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Abstract Background Intracranial aneurysm (IA) is a severe cerebrovascular disease, and effective gene therapy and drug interventions for its treatment are still lacking. Oxidative stress (OS) is closely associated with the IA, but the key regulatory genes involved are still unclear. Through multiomics analysis and experimental validation, we identified two diagnostic markers for IA associated with OS. Methods In this study, we first analyzed the IA dataset GSE75436 and conducted a joint analysis of oxidative stress-related genes (ORGs). Differential analysis, functional enrichment analysis, immune infiltration, WGCNA, PPI, LASSO, and other methods were used to identify IA diagnostic markers related to OS. Next, the functions of TLR4 and ALOX5 expression in IA and their potential targeted therapeutic drugs were analyzed. We also performed single-cell sequencing of patient IA and control (superficial temporal artery, STA) tissues. 23,342 cells were captured from 2 IA and 3 STA samples obtained from our center. Cell clustering and annotation were conducted using R software to observe the distribution of TLR4 and ALOX5 expression in IAs. Finally, the expression of TLR4 and ALOX5 were validated in IA patients and in an elastase-induced mouse IA model using experiments such as WB and immunofluorescence. Results Through bioinformatics analysis, we identified 16 key ORGs associated with IA pathogenesis. Further screening revealed that ALOX5 and TLR4 were highly expressed to activate a series of inflammatory responses and reduce the production of myocytes. Methotrexate (MTX) may be a potential targeted drug. Single-cell analysis revealed a notable increase in immune cells in the IA group, with ALOX5 and TLR4 primarily localized to monocytes/macrophages. Validation through patient samples and mouse models confirmed high expression of ALOX5 and TLR4 in IAs. Conclusions Bioinformatics analysis indicated that ALOX5 and TLR4 are the most significant ORGs associated with the pathogenesis of IA. Single-cell sequencing and experiments revealed that the high expression of ALOX5 and TLR4 are closely related to IA. These two genes are promising new targets for IA therapy.

Abstract Recent research in computational imaging largely focuses on developing machine learning (ML) techniques for image recognition in the medical field, which requires large-scale and high-quality training datasets consisting of raw images and annotated images. However, suitable experimental datasets for cervical spine X-ray are scarce. We fill the gap by providing an open-access Cervical Spine X-ray Atlas (CSXA), which includes 4963 raw PNG images and 4963 annotated images with JSON format (JavaScript Object Notation). Every image in the CSXA is enriched with gender, age, pixel equivalent, asymptomatic and symptomatic classifications, cervical curvature categorization and 118 quantitative parameters. Subsequently, an efficient algorithm has developed to transform 23 keypoints in images into 77 quantitative parameters for cervical spine disease diagnosis and treatment. The algorithm’s development is intended to assist future researchers in repurposing annotated images for the advancement of machine learning techniques across various image recognition tasks. The CSXA and algorithm are open-access with the intention of aiding the research communities in experiment replication and advancing the field of medical imaging in cervical spine.

Background: Chronic total occlusion (CTO) is the most challenging subset in percutaneous coronary intervention (PCI), but the optimal selection of patients and indication for such procedures remain a subject of debate. We sought to investigate the role of physiological function in treatment decisions of CTO PCI by measuring fractional flow reserve (FFR) and Dynamic SPECT imaging in this study. Methods: All the FFR of CTO vessel were measured before and immediately after CTO revascularization, and Dynamic SPECT imaging were detected before PCI in patients with an identified CTO. Results: A total of 53 patients with single-vessel CTO lesions were included in this cohort study. The mean FFR value was 0.34 ± 0.09 at baseline. Immediately after successful CTO PCI, the FFR value significantly increased to 0.79 ± 0.11. The regional coronary flow reserve (CFR) of CTO vessels was 1.62 ± 0.64, which was significantly and positively correlated with the baseline FFR value (r = 0.607, p = 0.005). The area under the ROC curve of the baseline FFR for the detection of ischemia was 0.923 (p

