Exploring changes in brain function in IBD patients using SPCCA: a study of simultaneous EEG-fMRI.

Research on functional changes in the brain of inflammatory bowel disease (IBD) patients is emerging around the world, which brings new perspectives to medical research. In this paper, the methods of canonical correlation analysis (CCA), kernel canonical correlation analysis (KCCA), and sparsity preserving canonical correlation analysis (SPCCA) were applied to the fusion of simultaneous EEG-fMRI data from 25 IBD patients and 15 healthy individuals. The CCA, KCCA and SPCCA fusion methods were used for data processing to compare the results obtained by the three methods. The results clearly show that there is a significant difference in the activation intensity between IBD and healthy control (HC), not only in the frontal lobe (p < 0.01) and temporal lobe (p < 0.01) regions, but also in the posterior cingulate gyrus (p < 0.01), gyrus rectus (p < 0.01), and amygdala (p < 0.01) regions, which are usually neglected. The mean difference in the SPCCA activation intensity was 60.1. However, the mean difference in activation intensity was only 36.9 and 49.8 by using CCA and KCCA. In addition, the correlation of the relevant components selected during the SPCCA calculation was high, with correlation components of up to 0.955; alternatively, the correlations obtained from CCA and KCCA calculations were only 0.917 and 0.926, respectively. It can be seen that SPCCA is indeed superior to CCA and KCCA in processing high-dimensional multimodal data. This work reveals the process of analyzing the brain activation state in IBD disease, provides a further perspective for the study of brain function, and opens up a new avenue for studying the SPCCA method and the change in the intensity of brain activation in IBD disease.

lncRNA JPX-Enriched Chromatin Microenvironment Mediates Vascular Smooth Muscle Cell Senescence and Promotes Atherosclerosis.

BACKGROUND: Senescence is a series of degenerative changes in the structure and physiological function of an organism. Whether JPX (just proximal to XIST)-a newly identified age-related noncoding RNA by us-is associated with atherosclerosis is still unknown. Our study was to investigate the role of JPX and provide insights into potential therapies targeting atherosclerosis. METHODS: We analyzed clinical data from multiple tissues including meniscus tissue, leukemia cells, and peripheral blood monocytes to identify age-related noncoding RNAs in senescent vascular smooth muscle cells (VSMCs). The molecular mechanism of JPX was investigated by capture hybridization analysis of RNA targets and chromatin immunoprecipitation. IGVTools and real-time quantitative polymerase chain reaction were used to evaluate the JPX expression during phenotype regulation in age-related disease models. The therapeutic potential of JPX was evaluated after establishing an atherosclerosis model in smooth muscle-specific Jpx knockout mice. RESULTS: JPX expression was upregulated in activated ras allele (H-rasV12)-induced senescent VSMCs and atherosclerotic arteries. JPX knockdown substantially reduced the elevation of senescence-associated secretory phenotype (SASP) genes in senescent VSMCs. Cytoplasmic DNA leaked from mitochondria via mitochondrial permeability transition pore formed by VDAC1 (voltage-dependent anion channel 1) oligomer activates the STING (stimulator of interferon gene) pathway. JPX could act as an enhancer for the SASP genes and functions as a scaffold molecule through interacting with phosphorylated p65/RelA and BRD4 (bromodomain-containing protein 4) in chromatin remodeling complex, promoting the transcription of SASP genes via epigenetic regulation. Smooth muscle knockout of Jpx in ApoeKO mice resulted in a decrease in plaque area, a reduction in SASP gene expression, and a decrease in senescence compared with controls. CONCLUSIONS: As an enhancer RNA, JPX can integrate p65 and BRD4 to form a chromatin remodeling complex, activating SASP gene transcription and promoting cellular senescence. These findings suggest that JPX is a potential therapeutic target for the treatment of age-related atherosclerosis.

Divergent total synthesis of the revised structures of marine anti-cancer meroterpenoids (+)-dysiherbols A-E.

