ABSTRACT Introduction: The objective of this study is to investigate the possible impact of coronary artery disease (CAD) on clinical outcomes of catheter ablation in patients with atrial fibrillation (AF). Methods: Patients with AF who underwent coronary computed tomography and catheter ablation were enrolled. The presence of stenotic severity and plaque, characteristics of coronary arteries, clinical data, and adverse outcomes of catheter ablation were analysed. Results: A total of 243 patients were enrolled, 100 (41%) patients with CAD. The CHA2DS2-VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke or transient ischemic attack, vascular disease, age 65-74 years, and sex category) score of AF patients with CAD was significantly (P<0.001) higher than of those without CAD. Presence of stenotic artery and plaques increased significantly with increase of CHA2DS2-VASc score (P<0.05). There was no significant (P=0.342) difference in AF recurrence between patients with and without CAD (30% versus 24%). Age, AF type, duration of AF, heart failure, CHA2DS2-VASc score, left ventricular ejection fraction, and left atrial diameter were significantly (P<0.05) correlated with AF recurrence in univariant analysis. Multivariable analysis revealed that duration of AF (hazard ratio [HR] 1.769), heart failure (HR 1.821), and left atrial diameter (HR 1.487, P=0.022) remained significant independent predictors of AF recurrence. Patients with AF and concomitant CAD were significantly (P=0.030) associated with a worse outcome. Conclusion: CAD concomitant with AF may be associated with a worse clinical outcome even though CAD does not significantly affect the risk of AF recurrence after ablation therapy. Introduction (CAD AF. . (AF) Methods enrolled plaque arteries data analysed Results 24 10 41% 41 (41% CHA2DS2VASc CHADSVASc CHA2DS2 VASc CHA DS congestive hypertension 7 years mellitus attack 6574 65 74 65-7 category P<0.001 P0001 P 0 001 (P<0.001 P<0.05. P005 P<0.05 05 P=0.342 P0342 342 (P=0.342 30% 30 (30 24%. 24% 24%) Age type fraction (P<0.05 hazard HR [HR 1.769, 1769 1.769 , 1 769 1.769) 1.821, 1821 1.821 821 1.821) 1487 487 1.487 P=0.022 P0022 022 P=0.030 P0030 030 (P=0.030 Conclusion therapy (AF 2 4 (41 CHADS CHA2DS 657 6 65- P<0.00 P000 00 (P<0.00 P00 P<0.0 P=0.34 P034 34 (P=0.34 3 (3 (P<0.0 176 1.76 76 182 1.82 82 148 48 1.48 P=0.02 P002 02 P=0.03 P003 03 (P=0.03 (4 P0 P<0. P=0.3 P03 (P=0.3 ( (P<0. 17 1.7 18 1.8 8 14 1.4 P=0.0 (P=0.0 P<0 P=0. (P=0. (P<0 1. P< P=0 (P=0 (P< P= (P= (P

Abstract Objective Abnormal complement activation is associated with periodontitis. W54011 is a novel non-peptide C5aR antagonist (C5aRA) that exhibits favorable anti-inflammatory effects in various inflammatory models. However, whether W54011 inhibits periodontitis has not yet been fully elucidated. To address this, we have investigated the probable anti-inflammatory mechanism of W54011 in LPS-treated inflammation in human gingival fibroblasts (HGFs). Methodology HGFs were isolated from healthy gingival tissue samples using the tissue block method and were identified with immunofluorescence staining. The CCK8 assay and reverse transcription-PCR (RT-PCR) were used to select the optimal induction conditions for Lipopolysaccharide (LPS) and C5aRA (according to supplementary data S1, S2 and S3). The levels of inflammatory cytokines, C5aR, and the activation of NF-κB/MAPK signaling pathways were determined by RT-quantitative PCR (RT-qPCR) and Western blotting. Results Immunofluorescence results showed that vimentin and FSP-1 were positive in HGFs and Keratin was negative in HGFs. Immunofluorescence staining demonstrated that C5aRA inhibited LPS-stimulated nuclear translocation of p-p65. RT-qPCR and Western blotting showed that C5aRA reduced the expression of IL-1β, IL-6, TNF-α, C5aR, p-p65, p-IκBα, p-JNK, p-c-JUN, and TLR4 in LPS-induced HGFs. Conclusion These findings suggested that C5aRA attenuated the release of inflammatory cytokines in LPS-induced HGFs by blocking the activation of the NF-κB and MAPK signaling pathways. W W5401 nonpeptide non peptide CaR C aR CaRA aRA (C5aRA antiinflammatory anti models However elucidated this LPStreated LPS treated . (HGFs) CCK transcriptionPCR transcription RTPCR RT (RT-PCR (LPS according S1 S S3. S3 S3) NFκB/MAPK NFκBMAPK NF κB/MAPK κB RTquantitative quantitative RTqPCR qPCR (RT-qPCR FSP1 FSP 1 FSP- LPSstimulated stimulated pp65. pp65 pp p p65. p65 p-p65 IL1β, IL1β ILβ IL 1β, 1β β IL-1β IL6, IL6 6, 6 IL-6 TNFα, TNFα TNF α, α TNF-α pp65, p65, pIκBα, pIκBα IκBα, IκBα p-IκBα pJNK, pJNK JNK, JNK p-JNK pcJUN, pcJUN c JUN, JUN p-c-JUN TLR LPSinduced induced NFκB W540 (HGFs κBMAPK pp6 p6 p-p6 IL- W54 p-p W5

