The Value of Adjunctive Left Atrial Posterior Wall Isolation on Clinical Outcomes in Atrial Fibrillation Patients: A Systematic Review and Meta-Analysis.

Background: Although pulmonary vein isolation (PVI) remains the mainstream way of atrial fibrillation (AF) ablation. The left atrial posterior wall (LAPW) may contributes to the development of AF as an arrhythmogenic substrate. The efficacy of additional left atrial posterior wall isolation (LAPWI) beyond PVI is in AF patients remains undefined. This study explored the influence of posterior wall isolation (PWI) on clinical outcomes in AF patients. Methods: PubMed, EMBASE, and Cochrane Library databases were searched for studies comparing the outcomes of AF with and without PWI. The efficacy outcomes were recurrence of all atrial arrhythmia (AA), atrial fibrillation (AF), and atrial flutter (AFL)/atrial tachycardia (AT). The safety outcomes were mainly focused on procedural adverse events. Results: A total of 16 studies (7 randomized controlled trials (RCTs), 3 prospective studies and 6 retrospective analyses) with 3340 AF patients were enrolled (1550 patients in PVI with PWI group and 1790 in PVI alone group). 12 studies included persistent atrial fibrillation patients, 3 studies with paroxysmal AF patients and 1 study with paroxysmal AF and persistent AF concurrently. Mean follow-up period was 16.56 months. In AF patients, adjunctive PWI obviously reduced the recurrence of all atrial arrhythmias (risk ratio (RR) 0.78 [95% CI 0.64-0.95], I 2 = 79%, p = 0.01) and the recurrence of AF (RR 0.68 [95% CI 0.53-0.88], I 2 = 75%, p = 0.004); Meanwhile, additional PWI left no impact substantially on lower recurrence of AFL/AT (RR 1.23 [95% CI 0.94-1.60], I 2 = 49%, p = 0.12). The results seemed to be no significant differences in occurrence rate of procedural complications between the PVI only and PWI+PVI (RR 1.19 [95% CI 0.80-1.79], I 2 = 0%, p = 0.39). In subgroup analyses, the benefit of adjunctive PWI compared with PVI only was more distinct in persistent AF group and cryoballoon ablation group. Notably, adjunctive PWI with radiofrequency ablation may induce a slight increase of recurrent AFL/AT compared with PVI only (RR 1.56 [95% CI 1.02-2.39], I 2 = 30%, p = 0.04). Conclusions: Compared with PVI alone, additional PWI to PVI appeared to be associated with decreased recurrence of AF and atrial arrhythmias without an increased occurrence of procedural complications, especially in persistent AF patients. Cryoballoon ablation seemed more suitable for PWI compared with radiofrequency ablation. More RCTs are needed to verify the conclusion.

Non-enhanced MRI in combination with color Doppler flow imaging for improving diagnostic accuracy of parotid gland lesions.

PURPOSE: To determine the value of non-enhanced MRI in combination with color Doppler flow imaging (CDFI) for differentiating malignant parotid tumors from benign ones. METHODS: This retrospective study analyzed 51 parotid gland lesions (39 benign and 12 malignant) in 51 patients who underwent preoperative CDFI as well as non-enhanced MRI including T1-weighted, T2-weighted, and diffusion-weighted imaging (DWI). Degrees of intratumor vascularity were categorized into four grades basing on CDFI findings. The relationships between the lesion and its adjacent external carotid artery and retromandibular vein were inspected on T1-weighted and T2-weighted images. Apparent diffusion coefficient (ADC) values were calculated from diffusion-weighted images, and were used to classify the parotid gland lesions with and without reference to the CDFI findings. The classification results were compared using the McNemar test. Sensitivity, specificity, and accuracy percentages were calculated when the non-enhanced MRI/CDFI findings were used to differentiate benign lesions from malignant ones. RESULTS: The diagnostic accuracy (96.1 vs 82.4%) was significantly improved when ADCs were used together with CDFI findings for classifying parotid gland lesions compared to when ADCs were used alone. Pleomorphic adenomas had the highest ADCs. The ADC thresholds were 1.425 × 10-3 mm2/s for differentiating pleomorphic adenomas from carcinomas, 0.999 × 10-3 mm2/s for differentiating pleomorphic adenomas from other benign lesions, and 0.590 × 10-3 mm2/s for differentiating benign lesions other than pleomorphic adenomas from lymphomas. CONCLUSION: Combining CDFI with non-enhanced MRI can improve the diagnostic accuracy of MRI for classifying parotid gland lesions.

Exogenous nitric oxide enhances the prophylactic effect of aminoguanidine, a preferred iNOS inhibitor, on bleomycin-induced fibrosis in the lung: Implications for the direct roles of the NO molecule in vivo.