We report here a concise and divergent enantioselective total synthesis of the revised structures of marine anti-cancer sesquiterpene hydroquinone meroterpenoids (+)-dysiherbols A-E (6-10) using dimethyl predysiherbol 14 as a key common intermediate. Two different improved syntheses of dimethyl predysiherbol 14 were elaborated, one starting from Wieland-Miescher ketone derivative 21, which is regio- and diastereoselectively α-benzylated prior to establishing the 6/6/5/6-fused tetracyclic core structure through intramolecular Heck reaction. The second approach exploits an enantioselective 1,4-addition and a Au-catalyzed double cyclization to build-up the core ring system. (+)-Dysiherbol A (6) was prepared from dimethyl predysiherbol 14via direct cyclization, while (+)-dysiherbol E (10) was synthesized through allylic oxidation and subsequent cyclization of 14. Epoxidation of 14 afforded allylic alcohol 45 or unexpectedly rearranged homoallylic alcohol 44. By inverting the configuration of the hydroxy groups, exploiting a reversible 1,2-methyl shift and selectively trapping one of the intermediate carbenium ions through oxy-cyclization, we succeeded to complete the total synthesis of (+)-dysiherbols B-D (7-9). The total synthesis of (+)-dysiherbols A-E (6-10) was accomplished in a divergent manner starting from dimethyl predysiherbol 14, which led to the revision of their originally proposed structures.

Real-world evaluation of the Stemoscope electronic tele-auscultation system.

BACKGROUND: With the spread of COVID-19, telemedicine has played an important role, but tele-auscultation is still unavailable in most countries. This study introduces and tests a tele-auscultation system (Stemoscope) and compares the concordance of the Stemoscope with the traditional stethoscope in the evaluation of heart murmurs. METHODS: A total of 57 patients with murmurs were recruited, and echocardiographs were performed. Three cardiologists were asked to correctly categorize heart sounds (both systolic murmur and diastolic murmur) as normal vs. abnormal with both the Stemoscope and a traditional acoustic stethoscope under different conditions. Firstly, we compared the in-person auscultation agreement between Stemoscope and the conventional acoustic stethoscope. Secondly, we compared tele-auscultation (recorded heart sounds) agreement between Stemoscope and acoustic results. Thirdly, we compared both the Stemoscope tele-auscultation results and traditional acoustic stethoscope in-person auscultation results with echocardiography. Finally, ten other cardiologists were asked to complete a qualitative questionnaire to assess their experience using the Stemoscope. RESULTS: For murmurs detection, the in-person auscultation agreement between Stemoscope and the acoustic stethoscope was 91% (p = 0.67). The agreement between Stemoscope tele-auscultation and the acoustic stethoscope in-person auscultation was 90% (p = 0.32). When using the echocardiographic findings as the reference, the agreement between Stemoscope (tele-auscultation) and the acoustic stethoscope (in-person auscultation) was 89% vs. 86% (p = 1.00). The system evaluated by ten cardiologists is considered easy to use, and most of them would consider using it in a telemedical setting. CONCLUSION: In-person auscultation and tele-auscultation by the Stemoscope are in good agreement with manual acoustic auscultation. The Stemoscope is a helpful heart murmur screening tool at a distance and can be used in telemedicine.

Autophagy enhanced by curcumin ameliorates inflammation in atherogenesis via the TFEB-P300-BRD4 axis.

Disturbance of macrophage-associated lipid metabolism plays a key role in atherosclerosis. Crosstalk between autophagy deficiency and inflammation response in foam cells (FCs) through epigenetic regulation is still poorly understood. Here, we demonstrate that in macrophages, oxidized low-density lipoprotein (ox-LDL) leads to abnormal crosstalk between autophagy and inflammation, thereby causing aberrant lipid metabolism mediated through a dysfunctional transcription factor EB (TFEB)-P300-bromodomain-containing protein 4 (BRD4) axis. ox-LDL led to macrophage autophagy deficiency along with TFEB cytoplasmic accumulation and increased reactive oxygen species generation. This activated P300 promoted BRD4 binding on the promoter regions of inflammatory genes, consequently contributing to inflammation with atherogenesis. Particularly, ox-LDL activated BRD4-dependent super-enhancer associated with liquid-liquid phase separation (LLPS) on the regulatory regions of inflammatory genes. Curcumin (Cur) prominently restored FCs autophagy by promoting TFEB nuclear translocation, optimizing lipid catabolism, and reducing inflammation. The consequences of P300 and BRD4 on super-enhancer formation and inflammatory response in FCs could be prevented by Cur. Furthermore, the anti-atherogenesis effect of Cur was inhibited by macrophage-specific Brd4 overexpression or Tfeb knock-out in Apoe knock-out mice via bone marrow transplantation. The findings identify a novel TFEB-P300-BRD4 axis and establish a new epigenetic paradigm by which Cur regulates autophagy, inhibits inflammation, and decreases lipid content.

