A novel intracoronary hypothermia device reduces myocardial reperfusion injury in pigs.

BACKGROUND: Hypothermia therapy has been suggested to attenuate myocardial necrosis; however, the clinical implementation as a valid therapeutic strategy has failed, and new approaches are needed to translate into clinical applications. This study aimed to assess the feasibility, safety, and efficacy of a novel selective intracoronary hypothermia (SICH) device in mitigating myocardial reperfusion injury. METHODS: This study comprised two phases. The first phase of the SICH was performed in a normal porcine model for 30 minutes ( n = 5) to evaluate its feasibility. The second phase was conducted in a porcine myocardial infarction (MI) model of myocardial ischemia/reperfusion was performed by balloon occlusion of the left anterior descending coronary artery for 60 minutes and maintained for 42 days. Pigs in the hypothermia group ( n = 8) received hypothermia intervention onset reperfusion for 30 minutes and controls ( n = 8) received no intervention. All animals were followed for 42 days. Cardiac magnetic resonance analysis (5 and 42 days post-MI) and a series of biomarkers/histological studies were performed. RESULTS: The average time to lower temperatures to a steady state was 4.8 ± 0.8 s. SICH had no impact on blood pressure or heart rate and was safely performed without complications by using a 3.9 F catheter. Interleukin-6 (IL-6), tumor necrosis factor-α, C-reactive protein (CRP), and brain natriuretic peptide (BNP) were lower at 60 min post perfusion in pigs that underwent SICH as compared with the control group. On day 5 post MI/R, edema, intramyocardial hemorrhage, and microvascular obstruction were reduced in the hypothermia group. On day 42 post MI/R, the infarct size, IL-6, CRP, BNP, and matrix metalloproteinase-9 were reduced, and the ejection fraction was improved in pigs that underwent SICH. CONCLUSIONS: The SICH device safely and effectively reduced the infarct size and improved heart function in a pig model of MI/R. These beneficial effects indicate the clinical potential of SICH for treatment of myocardial reperfusion injury.

Comparison of CT-derived Plaque Characteristic Index With CMR Perfusion for Ischemia Diagnosis in Stable CAD.

BACKGROUND: Coronary computed tomography angiography (CCTA) and cardiac magnetic resonance (CMR) have been used to diagnose lesion-specific ischemia in patients with coronary artery disease. The aim of this study was to investigate the diagnostic performance of CCTA-derived plaque characteristic index compared with myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) derived from CMR perfusion in the assessment of lesion-specific ischemia. METHODS: Between October 2020 and March 2022, consecutive patients with suspected or known coronary artery disease, who were clinically referred for invasive coronary angiography were prospectively enrolled. All participants sequentially underwent CCTA and CMR and invasive fractional flow reserve within 2 weeks. The diagnostic performance of CCTA-derived plaque characteristics, CMR perfusion-derived stress MBF, and MPR were compared. Lesions with fractional flow reserve ≤0.80 were considered to be hemodynamically significant stenosis. RESULTS: Nighty-two patients with 141 vessels were included in this study. Plaque length, minimum luminal area, plaque area, percent area stenosis, total atheroma volume, vessel volume, lipid-rich volume, spotty calcium, napkin-ring signs, stress MBF, and MPR in flow-limiting stenosis group were significantly different from nonflow-limiting group. The overall accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of lesion-specific ischemia diagnosis were 61.0%, 55.3%, 63.1%, 35.6%, and 79.3% for stress MBF, and 89.4%, 89.5%, 89.3%, 75.6%, 95.8% for MPR; meanwhile, 82.3%, 79.0%, 84.5%, 65.2%, and 91.6% for CCTA-derived plaque characteristic index. CONCLUSIONS: In our prospective study, CCTA-derived plaque characteristics and MPR derived from CMR performed well in diagnosing lesion-specific myocardial ischemia and were significantly better than stress MBF in stable coronary artery disease.

In vivo evaluation of intravascular lithotripsy in a healthy porcine coronary model.

