Comparison of one-month versus twelve-month dual antiplatelet therapy after implantation of drug-eluting stents guided by either intravascular ultrasound or angiography in patients with acute coronary syndrome: rationale and design of prospective, multicenter, randomized, controlled IVUS-ACS and ULTIMATE-DAPT trial.

BACKGROUND: Current guidelines recommend administering dual antiplatelet therapy (DAPT) for 12 months to patients with acute coronary syndromes (ACS) and without contraindications after drug-eluting stent (DES) implantation. A recent study reported that 3 months of DAPT followed by ticagrelor monotherapy is effective and safe in ACS patients undergoing DES implantation compared with the standard duration of DAPT. However, it is unclear whether antiplatelet monotherapy with ticagrelor alone versus ticagrelor plus aspirin reduces the incidence of clinically relevant bleeding without increasing the risk of major adverse cardiovascular and cerebrovascular events (MACCEs) in ACS patients undergoing percutaneous coronary intervention (PCI) with DES implantation guided by either intravascular ultrasound (IVUS) or angiography who have completed a 1-month course of DAPT with aspirin plus ticagrelor. METHODS: The IVUS-ACS and ULTIMATE-DAPT is a prospective, multicenter, randomized, controlled trial designed to determine (1) whether IVUS-guided versus angiography-guided DES implantation in patients with ACS reduces the risk of target vessel failure (TVF) at 12 months and (2) whether ticagrelor alone versus ticagrelor plus aspirin reduces the risk of clinically relevant bleeding without increasing the risk of MACCE 1-12 months after the index PCI in ACS patients undergoing DES implantation guided by either IVUS or angiography. This study will enroll 3486 ACS patients eligible for DES implantation, as confirmed by angiographic studies. The patients who meet the inclusion criteria and none of the exclusion criteria will be randomly assigned in a 1:1 fashion to the IVUS- or angiography-guided group (first randomization). All enrolled patients will complete a 1-month course of DAPT with aspirin plus ticagrelor after the index PCI. Patients with no MACCEs or major bleeding (≥Bleeding Academic Research Consortium (BARC) 3b) within 30 days will be randomized in a 1:1 fashion to either the ticagrelor plus matching placebo (SAPT)group or ticagrelor plus aspirin (DAPT)group for an additional 11 months (second randomization). The primary endpoint of the IVUS-ACS trial is TVF at 12 months, including cardiac death, target vessel myocardial infarction (TVMI), or clinically driven target vessel revascularization (CD-TVR). The primary superiority endpoint of the ULTIMATE-DAPT trial is clinically relevant bleeding, defined as BARC Types 2, 3, or 5 bleeding, and the primary non-inferiority endpoint of the ULTIMATE-DAPT trial is MACCE, defined as cardiac death, myocardial infarction, ischemic stroke, CD-TVR, or definite stent thrombosis occurring 1-12 months in the second randomized population. CONCLUSION: The IVUS-ACS and ULTIMATE-DAPT trial is designed to test the efficacy and safety of 2 different antiplatelet strategies in ACS patients undergoing PCI with DES implantation guided by either IVUS or angiography. This study will provide novel insights into the optimal DAPT duration in ACS patients undergoing PCI and provide evidence on the clinical benefits of IVUS-guided PCI in ACS patients.

Systematically characterize the substance basis of Jinzhen oral liquid and their pharmacological mechanism using UPLC-Q-TOF/MS combined with network pharmacology analysis.

Jinzhen oral liquid (JZ) is a classical traditional Chinese medicine formula used for the treatment of children lung disease. However, the effective substance of JZ is still unclear. In this study, we used lung injury rat model to study the protective effect of JZ, through UPLC-Q-TOF/MS detection coupled with metabolic research and network pharmacology analysis. Fortunately, 31 absorbed prototype constituents and 41 metabolites were identified or tentatively characterized based on UPLC-Q-TOF/MS analysis, and the possible metabolic pathways were hydroxylation, sulfation and glucuronidation. We optimized the data screening in the early stage of network pharmacology by collecting targets based on adsorbed constituents, and further analyzed the main biological processes and pathways. 24 selected core targets were frequently involved in reactive oxygen species metabolic process, dopaminergic synapse pathway and so on, which might play important roles in the mechanisms of JZ for the treatment of lung injury. Overall, the absorbed constituents and their possible metabolic pathways, as well as the absorbed constituent-target-disease network provided insights into the mechanisms of JZ for the treatment of lung injury. Further studies are needed to validate the biological processes and effect pathways of JZ.

