Short QRS Duration After His-Purkinje Conduction System Pacing Predicts Left Ventricular Complete Reverse Remodeling in Patients With True Left Bundle Branch Block and Heart Failure.

Objective: This study aimed to explore the outcomes of His-Purkinje conduction system pacing (HPCSP) and to screen the predictors of left ventricular (LV) complete reverse remodeling in patients with true left bundle branch block (LBBB) and heart failure with reduced ejection fraction (HFrEF). Methods: Patients who underwent HPCSP for true LBBB and HFrEF from April 2018 to August 2020 were consecutively enrolled. All participants were followed up for at least 1 year. Thrombosis, infection, lead dislodgement, perforation, and other complications were observed after HPCSP. Clinical data, including echocardiographic parameters, electrocardiogram measurements, and cardiac function, were assessed before and after the procedure. Results: A total of 46 patients were enrolled. HPCSP was successfully deployed in 42 cases (91.30%), which included 37 cases with His bundle pacing (HBP) and 5 cases with left bundle branch pacing (LBBP). The QRS duration decreased significantly (169.88 ± 19.17 ms vs. 113.67 ± 20.68 ms, P < 0.001). Left ventricular end-systolic volume (LVESV) (167.67 ± 73.20 ml vs. 85.97 ± 62.24 ml, P < 0.001), left ventricular end-diastolic diameter (LVEDD) (63.57 ± 8.19 mm vs. 55.46 ± 9.63 mm, P = 0.003) and left ventricular ejection fraction (LVEF) (26.52 ± 5.60% vs. 41.86 ± 11.56%, P < 0.001) improved dramatically. Complete reverse remodeling of the LV with normalized LVEF and LVEDD was found in nearly half of the patients (45.24%). A short QRS duration after HPCSP was a strong predictor of normalized LVEF and LVEDD (P < 0.001). The thresholds increased markedly in two patients approximately 6 months after HBP. No patients died during the total follow-up period of 20.07 ± 6.45 months. Conclusion: Complete reverse remodeling of the LV could be found in nearly half of the patients with HFrEF and true LBBB after HPCSP, and the short QRS duration after HPCSP was a strong predictor.

Brady-arrhythmias in patients with atrial fibrillation and heart failure of reduced ejection fraction: is his-bundle pacing superior to biventricular pacing？.

OBJECTIVE: To investigate the efficacy and safety of His-bundle pacing (HBP) compared with the traditional biventricular pacing (BVP) on patients with brady-arrhythmias, who suffer from permanent atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF). METHODS: All patients with brady-arrhythmias, permanent AF and HFrEF were continuously enrolled from January 2017 to July 2019 and followed up for at least 12 months. The differences in QRS duration (QRSd), New York Heart Association (NYHA) classification, left ventricular ejection fraction (LVEF), tricuspid regurgitation grade, mitral regurgitation grade, left ventricular end-diastolic diameter (LVEDD), and left atrial size were compared. RESULTS: A total of 52 patients were enrolled: 37 patients were with HBP and 15 patients with BVP. There was no electrode dislodged, perforation, infection or thrombosis during the follow-up of 18.12 ± 4.45 months. The success rate for HBP implantation was 88.10%. The capture threshold of his-bundle and the threshold of the left ventricular lead remained stable during follow-up. LVEF increased to higher than 50% in 11 patients with HBP (29.73%). The NYHA classification (both p < .001), LVEF (both p < .001) and LVEDD improved significantly during the follow-up in both groups. NYHA (p = .030), LVEF (p = .013), and LVEDD (p = .003) improved in patients with HBP compared with BVP. CONCLUSION: HBP was safe and more effective in improving the cardiac function and remodeling in patients with brady-arrhythmias, permanent AF and HFrEF compared with BVP.