Melatonin antagonizes ovarian aging via YTHDF2-MAPK-NF-κB pathway.

Cellular senescence is closely associated with age-related diseases. Ovarian aging, a special type of organ senescence, is the pathophysiological foundation of the diseases of the reproductive system. It is characterized by the loss of integrity of the surface epithelium and a gradual decrease in the number of human ovarian surface epithelial cells (HOSEpiCs). To contribute to the research on delaying ovarian aging, we aimed to investigate the novel epigenetic mechanism of melatonin in protecting HOSEpiCs. We discovered that melatonin has antagonistic effects against the oncogene-induced senescence (OIS) of HOSEpiCs. Mechanistically, the oncogene Ras decreased the expression of YTHDF2, which is the reader of RNA-m6A, by stimulating the generation of reactive oxygen species (ROS). Moreover, we found that the suppression of YTHDF2 increased the expression of MAP2K4 and MAP4K4 by enhancing the stability of the transcription of their mRNAs, thereby upregulating the expression of the senescence-associated secretory phenotype (SASP) through the activation of the MAP2K4 and MAP4K4-dependent nuclear factor-κB (NF-κB) signaling pathways. We further determined that melatonin has antagonistic effects against the OIS of HOSEpiCs by inhibiting the ROS-YTHDF2-MAPK-NF-κB pathway. These findings provide key insights into the potential avenues for preventing and treating ovarian aging.

Single-shot imaging through scattering media under strong ambient light interference.

Speckle correlation imaging (SCI) has found tremendous versatility compared with other scattering imaging approaches due to its single-shot data acquisition strategy, relatively simple optical setup, and high-fidelity reconstruction performance. However, this simplicity requires SCI experiments to be performed strictly in a darkroom condition. As background noise increases, the speckle contrast rapidly decreases, making precise interpretation of the data extremely difficult. Here, we demonstrate a method by refining the speckle in the autocorrelation domain to achieve high-performance single-shot imaging. Experiment results prove that our method is adapted to estimate objects in a low signal-to-background ratio (SBR) circumstance even if the SBR is about -23dB. Laboratory and outdoor SCI experiments are performed.

PM2.5 induces endothelial dysfunction via activating NLRP3 inflammasome.

PM2.5 (particulate matter <2.5 µm in diameter) is proven to contribute to the development of atherosclerosis. Endothelial cell dysfunction is the initial step of atherosclerosis. The underlying mechanisms of endothelial cell damage exposed to PM2.5 are still obscure. In our study, PM2.5 was administrated to C57BL/6 male mice by intranasal instillation for 2 weeks. Human umbilical vein endothelial cells (HUVECs) were also treated with PM2.5 to evaluate the adverse effect in vitro. The immunohistochemical staining of aortas showed that the expressions of proinflammatory cytokines and endothelial adhesion markers were significantly increased in PM2.5-exposed mice than that in saline-exposed mice. In vitro, PM2.5 could inhibit HUVECs viability and impair cell migration in a concentration-dependent manner. Besides, PM2.5 exposure downregulated eNOS expression while upregulated reactive oxygen species (ROS) levels. Mechanistically, PM2.5 activated the NLRP3 inflammasome in HUVECs while knockdown of NLRP3 could effectively reverse the downregulation of eNOS expression and production of ROS after PM2.5 exposure. In summary, our data showed that PM2.5 could cause endothelial dysfunction, and probably via NLRP3 inflammasome activation.

Total Synthesis of Anti-Cancer Meroterpenoids Dysideanone†B and Dysiherbol†A and Structural Reassignment of Dysiherbol†A.

The first total synthesis of marine anti-cancer meroterpenoids dysideanone B and dysiherbol A have been accomplished in a divergent way. The synthetic route features: 1) a site and stereoselective α-position alkylation of a Wieland-Miescher ketone derivative with a bulky benzyl bromide to join the terpene and aromatic moieties together and set the stage for subsequent cyclization reactions; 2) an intramolecular radical cyclization to construct the 6/6/6/6-tetracycle of dysideanone B and an intramolecular Heck reaction to forge the 6/6/5/6-fused core structure of dysiherbol A. A late-stage introduction of the ethoxy group in dysideanone B reveals that this group might come from the solvent ethanol. The structure of dysiherbol A has been revised based on our chemical total synthesis.

