Research progress in plasma concentration monitoring of rivaroxaban / 中国临床药理学与治疗学

Rivaroxaban, a novel oral anticoagulant drug, is widely prescribed in clinical practice. Rivaroxaban offers predictable pharmacokinetic and pharmacodynamic properties, a lowprobability of drug-drug and food-drug interactions. Compared with warfarin, rivaroxaban does not require continuous therapeutic monitoring and can be administered in fixed doses.However,in certain emergency clinical situations, such as bleeding, acute stroke, acute kidney injury, prior to urgent surgery and in the suspected accumulation of durg, plasma concentration monitoring of rivaroxaban is necessary and important for patients. Existing studies proved that there were significant individual variability and wide range in the plasma rivaroxaban concentration, which increased the risk of clinical use. Therefore, Data in the degree of rivaroxaban concentration may provide recommendations for the clinical application to promote medication safety and individuality in the future. This article collected the latest literatures and case reports related to research progress of rivaroxaban plasma concentration monitoring, and Summarized influencing factors, monitoring methods, so as to provide a basis for further study on rational use of rivaroxaban in clinical.

Efficacy and safety of new oral anticoagulants in patients with nonvalvular atrial fibrillation after left atrial appendage occlusion：a meta-analysis / 中国药房

OBJECTIVE To systematically evaluate the efficacy and safety of new oral anticoagulants （NOACs） in patients with nonvalvular atrial fibrillation after left atrial appendage occlusion （LAAO）. METHODS Retrieved from PubMed， Embase， Web of Science， the Cochrane Library， CNKI and Wanfang data， randomized controlled trials （RCTs） and cohort studies about NOACs （trial group） versus warfarin or dual antiplatelet agents （control group） were collected during the inception and November 2022. After literature screening， data extraction and quality evaluation， meta-analysis was performed by using RevMan 5.4 software. RESULTS A total of 10 studies were included， involving 2 RCTs and 8 cohort studies， with a total of 2 653 patients. RCT results showed that there was no statistically significant difference in the incidence of device-related thrombosis （DRT）， stroke/ systemic embolism （SSE）， major bleeding events， total bleeding events or all-cause mortality between 2 groups （P＞0.05）. Results of cohort studies showed that compared with dual antiplatelet agents， there was no statistically significant difference in the incidence of DRT， stroke/SSE， major bleeding events or all-cause mortality in the trial group （P＞0.05）. Compared with warfarin， the incidence of DRT [RR＝0.40， 95%CI　（0.19，0.82）， P＝0.01] and total bleeding events [RR＝0.28， 95%CI　（0.18， 0.44）， P＜ 0.000 01] in the trial group were decreased significantly； there was no statistical significance in the incidence of stroke/SSE， major bleeding events or all-cause mortality （P＞0.05）. CONCLUSIONS For patients with nonvalvular atrial fibrillation after LAAO， NOACs have comparable antithrombotic efficacy and safety with dual antiplatelet agents， and the incidence of DRT and total bleeding events are lower than warfarin.

Research progress of finerenone in the treatment of type 2 diabetes mellitus complicated with chronic kidney disease / 中国临床药理学与治疗学

Finerenone is a new non-steroidal mineralocorticoid receptor antagonists, which can prevent and treat type 2 diabetes mellitus complicated with chronic kidney disease through antioxidant, anti-inflammatory and anti-fibrosis effects, and has a significant cardiovascular protection effect. Compared with traditional mineralocorticoid receptor antagonists, finerenone has a higher selectivity. In this review, the basic introduction, basic research, clinical research and limitations of finerenone were reviewed in order to provide more ideas and options for the treatment of type 2 diabetes mellitus complicated with chronic kidney disease.

