The relationship between leukocyte to albumin ratio and atrial fibrillation severity.

BACKGROUND: An increased leukocyte count is a sign of inflammation and has been demonstrated to be a predisposing factor and complication of atrial fibrillation. Similarly, albumin, the major protein in the serum, is also considered an acute phase reactant protein that has osmotic and anti-inflammatory properties, and a low albumin level is a known factor associated with severity in many pathologies, including atrial fibrillation. The neutrophil percentage-to-albumin ratio (NPAR) and other emerging leukocyte counts/albumin ratios have been reliable systemic inflammation-based predictors of mortality and complications in various diseases, but they have not yet been used with atrial fibrillation. This study's aim was to explore whether the leukocyte to albumin ratio could also serve as a useful index in estimating atrial fibrillation severity, including the severity of atrial fibrillation secondary to stroke, to provide a new and more objective tool than the conventional and medical history-based CHA2DS2-VASc score. MATERIALS AND METHODS: Data were retrospectively collected from the Wuhan University Zhongnan Hospital database from January 1st to December 31st, 2021. The patients were classified into 2 groups: Group 1-low severity and Group 2- moderate to high severity, and diverse statistical analyses were conducted to evaluate the relationship between the leukocyte-to-albumin ratio and AF severity. RESULTS: Only 2329 test subjects met the inclusion criteria. We had 727 test subjects (381 males and 346 females) categorized into the low severity cohort and 1601 test subjects (932 males and 670 females) in the moderate to high severity group. The difference in mean age between the two groups was significant (95% CI [-2.682 to -0.154] p = 0.028), and the difference in the LAR mean rank between the two groups was significant (p = 0.00). The Chi-square test of association yielded the following results: the relationship between the LAR level and category of severity was statistically significant (p = 0.00), and the Mantel‒Haenszel statistic association odds ratio was OR = 0.657. 95% CI OR [0.549-0.787] p = 0.000. The association between sex and atrial fibrillation severity also reached statistical significance. However, sex and LAR were found to be independent factors in atrial fibrillation (Chi-square p value = 0.564). CONCLUSION: It has been demonstrated throughout this investigation that the leukocyte to albumin ratio could provide key clues in clinical practice and contribute to thromboembolism risk assessment in the setting of atrial fibrillation.

Catheter ablation of ventricular arrhythmias originating from the para-Hisian region with reversed C-curve technique.

AIMS: Ventricular arrhythmias (VAs) originating from the para-Hisian region represent a challenging location. The long-term success rate of catheter ablation above the septal leaflet of the tricuspid valve is not ideal. This study aimed to investigate the safety and efficacy of catheter ablation for para-Hisian VAs via a direct approach under the septal valve with reversed C-curve technique. METHODS AND RESULTS: Twenty-five consecutive patients with para-Hisian VAs were included. Systematic mapping was performed in the right ventricle septum, including both the regions above and under the septal valve. Radiofrequency (RF) ablation was preferentially performed under the valve with reversed C-curve technique in all patients. If the ablation failed under the valve, it was then performed above the valve and even in aortic sinus cusps. The earliest ventricular activation preceding surface QRS (V-QRS) under the valve was significantly larger than that above the valve (34.8 ± 5.3 vs 27.8 ± 5.7 ms, P < .01). RF ablation under the valve with reversed C-curve technique achieved acute success in 22 of 25 (88%) patients. Junctional rhythm developed during ablation in 3 of 25 (12%) patients and no atrioventricular block occurred. In the remaining three patients, RF application above the valve failed to eliminate the VAs and one of them achieved successful ablation in the right coronary cusp. During a mean follow-up of 17.8 ± 9.4 months, no patients presented with VAs recurrence and no postprocedure complications occurred. CONCLUSIONS: Catheter ablation under the valve with reversed C-curve technique shows to be effective and safe for para-Hisian VAs.

Clinical Features of Post Cardiac Injury Syndrome Following Catheter Ablation of Arrhythmias: Systematic Review and Additional Cases.

