Search

Aims To describe the role of left atrial (LA) epicardial conduction and targets of ablation in biatrial tachycardias (BiATs). Methods and results Consecutive patients with BiAT diagnosed by high-density mapping and appropriate entrainment were enrolled. A systematic review of case reports or series was then performed. Biatrial tachycardia was identified in 20 patients aged 63.5 ± 11.1 years. Among them, eight had LA epicardial conduction, including four via the ligament of Marshall, two via myocardial fibres between the great cardiac vein (GCV) and LA, one via septopulmonary bundle, and one via myocardial fibres between the posterior wall and coronary sinus. Ablation was targeted at the anatomical isthmus in 14, including 5 undergoing vein of Marshall ethanol infusion and 2 undergoing ablation in the GCV. Another six underwent ablation at interatrial connections, including one with septopulmonary bundle at the fossa ovalis and five at the atrial insertions of Bachmann’s bundle. After a mean follow-up of 8.7 ± 3.8 months, five patients had recurrence of atrial fibrillation/flutter. Systematic review enrolled 87 patients in previous and the present reports, showing a higher risk of impairment in atrial physiology in those targeting interatrial connections (30.4 vs. 5.0%, P < 0.001) but no significant difference in short- and long-term effectiveness. Conclusion Left atrial epicardial conduction is common in BiATs and affects the ablation strategy. Atrial physiology is a major concern in selecting the target of intervention.

ObjectiveThis study sought to assess the effect of ethanol infusion into the vein of Marshall (EIVOM) on the acute success of left pulmonary vein (LPV) isolation in persistent atrial fibrillation (PeAF).Methods and resultsA total of 313 patients with drug-resistant PeAF were enrolled (135 in Group 1 and 178 in Group 2). In Group 1, EIVOM was firstly performed, followed by radiofrequency ablation (RFA) including bilateral pulmonary vein isolation (PVI) and linear ablation at roofline, cavotricuspid isthmus, and mitral isthmus (MI). In Group 2, PVI and linear ablations were completed with RFA. First-pass isolation of the LPV was achieved in 119 (88.1%) and 132 (74.2%) patients in Groups 1 and 2, respectively (P = 0.002). The rate of acute pulmonary vein reconnection (PVR) was significantly lower in Group 1 (9.6% vs. 22.5%, P = 0.003). About half of acute PVR occurred in the carina with or without EIVOM.ConclusionEIVOM is effective in achieving a higher first-pass isolation and a lower acute PVR of LPV in PeAF.

Periodontitis is the most important oral disease causing human tooth loss. Although supragingival and subgingival scaling is the main strategy of periodontitis clinical treatments, drug treatment has an indispensable auxiliary role to some degree. Periodontitis medical treatment is divided into systemically administered treatments and local periodontally administered treatments. Compared with systemic administration, local administration can increase local drug concentrations, reduce dosages, and prolong action times while also improving patient compliance and avoiding possible adverse effects due to systemic administration responses. However, some studies show that minocycline ointment, a clinical local drug commonly used in periodontal pockets, has an unstable release rate; 80% of the drug is usually released within 2-3 days after pocket placement. This release is not conducive to controlling periodontal infection and may hinder the periodontal tissue repair and regeneration. Therefore, choosing a suitable carrier for minocycline hydrochloride is necessary to control its local release in periodontal tissue. Phase transition lysozyme (PTL) has been widely used in many studies and the development of macromolecular carrier material, and we selected PTL as the carrier for minocycline hydrochloride drugs because of its good biocompatibility, good drug-carrying capacity, and stable release. Due to its release characteristics and simple preparation, PTL is a promising carrier material.

In view of increasing drug resistance, ecofriendly photoelectrical materials are promising alternatives to antibiotics. Here we design an interfacial Schottky junction of Bi2S3/Ti3C2Tx resulting from the contact potential difference between Ti3C2Tx and Bi2S3. The different work functions induce the formation of a local electrophilic/nucleophilic region. The self-driven charge transfer across the interface increases the local electron density on Ti3C2Tx. The formed Schottky barrier inhibits the backflow of electrons and boosts the charge transfer and separation. The photocatalytic activity of Bi2S3/Ti3C2Tx intensively improved the amount of reactive oxygen species under 808 nm near-infrared radiation. They kill 99.86% of Staphylococcus aureus and 99.92% of Escherichia coli with the assistance of hyperthermia within 10 min. We propose the theory of interfacial engineering based on work function and accordingly design the ecofriendly photoresponsive Schottky junction using two kinds of components with different work functions to effectively eradicate bacterial infection.

Photodynamic therapy (PDT), an emerging approach that involves photosensitizers, light, and molecular oxygen, has shown promise for fighting periodontitis. However, PDT does not always acquire the desired therapeutic outcomes since some photosensitizers have strong hydrophobic properties and are difficult to absorb efficiently by periodontal pathogenic bacteria. Here, a hydrophobic photosensitizer chlorin e6 (Ce6) was hydrophilically modified via conjugation with TAT peptide, a cationic cell-penetrating peptide, to improve its solubility and enhance its bacterial adsorption by promoting its interaction with the negatively charged cell walls and penetration through the cell membranes. The obtained TAT-Ce6 conjugate (TAT-Ce6) was used to prepare self-assembled nanoparticles (NPs) for loading tinidazole (TDZ), a clinically used antibiotic agent, thus hoping to achieve synergistic antiperiodontitis effects through combining PDT and antibiotic therapy. Compared to free Ce6, TAT-Ce6 nanoparticles (TAT-Ce6 NPs) had greatly enhanced adsorption and penetration abilities for periodontal pathogen bacteria and also exhibited significantly increased PDT efficiencies in both periodontal pathogen bacteria and monocyte macrophages. Upon 635 nm laser irradiation, TDZ-loaded TAT-Ce6 (TAT-Ce6/TDZ) NPs exerted remarkable synergistic antiperiodontitis effects of PDT and antibiotic therapy, reflecting in the effective killing of periodontal pathogenic bacteria in vitro and the reduced adsorption of alveolar bone in the Sprague-Dawley rat model of periodontitis. Altogether, this study develops a novel photosensitizer that can be efficiently absorbed by the periodontal pathogenic bacteria and also provides a potent combination strategy of PDT with antibiotic therapy for clinical periodontitis treatment.