Abstract Background Indobufen is widely used in patients with aspirin intolerance in East Asia. The OPTION trial launched by our cardiac center examined the performance of indobufen based dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). However, the vast majority of patients with acute coronary syndrome (ACS) and aspirin intolerance were excluded. We aimed to explore this question in a real-world population. Methods Patients enrolled in the ASPIRATION registry were grouped according to the DAPT strategy that they received after PCI. The primary endpoints were major adverse cardiovascular and cerebrovascular events (MACCE) and Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding. Propensity score matching (PSM) was adopted for confounder adjustment. Results A total of 7135 patients were reviewed. After one-year follow-up, the indobufen group was associated with the same risk of MACCE versus the aspirin group after PSM (6.5% vs. 6.5%, hazard ratio [HR] = 0.99, 95% confidence interval [CI] = 0.65 to 1.52, P = 0.978). However, BARC type 2, 3, or 5 bleeding was significantly reduced (3.0% vs. 11.9%, HR = 0.24, 95% CI = 0.15 to 0.40, P

Abstract PARP inhibitors (PARPi) hold substantial promise in treating glioblastoma (GBM). However, the adverse effects have restricted their broad application. Through unbiased transcriptomic and proteomic sequencing, it is discovered that the BET inhibitor (BETi) Birabresib profoundly alters the processes of DNA replication and cell cycle progression in GBM cells, beyond the previously reported impact of BET inhibition on homologous recombination repair. Through in vitro experiments using established GBM cell lines and patient‐derived primary GBM cells, as well as in vivo orthotopic transplantation tumor experiments in zebrafish and nude mice, it is demonstrated that the concurrent administration of PARPi and BETi can synergistically inhibit GBM. Intriguingly, it is observed that DNA damage lingers after discontinuation of PARPi monotherapy, implying that sequential administration of PARPi followed by BETi can maintain antitumor efficacy while reducing toxicity. In GBM cells with elevated baseline replication stress, the sequential regimen exhibits comparable efficacy to concurrent treatment, protecting normal glial cells with lower baseline replication stress from DNA toxicity and subsequent death. This study provides compelling preclinical evidence supporting the development of innovative drug administration strategies focusing on PARPi for GBM therapy.

Restrictive cardiomyopathy (RCM) is a rare cardiomyopathy characterized by diastolic dysfunction, which affects cardiac systolic function. We successfully established human induced pluripotent stem cells (hiPSCs) from peripheral blood mononuclear cells of 24-year-old male with restrictive cardiomyopathy (RCM). The patient-derived hiPSCs carried heterozygous mutation of CRYAB gene (c.326A > G, p.D109G), which was consistent with clinical whole exon sequencing results. We confirmed the pluripotency, multipotential differentiation and karyotype of hiPSCs. The hiPSCs will be useful for studying the pathogenesis of RCM caused by CRYAB (c.326A > G) mutation.

Abstract Background Early diagnosis and treatment effectiveness of early-onset coronary artery disease (EOCAD) are crucial, and non-invasive predictive biomarkers are needed for young adults. We aimed to evaluate the usefulness of the triglyceride-glucose (TyG) index, a novel marker of insulin resistance, in identifying young CAD patients and predicting their risk of developing target lesion failure (TLF). Methods We recruited EOCAD patients (luminal narrowing ≥ 70%) and controls free from CAD (luminal narrowing

Abstract Inhibition of pathological cardiac hypertrophy is recognized as an important therapeutic strategy for heart failure, although effective targets are still lacking in clinical practice. Homeodomain interacting protein kinase 1 (HIPK1) is a conserved serine/threonine kinase that can respond to different stress signals, however, whether and how HIPK1 regulates myocardial function is not reported. Here, it is observed that HIPK1 is increased during pathological cardiac hypertrophy. Both genetic ablation and gene therapy targeting HIPK1 are protective against pathological hypertrophy and heart failure in vivo. Hypertrophic stress‐induced HIPK1 is present in the nucleus of cardiomyocytes, while HIPK1 inhibition prevents phenylephrine‐induced cardiomyocyte hypertrophy through inhibiting cAMP‐response element binding protein (CREB) phosphorylation at Ser271 and inactivating CCAAT/enhancer‐binding protein β (C/EBPβ)‐mediated transcription of pathological response genes. Inhibition of HIPK1 and CREB forms a synergistic pathway in preventing pathological cardiac hypertrophy. In conclusion, HIPK1 inhibition may serve as a promising novel therapeutic strategy to attenuate pathological cardiac hypertrophy and heart failure.