OBJECTIVES: In this study, we aimed to investigate the vascular response to an intravascular lithotripsy (IVL) shockwave balloon in a healthy porcine coronary artery model. BACKGROUND: IVL is a novel clinical technique for modifying heavily calcified atherosclerotic plaques. METHODS: A total of 24 porcine coronary arteries were treated with IVL or plain old balloon angioplasty (POBA). Histology, histomorphometry, quantitative coronary angiography analysis (QCA), and optical coherence tomography (OCT) were performed postprocedure and at 1-month follow-up (1M-FU). RESULTS: There was no significant difference in the late lumen loss and diameter stenosis (determined by QCA) and the minimal lumen area (evaluated by OCT) of the IVL and POBA groups at 1M-FU. Pathological analysis revealed that the lumen and neointima areas were similar between the two groups. However, the medial and adventitial layers were more prominent in the IVL than in the POBA group. The injury score and inflammation of the media and adventitia increased dramatically in the IVL group postprocedure and at 1M-FU. At 1M-FU, media fibrin deposition and adventitial fibrosis were also significantly increased in the IVL group. However, there was no significant difference in neointima fibrin deposition, endothelialization, and thrombosis between both groups. Layered separation of the media and adventitia was observed in the IVL group. CONCLUSION: The findings indicate that the IVL balloon did not cause serious intimal hyperplasia and endothelial damage compared with the effects of POBA in the healthy coronary artery. However, shock waves may cause unique damage to the vascular media and adventitia in the coronary artery, which was not observed in the peripheral artery.

Treatment strategy for spontaneous coronary artery dissection based on anatomical characteristics.

OBJECTIVES: To compare the clinical and angiographic characteristics of high-risk and low-risk spontaneous coronary artery dissection (SCAD) patients to determine the optimal treatment strategy. BACKGROUND: SCAD is a rare and emerging cause of acute coronary syndrome and sudden cardiac death, especially in young female patients. However, the indication of percutaneous coronary intervention (PCI) in patients with SCAD remains elusive. METHODS: We evaluated the clinical and angiographic characteristics of all SCAD patients admitted to our center from 2012 to 2020. The outcomes of the high-risk and low-risk SCAD patients according to the location of the lesion segment with dissection or intramural hematoma were compared. Further analyses were performed to evaluate the vessel healing or residual dissection in the patients receiving the follow-up angiography. RESULTS: A total of 81 SCAD patients were enrolled in the present study, in which 38 patients were categorized as high-risk group, defined as involvement of the left main artery or proximal segment of any main coronary artery. PCI was the more common treatment approach in the high-risk group (68.4%), while conservative treatment was more common in the low-risk group (62.8%). The incidence of major adverse cardiac events, defined as cardiac death, myocardial infarction, unstable angina pectoris, severe arrhythmias, or heat failure, within 1 year follow-up was similar between the two groups. 57 patients (70.4%) received the follow-up angiography after 1 year. The high- and low-risk groups had a similar rate of vessel healing among the PCI treatment patients. However, more patients achieved spontaneous healing in the low-risk group than the high-risk group among the conservative treatment patients (86.4% vs. 33.3%, p < 0.05). CONCLUSIONS: Conservative management remains the recommended treatment strategy for the low-risk SCAD patients. PCI could be considered in high-risk SCAD patients with favorable clinical outcomes and vessel healing. Characterization of lesion anatomy may be an important indicator for treatment decision.

The standard versus prolonged dual antiplatelet therapy after the XINSORB bioresorbable scaffold implantation (SPARTA) trial: study protocol for a randomized controlled trial.

BACKGROUND: Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is the standard of care after coronary stenting, including coronary stenting involving bioresorbable scaffolds (BRSs). Current clinical guidelines recommend at least 12 months of DAPT after BRS implantation. However, the correlation between prolonged DAPT and net clinical benefits remains unknown. METHODS: The SPARTA trial is designed to be a prospective, randomized, parallel-group, clinical trial. It aims to compare the benefits and risks of DAPT applied for either 12 or 36 months after XINSORB BRS implantation. The primary endpoints are the incidence of the composite endpoint of major adverse cardiac events (MACEs), including all-cause death, any myocardial infarction (MI), and all revascularizations, as well as Bleeding Academic Research Consortium Definition (BARC) type 3 or 5 bleeding events. The secondary endpoints of the study include the device-oriented composite endpoint of target lesion failure (defined as cardiac death, target vessel-related MI, or ischemia-driven target lesion revascularization), target vessel failure (defined as cardiac death, MI, or ischemia-driven target vessel revascularization), scaffold thrombosis, and minor bleeding events. This trial will enroll 2106 subjects treated with the XINSORB BRS only. All subjects will receive DAPT after the index procedure for 12 (± 1) months. Subjects without MACEs or major bleeding will be randomized to receive either 24 additional months of DAPT or aspirin alone. DISCUSSION: This trial is designed to investigate the impact of extending the duration of DAPT up to 3 years after XINSORB BRS implantation by investigating the balance of risks and benefits in a broad population of treated patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT04501900 . Registered on 6 August 2020.

