Conformational transitions and activation of the adhesion receptor CD97.

Adhesion G protein-coupled receptors (aGPCRs) are evolutionarily ancient receptors involved in a variety of physiological and pathophysiological processes. Modulators of aGPCR, particularly antagonists, hold therapeutic promise for diseases like cancer and immune and neurological disorders. Hindered by the inactive state structural information, our understanding of antagonist development and aGPCR activation faces challenges. Here, we report the cryo-electron microscopy structures of human CD97, a prototypical aGPCR that plays crucial roles in immune system, in its inactive apo and G13-bound fully active states. Compared with other family GPCRs, CD97 adopts a compact inactive conformation with a constrained ligand pocket. Activation induces significant conformational changes for both extracellular and intracellular sides, creating larger cavities for Stachel sequence binding and G13 engagement. Integrated with functional and metadynamics analyses, our study provides significant mechanistic insights into the activation and signaling of aGPCRs, paving the way for future drug discovery efforts.

Bitter taste TAS2R14 activation by intracellular tastants and cholesterol.

Bitter taste receptors, particularly TAS2R14, play central roles in discerning a wide array of bitter substances, ranging from dietary components to pharmaceutical agents1,2. TAS2R14 is also widely expressed in extra-gustatory tissues, suggesting its additional roles in diverse physiological processes and potential therapeutic applications3. Here, we present cryo-electron microcopy structures of TAS2R14 in complex with aristolochic acid, flufenamic acid and compound 28.1, coupling with different G protein subtypes. Uniquely, a cholesterol molecule is observed occupying what is typically an orthosteric site in class A GPCRs. The three potent agonists bind, individually, to the intracellular pockets, suggesting a distinct activation mechanism for this receptor. Comprehensive structural analysis, combined with mutagenesis, and molecular dynamic simulations studies, illuminate the receptor's broad-spectrum ligand recognition and activation via intricate multiple ligand-binding sites. Additionally, our study uncovers the specific coupling modes of TAS2R14 with gustducin and Gi1 proteins. These findings should be instrumental in advancing our knowledge underlying bitter taste perception and its broader implications in sensory biology and drug discovery.

Coronary sodium [18F]fluoride activity predicts outcomes post-CABG: a comparative evaluation with conventional metrics.

PURPOSE: The value of preoperative multidisciplinary approach remains inadequately delineated in forecasting postoperative outcomes of patients undergoing coronary artery bypass grafting (CABG). Herein, we aimed to ascertain the efficacy of multi-modality cardiac imaging in predicting post-CABG cardiovascular outcomes. METHODS: Patients with triple coronary artery disease underwent cardiac sodium [18F]fluoride ([18F]NaF) positron emission tomography/computed tomography (PET/CT), coronary angiography, and CT-based coronary artery calcium scoring before CABG. The maximum coronary [18F]NaF activity (target-to-blood ratio [TBR]max) and the global coronary [18F]NaF activity (TBRglobal) was determined. The primary endpoint was perioperative myocardial infarction (PMI) within 7-day post-CABG. Secondary endpoint included major adverse cardiac and cerebrovascular events (MACCEs) and recurrent angina. RESULTS: This prospective observational study examined 101 patients for a median of 40 months (interquartile range: 19-47 months). Both TBRmax (odds ratio [OR] = 1.445; p = 0.011) and TBRglobal (OR = 1.797; P = 0.018) were significant predictors of PMI. TBRmax>3.0 (area under the curve [AUC], 0.65; sensitivity, 75.0%; specificity, 56.8%; p = 0.036) increased PMI risk by 3.661-fold, independent of external confounders. Kaplan-Meier test revealed a decrease in MACCE survival rate concomitant with an escalating TBRmax. TBRmax>3.6 (AUC, 0.70; sensitivity, 76.9%; specificity, 73.9%; p = 0.017) increased MACCEs risk by 5.520-fold. Both TBRmax (hazard ratio [HR], 1.298; p = 0.004) and TBRglobal (HR = 1.335; p = 0.011) were significantly correlated with recurrent angina. No significant associations were found between CAC and SYNTAX scores and between PMI occurrence and long-term MACCEs. CONCLUSION: Quantification of coronary microcalcification activity via [18F]NaF PET displayed a strong ability to predict early and long-term post-CABG cardiovascular outcomes, thereby outperforming conventional metrics of coronary macrocalcification burden and stenosis severity. TRIAL REGISTRATION: The trial was registered with the Chinese Clinical Trial Committee (number: ChiCTR1900022527; URL: www.chictr.org.cn/showproj.html?proj=37933 ).