OBJECTIVE: Inducible nitric oxide synthase (iNOS) aggravates and endothelial nitric oxide synthase (eNOS) ameliorates fibrosis in the lung. Our previous study demonstrated that aminoguanidine (AG), a preferred iNOS inhibitor, prevents bleomycin-induced injury and fibrosis in the lung. The diethylenetriamine nitric oxide adduct (DETA/NO) is a slow-release NO donor. Here, to clarify the exact role of the nitric oxide (NO) molecule in the pathogenesis of pulmonary fibrosis in vivo, we observed the effects of inhalation of aerosolized DETA/NO on fibrosis in the lungs of bleomycin-exposed rats with AG treatment, including the effects on the myofibroblast number, collagen deposition, peroxynitrite anion (ONOO-) formation, and injury in the lung. DESIGN AND METHODS: Rats received a single intratracheal instillation of bleomycin or normal saline (NS) on day 0, followed by a daily intraperitoneal injection of AG or NS from day 1 to day 13. Each group was additionally given a daily inhalation of DETA/NO or placebo from day 1 to day 13. On day 14, half of the rats in each group was euthanized, and plasma nitrite and nitrate (NOx), myofibroblasts, type I collagen, ONOO- and injury in the lung were estimated by the Griess reaction, western blotting, immunohistochemical staining, sirius red staining, and hematoxylin and eosin (HE) staining, respectively. On day 28, the other half of the rats in each group was euthanized, and the total collagen of the lung was evaluated by hydroxyproline assay. RESULTS: ① At the day 14 time point, AG reduced the plasma NOx level in bleomycin rats, while this drug had no significant effect on sham rats. Inhalation of aerosolized DETA/NO increased the plasma NOx level of bleomycin + AG rats, sham rats and sham + AG rats. However, due to large areas of airspace obliteration in the lungs of bleomycin rats, DETA/NO inhalation had no significant effect on the plasma NOx level in these rats. ② At the day 14 time point, AG reduced ONOO- formation (marked by nitrotyrosine, NT), injury, myofibroblast number, and type I collagen deposition in the lungs of bleomycin rats, while this drug had no significant impact on the above parameters in the lungs of sham rats. Interestingly, DETA/NO inhalation enhanced the preventive effects afforded by AG on myofibroblast number and type I collagen deposition, but had no significant impact on ONOO- and injury in lung. ③ At the day 28 time point, because rats were not exposed to DETA/NO after day 13, there was no significant difference of the plasma NOx level in sham rats, sham + AG rats, bleomycin rats, and bleomycin + AG rats between DETA/NO inhalation and placebo inhalation. Interestingly, rats administered both DETA/NO and AG still showed a reduction in total collagen of the entire lung compared to rats administered AG alone at this time point. CONCLUSIONS: Exogenous NO enhances the prophylactic effect afforded by AG on the myofibroblast number and collagen deposition in the lungs of bleomycin-treated rats in vivo. These results suggest that NO has a direct antifibrotic effect in lungs, except for the formation of ONOO- in the development of pulmonary fibrosis in vivo.

Joint effects of CD8A and ICOS in Long QT Syndrome (LQTS) and Beckwith-Wiedemann Syndrome (BWS).

BACKGROUND: Long QT Syndrome (LQTS) and Beckwith-Wiedemann Syndrome (BWS) are complex disorders with unclear origins, underscoring the need for in-depth molecular investigations into their mechanisms. The main aim of this study is to identify the shared key genes between LQTS and BWS, shedding light on potential common molecular pathways underlying these syndromes. METHODS: The LQTS and BWS datasets are available for download from the GEO database. Differential expression genes (DEGs) were identified. Weighted gene co-expression network analysis (WGCNA) was used to detect significant modules and central genes. Gene enrichment analysis was performed. CIBERSORT was used for immune cell infiltration analysis. The predictive protein interaction (PPI) network of core genes was constructed using STRING, and miRNAs regulating central genes were screened using TargetScan. RESULTS: Five hundred DEGs associated with Long QT Syndrome and Beckwith-Wiedemann Syndrome were identified. GSEA analysis revealed enrichment in pathways such as T cell receptor signaling, MAPK signaling, and adrenergic signaling in cardiac myocytes. Immune cell infiltration indicated higher levels of memory B cells and naive CD4 T cells. Four core genes (CD8A, ICOS, CTLA4, LCK) were identified, with CD8A and ICOS showing low expression in the syndromes and high expression in normal samples, suggesting potential inverse regulatory roles. CONCLUSION: The expression of CD8A and ICOS is low in long QT syndrome and Beckwith-Wiedemann syndrome, indicating their potential as key genes in the pathogenesis of these syndromes. The identification of shared key genes between LQTS and BWS provides insights into common molecular mechanisms underlying these disorders, potentially facilitating the development of targeted therapeutic strategies.

