis indicated that Hippo signaling pathway was associated with anti-metastasis function of PZH. Mechanical study showed PZH significantly inhibited the expressions of platelet derived growth factor receptor beta (PDGFRB), YAP, connective tissue growth factor (CCN2), N-cadherin, vimentin and matrix metallopeptidase 2 (MMP2, P<0.01). Meanwhile, the phosphorylation of YAP was also enhanced by PZH treatment in vitro and in vivo. Furthermore, PZH played roles in inhibiting the transcriptional activity of YAP. CONCLUSION: PZH restrained migration, invasion and epithelial-mesenchymal transition of HCC cells through repressing PDGFRB/YAP/CCN2 axis.

[Antihypertensive effect and pharmacokinetics of low molecular mass potassium alginate].

OBJECTIVE: To investigate the effect of low molecular weight potassium alginate (L-PA) on blood pressures in spontaneously hypertensive rats (SHRs) and its pharmacokinetics characteristics in mice. METHODS: The systolic blood pressure (SBP) was measured by tail-cuff method in conscious SHRs. Forty rats were randomly assigned to the following five groups: control, hydrochlorothiazide (HCT, 6.25 mg/kg), L-PA in low, middle or high dose groups (100, 250, 500 mg/kg). SHRs were intragastrically (i. g.) administrated once daily for 28 days. The SBP was measured once weekly during drug treatment, and 3 and 6 days after drug with drawal. KM mice were i. g. administered with 100 mg/kg (74 MBq/kg) of 3H-L-PA. Ten microl blood samples were obtained from the tail vein at 2, 5, 10, 20, 30 min and 1, 2, 4, 6, 12, 24, 48, 72, 96, 120 or 144 h after drug administration for measuring radioactivities. Pharmacokinetics parameters of the oral administration of L-PA were analysed with DAS 2.0 software. RESULTS: Twenty-one or 28 days after administration, the rats in the groups treated with HCT or L-PA at 100, 250 or 500 mg/kg had a significant decrease in SBP (P<0.01 vs control group). Three or 6 days after drug withdrawal, the antihypertensive effect of HCT disappeared (P>0.05), whereas the rats treated with 250 or 500 mg/kg L-PA still had lower SBP than the controls (P<0.01). The L-PA at a dose of 100 mg/kg also led to a significant decrease in SBP 3 days after drug withdrawal (P<0.05). The pharmacokinetics of L-PA (i. g.) was consistent with a two-compartment model, with 2.76 h of absorption half-life (t1/2, Ka), 42. 30 h of distributional half-life (t1/2alpha), 42. 31 h of elimination half-life (t1/2beta), and 36.28 h of terminal phase elimination half-life (t1/2z). CONCLUSION: Oral administration of L-PA has significant anti-hypertensive effect, which can be maintained to 6 days after drug withdrawal. The sustaining anti-hypertensive effect of L-PA is probably associated with its slow elimination in vivo.

Emodin-induced autophagy against cell apoptosis through the PI3K/AKT/mTOR pathway in human hepatocytes.

BACKGROUND: Emodin, a major component of Polygonum multiflorum (PM), has been reported to exert both protective and toxic effects in several cell types. However, the effects and underlying mechanisms of action of emodin in hepatic cells are still obscure. METHODS: The present study used the normal human liver cell line L02 to investigate the effects and mechanisms of emodin in hepatic cells. After treatment with emodin, L02 cells were examined for viability, apoptosis and autophagy with the Cell Counting Kit-8 (CCK-8), annexin V/PerCP staining and GFP-LC3 plasmid transfection. The expression of proteins including cleaved caspase-3, LC3B-I/II, p-PI3K, PI3K, p-AKT, AKT, p-mTOR, mTOR and actin was examined by using Western blot. RESULTS: Emodin significantly inhibited the viability of and induced apoptosis in L02 cells in a dose- and time-dependent manner. In addition, emodin increased the number of GFP-LC3 puncta in L02 cells and upregulated the expression of LC3B-II compared to those in control cells. Furthermore, emodin significantly decreased the expression of p-PI3K, p-AKT and p-mTOR in a dose-dependent manner compared to that in control cells without altering the expression of PI3K, AKT and mTOR. Notably, cotreatment with emodin and 3-methyladenine (3-MA) or rapamycin significantly increased and decreased the apoptosis rate of L02 cells, respectively, compared to that of cells treated with emodin alone. CONCLUSION:  In conclusion, emodin exhibited cytotoxicity in the L02 human hepatic cell line by promoting apoptosis, and it also induced autophagy through the suppression of the PI3K/AKT/mTOR signalling pathway. The autophagy could play a protective role following emodin treatment.

[Inhibitory effects and mechanism of tanshinone IIA on proliferation of rat aortic smooth muscle cells].

OBJECTIVE: To investigate the effects of tanshinone IIA (TA, one of the active components of Salvia miltiorrhiza Bge), on the proliferation of cultured rat vascular smooth muscle cells (VSMC), and to clarity the probable mechanism. METHOD: Cell culture technique was used in vitro and treated with or without 10% FBS. The inhibitory effect of TA on proliferation of VSMC was observed by cell count, MTU metabolism measuring and BrdU incorporation assay. Flow cytometry was performed to track cell cycle progression. Western bolts were performed to evaluate ERK1/2 activity. The expression of c-fos was examined by RT-PCR. RESULT: The results of cell number, MTU assay and BrdU incorporation showed that TA cound significantly inhibit 10% FBS induced proliferation in a dose-dependent manner. Flow cytometry (FCM) analysis indicated that the G5/G1 phase fraction ratio of TA group was higher than that of 10% FBS group, while the S-phase fraction ratio was lower than that of 10% FBS group. Western blot's results displayed that TA inhibited the phosphorylation of ERK1/2, and in accordance with this findings. TA could decrease the early elevation of c-fos expression. CONCLUSION: These results suggest that TA can inhibit 10% FBS induced the proliferation of VSMC. This effect may be related to its blocking VSMCs cell cycle in G0/G1 phase, inhibiting of the ERK1/2 activity, and decreasing the expression of c-fos.