Administration of a new nano delivery system coated with Tirofiban to prevent early thrombosis of vein graft.

OBJECTIVE: To verify the administration of a new nano delivery system coated with Tirofiban on preventing early thrombosis in vein graft. METHODS: Forty New Zealand white rabbits were randomly divided into five groups with eight rabbits in each group. The rabbits of all groups underwent jugular vein transplantation, except group I with only neck opening and closing operation. Vein grafts of group II were preprocessed by intravenous injection of normal saline; group III were preprocessed by tirofiban alone; group IV were preprocessed by unloaded nanoparticles of PLGA-PEG; group V were preprocessed by PLGA-PEG coated with tirofiban. Coagulation and platelet function of peripheral and vein graft blood were detected at 1, 2, 4, 12 h and 1, 3, 7, 10, 14 days after operation. Patency rate of vein graft and blood flow index were measured by vascular ultrasound at third, seventh, 10th, and 14th days after operation; two rabbits in each group were randomly sacrificed at the corresponding time of detection. Pathological differences of vein grafts were observed by HE stainin. RESULTS: The patency rate of vein grafts in group V was significantly higher than that in group II to IV. The platelet and platelet aggregation rate in group V were inhibited in vein graft blood significantly. The post-operative PT and APTT in vein graft blood in group V were increased obviously while the FBG, D-dimer and FDP were significantly inhibited. Except group I, the lumen loss rate of vein grafts in group V was significantly lower than that in other groups, and vein graft blood in group V had a significant lower expression of platelet P-selectin and GP IIb/IIIa receptor than that in other groups. CONCLUSION: This study proves that PEG-PLGA coated with tirofiban can effectively prevent early vein graft stenosis from thrombosis by inhibition of platelet function, coagulation function.

Ultrafast Modulation of THz Waves Based on MoTe2-Covered Metasurface.

The sixth generation (6G) communication will use the terahertz (THz) frequency band, which requires flexible regulation of THz waves. For the conventional metallic metasurface, its electromagnetic properties are hard to be changed once after being fabricated. To enrich the modulation of THz waves, we report an all-optically controlled reconfigurable electromagnetically induced transparency (EIT) effect in the hybrid metasurface integrated with a 10-nm thick MoTe2 film. The experimental results demonstrate that under the excitation of the 800 nm femtosecond laser pulse with pump fluence of 3200 µJ/cm2, the modulation depth of THz transmission amplitude at the EIT window can reach 77%. Moreover, a group delay variation up to 4.6 ps is observed to indicate an actively tunable slow light behavior. The suppression and recovery of the EIT resonance can be accomplished within sub-nanoseconds, enabling an ultrafast THz photo-switching and providing a promising candidate for the on-chip devices of the upcoming 6G communication.

Prognostic value of ventricular mechanical dyssynchrony in patients with left ventricular aneurysm: A comparative study of medical and surgical treatment.

BACKGROUND: The prognostic value of left ventricular (LV) mechanical dyssynchrony (MD) in patients with LV aneurysm (LVA) is unclear. This study aimed to investigate the long-term prognostic value of LVMD in LVA patients. METHODS: 92 consecutive patients who underwent 99mTc-sestamibi-gated SPECT myocardial perfusion imaging (GSPECT) were retrospectively analyzed and followed-up for a median of 63 months (range, 1-73 months). LV function and histogram bandwidth (BW) were analyzed by QGS software. LVMD was defined by ROC analysis. Cardiac death was defined as the primary endpoint, and the composite of cardiac deaths and severe or acute heart failure (MACE) as the secondary endpoint. RESULTS: The annual cardiac mortality rate of LVA patients with LVMD and treated by surgical therapy was significantly lower than those treated by medical therapy (2.40% vs. 6.40%, P < .05) but not annual MACE rate (6.61% vs. 10.06%, P > .05). In patients without LVMD, no significant difference in survival and MACE-free survival between medical and surgical treatment. In addition, the occurrence of LVMD is related to the worsen cardiac outcome in terms of MACE and cardiac death, independent of the treatment methods. BW was an independent predictor for MACE (HR 1.010, P < .01) and LVEF (HR .928, P < .05) was an independent predictor for cardiac death in all LVA patients. CONCLUSIONS: LVA patients with LVMD might be associated with high risk for cardiac death and surgical treatment might improve cardiac survival compared to medical therapy in these patients.