Lung Auscultation of Hospitalized Patients with SARS-CoV-2 Pneumonia via a Wireless Stethoscope.

Objective: SARS-CoV-2 (originally named COVID-2019) pneumonia is currently prevalent worldwide. The number of cases has increased rapidly but the auscultatory characteristics of affected patients and how to use it to predict who is most likely to survive or die are not available. This study aims to describe the auscultatory characteristics and its clinical relativity of SARS-CoV-2 pneumonia by using a wireless stethoscope. Material and methods: A cross-sectional, observational, single-center case series of 30 consecutive hospitalized patients with confirmed SARS-CoV-2 pneumonia at Leishenshan Hospital in Wuhan, China, were enrolled from March 9 to April 5, 2020. Clinical, laboratory, radiological, treatment data and lung auscultation were collected and analyzed. Lung auscultation was acquired by a wireless electronic stethoscope. Auscultatory characteristics of the moderate, severe, and critically ill patients were compared. Results: Kinds of crackles including fine crackles and wheezing were heard and recorded in these patients. Velcro crackles were heard in most critically ill patients (6/10). Besides, patients with Velcro crackles were all dead (6/6). There was no positive lung auscultatory finding in the moderate group and little positive lung auscultatory findings (4/10) in the severe group. Conclusion: Velcro crackles can be auscultated by this newly designed electronic wireless stethoscope in most critically ill patients infected by SARS-CoV-2 and predicts a poor prognosis. Moderate and severe patients without positive auscultatory findings may have a better prognosis.

Correction to: MicroRNA-325-3p protects the heart after myocardial infarction by inhibiting RIPK3 and programmed necrosis in mice.

The original article [1] contains an error whereby Fig. 7 displays incorrect results; the correct version of Fig. 7 can be viewed ahead in this Correction article and should be considered in place of the original article's version of Fig. 7.

MicroRNA-325-3p protects the heart after myocardial infarction by inhibiting RIPK3 and programmed necrosis in mice.

BACKGROUND: Receptor-interacting serine-threonine kinase 3 (RIPK3)-mediated necroptosis has been implicated in the progression of myocardial infarction (MI), but the underlying mechanisms, particularly whether microRNAs (miRNAs) are involved, remain largely unknown. RESULTS: A microarray analysis was used to screen for miR-325-3p expression in myocardial tissues from MI mice, and the expression was confirmed with qRT-PCR. The levels of myocardial enzymes were measured using commercial kits, and an echocardiography system was utilized for the detection of cardiac function parameters. The pathological features and infarction sizes of cardiac tissues were examined using H&E, TCC and Masson's trichrome staining, and the amount of cell apoptosis was determined using an in situ TUNEL assay. Cardiomyocytes were isolated and then subjected to hypoxia induction in vitro. The expression of the RIPK1, RIPK3 and phosphorylated MLKL (p-MLKL) proteins was measured using a Western blot. The mouse cardiomyocyte cell viability was analyzed by an MTT assay. The mRNA target of miR-325-3p was predicted using TargetScan v7.2 and then validated using a dual-luciferase reporter assay. The overexpression of miR-325-3p evidently decreased the expression levels of lactate dehydrogenase (LDH), phosphocreatine kinase (CK), superoxide dismutase (SOD) and malondialdehyde (MDA), inhibited left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD), and promoted left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVES). In addition, miR-325-3p overexpression attenuated the degree of injury to the cardiac tissue, decreased the infarct sizes and downregulated the expression of the necrosis-related proteins RIPK1, RIPK3 and p-MLKL. CONCLUSIONS: The RIPK1/RIPK3/p-MLKL axis-induced necroptosis that occurred during MI was mediated by a miRNA module, miR-325-3p, which can effectively ameliorate the symptoms of MI by suppressing the expression of RIPK3.

PM2.5 promotes plaque vulnerability at different stages of atherosclerosis and the formation of foam cells via TLR4/MyD88/NFκB pathway.