Higher expression of TSR2 aggravating hypertension via the PPAR signaling pathway.

Hypertension is a complex disease with unknown causes. Therefore, it's crucial to deeply study its molecular mechanism. The hypertension dataset was obtained from Gene Expression Omnibus data base (GEO), and miRNA regulating central hub genes was screened via weighted gene co-expression network (DEGs) and gene set enrichment (GSEA). Cell experiments validated TSR2's role and the PPAR signaling pathway through western blotting. 500 DEGs were identified for hypertension, mainly enriched in actin cross-linking, insulin signaling, PPAR signaling, and protein localization. Eight hub genes (SEC61G, SRP14, Liy AR, NIP7, SDAD1, POLR1D, DYNLL2, TSR2) were identified. Four hub genes (LYAR, SDAD1, POLR1D, TSR2) exhibited high expression levels in the hypertensive tissue samples, while showing low expression levels in the normal tissue samples. This led us to speculate that they may have relevant regulatory effects on hypertension. When TSR2 was knocked down in the hypertension peripheral blood mononuclear cells (PBMC) model, the critical proteins in the PPAR signaling pathway (FABP, PPAR, PLTP, ME1, SCD1, CYP27, FABP1, OLR1, CPT-1, PGAR, CAP, ADIPO, MMP1, UCP1, ILK, PDK1 UBC AQP7) were downregulated. This also occurred in the hypertension peripheral blood mononuclear cells (PBMC) + TSR2_ OV model. TSR2 is highly expressed in individuals with hypertension and may play a significant role in the development of hypertension through the PPAR signaling pathway. TSR2 could serve as a molecular target for the early diagnosis and precise treatment of hypertension, providing a valuable direction for the mechanism research of this condition.

Proteins extracted from pearl oyster (Pinctada martensii) with efficient accelerated wound healing in vitro through promoting cell proliferation, migration, and collagen formation.

Ethnopharmacological relevance: Pearl oyster (Pinctada martensii) is used in Chinese traditional medicine use in photoprotective, anti-inflammatory, and wound treatment.Aim of the study: This study explored whether the mucus protein of Pearl oyster (protein of Pinctada martensii, PMP) affects human skin fibroblast (HSF) proliferation, migration, collagen-related gene expression related to collagen formation, and in vivo healing effects. Materials and methods: The PMP component was analyzed by LC-MS/MS. The cell viability was evaluated using a CCK-8 kit. The expression genes were measured by reverse transcription polymerase chain reaction. A full-thickness excisional wounding model in Sprague-Dawley (SD) rats was used to test the repairing effect of PMP in vivo, and Hematoxylin-Eosin (H&E) and Masson's Trichrome staining were applied to evaluate skin structure. Results: The components of PMP were identified using LC-MS/MS proteomics, and a total of 3023 proteins were detected. The results of PMP-treated HSF showed that PMP effectively promoted cell proliferation by 1.6-fold and cell migration by 1.5-fold at a concentration of 1 mg/mL. Additionally, PMP treatment up-regulated the expression levels of collagen-related genes COL1A1, COL3A1, and MMP-1 in fibroblasts. Furthermore, PMP was applied in the therapy of full-thickness excisional wounds in rats. The results demonstrated that PMP significantly accelerated wound healing time, resulted in the recovery of dermal and epithelial thickness, and stimulated collagen regeneration. The regenerated skin closely resembled the structure of normal skin. Conclusions: These findings provide solid evidence supporting the potential of PMP as a promising candidate for the treatment of skin wounds.

Comprehensive investigating of mismatch repair genes (MMR) polymorphisms in participants with chronic hepatitis B virus infection.

