Enterocytozoon bieneusi and Cryptosporidium bat genotype XXI and bat genotype XXII in fruit bats (Rousettus leschenaultii) inhabiting a tropical park in Hainan Province, China.

Bats stand as one of the most diverse groups in the animal kingdom and are key players in the global transmission of emerging pathogens. However, their role in transmitting Enterocytozoon bieneusi and Cryptosporidium spp. remains unclear. This study aimed to evaluate the occurrence and genetic diversity of the two pathogens in fruit bats (Rousettus leschenaultii) in Hainan, China. Ten fresh fecal specimens of fruit bats were collected from Wanlvyuan Gardens, Haikou, China. The fecal samples were tested for E. bieneusi and Cryptosporidium spp. using Polymerase Chain Reaction (PCR) analysis and sequencing the internal transcribed spacer (ITS) region and partial small subunit of ribosomal RNA (SSU rRNA) gene, respectively. Genetic heterogeneity across Cryptosporidium spp. isolates was assessed by sequencing 4 microsatellite/minisatellite loci (MS1, MS2, MS3, and MS16). The findings showed that out of the ten specimens analyzed, 2 (20 %) and seven (70.0 %) were tested positive for E. bieneusi and Cryptosporidium spp., respectively. DNA sequence analysis revealed the presence of two novel Cryptosporidium genotypes with 94.4 to 98.6 % sequence similarity to C. andersoni, named as Cryptosporidium bat-genotype-XXI and bat-genotype-XXII. Three novel sequences of MS1, MS2 and MS16 loci identified here had 95.4 to 96.9 % similarity to the known sequences, which were deposited in the GenBank. Two genotypes of E. bieneusi were identified, including a novel genotype named HNB-I and a zoonotic genotype PigEbITS7. The discovery of these novel sequences provides meaningful data for epidemiological studies of the both pathogens. Meanwhile our results are also presented that the fruit bats infected with E. bieneusi, but not with Cryptosporidium, should be considered potential public health threats.

Molecular prevalence and subtype distribution of Blastocystis spp. among children who have diarrheia or are asymptomatic in Wenzhou, Zhejiang Province, China.

Blastocystis sp., a significant zoonotic parasite with a global distribution, was the focus of this study, which aimed to investigate its prevalence and genetic diversity among diarrheic and asymptomatic children in Wenzhou, China. We collected 1,032 fecal samples from Yuying Children's Hospital, Wenzhou, China, comprising 684 from children with diarrhea and 348 from asymptomatic children. Genomic DNA extracted from these samples was used to detect Blastocystis spp. by PCR, targeting the small subunit ribosomal RNA gene. Subsequently, a phylogenetic tree was constructed, applying the maximum likelihood method. Blastocystis spp. were detected in 67 (6.5%) of the fecal samples. The prevalence rate of Blastocystis spp. in diarrheic children (8.8%; 60/684) was significantly higher than that in asymptomatic children (2.0%; 7/348) (χ 2 = 17.3, p < 0.001). Sequence analysis of the SSU rRNA gene identified five known Blastocystis spp. subtypes, ST1 (n = 12), ST2 (n = 5), ST3 (n = 35), ST4 (n = 12), and ST7 (n = 3). ST1 and ST3 were present in both diarrheic and asymptomatic children, while ST2, ST4, and ST7 were exclusive to diarrheic children. Intra-subtype genetic polymorphisms were identified, comprising four variations in ST1 (ST1-1 to ST1-4), five in ST3 (ST3-1 to ST3-5), two in ST4 (ST4-1 and ST4-2), and two in ST7 (ST7-1 and ST7-2). Notably, ST1-2 to ST1-4, ST3-3 to ST3-5, and ST7-1 and ST7-2 represent newly identified variations. The composition and genetic characteristics of subtypes among children in this region suggest various sources of infection, including human-to-human and animal-to-human transmission.

