Biomechanical evaluation of various rigid internal fixation modalities for condylar-base-associated multiple mandibular fractures: A finite element analysis.

Condylar-base-associated multiple mandibular fractures are more prevalent than single ones. Direct trauma to mandibular symphysis, body or angle are prone to induce indirect condylar fracture. However, little is known about the effects of various rigid internal fixation modalities in condylar base for relevant multiple mandibular fractures, especially when we are confused in the selection of operative approach. Within the finite element analysis, straight-titanium-plate implanting positions in condylar base contained posterolateral zone (I), anterolateral zone (II), and intermediate zone (III). Von Mises stress (SS) in devices and bone and mandibular displacement (DT) were solved, while maximum values (SSmax and DTmax) were documented. For rigid internal fixation in condylar-base-and-symphysis fractures, I + II modality exhibited least SSmax in screws and cortical bone and least DTmax, I + III modality exhibited least SSmax in plates. For rigid internal fixation in condylar-base-and-contralateral-body fractures, I + III modality exhibited least SSmax in screws and cortical bone, I + II modality exhibited least SSmax in plates and least DTmax. For rigid internal fixation in condylar-base-and-contralateral-angle fractures, I + III modality exhibited least DTmax. The findings suggest that either I + II or I + III modality is a valid guaranty for rigid internal fixation of condylar base fractures concomitant with symphysis, contralateral body or angle fractures.

Predictive value of valvular calcification for the recurrence of persistent atrial fibrillation after radiofrequency catheter ablation.

BACKGROUND: Valvular calcification (VC) is an independent risk factor for cardiovascular diseases. The relationship between VC and atrial fibrillation is not clear. HYPOTHESIS: We treated the aortic valve, mitral valve, and tricuspid valve as a whole and considered the possible association between VC and recurrence of persistent atrial fibrillation (PsAF) after radiofrequency catheter ablation (RFCA). METHODS: This study involved 2687 PsAF patients who underwent RFCA. Data were collected to explore the relationship between VC and outcome. VC was defined by echocardiography in aortic valve, mitral valve, or tricuspid valve. After 1 year follow-up, subgroup analysis, mixed model regression analysis, and score system analysis were performed. The external validation of 133 patients demonstrated the accuracy of this clinical prediction model. RESULTS: Overall, 2687 inpatients were assigned to the recurrence group (n = 682) or the no recurrence group (n = 2005) with or without VC. Compared to patients with no recurrence, the incidence of VC was higher in recurrence patients. Recurrence was present in 18.5%, 34.9%, 39.3%, and 52.0% of the four groups, which met VC numbers of 0, 1, 2, and 3, respectively. After adjustment for potential confounding factors, VC was an independent risk factor for AF recurrence in several models. For multivariable logistic regression, a scoring system was established based on the regression coefficient. The receiver operating characteristic area of the scoring system was 0.787 in the external validation cohort. CONCLUSIONS: VC was an independent risk factor for AF recurrence in PsAF after RFCA. The scoring system may be a useful clinical tool to assess AF recurrence.

Prospective randomized comparison between upgraded '2C3L' vs. PVI approach for catheter ablation of persistent atrial fibrillation: PROMPT-AF trial design.

BACKGROUND: In randomized studies, the strategy of pulmonary vein antral isolation (PVI) plus linear ablation has failed to increase success rates for persistent atrial fibrillation (PeAF) ablation when compared with PVI alone. Peri-mitral reentry related atrial tachycardia due to incomplete linear block is an important cause of clinical failures of a first ablation procedure. Ethanol infusion (EI) into the vein of Marshall (EI-VOM) has been demonstrated to facilitate a durable mitral isthmus linear lesion. OBJECTIVE: This trial is designed to compare arrhythmia-free survival between PVI and an ablation strategy termed upgraded '2C3L' for the ablation of PeAF. STUDY DESIGN: The PROMPT-AF study (clinicaltrials.gov 04497376) is a prospective, multicenter, open-label, randomized trial using a 1:1 parallel-control approach. Patients (n = 498) undergoing their first catheter ablation of PeAF will be randomized to either the upgraded '2C3L' arm or PVI arm in a 1:1 fashion. The upgraded '2C3L' technique is a fixed ablation approach consisting of EI-VOM, bilateral circumferential PVI, and 3 linear ablation lesion sets across the mitral isthmus, left atrial roof, and cavotricuspid isthmus. The follow-up duration is 12 months. The primary end point is freedom from atrial arrhythmias of >30 seconds, without antiarrhythmic drugs, in 12 months after the index ablation procedure (excluding a blanking period of 3 months). CONCLUSIONS: The PROMPT-AF study will evaluate the efficacy of the fixed '2C3L' approach in conjunction with EI-VOM, compared with PVI alone, in patients with PeAF undergoing de novo ablation.