ABSTRACT Introduction: The objective of this study is to investigate the possible impact of coronary artery disease (CAD) on clinical outcomes of catheter ablation in patients with atrial fibrillation (AF). Methods: Patients with AF who underwent coronary computed tomography and catheter ablation were enrolled. The presence of stenotic severity and plaque, characteristics of coronary arteries, clinical data, and adverse outcomes of catheter ablation were analysed. Results: A total of 243 patients were enrolled, 100 (41%) patients with CAD. The CHA2DS2-VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke or transient ischemic attack, vascular disease, age 65-74 years, and sex category) score of AF patients with CAD was significantly (P<0.001) higher than of those without CAD. Presence of stenotic artery and plaques increased significantly with increase of CHA2DS2-VASc score (P<0.05). There was no significant (P=0.342) difference in AF recurrence between patients with and without CAD (30% versus 24%). Age, AF type, duration of AF, heart failure, CHA2DS2-VASc score, left ventricular ejection fraction, and left atrial diameter were significantly (P<0.05) correlated with AF recurrence in univariant analysis. Multivariable analysis revealed that duration of AF (hazard ratio [HR] 1.769), heart failure (HR 1.821), and left atrial diameter (HR 1.487, P=0.022) remained significant independent predictors of AF recurrence. Patients with AF and concomitant CAD were significantly (P=0.030) associated with a worse outcome. Conclusion: CAD concomitant with AF may be associated with a worse clinical outcome even though CAD does not significantly affect the risk of AF recurrence after ablation therapy.

ABSTRACT Purpose: Spontaneous intracerebral hemorrhage (ICH) is a major public health problem with a huge economic burden worldwide. Ulinastatin (UTI), a serine protease inhibitor, has been reported to be anti-inflammatory, immune regulation, and organ protection by reducing reactive oxygen species production, and inflammation. Necroptosis is a programmed cell death mechanism that plays a vital role in neuronal cell death after ICH. However, the neuroprotection of UTI in ICH has not been confirmed, and the potential mechanism is unclear. The present study aimed to investigate the neuroprotection and potential molecular mechanisms of UTI in ICH-induced EBI in a C57BL/6 mouse model. Methods: The neurological score, brain water content, neuroinflammatory cytokine levels, and neuronal damage were evaluated. The anti-inflammation effectiveness of UTI in ICH patients also was evaluated. Results: UTI treatment markedly increased the neurological score, alleviate the brain edema, decreased the inflammatory cytokine TNF-α, interleukin‑1β (IL‑1β), IL‑6, NF‑κB levels, and RIP1/RIP3, which indicated that UTI-mediated inhibition of neuroinflammation, and necroptosis alleviated neuronal damage after ICH. UTI also can decrease the inflammatory cytokine of ICH patients. The neuroprotective capacity of UTI is partly dependent on the MAPK/NF-κB signaling pathway. Conclusions: UTI improves neurological outcomes in mice and reduces neuronal death by protecting against neural neuroinflammation, and necroptosis.