Endoplasmic reticulum (ER) homeostasis is regulated by ER-resident E3 ubiquitin ligase Hrd1, which has been implicated in inflammatory bowel disease (IBD). Ginsenoside Rb1 (GRb1) is the major ginsenoside in ginseng with multiple pharmacological activities. In this study we investigated the role of Hrd1 in IBD and its regulation by GRb1. Two mouse colitis models were established to mimic human IBD: drinking water containing dextran sodium sulfate (DSS) as well as intra-colonic infusion of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). Colitis mice were treated with GRb1 (20, 40 mg·kg(−1)·d(−1), ig) or a positive control drug sulfasalazine (500 mg·kg(−1)·d(−1), ig) for 7 days. The model mice showed typical colitis symptoms and pathological changes in colon tissue. In addition to significant inflammatory responses and cell apoptosis in colon tissue, colon epithelial expression of Hrd1 was significantly decreased, the expression of ER stress markers GRP78, PERK, CHOP, and caspase 12 was increased, and the expression of Fas was increased (Fas was removed by Hrd1-induced ubiquitination). These changes were partially, or completely, reversed by GRb1 administration, whereas injection of Hrd1 inhibitor LS102 (50 mg·kg(−1)· d(−1), ip, for 6 days) exacerbated colitis symptoms in colitis mice. GRb1 administration not only normalized Hrd1 expression at both the mRNA and protein levels, but also alleviated the ER stress response, Fas-related apoptosis, and other colitis symptoms. In intestinal cell line IEC-6, the expression of Hrd1 was significantly decreased by LPS treatment, but was normalized by GRb1 (200 μM). GRb1 alleviated LPS-induced ER stress and cell apoptosis in IEC-6 cells, and GRb1 action was inhibited by knockdown of Hrd1 using small interfering RNA. In summary, these results reveal a pathological role of Hrd1 in colitis, and provide a novel insight into alternative treatment of colitis using GRb1 activating Hrd1 signaling pathway.

UK surgeons often spend their working lives repeatedly performing a series of operations routine to them. Few data are collected on the outcomes of surgeons’ routine work. Any information given to patients about the success of a planned procedure will likely be derived from the literature. Mandatory collection of surgeons’ data is currently limited to specialist registers concerning arthroplasty and other complex surgery. The Paterson inquiry report, published in 2020, fell short of suggesting a comprehensive collection of outcomes data but recommended publication of a list of operations commonly performed by a surgeon. The idea of comprehensive data collection is not new. In 1905, an American shoulder surgeon, Ernest Codman, suggested the ‘end result’ idea, which involved publishing data regarding the outcome of every operation performed. Codman’s scheme (and his career) failed. This paper looks at the reasons for the failure of Codman’s idea and surveys the current schemes of surgical outcomes data collection. For future successful data collection, the interested parties need to agree why data should be collected, how the system will be paid for, what data will be collected, how data quality and interfering variables will be managed, and how the data will be analysed and presented to interested groups. With many barriers to data collection still present, what lies ahead for quality assessment?

Objective. To investigate the intervention effect and mechanism of Aconite and Angelica sinensis on myocardial ischemia rats with Yang deficiency and blood stasis. Methods. SPF-class SD rats were randomly divided into low-dose and high-dose groups. Each group was divided into control group, model group, and drug-administered group (FZ, DG, FG; 1 : 0.5, 1 : 1, 1 : 2). A rat model was prepared by intraperitoneal injection of hydrocortisone and isoproterenol plus cold stimulation. Each group was given corresponding decoction or distilled water for 14 days. The behavioral changes of rats in each group were observed. The morphological changes of rats cardiomyocytes were observed by HE staining. The average optical density (MOD value) and percentage of positive cells of Bcl-2, Bax, and Akt were determined by immunohistochemical staining method, and PEIs were calculated. Western blot and RT-PCR were used to determine the expression of PI3K, Caspase-3, Akt protein, and gene expression. Results. The compatibility of Aconite and Angelica sinensis improved the morphology of rat cardiomyocytes, increased the PEI values of Akt and Bcl-2 protein, and decreased the PEI values of Bax protein (P<0.01). The compatibility reduced the expression of Caspase-3 protein of rat myocardium and increased the protein expression of p-Akt, PI3K, and p-PI3K (P<0.01). The compatibility also significantly reduced the expression of Caspase-3 mRNA and increased the expression of PI3K mRNA and Akt mRNA (P<0.05 or P<0.01), and the effect of high-dose FG (1 : 2) group is the best. Conclusions. The method of preparing a rat model of myocardial ischemia with Yang deficiency and blood stasis was feasible. The compatibility of Aconite and Angelica sinensis reduced myocardial fibrosis and inflammatory reaction, protected ischemic cardiomyocytes, and reduced myocardial injury, whose mechanism may be related to the regulation of PI3K/Akt pathway. The compatible group had better intervention effects than Aconite or Angelica sinensis alone. The best one was high-dose FG (1 : 2).