Anti-inflammatory action of physalin A by blocking the activation of NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Physalis Calyx seu Fructus is typically used to treat inflammatory diseases such as upper respiratory tract infection and acute tonsillitis in clinical practice of China. Physalin A, a main active ingredient of this traditional Chinese medicine (TCM), has been reported for its significant anti-tumor activity. However, most reports focused on the studies of its anti-tumor activity, the anti-inflammatory activity of physalin A and its molecular mechanism are still not elucidated clearly. AIM OF THE STUDY: The aim of the study was to investigate the anti-inflammatory activities both in vitro and in vivo and molecular mechanism of physalin A. MATERIALS AND METHODS: The potential anti-inflammatory properties of physalin A were evaluated in vitro by lipopolysaccharide (LPS)-induced RAW 264.7 macrophage cells, and in vivo via two typical acute inflammation murine models. Some important inflammation-related molecules were analyzed by enzyme-linked immuno sorbent assay (ELISA) and Western blotting. RESULTS: The results showed that physalin A inhibited carrageenan-induced paw edema of rats and capillary permeability of mice induced by acetic acid in vivo. Furthermore, physalin A also significantly reduced the release of inflammatory mediators nitric oxide (NO), prostaglandin E2 (PGE2), and tumor necrosis factor-α (TNF-α) induced by lipopolysaccharide (LPS) in RAW 264.7 in vitro. Further investigations indicated that physalin A can down-regulate the high expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in a dose-dependent manner. Physalin A remarkably blocked the degradation of inhibitor of nuclear factor kappa B alpha (IκB-α) and the nuclear translocation of nuclear factor-κB (NF-κB) p65 induced by LPS in RAW 264.7 cells. However, physalin A did not significantly inhibit the phosphorylation of mitogen-activated protein kinases (MAPKs) family proteins c-Jun N-terminal kinase (JNK) or extracellular signal-regulated kinase (ERK) or p38. CONCLUSIONS: All the results clearly illustrated that the anti-inflammatory action of physalin A is due to the inactivation of NF-κB signal pathway, but is irrelevant to the MAPKs pathway.

Correlation between monocyte chemoattractant protein-1/chemokine (C-C motif) ligand 2 and coronary plaque characteristics.

IMPACT STATEMENT: Vulnerable plaques are plaques which are susceptible to rupture or thrombosis and trigger a series of adverse events such as coronary disorders. CCL2 is a soluble basic protein belonging to the CC subfamily. Previous studies have been investigated on the correlation between inflammatory factors and clinical events, but there are few studies on the correlation between CCL2 and plaque characteristics. Our study found that the high expression of CCL2 is involved in multiple processes in the genesis and progression of coronary artery disease, and would be a potential clinical prognostic indicator. In addition, high expression of CCL2 may be related to gene pathways such as Nod-like receptor signaling pathway, suggesting that CCL2 is involved in the inflammatory response and immune process of coronary artery disease.

Three-dimensional position of mandibular third molars and its association with distal caries in mandibular second molars: a cone beam computed tomographic study.

OBJECTIVE: To analyze the prevalence of distal caries in mandibular second molars (M2Ms) and its correlation with the three-dimensional position of mandibular third molars (M3Ms) by cone beam computed tomography (CBCT) images. MATERIALS AND METHODS: CBCT scans involving 421 M3Ms were assessed. The presence of distal caries of M2Ms, patient age and gender, impaction depths and mesial angulation of M3Ms, the cementoenamel junction (CEJ) distances and contact point localization, and the horizontal positions of M3Ms were assessed. Risk factors were identified by multivariate logistic regression analysis. RESULTS: The overall prevalence of distal caries in M2Ms was 31.6%. Mesial angulation (16°-75°) of M3Ms, contact point localization at or below the CEJ of M2Ms, and a buccal or lingual position of M3Ms relative to the molar line were identified as risk factors for the prevalence of distal caries in M2Ms (p < 0.05). Distal caries was more severe when the mesial angulation of M3Ms was 16°-75° (p < 0.05). CONCLUSIONS: Buccal or lingual position of M3Ms may represent a new risk factor for the distal caries in M2Ms. Mesial angulation (16°-75°) of M3Ms is a predictive parameter for both the presence and severity of distal caries in M2Ms. CLINICAL RELEVANCE: As the presence of distal caries in M2Ms is significantly associated with the three-dimensional position of M3Ms, watchful monitoring or prophylactic removal of M3Ms should be deliberated when M3Ms are mesially angulated (16°-75°), buccally or lingually positioned, and with the contact point localization at or below the CEJ of M2Ms.