Vein of Marshall ethanol infusion: First-step or adjunctive choice for perimitral atrial tachycardia?

BACKGROUND: Perimitral atrial tachycardia (PMAT) is the most frequent type of iatrogenic atrial tachycardia (AT) after atrial fibrillation (AF) ablation. Vein of Marshall ethanol infusion (EIVOM) is a promising technique in mitral isthmus (MI) ablation. METHODS: A total of 165 patients with PMAT were divided into three groups according to ablation strategies, including RF only group (n = 89), RF-EIVOM group (initial RF ablation with adjunctive EIVOM, n = 28), and EIVOM-RF group (first-step EIVOM with touch-up RF ablation, n = 48). Acute and follow-up procedure outcomes were evaluated. RESULTS: PMAT terminated in 89.9%, 89.3%, and 93.7% of patients in RF only, RF-EIVOM and EIVOM-RF groups, respectively (p = .715), with complete MI block achieved in 80.9%, 89.3%, and 95.8% of patients (EIVOM-RF vs. RF only, p = .012). First-step utilization of EIVOM was associated with a significant shortening of RF ablation time at MI (EIVOM-RF 2.1 ± 1.3 min, RF only 7.9 ± 5.9 min, RF-EIVOM 6.8 ± 5.8 min; p < .001) and a decrease in the proportion of patients need ablation within coronary sinus (CS, EIVOM-RF 14.6%, RF only 61.8%, RF-EIVOM 64.3%; p < .001). After a mean follow-up of 12.1 ± 6.2 months, AF/AT recurred in 39 (43.8%), 6 (21.4%), and 12 (25.0%) patients in RF only, RF-EIVOM, and EIVOM-RF group (RF-EIVOM vs. RF only, p = .026; EIVOM-RF vs. RF only, p = .022). CONCLUSIONS: EIVOM was associated with an enhanced acute MI block rate as well as reduced AF/AT recurrence. First-step utilization of EIVOM promises to significantly simplify the RF ablation process. CONDENSED ABSTRACT: PMAT is the most common type of iatrogenic AT after AF ablation procedures. EIVOM contributed to a higher acute MI block rate and lower arrhythmia recurrence risk during follow-up. First-step utilization of EIVOM significantly reduced the need for radiofrequency ablation at MI and inside CS with the advantage of creating a homogenous, transmural lesion and eliminating epicardial connections.

Sacubitril/Valsartan Decreases Atrial Fibrillation Susceptibility by Inhibiting Angiotensin II-Induced Atrial Fibrosis Through p-Smad2/3, p-JNK, and p-p38 Signaling Pathways.

Sacubitril/valsartan (SAC/VAL) prevents angiotensin II (AngII) from binding AT1-R and blocks degradation of natriuretic peptides. Despite its efficacy in reducing ventricular fibrosis and preserving cardiac functions, which has been extensively demonstrated in myocardial infarction or pressure overload models, few studies have been conducted to determine whether SAC/VAL could attenuate atrial fibrosis and decrease atrial fibrillation (AF) susceptibility. Our study provided evidence for the inhibition of atrial fibrosis and reduced susceptibility to AF by SAC/VAL. After 28 days of AngII continuous subcutaneous stimulation, rats in SAC/VAL group exhibited reduced extent of atrial fibrosis, inhibited proliferation, migration, and differentiation of atrial fibroblasts, and decreased susceptibility to AF. We further found that inhibition of p-Smad2/3, p-JNK, and p-p38MAPK pathways is involved in the role of SAC/VAL on AngII-induced atrial fibrosis in vivo. These results emphasize the importance of SAC/VAL in the prevention of AngII-induced atrial fibrosis and may help to enrich the options for AF pharmacotherapy.