Effects of Panax notoginseng saponins on proliferation, apoptosis and cell cycle of K562 cells in vitro and the mechanisms / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of Panax notoginseng saponins (PNS) on the proliferation, apoptosis and cell cycle of K562 cells and explore the molecular mechanisms underlying these effects.</p><p><b>METHODS</b>PNS-induced growth inhibition of K562 cells was detected by MTT assay; the cell apoptosis was evaluated by AO/EB staining and Annexin V-FITC/ PI staining; flow cytometry was used to detect cell cycle changes in the treated cells. The mRNA expressions of the molecules in mTOR signaling pathway were examined by RT-PCR, and the cellular expressions of cleaved caspeas-3, cyclin D1 and major proteins in mTOR signaling pathway were detected using Western blotting.</p><p><b>RESULTS</b>MTT assay showed that treatment with 100-800 µg/mL PNS significantly inhibited the proliferation, promoted the cell apoptosis, and caused cell cycle arrest in G0/G1 phase in K562 cells. Western blotting revealed increased protein expression of cleaved caspase-3 and decreased expression of cyclin D1 in PNS-treated cells, in which the proteins expressions of mTOR, p-mTOR, p-p70S6K and p-4E-BP 1 and the mRNA expression of mTOR were all decreased.</p><p><b>CONCLUSION</b>PNS can inhibit the proliferation, induce apoptosis and cause cell cycle arrest in K562 cells possibly by up-regulating cleaved caspase 3 and down-regulating cyclin D1 and mTOR signaling pathway.</p>

Lentivirus-mediated stable Fas gene silencing in human umbilical cord-derived mesenchymal stem cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To construct a lentivirus-mediated vector for RNA interference (RNAi) of Fas and establish a human umbilical cord-derived mesenchymal stem cells (UC-MSCs) line with stable Fas gene silencing.</p><p><b>METHODS</b>Four short hairpin RNA sequences targeting the coding region of human Fas mRNA were designed. The synthesized oligonucleotides were ligated with the lentivirus vectors harvested from BamHI and EcoRI double digestion of LV3 recombinant vector. The recombinant lentivirus vectors were transfected into the packaging cells 293T, and the lentivirus titers were determined. Cultured UC-MSCs were infected with the lentivirus, and real-time PCR and Western blotting were used to detect the expressions of Fas mRNA and protein in the transfected cells.</p><p><b>RESULTS</b>Restriction digestion and DNA sequencing showed that the lentiviral vectors were successfully constructed, and the titer of lentivirus reached 3 × 10⁸ TU/ml in the packaging cells. Real-time PCR and Western blot demonstrated significantly suppressed Fas gene expression in UC-MSCs after infection with the recombinant lentivirus.</p><p><b>CONCLUSION</b>Lentivirus-mediated RNAi can effectively inhibit Fas gene expression in cultured UC-MSCs.</p>

Incidence of human herpes virus 1-4 type in saliva of 245 human immunodeficiency virus-infected patients / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To determine the incidence of human herpes virus (HHV) 1-4 type including herpes simplex virus type-1 (HSV-1), herpes simplex virus type-2 (HSV-2), varicella-zoster virus (VZV), Epstein-Barr virus(EBV) in the saliva of human immunodeficiency virus (HIV) -infected patients.</p><p><b>METHODS</b>The incidence of salivary HSV-1, HSV-2, VZV and EBV from 245 HIV-seropositive individuals and control group was used to investigate by polymerase chain reaction(PCR) or nested PCR. The data was analyzed by SPSS 18.0 statistical software.</p><p><b>RESULTS</b>In the 245 HIV-seropositive individuals, the detection rates of HSV-1, HSV-2, VZV, EBV were 29.0%, 3.3%, 4.1%, 82.0%. In the control group, the detection rates of HSV-1, HSV-2, VZV, EBV were 13.3%, 0, 0, 36.7%. Four HHVs were significantly more prevalent in the salivas of HIV-seropositive persons than those in the control group (P < 0.01). The detection rates of HSV-1, HSV-2, VZV and EBV DNA were no difference between the HIV-positive group with highly active antiretroviral therapy (HAART) and HIV-positive group without HAART (P > 0.05).</p><p><b>CONCLUSION</b>There is a high prevalence of HHV infection in HIV-infected people in Yunnan. The most common virus are EBV, followed by HSV-1, but VZV and HSV-2 are rarely detected. HHV co-infection is also observed.</p>