Background Alterations in the gut microbiota have been observed in patients with pulmonary hypertension (PH), though whether the roles of the gut microbiota in PH at different altitudes are the same is unknown. This study aims to evaluate the associations of the gut microbiome with PH in highlanders and lowlanders. Methods PH patients and controls were recruited from those who permanently live on the Tibetan plateau (highlanders) or the plains (lowlanders), and underwent transthoracic echocardiography close to their altitude of residence (at 5070 m for highlanders versus6 m for lowlanders). The gut microbiome was profiled using metagenomic shotgun sequencing. Results In total, 13 PH patients (46% highlanders) and 88 controls (70% highlanders) were included. The overall microbial composition was different in PH patients compared to controls (p=0.003). Notably, among lowlanders, a composite microbial score of pro-atherosclerotic trimethylamine-producing species was increased in PH patients compared with that in controls (p=0.028), while among highlanders no such difference was observed (p=0.087). Another composite gut microbial score including eight species of Lactobacillus, which has shown beneficial effects on cardiovascular functions, was higher in highlanders than lowlanders (p

Abstract Lumbar disc herniation (LDH) can be spontaneously absorbed without surgical treatment. However, the pathogenesis and physiological indications for predicting protrusion reabsorption are still unclear, which prevents clinicians from preferentially choosing conservative treatment options for LDH patients with reabsorption effects. The purpose of this review was to summarize previous reports on LDH reabsorption and to discuss the clinical and imaging features that favor natural absorption. We highlighted the biological mechanisms involved in the phenomenon of LDH reabsorption, including macrophage infiltration, inflammatory responses, matrix remodeling, and neovascularization. In addition, we summarized and discussed potential clinical treatments for promoting reabsorption. Current evidence suggests that macrophage regulation of inflammatory mediators, matrix metalloproteinases, and specific cytokines in intervertebral disc is essential for the spontaneous reabsorption of LDH.

Improving the survival rate of cardiomyocytes is the key point to treat most of the heart diseases, and targeting autophagy is a potential advanced therapeutic approach. Monitoring autophagic activity in cardiomyocytes in situ will be useful for studying autophagy-related heart disease and screening autophagy-modulating drugs. Zebrafish, Danio rerio, has been proven as an animal model for studying heart diseases in situ. Taken the advantage of zebrafish, especially the imaging of intact animals, here we generated two stable transgenic zebrafish lines that specifically expressed EGFP-map1lc3b or mRFP-EGFP-map1lc3b in cardiomyocytes under the promoter of myosin light chain 7. We first used a few known autophagy-modulating drugs to confirm their usefulness. By quantifying the density of autophagosomes and autolysosomes, autophagy inducers and inhibitors showed their regulatory functions, which were consistent with previous studies. With the two lines, we then found a significant increase in the density of autophagosomes but not autolysosomes in zebrafish cardiomyocytes at the early developmental stages, indicating the involvement of autophagy in early heart development. To prove their applicability, we also tested five clinical statins by the two lines. And we found that statins did not change the density of autophagosomes but reduced the density of autolysosomes in cardiomyocytes, implying their regulation in autophagic flux. Our study provides novel animal models for monitoring autophagic activity in cardiomyocytes in situ, which could be used to study autophagy-related cardiomyopathy and drug screening.

Background: Lower-grade gliomas (LGGs) carry a high risk of malignant transformation, leading to severe neurologic deterioration and ultimately, death. The tumor microenvironment (TME) plays an essential role in tumor maintenance, progression, and immunotherapy resistance. Therefore, the LGG TME deserves comprehensive exploration for a novel therapeutic target.Methods: The ESTIMATE algorithm was used to estimate infiltrating stromal and immune cells of LGG patients obtained from the Cancer Genome Atlas (TCGA) database. Kaplan–Meier analysis was performed to classify survival differences. TME-related differentially expressed genes were identified between the low- and high-immune/stromal groups. Hub genes were screened by constructing protein–protein interaction networks and performing the Cox regression analysis. Differential analysis, survival analysis, gene set enrichment analysis, and clinical relevance analysis specific to hub genes were evaluated by using the TCGA and the Chinese Glioma Genome Atlas datasets, and the results were validated by qRT-PCR, Western blotting, and immunohistochemistry in tissues from LGG patients.Results: The immune and stromal components in TME were negatively related to patient prognosis. Differentially expressed genes sharing immune score and stromal score were mainly involved in the immune response. C-C chemokine receptor type 5 (CCR5), as only a hub gene, was significantly higher in LGG patients than normal patients and negatively correlated with the prognosis of patients. High-expression CCR5 was positively related to immune-related and tumor progression pathways. CCR5 protein expression was higher in LGG with isocitrate dehydrogenase wildtype. Validated results showed that CCR5 was upregulated in LGG tissues at mRNA and protein levels and could affect immune cell infiltration. These results suggested that CCR5 was a potential indicator for the status of TME.Conclusion: Glioma cells remodel the immune microenvironment through the high expression of CCR5 and lead to a poor prognosis in patients with LGG. The inhibition of CCR5 may contribute to the efficacy of LGG immunotherapy.