Porphyromonas gingivalis Gingipains-Mediated Degradation of Plasminogen Activator Inhibitor-1 Leads to Delayed Wound Healing Responses in Human Endothelial Cells.

Plasminogen activator inhibitor-1 (PAI-1), a serine protease inhibitor, is constitutively produced by endothelial cells and plays a vital role in maintaining vascular homeostasis. Chronic periodontitis is an inflammatory disease characterized by bleeding of periodontal tissues that support the tooth. In this study, we aimed to determine the role of PAI-1 produced by endothelial cells in response to infections caused by the primary periodontal pathogen Porphyromonas gingivalis. We demonstrated that P. gingivalis infection resulted in significantly reduced PAI-1 levels in human endothelial cells. This reduction in PAI-1 levels could be attributed to the proteolysis of PAI-1 by P. gingivalis proteinases, especially lysine-specific gingipain-K (Kgp). We demonstrated the roles of these degradative enzymes in the endothelial cells using a Kgp-specific inhibitor and P. gingivalis gingipain-null mutants, in which the lack of the proteinases resulted in the absence of PAI-1 degradation. The degradation of PAI-1 by P. gingivalis induced a delayed wound healing response in endothelial cell layers via the low-density lipoprotein receptor-related protein. Our results collectively suggested that the proteolysis of PAI-1 in endothelial cells by gingipains of P. gingivalis might lead to the deregulation of endothelial homeostasis, thereby contributing to the permeabilization and dysfunction of the vascular endothelial barrier.

Review of Breast Cancer Pathologigcal Image Processing.

Breast cancer is one of the most common malignancies. Pathological image processing of breast has become an important means for early diagnosis of breast cancer. Using medical image processing to assist doctors to detect potential breast cancer as early as possible has always been a hot topic in the field of medical image diagnosis. In this paper, a breast cancer recognition method based on image processing is systematically expounded from four aspects: breast cancer detection, image segmentation, image registration, and image fusion. The achievements and application scope of supervised learning, unsupervised learning, deep learning, CNN, and so on in breast cancer examination are expounded. The prospect of unsupervised learning and transfer learning for breast cancer diagnosis is prospected. Finally, the privacy protection of breast cancer patients is put forward.

Alcohol inhibits alveolar fluid clearance through the epithelial sodium channel via the A2 adenosine receptor in acute lung injury.

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, ß­ENaC and γ­ENaC expression levels in the lung tissue of mice and ATII cells. Furthermore, alcohol decreased α­ENaC, ß­ENaC and γ­ENaC 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, ß­ENaC and γ­ENaC expression levels by the A2AR­mediated cAMP pathway may be responsible for the exacerbated effects of chronic alcohol consumption in lung injury.