A TEMPOL and rapamycin loaded nanofiber-covered stent favors endothelialization and mitigates neointimal hyperplasia and local inflammation.

An increased level of reactive oxygen species (ROS) plays a major role in endothelial dysfunction and vascular smooth muscle cell (VSMC) proliferation during in-stent thrombosis and restenosis after coronary artery stenting. Herein, we report an electrospun core-shell nanofiber coloaded with 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPOL) and rapamycin (RAPA) that correspondingly serves as an ROS scavenger and VSMC inhibitor. This system has the potential to improve the biocompatibility of current drug-eluting stent (DES) coatings with the long-term and continuous release of TEMPOL and rapamycin. Moreover, the RAPA/TEMPOL-loaded membrane selectively inhibited the proliferation of VSMCs while sparing endothelial cells (ECs). This membrane demonstrated superior ROS-scavenging, anti-inflammatory and antithrombogenic effects in ECs. In addition, the membrane could maintain the contractile phenotype and mitigate platelet-derived growth factor BB (PDGF-BB)-induced proliferation of VSMCs. In vivo results further revealed that the RAPA/TEMPOL-loaded covered stents promoted rapid restoration of vascular endothelium compared with DES and persistently impeded inflammation and neointimal hyperplasia in porcine models.

Drug-coated balloon for the treatment of small vessel disease: 9 months of angiographic results and 12 months of clinical outcomes of the PEPCAD China SVD study.

BACKGROUND: Whether the drug-coated balloons (DCBs)-alone strategy was superior to plain old balloon angioplasty (POBA) in treating SVD remains unknown. AIMS: We aimed to evaluate the efficacy and safety of DCBs for the treatment of coronary de novo small vessel disease (SVD) and provide further evidence for extending the clinical indications of DCBs. (ChiCTR1800014966). METHODS: Eligible patients were randomized at a 2:1 ratio to receive DCB treatment or POBA in this prospective, multicenter clinical trial. The reference vessel diameter of lesions was visually assessed to be 2.0 to 2.75 mm. The primary endpoint of the study was angiographic in-segment late luminal loss (LLL) at the 9-month follow-up to demonstrate the superiority of DCB treatment to POBA in SVD. The composite clinical endpoints included clinically driven target lesion revascularization (CD-TLR), target lesion failure (TLF), major adverse cardiac events (MACEs), and thrombosis at the 12-month follow-up. RESULTS: A total of 270 patients were enrolled (181 for DCB, 89 for POBA) at 18 centers in China. The primary endpoint of 9-month in-segment LLL in the intention-to-treat population was 0.10 ± 0.33 mm with DCB and 0.25 ± 0.38 mm with POBA (p = 0.0027). This difference indicated significant superiority of DCB treatment (95% CI: -0.22, -0.04, psuperiority = 0.0068). The rates of the clinical endpoints-CD-TLR, TLF, and MACEs-were comparable between groups. No thrombosis events were reported. CONCLUSIONS: DCB treatment of de novo SVD was superior to POBA with lower 9-month in-segment LLL. The rates of clinical events were comparable between the two devices.

Age-related alterations in the nutritional quality of Arctic grayling (Thymallus arcticus).

The biochemical composition of the muscle in Arctic graylings at three age stages was evaluated and compared. For conventional biochemical composition, there was no significant difference in the crude protein content among the three age stages, but the crude fat content in the 1 year old was significantly lower than that of the others (P < 0.05). For amino acids composition, there was no significant difference in the content of essential amino acids and delicious amino acids among the three age stages, but the essential amino acid index of the 2 year old was the highest (72.205), indicating that its essential amino acid composition was more suitable for human needs. For fatty acids composition, the content of monounsaturated fatty acids (2.759 mg/g) and polyunsaturated fatty acids (3.422 mg/g) of the 3 year old was significantly higher than that of the others (P < 0.05), and it also had relatively lowest atherogenicity index (0.419) and thrombogenicity index (0.179) and the highest hypocholesterolemic/hypercholesterolemic fatty acid ratio (2.404), indicating that its fatty acid composition was healthier and more beneficial to the prevention of human cardiovascular and cerebrovascular diseases. For minerals composition, the contents of iron, zinc, and copper increased with age, while the contents of selenium and manganese decreased with age, with the highest selenium content in the 1 year old (1.522 mg/kg). The chromium, arsenic, lead, and cadmium contents were all lower than the Chinese national standard. In conclusion, the nutritional composition of Arctic graylings variated with age and consumers could select suitable Arctic graylings based on their nutritional needs. PRACTICAL APPLICATION: This work analyzed the nutritional components in the muscle of Arctic graylings at different ages, which can provide an effective reference for consumers when purchasing Arctic graylings.