We aimed to investigate prognostic factors of in-stent restenosis (ISR) within 3 years in older acute coronary syndrome (ACS) patients after drug-eluting stent (DES) implantation and establish a clinical model for predicting ISR. We retrospectively collected 215 older ACS patients who followed coronary angiography (CAG) after DES implantation, divided into ISR group and non in-stent restenosis (non-ISR) group according to the results of reviewed CAG. Logistic regression analysis was performed to screen independent predictors related to ISR and build the clinical predictive model, which clinical application was assessed by decision curve analysis (DCA) and clinical impact curve (CIC). Kaplan-Meier survival curves for ISR by independent predictors. In multivariate logistic regression analysis showed that the red cell distribution width (RDW) was higher in ISR group compared with non-ISR (odds ratio (OR) = 1.54, 95% confidence interval (CI): 1.14–2.08, p

Abstract Background The jailed balloon technique is widely used for coronary bifurcation lesions, but a residual risk of SB occlusion remains, necessitating SB rewiring and further interventions, including balloon inflation or stenting, which may result in failure and SB loss. This study introduced a novel modified technique of small side branch (SB) protection, namely, double kissing inflation outside the stent (DKo) technique, for coronary bifurcations without the need for SB rewiring. Methods We performed the DKo technique in consecutive patients in our center from 1/2019 to 12/2019. The procedure was as follows. We inserted a guide wire into both branches followed by proper preparation. The SB balloon was simultaneously inflated with main vessel (MV) stenting. The SB balloon remained in situ until it was kissing inflated with postdilation of the bifurcation core, which is different from traditional strategies. The proximal optimization technique was performed with a short noncompliant balloon strictly not exceeding the bifurcation. Rates of SB loss and in-hospital outcomes were evaluated. Results The technique was successfully performed in all 117 enrolled patients without any rewiring or SB loss. The mean lesion lengths of the MV and SB were 38.3 ± 19.9 mm and 11.7 ± 7.1 mm, respectively. On average, 1.5 ± 0.6 stents were used per patient, while the mean pressure of the SB balloon was 7.4 ± 3.1 atm. DKo achieved excellent procedural success in the proximal and distal MVs: increased minimal lumen diameter (0.64 ± 0.58 mm to 3.05 ± 0.38 mm, p

Background: Hemorrhage is the most common during microvascular decompression (MVD) for hemifacial spasm (HFS), trigeminal neuralgia (TN) and glossopharyngeal neuralgia (GN). However, remote supratentorial subdural hematoma is very rare, especially for those patients who reveal severe intraoperative venous bleeding without a definite bleeding source in the suboccipital surgical area, and immediate postoperative computed tomography (CT) reveals supratentorial subdural hematoma. The underlying mechanisms remain obscure. We report 10 cases to discuss the pathophysiology and develop appropriate therapeutic strategies for prevention and treatment. Patients and methods: We retrospectively analyzed clinical data of patients who underwent microvascular decompression in Nanjing Drum Tower Hospital between December 1, 2018 and December 31, 2020. Among 764 patients, bleeding events occurred in 10 cases, whose bleeding origin was not confirmed intraoperatively and immediate postoperative CT revealed supratentorial subdural hematoma. We reviewed characteristics, the intraoperative situations and the prognosis of the 10 cases. Results: The mean age of the patients was 55.4 years; 2 was male and 8 were female. All patients revealed draining large amounts of intraoperative cerebrospinal fluid (CSF) during the operation. Primary unknown cause of severe venous bleeding of 8 patients occurred in different time periods intraoperatively. However, hemorrhage all occurred in a very early stage before decompression. The operation was completed successfully in the 8 patients through the irrigation and drainage of the bloody cerebrospinal fluid. patient Postoperative CT indicated supratentorial acute subdural hematoma (ASDH) with hematoma volume

