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Background: Chronic total occlusions (CTO) occur in about 20% of patients referred for coronary angiography, and right coronary artery (RCA) CTO has been reported in 38-50% of the entire CTO population. Limited data on angiographic and procedural characteristics of RCA-CTO and the risk of adverse cardiac events asks for a detailed study., Methods: From 2010 to 2013, patients with attempted revascularization of at least one CTO lesion were included and followed up to 5 years after PCI. Eligible patients are assigned to RCA-CTO and non-RCA-CTO groups based on their target vessels. The primary endpoint was major adverse cardiovascular events (MACEs; a composite of all-cause death, myocardial infarction (MI) or rehospitalization for heart failure), and secondary endpoints were cardiac death, target lesion revascularization (TLR) and target vessel revascularization (TVR)., Results: The present study included 2659 eligible patients, among which 1285 patients were assigned to the RCA-CTO group, whereas 1374 patients were assigned to the non-RCA-CTO group. Lesions in RCA had longer lesion length, higher J-CTO score, higher rates of severe vessel tortuosity, a higher percentage of Rentrop grade 2-3, and more likely to be re-try lesion than those in LAD or LCX (all P < 0.01). CTO lesions in RCA reached less successful recanalization and post-procedural TIMI 3 flow (all <0.01). Multivariate Cox analysis revealed that RCA-CTO was not associated with primary outcome MACEs. Besides MACEs, RCA-CTO was also not associated with cardiac death, but was significantly associated with TLR and TVR (adjusted HR: 1.37 [95% CI:1.07-1.76], P = 0.01; adjusted HR: 1.43 [95% CI:1.13-1.82], P = 0.003)., Conclusion: RCA-CTO lesions, which had more complex angiographic features, independently contributed to TLR and TVR but not to MACEs or cardiac death in the 5 years of follow-up., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: PI3Kδ is expressed predominately in leukocytes and is commonly found to be aberrantly activated in human B-cell lymphomas. Although PI3Kδ has been intensively targeted for discovering anti-lymphoma drugs, the application of currently approved PI3Kδ inhibitors has been limited due to unwanted systemic toxicities, thus warranting the development of novel PI3Kδ inhibitors with new scaffolds., Main Methods: We designed TYM-3-98, an indazole derivative, and evaluated its selectivity for all four PI3K isoforms, as well as its efficacy against various B-cell lymphomas both in vitro and in vivo., Key Findings: We identified TYM-3-98 as a highly selective PI3Kδ inhibitor over other PI3K isoforms at both molecular and cellular levels. It showed superior antiproliferative activity in several B-lymphoma cell lines compared with the approved first-generation PI3Kδ inhibitor idelalisib. TYM-3-98 demonstrated a concentration-dependent PI3K/AKT/mTOR signaling blockage followed by apoptosis induction. In vivo, TYM-3-98 showed good pharmaceutical properties and remarkably reduced tumor growth in a human lymphoma xenograft model and a mouse lymphoma model., Significance: Our findings establish TYM-3-98 as a promising PI3Kδ inhibitor for the treatment of B-cell lymphoma., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The use of β-blockers for acute coronary syndrome (ACS) patients without heart failure (HF) is controversial, and lacks of evidence in the era of reperfusion and intensive secondary preventions. This study aimed to investigate the prognostic impacts of β-blockers on patients with ACS but no HF treated by percutaneous coronary intervention (PCI)., Methods: A total of 2397 consecutive patients with ACS but no HF treated by PCI were retrospectively recruited from January 2010 to June 2017. Univariable Cox regression was used to assess the prognostic impacts of β-blockers, followed by adjusted analysis, one-to-one propensity score matching (PSM), and inverse probability treatment weighting (IPTW) analysis, in order to control for systemic between-group differences. The primary outcome was all-cause death., Results: Among the included patients, 2060 (85.9%) were prescribed with β-blockers at discharge. The median follow-up time was 727 (433-2016) days, with 55 (2.3%) cases of all-cause death. Unadjusted analysis showed that the use of β-blockers was associated with lower risk of death (hazard ratio [HR]: 0.42, 95% confidence interval [CI]: 0.23-0.76, P = 0.004), which was sustained in adjusted analysis (HR: 0.53, 95% CI: 0.29-0.98, P = 0.044), PSM analysis (HR: 0.44, 95% CI: 0.20-0.96, P = 0.039) and IPTW analysis (HR: 0.49. 95% CI: 0.35-0.70, P < 0.001). Risk reduction was also seen in β-blocker users for cardiac death, but not for major adverse cardiovascular events., Conclusions: The use of β-blockers was associated with reduced long-term mortality for ACS-PCI patients without HF., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Polysaccharide from Phellinus igniarius (PPI) is known for its immune-regulating effect with low toxicity. Toll like receptor 4 (TLR4) is important in both innate and adaptive immune responses and considered to be a promising target for new immune adjuvants. In this study, PPI was investigated for its effect on activating TLR4 in RAW264.7 and peritoneal macrophages. The adjuvant potential of PPI was evaluated in OVA-immunized mice. The results showed PPI treatment significantly increased the secretion and the mRNA expression of both MyD88 dependent and TRIF dependent cytokines. IRAK-1, a key molecule on the downstream of MyD88, was polyubiquitinated while IRF-3, another key molecule on the downstream of TRIF, was phosphorylated obviously after the treatment of PPI. The phosphorylation of molecules involved in both NF-κB pathway and MAPK pathway were significantly up-regulated after PPI treatment. In addition, the effects of PPI on the macrophages almost completely disappeared after treating the cells with the TLR4 antagonist TAK-242. Further in vivo results showed PPI significantly increased the serum OVA-specific antibody and the OVA-specific spleen cell proliferation. Taken together, PPI can specifically stimulate TLR4 and activate both MyD88 and TRIF pathways. PPI has immune adjuvant activity and may become a new potential immune adjuvant., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Accumulated data indicate that placental hypoxia is implicated in the pathogenesis of preeclampsia (PE). Tight junction (TJ) is important structure that sustains normal placental barrier function, its dysregulation under hypoxia has been observed. This study was designed to explore hypoxia-induced TJ dysfunction in trophoblast cells and its possible involvement in PE pathophysiology., Methods: Choriocarcinoma cells were grown in a monolayer and treated with cobalt chloride (CoCl 2 ) to induce hypoxia. TJ architecture was assessed using transmission electron microscopy, and locations of TJ proteins were determined by immunofluorescence. TJ functions were assessed by transepithelial electrical resistance (TER) and increased cell paracellular permeability (CPP), and the expression of TJ-related proteins, HIF-1α and VEGF was measured., Results: The TJ functions of trophoblast cells were significantly altered by hypoxia; TER decreased and CPP increased in a time- and concentration-dependent manner. Significant alterations in TJ protein expression and increases in HIF1α and VEGF expression were observed in hypoxic cells, and these effects were attenuated by pretreatment with YC-1. Moreover, corresponding changes in TJ protein expression were also detected in preeclamptic placentas., Conclusion: These data demonstrate that trophoblast cells undergo significant changes in TJ protein expression under hypoxic conditions and highlight the potential significance of the HIF1α-VEGF axis in the regulation of TJ structure and function in the preeclamptic placenta., (Copyright © 2017. Published by Elsevier B.V.)

