Comparing the modified socket-shield technique with the conventional immediate implantation technique in the anterior dentition: A 5-year retrospective clinical study.

AIMS: The aim of this retrospective clinical study was to compare the 5-year radiological and clinical outcomes of patients undergoing immediate implantation with or without the modified socket-shield technique. MATERIALS AND METHODS: Patients who underwent anterior tooth replacement via the modified socket-shield technique (MSST) or the conventional immediate implantation technique (CIIT) between 2016 and 2017 were included. The labial bone thickness was assessed at different measurement levels (0, 2, 4 and 6 mm apical to the implant shoulder (IS)) postoperatively (T1), 6 months postoperatively (T2) and 5 years postoperatively (T3). The pink aesthetic score (PES) was evaluated before surgery (T0) and at T2 and T3. Implant success, complications and patient satisfaction were evaluated at every visit. RESULTS: Thirty-six patients (18 in the MSST group) underwent follow-up for 5 years, with no cases of implant failure. Two cases of exposure were detected in the MSST group, but there were no significant effects on hard or soft tissue. Patients in the MSST group showed less and more stable bone resorption than did those in the CIIT group at any measurement level and any time. A higher PES was achieved in the MSST group. Patient satisfaction was similar in both groups. CONCLUSIONS: The MSST is a reliable immediate implantation method because of its ability to preserve the alveolar bone and provide superior recovery of aesthetics.

Impact of heart rate changes during hospitalization on outcome in heart failure with preserved ejection fraction.

AIMS: The benefits of lowering heart rate (HR) in heart failure (HF) with preserved ejection fraction (HFpEF) patients are still a matter of debate. This study aimed to investigate the relationship between changes in HR during hospitalization and cardiovascular (CV) events and all-cause death in hospitalized HFpEF patients. METHODS AND RESULTS: Hospitalized HF patients between January 2017 and December 2021 were consecutively enrolled in a national, multicentred, and prospective registry database, the China Cardiovascular Association Database-HF Center Registry. HF patients with a left ventricular ejection fraction of ≥50% were defined as HFpEF patients. The study analysed admission/discharge HR, change in HR during hospitalization (∆HR), and ∆HR ratio (∆HR/admission HR). The patients were categorized into three groups: no HR dropping group (ΔHR ratio > 0.0%), moderate HR dropping group (-15% < ΔHR ratio ≤ 0.0%), and excessive HR dropping group (ΔHR ratio ≤ -15%). All patients were followed up for 12 months. The primary endpoint was CV events (CV death or HF rehospitalization). The secondary endpoint was all-cause death. A total of 19 510 HFpEF patients (9750 males, mean age 71.9 ± 12.2 years) were included, with 4575 in the no HR dropping group, 8434 in the moderate HR dropping group, and 6501 in the excessive HR dropping group. Excessive HR dropping during hospitalization was significantly associated with an increased risk of CV events (17.1%) compared with the no HR dropping group (14.5%, P < 0.001) or the moderate HR dropping group (14.0%, P < 0.001), although all-cause mortality was similar among the three groups. After adjusting for multiple confounding factors, excessive HR dropping remained an independent predictor of increased CV event risk [hazard ratio 1.197, 95% confidence interval (CI) 1.078-1.328]. Subgroup analysis revealed that the prognostic impact of excessive HR dropping on increased CV event risk remained in the subgroups of older age, New York Heart Association class IV, ischaemic HF, higher left ventricular ejection fraction, absence of chronic kidney disease, and use of beta-blockers or ivabradine. Independent determinants associated with excessive HR dropping during admission included use of beta-blockers [odds ratio (OR) 1.683, 95% CI 1.558-1.819], lower discharge diastolic blood pressure (OR 0.988, 95% CI 0.985-0.991), no pacemaker (OR 0.501, 95% CI 0.416-0.603), coexisting atrial fibrillation or atrial flutter (OR 1.327, 95% CI 1.218-1.445), and use of digoxin (OR 1.340, 95% CI 1.213-1.480). CONCLUSIONS: In hospitalized HFpEF patients, excessive HR dropping during hospitalization is associated with an increased risk of CV death or HF rehospitalization. These findings highlight the importance of HR monitoring and avoiding excessively slowing down HR in hospitalized HFpEF patients to reduce the risk of CV events.

Effectiveness and safety of ivabradine in Chinese patients with chronic heart failure: an observational study.