BACKGROUND: Post cardiac injury syndrome (PCIS) is a troublesome but not uncommon complication following catheter ablation of arrhythmias. We aimed to study the clinical features of ablation-associated PCIS. METHODS: For this purpose, we conducted a computerised literature search that identified 19 published cases, and we additionally included another two new cases from our centres. Twenty-one (21) cases of PCIS following ablation were analysed. RESULTS: Among the 21 cases, PCIS most commonly occurred after atrial flutter/fibrillation (AFL/AF) ablation (71.4%), followed by atrioventricular re-entrant tachycardia (AVRT) ablation (9.5%), atrioventricular node (AVN) ablation (9.5%), atrioventricular nodal re-entrant tachycardia (AVNRT) ablation (4.8%) and ventricular tachycardia (VT) ablation (4.8%). Thirty-eight (38) per cent of PCIS was suggested to be secondary to cardiac perforation. Specific symptoms or features include pleuritic chest pain (76.2%), fever (76.2%), elevated markers of inflammation (76.2%), pericardial effusion (90.5%), pleural effusion (71.4%) and pulmonary infiltrates (28.6%). Interestingly, all the six cases with pulmonary infiltrates were following AFL/AF ablation (6/15, 40%). Serious clinical manifestations include cardiac tamponade, massive pleural effusion with hypoalbuminaemia and hyponatraemia, and massive pulmonary infiltrates with hypoxaemia. Notably, empiric antibiotic therapy was used in seven cases including five with pulmonary infiltrates but failed to work. No mortality occurred during a mean follow-up of 4.1±5.3 (1 to 19) months. CONCLUSIONS: Catheter ablation of AFL/AF was most commonly involved in ablation-associated PCIS. Pulmonary infiltrate is an important feature of PCIS following AFL/AF ablation and may be misdiagnosed as pneumonia. Although PCIS is troublesome and even dangerous, it does carry a benign prognosis.

Perioperative Use of Levosimendan Improves Clinical Outcomes in Patients After Cardiac Surgery: A Systematic Review and Meta-Analysis.

Severe postoperative complications can affect cardiac surgery patients. Levosimendan is a novel calcium sensitizer commonly administered after cardiac surgery. However, the patient benefits are controversial. PubMed, Embase, and the Cochrane library were systematically searched for randomized controlled trials comparing levosimendan with control in adult cardiac surgery patients. Twenty-five studies (3247 patients) were included. Pooled data indicated that levosimendan reduced mortality after cardiac surgery [odds ratio (OR) 0.63, 95% confidence interval (CI): 0.47-0.84, P = 0.001]. However, this reduction was restricted to patients with low (<50%) left ventricular ejection fraction (OR 0.49, 95% CI: 0.35-0.70, P = 0.0001). It significantly reduced the incidence of postoperative acute kidney injury (OR 0.55, 95% CI: 0.41-0.74, P < 0.0001) and renal replacement therapy use (OR 0.56, 95% CI: 0.39-0.80, P = 0.002). Moreover, levosimendan significantly shortened the duration of the intensive care unit stay (weighted mean differences -0.49 day, 95% CI: -0.75 to -0.24, P = 0.0002) and mechanical ventilation use (weighted mean differences -2.30 hours, 95% CI: -3.76 to -0.84, P = 0.002). In conclusion, levosimendan reduced the mortality in patients with low left ventricular ejection fraction and decreased the incidence of acute renal injury and renal replacement therapy use. In addition, it shortened the duration of the intensive care unit stay and mechanical ventilation use.

De novo characterization of the Iris lactea var. chinensis transcriptome and an analysis of genes under cadmium or lead exposure.

Iris lactea var. chinensis (I. lactea var. chinensis) is tolerant to accumulations of cadmium (Cd) and lead (Pb). In this study, the transcriptome of I. lactea var. chinensis was investigated under Cd or Pb stresses. Using the gene ontology database, 31,974 unigenes were classified into biological process, cellular component and molecular function. In total, 13,132 unigenes were involved in enriched Encyclopedia of Genes and Genomes (KEGG) metabolic pathways, and the expression levels of 5904 unigenes were significantly changed after exposure to Cd or Pb stresses. Of these, 974 were co-up-regulated and 1281 were co-down-regulated under the two stresses. The transcriptome expression profiles of I. lactea var. chinensis under Cd or Pb stresses obtained in this study provided a resource for identifying common mechanisms in the detoxification of different heavy metals. Furthermore, the identified unigenes may be used for the genetic breeding of heavy-metal tolerant plants.