Associations between coronary/aortic 18F-sodium fluoride uptake and pro-atherosclerosis factors in patients with multivessel coronary artery disease.

BACKGROUND: 18F-NaF PET/CT is a novel approach to detect and quantify microcalcification in atherosclerosis. We aimed to explore the underlying systematic vascular osteogenesis in the coronary artery and aorta in patients with multivessel coronary artery disease (CAD). METHODS: Patients with multivessel CAD prospectively underwent 18F-NaF PET/CT. The coronary microcalcification activity (CMA) and aortic microcalcification activity (AMA) were calculated based on both the volume and intensity of 18F-NaF PET activity. Peri-coronary adipose tissue (PCAT) density was measured in adipose tissue surrounding the coronary arteries and the 18F-NaF tissue-to-blood ratio (TBR) was measured in the coronary arteries. RESULTS: 100 patients with multivessel CAD were prospectively recruited. The CMA was significantly associated with the AMA (r = 0.70; P < .001). After multivariable adjustment, the CMA was associated with the AMA (Beta = 0.445 per SD increase; P < .001). The coronary TBR was also significantly associated with the PCAT density (r = 0.56; P < .001). The PCAT density was independently associated with the coronary TBR after adjusting confounding factors. CONCLUSIONS: Coronary 18F-NaF uptake was significantly associated with the PCAT density. There was a significant relationship between the coronary and the aortic 18F-NaF uptake. It might indicate an underlying systematic vascular osteogenesis in patients with multivessel CAD.

Effects of obstructive sleep apnea hypopnea syndrome on postoperative complications in patients who undergo off-pump coronary artery bypass grafting.

PURPOSE: To investigate the prevalence of obstructive sleep apnea hypopnea syndrome (OSAHS) in patients undergoing off-pump coronary artery bypass grafting (OPCABG) and analyze the effects of OSAHS on the incidence of post-OPCABG complications, length of stay in intensive care unit (ICU) and hospitalization, and hospital expense. MATERIALS AND METHODS: This prospective study included patients undergoing OPCABG at Beijing An Zhen hospital from January 2018 to December 2018. OSAHS was diagnosed by using a portable sleep monitor before surgery. RESULTS: Among 74 patients, the prevalence of OSAHS and moderate to severe OSAHS (apnea hypopnea index (AHI) ≥ 15) was 70% and 53%, respectively. Compared with the no to mild OSAHS group (AHI < 15), the moderate to severe OSAHS group presented a lower ejection fraction (P = 0.013). Between these two groups, the incidence of post-OPCABG complications; the duration of intubation, ICU stay, and hospitalization; and the hospital expense did not differ. Notably, the ejection fraction was significantly negatively correlated with the duration of ICU stay and hospital expense. CONCLUSIONS: Patients undergoing OPCABG with severe OSAHS are likely to exhibit a low ejection fraction and poor heart function, which may require a longer ICU stay and incur higher hospital expenses.

The effects of high-sensitivity C-reactive protein on the clinical outcomes in obstructive sleep apnea patients undergoing off-pump coronary artery bypass grafting.

PURPOSE: To investigate the relationship between obstructive sleep apnea (OSA) severity and high-sensitivity C-reactive protein (Hs-CRP), and their respective impact on the clinical outcomes in patients undergoing off-pump cardiac artery bypass grafting (OPCABG). METHODS: We enrolled consecutive eligible patients listed for elective OPCABG who underwent cardiorespiratory polygraphy before surgery between January 2019 and December 2019 in this prospective observational single-center study. Baseline, intraoperative, and postoperative clinical data were compared between absent-mild and moderate-severe OSA groups. Regression analysis investigated the relationship between Hs-CRP level and severity of OSA, and further assessed the factors influencing postoperative atrial fibrillation, duration of hospitalization, and hospital cost. RESULTS: Patients with moderate-severe OSA accounted for 42.3% (52/123) of the cohort. Partial pressure of carbon dioxide (PCO2), Hs-CRP, apnea hypopnea index (AHI), mean apnea time, maximum apnea time, and oxygen desaturation index ODI ≥ 3% were significantly higher in the moderate-severe OSA group than in the absent-mild OSA group. Left ventricle ejection fraction (LVEF), lowest arterial oxygen saturation (SaO2), and mean SaO2 were significantly lower in the moderate-severe OSA group. Moderate-severe OSA was associated with elevated Hs-CRP level (OR = 2.356, 95% CI 1.101-5.041, P = 0.027). Hs-CRP was an independent risk factor for post-CABG atrial fibrillation (POAF) (OR = 1.212, P = 0.01). Hs-CRP level independently correlated with duration of hospitalization (B = 0.456, P = 0.001) and hospital cost (B = 1.111, P = 0.044). CONCLUSION: Hs-CRP level was closely related to OSA severity and have potential utility in predicting POAF, duration of hospitalization, and hospital costs in patients undergoing OPCABG.