Title: Prévalence moléculaire et distribution des sous-types de Blastocystis spp. parmi les enfants diarrhéiques et asymptomatiques à Wenzhou, Province du Zhejiang, Chine. Abstract: Blastocystis sp., un parasite zoonotique important avec une distribution mondiale, était au centre de cette étude, qui visait à étudier sa prévalence et sa diversité génétique parmi les enfants diarrhéiques et asymptomatiques de Wenzhou, en Chine. Nous avons collecté 1 032 échantillons fécaux à l'hôpital pour enfants Yuying de Wenzhou, en Chine, dont 684 provenant d'enfants souffrant de diarrhée et 348 d'enfants asymptomatiques. L'ADN génomique extrait de ces échantillons a été utilisé pour détecter Blastocystis sp. par PCR, ciblant le gène de la petite sous-unité de l'ARN ribosomal. Par la suite, un arbre phylogénétique a été construit, en appliquant la méthode du maximum de vraisemblance. Blastocystis sp. a été détecté dans 67 (6,5 %) des échantillons fécaux. Le taux de prévalence de Blastocystis spp. chez les enfants diarrhéiques (8,8 % ; 60 / 684) était significativement plus élevé que chez les enfants asymptomatiques (2,0 % ; 7 / 348) (χ2 = 17,3, p < 0,001). L'analyse de la séquence du gène de l'ARNr SSU a identifié cinq sous-types de Blastocystis spp., ST1 (n = 12), ST2 (n = 5), ST3 (n = 35), ST4 (n = 12) et ST7 (n = 3). Les sous-types ST1 et ST3 étaient présents chez les enfants diarrhéiques et asymptomatiques, tandis que ST2, ST4 et ST7 étaient exclusifs aux enfants diarrhéiques. Des polymorphismes génétiques intra-sous-types ont été identifiés, comprenant quatre variations dans ST1 (ST1-1 à ST1-4), cinq dans ST3 (ST3-1 à ST3-5), deux dans ST4 (ST4-1 et ST4-2) et deux dans ST7 (ST7-1 et ST7-2). Notamment, ST1-2 à ST1-4, ST3-3 à ST3-5, ST7-1 et ST7-2 représentent des variations nouvellement identifiées. La composition et les caractéristiques génétiques des sous-types chez les enfants de cette région suggèrent diverses sources d'infection, notamment la transmission interhumaine et animale.

Bicanalicular-nasal silicone stent for deep canalicular laceration management.

We evaluated the efficacy and clinical outcomes of bicanalicular-nasal silicone stents for deep canalicular lacerations and their anatomical restoration advantages. This retrospective case series study included patients with deep canalicular lacerations who underwent bicanalicular-nasal silicone stent intubation between January 2010 and June 2021 at a Chinese tertiary hospital and two primary hospitals. Intra- and post-operative complications were recorded. Anatomical, functional, and cosmetic outcomes were evaluated as anatomical restoration assessments at the last follow-up. We defined anatomical success as a free passage with no reflux during irrigation. Functional success was evaluated using the Munk epiphora scale and fluorescein dye disappearance test. Cosmetic outcomes were evaluated by examining the eyelid, lacrimal punctum, and medial canthus for any structural abnormalities and recorded objectively using a grading scale. We evaluated 92 eyes of 92 patients (63 men and 29 women); the mean distance from the lateral lacerated end to the punctum was 7.74 mm (range 7-10 mm). Bicanalicular-nasal silicone stents were successfully used in all 92 eyes with no severe intra- or post-operative complications noted. The stent placement duration ranged from 12 to 16 weeks (mean, 13.18 weeks). The follow-up period after stent removal ranged from 3 to 12 months (mean, 6.04 months). The anatomical and functional restoration success rates were 96.74% (89/92) and 100% (92/92), respectively. Satisfactory eyelid position realignment was achieved in all patients. Bicanalicular-nasal silicone stent placement sufficiently relieved orbicularis muscle tension during deep canalicular laceration repair, providing good functional results and excellent cosmetic realignment and anatomical restoration of the eyelid.

DIRICHLET-TREE MULTINOMIAL MIXTURES FOR CLUSTERING MICROBIOME COMPOSITIONS.

Studying the human microbiome has gained substantial interest in recent years, and a common task in the analysis of these data is to cluster microbiome compositions into subtypes. This subdivision of samples into subgroups serves as an intermediary step in achieving personalized diagnosis and treatment. In applying existing clustering methods to modern microbiome studies including the American Gut Project (AGP) data, we found that this seemingly standard task, however, is very challenging in the microbiome composition context due to several key features of such data. Standard distance-based clustering algorithms generally do not produce reliable results as they do not take into account the heterogeneity of the cross-sample variability among the bacterial taxa, while existing model-based approaches do not allow sufficient flexibility for the identification of complex within-cluster variation from cross-cluster variation. Direct applications of such methods generally lead to overly dispersed clusters in the AGP data and such phenomenon is common for other microbiome data. To overcome these challenges, we introduce Dirichlet-tree multinomial mixtures (DTMM) as a Bayesian generative model for clustering amplicon sequencing data in microbiome studies. DTMM models the microbiome population with a mixture of Dirichlet-tree kernels that utilizes the phylogenetic tree to offer a more flexible covariance structure in characterizing within-cluster variation, and it provides a means for identifying a subset of signature taxa that distinguish the clusters. We perform extensive simulation studies to evaluate the performance of DTMM and compare it to state-of-the-art model-based and distance-based clustering methods in the microbiome context, and carry out a validation study on a publicly available longitudinal data set to confirm the biological relevance of the clusters. Finally, we report a case study on the fecal data from the AGP to identify compositional clusters among individuals with inflammatory bowel disease and diabetes. Among our most interesting findings is that enterotypes (i.e., gut microbiome clusters) are not always defined by the most dominant species as previous analyses had assumed, but can involve a number of less abundant OTUs, which cannot be identified with existing distance-based and method-based approaches.