Docosahexaenoic Acid Attenuates Doxorubicin-induced Cytotoxicity and Inflammation by Suppressing NF-κB/iNOS/NO Signaling Pathway Activation in H9C2 Cardiac Cells.

Doxorubicin (DOX) is a widely used antineoplastic agent for a variety of carcinomas. However, it is cardiotoxic and leads to cardiomyopathy. Previous studies have indicated that omega-3 polyunsaturated acids (ω-3 PUFAs) have therapeutic effects on dilated and diabetic cardiomyopathies. However, whether ω-3 PUFAs exert therapeutic effects on DOX-induced cardiomyopathy remains unclear. In this study, we explored the effect and underlying mechanisms of docosahexaenoic acid (DHA), an important type of ω-3 PUFA, on DOX-induced cardiotoxicity and inflammation. H9C2 cardiac cells were exposed to DOX (5 µM) and interfered with by DHA (10 µM) for 4 hours. The effect of DHA on H9C2 cell viability was measured by Cell Counting Kit-8 assay. The levels of mRNA and protein expression of inflammatory cytokines were determined by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Reactive oxygen species and nitric oxide (NO) levels were determined by corresponding kits. The protein expression of key molecules in the nuclear factor-kappa B/inducible isoform of nitric oxide synthase/nitric oxide (NF-κB/iNOS/NO) signaling pathway was determined by western blotting. DOX-induced significant cytotoxicity and reactive oxygen species production in H9C2 cardiac cells. It also induced cardiac inflammation as evidenced by significantly increased expressions of inflammatory cytokines, including tumor necrosis factor-α, interleukin-6, interleukin-1ß, monocyte chemoattractant protein-1, and inducible isoform of NO synthase. However, DHA effectively attenuated DOX-induced cytotoxicity and inflammation. A further mechanistic study revealed that DHA suppressed DOX-induced activation of the NF-κB/iNOS/NO signaling pathway in H9C2 cells. Our results indicate that DHA may protect against DOX-induced cardiotoxicity by inhibiting NF-κB/iNOS/NO signaling pathway activation.

Effects of ginseng-spikenard heart-nourishing capsule on inactivation of C-type Kv1.4 potassium channel.

This research is to explore the effects of traditional Chinese medicine Ginseng-spikenard heart-nourishing capsule on the inactivation of c-type Kv1.4 channels (Kv1.4∆N) in Xenopus laevis oocytes with two-electrode voltageclamp technique. Defolliculated oocytes (stage V-VI) were injected with transcribed cRNAs of ferret Kv1.4δN channels. During recording, oocytes were continuously perfused with ND96 solution (control group) and solution prepared from Ginseng-spikenard heart-nourishing capsule (experimental group). Results found that, at the command potential of +50 mV, the current of experimental group was reduced to 48.33±4.0% of that in control group. The inactivation time constants in control and experimental groups were 2962.56±175.35 ms and 304.13±36.22ms, respectively (P<0.05, n=7). The recovery time of fKv1.4∆N channel after inactivation in control group and experimental groups was 987±68.39 ms and 1734.15±98.45 ms, respectively (P<0.05, n=5). Ginseng-spikenard heart-nourishing capsule can inhibit the Kv1.4δN channel, which may be one of the mechanisms of underlying antiarrhythmia.

Overexpression of microRNA-133a inhibits ischemia-reperfusion-induced cardiomyocyte apoptosis by targeting DAPK2.