Purpose Zinc (Zn), an essential trace element in the body, has stable chemical properties, excellent osteogenic ability and moderate immunomodulatory property. In the present study, a Zn-incorporated TiO2 nanotube (TNT) was fabricated on titanium (Ti) implant material. We aimed to evaluate the influence of nano-scale topography and Zn on behaviors of murine RAW 264.7 macrophages. Moreover, the effects of Zn-incorporated TNT surface-regulated macrophages on the behaviors and osteogenic differentiation of murine MC3T3-E1 osteoblasts were also investigated. Methods TNT coatings were firstly fabricated on a pure Ti surface using anodic oxidation, and then nano-scale Zn particles were incorporated onto TNTs by the hydrothermal method. Surface topography, chemical composition, roughness, hydrophilicity, Zn release pattern and protein adsorption ability of the Zn-incorporated TiO2 nanotube surface were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS), surface profiler, contact angle test, Zn release test and protein adsorption test. The cell behaviors and both pro-inflammatory (M1) and pro-regenerative (M2) marker gene and protein levels in macrophages cultured on Zn-incorporated TNTs surfaces with different TNT diameters were detected. The supernatants of macrophages were extracted and preserved as conditioned medium (CM). Furthermore, the behaviors and osteogenic properties of osteoblasts cultured in CM on various surfaces were evaluated. Results The release profile of Zn on Zn-incorporated TNT surfaces revealed a controlled release pattern. Macrophages cultured on Zn-incorporated TNT surfaces displayed enhanced gene and protein expression of M2 markers, and M1 markers were moderately inhibited, compared with the LPS group (the inflammation model). When cultured in CM, osteoblasts cultured on Zn-incorporated TNTs showed strengthened cell proliferation, adhesion, osteogenesis-related gene expression, alkaline phosphatase activity and extracellular mineralization, compared with their TNT counterparts and the Ti group. Conclusion This study suggests that the application of Zn-incorporated TNT surfaces may establish an osteogenic microenvironment and accelerate bone formation. It provided a promising strategy of Ti surface modification for a better applicable prospect.

BACKGROUND. Endobronchial ultrasound (EBUS) transbronchial needle aspiration (TBNA) has a high diagnostic yield when evaluating mediastinal and hilar lymphadenopathy (LAD). Having previously demonstrated the safety of EBUS-guided cautery-assisted transbronchial nodal forceps biopsy (ca-TBFB), we report disease-specific improvements in diagnostic yield and tissue acquisition when supplementing the EBUS-TBNA–based standard ofcare (SOC) with ca-TBFB. METHODS. We retrospectively reviewed 213 patients who sequentially underwent SOC and ca-TBFB during the same procedure. We determined 3 clinical scenarios of interest based on preprocedural imaging: isolated mediastinal/hilar LAD, LAD associated with a nodule or mass suspicious for malignancy, and LAD associated with parenchymal findings suggestive of sarcoidosis. Using validated methods, we assessed diagnostic yield on a per-patient basis and specimen quality on a per-node basis on the 136 patients meeting diagnostic criteria. RESULTS. Administration of disease-specific SOC with ca-TBFB yielded gains that varied by diagnosis. Diagnostic yields of SOC and its supplementation with ca-TBFB were 91.8% and 93.4% (P = .50) of the 61 patients diagnosed with solid-organ malignancy, 62.7% and 94.9% (P < .001) of the 59 patients diagnosed with sarcoidosis, and 62.5% and 93.8% (P = .042) of the 16 patients diagnosed with lymphoma, the. For each disease process, specimens obtained with ca-TBFB exhibited statistically higher quality. CONCLUSIONS. We suggest that relative to SOC, ca-TBFB improves diagnostic yield for sarcoidosis and lymphoma while providing uniformly better tissue quality and cellularity. We propose a protocol for use of this innovative technique.

Aims Although several studies have proved that repeat catheter ablation is beneficial to recurrent atrial tachycardia (AT)/atrial fibrillation (AF) after AF catheter ablation, the hard endpoints of the effect of catheter ablation on recurrent AT/AF patients after AF catheter ablation remains unclear. Our study aims to compare the effect of catheter ablation and drug therapy on recurrent AT/AF patients after AF catheter ablation. Methods and results Four thousand nine hundred and thirteen consecutive patients with recurrent AT/AF after catheter ablation from the China-AF registry were enrolled. The patients were divided into two study groups: the repeat catheter ablation group and the medical therapy group. The primary endpoint is a composite of cardiovascular mortality or ischaemic stroke or major bleeding events. Secondary endpoints were each component of the primary endpoints and AF recurrence rate. Landmark analysis and Cox regression were used in the statistical analysis. We chose landmark 36 months as the primary landmark date. Over a median follow-up period of 40 ± 24 months, 4913 patients were divided into either the repeat ablation group or the medical therapy group. The cumulative incidence of the composite primary outcome was significantly lower in the repeat ablation group than the medical therapy group (adjusted hazard ratio = 0.56; 95% confidence interval: 0.35–0.89; P = 0.015) of landmark 36 months (2359 patients were included in medical therapy group and 704 patients were included in repeat ablation group at landmark 36 months). However, all secondary endpoints were not statistically different in the two groups, including cardiovascular mortality, ischaemic stroke, major bleeding events, and AF recurrence rate. Conclusion Based on this research, in recurrent AT/AF patients after a catheter ablation procedure, compared with medical therapy, repeat catheter ablation may significantly reduce the risk of the endpoint of composite cardiovascular mortality, ischaemic stroke, and major bleeding events.