Comparative Analysis of Expression Profiles of Reg Signaling Pathways-Related Genes Between AHF and HCC.

Regenerating islet-derived protein (Reg) could participate in the occurrence of diabetes mellitus, inflammation, tumors, and other diseased or damaged tissues. However, the correlation of Reg with acute hepatic failure (AHF) and hepatocellular carcinoma (HCC) is poorly defined. To reveal the expression profiles of Reg family and their possible regulatory roles in AHF and HCC, rat models of HCC and AHF were separately established, and Rat Genome 230 2.0 was used to detect expression profiles of Reg-mediated signaling pathways-associated genes from liver tissues in AHF and HCC. The results showed that a total of 79 genes were significantly changed. Among these genes, 67 genes were the AHF-specific genes, 45 genes were the HCC-specific genes, and 33 genes were the common genes. Then, K-means clustering classified these genes into 4 clusters based on the gene expression similarity, and DAVID analysis showed that the above altered genes were mainly associated with stress response, inflammatory response, and cell cycle regulation. Thereafter, IPA software was used to analyze potential effects of these genes, and the predicted results suggested that the Reg-mediated JAK/STAT, NF-κB, MAPK (ERK1/2, P38 and JNK), PLC, and PI3K/AKT signaling pathways may account for the activated inflammation and cell proliferation, and the attenuated apoptosis and cell death during the occurrence of AHF and HCC.

Distal end side-to-side anastomoses of sequential vein graft to small target coronary arteries improve intraoperative graft flow.

BACKGROUND: End-to-side anastomoses to connect the distal end of the great saphenous vein (GSV) to small target coronary arteries are commonly performed in sequential coronary artery bypass grafting (CABG). However, the oversize diameter ratio between the GSV and small target vessels at end-to-side anastomoses might induce adverse hemodynamic condition. The purpose of this study was to describe a distal end side-to-side anastomosis technique and retrospectively compare the effect of distal end side-to-side versus end-to-side anastomosis on graft flow characteristics. METHODS: We performed side-to-side anastomoses to connect the distal end of the GSV to small target vessels on 30 patients undergoing off-pump sequential CABG in our hospital between October 2012 and July 2013. Among the 30 patients, end-to-side anastomoses at the distal end of the GSV were initially performed on 14 patients; however, due to poor graft flow, those anastomoses were revised into side-to-side anastomoses. We retrospectively compared the intraoperative graft flow characteristics of the end-to-side versus side-to-side anastomoses in the 14 patients. The patient outcomes were also evaluated. RESULTS: We found that the side-to-side anastomosis reconstruction improved intraoperative flow and reduced pulsatility index in all the 14 patients significantly. The 16 patients who had the distal end side-to-side anastomoses performed directly also exhibited satisfactory intraoperative graft flow. Three-month postoperative outcomes for all the patients were satisfactory. CONCLUSIONS: Side-to-side anastomosis at the distal end of sequential vein grafts might be a promising strategy to connect small target coronary arteries to the GSV.

The sphingosine-1-phosphate receptor 1 mediates the atheroprotective effect of eicosapentaenoic acid.