Updating Urinary Microbiome Analyses to Enhance Biologic Interpretation.

Objective: An approach for assessing the urinary microbiome is 16S rRNA gene sequencing, where analysis methods are rapidly evolving. This re-analysis of an existing dataset aimed to determine whether updated bioinformatic and statistical techniques affect clinical inferences. Methods: A prior study compared the urinary microbiome in 123 women with mixed urinary incontinence (MUI) and 84 controls. We obtained unprocessed sequencing data from multiple variable regions, processed operational taxonomic unit (OTU) tables from the original analysis, and de-identified clinical data. We re-processed sequencing data with DADA2 to generate amplicon sequence variant (ASV) tables. Taxa from ASV tables were compared to the original OTU tables; taxa from different variable regions after updated processing were also compared. Bayesian graphical compositional regression (BGCR) was used to test for associations between microbial compositions and clinical phenotypes (e.g., MUI versus control) while adjusting for clinical covariates. Several techniques were used to cluster samples into microbial communities. Multivariable regression was used to test for associations between microbial communities and MUI, again while adjusting for potentially confounding variables. Results: Of taxa identified through updated bioinformatic processing, only 40% were identified originally, though taxa identified through both methods represented >99% of the sequencing data in terms of relative abundance. Different 16S rRNA gene regions resulted in different recovered taxa. With BGCR analysis, there was a low (33.7%) probability of an association between overall microbial compositions and clinical phenotype. However, when microbial data are clustered into bacterial communities, we confirmed that bacterial communities are associated with MUI. Contrary to the originally published analysis, we did not identify different associations by age group, which may be due to the incorporation of different covariates in statistical models. Conclusions: Updated bioinformatic processing techniques recover different taxa compared to earlier techniques, though most of these differences exist in low abundance taxa that occupy a small proportion of the overall microbiome. While overall microbial compositions are not associated with MUI, we confirmed associations between certain communities of bacteria and MUI. Incorporation of several covariates that are associated with the urinary microbiome improved inferences when assessing for associations between bacterial communities and MUI in multivariable models.

Prevalence and characteristics of somatic symptom disorder in the elderly in a community-based population: a large-scale cross-sectional study in China.

INTRODUCTION AND OBJECTIVES: The aging population is expected to reach 2 billion by 2050, but the impact of somatic symptom disorder (SSD) on the elderly has been insufficiently addressed. We aimed to clarify the prevalence of SSD in China and to identify physical and psychological differences between the elderly and non-elderly. METHODS: In this prospective multi-center study, 9020 participants aged (2206 non-elderly adults and 6814 elderly adults) from 105 communities of Shanghai were included (Assessment of Somatic Symptom in Chinese Community-Dwelling People, clinical trial number NCT04815863, registered on 06/12/2020). The Somatic Symptom Scale-China (SSS-CN) questionnaire was used to measure SSD. Depressive and anxiety disorders were assessed by the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), respectively. RESULTS: The prevalence of SSD in the elderly was higher than that in the non-elderly (63.2% vs. 45.3%). The elderly suffered more severe SSD (20.4% moderate and severe in elderly vs. 12.0% in non-elderly) and are 1.560 times more likely to have the disorder (95%CI: 1.399-1.739; p < .001) than the non-elderly. Comorbidity of depressive or anxiety disorders was 3.7 times higher than would be expected in the general population. Additionally, the results of adjusted multivariate analyses identified older age, female sex, and comorbid physical diseases as predictive risk factors of SSD in the elderly group. CONCLUSIONS: With higher prevalence of common physical problems (including hypertension, diabetes mellitus and cardio/cerebrovascular disease), the elderly in Shanghai are more vulnerable to have SSD and are more likely to suffer from comorbid depressive and anxiety disorders. SSD screening should be given more attention in the elderly, especially among older females with several comorbid physical diseases.

Efferocytosis in the Central Nervous System.