Senescence of bone marrow mesenchymal stem cells (BMSCs) impairs stemness and osteogenic differentiation, but the key regulators for senescence and the related osteogenesis are not well defined. Herein, we screened the gene expression profiles of human BMSCs from young and old donors and identified that elevation of the nucleosome assembly protein 1-like 2 (NAP1L2) expression was correlated with BMSC senescence and impaired osteogenesis. Elevated NAP1L2 expression was observed in replicative cell senescence and induced cell senescence in vitro, and in age-related senescent human and mouse BMSCs in vivo, concomitant with significantly augmented chromatin accessibility detected by ATAC-seq. Loss- and gain-of-functions of NAP1L2 affected activation of NF-κB pathway, status of histone 3 lysine 14 acetylation (H3K14ac), and chromatin accessibility on osteogenic genes in BMSCs. Mechanistic studies revealed that NAP1L2, a histone chaperone, recruited SIRT1 to deacetylate H3K14ac on promoters of osteogenic genes such as Runx2, Sp7, and Bglap and suppressed the osteogenic differentiation of BMSCs. Importantly, molecular docking analysis showed a possible bond between NAP1L2 and an anti-aging reagent, the nicotinamide mononucleotide (NMN), and indeed, administration of NMN alleviated senescent phenotypes of BMSCs. In vivo and clinical evidence from aging mice and patients with senile osteoporosis also confirmed that elevation of NAP1L2 expression was associated with suppressed osteoblastogenesis. Taken together, our findings suggest that NAP1L2 is a regulator of both BMSC cell senescence and osteogenic differentiation, and provide a new theoretical basis for aging-related disease.

Three-phase unbalanced and nonlinear loads aggravate harmonic problems in low-voltage distribution networks. In this paper, a hybrid inductive and active filter (HIAF) system with a Ddy converter transformer is proposed. By establishing the circuit and corresponding mathematical models, the working mechanism of the HIAF system in harmonic suppression is analyzed. In the designed HIAF system, we install the detection point on the grid-side winding and the compensation point on the filtering winding. Since both windings have the same connection, no phase compensation between the harmonic detection point and compensation point is demanded. Eventually, we apply a harmonic damping control and zero-value impedance control strategy to realize harmonic suppression under both balanced and unbalanced loads. The simulation results show that the HIAF system can effectively suppress harmonics under various load conditions.

BACKGROUND Serum amyloid A (SAA) has been identified to trigger inflammation response, and play a crucial role in chronic inflammatory diseases. However, the regulatory mechanism of SAA still remains unclear during the development of periodontitis METHODS: SAA mRNA and protein expression were detected in healthy and inflammatory gingival tissues using real-time polymerase chain reaction (PCR) and immunohistochemistry. Human recombinant SAA (Apo-SAA), Pam3CSK4 (a Toll-like receptor (TLR) 2 ligand), siRNA-SAA, or TLR2 neutralizing antibody was applied to treat human gingival fibroblasts, respectively, or combined. SAA, TLRs, and inflammatory cytokines interleukin (IL)-6 and IL-8 were analyzed by real-time PCR, western blotting, or enzyme-linked immunosorbent assay. RESULTS SAA expression increased in human inflammatory gingival tissues from patients with periodontitis (P

While many synthetic nanotubes with a hydrophobic lumen and fast molecular transport have been developed, decorating the interior of these channels with polar and/or responsive functional groups remains challenging. In transmembrane proteins like the aquaporin and M2 channels, the presence of histidine residues in a mostly hydrophobic channel has led to enhanced selectivity and pH-based activation. Herein, we report the synthesis of Bzim-CP, a cyclic octapeptide that contains a benzimidazole functionality as a chemical and structural mimic of histidine. Bzim-CP undergoes different protonation states, forms subnanometer nanotubes, and projects two different ionizable functionalities into the lumen. Present studies open up synthetic possibilities to functionalize subnanometer porous channels as a basis toward understanding new transport phenomena.

To improve initial osteoblast adhesion and subsequent osseointegration, TiO2 nanotubes layer was constructed on the titanium (Ti) surface by anodic oxidation (AO), with an additional hydroxyapatite (HA) coating to form the AO/HA surface. Tests on in vitro cellular activity displayed that the AO surface, especially the AO/HA surface, promoted initial adhesion, proliferation and differentiation of osteoblast cells. The modified AO and AO/HA surfaces further presented an up-regulated gene expression of osteogenic and adhesion markers collagen type 1 (COL), osteopontin (OPN), osteocalcin (OCN) and vinculin. In addition, in vivo experiments with a rat model demonstrated that the AO surface, particularly the AO/HA surface, achieved earlier osseointegration and a superior bone bonding ability compared with Ti. Our study shed light on a synergistic role played by nanotopography and HA in promoting osteoblast adhesion, proliferation, differentiation and osseointegration, thus suggesting a promising method for better modifying the implant surface.

Although titanium (Ti) alloys have been widely used as implant materials, the bioinertness of pristine Ti impairs their bioactivity and early osseointegration. In the present work, we prepared TiO2 nanotubes (TNT) layer on the titanium (Ti) surface by anodic oxidation. The anodized surface was functionalized with human bone morphogenetic protein-2 coating to form the hBMP-2/TNT surface. The release behavior of hBMP-2 on the hBMP-2/TNT surface displayed a controlled and sustained pattern, compared to that on the hBMP-2/Ti surface, which showed a rapid release. In vitro cellular activity tests demonstrated that both TNT and hBMP-2/Ti surfaces, particularly the hBMP-2/TNT surface, enhanced adhesion, proliferation, and differentiation of osteoblast cells. Increased cell adhesion, improved cytoskeleton organization, and immunofluorescence staining of vinculin were observed on the modified surfaces. The TNT, hBMP-2/Ti, and hBMP-2/TNT surfaces, especially the hBMP-2/TNT surface, further displayed an upregulated gene expression of adhesion and osteogenic markers vinculin, collagen type 1, osteopontin, and osteocalcin, compared to the pristine Ti surface. In vivo experiments using a rat model demonstrated that the TNT and hBMP-2/Ti surfaces, in particular the hBMP-2/TNT surface, improved osseointegration and showed a superior bone bonding ability compared to Ti. Our study revealed a synergistic role played by TiO2 nanotubes nanotopography and hBMP-2 in promoting initial osteoblast adhesion, proliferation, differentiation, and osseointegration, thus suggesting a promising method for better modifying the implant surface.