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) have been associated with potential cardiovascular benefits, partly attributed to their bioactive metabolites. However, the underlying mechanisms responsible for these advantages are not fully understood. We previously reported that metabolites of the cytochrome P450 pathway derived from eicosapentaenoic acid (EPA) mediated the atheroprotective effect of ω-3 PUFAs. Here, we show that 17,18-epoxyeicosatetraenoic acid (17,18-EEQ) and its receptor, sphingosine-1-phosphate receptor 1 (S1PR1), in endothelial cells (ECs) can inhibit oscillatory shear stress- or tumor necrosis factor-α-induced endothelial activation in cultured human ECs. Notably, the atheroprotective effect of 17,18-EEQ and purified EPA is circumvented in male mice with endothelial S1PR1 deficiency. Mechanistically, the anti-inflammatory effect of 17,18-EEQ relies on calcium release-mediated endothelial nitric oxide synthase (eNOS) activation, which is abolished upon inhibition of S1PR1 or Gq signaling. Furthermore, 17,18-EEQ allosterically regulates the conformation of S1PR1 through a polar interaction with Lys34Nter. Finally, we show that Vascepa, a prescription drug containing highly purified and stable EPA ethyl ester, exerts its cardiovascular protective effect through the 17,18-EEQ-S1PR1 pathway in male and female mice. Collectively, our findings indicate that the anti-inflammatory effect of 17,18-EEQ involves the activation of the S1PR1-Gq-Ca2+-eNOS axis in ECs, offering a potential therapeutic target against atherosclerosis.

Efficacy of ketamine versus esketamine in the treatment of perioperative depression: A review.

Depression is a significant factor contributing to postoperative occurrences, and patients diagnosed with depression have a higher risk for postoperative complications. Studies on cardiovascular surgery extensively addresses this concern. Several studies report that people who undergo coronary artery bypass graft surgery have a 20% chance of developing postoperative depression. A retrospective analysis of medical records spanning 21 years, involving 817 patients, revealed that approximately 40% of individuals undergoing coronary artery bypass grafting (CABG) were at risk of perioperative depression. Patients endure prolonged suffering from illness because each attempt with standard antidepressants requires several weeks to be effective. In addition, multi-drug combination adjuvants or combination medication therapy may alleviate symptoms for some individuals, but they also increase the risk of side effects. Conventional antidepressants primarily modulate the monoamine system, whereas different therapies target the serotonin, norepinephrine, and dopamine systems. Esketamine is a fast-acting antidepressant with high efficacy. Esketamine is the S-enantiomer of ketamine, a derivative of phencyclidine developed in 1956. Esketamine exerts its effect by targeting the glutaminergic system the glutaminergic system. In this paper, we discuss the current depression treatment strategies with a focus on the pharmacology and mechanism of action of esketamine. In addition, studies reporting use of esketamine to treat perioperative depressive symptoms are reviwed, and the potential future applications of the drug are presented.

Differential contributions of G protein- or arrestin subtype-mediated signalling underlie urocortin 3-induced somatostatin secretion in pancreatic δ cells.

BACKGROUND AND PURPOSE: Pancreatic islets are modulated by cross-talk among different cell types and paracrine signalling plays important roles in maintaining glucose homeostasis. Urocortin 3 (UCN3) secreted by pancreatic ß cells activates the CRF2 receptor (CRF2R) and downstream pathways mediated by different G protein or arrestin subtypes in δ cells to cause somatostatin (SST) secretion, and constitutes an important feedback circuit for glucose homeostasis. EXPERIMENTAL APPROACH: Here, we used Arrb1-/-, Arrb2-/-, Gsfl/fl and Gqfl/fl knockout mice, the G11-shRNA-GFPfl/fl lentivirus, as well as functional assays and pharmacological characterization to study how the coupling of Gs, G11 and ß-arrestin1 to CRF2R contributed to UCN3-induced SST secretion in pancreatic δ cells. KEY RESULTS: Our study showed that CRF2R coupled to a panel of G protein and arrestin subtypes in response to UCN3 engagement. While RyR3 phosphorylation by PKA at the S156, S2706 and S4697 sites may underlie the Gs-mediated UCN3- CRF2R axis for SST secretion, the interaction of SYT1 with ß-arrestin1 is also essential for efficient SST secretion downstream of CRF2R. The specific expression of the transcription factor Stat6 may contribute to G11 expression in pancreatic δ cells. Furthermore, we found that different UCN3 concentrations may have distinct effects on glucose homeostasis, and these effects may depend on different CRF2R downstream effectors. CONCLUSIONS AND IMPLICATIONS: Collectively, our results provide a landscape view of signalling mediated by different G protein or arrestin subtypes downstream of paracrine UCN3- CRF2R signalling in pancreatic ß-δ-cell circuits, which may facilitate the understanding of fine-tuned glucose homeostasis networks.