The essential oil from the twigs of Cinnamomum cassia Presl inhibits oxytocin-induced uterine contraction in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: The twigs and bark of Cinnamomum cassia Presl (Lauraceae) are widely used in traditional Chinese medicine in the treatment of tumor, abdominal pain, dysmenorrhea, digestive system disease and inflammatory diseases. The aim of this study was to determine the inhibitory effect of the essential oil from the twigs of Cinnamomum cassia Presl (EOCC) on uterine contraction in vitro and in vivo. MATERIALS AND METHODS: The Institute of Cancer Research (ICR) mouse uterine contraction was induced by oxytocin (OT) exposure following estradiol benzoate pretreatment. Mice were given the EOCC (60, 30, and 15mg/kg) by gavage. The level of prostaglandin F2α (PGF2α) in uterine tissue were determined according to specification of enzyme linked immunosorbent assay (ELISA) kit. Uterine tissue was collected for histopathological analysis (H&E). Myosin light chain 20 (MLC20), phosphorylation of myosin light chain 20 (p-MLC20) and cyclooxygenase-2 (COX-2) proteins in uterine tissue were assessed by Western Blot. Mouse isolated uterus strips were mounted in tissue organ baths containing Locke's solution. The contractile responses were recorded with Power Lab recording system. The effect of the EOCC on uterine contraction induced by OT, PGF2α, and acetylcholine (Ach) was observed. Myometrial cells were exposed to OT (7µM) to induce Ca2+ release, and the effect of the EOCC (100, 50, and 25µg/ml) on intracellular Ca2+ was analysed with fluorometry imaging. RESULTS: In vivo study demonstrated that the EOCC significantly reduced OT-induced writhing responses with a maximal inhibition of 66.5%. It also decreased the level of PGF2α in OT-induced mice uterine tissue. Moreover, Western blot analysis showed that COX-2 and p-MLC20 expressions in uterine tissue of dysmenorrhea mice were significantly reduced. EOCC inhibited spontaneous uterus contractions in a dose-dependent manner, and the concentration of the EOCC giving 50% of maximal contraction (IC50) value was 61.3µg/ml. The IC50 values of the EOCC on OT, PGF2α, and Ach-induced contractions were 113.0µg/ml, 94.7µg/ml, and 61.5µg/ml, respectively. Further in vitro studies indicated that the EOCC could restrain intracellular Ca2+ levels in favour of uterine relaxation. CONCLUSION: Both in vivo and in vitro results suggest that the EOCC possesses significant spasmolytic effect on uterine contraction. Thus, the EOCC yields a possible therapeutic choice for the prevention and treatment of primary dysmenorrhea.

The essential oil from the twigs of Cinnamomum cassia Presl alleviates pain and inflammation in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Cinnamomum cassia Presl (Lauraceae) can be found southern China and its bark is commonly used for centuries as ingredient in food and cosmetic industry. The twigs of Cinnamomum cassia Presl is popularly used in China to treat inflammatory processes, pain, menstrual disorders, hypertension, fever etc. The aim of this study is to evaluate the antinociceptive and anti-inflammatory properties of the essential oil (EO) from the twigs of Cinnamomum cassia Presl. MATERIAL AND METHODS: The chemical characterization of the EO was performed by gas chromatography coupled with mass spectrometry (GC-MS). The EO doses of 15, 30, and 60mg/kg were employed in the biological assays. The antinociceptive effects of the EO were evaluated using the models of acetic acid-induced writhing, oxytocin-induced writhing, and formalin and complete Freund's adjuvant (CFA) -induced overt pain tests. we also investigated the effect of the EO in pain intensity to a mechanical stimulus (mechanical hyperalgesia) after carrageenan by using an electronic version of von Frey filaments. Evaluation of anti-inflammatory activity was based on paw edema induced by carrageenan (300µg/25µL/paw) in mice. The levels of cytokines, NO, and PGE2 in paw skin tissue were determined according to instructions. COX-2 and iNOS proteins in paw skin tissue were assessed by Western Blot. RESULTS: The EO (15, 30, and 60mg/kg) reduced the number of abdominal writhings induced by acetic acid with inhibition of 38.0%, 55.4% and 58.7%, respectively. The EO (15, 30, and 60mg/kg) also reduced the number of abdominal writhings induced by oxytocin with inhibition of 27.3%, 51.7% and 69.0%, respectively. The EO significant inhibited the inflammatory (second phase: 10-30min) phase of the formalin-induced paw flinching and licking at the doses of 15, 30, and 60mg/kg. The EO at the tested doses of 15, 30, and 60mg/kg showed inhibited CFA-induced paw flinching and licking. The EO (15, 30, and 60mg/kg) also inhibited carrageenan-induced mechanical hyperalgesia and paw edema. It also decreased the levels of cytokines (TNF-α, and IL-1ß), NO, and PGE2 in carrageenan-induced mice paw skin tissue. Moreover, Western blot analysis showed that COX-2 and iNOS expressions in paw skin tissue of mice were significantly reduced. CONCLUSIONS: These results demonstrate that the antinociceptive and anti-inflammatory properties of the EO from the twigs of Cinnamomum cassia Presl, corroborating its use in folk medicine.