Clinical evidence has shown an elevated myocardial infarction (MI) risk after PM2.5 (particulate matter < 2.5 µm) exposure. Incident MI may result from rupture of vulnerable plaques. To test whether PM2.5 could promote plaque vulnerability, we exposed PM2.5 to apoe-/- mice by intranasal instillation. We detected the lipid, collagen, macrophage and smooth muscle cells (SMCs) content, and fibrous cap thickness to evaluate the plaque vulnerability. Plaques in HFD-fed mice with PM2.5 treatment for 24 weeks had increased lipid content and macrophage recruitment, and reduced collagen content, fibrous cap thickness and SMCs infiltration. Besides, 4-week exposure to PM2.5 could reduce the fibrous cap thickness, collagen content, but increase the macrophage infiltration and SMCs loss in a rapid atherosclerosis model. In existing plaques, PM2.5 could also decrease the fibrous cap thickness, collagen content. In RAW264.7, PM2.5 could promote the transformation of macrophage into foam cells. The expression of TLR4/MyD88/NFκB and CD36 were upregulated by PM2.5 treatment. Besides, the expression of CD36 promoted by PM2.5 was downregulated by the TLR4 inhibitor or MyD88/NFκB SiRNA. In conclusion, our data indicated that short- and long-term PM2.5 exposure increased plaque vulnerability. The underlying mechanism might be the PM2.5-enhanced formation of foam cells via TLR4/MyD88/NFκB pathway.

lncRNA HOTAIR Protects Myocardial Infarction Rat by Sponging miR-519d-3p.

Myocardial infarction (MI) is a cardiovascular disease with high morbidity and mortality. In this study, we focused on exploring the roles and underlying regulatory mechanisms of Hox transcript antisense intergenic RNA (HOTAIR) and miR-519d-3p in myocardial infarction. To comprehensively understand the role of microRNA in MI rat, we construct MI rat model by permanent ligation of the left anterior descending (LAD) coronary artery. Cardiac troponin I and creatine kinase-MB concentration measured by ELISA and infract size of heart section analyzed by TTC staining were served as evaluation indicators to confirmed the established model. Based on the bioinformatics assay and qRT-PCR, we found that the expression of miR-519d-3p was upregulated remarkably. Dual-luciferase reporter assays were performed to investigate the interaction of lncRNA HOTAIR and miR-519d-3p. In order to investigate the potential mechanism of lncRNA HOTAIR and miR-519d-3p, flow cytometry was applied to measure apoptotic cardiomyocytes and western blot was used to detect expressions of apoptotic related protein Bax, Bcl-2, and caspase-3 in cardiomyocytes in vitro and myocardial infraction in vivo. Downregulating miR-519d-3p or overexpressing HOTAIR alleviated MI or hypoxia-induced cardiomyocytes apoptosis. Taken together, our results showed that the interaction of miR-519d-3p and HOTAIR can protect MI and hypoxia-induced cardiomyocytes apoptosis, providing the potential therapeutic target for MI treatment.

Berberine treatment reduces atherosclerosis by mediating gut microbiota in apoE-/- mice.

BACKGROUND: Berberine (BBR) has long been used for treating bacterial diarrhea due to its antimicrobial effect and is currently used to treat obesity, diabetes, hyperlipemia and atherosclerosis. Given the poor oral bioavailability of BBR, the mechanisms through which BBR mediates metabolic disorders are not well understood. The present study was designed to explore the role of BBR-induced gut microbiota modulation in the development of atherosclerosis. METHODS: Male apoE-/- mice were fed a high-fat diet (HFD) with or without the intragastric administration of BBR. Because mice are coprophagic and can transfer their gut microbiota to each other, we cohoused BBR-treated HFD-mice with non-BBR-treated HFD-fed mice. RESULTS: After 12 weeks of HFD feeding, compared with non-BBR-treated HFD-fed mice, BBR-treated HFD-fed mice exhibited a significant reduction in both atherosclerosis development and inflammatory cytokine expression. In addition, cohousing BBR-treated HFD-fed mice with non-BBR-treated HFD-fed mice decreased atherosclerosis development and inflammatory cytokine expression. The denaturing gradient gel electrophoresis and principal component analyses showed that the gut microbial profiles of BBR-treated HFD-fed mice were significantly different from those of HFD-fed mice but were similar to those of cohoused mice. The abundances ofFirmicutes and Verrucomicrobia in cohoused and BBR-treated mice were different from those in HFD-fed and normal chow-fed mice. Moreover, BBR reduced hepatic FMO3 expression and serum trimethylamine N-oxide levels. CONCLUSION: The antiatherosclerotic effect of BBR is related to alterations in gut microbiota compositions, indicating the potential therapeutic value of pharmacological approaches that may modulate the gut microbiota in treating atherosclerosis.