In vitro anti-inflammatory activities of naucleoffieine H as a natural alkaloid from Nauclea officinalis Pierrc ex Pitard, through inhibition of the iNOS pathway in LPS-activated RAW 264.7 macrophages.

Naucleoffieine H, a natural indole alkaloid, was isolated and identified from Nauclea officinalis Pierrc ex Pitard which is a traditional Chinese medicine used for the treatment of various diseases, such as cold, fever, bronchitis, pneumonia, acute tonsillitis, etc. In the present study, the effect of naucleoffieine H on the anti-inflammatory activities was investigated in LPS-induced RAW 264.7 macrophages. The results showed that naucleoffieine H significantly inhibited the release of nitric oxide (the level of nitrite as a stable biomarker of NO production) and tumor necrosis factor-α (TNF-α). Interesting, naucleoffieine H down-regulated the overexpression of inflammatory protein induced nitric oxide synthase (iNOS), but no effect on the expression cyclooxygenase-2 (COX-2) protein. In addition, this bioactive alkaloid suppressed enzymatic activity of iNOS activated by LPS. The above results indicated that naucleoffieine H suppress NO and TNF-α overproduction via block the iNOS pathway in LPS-induced RAW 264.7 macrophages.

Association between Increased Inducible Costimulator/Inducible Costimulator Ligand Expression with Bone Destruction in Apical Periodontitis.

INTRODUCTION: The aim was to assess the association of inducible costimulator (ICOS) and ICOS ligand with bone destruction in apical periodontitis (AP). METHODS: Specimens from patients presenting with AP were obtained during apicoectomy and subjected to histopathologic analysis and molecular assessment of ICOS/ICOS ligand. In addition, the experimental AP was induced by exposing the pulp of first mandibular molars of rats. Histologic and radiographic examinations were performed to validate the periapical lesions. The immunolocalization and messenger RNA expression of ICOS/ICOS ligand were evaluated by immunofluorescence staining and quantitative real-time polymerase chain reaction. The osteoclastic activities in periapical lesions, including the lesion size and the expression of tartrate-resistant acid phosphatase and the receptor activator of nuclear factor kappa B ligand, were recorded and followed by correlation analysis with ICOS/ICOS ligand expression. RESULTS: In excisional specimens from AP patients, a significantly increased expression of ICOS/ICOS ligand was found compared with the healthy control. In the experimental AP samples, the expression of ICOS/ICOS ligand, tartrate-resistant acid phosphatase, and receptor activator of nuclear factor kappa B ligand was significantly elevated in inflamed periapical tissues (AP group) when compared with the healthy control. The number of ICOS+/ICOS ligand+ cells was highly correlated with the periapical lesion size (r = 0.892, P < .01 and r = 0.930, P < .01, respectively). CONCLUSIONS: The increased expression of ICOS/ICOS ligand in periapical lesions was associated with the inflammatory infiltration and alveolar bone destruction of AP.

(3R, 7R)-7-Acetoxyl-9-Oxo-de-O-Methyllasiodiplodin, a Secondary Metabolite of Penicillium Sp., Inhibits LPS-Mediated Inflammation in RAW 264.7 Macrophages through Blocking ERK/MAPKs and NF-κB Signaling Pathways.