Background: Periodontitis is a chronic inflammatory disease in oral cavity owing to bacterial infection. Photothermal therapy (PTT) and photodynamic therapy (PDT) have many advantages for antibacterial treatment. As an excellent photosensitizer, indocyanine green (ICG) shows prominent photothermal and photodynamic performances. However, it is difficult to pass through the negatively charged bacterial cell membrane, thus limits its antibacterial efficacy for periodontitis treatment.Results: In this work, we developed a nanosystem from self-assembly of ICG and polycationic brush for synergistic PTT and PDT against periodontitis. A star-shaped polycationic brush, poly(2-(dimethylamino)ethyl methacrylate) (sPDMA), was synthesized via atom transfer radical polymerization (ATRP) of DMA monomer from bromo-substituted β-cyclodextrin initiator (CD-Br). ICG was then self-assembled with sPDMA to form ICG-loaded sPDMA (sPDMA@ICG) nanoparticles (NPs), and the physicochemical properties of these NPs were characterized in detail. In vitro antibacterial effects of sPDMA@ICG NPs were evaluated in porphyromonas gingivalis (Pg), one of the recognized periodontitis pathogens, and in vivo anti-periodontitis effects of NPs were investigated in a rat periodontitis model. Benefiting from the unique brush-shaped architecture of sPDMA polycation, sPDMA@ICG NPs efficiently delivered ICG into the bacterial cells through promoting their adsorption and penetration abilities, and also exhibited effective antibacterial and anti-periodontitis actions via synergistic PTT and PDT both in vitro and in vivo.Conclusions: This work developed a promising nano-photosensitizer for synergistic PTT and PDT for antibacterial and periodontitis treatments in clinic.

Chronic alcohol abuse increases the risk of mortality and poor outcomes in patients with acute respiratory distress syndrome. However, the underlying mechanisms remain to be elucidated. The present study aimed to investigate the effects of chronic alcohol consumption on lung injury and clarify the signaling pathways involved in the inhibition of alveolar fluid clearance (AFC). In order to produce rodent models with chronic alcohol consumption, wild­type C57BL/6 mice were treated with alcohol. A2a adenosine receptor (AR) small interfering (si)RNA or A2bAR siRNA were transfected into the lung tissue of mice and primary rat alveolar type II (ATII) cells. The rate of AFC in lung tissue was measured during exposure to lipopolysaccharide (LPS). Epithelial sodium channel (ENaC) expression was determined to investigate the mechanisms underlying alcohol­induced regulation of AFC. In the present study, exposure to alcohol reduced AFC, exacerbated pulmonary edema and worsened LPS­induced lung injury. Alcohol caused a decrease in cyclic adenosine monophosphate (cAMP) levels and inhibited α­ENaC, s­ENaC and I³­ENaC expression levels in the lung tissue of mice and ATII cells. Furthermore, alcohol decreased α­ENaC, s­ENaC and I³­ENaC expression levels via the A2aAR or A2bAR­cAMP signaling pathways in vitro. In conclusion, the results of the present study demonstrated that chronic alcohol consumption worsened lung injury by aggravating pulmonary edema and impairing AFC. An alcohol­induced decrease of α­ENaC, s­ENaC and I³­ENaC expression levels by the A2AR­mediated cAMP pathway may be responsible for the exacerbated effects of chronic alcohol consumption in lung injury.

Naringin has been shown to exert protective effects in an animal model of ulcerative colitis, but detailed mechanisms remain unclear. This study aimed to investigate function and signaling mechanisms underlying naringin-induced therapeutic effects on colitis. Two mouse models were established to mimic human Inflammatory bowel disease (IBD) by treating drinking water with dextran sodium sulphate or intra-colonic administration of 2, 4, 6-trinitrobenzene sulfonic acid. Transcriptomics combined with functional experiments were used to investigate underlying mechanisms. Colitis symptoms, including weight loss and high disease activity index were significantly reversed by naringin. The inflammatory response, oxidative reactions, and epithelial cell apoptosis that occur with colitis were also alleviated by naringin. After naringin treatment, transcriptomics results identified 753 differentially expressed mRNAs that were enriched in signaling pathways, including the neuroactive ligand-receptor interaction, calcium signaling, and peroxisome proliferator-activated receptor (PPAR) signaling. The naringin-induced alleviation of colitis was significantly inhibited by the PPAR-γ inhibitor BADGE. In IEC-6 and RAW264.7 cells incubated with lipopolysaccharide (LPS), NF-κB-p65, a downstream protein of PPAR-γ, was significantly increased. Naringin suppressed LPS-induced high expression of NF-κB-p65, which was inhibited by small interfering RNA targeting PPAR-γ. Our study clarifies detailed mechanisms underlying naringin-induced therapeutic effects on mice colitis, and PPAR-γ was found to be the main target of naringin by functional experiments both in vivo and in vitro. Our study supplies new scientific information for the use of naringin in colitis treatment.