Identification and validation of an epithelial mesenchymal transition-related gene pairs signature for prediction of overall survival in patients with skin cutaneous melanoma.

BACKGROUND: We aimed to construct a novel epithelial-mesenchymal transition (EMT)-related gene pairs (ERGPs) signature to predict overall survival (OS) in skin cutaneous melanoma (CM) patients. METHODS: Expression data of the relevant genes, corresponding clinicopathological parameters, and follow-up data were obtained from The Cancer Genome Atlas database. Univariate Cox regression analysis was utilized to identify ERGPs significantly associated with OS, and LASSO analysis was used to identify the genes used for the construction of the ERGPs signature. The optimal cutoff value determined by the receiver operating characteristic curve was used to classify patients into high-risk and low-risk groups. Survival curves were generated using the Kaplan-Meier method, and differences between the two groups were estimated using the log-rank test. The independent external datasets GSE65904 and GSE19234 were used to verify the performance of the ERGPs signature using the area under the curve (AUC) values. In addition, we also integrated clinicopathological parameters and risk scores to develop a nomogram that can individually predict the prognosis of patients with CM. RESULTS: A total of 104 ERGPs related to OS were obtained, of which 21 ERGPs were selected for the construction of the signature. All CM patients were stratified into high-and low-risk groups based on an optimal risk score cutoff value of 0.281. According to the Kaplan-Meier analysis, the mortality rate in the low-risk group was lower than that in the high-risk group in the TCGA cohort (P < 0.001), GSE65904 cohort (P = 0.006), and GSE19234 cohort (P = 0.002). Multivariate Cox regression analysis indicated that our ERGP signature was an independent risk factor for OS in CM patients in the three cohorts (for TCGA: HR, 2.560; 95% CI [1.907-3.436]; P < 0.001; for GSE65904: HR = 2.235, 95% CI [1.492-3.347], P < 0.001; for GSE19234: HR = 2.458, 95% CI [1.065-5.669], P = 0.035). The AUC value for predicting the 5-year survival rate of patients with CM of our developed model was higher than that of two previously established prognostic signatures. Both the calibration curve and the C-index (0.752, 95% CI [0.678-0.826]) indicated that the developed nomogram was highly accurate. Most importantly, the decision curve analysis results showed that the nomogram had a higher net benefit than that of the American Joint Committee on Cancer stage system. CONCLUSION: Our study established an ERGPs signature that could be potentially used in a clinical setting as a genetic biomarker for risk stratification of CM patients. In addition, the ERGPs signature could also predict which CM patients will benefit from PD-1 and PD-L1 inhibitors.

Evaluation of qPCR reference genes for taimen (Hucho taimen) under heat stress.

As a powerful and attractive method for detecting gene expression, qRT-PCR has been broadly used in aquaculture research. Understanding the biology of taimen (Hucho taimen) has drawn increasing interest because of its ecological and economic value. Stable reference genes are required for the reliable quantification of gene expression, but such genes have not yet been optimized for taimen. In this study, the stability levels of 10 commonly used candidate reference genes were evaluated using geNorm, NormFinder, BestKeeper, and RefFinder. The expression levels of the 10 genes were detected using 240 samples from 48 experimental groups consisting of 40 individuals treated under four heat-stress conditions (18, 20, 22, and 24 °C) for 24 h and 26 °C for 4, 24, 48, and 72 h. Six tissues (blood, heart, brain, gill, skin, and liver) were collected from each individual. Ribosomal protein S29 (RPS29) and ribosomal protein L19 (RPL19) were the most stable genes among all of the samples, whereas 28S ribosomal RNA (28S rRNA), attachment region binding protein (ARBP), and 18S ribosomal RNA (18S rRNA) were the least stable. These results were verified by an expression analysis of taimen heat-stress genes (heat shock protein 60, hsp60, and heat shock protein 70, hsp70). In conclusion, RPS29 and RPL19 are the optimal reference genes for qRT-PCR analyses of taimen, irrespective of the tissue and experimental conditions. These results allow the reliable study of gene expression in taimen.