Phase transition and switchable dielectric behaviours in an organic-inorganic hybrid compound: (3-nitroanilinium)2(18-crown-6)2(H2PO4)2(H3PO4)3(H2O).

An organic-inorganic hybrid compound with an extensive three-dimensional (3D) crystal structure, (3-nitroanilinium)2(18-crown-6)2(H2PO4)2(H3PO4)3(H2O) (1), was synthesized under slow evaporation conditions. Differential scanning calorimetry measurements indicated that 1 underwent a reversible phase transition at ca 231 K with a hysteresis width of 10 K. Variable-temperature X-ray single-crystal diffraction revealed that the phase transition of 1 can be ascribed to coupling of pendulum-like motions of its nitro group with proton transfer in O-H···O hydrogen bonds of the 3D framework. The temperature dependence of its dielectric permittivity demonstrated a step-like change in the range of 150-280 K with remarkable dielectric anisotropy, making 1 a promising switchable dielectric material. Potential energy calculations further supported the possibility of dynamic motion of the cationic nitro group. Overall, our findings may inspire the development of other switchable dielectric phase transition materials by introducing inorganic anions into organic-inorganic hybrid systems.

Left Atrial Appendage Thrombus Formation in a Patient on Dabigatran Therapy Associated With ABCB1 and CES-1 Genetic Defect.

Dabigatran, directly targeting thrombin, is widely used for the prevention of stroke in nonvalvular atrial fibrillation (NVAF). We reported a rare case of left atrial appendage thrombus formation in a persistent NVAF patient despite the 31 months uninterrupted treatment with dabigatran 110 mg twice daily. The patient is a carrier of ABCB1 variant alleles with 7 heterozygote single nucleotide polymorphisms (SNPs: rs4148738, rs2235046, rs1128503, rs10276036, rs1202169, rs1202168, rs1202167) as well as CES-1 variant alleles with 2 homozygote SNPs (rs2244613 and rs4122238) and 2 heterozygote SNPs (rs8192935 and rs4580160), which may contribute to the changes of dabigatran plasma concentration. In addition, Drug-drug interaction with atorvastatin may also play a role to decrease dabigatran plasma concentration. There are only four such cases till date, of which had thrombus in the left atrium, reported in the literature. We firstly reported the documented case in a Chinese patient carrying multiple alleles of ABCB1 and CES-1, who suffered from thrombus in the left atrial appendage despite long-term anticoagulation with dabigatran. More clinical data are required to elucidate the impact of CES-1 and ABCB1 polymorphism on dabigatran pharmacokinetics, especially for Asian.

[Experimental study of effect of tanshinone on artery restenosis in rat carotid injury model].

OBJECTIVE: To observe the preventive and therapeutic effect of tanshinone (TA) on artery restenosis in the rat carotid injury model and explor the mechanism. METHOD: Male SD rats were randomly divided into model control group, and low dose, moderate dose and high dose TA groups. Each group had 10 rats. The rats in the high, moderate and low dose groups were respectively fed with TA 120, 40,13.3 mg x kg(-1) x d(-1) by gast rogavage; the rats in the model control group were fed with the same volume solvent. Two days later, the rat's right carotid artery was injuried by balloon dilatation to induce intimal thickening for establishing the restenosis model. After 2 weeks of treatment, the artery was harvested and stained by hematoxylin-elsin (HE) and immunohistochemistry of PCNA, NF-kappaB and iNOS. The morphological changes were checked under microscope. The area of the intimal and medial layer of the vessels, and their ratios were analyzed with image analysis software. The expression level of PCNA, NF-kappaB and iNOS were used as the positive index. RESULT: The intimal area and intima-to-media ratio of the injuried artery increased obviously, suggesting the model was successful. Compared with the model group, TA significantly decreased the intimal area and intima-to-media ratio (P < 0.05), and also decreased the positive index of PCNA and the positive ratio of NF-kappaB and iNOS (P < 0.05). CONCLUSION: TA can effectively inhibit intimal thickening and inflammation. This result suggestes that TA may play a positive role in the prevention of restenosis after PTCA.

Tanshinone IIA inhibits smooth muscle proliferation and intimal hyperplasia in the rat carotid balloon-injured model through inhibition of MAPK signaling pathway.

AIM OF THE STUDY: To investigate the effect of tashinone IIA (TA) on intimal hyperplasia in a rat model of carotid artery balloon injury and on the proliferation of cultured vascular smooth muscle cells (VSMCs) induced by fetal bovine serum (FBS) and its underlying mechanisms. MATERIALS AND METHODS: Carotid artery injury was induced in rats by balloon dilatation and they were treated with TA or vehicle for 2 weeks until killed for assessment of neointimal formation and lumen area. VSMC was cultured in vitro and proliferation was assessed by determining cell number, bromodeoxyuridine (BrdU) incorporation and cell cycle analysis. The extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and c-fos expression were assessed by Western blot and reverse transcription-polymerase chain reaction (RT-PCR) respectively. RESULTS: TA could significantly decrease intimal thickening, suppress cell proliferation and BrdU incorporation into DNA, block cell cycle in G(0)/G(1) phase, inhibit ERK1/2 phosphorylation and c-fos expression. CONCLUSIONS: TA abolishes VSMC proliferation and reduces intimal hyperplasia through inhibition of mitogen-activated protein kinase (MAPK) signaling pathway and down-regulation of c-fos expression.