BACKGROUND: Whether preoperative biopsy before radical resection can lead to recurrence and impact patient survival in non-small cell lung cancer (NSCLC) remains controversial. In this study, we carried out a retrospective analysis to determine whether preoperative biopsy can cause disease recurrence and influence disease-free survival (DFS) in patients with stage IA NSCLC. METHODS: Patients diagnosed with stage IA NSCLC (solid nodule) between January 2010 and December 2014 were identified from the databases of 7 Chinese medical centers and divided into two groups: a preoperative computed tomography (CT)-guided needle biopsy (CTNB) plus radical resection group, and a non-CTNB group. The propensity score matching (PSM) method was adopted to balance the observed covariates, and Kaplan-Meier estimates were used for survival analysis. Cox regression was used in a single-factor analysis to identify the factors affecting DFS in stage IA NSCLC. RESULTS: After initial screening, 730 patients were enrolled in this study, with 186 and 544 patients in the CTNB group and the non-CTNB group, respectively. After PSM, 186 patients were eventually included in each group. No significant differences in basic clinical features were identified between the two groups (P>0.05). The rates of recurrence were 17.2% and 14.0% in the CTNB and non-CTNB groups (χ(2)=0.735, P=0.391), respectively. No notable differences in DFS (χ(2)=1.895, P=0.173) or overall survival (OS, χ(2)=1.785, P=0.182) were observed. Lung adenocarcinoma [hazard ratio (HR), 0.167, P=0.001] and lesion size (>2 cm) (HR, 2.712, P=0.000) were identified as risk factors for DFS in stage IA NSCLC. CONCLUSIONS: CTNB does not increase the incidence of recurrence in stage IA NSCLC or affect patient survival; therefore, it is not a risk factor for DFS. Lung adenocarcinoma and lesion size are risk factors for DFS.

BACKGROUND This study aimed to compare the size and location of the traditional and conservative endodontic access cavities of the right maxillary first molar teeth, projected on the occlusal surface using cone-beam computed tomography (CBCT), to obtain an ideal access cavity. MATERIAL AND METHODS Five hundred CBCT images of the right maxillary first molars, including 198 males and 302 females, were retrospectively evaluated using KaVo eXam Vision software. First, a rectangular coordinate system was established. The coordinates of 4 pulp horns and 3 root canal orifices, which projected on the occlusal surface, were marked on it. Two different access cavities were then created by connecting these points: (1) traditional endodontic access cavity (TEC) required removal of the entire roof of the pulp chamber to establish a straight-line access to the root canal system; (2) conservative endodontic access cavity (CEC) was formed by connecting the projection of each root canal orifice on the occlusal. Data were analyzed using Kruskal-Wallis and Pearson's correlation tests at a 5% significance level. RESULTS The area of TEC was approximately 9.61 mm2 for males and 8.91 mm² for females. The area of CEC was approximately 3.4 mm² for males and 3.16 mm² for females. The projections of all pulp horns and root canal orifices were in or near the central area of nine-rectangle-grid. CONCLUSIONS Compared with the traditional access cavity, creating a conservative access cavity was less invasive. Meanwhile, the access cavity should be limited to the central or near the central area of nine-rectangle-grid.

Preventing deep bacterial infection and simultaneously enhancing osteogenic differentiation are in great demand for osteomyelitis. Microwave (MW) dynamic therapy is attracting attention due to its excellent penetration ability, but the mechanism of MW-induced reactive oxygen species (ROS) is still unknown. Herein, MW-responsive engineered pseudo-macrophages (M-Fe3 O4 /Au nanoparticles (NPs)) are fabricated to clear Staphylococcus aureus infections and induce M2 polarization of macrophages to improve osteogenic differentiation of bone marrow mesenchymal stem cells (MSCs) under MW irradiation. Fe3 O4 /Au NPs can generate ·O2 - and heat under MW irradiation in a saline solution, and the mechanism is put forward via finite element modeling and density functional theory calculations. Due to the gap plasmon, electromagnetic hotspots are produced at Fe3 O4 -Au interface at 2.45 GHz. Because of these induced electromagnetic hotspots, the sodium species is field-ionized and subsequently reacts with oxygen to produce ·O2 - . Meanwhile, the Fe3 O4 /Au NPs have a stronger ability than Fe3 O4 NPs to fix oxygen, favoring the production of ROS. Additionally, MW-treated macrophages diminish to secrete inflammatory cytokines, resulting in the decrease of ROS production in MSCs and thus enhancing their osteogenic differentiation. These engineered pseudo-macrophages will be promising for effectively treating bacterial infections and promoting osteoblast differentiation simultaneously in deep tissues under MW irradiation.

Correction for ‘Hierarchical microgroove/nanopore topography regulated cell adhesion to enhance osseointegration around intraosseous implants in vivo’ by Yujuan Tian et al., Biomater. Sci., 2022, 10, 560–580. DOI: 10.1039/D1BM01657A

Background/Objectives: This study was designed to investigate serum protein levels in acne patients.Method: Acne patients (n=362) and healthy volunteers (n=272) were matched in terms of both age and sex. Serum levels were measured.Results: Among the 362 acne patients and 272 age- and sex-matched healthy controls, serum albumin levels in female acne patients were lower than in the healthy controls (P < 0.05), serum albumin levels in male acne patients were lower than in the healthy controls (P < 0.01). Additionally, serum globulin and total protein levels were significantly lower in acne patients than in the healthy control group (P < 0.01). Serum levels of prealbumin were significantly lower in female acne patients than in the control group (P < 0.05). Finally, the severity of female and male acne patients was negatively correlated with serum total protein, albumin, globulin, and prealbumin levels. Conclusions: The results of this study suggested that acne patients are potentially accompanied with protein malnutrition.