The aim of this study is to investigate whether arsenic (As) could induce testicular poisoning and influence the oxidative stress, apoptosis and autophagy in chickens. Seventy-two 1-day-old male Hy-line chickens were divided into 4 groups which were exposed to 0, 0.625, 1.25, and 2.5 mg/kg body weight (BW) of arsenic trioxide (As2O3) for 30, 60 and 90 days, respectively. Histological and ultrastructural changes, antioxidant enzyme activity, mRNA and protein levels of apoptosis and autophagy-related genes were detected. Oxidative stress injuries were obvious in the testes exposure to As2O3, which resulted in the decreased activities of antioxidant enzymes, such as catalase (CAT) and superoxide dismutases (SOD). Meanwhile, the changes of mRNA and protein levels of apoptosis and autophagy-related genes showed that As2O3 exposure induced enhanced testicular apoptosis and increased the levels of autophagy markers such as Microtubule associated protein light chains 3-II (LC3-II), dynein, Beclin-1, Autophagy associated gene 5 (ATG5) and ATG4B but not LC3-I and mammalian target of rapamycin (mTOR), and demonstrated the cross-talk between apoptosis and autophagy. Histological and ultrastructural abnormalities confirm the changes of the above indicators. Taken together, our findings provide deeper insights into roles of excessive apoptosis and autophagy in the aggravation of testicular damage, which could contribute to a better understanding of As2O3-induced testicular poisoning in chickens.

The contents of 28 trace elements, 17 amino acid were evaluated in muscular tissues (wings, crureus and pectoralis) of chickens in response to arsenic trioxide (As 2 O 3 ). A total of 200 one-day-old male Hy-line chickens were fed either a commercial diet (C-group) or an As 2 O 3 supplement diet containing 7.5mg/kg (L-group), 15mg/kg (M-group) or 30mg/kg (H-group) As 2 O 3 for 90 days. The elements content was analyzed by inductively coupled plasma mass spectrometry (ICP-MS). Under As 2 O 3 exposure, the concentration of As were elevated 8.87-15.76 fold, 7.93-15.63 fold and 5.94-12.45 fold in wings, crureus and pectoralis compared to the corresponding C-group, respectively. 19 element levels (lithium (Li), magnesium (Mg), aluminum (Al), silicon (Si), kalium (K), vanadium (V), chromium (Cr), manganese (Mn), nickel (Ni), copper (Cu), selenium (Se), strontium (Sr), molybdenum (Mo), cadmium (Cd), tin (Sn), antimony (Sb), barium (Ba), mercury (Hg) and lead (Pb), 9 element levels (K, Co, Ni, Cu, As, Se, Sr, Sn, Ba and Hg) and 4 element levels (Mn, cobalt (Co), As, Sr and Ba) were significantly increased (P < 0.05) in wing, crureus and pectoralis, respectively. 2 element levels (sodium (Na) and zinc (Zn)), 5 element levels (Li, Na, Si, titanium (Ti and Cr), 13 element levels (Li, Na, Mg, K, V, Cr, iron (Fe), Cu, Zn, Mo, Sn, Hg and Pb) were significantly decreased (P < 0.05) in wing muscle, crureus and pectoralis, respectively. Additionally, in crureus and pectoralis, the content of total amino acids (TAA) was no significant alterations in L and M-group and then increased approximately 10.2% and 7.6% in H-group, respectively (P < 0.05). In wings, the level of total amino acids increased approximately 10% in L-group, whereas it showed unchanged in M and H-group compared to the corresponding C-group. We also observed that significantly increased levels of proline, cysteine, aspartic acid, methionine along with decrease in the tyrosine levels in muscular tissues compared to the corresponding C-group. In conclusion, the residual of As in the muscular tissues of chickens were dose-dependent and disrupts trace element homeostasis, amino acids level in muscular tissues of chickens under As 2 O 3 exposure. Additionally, the response (trace elements and amino acids) were different in wing, thigh and pectoral of chick under As 2 O 3 exposure. This study provided references for further study of heavy metal poisoning and may be helpful to understanding the toxicological mechanism of As 2 O 3 exposure in muscular tissues of chickens., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Evidence describing the association between pulmonary function and carotid atherosclerosis has been inconclusive and the role of smoking in this association is unclear. We therefore examined this association in the Guangzhou Biobank Cohort Study-CVD Subcohort., Methods: Common carotid artery (CCA) intima-media thickness (IMT) and carotid plaques were measured by B-mode ultrasonography and lung