The effective clearance of apoptotic cells is essential for maintaining central nervous system (CNS) homeostasis and restoring homeostasis after injury. In most cases of physiological apoptotic cell death, efferocytosis prevents inflammation and other pathological conditions. When apoptotic cells are not effectively cleared, destruction of the integrity of the apoptotic cell membrane integrity, leakage of intracellular contents, and secondary necrosis may occur. Efferocytosis is the mechanism by which efferocytes quickly remove apoptotic cells from tissues before they undergo secondary necrosis. Cells with efferocytosis functions, mainly microglia, help to eliminate apoptotic cells from the CNS. Here, we discuss the impacts of efferocytosis on homeostasis, the mechanism of efferocytosis, the associations of efferocytosis failure and CNS diseases, and the current clinical applications of efferocytosis. We also identify efferocytosis as a novel potential target for exploring the causes and treatments of CNS diseases.

Outcomes and Complications of Sutured Scleral-Fixated Foldable Intraocular Lens Implantation: A Retrospective Study of 5-Year Follow-Up.

PURPOSE: To evaluate long-term outcomes and complications of sutured scleral-fixated foldable intraocular lens (IOL) implantation. DESIGN: Retrospective study. METHODS: Patients who underwent sutured scleral-fixated foldable IOL implantation using 10-0 polypropylene suture were followed up for at least 5 years at one Chinese tertiary hospital and two primary hospitals. RESULTS: 52 eyes among 48 patients (35 male and 13 female) were evaluated. The mean age (years) was 50.27 ± 20.08 (range: 6 to 81). The mean postoperative follow-up time (months) was 79.70 ± 18.84 (range: 60 to 121). The mean best-corrected visual acuity (BCVA) improved from 0.83 ± 0.69 logarithm of the minimum angle of resolution (logMAR) at baseline to 0.50 ± 0.45 logMAR at the last follow-up visit. There was improved or unchanged BCVA in 44 eyes (84.62%) and reduced BCVA in 8 eyes (15.38%). Mild intraoperative intravitreal hemorrhage was observed in 3 eyes (5.77%). Early postoperative complications included transient elevated intraocular pressure (IOP) in 5 eyes (9.62%) and hypotony in 1 eye (1.92%). Secondary epimacular membrane occurred in 5 eyes (9.62%) and retinal detachment (RD; 3 years postsurgery), subconjunctival suture knot exposure (5 years postsurgery), and persistent elevated IOP (in a GRAVES patient) occurred in 1 eye (1.92%) each. No suture erosion or breakage nor IOL dislocation was observed. No visually threatening IOL tilt or decentration was reported in any patient. CONCLUSION: Sutured scleral-fixated foldable IOL implantation demonstrated satisfactory long-term outcomes and rare suture-related complications. This technology was safe and did not require complicated equipment and is of considerable interest in the setting of aphakia without adequate capsule support.

Decline of anterior cingulate functional network efficiency in first-episode, medication-naïve somatic symptom disorder and its relationship with catastrophizing.

The high prevalence of somatic symptom disorder (SSD) led to cumulative burdens to the medical system. However, the pathogenesis of this disease still remains unclear. Graph theoretical analysis discovered altered network topology across various psychiatric disorders, yet alteration in the topological structure of brain functional network in SSD patients is still unexplored. Catastrophizing is a common cognitive distortion in SSD. We hypothesize that the network topological metrics of SSD should be altered, and should correlate with catastrophizing scales. 32 medication-naïve, first-episode SSD patients and 30 age, gender matched HCs were recruited. The 17-item Hamilton Depression Rating Scale (HAMD-17), Hamilton Anxiety Rating Scale (HAMA) and Cognitive Emotion Regulation Questionnaire (CERQ) were accessed. Functional MRI were scanned and brain functional networks were constructed based on 166 anatomically cerebrum regions from the automated anatomical labeling 3 (AAL3) template. Network topological metrics were calculated and compared between the two groups. Correlation between these metrics and clinical scales were also calculated. Network global efficiency of SSD was significantly lower than that of HC. Nodal global efficiency of the left subgenual anterior cingulate cortex (sgACC) of SSD was significantly lower than that of HC. FCs between the left sgACC and other 21 seed nodes were significantly declined in SSD in comparison with HC. In SSD group, HAMD total score was significantly negatively correlated with the connection between the left medial superior frontal gyrus and the left sgACC. CERQ catastrophizing score was significantly negatively correlated with nodal global efficiency of left sgACC and with the FCs between the left sgACC and other 13 seed nodes. Catastrophizing could reflect the specific sgACC-centered dysfunction of brain network global efficiency of SSD. The left sgACC may be a future treatment target of dealing with catastrophizing, which is a core cognitive distortion of SSD.