Early tirofiban versus heparin for bridging dual antiplatelet therapy in patients undergoing coronary endarterectomy combined with coronary artery bypass grafting: a multicenter randomized controlled trial protocol (the THACE-CABG trial).

BACKGROUND: For complete revascularization, patients with diffuse coronary artery disease should have a coronary endarterectomy and a coronary artery bypass graft (CE-CABG). Sadly, CE can lead to a lack of endothelium, which raises the risk of thrombotic events. Even though daily dual antiplatelet therapies (DAPT) have been shown to reduce thrombotic events, the risk of perioperative thrombotic events is high during the high-risk period after CE-CABG, and there is no consistent protocol to bridge DAPT. This trial aims to compare safety and efficacy between tirofiban and heparin as DAPT bridging strategies after CE-CABG. METHODS: In phase I, 266 patients undergoing CE-CABG will be randomly assigned to tirofiban and heparin treatment groups to compare the two treatments in terms of the primary safety endpoint, chest tube drainage in the first 24 h. If the phase I trial shows tirofiban non-inferiority, phase II will commence, in which an additional 464 patients will be randomly assigned. All 730 patients will be studied to compare major cardiovascular and cerebrovascular events (MACCEs) between the groups in the first 30 days after surgery. DISCUSSION: Given the possible benefits of tirofiban administration after CE-CABG, this trial has the potential to advance the field of adult coronary heart surgery. TRIAL REGISTRATION: chictr.org.cn, ChiCTR2200055697. Registered 6 January 2022. https://www.chictr.org.cn/com/25/showproj.aspx?proj=149451 . Current version: 20,220,620.

Intratracheal antitumor necrosis factor-α antibody attenuates lung tissue damage following cardiopulmonary bypass.

The aim of this study is to investigate the protective effect and underlying mechanism of antitumor necrosis factor-α antibody (TNF-α Ab) on lung tissue injury after cardiopulmonary bypass (CPB). Twenty-eight healthy New Zealand white rabbits were randomly divided into four groups. Group I received only an open chest operation. Groups II-IV all received CPB. Furthermore, groups III and IV received post-CPB endotracheal intubation with phosphate buffered saline or TNF-α Ab (2400 pg/kg), respectively. Perioperative blood neutrophil count, TNF-α level, and malondialdehyde (MDA) levels were determined in both the right and left atriums. Lung water content, TNF-α messenger RNA, protein, apoptosis in situ, and pathomorphological changes were also measured. The results show that TNF-α Ab can significantly inhibit leukocyte accumulation, reduce secretion of TNF-α and MDA, decrease lung tissue apoptosis, and attenuate post-CPB pathomorphological changes. TNF-α Ab administration, however, cannot suppress the expression of TNF-α, suggesting that the protective effects of TNF-α Ab originate from inhibiting the numerous biological functions of TNF-α. Intratracheal TNF-α Ab administration demonstrates a notable protective effect against lung injury after CPB.

A new means of energy supply driven by terahertz photons recovers related neural activity.

Continuous and efficient energy capture represents a long-sought dream of mankind. The brain is a major energy-consuming organ; an adult brain accounts for about 2% of the body weight but consumes about 20% of the body's energy. However, it is still unclear how the brain achieves efficient use of energy. Here, using nerve cells as test subjects, we found that THz photons with a specific frequency can effectively restore the reduced frequency of action potentials caused by inadequate ATP supply, which has been demonstrated as a novel mode of energy supply, present photons emission at a particular frequency from the breaking of the ATP phosphate bond. This energy supply mechanism may play a key biophysical basis for explaining how the body efficiently obtains energy, because the quantized chemical reactions could have a high energy efficiency and ultrahigh selectivity compared with the traditional thermochemistry and photochemistry.

Selective coronary vein bypass graft improves outcomes of patients with right coronary artery lesion.