To examine microRNA-133a (miR-133a) endogenous expression in cardiomyocytes after ischemia-reperfusion (I/R) injury and study the effects of miR-133a overexpression on I/R injury-induced cardiomyocyte apoptosis. Dual-Luciferase Reporter Assay detected dynamic expression of miR-133a. In an in vitro hypoxia-reoxygenation (HR) injury model and an in vivo rat model of I/R injury, rat cardiomyocytes were transfected with miR-133a mimic to test the effects of miR-133a overexpression on apoptosis. MiR-133a and Death Associated Protein Kinase 2 (DAPK2) mRNA expression was measured using real-time-PCR, and DAPK2 protein expression was detected by western blotting. Annexin V-fluorescein isothiocyanate/propidium iodide (PI) double-staining measured the apoptosis rate in H9C2 cells and transferase dUTP nick end labeling assay quantified the cardiomyocyte apoptosis rate in tissues obtained from in vivo the rat model. DAPK2 is a target of miR-133a. Both in vitro and in vivo results confirmed that after expression of miR-133a mimics, miR-133a levels increased, which was accompanied by decrease in DAPK2 mRNA and protein expression. In H9C2 cells, HR injury caused a sharp decrease in miR-133a expression and a significant upregualtion of DAPK2 mRNA and protein levels. However, exogenous miR-133a expression led to a significant reduction in DAPK2 mRNA and protein levels despite HR injury. Similar results were obtained from in vivo I/R injury model. After HR injury or I/R injury the apoptosis rate of myocardial cells was highly elevated and decreased significantly only after transfection of miR-133a into cardiomyocytes. MiR-133a overexpression may inhibit I/R injury-mediated cardiomyocyte apoptosis by targeting DAPK2, leading to reduced DAPK2 protein, thus miR-133a may potentially have a high therapeutic value in I/R injury.

Digoxin Is Associated With Increased All-cause Mortality in Patients With Atrial Fibrillation Regardless of Concomitant Heart Failure: A Meta-analysis.

For decades, digoxin has been widely used to control ventricular rate in atrial fibrillation (AF). However, it remains controversial as to whether digoxin is associated with increased mortality in AF. In this study, we searched relevant studies that were published before December 1, 2014, in PubMed, EMBASE, and the Cochrane central databases. We systematically reviewed the references and performed a meta-analysis of 8 carefully selected studies with 302,738 patients who were included for the final analysis. It was shown that digoxin use was associated with increased risk of all-cause mortality in AF overall [hazard ratio (HR) = 1.375, 95% confidence intervals (CI), 1.201-1.574, P = 0.0001]. Subgroup analysis further revealed that digoxin was associated with increased all-cause mortality in patients with AF, which was complicated by heart failure (HF) (HR = 1.201, CI, 1.074- 1.344, P = 0.001), and in those subjects without HF (HR = 1.172, CI, 1.148-1.198, P = 0.0001). Sensitivity analyses found results to be robust. Our findings indicated that digoxin use was associated with significantly increased all-cause mortality in patients with AF regardless of concomitant HF. We suggest that digoxin should not be preferentially used over other rate control medications in AF.

Pharmacogenetics-based warfarin dosing algorithm decreases time to stable anticoagulation and the risk of major hemorrhage: an updated meta-analysis of randomized controlled trials.

Warfarin is yet the most widely used oral anticoagulant for thromboembolic diseases, despite the recently emerged novel anticoagulants. However, difficulty in maintaining stable dose within the therapeutic range and subsequent serious adverse effects markedly limited its use in clinical practice. Pharmacogenetics-based warfarin dosing algorithm is a recently emerged strategy to predict the initial and maintaining dose of warfarin. However, whether this algorithm is superior over conventional clinically guided dosing algorithm remains controversial. We made a comparison of pharmacogenetics-based versus clinically guided dosing algorithm by an updated meta-analysis. We searched OVID MEDLINE, EMBASE, and the Cochrane Library for relevant citations. The primary outcome was the percentage of time in therapeutic range. The secondary outcomes were time to stable therapeutic dose and the risks of adverse events including all-cause mortality, thromboembolic events, total bleedings, and major bleedings. Eleven randomized controlled trials with 2639 participants were included. Our pooled estimates indicated that pharmacogenetics-based dosing algorithm did not improve percentage of time in therapeutic range [weighted mean difference, 4.26; 95% confidence interval (CI), -0.50 to 9.01; P = 0.08], but it significantly shortened the time to stable therapeutic dose (weighted mean difference, -8.67; 95% CI, -11.86 to -5.49; P < 0.00001). Additionally, pharmacogenetics-based algorithm significantly reduced the risk of major bleedings (odds ratio, 0.48; 95% CI, 0.23 to 0.98; P = 0.04), but it did not reduce the risks of all-cause mortality, total bleedings, or thromboembolic events. Our results suggest that pharmacogenetics-based warfarin dosing algorithm significantly improves the efficiency of International Normalized Ratio correction and reduces the risk of major hemorrhage.

Enrichment of cardiac differentiation by a large starting number of embryonic stem cells in embryoid bodies is mediated by the Wnt11-JNK pathway.