The Urinary Microbiome in Postmenopausal Women with Recurrent Urinary Tract Infections.

PURPOSE: The etiology of postmenopausal recurrent urinary tract infection (UTI) is not completely known, but the urinary microbiome is thought to be implicated. We compared the urinary microbiome in menopausal women with recurrent UTIs to age-matched controls, both in the absence of acute infection. MATERIALS AND METHODS: This is a cross-sectional analysis of baseline data from 64 women enrolled in a longitudinal cohort study. All women were using topically applied vaginal estrogen. Women >55 years of age from the following groups were enrolled: 1) recurrent UTIs on daily antibiotic prophylaxis, 2) recurrent UTIs not on antibiotic prophylaxis and 3) age-matched controls without recurrent UTIs. Catheterized urine samples were collected at least 4 weeks after last treatment for UTI and at least 6 weeks after initiation of vaginal estrogen. Samples were evaluated using expanded quantitative urine culture (EQUC) and 16S rRNA gene sequencing. RESULTS: With EQUC, there were no significant differences in median numbers of microbial species isolated among groups (p=0.96), even when considering Lactobacilli (p=0.72). However, there were trends toward different Lactobacillus species between groups. With 16S rRNA sequencing, the majority of urine samples contained Lactobacillaceae, with nonsignificant trends in relative abundance among groups. Using a Bayesian analysis, we identified significant differences in anaerobic taxa associated with phenotypic groups. Most of these differences centered on Bacteroidales and the family Prevotellaceae, although differences were also noted in Actinobacteria and certain genera of Clostridiales. CONCLUSIONS: Associations between anaerobes within the urinary microbiome and postmenopausal recurrent UTI warrants further investigation.

Cardiac device implant wound closure with a novel low-density suture spacing single layer method.

BACKGROUND: To establish a novel time-saving and safe suture method for cardiac implantable electronic device (CIED) implantation. METHODS: From January 2017 to April 2020, a total of 1317 patients scheduled for CIED procedure were consecutively enrolled in this study. Wound closure of all patients were prospectively assigned either to low-density suture spacing single layer suture group (single-layer group) or traditional two layer suture group (two-layer group). The effects of two closure methods on wound healing and pocket related complications were compared. RESULTS: There were no significant differences in age, gender, BMI, comorbid diseases (diabetes, hypertension, coronary heart disease, and chronic kidney disease), and antiplatelet or anticoagulant drug use between the two groups. The number of suture stitches in the single-layer group was significantly less than that in the two-layer group [3.03(3-4) vs. 7.17(7-10), p < .001], the suture time in the single-layer group was significantly shorter than that in the two-layer group [190.57(167-256) s vs. 493.36(452-655) s, p < .001], and the incidence of clinically significant hematoma in the single-layer group was comparable to that in the two-layer group (0.7% vs. 0.3%, p = .742). Additionally, there were no significant differences in the incidence of pocket infection, dehiscence and keloid between the two groups. CONCLUSION: Novel single-layer suture with low-density suture spacing is feasible and associated with a low incidence of wound dehiscence or infection for CIED implantation.

Circulating primary bile acid is correlated with structural remodeling in atrial fibrillation.

BACKGROUND: Circulating primary bile acid was involved in the regulation of cardiac ionic channel currents and ventricular myocyte apoptosis, but it was unknown whether or not it played a role in structural remodeling of AF. This study was aimed to testify the hypothesis that elevated chenodeoxycholic acid (CDCA) concentration correlated with left atrial low voltage area (LVA) and could induce apoptosis of atrial myocytes in AF. METHODS AND RESULTS: Serum concentrations of 12 types of bile acids were determined in patients with paroxysmal (n = 21), persistent AF (n = 20), and type A pre-excitation and paroxysmal supraventricular tachycardia (PSVT) (n = 19) and were correlated with LVA in AF, which was obtained by electroanatomical mapping during ablation. Additionally, the impact of CDCA incubation on apoptosis of mouse atrial myocytes was evaluated. Serum levels of CDCA and cholic acid were significantly higher in AF than in PSVT. CDCA serum concentration was significantly higher in persistent AF than in paroxysmal AF. CDCA serum level was positively correlated with the size (r = 0.78, P < 0.05) and proportion of LVA (r = 0.89, P < 0.05) in AF patients. CDCA (75 µM, 100 µM) promoted atrial myocyte apoptosis in a concentration-dependent manner. CONCLUSIONS: The higher circulating level of CDCA in AF than in PSVT, positive correlation of CDCA with LVA in AF, and incubation dose-dependent increase of mouse atrial myocyte apoptosis indicated that CDCA might play a significant role in the progress of structural remodeling of AF.