BackgroundCurrent guidewires for transradial coronary angiography had defects of passage difficulty or branch injury. This study sought to investigate the safety and efficiency of a novel method of active knuckle-angle 0.035-inch hydrophilic guidewire in transradial coronary angiography.MethodsPatients undergoing a transradial coronary procedure in our team from August 2015 to June 2020 were retrospectively investigated. We compared the demographic and interventional characteristics of 1,457 patients receiving advancement of unmodified guidewires (Traditional group) and 1,322 patients receiving advancement of the knuckle guidewire (Knuckle group). Afterwards we included 239 patients and randomized them according to a random number table to either the unmodified or the knuckle guidewire to further confirm the efficiency and safety of knuckle guidewire advancement.ResultsIn the retrospective analysis, unwilling passage of guidewire into branches occurred more in the Traditional group than in the Knuckle group (9.5 vs. 0.08%, p < 0.001). Two patients in the Traditional group experienced guidewire-associated perforation. One patient was treated with covered stent for internal mammarian artery perforation, while the other was managed with compression for brachial branch perforation. In the randomized controlled study, unwilling passage of guidewire also occurred more in the Traditional group (10.8 vs. 1%, p < 0.001). Median duration of guidewire advancement from the sheath to aortic root significantly decreased from 33 seconds in the Traditional group to 21 seconds in the Knuckle group.ConclusionActive knuckle angle guidewire represented a novel method to prevent unwilling passage and associated perforation with efficiency improvement and a reduction in radiation exposure.

AimThe purpose of this study was to investigate the predicting value of platelet distribution width (PDW) and fibrinogen for in-stent restenosis (ISR) in patients with stable angina pectoris and type 2 diabetes mellitus (T2DM) after drug-eluting stent (DES) implantation.MethodsWe enrolled 161 patients who were readmitted with recurrent chest pain and successfully reviewed for coronary angiography and were divided into the ISR and non-ISR groups. We compared the levels of PDW and fibrinogen between the two groups. Logistic regression was used for analyzing independent predictors of ISR. The receiver operating characteristic (ROC) curve analysis was used to determine the optimum cutoff points of PDW and fibrinogen to predict ISR. The Kaplan–Meier survival curves for target lesion failure (TLF) by levels of PDW and fibrinogen.ResultsThe multivariate logistic regression analysis showed that PDW and fibrinogen were independent predictors of ISR [odds ratio (OR) = 1.209, 95% CI: 1.024–1.427, p = 0.025; OR = 1.006, 95% CI: 1.002–1.011, p = 0.010, respectively]. The ROC analyses showed that PDW ≥ 13.15% and fibrinogen ≥ 333.5 mg/dl were predictive of ISR in patients with stable angina pectoris and T2DM after DES implantation. However, the Kaplan–Meier estimate for TLF showed no statistical significance.ConclusionHigher levels of PDW and fibrinogen were associated with the incidence of ISR in patients with stable angina with T2DM after DES implantation, but were not independent predictors of TLF.

Corex process can produce hot metal without using coke and has some advantages in reducing pollution. However, the silicon content of hot metal produced by Corex furnace is 0.6–1.5 mass%, which results in the serious corrosion of lining. In order to study the mechanism of lining corrosion, the sample of corrosion lining was taken, and the morphology of the corrosion region was analyzed by SEM. The optimum composition of slag for splashing was determined through a combination of plant experiments and theoretical calculation. The results show that the chemical reaction and the dissolution of (MgO) lead to the lining corrosion of BOF. Concentration gradient of Mg and Fe were found between slag and refractory brick, which promote the mass exchange and reaction between slag and refractory brick. The low basicity of slag leads to low melting point and less formation of solid phase at the same temperature, which result in the scouring down of slag at early stage of steelmaking in BOF. In addition, the low basicity lead to high saturated solubility of (MgO), which is beneficial to the dissolution of (MgO) of refractory lining. The constant reaction and dissolution of (MgO) between lining and slag lead to the lining corrosion. The basicity of slag should be 1.0–1.2. The content of (FeO) should be controlled less than 5 mass%, and the content of (MgO) should be 5–7 mass%.