Trillium tschonoskii rhizomes' saponins induces oligodendrogenesis and axonal reorganization for ischemic stroke recovery in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Trillium tschonoskii Maxim. is one of traditional Chinese medical herbs that has been utilized to treat brain damages and cephalalgia. The neuroprotective effect of total saponins from Trillium tschonoskii rhizome (TSTT) has been demonstrated efficacy in rats following ischemia. However, the axonal remodeling effect of TSTT and the detailed mechanisms after ischemic stroke have not been investigated. AIM OF THE STUDY: We aimed to estimate therapeutic role of TSTT in axonal remodeling using magnetic resonance imaging (MRI) technique, and explored possible mechanisms underlying this process followed by histological assays in ischemic rats. METHODS: Male Sprague-Dawley (SD) rats underwent permanently focal cerebral ischemia induced by occluding right permanent middle cerebral artery. TSTT was intragastrically administrated 6 h after surgery and once daily for consecutive 15 days. Neurological function was assessed by the motor deficit score and beam walking test. T2 relaxation mapping and diffusion tensor imaging (DTI) were applied for detecting cerebral tissues damages and microstructural integrity of axons. Luxol fast blue (LFB) and transmission electron microscope (TEM) were performed to evaluate histopathology in myelinated axons. Double immunofluorescent staining was conducted to assess oligodendrogenesis. Furthermore, the protein expressions regarding to axonal remodeling related signaling pathways were detected by Western blot assays. RESULTS: TSTT treatment (65, 33 mg/kg) markedly improved motor function after ischemic stroke. T2 mapping MRI demonstrated that TSTT decreased lesion volumes, and DTI further confirmed that TSTT preserved axonal microstructure of the sensorimotor cortex and internal capsule. Meanwhile, diffusion tensor tractography (DTT) showed that TSTT elevated correspondent density and length of fiber in the internal capsule. These MRI measurements were confirmed by histological examinations. Notably, TSTT significantly increased Ki67/NG2, Ki67/CNPase double-labeled cells along the boundary zone of ischemic cortex and striatum. Meanwhile, TSTT treatment up-regulated the phosphorylation level of Ser 9 in GSK-3ß, and down-regulated phosphorylated ß-catenin and CRMP-2 expression. CONCLUSION: Taken together, our findings indicated that TSTT (65, 33 mg/kg) enhanced post-stroke functional recovery, amplified endogenous oligodendrogenesis and promoted axonal regeneration. The beneficial role of TSTT might be correlated with GSK-3/ß-catenin/CRMP-2 modulating axonal reorganization after ischemic stroke.

Atrial fibrosis underlying atrial fibrillation (Review).

Atrial fibrillation (AF) is one of the most common tachyarrhythmias observed in the clinic and is characterized by structural and electrical remodelling. Atrial fibrosis, an emblem of atrial structural remodelling, is a complex multifactorial and patient­specific process involved in the occurrence and maintenance of AF. Whilst there is already considerable knowledge regarding the association between AF and fibrosis, this process is extremely complex, involving intricate neurohumoral and cellular and molecular interactions, and it is not limited to the atrium. Current technological advances have made the non­invasive evaluation of fibrosis in the atria and ventricles possible, facilitating the selection of patient­specific ablation strategies and upstream treatment regimens. An improved understanding of the mechanisms and roles of fibrosis in the context of AF is of great clinical significance for the development of treatment strategies targeting the fibrous region. In the present review, a focus was placed on the atrial fibrosis underlying AF, outlining its role in the occurrence and perpetuation of AF, by reviewing recent evaluations and potential treatment strategies targeting areas of fibrosis, with the aim of providing a novel perspective on the management and prevention of AF.

Lefty1 Ameliorates Post-infarction Fibrosis by Suppressing p-Smad2 and p-ERK1/2 Signaling Pathways.

Transforming growth factor-ß1 signaling pathways are known to involve in the development of post-infarction fibrosis, a process characterized by the aberrant activation, proliferation, and differentiation of fibroblasts, as well as the unbalanced turnover of extracellular matrix proteins. Recent studies have shown that Lefty1, a novel member of TGF-ß superfamily, acts as a brake on the TGF-ß signaling pathway in non-cardiac tissues. However, its role in myocardial infarction (MI)-induced fibrosis and left ventricular remodeling has not been fully elucidated. Here, for the first time, we reported that Lefty1 alleviated post-MI fibroblast proliferation, differentiation, and secretion through suppressing p-Smad2 and p-ERK1/2 signaling pathways in vivo and in vitro. In MI mice or TGF-ß1-treated neonatal rat cardiac fibroblasts (CFBs), the expression of Lefty1 was upregulated. Adenovirus-mediated overexpression of Lefty1 significantly attenuated TGF-ß1-induced CFBs' proliferation, differentiation, and collagen production. Using the adeno-associated virus approach, we confirmed that Lefty1 attenuates MI-induced cardiac injury, as evidenced by the decreased infarct size and preserved cardiac function. These results highlight the importance of Lefty1 in the prevention of post-MI fibrosis and may help identify potential targets for therapeutic intervention of cardiac fibrosis. Graphical abstract.