Clinical effect of selective interventional therapy on sub-acute ST-segment elevation myocardial infarction under the guidance of fractional flow reserve and coronary arteriography.

OBJECTIVE: This study aims to compare the clinical effects of selective interventional therapy (PCI) under the guidance of fractional flow reserve (FFR) and coronary arteriography. METHODS: Patients with sub-acute ST-segment elevation myocardial infarction (sub-acute STEMI), who were under selective PCI treatment between April 2012 and June 2014, were included into this study. These patients were divided into two groups, based on FFR measurements: FFR-PCI group and radiography-PCI group. Then, differences in clinical symptoms, coronary angiography, intervention, and endpoint events were compared between these two groups. RESULTS: A total of 592 patients with sub-acute STEMI were included in this study (207 patients in the FFR-PCI group and 385 patients in the radiography-PCI group). No statistical differences were observed in baseline clinical data and coronary angiography results between these two groups. Mean stent number was greater in the radiography-PCI group (1.22 ± 0.32) than in the FFR-PCI group (1.10 ± 0.29), and the difference was statistically significant (P = 0.019). During the follow-up period, 78 adverse events occurred (21 adverse events in the FFR-PCI group and 57 adverse events in the radiography-PCI group); and no statistical significance was observed between these two groups (log-rank P = 0.112). CONCLUSION: Selective PCI treatment in patients with sub-acute STEMI under FFR acquired similar effects, compared to PCI treatment under the guidance of radiography, which can reduce the mean stent number.

Polymorphism in the promoter region of lncRNA GAS5 is functionally associated with the risk of gastric cancer.

BACKGROUND AND AIMS: Previous studies showed that down-regulation of GAS5 was involved in the development of gastric cancer (GC). However, the regulatory mechanism of down-expressed GAS5 in GC remains obscure. We aimed to investigate the role of rs145204276 of GAS5 in the development and metastasis process of GC. METHODS: 853 GC patients and 954 healthy controls were recruited. The variant rs145204276 was genotyped and the Chi2 test was used to compare the frequency of the genotype and the allele between the patients and the controls. Odds ratio (OR) and 95% confidence intervals (95% CIs) were calculated to estimate the association of rs145204276 with the risk of development and metastasis of GC. RESULTS: Patients were found to have significantly lower rate of genotype del/del than the controls (7.2% vs. 8.9%, P=0.016). The allele del was significantly associated with a decreased risk of GC (26.4% vs. 30.7%, P=0.005) with an OR of 0.81 (95% CI=0.70-0.94). Patients with allele del were less likely to develop lymph node metastasis (P=0.01), with an OR of 0.75 (95% CI=0.60-0.93). Comparably, rs145204276 was also significantly associated with a decreased risk of distant metastasis of GC (P=0.007; OR=0.55). CONCLUSION: We confirmed that rs145204276 of GAS5 is a functional variant associated with the susceptibility and metastasis of GC. It plays a protective role in the development of GC possibly through the regulation of GAS5.

Trimethylamine N-oxide promotes atherosclerosis via CD36-dependent MAPK/JNK pathway.

BACKGROUND: Many studies have identified trimethylamine N-oxide (TMAO) as a new risk factor of cardiovascular diseases. It has been suggested that TMAO promotes atherosclerosis development. However, the underlying mechanism is still unclear. METHODS: Apoe-/- mice were fed a high-fat diet and given water with or without TMAO for 8-week. Histological and immunohistological analyses were used to evaluate the atherogenic effect of TMAO in vivo. We also employed peritoneal elicited macrophages and RAW264.7 to assess the role of MAPK/JNK pathway in TMAO-induced formation of foam cells. RESULTS: TMAO significantly promoted plaque progression in apoe-/- mice fed with high-fat diet for 8 weeks. Besides, macrophage recruitment, CD36 and proinflammatory cytokine expressions were enhanced by TMAO in plaque lesions. In vitro, TMAO increased the macrophage migration and the expression of TNF-α, IL-6 and ICAM1. In addition, CD36 expression and foam cell formation induced by ox-LDL were also enhanced by TMAO, which could be attenuated by siRNA-mediated knockdown of CD36. We additionally used MAPK inhibitor (SB230580) and JNK inhibitor (SP600125) to assess the MAPK/JNK pathway in TMAO-induced CD36 expression. Western blotting showed that both SB230580 and SP600125 could reduce the expression of CD36 induced by ox-LDL and TMAO. Moreover, SB230580 and SP600125 could also reduce the formation of foam cells. CONCLUSIONS: TMAO promotes the atherosclerosis in vivo and in vitro.CD36/MAPK/JNK pathway may play a crucial role in TMAO-induced formation of foam cells.