Abstract Background Accumulating evidence shows that circulating levels of trimethylamine N-oxide, which is generated from the metabolism of dietary choline, may predict cardiovascular disease among Caucasians. Acute coronary syndrome (ACS), one common presentation of cardiovascular disease, is a spectrum of signs and symptoms due to acute decreased blood flow in the coronary arteries. The relationship between the metabolites from choline pathway and ACS remains unclear. We aimed to assess the associations of circulating metabolites from the choline pathway with ACS among a Chinese population, who consume a different dietary pattern than their Western counterparts. Methods We recruited 501 participants who were admitted to the Department of Cardiology, Zhongshan Hospital,Shanghai China between March 2017 and June 2018, including 254 ACS cases and 247 controls. Liquid chromatography-tandem mass spectrometry was used to measure circulating concentrations of metabolites in the choline pathway, including betaine, choline, trimethylamine, and trimethylamine N-oxide. A composite metabolite score using a weighted sum of these four metabolites, and the betaine/choline ratio were calculated. Multivariable logistic regressions were applied to estimate the association of metabolites with ACS, with adjustment of age, sex, body mass index, smoking index, history of diseases, and kidney function. Results After adjusting for traditional risk factors, per 1-standard deviation (SD) increment in choline was positively associated with the odds of ACS [odds ratio (OR), 95% confidence interval (CI), 1.77(1.44–2.18)], and the other metabolites were not associated with ACS at a statistical significance level. Compared with participants in the lowest quartile of the metabolite score, those in the highest quartile had higher odds of ACS [OR (95% CI), 3.18(1.85–5.54), p

Background: Contrast induced nephropathy (CIN) is a common complication in patients receiving intravascular contrast media. In 2020, the American College of Radiology and the National Kidney Foundation issued a new contrast induced acute kidney injury (CI-AKI) criteria. Therefore, we aimed to explore the potential risk factors for CIN under the new criteria, and develop a predictive model for patients with coronary artery disease (CAD) with relatively normal renal function (NRF).Methods: Patients undergoing coronary angiography or percutaneous coronary intervention at Zhongshan Hospital, Fudan University between May 2019 and April 2020 were consecutively enrolled. Eligible candidates were selected for statistical analysis. Univariate and multivariate logistic regression analyses were used to identify the predictive factors. A stepwise method and a machine learning (ML) method were used to construct a model based on the Akaike information criterion. The performance of our model was evaluated using the area under the receiver operating characteristic curves (AUC) and calibration curves. The model was further simplified into a risk score.Results: A total of 2,009 patients with complete information were included in the final statistical analysis. The results showed that the incidence of CIN was 3.2 and 1.2% under the old and new criteria, respectively. Three independent predictors were identified: baseline uric acid level, creatine kinase-MB level, and log (N-terminal pro-brain natriuretic peptide) level. Our stepwise model had an AUC of 0.816, which was higher than that of the ML model (AUC = 0.668, P = 0.09). The model also achieved accurate predictions regarding calibration. A risk score was then developed, and patients were divided into two risk groups: low risk (total score < 10) and high risk (total score ≥ 10).Conclusions: In this study, we first identified important predictors of CIN in patients with CAD with NRF. We then developed the first CI-AKI model on the basis of the new criteria, which exhibited accurate predictive performance. The simplified risk score may be useful in clinical practice to identify high-risk patients.