function by spirometry using a turbine flowmeter. Chronic obstructive pulmonary disease (COPD) was defined as the ratio of forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) of less than 0.70. Predicted FEV1 and FVC were derived using equations for Chinese., Results: Of 1625 participants aged 50 + years, 382 (23.5%) had evidence of carotid plaque. The mean CCA-IMT was higher in those with COPD than those without (0.82 ± 0.29 mm versus 0.76 ± 0.31 mm, P = 0.02). We found no evidence that the association of pulmonary function with CCA-IMT varied by smoking status (P values interaction: 0.23-0.83). After adjustment for a wide range of potential confounders, the increased risks of thickened CCA-IMT (CCA-IMT ≥1.0 mm) in those with COPD became marginally nonsignificant (adjusted odds ratio (OR) 1.45, 95% confidence interval (CI) 0.91-2.29; P = 0.12). Compared to those in the highest tertile, participants in the lowest tertile of FEV1 observed to predicted ratio had increased risk of thickened CCA-IMT (adjusted OR 2.18, 95% CI 1.42-3.34) and carotid plaque (adjusted OR 1.50, 95% CI 1.08-2.09), while participants in the lowest tertile of FVC observed to predicted ratio had increased risk of thickened CCA-IMT (adjusted OR 2.29, 95% CI 1.46-3.58), but the adjusted OR for carotid plaque was marginally nonsignificant (adjusted OR 1.29, 95% CI 0.93-1.80; P = 0.13)., Conclusion: Independent of smoking status, poor pulmonary function was dose-dependently associated with carotid atherosclerosis in older Chinese. (281 words)., (Crown Copyright © 2015. Published by Elsevier Ireland Ltd. All rights reserved.)

Seven neo-clerodane diterpenes, teufruintins A-G (1-7), together with eight known compounds (8-15) were isolated from the CHCl3-soluble fraction of the aerial parts of Teucrium fruticans cultivated in China. The chemical structures of the isolated compounds were elucidated using different spectroscopic methods. All of the isolated diterpenes were evaluated for their cytotoxic activities on three human cancer cell lines, and for their ability to inhibit LPS-induced nitric oxide production in RAW 264.7 macrophages. None of the compounds displayed cytotoxic activities on the cancer cell lines, and only 15 showed weak NO inhibitory activity., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the efficacy and safety of auricular therapy (AT) on chronic pain., Methods: A systematic review. Randomized controlled trials investigating AT for chronic pain were retrieved and RevMan 5.3 was used for meta-analysis., Results: Fifteen trials were included. The overall assessment indicated that AT could be a promising intervention for chronic pain relief. Meta-analyses showed that AT decreased pain intensity, especially for chronic low back pain and chronic tension headache. The lasting effect of AT was not obvious, and it began to diminish 3 months after the completion of treatment., Conclusions: AT may positively control pain intensity for patients with chronic pain. However, due to the significant heterogeneity and methodological flaws identified in the analyzed trials, the current evidence on AT for chronic pain management is still uncertain. More rigorously designed large-scale randomized controlled trials are required to evaluate the efficacy of AT for patients with chronic pain., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: There is no data that demonstrates what anaesthesia is suitable for patients who have a high risk of fat embolism syndrome (FES). We investigated the mortality rates of rats that received a half lethal dose (LD(50)) of fat by intravenous injection after induction of general or spinal anaesthesia., Methods: An LD(50) of fat for rats was determined by using a toxicological method. Three hundred and seventy five rats were randomly assigned to receive general anaesthesia (group GA, n=125), or spinal block (group SA, n=125), or no anaesthesia (group C, n=125). The rats were injected with the LD(50) of fat at 20 min after anaesthesia induction. The mortality rates were recorded at 2, 8, 12, and 24h after fat injection., Results: The LD(50) of fat was 0.706 ml/kg and its 95% CI was 0.622 ml/kg-0.801 ml/kg. The mortality rate was lower in the group GA than in the group SA (p<0.01), whilst there was no statistical difference between the group SA and the group C (p=0.442)., Conclusion: It is feasible to assess the efficacy of various treatments for FES by comparing the mortality rates of animals after injection of an LD(50) of