Background: The benefits of selective coronary vein bypass grafting (SCVBG) for patients with severe diffuse lesions of the right coronary artery (RCA) who are unsuitable for coronary endarterectomy (CE) are unclear. Methods: We recruited patients with diffuse lesions of the RCA undergoing coronary artery bypass surgery between January 2015 and December 2018 and matched SCVBG and CE patients on propensity score (PS). We evaluated the degree of single-stenosis in the RCA, incidence of perioperative myocardial infarction (MI) and major adverse cardiovascular and cerebrovascular events (MACCE), influencing factors of perioperative MACCE, long-term survival rate, and long-term MACCE incidence. Results: Overall, 430 patients were enrolled: 344 (80%) underwent CE and 86 (20%) underwent SCVBG (n=78 and n=64, respectively, after PS matching). The incidence of perioperative MI and MACCE were significantly lower in the SCVBG group (5.1% vs. 1.5%, P<0.05; and 10.2% vs. 4.7%, P<0.05). When the vascular flow rate of the graft anastomosed to RCA in the SCVBG group was above 100 mL/min, the incidence of perioperative MACCE significantly increased [odds ratio (OR): 1.94, 95% confidence interval (CI): 1.42-2.03]. Choosing the bilateral internal mammary artery for SCVBG reduced the incidence of perioperative MACCE (OR: 0.82, 95% CI: 0.68-0.92). There was no significant difference in the rates of long-term survival or MACCE between the two groups before or after PS matching (P>0.05). Conclusions: SCVBG is an acceptable surgical intervention for patients with severe diffuse RCA lesions.

Coronary plaque burden predicts perioperative cardiovascular events after coronary endarterectomy.

Background and aims: The risk factors of perioperative and long-term cardiovascular events in patients undergoing coronary artery bypass grafting (CABG) with adjunctive coronary endarterectomy (CE) are not well determined. This study evaluated the clinical value of coronary plaque burden, coronary anatomic stenosis, and serum biomarkers for predicting perioperative cardiovascular events after off-pump CABG + CE. Methods: This retrospective cohort single-center study enrolled 125 patients undergoing off-pump CABG + CE between February 2018 and September 2021 in China. Coronary plaque burden was reflected by the length of plaque removed by CE. Plaque length-max, which represents the plaque length in patients undergoing single-vessel CE and the maximum plaque length in patients undergoing multivessel CE, was calculated. The primary endpoint was perioperative myocardial infraction (PMI). Results: Plaque length-max was significantly higher in patients with PMI than in those without PMI (2.4 ± 1.5 vs. 1.6 ± 0.9, p = .001). A threshold plaque length-max of 1.15 cm was an independent predictor of PMI (area under the curve: 0.67; sensitivity 87.9%; specificity 59.8%; p = .005). Patients with plaque length-max ≥1.15 had a > 5-fold increase in PMI after adjusting for confounding factors (odds ratio = 5.89; p = .002). Furthermore, interleukin-6 (Beta = .32: p = .028), CD68 (Beta = .34; p = .045), and osteopontin (Beta = .43; p = .008) were significantly correlated with plaque length-max. Conclusions: Plaque length-max was superior to clinical cardiovascular risk factors in predicting PMI occurrence after off-pump CABG + CE, which might be associated with systemic and plaque inflammation state.

Trends and hotspots in familial hypercholesterolemia: A bibliometric systematic review from 2002 to 2022.

BACKGROUND: We visually assessed the research hotspots of familial hypercholesterolemia (FH) using bibliometrics and knowledge mapping in light of the research state and development trend of FH. METHODS: We employed bibliometric tools, such as CiteSpace and the alluvial generator, to illustrate the scientific accomplishments on FH by extracting pertinent literature on FH from the Web of Science Core Collection database from January 1, 2002, to December 31, 2022. RESULTS: A total of 4402 papers in total were selected for study; 29.2% of all articles globally were from the USA, followed by the Netherlands and England. The University of Amsterdam, University of Oslo, and University of Western Australia are the 3 institutions with the most publications in this area. Gerald F. Watts, Raul D. Santos, and John J. P. Kastelein wrote the majority of the pieces that were published. The New England Journal of Medicine, Circulation, and Atherosclerosis were the journals with the greatest number of papers in this field. Prevalence and genetic analysis of FH, proprotein convertase subtilisin/kexin 9 inhibitors, and inclisiran are current research hotspots for the condition. Future research in this area will be focused on gene therapy. CONCLUSIONS: FH research has shown shows a trend of ascending followed by leveling off. The prevalence and diagnosis of FH, proprotein convertase subtilisin/kexin 9 inhibitors, inclisiran, and gene therapy are current research hotspots. This report may serve as a reference for current research trends.