Identifying and measuring the severity of somatic symptom disorder using the Self-reported Somatic Symptom Scale-China (SSS-CN): a research protocol for a diagnostic study.

INTRODUCTION: The detection rate of somatic symptom disorder (SSD) in general hospitals is unsatisfactory. Self-report questionnaires that assess both somatic symptoms and psychological characteristics will improve the process of screening for SSD. The Somatic Symptom Scale-China (SSS-CN) questionnaire has been developed to meet this urgent clinical demand. The aim of this research is to validate the self-reported SSS-CN as a timely and practical instrument that can be used to identify SSD and to assess the severity of this disorder. METHODS AND ANALYSIS: At least 852 patients without organic disease but presenting physical discomfort will be recruited at a general hospital. Each patient will undergo a Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5)-guided physician diagnosis, including disease identification and severity assessment, as the reference standard. This research will compare the diagnostic performance of the SSS-CN for SSD, the Patient Health Questionnaire-15 (PHQ-15) and other SSD-related questionnaires. Statistical tests to measure the area under the curve (AUC) and volume under the surface of the receiver operating curve will be used to assess the accuracy of the SSD identification and the severity assessment, respectively. In addition to this standard diagnostic study, we will conduct follow-up investigations to explore the effectiveness of the SSS-CN in monitoring treatment effects. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Renji Hospital Human Research Ethics Committee, approval number 2 015 016. The findings of this study will be disseminated via peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: NCT03513185.

Low voltage areas in paroxysmal atrial fibrillation: The prevalence, risk factors and impact on the effectiveness of catheter ablation.

BACKGROUND: The prevalence, risk factors of left atrial low voltage areas (LVA) in paroxysmal atrial fibrillation (PAF) and the impact of LVA on the effectiveness of circumferential pulmonary vein isolation (CPVI) were not fully clarified. METHODS: One hundred fifty patients (mean age 64.7 years, 89 males) with PAF were consecutively enrolled to undergo CPVI. Prior to ablation a contact force sensing ablation catheter was utilized for LVA mapping in sinus rhythm. The patients were graded based on the proportion of LVA (LVA%): non LVA, mild (LVA% ≤ 10%), moderate (LVA% 10%-<20%) and severe (LVA% ≥ 20%), and were followed up for 12 months after initial CPVI. RESULTS: There were 56 in non LVA, 54 in mild LVA, 22 in moderate LVA and 18 in severe LVA. The prevalence of LVA was 62.7% in this PAF cohort, with the most frequent localization at anterior free wall (35.3%), PV antrum (22%) and septum (14.7%). Female gender (OR 3.634, 95% CI 1.704-7.751, P = 0.001) and left atrial surface area (LASA) (OR 1.024, 95% CI 1.000-1.048, P = 0.048) were risk factors of LVA. LVA% exceeding10% was associated with poor effectiveness of CPVI. LVA grade (HR 1.633, 95% CI 1.122-2.378, P = 0.011) was an independent predictor for AF recurrence after initial ablation. CONCLUSIONS: LVA affected >60% of patients with PAF. Female gender and LASA were two risk factors of LVA. LVA grade was an independent predictor for AF recurrence following CPVI.

Simvastatin inhibits inflammatory response in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages through the microRNA-22/Cyr61 axis.

Simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has been shown to improve atherosclerosis (AS) via its anti-inflammatory activity. Recently, several studies have reported the involvement of macrophages in chronic inflammation associated with AS. However, it is unknown whether macrophages participate in the anti-inflammatory activity of simvastatin in AS. This study was designed to investigate the roles and underlying mechanisms of simvastatin in LPS-stimulated RAW264.7 macrophages. First, we examined the anti-inflammatory effects of simvastatin on LPS-treated macrophage RAW264.7 cells using an enzyme-linked immunosorbent assay (ELISA) and a quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Then, a microarray assay was used to analyze the microRNA (miRNA) expression profile in RAW264.7 cells incubated with or without simvastatin in the presence of LPS. MicroRNA-22 (miR-22) with the highest change was validated independently by qRT-PCR. Luciferase reporter assays were conducted to determine the association between miR-22 and the cysteine-rich protein 61 (Cyr61). Subsequently, we investigated the molecular mechanism by which miR-22 functions in the anti-inflammation of simvastatin in LPS-stimulated macrophages. We found that simvastatin treatment could significantly inhibit inflammation by modulating the expression of mediators, such as IL-1ß, TNF-α and IL-6, whose expression were increased remarkably in the activated RAW264.7 cells. miR-22 was found to be one of the most significantly upregulated miRNAs in LPS-stimulated RAW264.7 macrophages after treatment with simvastatin. Pre-treatment of simvastatin in LPS-stimulated RAW264.7 macrophages enhanced miR-22 expression in a dose dependent manner. Interestingly, Cyr61, a novel pro-inflammatory factor involved in the pathogenesis of atherosclerosis (AS), was identified as a direct target of miR-22. Overexpression of miR-22 enhanced the anti-inflammatory effects of simvastatin, whereas inhibition of miR-22 had an opposite effect. More importantly, further study demonstrated that the knockdown of Cyr61 by siRNA could attenuate the inhibitory effects of miR-22 inhibition on anti-inflammatory activities of simvastatin. The results clearly show that simvastatin inhibits the inflammation response in LPS-stimulated RAW264.7 macrophages through the miR-22/Cyr61 axis and suggests that targeting the miR-22/Cyr61 axis may be a promising molecular target for AS therapy.