Embryoid bodies (EBs) with large starting numbers of embryonic stem cells (ESCs) have a greater degree of cardiac differentiation than from low numbers of EBs. However, the biological roles of signaling molecules in these effects are not well understood. Here, we show that groups of EBs with different starting numbers of ESCs had differential gene expression patterns for Wnt5a and Wnt11. Wnt11 significantly increased the percentage of beating EBs by up-regulating the expression of the cardiac-specific genes. Wnt5a did not show these effects. Moreover, Wnt11 significantly increased the level of phosphorylated Jun N-terminal kinase. The inhibition of the JNK pathway by SP600125 blocked the effects of Wnt11. Thus, enrichment of cardiac differentiation in groups of EBs with a larger starting number of ESCs is mediated by the Wnt11-JNK pathway.

Ubiquitinome Analysis Uncovers Alterations in Synaptic Proteins and Glucose Metabolism Enzymes in the Hippocampi of Adolescent Mice Following Cold Exposure.

Cold exposure exerts negative effects on hippocampal nerve development in adolescent mice, but the underlying mechanisms are not fully understood. Given that ubiquitination is essential for neurodevelopmental processes, we attempted to investigate the effects of cold exposure on the hippocampus from the perspective of ubiquitination. By conducting a ubiquitinome analysis, we found that cold exposure caused changes in the ubiquitination levels of a variety of synaptic-associated proteins. We validated changes in postsynaptic density-95 (PSD-95) ubiquitination levels by immunoprecipitation, revealing reductions in both the K48 and K63 polyubiquitination levels of PSD-95. Golgi staining further demonstrated that cold exposure decreased the dendritic-spine density in the CA1 and CA3 regions of the hippocampus. Additionally, bioinformatics analysis revealed that differentially ubiquitinated proteins were enriched in the glycolytic, hypoxia-inducible factor-1 (HIF-1), and 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathways. Protein expression analysis confirmed that cold exposure activated the mammalian target of rapamycin (mTOR)/HIF-1α pathway. We also observed suppression of pyruvate kinase M2 (PKM2) protein levels and the pyruvate kinase (PK) activity induced by cold exposure. Regarding oxidative phosphorylation, a dramatic decrease in mitochondrial respiratory-complex I activity was observed, along with reduced gene expression of the key subunits NADH: ubiquinone oxidoreductase core subunit V1 (Ndufv1) and Ndufv2. In summary, cold exposure negatively affects hippocampal neurodevelopment and causes abnormalities in energy homeostasis within the hippocampus.

Time-dependent regulation of neuregulin-1ß/ErbB/ERK pathways in cardiac differentiation of mouse embryonic stem cells.

Neuregulin-1ß (NRG-1ß)/ErbB signaling plays crucial roles in the cardiac differentiation of mouse embryonic stem cells (ESCs), but its roles and the underlying mechanisms in cardiac differentiation are incompletely understood. This study showed that NRG-1ß significantly increased the percentage of beating embryoid bodies (EBs) and up-regulated the gene expressions of Nkx2.5, GATA4, α-actin, MLC-2v, and ANF in a time-dependent manner, with no effect on the gene expressions of HCN4 and Tbx3. Inhibition of ErbB receptors with AG1478 significantly decreased the percentage of beating EBs; down-regulated the gene expressions of Nkx2.5, GATA4, MLC-2v, ANF, and α-actin; and concomitantly up-regulated the gene expressions of HCN4 and Tbx3 in a time-dependent manner. Moreover, the up-regulation of transcripts for Nkx2.5 and GATA4 by NRG-1ß was blocked by the extracellular signal-related kinases (ERK) 1/2 inhibitor, U0126. However, U0126 could not inhibit the transcript up-regulations of MLC-2v and ANF by NRG-1ß. The protein quantitation results were consistent with those of gene quantitation. Our results suggest that NRG-1ß/ErbB signaling plays critical roles in the cardiac differentiation of mouse ESCs and in the subtype specification of cardiomyocytes in a time-dependent manner. The ERK1/2 pathway may be involved in the early cardiogenesis, but not in the subtype specification of cardiomyocytes.

A comprehensive review on immune checkpoint inhibitors induced cardiotoxicity characteristics and associated factors.