Immediate Renal Denervation After Acute Myocardial Infarction Mitigates the Progression of Heart Failure via the Modulation of IL-33/ST2 Signaling.

Objective: Previous studies have demonstrated the protective effects of renal denervation (RDN) in pre-existing heart failure, but the effects of immediate RDN after acute myocardial infarction (AMI) on subsequent cardiac remodeling have not been reported. This study aimed to investigate the cardioprotective effects of immediate RDN after AMI and its underlying mechanism. Methods: AMI was induced by intracoronary gelatin sponge embolization in 14 Shanghai white pigs that were randomized to undergo either renal angiography (AMI+sham group) or RDN (AMI+RDN group) after 1 h of hemodynamic monitoring. Cardiac function of the two groups was measured at baseline, 1 h post-AMI and at the 1 month follow-up (1M-FU) by transthoracic echocardiography (TTE). Plasma NT-proBNP, soluble ST2 (sST2), norepinephrine (NE), and renin-angiotensin-aldosterone system activity were detected simultaneously. The renal cortex was harvested for NE measurement after the 1M-FU, and the renal arteries were stained with tyrosine hydroxylase for the evaluation of sympathetic activity. Heart tissues in the non-ischemic areas were collected to assess histological and molecular left ventricular (LV) remodeling by pathological staining, RT-PCR, and western blotting. Results: There was no difference in the hemodynamic stability or cardiac function between the two groups at baseline and 1 h post-AMI. Six pigs from each of the two groups completed the 1M-FU. TTE analysis revealed the improved cardiac function of immediate RDN in the AMI+RDN group and circulating NT-proBNP levels were lower than those in the AMI+sham group. Further analysis showed significantly less interstitial fibrosis in the remote non-ischemic myocardium after immediate RDN, together with decreased cardiomyocyte hypertrophy and inflammatory cell infiltration. sST2 levels in circulating and myocardial tissues of animals in the AMI+RDN group were significantly higher than those in the AMI+sham group, accompanied by corresponding alterations in IL-33/ST2 and downstream signaling. Conclusions: Immediate RDN can improve cardiac function and myocardial remodeling after AMI via modulation of IL-33/ST2 and downstream signaling.

Peripheral Artery Tonometry Reveals Impaired Endothelial Function before Percutaneous Coronary Intervention in Patients with Periprocedural Myocardial Injury.

BACKGROUND: Periprocedural myocardial injury (PMI) is a most common complication of percutaneous coronary intervention (PCI). Microembolization and inflammation underlying PMI could lead to coronary microvascular dysfunction (CMD) and vice versa. Reactive hyperemia index (RHI) assessed by peripheral artery tonometry (PAT) has been considered as a noninvasive method to assess endothelial function and CMD, which could be useful to predict PMI. METHODS: 268 patients suspected with stable coronary artery disease (CAD) and scheduled for elective coronary angiography were enrolled. RHI was measured by using the Endo-PAT2000™ device before angiography. The association among RHI, PMI, and cardiovascular events was further assessed. RESULTS: In this cohort, 189 patients (70.5%) were diagnosed with CAD and 119 patients (44.4%) underwent drug-eluting stent (DES) implantation. Compared with patients without CAD, CAD patients had lower RHI (1.88 ± 0.55 vs. 2.02 ± 0.58, P < 0.05). Patients with PMI had a lower RHI before angiography (1.75 ± 0.37 vs. 1.95 ± 0.50, P < 0.05). Receiver operating characteristic curve analysis of RHI revealed an area under the curve (AUC) of 0.61, with a sensitivity of 62.7% and specificity of 50.0% to predict PMI. Moreover, we found that CAD patients with RHI ≤ 1.81 had a higher incidence of composite cardiac events after stenting (adjusted hazard ratio (HR) 3.31, 95% confidence interval (CI) 1.07-10.22, P < 0.05). CONCLUSIONS: RHI assessment through PAT could be a promising method to predict PMI before the procedure. RHI is associated with increased risk of long-term adverse cardiac events after DES implantation.