Polydatin, a small molecule from Polygonum cuspidatum, has many biological functions, particularly anti-cancer effects. However, the anti-cancer effects of polydatin in hepatocellular carcinoma (HCC) have not been examined yet. In the present study, MTT assay, BrdU assay, transwell invasion assay, and wound healing assay were performed to determine cell proliferation, invasion and migration. Flow cytometry and TUNEL assay were used to measure cell apoptosis. Quantitative real-time PCR and western blotting assays were used to determine mRNA and protein expression levels. Xenograft experiment was performed to determine the in vivo anti-tumor effect of polydatin. Immunostaining was performed to analyze the expression of caspase-3 and Ki-67. Our results showed that polydatin inhibited cell proliferation in a concentration-dependent and time-dependent manner in the HCC cell lines. Polydatin also induced cell apoptosis in a concentration-dependent manner possibly via increasing the caspase-3 activity, and up-regulating the protein expression of caspase-3, caspase-9, Bax, and down-regulating the protein expression of Bcl-2. In addition, polydatin treatment had an inhibitory effect on cell proliferation, invasion and migration in HCC cell lines. Polydatin treatment also suppressed the Wnt/beta-catenin signaling activities in HCC cells. Polydatin treatment significantly reduced tumor growth in nude mice inoculated with HepG2 cells, suppressed the expression of Ki-67, and increased caspase-3 expression and TUNEL activity. Our data indicated the important role of polydatin for the suppression of HCC progression.

OBJECTIVES: Behcet’s disease is a form of systematic vasculitis that affects vessels of various sizes. Aortic pseudoaneurysm is one of the most important causes of death among patients with Behcet’s disease due to its high risk of rupture and associated mortality. Our study aimed to investigate the outcomes of Behcet’s disease patients with aortic pseudoaneurysms undergoing open surgery and endovascular aortic repair. METHODS: From January 2003 to September 2014, ten consecutive patients undergoing surgery for aortic pseudoaneurysm met the diagnostic criteria for Behcet’s disease. Endovascular repair was the preferred modality and open surgery was performed as an alternative. Systemic immunosuppressive medication was administered after Behcet’s disease was definitively diagnosed. RESULTS: Eight patients initially underwent endovascular repair and two patients initially underwent open surgery. The overall success rate was 90% and the only failed case involved the use of the chimney technique to reach a suprarenal location. The median follow-up duration was 23 months. There were 7 recurrences in 5 patients. The median interval between operation and recurrence was 13 months. No significant risk factors for recurrence were identified, but a difference in recurrence between treatment and non-treatment with preoperative immunosuppressive medication preoperatively was notable. Four aneurysm-related deaths occurred within the follow-up period. The overall 1-year, 3-year and 5-year survival rates were 80%, 64% and 48%, respectively. CONCLUSIONS: Both open surgery and endovascular repair are safe and effective for treating aortic pseudoaneurysm in Behcet’s disease patients. The results from our retrospective study indicated that immunosuppressive medication was essential to defer the occurrence and development of recurrent aneurysms.

Para investigar os efeitos da sanguinarina (SAN) em lesões induzidas em ratos por radiação aguda, 45 ratos foram aleatoriamente divididos em grupo controle, grupo 10 Gy e grupo SAN+10 Gy. Os ratos dos grupos 10 Gy e SAN+10 Gy foram expostos à radiação de raio-X simples com uma dose acumulada de 10 Gy. Aos ratos do grupo SAN+10 Gy administraram-se, intraperitonealmente, 2.5 mg/kg de peso de SAN antes da radiação. Aos 5 dias de exposição à radiação, sacrificaram-se 5 ratos de cada grupo e retiraram-se amostras do intestino delgado, pulmões, baço e fígado para exames histopatológicos. Comparando com o grupo 10 Gy, a doença por radiação foi claramente atrasada e atenuada no grupo SAN+10 Gy. A análise de sobrevivência mostrou diferença significativa entre os dois grupos de radiação (P<0.05) e o tempo de sobrevivência média foi de mais 3 dias no grupo SAN+10 Gy do que no grupo 10 Gy (7.21±0.19 vs 4.20±0.13, P<0.001). Danos induzidos nos órgãos por radiação, baseados em exames histopatológicos, foram reduzidos pelo pré-tratamento com SAN. As pontuações de classificação da patologia Chiu, um índice para os danos intestinais, foi significativamente menor no grupo SAN+10 Gy do que no grupo 10 Gy (2.77±0.48 vs 4.37±0.31, P<0.01). Resultado semelhante foi obtido na pontuação patológica do pulmão (1.67±0.21 vs 2.33±0.38, P<0.01). As nossas descobertas preliminares mostram que SAN protege os animais contra doenças induzidas pela radiação e danos agudos nos órgãos seguidos de morte animal.