Background: Whether the role of plasma heat shock protein 70 (HSP70) in acute myocardial infarction (AMI) is protective or detrimental remains debated, and the relationship between HSP70 and total occlusion remains elusive.Methods: A total of 112 patients with primary diagnosis of AMI and 52 patients with chronic coronary syndrome (CCS) were enrolled into the study. Plasma HSP70 level was determined by ELISA on day 1 and day 7 after the onset of AMI and was examined before angiography in patients with CCS. Peak NT-proBNP, high-sensitivity C-reactive protein (CRP), troponin T (cTnT), and left ventricular ejection fraction were measured.Results: Plasma HSP70 was significantly higher in CCS than AMI (P < 0.0001), and it showed a significant decrease from day 1 to day 7 after AMI (P < 0.01). Elevated HSP70 was associated with decreased levels of LDL-C (P < 0.05), peak cTnT (R = −0.3578, P < 0.0001), peak NT-proBNP (R = −0.3583, P < 0.0001), and peak CRP (R = −0.3539, P < 0.0001) and a lower diagnosis of AMI (R = −0.4016, P < 0.0001) and STEMI (R = −0.3675, P < 0.0001), but a higher diagnosis of total occlusion in target vessels (R = 0.1702, P < 0.05). HSP70 may provide certain predictive value for the diagnosis of AMI, STEMI, and total occlusion in target vessels, and the area under the receiver operating characteristic curves were 0.7660, 0.7152, and 0.5984, respectively. HSP70 was also negatively associated with in-hospital stay (P < 0.001) and positively correlated with left ventricular ejection fraction (LVEF) at 1-year follow-up (P < 0.05), despite no association with in-hospital major adverse cardiovascular events (MACE).Conclusion: Plasma HSP70 level was found to decrease from day 1 to day 7 post-AMI, but the overall level of patients with AMI was lower than that of patients with CCS. However, the ability of HSP70 to identify clinically significant AMI and STEMI was moderate, and the predictive value to total occlusion was slight.

Objective: We aimed to assess the association of erectile dysfunction (ED) with the extent of coronary atherosclerosis, and to examine whether revascularization and medication use have an impact on ED status in patients with early onset of coronary artery disease (EOCAD).Methods: International Index of Erectile Function (IIEF-5) was used to evaluate sexual function in 296 male patients with EOCAD (age, 39.9 ± 4.8 years), and 354 male controls (age, 40.6 ± 4.4 years). The extent of coronary atherosclerosis was measured by Gensini score. Endothelial function was evaluated by two vasomotor indexes including endothelin-1 (ET-1) and nitric oxide (NO) by ELISA.Results: ED was more frequent (57.8 vs. 31.1%, P < 0.001) and serious (IIEF-5 score:17.7 ± 6.0 vs. 21.6 ± 5.0, P < 0.001) among EOCAD patients than that among controls. IIEF-5 score was negatively correlated with Gensini score (r = −0.383, P < 0.001). The adjusted odds ratio (OR) for the presence of ED (EOCAD vs. controls) was 1.88 [95% confidential interval (CI), 1.12-3.18]. However, ET-1 and NO attenuated the association between ED and EOCAD (adjusted OR: 1.54, 95% CI: 0.84-2.80). IIEF-5 score increased after coronary revascularization in patients not on beta-blockers (18.71 ± 4.84 vs. 17.59 ± 6.05, P < 0.001) as compared with baseline, while stayed unchanged in the subgroup using beta-blockers (17.82 ± 5.12 vs. 17.70 ± 5.98, P = 0.09).Conclusions: ED was common in patients with EOCAD, and associated with the severity of coronary atherosclerosis. Endothelial dysfunction may be a pathophysiologic mechanism underlying both ED and EOCAD. Coronary revascularization confers a benefit in ED amelioration, while this effect did not appear in patients using beta-blocker.

Abstract Background Primary percutaneous coronary intervention (PCI) for patients presenting with acute myocardial infarction (AMI) caused by left main coronary artery occlusion is associated with significantly higher mortality and risks of major adverse cardiovascular events. Deferred stent implantation may improve prognosis of primary PCI by reducing distal embolization and no-reflow phenomenon. There is no randomized clinical trial focusing on the effect and outcome of deferred stent implantation on primary PCI for left main coronary artery occlusion in contrast with conventional strategy. Methods The Optimal Strategy of Primary Percutaneous Coronary Intervention for Acute Myocardial Infarction due to Unprotected Left Main Coronary Artery Occlusion (OPTIMAL) study (ClinicalTrials.gov Identifier: NCT03282773) is an open-label, randomized, multicenter clinical trial in which 480 patients presenting with AMI caused by left main coronary artery occlusion recruited from 30 hospitals in mainland China will be randomly assigned 1:1 to immediate stenting or deferred stenting (scheduled 4–10 days after primary angioplasty) groups. The primary endpoint is a composite of all-cause mortality or recurrent myocardial infarction at 30 days after randomization. The secondary outcomes include all-cause mortality, cardiac death, recurrent myocardial infarction, and unplanned target vessel revascularization at 30 days, 6 months, and 12 months. Discussion The OPTIMAL study is designed to compare the clinical performance of deferred stenting with that of immediate stenting for AMI caused by left main coronary artery occlusion. Trial registration ClinicalTrials.gov Identifier: NCT03282773. Registered on 10 September 2017.