Gene expression profile of the taimen Hucho taimen in response to acute temperature changes.

The endangered cold-water fish species taimen (Hucho taimen) suffer acute temperature changes in culture and wild conditions. Understanding the effects of acute temperature changes on physiological processes of this species is essential for aquaculture practices and conservation. Liver transcriptomic profiles of the taimen (n = 24) exposed to acute temperature decrease (from 20 °C to 10 °C) and acute temperature increase (from 10 °C to 20 °C) was evaluated using high-throughput RNA-Sequencing. Samples were collected at day 0, 1, 7 and 35 in both treatments. Compared to day 0, the total numbers of differentially expressed genes (DEGs) in the taimen after acute temperature decrease were 173, 226 and 42 at day 1, 7 and 35, respectively, and the total numbers of DEGs following acute temperature increase were 260, 253 and 282 at day 1, 7 and 35, respectively. Particularly, 14 key regulatory genes were commonly found between both acute temperature treatments. Functional analysis based on the commonly identified DEGs revealed important metabolic pathways related to metabolism and immune function, suggesting a specific response mechanism of taimen against cold and heat shock. The results may assist in developing management strategies for stress mediation caused by acute temperature changes in the taimen and other cold water fish.

Three-year clinical outcomes of a sirolimus-eluting bioresorbable scaffold (XINSORB) and a metallic stent to treat coronary artery stenosis.

BACKGROUND: Recent studies have shown increased risks of late target lesion failure (TLF) and thrombosis using a bioresorbable scaffold (BRS). However, the results of the ABSORB China study offered a different means of understanding the long-term performance of BRSs. We tested the 3-year clinical outcome of the XINSORB BRS in a multicenter, randomized controlled clinical trial (ChiCTR1800014966). METHODS: Eligible patients with one or two de novo coronary lesions were randomly assigned 1:1 to be treated with XINSORB scaffolds and metallic sirolimus-eluting stents (SESs). The clinical endpoints include TLF [cardiac death, target vessel-related myocardial infarction (TV-MI), or ischemia-driven target lesion revascularization (ID-TLR)], its components, and devised thrombosis. RESULTS: Three hundred ninety-five patients were enrolled and randomized to the XINSORB (N=200) and SES (N=195) arms. The clinical 3-year follow-up included 95.5% of the XINSORB-treated patients and 92.8% of the SES-treated patients. Dual antiplatelet therapy was at 59.0% of the XINSORB-treated and 52.8% of the SES-treated patients (P=0.34). There were no significant differences in the clinical outcomes between the XINSORB and SES arms, including in TLF (4.0% vs. 6.2%, P=0.29), cardiac death (1.0% vs. 0%, P=NA), TV-MI (1.0% vs. 0%, P=NA), and ID-TLR (3.5% vs. 6.2%, P=0.19). The rate of confirmed/probable device thrombosis in the XINSORB-treated patients was only 1.0% (2/200). CONCLUSIONS: In this XINSORB randomized clinical trial, the XINSORB scaffolds and SESs showed similar efficacy and safety up to the 3-year follow-up. The rates of TLF and device thrombosis were low and comparable between the two arms.

Final report of the 5-year clinical outcomes of the XINSORB bioresorbable sirolimus-eluting scaffold in the treatment of single de novo coronary lesions in a first-in-human study.

BACKGROUND: We aimed to report the 5-year outcomes of XINSORB bioresorbable sirolimus-eluting scaffolds in the treatment of single de novo coronary lesions in a first-in-human (FIM) study. This is the final report of the long-term clinical outcomes of the study. Recent studies have shown that bioresorbable scaffolds (BRSs) increase the risks of late target lesion failure (TLF) and thrombosis. METHODS: In this prospective, single-arm study, eligible patients with single de novo coronary lesions were enrolled and treated with XINSORB scaffolds. The scaffolds measured 3.0 mm in diameter and 12, 15, and 18 mm in length. The clinical endpoints included TLF [cardiac death, target vessel-related myocardial infarction (TV-MI), or ischaemia-driven target lesion revascularization (ID-TLR)], its components, major adverse cardiac events (MACE), and scaffold thrombosis. RESULTS: From September 2013 to January 2014, 30 patients were enrolled and treated with XINSORB scaffolds. The procedure had a 100% success rate. None of the patients died during the 5 years of follow-up. The primary endpoint of TLF occurred in 4 patients (13.3%). Six patients were recanalized by intervention, including 4 by ID-TLR. The rate of MACE was 16.7% (5/30). One very late case of scaffold thrombosis was recorded, which led to TV-MI. No more cases of thrombosis were recorded beyond 2 years of follow-up. The rates of clinical endpoints remained steady with no changes after 3 years of follow-up. CONCLUSIONS: Considering that this FIM study was launched at an early stage of the BRS era and without optimal implantation techniques, the clinical outcomes of TLF during the 5-year follow-up were acceptable. The rate of thrombosis was relatively low.