Twelve polyketones were isolated from the fermentation broth of Penicillium sp., including six new compounds (supplementary material). Penicillium sp. is widely used in clinic as a highly effective and low toxic antibiotic. Among these compounds, (3R, 7R)-7-acetoxyl-9-oxo-de-O-methyllasiodiplodin named PS-2 showed significant anti-inflammatory activity. So, the anti-inflammatory mechanism of PS-2 was investigated by using lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. The results showed that PS-2 can significantly inhibit the overproduction of nitric oxide (NO), prostaglandin E2 (PGE2), and interleukin-6 (IL-6), whereas it showed no inhibition on the release of pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α). Cell-free colorimetric method demonstrated that PS-2 could obviously inhibit the enzymatic activity of cyclooxygenase-2 (COX-2). Western blot results indicated that PS-2 could significantly inhibit high expression of iNOS and COX-2 proteins. Further investigations on the anti-inflammatory mechanism showed that PS-2 could suppress the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), but did not exhibit obvious inhibition on the phosphorylation of c-JunN-terminal kinase (JNK) and phosphorylated 38 (p38). In addition, PS-2 inhibited the degradation of inhibitor of kappa-B alpha (IκB-α) and translocation to nucleus of nuclear factor kappa-B (NF-κB) p65 in RAW 264.7 macrophages. These results suggested that PS-2 might be an effective intervention against inflammatory diseases.

Correction to: Identification of ß­carboline and canthinone alkaloids as anti­inflammatory agents but with different inhibitory profile on the expression of iNOS and COX­2 in lipopolysaccharide­activated RAW 264.7 macrophages.

The article Identification of ß­carboline and canthinone alkaloids as anti­inflammatory agents but with different inhibitory profile on the expression of iNOS and COX­2 in lipopolysaccharide­activated RAW 264.7 macrophages, written by Pan Liu, Huixiang Li, Ruiling Luan, Guiyan Huang, Yanan Liu, Mengdi Wang, Qiuli Chao, Liying Wang, Danna Li, Huaying Fan, Daquan Chen, Linyu Li, Keiichi Matsuzaki, Wei Li, Kazuo Koike, Feng Zhao, was originally published electronically on the publisher's internet portal (currently SpringerLink) on 15 October 2018 without open access.

External root resorption in maxillary and mandibular second molars associated with impacted third molars: a cone-beam computed tomographic study.

OBJECTIVE: To separately investigate the prevalence and risk factors of external root resorption (ERR) in maxillary and mandibular second molars (M2s) adjacent to impacted third molars (M3s). MATERIALS AND METHODS: CBCT scans involving 184 maxillary and 323 mandibular impacted M3s were included. Age, gender, the impaction status of M3, the presence, severity, and location of ERR in M2 were assessed. Risk factors were identified by multivariate logistic regression analyses. RESULTS: The prevalence of ERR was 32.6% in maxillary and 52.9% in mandibular M2s (P < 0.001). Mesio-angulated and deeply impacted M3s were identified as risk factors for both ERR in maxillary and mandibular M2s (P < 0.05). Besides, age over 25 increased the risk of ERR in maxillary M2s (P < 0.05). ERR in maxillary M2s was overall more severe than that in mandibular M2s (P < 0.001). For maxillary M2s, ERR mostly occurred at the apical third, while the mandibular M2s ERR was most frequently detected at the cervical third. CONCLUSIONS: ERR occurring in M2s adjacent to impacted M3s is common, especially in mandibular M2s. ERR in maxillary M2s cannot be neglected because of its relatively high severity. Mesial angulation and impaction depth of M3 are significantly associated with ERR in M2s. For ERR in maxillary M2s, age is another predictive parameter. CLINICAL RELEVANCE: Considering the presence of ERR is associated with M3s' impaction, watchful monitoring or prophylactic removal of impacted M3s should be deliberated especially for the patients over 25 years and with mesially inclined and deeply positioned M3s.

Identification of ß-carboline and canthinone alkaloids as anti-inflammatory agents but with different inhibitory profile on the expression of iNOS and COX-2 in lipopolysaccharide-activated RAW 264.7 macrophages.