The purpose of this study was to prepare carboxymethyl chitosan (CMC) and lysozyme nanogels that could encapsulate amorphous calcium phosphate (ACP) for achieving its controlled delivery, thus forming an aprismatic enamel-like layer on the demineralized enamel surface.CMC/LYZ-ACP nanogels were developed, and the controlled delivery of ACP from the nanogels was induced by the presence of NaCl. The nanogel morphologies at various NaCl concentrations was measured by transmission electron microscopy (TEM). The particle sizes and zeta potentials (ζ-potential) of the samples were determined using a combined dynamic light scattering/particle electrophoresis instrument. Comparing the remineralization effect of the CMC/LYZ-ACP nanogels on the demineralized enamel surface with that of a fluoride treatment, the remineralization effect was examined by nanoindentation tests, X-ray diffraction (XRD), confocal laser scanning microscopy (CLSM), and scanning electron microscopy (SEM).CMC/LYZ-ACP nanogels were negatively charged spherical structures with a particle size of approximately 300 nm. At high concentrations of NaCl (0.15 M), ACP was dissociated from the disassembled nanogels and transformed into hydroxyapatite (HAP). Groups treated with the CMC/LYZ-ACP nanogels showed the regeneration of an aprismatic enamel-like layer on an acid-etched enamel surface, which provided increased mechanical properties (P0.05) and a high impermeability (P0.01) compared to those of the fluoride-treated group.This research provides a new idea for the stable and controllable delivery of ACP from CMC/LYZ-ACP nanogels, which can form an aprismatic enamel-like layer in situ on the surface of demineralized enamel. In regard to further clinical development, this material and method may be promising for treating early enamel caries.

Background Since December 2019, over 80,000 patients with coronavirus disease 2019 (COVID-19) have been confirmed in China. With the increasing number of recovered patients, more attention should be paid to the follow-up of these patients. Methods In the study, 576 patients with COVID-19 discharged from hospital in Chongqing, China from January 24, 2020, to March 10, 2020 were evaluated by viral nucleic acid tests for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) to determine if they could be released from quarantine. Among the 576 patients, 61 patients (10.6%) had positive RT-PCR test results of SARS-CoV-2. We aimed to analyze the demographics, clinical characteristics and treatment of 61 patients. Results These positive patients were characterized by older age, chronic medical illness and mild conditions. 38 (62.3%) patients who were asymptomatic without abnormalities on chest radiographs were found in the positive with COVID-19. Also, they showed positive results of stool or sputum specimens with negative results of nasal and pharyngeal swab specimens. The median duration of positive result of SARS-CoV-2 was varied from 3 days to 35 days in the patients discharged from hospital with no family member infection. Conclusions Multi-site screening of SARS-CoV-2 including nasal and pharyngeal swabs, stool and sputum specimens could be considered to improve the diagnosis, treatment and infection control in patients with COVID-19. Our findings provide the important information and clinical evidence for the improved management of patients recovered from COVID-19.

Dysfunction of intestinal epithelial Cl− currents and channels have previously been reported in inflammatory intestinal diseases. However, the expression and function of the newly identified Ca2+-activated Cl− channel transmembrane member 16A (TMEM16A) in the intestinal epithelium is unclear. In this study, we investigated the effects of TMEM16A on intestinal epithelial barrier function in vitro. Intestinal epithelial barrier dysfunction was modeled by lipopolysaccharide (LPS)-induced cell damage in intestinal epithelial IEC-6 cells and the effects of TMEM16A knockdown and overexpression on cell apoptosis and tight junctions were studied. Corresponding mRNA and protein expression levels were measured by quantitative real-time polymerase chain reaction, western blotting, and immunofluorescence analysis, respectively. TMEM16A expression was significantly increased by LPS, possibly via a process involving the transcription factor nuclear factor-κB and both Th1 and Th2 cytokines. Low- and high-dose LPS dysregulated tight junctions (high-myosin light-chain kinase expression) and cell apoptosis-dependent cell barrier dysfunction, respectively. TMEM16A aggravated cell barrier dysfunction in IEC-6 cells pretreated with low-dose LPS by activating ERK1/MLCK signaling pathways, but protected against cell barrier dysfunction by activating ERK/Bcl-2/Bax signaling pathways in IEC-6 cells pretreated with high-dose LPS. We concluded that TMEM16A played a dual role in LPS-induced epithelial dysfunction in vitro. The present results indicated the complex regulatory mechanisms and targeting of TMEM16A may provide potential treatment strategies for intestinal epithelial barrier damage, as well as forming the basis for future studies of the expression and function of TMEM16A in normal and inflammatory intestinal diseases in vivo.

Transseptal passage is sometimes difficult to obtain. This study evaluates the feasibility and safety of a novel and easy transseptal puncture (TSP) technique named 2D2G (using two dilators and two guidewires) in patients with difficult TSP.Forty-four paroxysmal atrial fibrillation patients with difficult TSP were enrolled in this study. They were allocated to the 2D2G group or the conventional group in a 1:1 fashion. The primary endpoint in both groups was successful TSP without changing the puncture site or using auxiliary tools. The secondary endpoints were the safety, total transseptal puncture time, and ablation time. There were no differences in baseline demographic or clinical characteristics between the two groups. Successful LA access in the 2D2G group was 100% (vs. 64%, P 0.05). The total TSP time (10 ± 3 min vs. 5 ± 1 min, P 0.05) and ablation time (42 ± 19 min vs. 58 ± 22 min, P 0.05) in the conventional group were significantly longer than those in the 2D2G group. No major complications occurred in either group, and all the patients underwent successful circumferential pulmonary vein isolation (CPVI).In AF patients with difficult TSP, the 2D2G technique is safe, feasible, and time-saving.