Newly approved cancer drugs called ICIs have shown remarkable success in improving patient survival rates, but they also have the potential for inflammatory and immune-related side effects, including those affecting the cardiovascular system. Research has been conducted to understand the development of these toxicities and identify risk factors. This review focuses on the characteristics of ICI-induced cardiotoxicity and discusses the reported risk factors. It is important for cardio-oncologists to understand the basic concepts of these drugs to better understand how cardiotoxicities occur. It might be hard to find reports, where all patients treated with ICIs had developed cardiac toxicity, because there could be other existing and variable factors that influence the likelihood or risk of developing cardiotoxicity during treatment. Various clinical parameters have been explored as potential risk factors, and further investigation is needed through large-scale studies.

The BNP to Albumin Ratio and Heart Rate in Stroke Complicating Atrial Fibrillation.

Heart rate is still a controversial and unclear factor of stroke risk in atrial fibrillation. Indices combining parameters are more accurate predictors than single parameters. This article assessed the association of the BNP-to-albumin ratio (BAR), with the risk of stroke, and evaluated the relationship between heart rate and stroke risk. Data were retrospectively collected from the Zhongnan Hospital electronic records. Binary logistic regression assessed the association between BAR and the prediction of acute stroke in atrial fibrillation. Spearman's correlation analysis evaluated the correlation between heart rate and BAR. The specificity and sensitivity of the BAR index were determined by ROC curve analysis. A total of 197 participants were involved, including 119 cases and 78 controls. The mean BAR was significantly higher for cases than for controls P = 0.00 while the difference in mean heart rate did not reach statistical significance P = 0.08. Using binary logistic analysis, BAR was a significant predictor of stroke in AF, OR = 1.67 95%CI [1.09-2.55] P = 0.018. The correlation between BAR and heart rate was significant, the correlation coefficient was r = 0.15 P = 0.03. ROC curve analysis showed that at a cut-off value of 2.01*10-9 g/L 93% of patients with a BAR of less than 2.01 did not have an acute stroke and only the 60% with a BAR greater than 2.01 experienced an acute stroke. It's been suggested that the BNP to albumin ratio and heart rate could be used to estimate the risk of stroke among hospitalized atrial fibrillation patients, thus contributing to the implementation of appropriate measures.

Functional study of an aberrant splicing variant of the human luteinizing hormone (LH) receptor.

The luteinizing hormone receptor (LHR) is a member of a subfamily of G protein-coupled receptors that is characterized by its alternative splicing. In a previous study, we identified a splice site mutation of intron 6 (IVS6-3C>A) in a patient suffering from Leydig cell hypoplasia, which leads to aberrant splicing of LHR mRNA. In vitro expression analysis confirmed that this mutation results in the skipping of exon 7 in the mature mRNA of the LHR gene. In this study, we determined the impact of IVS6-3C>A on the RNA secondary structure and function of LHR-Del7. The three-dimensional structure of the leucine-rich repeats in LHR was predicted by molecular modeling. Radioactive ligand-binding assays verified that LHR-Del7 has no binding affinity for hCG. Furthermore, we detected negligible cAMP production in cells transfected with LHR-Del7. Cells co-expressing LHR-WT and LHR-Del7 were able to generate cAMP in response to hCG, but there was no significant difference between cells transfected with LHR-WT/vector and LHR-WT/LHR-Del7, although the variant was able to localize to cell surface, similar to wild-type receptor. These results indicated that LHR-Del7 does not have a dominant negative effect on LHR-WT cell surface expression, and although the pathological splicing variant LHR-Del7 was able to localize to cell membranes it failed to bind hCG and had no effect on wild-type LHR.

Altered polarization, morphology, and impaired innate immunity germane to resident peritoneal macrophages in mice with long-term type 2 diabetes.

Type 2 diabetes (T2D) is associated with perturbed innate immunity. Macrophages, bridging innate immunity and metabolic disturbances, play important roles in controlling immune homeostasis. However, the effect of long-term diabetic milieu (DM) on the functions and phenotypes of macrophages is still not clear. In this study, we used resident peritoneal macrophages (RPMs) from 5-month-old db/db mice to investigate the changes of macrophages. It was found that RPMs in db/db mice significantly reduced phagocytosis and adhesion capacity. After standardization with body weight, the number of F4/80(+) RPMs markedly reduced in db/db mice, and, furthermore, the macrophages skewed to M2-polarizated macrophages. The results of morphology found that the RPMs shape of db/db mice was nearly round, but the RPMs shape of control mice was spindle-shaped and irregular. In this study, we found the cell numbers, morphology, and innate immunity functions of RPMs in 5-month-old type 2 diabetic mice (db/db mice) obtained by abdominal cavity lavage were significantly altered. Importantly, we also found the remarkably increased M2-RPMs in diabetic mice for the first time.