Background and aim: In this study, we focused on the relationship between single nucleotide polymorphisms in MMR genes and the occurrence and development of HBV infection. Materials and methods: A total of 3,128 participants were divided into five groups: negative control group (NeC), spontaneous clearance group (SC), chronic hepatitis B group (CHB), liver cirrhosis group (LC) and hepatocellular carcinoma group (HCC), CHB, liver cirrhosis and hepatocellular carcinoma constitute HLD. We conducted three case-control studies: NeC (840 cases) vs. HLD (1792 cases), SC (486 cases) vs. HLD (1792 cases) and CHB + LC (1,371 cases) vs. HCC (421 cases). 11 polymorphic loci in MLH1, MLH3, MSH5, PMS1 and PMS2 were involved in genotyping by Sequenom MassArray. The SNPStats performed Hardy-Weinberg equilibrium test. Linkage disequilibrium patterns were visualized using Haploview4.2. The GMDR (v0.9) was conducted to generalized multifactor dimension reduction analysis. The correlation, multiplicative interaction and additive interaction analyses were calculated by Logistic Regression through SPSS21.0. Matrix and programmed excel were also involved in the calculation of additive interaction. Results: In NeC vs. HLD group, MSH5-rs1150793(G) was a risk base to HBV susceptibility (nominal p = 0.002, OR = 1.346). We found multiplicative interaction between MLH1-rs1540354 (AA + AT) and PMS1-rs1233255 (AA) (nominal p = 0.024, OR = 1.240). There was additive interaction between PMS1-rs1233255 (AA) and PMS1-rs256554(CA + CC). In SC vs. HLD group, MLH1-rs1540354 (TT) was a risk genotype (nominal p < 0.05, OR>1). Through haplotype analysis, we found the linkage disequilibrium of three loci in MLH1. The results of GMDR showed the optimal five-locus model about the spontaneous clearance of HBV. In CHB + LC vs. HCC group, PMS2-rs12112229(A) was related to the cancerization of liver. Conclusion: We found rs1150793(G), rs1540354(T) and rs12112229(A) were significantly related to HBV susceptibility, spontaneous clearance of HBV and cancerization after infection, respectively.

Natural Morin-Based Metal Organic Framework Nanoenzymes Modulate Articular Cavity Microenvironment to Alleviate Osteoarthritis.

Osteoarthritis (OA) is always characterized as excessive reactive oxygen species (ROS) inside articular cavity. Mimicking natural metalloenzymes with metal ions as the active centers, stable metal organic framework (MOF) formed by natural polyphenols and metal ions shows great potential in alleviating inflammatory diseases. Herein, a series of novel copper-morin-based MOF (CuMHs) with different molar ratios of Cu2+ and MH were employed to serve as ROS scavengers for OA therapy. As a result, CuMHs exhibited enhanced dispersion in aqueous solution, improved biocompatibility, and efficient ROS-scavenging ability compared to MH. On the basis of H2O2-stimulated chondrocytes, intracellular ROS levels were efficiently declined and cell death was prevented after treated by Cu6MH (Cu2+ and MH molar ratio of 6:1). Meanwhile, Cu6MH also exhibited efficient antioxidant and anti-inflammation function by down-regulating the expression of IL6, MMP13, and MMP3, and up-regulating cartilage specific gene expression as well. Importantly, Cu6MH could repair mitochondrial function by increasing mitochondrial membrane potential, reducing the accumulation of calcium ions, as well as promoting ATP content production. In OA joint model, intra-articular (IA) injected Cu6MH suppressed the progression of OA. It endowed that Cu6MH might be promising nanoenzymes for the prevention and treatment of various inflammatory diseases.

MicroRNA-587 Functions as a Tumor Suppressor in Hepatocellular Carcinoma by Targeting Ribosomal Protein SA.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most highly aggressive cancer worldwide with an extremely poor prognosis. Evidence has revealed that microRNA-587 (miR-587) is abnormally expressed in a series of cancers. However, its expressions and functions in HCC have not been clearly acknowledged. METHODS: We detected the expression level of miR-587 both in the Gene Expression Omnibus (GEO) database and 86 paired clinical HCC tissues together with paired adjacent normal tissues by quantitative real-time PCR (qRT-PCR). Afterwards, the transfected HCC cell line SMMC-7721 cells were collected for the cell proliferation assay, cell-cycle arrest, cell migration, and invasion assays to explore the roles of miR-587 in regulating cellular function. In addition, bioinformatics analysis, combined with qRT-PCR and dual-luciferase reporter assays, were performed to confirm whether ribosomal protein SA (RPSA) mRNA was the direct target gene of miR-587. Moreover, the Cancer Genome Atlas (TCGA) and GEO databases as well as 86 paired clinical HCC tissues were used to verify the negative regulation between miR-587 and RPSA. RESULTS: In the present study, both the GEO database (GSE36915 and GSE74618) analysis and qRT-PCR analysis of 86 paired clinical tissues showed that miR-587 was significantly downregulated in HCC tissues. The overexpression of miR-587 inhibited proliferation, cell cycle, migration, and invasion in SMMC-7721 cells. In addition, miR-587 directly interacted with the 3'-untranslated region (UTR) of RPSA. Moreover, miR-587 overexpression directly suppressed RPSA expression, and the two genes were inversely expressed in HCC based on the analyses in TCGA and GEO (GSE36376) databases and qPCR analysis of 86 paired clinical tissues. CONCLUSION: Our results demonstrate that miR-587 is downexpressed in HCC and regulates the cellular function by targeting RPSA.