Electrophysiological features and catheter ablation of symptomatic frequent premature atrial contractions.

AIMS: Frequent premature atrial contractions (PACs) are associated with increased risk of atrial fibrillation (AF), stroke, and death. This study aimed to explore the electrophysiological features of PACs with and without inducing AF and to evaluate the effectiveness of catheter ablation for PACs. METHODS AND RESULTS: Thirty-five consecutive patients with symptomatic, frequent, and drug-refractory PACs in the absence of AF (group A) and 35 patients with PACs-induced AF (group B) were enrolled. Coupling intervals (CoIs) of PACs were compared. Premature atrial contractions were mapped by the point-by-point and/or circular mapping technique. Focal ablation or pulmonary vein/superior vena cava isolation was applied as appropriate. A total of 35 ectopic foci were identified in group A. The majority of them were at pulmonary vein (PV) (n = 7), crista terminalis (n = 6), and para-Hisian area (n = 6). In group B, ectopic foci were in left-sided PVs in 21 patients, in right-sided PVs in 13 patients, and in SVC in 1 patient. There was significant difference in CoIs of PACs triggering AF and those from PVs and non-PV areas but without causing AF (362.8 ± 23.0 ms vs. 470.6 ± 60.1 ms vs. 515.6 ± 77.2 ms, P< 0.001). Premature atrial contractions were abolished in 32 of 35 patients from group A and in all patients from group B. At the end of follow-up, 29 patients in group A and 28 patients in group B were free of recurrence (off antiarrhythmic drugs) after the initial ablation (P =0.97). CONCLUSIONS: Frequent PACs in the absence of AF were characterized as having their predilection sites and longer CoIs than those inducing AF. Catheter ablation was effective to eliminate symptomatic, frequent, and drug-refractory PACs.

Image-guided left ventricular lead placement in cardiac resynchronization therapy for patients with heart failure: a meta-analysis.

BACKGROUND: Heart failure (HF) is a debilitating condition that affects millions of people worldwide. One means of treating HF is cardiac resynchronization therapy (CRT). Recently, several studies have examined the use of echocardiography (ECHO) in the optimization of left ventricular (LV) lead placement to increase the response to CRT. The objective of this study was to synthesize the available data on the comparative efficacy of image-guided and standard CRT. METHODS: We searched the PubMed, Cochrane, Embase, and ISI Web of Knowledge databases through April 2014 with the following combinations of search terms: left ventricular lead placement, cardiac resynchronization therapy, image-guided, and echocardiography-guided. Studies meeting all of the inclusion criteria and none of the exclusion criteria were eligible for inclusion. The primary outcome measures were CRT response rate, change in LV ejection fraction (LVEF), and change in LV end systolic volume (LVESV). Secondary outcomes included the rates of all-cause mortality and HF-related hospitalization. RESULTS: Our search identified 103 articles, 3 of which were included in the analysis. In total, 270 patients were randomized to the image-guided CRT and 241, to the standard CRT. The pooled estimates showed a significant benefit for image-guided CRT (CRT response: OR, 2.098, 95 % CI, 1.432-3.072; LVEF: difference in means, 3.457, 95 % CI, 1.910-5.005; LVESV: difference in means, -20.36, 95 % CI, -27.819 - -12.902). CONCLUSIONS: Image-guided CRT produced significantly better clinical outcomes than the standard CRT. Additional trials are warranted to validate the use of imaging in the prospective optimization of CRT.

A new score system for predicting response to cardiac resynchronization therapy.