Abstract It has been reported that Cavin1 deficiency causes lipodystrophy in both humans and mice by affecting lipid metabolism. The ablation of Cavin1 in rodents also causes a significant deviation from Mendelian ratio at weaning in a background‐dependent manner, suggesting the presence of undiscovered functions of Cavin1. In the current study, the results show that Cavin1 deficiency causes neonatal death in C57BL/6J mice by dampening the storage and mobilization of glycogen in the liver, which leads to lethal neonatal hypoglycemia. Further investigation by electron microscopy reveals that Cavin1 deficiency impairs the fenestration in liver sinusoidal endothelial cells (LSECs) and impacts the permeability of endothelial barrier in the liver. Mechanistically, Cavin1 deficiency inhibits the RhoA‐Rho‐associated protein kinase 2‐LIM domain kinase‐Cofilin signaling pathway and suppresses the dynamics of the cytoskeleton, and eventually causes the reduction of fenestrae in LSECs. In addition, the defect of fenestration in LSECs caused by Cavin1 deficiency can be rescued by treatment with the F‐actin depolymerization reagent latrunculin A. In summary, the current study reveals a novel function of Cavin1 on fenestrae formation in LSECs and liver glycogen metabolism, which provide an explanation for the neonatal death of Cavin1 null mice and a potential mechanism for metabolic disorders in patients with Cavin1 mutation.

Introduction. Although coronary artery disease (CAD) presentations and clinical outcomes differ by sex, little is known about premature CAD (PCAD). The present analysis aimed to evaluate the gender-related differences of PCAD in an Asian population from the FOCUS registry. Methods. A total of 1397 Asian young patients with angiographically confirmed CAD undergoing drug-eluting stent implantation were included in this analysis and divided into two groups according to the genders. Patients were followed up for three years and clinical outcomes were compared between groups. Results. Young women were older and more likely to have hypertension and diabetes than men (all p0.05). Conclusion. Despite remarkable differences in clinical characteristics between Asian males and females with PCAD, the two groups did not differ significantly in clinical outcomes.

BACKGROUND: In the past decade, a number of cohort studies studies have been carried out to investigate the relationship between the insertion/deletion polymorphism of the gene encoding angiotensin-converting enzyme and risk of restenosis after percutaneous transluminal coronary angioplasties in patients. However, these studies have yielded contradictory results. Genetic association studies addressing this issue are frequently hampered by insufficient power. We therefore performed a meta-analysis of the published studies to clarify this inconsistency and to establish a comprehensive picture of the relationship between ACE I/D polymorphism and post-PTCA restenosis risk. METHODS: Databases including Pubmed, EMBASE, ISI Web of Science, EBSCO, Cochrane Library databases and CNKI were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. The random-effects model was applied, addressing heterogeneity and publication bias. RESULTS: A total of 33 cohort studies involving 11,099 subjects were included. In a combined analysis, the OR for post-PTCA restenosis of the ACE DD genotype was 1.61 (95% CI: 1.27-2.04; P

Traumatic brain injury (TBI) can induce intestinal inflammatory response and mucosal injury. Antioxidant transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) has been shown in our previous studies to prevent oxidative stress and inflammatory response in gut after TBI. The objective of this study was to test whether tert-butylhydroquinone (tBHQ), an Nrf2 inducer, can protect against TBI-induced intestinal inflammatory response and mucosal injury in mice. Adult male ICR mice were randomly divided into three groups: (1) sham + vehicle group, (2) TBI + vehicle group, and (3) TBI + tBHQ group (n=12 per group). Closed head injury was adopted using Hall's weight-dropping method. Intestinal mucosa apoptosis and inflammatory-related factors, such as nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1), were investigated at 24 h after TBI. As a result, we found that oral treatment with 1% tBHQ prior to TBI for one week markedly decreased NF-κB activation, inflammatory cytokines production, and ICAM-1 expression in the gut. Administration of tBHQ also significantly attenuated TBI-induced intestinal mucosal apoptosis. The results of the present study suggest that tBHQ administration could suppress the intestinal inflammation and reduce the mucosal damage following TBI.