Ginsenoside Rb1 alleviates colitis in mice via activation of endoplasmic reticulum-resident E3 ubiquitin ligase Hrd1 signaling pathway.

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.

Positive results for patients with COVID-19 discharged form hospital in Chongqing, China.

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.

Atrioesophageal fistula post atrial fibrillation ablation: A multicenter study from China.

BACKGROUND AND OBJECTIVE: Atrioesophageal fistula (AEF) is a rare but devastating complication with high mortality post atrial fibrillation (AF) ablation. The purpose of current study was to determine the epidemiology, clinical features, pathogenesis, and management of AEF after AF ablation. METHODS AND RESULTS: Patients with diagnosed AEF were included and retrospectively analyzed according to the registry of 11 centers in China from January 2010 to December 2019. A total of 16 AEF cases were identified from 44 794 patients who received a left atrial ablation procedure (0.035% per procedure). The interval from procedure to clinical onset of AEF averaged 18.3 days (3-39 days). The fever ranked the most common symptom, occurred in 14 of the 16 cases, followed by neurological deficits (n = 11), chest pain (n = 5), and hematemesis (n = 4). Patients undergoing surgical repair had a better prognosis compared to those receiving nonsurgical management ([4 of 8] 50.0% vs [8 of 8] 100%, P < .05) with an overall mortality rate of 75.0%. CONCLUSION: AEF is highly characterized by varied manifestations. Early diagnosis and urgent surgical repair are vital to those patients and associated with improved survival rates.

Salvianolic acid B decreases interleukin-1ß-induced colitis recurrence in mice.

BACKGROUND: Degree of mucosal recovery is an important indicator for evaluating the therapeutic effects of drugs in treatment of inflammatory bowel disease (IBD). Increasing evidences has proved that tight junction (TJ) barrier dysfunction is one of the pathological mechanisms of IBD. The aim of this study was to observe whether enhancement of TJ can decrease colitis recurrence. METHODS: Eighty C57BL/6 mice were randomly divided into four groups including normal group, colitis group, sulfasalazine (SASP) treated group, and traditional Chinese drug salvianolic acid B (Sal B) treated group. Colitis was established in mice by free drinking water containing dextran sulfate sodium, after treatments by SASP and Sal B, recombinant human interleukin-1ß (IL-1ß) was injected intraperitoneally to induce colitis recurrence. RESULTS: Compared with sham control, cell apoptosis in colitis group was increased from 100.85 ±â€Š3.46% to 162.89 ±â€Š11.45% (P = 0.0038), and TJ dysfunction marker myosin light chain kinase (MLCK) was also significantly increased from 99.70 ±â€Š9.29% to 296.23 ±â€Š30.78% (P = 0.0025). The increased cell apoptosis was reversed by both SASP (125.99 ±â€Š8.45% vs. 162.89 ±â€Š11.45%, P = 0.0059) and Sal B (104.27 ±â€Š6.09% vs. 162.89 ±â€Š11.45%, P = 0.0044). High MLCK expression in colitis group was reversed by Sal B (182.44 ±â€Š89.42% vs. 296.23 ±â€Š30.78%, P = 0.0028) but not influenced by SASP (285.23 ±â€Š41.04% vs. 296.23 ±â€Š30.78%, P > 0.05). The recurrence rate induced by recombinant human IL-1ß in Sal B-treated group was significantly lower than that in SASP-treated group. CONCLUSIONS: These results suggested a link between intestinal mucosal barrier dysfunction, especially TJ barrier dysfunction, and colitis recurrence. The TJ barrier dysfunction in remission stage of colitis increased the colitis recurrence. This study might provide potential treatment strategies for IBD recurrence.

Emerging Role of TRIM Family Proteins in Cardiovascular Disease.