BACKGROUND: The aim of this study was to establish a score system derived from clinical, echocardiographic and electrocardiographic indexes and evaluate its clinical value for cardiac resynchronization therapy (CRT) patient selection. METHODS: Ninety-three patients receiving CRT were enrolled. A patient selection score system was generated by the clinical, echocardiographic and electrocardiographic parameters achieving a significant level by univariate and multivariate Cox regression model. The positive response to CRT was a left ventricular end systolic volume decrease of ≥ 15% and not reaching primary clinical endpoint (death or re-hospitalization for heart failure) at the end of follow-up. RESULTS: Thirty-nine patients were CRT non-responders (41.94%) and 54 were responders (58.06%). A 4-point score system was generated based on tricuspid annular plane systolic excursion (TAPSE), longitudinal strain (LS), and complete left bundle branch block (CLBBB) combined with a wide QRS duration (QRSd). The sensitivity and specificity for prediction of a positive response to CRT at a score > 2 were 0.823 and 0.850, respectively (AUC: 0.92295% CI 0.691-0.916, p< 0.001). CONCLUSIONS: A patient selection score system based on the integration of TAPSE, LS and CLBBB combined with a wide QRSd can help to predict positive response to CRT effectively and reliably.

A novel individualized substrate modification approach for the treatment of long-standing persistent atrial fibrillation: preliminary results.

BACKGROUND: The most effective approach for long-standing persistent atrial fibrillation (LPAF) ablation remained undetermined. Our goal was to explore the heterogeneous left atrial substrate in patients with LPAF and to evaluate the effectiveness of a novel individualized substrate modification (ISM) approach in LPAF ablation. METHODS: One hundred and twenty-four patients with LPAF were randomized to ISM group (n=64) or stepwise ablation (SA) group (n=60). After pulmonary vein isolation, ISM was performed in the ISM group and SA was applied in the SA group. The clinical effectiveness after a single and a repeated procedure was compared. RESULTS: The total procedural time was significantly shorter in ISM than that in SA. In the ISM group, mild left atrial substrate was observed in 17 (27.4%), moderate in 26 (41.9%) and severe in 19 (30.6%) patients after successful cardioversion of the 62 patients. The intention-to-treat analysis showed that sinus rhythm was maintained in 65.5% of patients in the ISM group and in 45.0% of patients in the SA group after a single procedure, P=0.04. Atrial tachycardia (AT) recurred in 5 of 22 in the ISM group and in 20 of 33 in the SA group, P=0.01. After a repeated procedure, 75% of patients in the ISM group and 63.3% of patients in the SA group were free of further recurrence, P=0.16. CONCLUSIONS: Left atrial substrate varied noticeably in patients with LPAF. The ISM approach was superior to SA approach in terms of procedural time, recurrence rate of AT and clinical effectiveness after a single procedure. However, they yielded comparable outcomes after a repeated procedure.

Beneficial effects of catheter ablation of frequent premature ventricular complexes on left ventricular function.

BACKGROUND: Frequent premature ventricular complexes (PVCs) are associated with a reversible form of LV dysfunction. OBJECTIVE: We performed a meta-analysis to evaluate the effects of catheter ablation on improvement of LV function in patients with frequent PVCs. METHODS: We searched MEDLINE for cohort studies of patients who underwent catheter ablation of frequent PVCs. LVEF both before and postablation was reported. The endpoints were changes from baseline in both LVEF and LV end-diastolic diameter (LVEDd) postablation. Quantitative analysis of continuous variables was performed according to random effect methods by MetaAnalyst Beta 3.13 software. Association between site of origin (SOO) of PVCs and degree of LVEF improvement was evaluated by meta-regression using STATA V.12.0 software. Subgroup analysis of patients with LV dysfunction at baseline was performed. RESULTS: Fifteen studies with a total of 712 patients were included. The mean PVC burden before catheter ablation was 24% (95% CI 19% to 29%). The long-term success rate of PVC ablation ranged from 66% to 90%. The overall mean increase from baseline in LVEF postablation was 7.7% (95% CI 6.1% to 9.4%) and the overall mean decrease in LVEDd was -4.6 mm (95% CI -6.0 to -3.1 mm). Meta-regression showed no significant association of SOO of PVCs with the degree of postablation LVEF improvement. Subgroup analysis showed that the overall mean increase from baseline in LVEF postablation was 12.4% (95% CI 8.1% to 16.6%) and the overall mean decrease in LVEDd was -4.8 mm (95% CI -6.2 to -3.4 mm) in patients with LV dysfunction at baseline. CONCLUSIONS: Ablation of frequent PVCs improves cardiac function, especially for patients with LV dysfunction.