Transthyretin-related hereditary amyloidosis in a Chinese family with TTR Y114C mutation.

BACKGROUND: Transthyretin-related hereditary amyloidosis is an autosomal dominant inherited disease caused by mutations in the transthyretin (TTR) gene. Corresponding to the various transthyretin gene mutations and a wide range of geographical distribution, transthyretin-related hereditary amyloidosis presents diverse characteristics in genotype-phenotype correlation. OBJECTIVE/METHOD: Here, we identify the clinical characteristics of a Chinese family affected by transthyretin-related hereditary amyloidosis with TTR Tyr114Cys mutation. RESULTS/CONCLUSION: The pathogenic mechanism studies showed that the protein encoded by TTR Tyr114Cys is more easily depolymerized to form amyloid fibrils. Moreover, the cytotoxicity of the TTR Tyr114Cys may be attributed to its ability to persistently activate the extracellular-signal-regulated kinase 1/2 pathway.

Image fusion of integrating fluoroscopy into 3D computed tomography in guidance of left atrial appendage closure.

AIMS: We evaluated the feasibility of left atrial appendage (LAA) closure guided by the image fusion of integrating fluoroscopy into 3D computed tomography (CT). METHODS AND RESULTS: A total of 117 consecutive patients who underwent LAA closure with or without the image fusion were matched (1:2). Each LAA closure step of the Image fusion group was guided by the preprocedure CT and image fusion, especially in the plan of LAA measurement and transseptal puncture. All patients were successfully implanted with a WATCHMAN closure device. Comparing the two groups, the mean number of recapture times and the number of devices per patient of the Image fusion group were significantly lower (0.4 ± 0.5 vs. 0.7 ± 0.8, P = 0.031 and 1.0 ± 0.2 vs. 1.1 ± 0.3, P = 0.027, respectively). The one-time successful deployment rate by the support of the image fusion was higher than in the control group (66.7% vs. 44.9%, P = 0.026). Each case of the Image fusion group was completely occluded with one transseptal puncture, while five of the Non-image fusion group required redo transseptal punctures. During the 45-day follow-up, both group cases presented occlusion efficiency and no major adverse cardiac events were observed. CONCLUSION: Image fusion technique integrating fluoroscopy into the 3D CT is safe and feasible which can be easily incorporated into the procedural work-flow of percutaneous LAA closure. The fusion image can play an important alternative role in the plan of LAA measurement and transseptal puncture site for improving the LAA closure procedure.

Identification of a locus for autosomal dominant high myopia on chromosome 5p13.3-p15.1 in a Chinese family.

PURPOSE: Myopia and its extreme form, high myopia, are common vision disorders worldwide, especially in Asia. Identifying genetic markers is a useful step toward understanding the genetic basis of high myopia, particularly in the Chinese population, where it is highly prevalent. This study was conducted to provide evidence of linkage for autosomal dominant high myopia to a locus on chromosome 5p13.3-p15.1 in a large Chinese family. METHODS: After clinical evaluation, genomic DNA from 29 members of this family was genotyped. A genome-wide screen was then performed using 382 markers with an average inter-marker distance of 10 cM, and two-point linkage was analyzed using the MLINK program. Mutation analysis of the candidate genes was performed using direct sequencing. RESULTS: Linkage to the known autosomal dominant high myopia loci was excluded. The genome-wide screening identified a maximum two-point LOD score of 3.71 at θ=0.00 with the microsatellite marker D5S502. Fine mapping and haplotype analysis defined a critical region of 11.69 cM between D5S2096 and D5S1986 on chromosome 5p13.3-p15.1. Sequence analysis of the candidate genes inside the linked region did not identify any causative mutations. CONCLUSIONS: A genetic locus was mapped to chromosome 5p13.3-p15.1 in a large Chinese family with autosomal dominant high myopia.