Ubiquitination is one of the basic mechanisms of cell protein homeostasis and degradation and is accomplished by 3 enzymes, E1, E2, and E3. Tripartite motif-containing proteins (TRIMs) constitute the largest subfamily of RING E3 ligases, with >70 current members in humans and mice. These members are involved in multiple biological processes, including growth, differentiation, and apoptosis as well as disease and tumorigenesis. Accumulating evidence has shown that many TRIM proteins are associated with various cardiac processes and pathologies, such as heart development, signal transduction, protein degradation, autophagy mediation, ion channel regulation, congenital heart disease, and cardiomyopathies. In this review, we provide an overview of the TRIM family and discuss its involvement in the regulation of cardiac proteostasis and pathophysiology and its potential therapeutic implications.

The interaction between serum amyloid A and Toll-like receptor 2 pathway regulates inflammatory cytokine secretion in human gingival fibroblasts.

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 <0.05). Apo-SAA could increase not only the mRNA expression of TLR2 (P <0.05), but also IL-6 and IL-8 mRNA and protein levels (P <0.05) which was suppressed by TLR2 antibody in human gingival fibroblasts. Pam3CSK4 increased SAA, IL-6, and IL-8 levels (P <0.05). However, the expression of SAA, IL-6, and IL-8 decreased after transfection of siRNA-SAA (P <0.05). CONCLUSION: SAA not only increases in inflammatory gingiva, but also triggers inflammatory cytokine secretion via interacting with TLR2 pathway in human gingival fibroblasts, which indicates that SAA is involved in periodontal inflammation.

A Review of the Epidemiological Evidence for Adducin Family Gene Polymorphisms and Hypertension.

Hypertension is one of the most common cardiovascular diseases that seriously endangers human health and has become a significant public health problem worldwide. In the vast majority of patients, the cause of hypertension is unknown, called essential hypertension (EH), accounting for more than 95% of total hypertension. Epidemiological and genetic studies of humans and animals provide strong evidence of a causal relationship between high salt intake and hypertension. Adducin is one of the important candidate genes for essential hypertension. Adducin is a heterodimeric or heterotetrameric protein that consists of α, ß, and γ subunits; the three subunits are encoded by genes (ADD1, ADD2, and ADD3) that map to three different chromosomes. Animal model experiments and clinical studies suggest that changes in single-nucleotide polymorphisms (SNPs) at part of the adducin family gene increase the Na+-K+-ATPase activity of the renal tubular basement membrane and increase the reabsorption of Na+ by renal tubular epithelial cells, which may cause hypertension. This review makes a summary on the structure, function, and mechanism of adducin and the role of adducin on the onset of EH, providing a basis for the early screening, prevention, and treatment of EH.

Insulin ameliorates pulmonary edema through the upregulation of epithelial sodium channel via the PI3K/SGK1 pathway in mice with lipopolysaccharide­induced lung injury.

Epithelial sodium channel (ENaC) provides the driving force for the removal of edema from the alveolar spaces in acute lung injury (ALI). Our previous study reported that insulin increased the expression of α­ENaC, possibly via the serum/glucocorticoid­inducible kinase­1 (SGK1) pathway in ALI; however, the upstream regulator of SGK1 activity remains unclear. In the current study, C3H/HeN mice were subjected to lipopolysaccharide (LPS)­induced lung injury without hyperglycemia. Exogenous insulin was administered intravenously using a micro­osmotic pump, and intratracheal delivery of SGK1 small interfering RNA (siRNA) was performed. Furthermore, alveolar epithelial type II cells transfected with phosphatidylinositol 3­kinase (PI3K) siRNA or SGK1 siRNA were incubated with insulin. Insulin protected the pulmonary epithelial barrier, reduced the apoptosis of alveolar epithelial cells, attenuated pulmonary edema, improved alveolar fluid clearance, and increased the expression levels of α­, ß­ and γ­ENaC in mice. In addition, in alveolar epithelial cells, insulin increased the expression levels of α­, ß­ and γ­ENaC, as well as the level of phosphorylated SGK1, which were then inhibited by the selective targeting of PI3K or SGK1 by siRNA. Taken together, the results of the present study demonstrated that insulin protected the lung epithelium and attenuated pulmonary edema through the upregulation of ENaC via the PI3K/SGK1 pathway in LPS­induced lung injury.