Effects of salvianolate on myocardial perfusion after primary percutaneous catheter intervention in patients with ST-segment elevation myocardial infarction: a multicenter, randomized, double-blind, placebo-controlled study.

BACKGROUND: Despite prompt revascularization following acute myocardial infarction, poor myocardial perfusion commonly occurs due to impaired microvascular circulation and is an independent predictor of adverse outcomes. The current trial sought to examine the effects of salvianolate on myocardial perfusion in patients with ST-segment-elevation myocardial infarction (STEMI) who were undergoing primary percutaneous coronary intervention (PCI). METHODS: This randomized, double-blind, placebo-controlled, multicenter study evaluated the effects of intravenous salvianolate on the achievement of complete epicardial and myocardial reperfusion after PCI, defined as thrombolysis in myocardial infarction flow grade 3 and thrombolysis in myocardial infarction myocardial perfusion grade 3. We also measured plasma total creatine kinase-mass band fraction (CK-MB)-estimated infarct size and echocardiography-derived left ventricular ejection fraction and recorded the 30-day clinical and safety outcomes. A total of 536 patients presenting with acute STEMI were randomized to receive either an i.v. infusion of salvianolate (n=265) or placebo (n=271). RESULTS: Salvianolate administration exerted beneficial effects on coronary microcirculation. There was a trend of reduced myocardial infarct size in the salvianolate group compared to the placebo group (P=0.070), although no significant difference in left ventricular ejection fraction was found between the two groups. CONCLUSIONS: Salvianolate administration is associated with improved myocardial perfusion in patients with STEMI undergoing PCI. A larger study is required to assess the impact of this therapy on clinical cardiac outcomes.

Renal denervation mitigates atherosclerosis in ApoE-/- mice via the suppression of inflammation.

Atherosclerosis is a chronic pathological process characterized by the accumulation of inflammation. Overactivation of the sympathetic nervous system accelerates the progression of atherosclerosis. Renal denervation (RDN) reduces the activity of the sympathetic nerve system (SNS) by disrupting sympathetic nerves surrounding renal arteries. We sought to determine whether RDN could mitigate atherosclerosis through the suppression of inflammation. First, we investigated the correlation between plasma norepinephrine concentrations and circulatory inflammation in the progression of atherosclerosis. Then, forty ApoE-/- mice underwent renal denervation or a sham operation after 6 weeks or 12 weeks of feeding with a high-fat diet. The effects of RDN on atherosclerosis in mice were explored. In the development of atherosclerosis, positive correlations were found between SNS activation and the accumulation of circulatory myeloid cells and inflammatory cytokines. In the second part of the study, inhibition of the increase in plaque size was found in both RDN groups compared with that in the sham operation (SO) groups (P<0.05), and RDN also ameliorated inflammation in plaques. Furthermore, RDN attenuated the accumulation of circulating neutrophils and monocytes (P<0.05), which is associated with a significant reduction in levels of several circulating inflammatory cytokines related to hemopoiesis (P<0.05). Flow cytometry analysis revealed comparable levels of neutrophils and monocytes in the bone marrow between all four groups. However, RDN decreased the production and proportions of neutrophils and monocytes in the spleen and reduced splenic sympathetic activity (P<0.05). In summary, our study reveals a novel link between SNS activity and inflammation in atherosclerosis and identifies RDN as a potential anti-inflammatory therapeutic strategy for the treatment of atherosclerosis by restricting the production of splenic immune cells.

Estimating the inbreeding level and genetic relatedness in an isolated population of critically endangered Sichuan taimen (Hucho Bleekeri) using genome-wide SNP markers.