Contrast-enhanced ultrasound for needle biopsy of thoracic lesions.

Two-dimensional ultrasound (US) and color doppler flow imaging are associated with certain limitations in the preprocedural evaluation and design of the puncture path for biopsies of thoracic lesions, such as a poorly defined boundary between the tumor and the atelectatic lesions in central lung cancer with atelectasis. Contrast-enhanced ultrasound (CEUS) can be valuable in the preoperative evaluation of the biopsy site and in increasing the accuracy of the biopsy. The present study investigated the value of clinical application of CEUS in US-guided core needle biopsy (US-CNB) in improving the diagnostic accuracy in thoracic lesions. A total of 120 patients with first-stage thoracic lesions from the Affiliated Tumor Hospital of Guangxi Medical University who underwent US-CNB were recruited and randomnly assigned to a conventional US group (n=66) and a CEUS group (n=54). All patients underwent preoperative evaluation and US-guided puncture of thoracic lesions. The intergroup differences in sonographic features, biopsy duration, biopsy success rate and complications were assessed. The CEUS group had a higher rate of detection of necrotic tissue (40.7% vs. 16.7%; χ2=8.633; P=0.003) and change of initial puncture path (48.1%) compared with the US group. In central lung cancer with atelectasis, the ability to distinguish between tumor and atelectasis was higher in the CEUS group compared with the conventional US group (31.5 vs. 7.6%; χ2=11.336; P=0.001). In addition, the CEUS group had a higher puncture success (96.3 vs. 80.3%; χ2=6.946; P=0.008) and a lower complication rate (3.7% vs. 18.2%; χ2=6.041; P=0.014) compared with the US group. CEUS can identify necrotic areas and occult tumors within atelectatic lung tissue and can be used for guiding puncture biopsy of thoracic lesions to improve the diagnostic accuracy with greater comparative clinical utility than conventional US. Pre-biopsy CEUS is especially useful for patients undergoing repeated US-CNB and those with hypovascular lesions, atelectasis or necrosis.

Contrast-Enhanced Ultrasound to Monitor Early Recurrence of Primary Hepatocellular Carcinoma after Curative Treatment.

OBJECTIVE: To evaluate contrast-enhanced ultrasound (CEUS) for monitoring early intrahepatic recurrence of primary hepatocellular carcinoma (HCC) after curative treatment. METHODS: We prospectively analyzed 97 patients (124 nodules) with primary HCC who underwent hepatic resection or radiofrequency ablation and subsequently experienced intrahepatic recurrence. Patients were assessed with conventional ultrasound and CEUS. They were also assessed with contrast-enhanced computed tomography (CECT) and/or magnetic resonance imaging (MRI). The image characteristics of CEUS of recurrent hepatocellular carcinoma and high-grade dysplastic nodules (HGDNs) were analyzed. In addition, the ability of CEUS and CECT/MRI to assess internal artery vascularization in recurrent disease was compared. RESULTS: CEUS of recurrent hepatocellular carcinoma showed hyperenhancement in the arterial phase in 96 of 99 nodules, and it showed hypo- or isoenhancement for portal venous and delayed phases. The most common enhancement patterns were "fast-in and slow-out" and "fast-in and fast-out". Based on the arterial hyperenhancement of lesions and with clinical data such as patient history of HCC and increased level of serum alpha-fetoprotein, the diagnostic accuracy of CEUS for recurrent HCC was significantly higher than that based on the enhancement pattern of "fast-in and fast-out". CEUS of HGDNs showed local or global hyperenhancement during the arterial phase, isoenhancement during the portal venous phase, and isoenhancement or slight hypoenhancement during the delayed phase. The enhancement pattern was "fast-in and slow-out". In some cases, it was difficult to differentiate HGDNs from recurrent disease using CEUS. Vascularization in recurrent disease was significantly higher when assessed by CEUS than when assessed with CECT/MRI (P < 0.05). For detecting recurrent disease, CEUS showed sensitivity of 97.0%, specificity of 68.0%, positive predictive value of 92.3%, and negative predictive value of 85.0%. The corresponding parameters for CECT/MRI were 71.7%, 72.0%, 88.8%, and 39.1%. CONCLUSION: Intrahepatic recurrent HCC and HGDNs with diameter ≤ 3.0 cm have a characteristic appearance on CEUS. This imaging modality may be effective for monitoring early intrahepatic recurrence after curative treatment of primary HCC.