Restoration of motor function after operative reconstruction of the acutely transected spinal cord in the canine model.

BACKGROUND: Cephalosomatic anastomosis or what has been called a "head transplantation" requires full reconnection of the respective transected ends of the spinal cords. The GEMINI spinal cord fusion protocol has been developed for this reason. Here, we report the first randomized, controlled study of the GEMINI protocol in large animals. METHODS: We conducted a randomized, controlled study of a complete transection of the spinal cord at the level of T10 in dogs at Harbin Medical University, Harbin, China. These dogs were followed for up to 8 weeks postoperatively by assessments of recovery of motor function, somato-sensory evoked potentials, and diffusion tensor imaging using magnetic resonance imaging. RESULTS: A total of 12 dogs were subjected to operative exposure of the dorsal aspect of the spinal cord after laminectomy and longitudinal durotomy followed by a very sharp, controlled, full-thickness, complete transection of the spinal cord at T10. The fusogen, polyethylene glycol, was applied topically to the site of the spinal cord transection in 7 of 12 dogs; 0.9% NaCl saline was applied to the site of transection in the remaining 5 control dogs. Dogs were selected randomly to receive polyethylene glycol or saline. All polyethylene glycol-treated dogs reacquired a substantial amount of motor function versus none in controls over these first 2 months as assessed on the 20-point (0-19), canine, Basso-Beattie-Bresnahan rating scale (P<.006). Somatosensory evoked potentials confirmed restoration of electrical conduction cranially across the site of spinal cord transection which improved over time. Diffusion tensor imaging, a magnetic resonance permutation that assesses the integrity of nerve fibers and cells, showed restitution of the transected spinal cord with polyethylene glycol treatment (at-injury level difference: P<.02). CONCLUSION: A sharply and fully transected spinal cord at the level of T10 can be reconstructed with restoration of many aspects of electrical continuity in large animals following the GEMINI spinal cord fusion protocol, with objective evidence of motor recovery and of electrical continuity across the site of transection, opening the way to the first cephalosomatic anastomosis. (Surgery 2017;160:XXX-XXX.).

Catheter ablation versus rate control in patients with atrial fibrillation and heart failure: A multicenter study.

Many trials have shown improvements in left ventricular function, exercise capacity, and quality of life after catheter ablation (CA) of atrial fibrillation (AF) in patients with heart failure (HF). We sought to evaluate the impact of CA on hard outcomes in a retrospective cohort study. AF patients with symptomatic HF from 3 hospitals were included. Our primary endpoint was major adverse cardiac events (MACEs), a composite of all-cause mortality, stroke, and unplanned hospitalization. In total, 90 patients underwent CA and 304 ones received rate control (RaC) were included. After a mean follow-up of 13.5 ±â€Š5.3 months, 82.2% of patients in CA group got freedom from AF; all patients in RaC group remained in AF. CA group had a significant decreased risk of MACEs compared with RaC group (13.3% vs 29.3%, hazard ratio [HR] 0.51, 95% confidence interval [CI]: 0.32-0.82, P = .005). After propensity score matched for confounding factors, difference in MACEs remained significant between groups (13.3% vs 25.6%, HR 0.50, 95% CI: 0.26-0.98, P = .044). Multivariate regression analysis also indicated that CA was significantly associated with a lower risk of MACEs in overall cohort (HR 0.486, 95% CI: 0.253-0.933, P = .030) and in propensity-matched cohort (HR 0.482, 95% CI: 0.235-0.985, P = .045). Besides, age and NYHA class were associated with an increased risk of MACEs. In conclusion, the present study demonstrated that CA for AF in HF patients could reduce the risk of MACEs in a mid-term follow-up. Thus, CA may be a reasonable option for this population.