fat. The mortality rate of rats was lower when FES was induced under general anaesthesia than under spinal anaesthesia which implies that general anaesthesia is superior to spinal anaesthesia for patients who have a high risk of FES., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: An increasing number of patients with an indication for long-term oral anticoagulation (OAC) have undergone percutaneous coronary intervention with stent implantation (PCI-s). However, the optimal antithrombotic treatment for these patients is currently unknown. The purpose of this study was to characterize the benefits and risks of triple antithrombotic therapy (combined aspirin, clopidogrel, and OAC) after stent implantation in patients under long-term OAC treatment compared with dual antiplatelet therapy (combined aspirin and clopidogrel)., Methods: The study consisted of clinical controlled trials with ≥ 3 months of follow-up that compared triple antithrombotic therapy with dual antiplatelet therapy after stent implantation in patients undergoing long-term OAC treatment., Results: Nine clinical trials included 1,996 participants. The meta-analysis was feasible because the grouping criterion was similar. The meta-analysis of the prevention of a major adverse cardiovascular event shows triple antithrombotic therapy to be more efficacious than dual antiplatelet therapy (OR, 0.60; 95% CI, 0.42-0.86; P = .005). There was a significant reduction in all-cause mortality with triple antithrombotic therapy compared with dual antiplatelet therapy. The meta-analysis of major bleeding in the first 6 months during follow-up shows significantly more events with triple antithrombotic therapy (OR, 2.12; 95% CI, 1.05-4.29; P = .04)., Conclusions: Based on our analysis, triple antithrombotic therapy is substantially more efficacious in reducing the occurrence of cardiovascular events and mortality in PCI-s patients with an indication for long-term OAC, compared with dual antiplatelet therapy. Although triple therapy predisposes patients to an increased risk of bleeding, especially major bleeding, it is the better choice for patients with a low bleeding risk.

233 SD rats weighing 100 approximately 120 g were divided randomly into 6 groups. The animals in group I and group II received 0.1 mg/kg selenium in the form of sodium selenite only and served as the negative control and positive control, respectively. Animals in groups III, IV and V were fed with selenium as Se-enriched malt supplemented diets (0.3, 1 and 3 mg/kg), and group VI with selenium by using sodium selenite supplemented diets (3 mg/kg). Animals of groups II approximately VI were induced hepatoma by diethylnitrosamine (100 mg/l) for 16 weeks, then drunk with sterilized water for 2 more weeks. Subsequently, the effects of Se-enriched malt and sodium selenite on hepatoma nodules, relative liver weight, the liver function indices including alanine aminotransferase (ALT), alkaline phosphatase (ALP), albumin (ALB), total bilirubin (TBIL), and the tumor markers, named as gamma-glutamyltranspeptidase (GGT), alpha-fetoprotein (AFP), insulin-like growth factor-II (IGF-II) were recorded. The calcium concentration, glucose content in plasma and values of the hormones regulating blood glucose, such as insulin, glucagons and thyroid hormones (3,5,3'-tetraiodothyronine, T(3); 3,5,3'5'-tetraiodothyronine, T(4)) were observed as well. At the same time, the correlations between the concentration of plasma glucose and related hormones were also analyzed. The results indicated that Se-enriched malt showed a better chemopreventive efficiency in decreasing the number of hepatoma nodules, relative liver weight and the contents of AFP, GGT, IGF-II, ALT, ALP and TBIL in the plasma, and delaying the descent of hormones in the serum, names as insulin, glucagons, T(3) and T(4) than those feeding with sodium selenite. Effect of Se-enriched malt excelled sodium selenite in the aspects of deadening the descent of glucose concentration in the plasma and the rise of calcium concentration in the serum of the rats with hepatoma induced by diethylnitrosamine. The values of glucose and calcium were significantly related to those items fore-named. In conclusion, the function of Se-enriched malt in deadening the lesion and delaying the development of hepatoma of rats induced by diethylnitrosamine was better than that of sodium selenite. Hypoglycemia and hypercalcemia were significantly correlated with the multifactors mentioned above.