Sichuan taimen (Hucho bleekeri) is critically endangered fish listed in The Red List of Threatened Species compiled by the International Union for Conservation of Nature (IUCN). Specific locus amplified fragment sequencing (SLAF-seq)-based genotyping was performed for Sichuan taimen with 43 yearling individuals from three locations in Taibai River (a tributary of Yangtze River) that has been sequestered from its access to the ocean for more than 30 years since late 1980s. Applying the inbreeding level and genetic relatedness estimation using 15,396 genome-wide SNP markers, we found that the inbreeding level of this whole isolated population was at a low level (2.6 × 10-3 ± 0.079), and the means of coancestry coefficients within and between the three sampling locations were all very low (close to 0), too. Genomic differentiation was negatively correlated with the geographical distances between the sampling locations (p < .001), and the 43 individuals could be considered as genetically independent two groups. The low levels of genomic inbreeding and relatedness indicated a relatively large number of sexually mature individuals were involved in reproduction in Taibai River. This study suggested a genomic-relatedness-guided breeding and conservation strategy for wild fish species without pedigree information records.

Effects of dietary myo-inositol on growth, antioxidative capacity, and nonspecific immunity in skin mucus of taimen Hucho taimen fry.

In this study, the effects of dietary myo-inositol on the skin mucosal immunity and growth of taimen (Hucho taimen) fry were determined. Triplicate groups of 500 fish (initial weight 5.58 ± 0.15 g) were fed different diets containing graded levels of myo-inositol (28.75, 127.83, 343.83, 565.81, and 738.15 mg kg-1) until satiation for 56 days. Thereafter, the nonspecific skin mucus immune parameters, antioxidative capacity, and growth performance were measured. The skin mucus protein and the activities of alkaline phosphatase were significantly higher than those in the control group (P < 0.05). However, there were no significant differences in lysozyme activity among the treatments (P > 0.05). The antimicrobial activity and minimum inhibitory concentration of the skin mucus were increased significantly by myo-inositol supplementation (P < 0.05). The superoxide dismutase, catalase, and glutathione peroxidase activities were significantly elevated in the treatment groups (P < 0.05), whereas the malondialdehyde contents were significantly decreased (P < 0.05). Low-level myo-inositol (28.75 mg kg-1) led to a significantly lower weight gain, feed efficiency, condition factor, and survival rate compared with the other treatments (P < 0.05). In conclusion, dietary myo-inositol deficiency (28.75 mg kg-1) adversely affects the skin mucus immune parameters, antioxidative capacity, and growth performance of Hucho taimen fry.

A chimeric recombinant infectious hematopoietic necrosis virus induces protective immune responses against infectious hematopoietic necrosis and infectious pancreatic necrosis in rainbow trout.

Infectious pancreatic necrosis virus (IPNV) and infectious hematopoietic necrosis virus (IHNV) are two common viral pathogens that cause severe economic losses in all salmonid species in culture, but especially in rainbow trout. Although vaccines against both diseases have been commercialized in some countries, no such vaccines are available for them in China. In this study, a recombinant virus was constructed using the IHNV U genogroup Blk94 virus as a backbone vector to express the antigenic gene, VP2, from IPNV via the reverse genetics system. The resulting recombinant virus (rBlk94-VP2) showed stable biological characteristics as confirmed by virus growth kinetic analyses, pathogenicity analyses, indirect immunofluorescence assays and western blotting. Rainbow trout were immunized with rBlk94-VP2 and then challenged with the IPNV ChRtm213 strain and the IHNV Sn1203 strain on day 45 post-vaccination. A significantly higher survival rate against IHNV was obtained in the rBlk94-VP2 group on day 45 post-vaccination (86%) compared with the PBS mock immunized group (2%). Additionally, IPNV loads decreased significantly in the rBlk94-VP2 immunized group in the liver (28.6-fold to 36.5-fold), anterior kidney (21.7-fold to 44.2-fold), and spleen (14.9-fold to 22.7-fold), as compared with the PBS mock control group. The mRNA transcripts for several innate and adaptive immune-related proteins (IFN-γ, IFN-1, Mx-1, CD4, CD8, IgM, and IgT) were also significantly upregulated after rBlk94-VP2 vaccination, and neutralizing antibodies against both IHNV and IPNV were induced on day 45 post-vaccination. Collectively, our results suggest that this recombinant virus could be developed as a vaccine vector to protect rainbow trout against two or more diseases, and our approach lays the foundations for developing live vaccines for rainbow trout.