Background: Serum cryptococcal antigen (CrAg) test is the most used noninvasive method to detect cryptococcal infection. However, false-negative CrAg test is not uncommon in clinical practice. Then, the aim of this study was to investigate the factors associated with false-negative CrAg test among non-human immunodeficiency virus (HIV) adult patients with pulmonary cryptococcosis and its clinical features. Methods: One hundred and fourteen non-HIV adult patients with pulmonary cryptococcosis, proven by biopsy, were retrospectively reviewed. Finally, 85 patients were enrolled; 56 were CrAg positive (CrAg+ group) and 29 were negative (CrAg− group). It was a cross-sectional study. Then, baseline characteristics, underlying diseases, clinical symptoms, laboratory findings, and chest radiological findings were reviewed and analyzed. Chi-square test was used to analyze categorical variable. Odds ratio (OR) was used to measure correlation. Student’s t-test was obtained to analyze continuous variable. Results: No difference in baseline characteristics, underlying diseases, clinical symptoms, and laboratory findings were found between two groups (P > 0.05 in all). Nevertheless, diffuse extent lesion was 82.1% in CrAg+ group and 10.3% in CrAg− group (χ2 = 40.34, P< 0.001; OR = 39.87). Conclusions: Among patients with limited pulmonary involvement, a negative serum CrAg does not preclude the diagnosis of pulmonary cryptococcosis. However, among patients with extensive pulmonary involvement, serum CrAg is a useful diagnostic tool for pulmonary cryptococcosis. Furthermore, we also noticed that the untypical and mild presentations with extensive pulmonary lesion might be the features of pulmonary cryptococcosis, which needs further investigation. Key words: Chest Radiological Findings; Cryptococcal Antigen; Extensive Pulmonary Lesion; Pulmonary Cryptococcosis

In this study, a reactive oxygen species (ROS)-responsive nanoparticle system was designed for combining photodynamic therapy (PDT) and chemotherapy for oral tongue squamous cell carcinoma (OTSCC)-targeted treatment. A PEGlated prodrug (RPTD) of doxorubicin (DOX) via thioketal linkage and cRGD peptide modification was synthesized and then used to prepare nanoparticles for encapsulating photosensitizer hematoporphyrin (HP). Thus, the obtained HP-loaded RPTD (RPTD/HP) nanoparticles had a regular spherical shape and small size, approximately 180 nm. The RPTD/HP nanoparticles showed a remarkable PDT efficiency and successfully induced ROS generation upon laser irradiation both in vitro and in vivo. DOX exhibited significant ROS-responsive release property from RPTD/HP nanoparticles because of the rupture of the thioketal linker. In OTSCC cells, RPTD/HP nanoparticles were efficiently internalized and showed potent effects on cell growth inhibition and apoptosis induction after laser irradiation. In OTSCC tumor-bearing mice, RPTD/HP nanoparticles displayed excellent tumor-targeting ability and notably suppressed tumor growth through multiple mechanisms after local laser irradiation. Taken together, we supplied a novel therapeutic nanosystem for OTSCC treatment through combining PDT and chemotherapy.

Foam cells are lipid-loaded macrophages and neutrophils that are generated from a massive uptake of oxidized lipid. Foam cells are a pathological hallmark of atherosclerosis, and have also been found in acne lesions. The same pathological changes determine the common pathogenesis. According to the pathological function of foam cells in these lesions, we put forward a viewpoint on the pathogenesis of acne and atherosclerotic plaques.

Introduction The purpose of this study was to evaluate the two-body wear resistances of natural enamel and four dental materials in vitro. Methods The testing machine was modified to form a type of pin-on-disk wear test apparatus. Four dental material specimens (Au-Pd alloy, Ag-Pd alloy, FiltekTMP60 and FiltekTMZ350 composite resins) and enamel were used as the pins, and a steatite ceramic grinding wheel was used as the abrasive counter face. The wear volume loss and the rigidity value was measured. The worn surface and the element analysis of the debris were analyzed. Result The wear volume loss of Au-Pd alloy and its steatite antagonists were the nearest to those of the dental enamel. SEM microphotographs showed that, the main wear mechanism of the dental materials was abrasive and adhesive wear. Conclusions Au-Pd alloy had good wear resistance and was more suitable for dental applications than other three dental materials.

Because guided bone regeneration (GBR) process is pronouncedly affected by the micro-environment in the defect, the surface stiffness of collagen membranes as a constituent part of the micro-environment was investigated in this study. The objective of this study was to manufacture biomimetically mineralized collagen membranes with controllable surface stiffness based on biomimetic strategy and to investigate the influences of surface stiffness on GBR process. The characterization and biocompatibility of membranes were examined in vitro. The mechanical properties of membranes were evaluated on macro and micro levels using tensile test and atomic force microscope, respectively. The critical-size cranial defect model and ectopic osteogenesis were chosen to employ their performances in vivo. The results indicated that the biomimetically mineralized collagen membranes with controllable surface stiffness were manufactured based on the biomimetic theory. The in vitro experiments showed that the mineralized collagen membrane with satisfactory surface stiffness can better promote the adhesion, proliferation, and osteogenic differentiation of mesenchymal stem cells. The membranes can perform excellently in both osteoinduction and osteoconduction, which results in effective manifestations in aspects of ectopic osteogenesis and GBR in vivo. Therefore, this biomimetically mineralized collagen membrane is a promising candidate for GBR treatment in future.