A compound library, which consists of 75 natural ß-carboline-type or canthinone-type alkaloids from Simaroubaceae plants and their chemical synthetic analogues, was screened for the anti-inflammatory activity by inhibition of the overproduction of inflammatory mediator nitric oxide (NO) in lipopolysaccharide (LPS)-activated RAW 264.7 macrophage cells. Six compounds, namely, benzalharman (23), kumujian (27), 1-ethyl-1,2,3,4-tetrahydro-ß-carboline-3-carboxylic acid (37), 1-acetophenone-1,2,3,4-tetrahydro-ß-carboline-3-carboxylic acid (42), cathin-6-one (46), and 9-methoxy-cathin-6-one (57), exhibited significant inhibitory activity on the overproduction of NO with good dose dependency. Further investigation demonstrated that all of the six compounds down-regulated the high expression of inducible nitric oxide synthase (iNOS) protein. Among them, two canthinone-type alkaloids (46 and 57) potently down-regulated cyclooxygenase-2 (COX-2) protein expression in a dose-dependent manner and also inhibited the overproduction of inflammatory mediator prostaglandin E2 (PGE2). However, the ß-carboline-type alkaloids (23, 27, 37, and 42) exhibited no obvious inhibition on the overproduction of PGE2 and the expression of COX-2 protein. The results suggested that ß-carboline-type alkaloids and canthinone-type alkaloids may exert an anti-inflammatory effect through different mechanism.

A New Up-conversion Material of Ho3+-Yb3+-Mg2+ Tri-doped TiO2 and Its Applications to Perovskite Solar Cells.

A new up-conversion nanomaterial of Ho3+-Yb3+-Mg2+ tri-doped TiO2 (UC-Mg-TiO2) was designed and synthesized with a sol-gel method. The UC-Mg-TiO2 presented enhanced up-conversion fluorescence by an addition of Mg2+. The UC-Mg-TiO2 was utilized to fabricate perovskite solar cells by forming a thin layer on the electron transfer layer. The results display that the power conversion efficiency of the solar cells based on the electron transfer layer with UC-Mg-TiO2 is improved to 16.3 from 15.2% for those without UC-Mg-TiO2. It is demonstrated that the synthesized UC-Mg-TiO2 can convert the near-infrared light to visible light that perovskite film can absorb to improve the power conversion efficiency of the devices.

Anti-inflammatory action of ambuic acid, a natural product isolated from the solid culture of Pestalotiopsis neglecta, through blocking ERK/JNK mitogen-activated protein kinase signaling pathway.

Ambuic acid is an organic acid isolated from the solid culture of Pestalotiopsis neglecta, which is an endophytic fungus that widely exists in many species of plants. Ambuic acid has been reported to exert antimicrobial activity against Gram-positive bacterium. The aim of the present study was to investigate the inhibitory effect of ambuic acid on lipopolysaccharide (LPS)-induced inflammation in RAW264.7 macrophages. The results demonstrated that ambuic acid significantly suppressed the overproduction of nitric oxide (NO) and prostaglandin E2 (PGE2) in a dose-dependent manner. Furthermore, ambuic acid also inhibited the release of the proinflammatory cytokine interleukin-6 (IL-6) however, no inhibition of the release of tumor necrosis factor-α (TNF-α) was observed. Further investigations indicated that ambuic acid downregulated the LPS-induced high expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins, as well as inhibited the enzymatic activity of iNOS and COX-2. In addition, ambuic acid suppressed the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK 1/2) and c-Jun N-terminal kinase (JNK) induced by LPS. However, ambuic acid did not inhibit the phosphorylation of p38 mitogen-activated protein kinase (MAPK), the degradation of IκB-α protein or the nuclear translocation of nuclear transcription factor-κB (NF-κB) p65 subunit. These results suggested that ambuic acid may exert anti-inflammatory action by blocking the activation of the ERK/JNK MAPK signaling pathway, without the involvement of the p38 MAPK or NF-κB signaling pathways.