To investigate the effects of sanguinarine (SAN) on acute radiation induced injury in mice, 45 mice were randomly divided into control, 10 Gy and SAN+10 Gy groups. Mice in the 10 Gy and SAN+10 Gy groups were exposed to single X-ray radiation with an accumulated dose of 10 Gy. Mice in the SAN+10 Gy group were administered intraperitoneally with 2.5 mg/kg body weight of SAN before radiation. Five days after radiation exposure, 5 mice from each group were sacrificed and samples of the small intestine, lung, spleen and liver were fixed for histopathological examinations. Compared with the 10 Gy group, radiation sickness was obviously delayed or attenuated in the SAN+10 Gy group. Survival analysis showed a significant difference between 2 radiation groups (P<0.05) and mean survival time was 3 days longer in the SAN+10 Gy group than in the 10 Gy group (7.21±0.19 vs. 4.20±0.13, P<0.001). Radiation-induced organ damage, based on histopathological examinations, was decreased by SAN pretreatment. Chiu’s pathology grading scores, which is an index of intestinal damage, was significantly lower in the SAN+10 Gy group than in the 10 Gy group (2.77±0.48 vs. 4.37±0.31, P<0.01). A similar result was obtained in the pathological score of lung (1.67±0.21 vs. 2.33±0.38, P<0.01). Our preliminary findings demonstrated that SAN protects animals against radiation-induced sickness and acute damage to organs and following animal death.

The present paper deals with a histological study of the blood cells of Bufo Bufo gargarizans in different months: January, March, May, July and October. The methods used are by routine blood smear in Wright stain and observation in vivo. We found that in smears and in vivo two main types of cells of the red cells: mitotic as well as amitotic. While amitotic occurs all the year round, particularly in July, mitosis so far had been seen only in July. It is also found that there are plenty of neutrophils in the blood cells of Bufo Bufo gargarizans, furthermore, the nuclei of these cells are polymorphic, especially in January and March. Meanwhile, the concentration of red cells was lowest in May and highest in January; The concentration of white blood cells was highest in October and lowest in March; As to granulocytes, eosinophils in July and October had higher proportion, while neutrophils and basophils in July; in agranulocytes, mononuclear cells reached the highest value in March, lowest in January, lymphocytes and the maximum value appeared in May, the lowest value appeared in July. Morphological changes of thrombocytes were not obvious.

Se realizó el presente estudio histológico de las células sanguíneas de Bufo Bufo gargarizans en diferentes meses del año: enero, marzo, mayo, julio y octubre. Fueron utilizados métodos de rutina por frotis de sangre con tinción de Wright y observación in vivo. Encontramos dos tipos principales de células de glóbulos rojos al frotis como también en células in vivo: mitóticas y amitóticas. Por cuanto amitosis se produce durante todo el año, sobre todo en el mes de julio, la mitosis hasta el momento se había observado solamente en julio. Además, se encontró una gran cantidad de neutrófilos en los glóbulos de Bufo Bufo gargarizans. Los núcleos de estas células son polimórficos, especialmente en enero y marzo. La concentración de glóbulos rojos era más bajo en mayo y más alta en enero; la concentración de las células blancas de la sangre fue mayor en octubre y menor en marzo. En cuanto a los granulocitos, eosinófilos estos presentaron una mayor proporción en julio y octubre, mientras que los neutrófilos y basófilos registraran una mayor proporción en el mes de julio. Los agranulocitos y las células mononucleares alcanzaron el valor más alto en marzo, y el valor más bajo en enero. Los linfocitos y el valor máximo fue registrado en mayo, el valor más bajo fue registrado en julio. No fueron evidentes los cambios morfológicos de trombocitos, lo que podría tener relación con su estabilidad.