AIMS: A therapeutic strategy for chronic heart failure (HF) is to lower resting heart rate (HR). Ivabradine is a well-known HR-lowering agent, but limited prospective data exist regarding its use in Chinese patients. This study aimed to evaluate the effectiveness and safety of ivabradine in Chinese patients with chronic HF. METHODS AND RESULTS: This multicentre, single-arm, prospective, observational study enrolled Chinese patients with chronic HF. The primary outcome was change from baseline in HR at 1 and 6 months, measured by pulse counting. Effectiveness was also evaluated using laboratory tests, the Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score (CSS) and overall summary score (OSS), and New York Heart Association (NYHA) class. Treatment-emergent adverse events (TEAEs) were assessed. A post hoc analysis examined the effectiveness and safety of ivabradine combined with an angiotensin receptor-neprilysin inhibitor (ARNI) or beta-blocker. A total of 1003 patients were enrolled [mean age 54.4 ± 15.0 years, 773 male (77.1%), mean baseline HR 88.5 ± 11.3 b.p.m., mean blood pressure 115.7/74.4 ± 17.2/12.3 mmHg, mean left ventricular ejection fraction 30.9 ± 7.6%, NYHA Classes III and IV in 48.8% and 22.0% of patients, respectively]. HR decreased by a mean of 12.9 and 16.1 b.p.m. after 1 and 6 months, respectively (both P < 0.001). At Month 6, improvements in the KCCQ CSS and OSS of ≥5 points were observed in 72.1% and 74.1% of patients, respectively (both P < 0.001). Left ventricular ejection fraction increased by 12.1 ± 11.6 (P < 0.001), and 66.7% of patients showed improvement in NYHA class (P < 0.001). At Month 6, the overall proportion of patients in NYHA Classes III and IV was reduced to 13.5% and 2.1%, respectively. Serum brain natriuretic peptide (BNP) and N-terminal pro-BNP changed by -331.9 ng/L (-1238.6, -134.0) and -1113.8 ng/L (-2202.0, -297.2), respectively (P < 0.001). HR reductions and improvements in NYHA and KCCQ scores with ivabradine were similar with and without use of ARNIs or beta-blockers. Of 498 TEAEs in 296 patients (29.5%), 73 TEAEs in 55 patients (5.5%) were considered related to ivabradine [most frequent sinus bradycardia (n = 7) and photopsia (n = 7)]. TEAEs were reported in a similar number of patients in ARNI and beta-blocker subgroups (21.9-35.6%). CONCLUSIONS: Ivabradine treatment reduced HR and improved cardiac function and health-related quality of life in Chinese patients with chronic HF. Benefits were seen irrespective of whether or not patients were also taking ARNIs or beta-blockers. Treatment was well tolerated with a similar profile to previous ivabradine studies.

2.3-µm single-frequency Tm: ZBLAN fiber amplifier with output power of 1.41 W.

We present here the first watt-level single-frequency thulium-doped ZBLAN fiber amplifier system operating at a wavelength of 2.3 µm. Continuous-wave output of up to 1.41 W was generated from a two-stage Tm: ZBLAN fiber amplifier with direct ground-state pumping at 793 nm. Seeded by a single-frequency distributed feedback diode laser at 2332 nm, the thulium-doped ZBLAN fiber amplifier emitted a laser with linewidth no more than 10 MHz at maximal output power. This study examines the impact of a 2.3-µm seed on the competitive laser transition of 2 µm. The findings indicate that direct pumping of a Tm fiber amplifier holds the potential for achieving higher power output within the 2.3-µm band.

Clinical outcomes by serum potassium levels for patients hospitalized for heart failure: Secondary analysis of data from the China National Heart Failure Registry.

BACKGROUND: Dyskalemia is a mortality risk factor in patients with heart failure (HF). HYPOTHESIS: We described the prevalence of dyskalemia, and clinical outcomes by serum potassium (sK) levels, in Chinese patients hospitalized for HF. METHODS: In this secondary analysis of the prospective China National Heart Failure Registry, adult patients hospitalized between January 1, 2013 and June 30, 2015 who had at least one baseline sK measurement were followed for up to 3 years after discharge. The use of renin-angiotensin-aldosterone system inhibitors at baseline and clinical outcomes during follow-up were compared among sK groups. RESULTS: Among 6950 patients, 5529 (79.6%) had normokalemia (sK >3.5-5.0 mmol/L), 1113 (16.0%) had hypokalemia (sK 0-3.5 mmol/L), and 308 (4.4%) had hyperkalemia (sK >5.0 mmol/L). Baseline characteristics that were most common in patients with hyperkalemia than those with hypo- and normokalemia included older age, HF with reduced ejection fraction, New York Heart Association Class III/IV status, hypertension, and chronic kidney disease. Use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) differed across sK groups (p = .0001); reported in 64.1%, 63.4%, and 54.5% of patients with hypo-, normo-, and hyperkalemia, respectively. Overall, 26.6%, 28.6%, and 36.0% of patients with hypo-, normo-, and hyperkalemia had rehospitalization for worsened HF, or cardiovascular mortality; p = .0057 for between-group comparison. CONCLUSIONS: Patients with hyperkalemia received ACEIs or ARBs for HF treatment at baseline less frequently than those with hypo- or normokalemia, and had worse prognoses. This warrants further investigation into effective hyperkalemia management in HF.

Different expression and prognostic value of troponin in ischemic cardiomyopathy and non-ischemic dilated cardiomyopathy.

BACKGROUND: Early risk stratification of patients with ischemic cardiomyopathy (ICM) and non-ischemic dilated cardiomyopathy (NIDCM) may be beneficial for therapies. METHODS: We retrospectively enrolled all patients admitted for acute heart failure (HF) between January 2019 and December 2021 in Zhongshan Hospital Fudan University, dividing them according to etiology (ICM or NIDCM). Cardiac troponin T (TNT) concentration was compared between two groups. Risk factors for positive TNT and in-hospital all-cause mortality were investigated with regression analysis. RESULTS: A total of 1525 HF patients were enrolled, including 571 ICM and 954 NIDCM. The TNT positive patients were not different between the two groups (41.3% in ICM group vs. 37.8% in NIDCM group, P = 0.215). However, the TNT value in ICM group were significantly higher than that in NIDCM group (0.025 (0.015-0.053) vs. 0.020 (0.014-0.041), P = 0.001). NT-proBNP was independently associated with TNT in both ICM and NIDCM group. Although the in-hospital all-cause mortality did not show much difference between the two groups (1.1% vs. 1.9%, P = 0.204), the NIDCM diagnosis was associated with reduced risk of mortality after multiple adjustments (OR 0.169, 95% CI 0.040-0.718, P = 0.016). Other independent risk factors included the level of NT-proBNP (OR 8.260, 95% CI 3.168-21.533, P < 0.001), TNT (OR 8.118, 95% CI 3.205-20.562, P < 0.001), and anemia (OR 0.954, 95% CI 0.931-0.978, P < 0.001). The predictive value of TNT and NT-proBNP for all-cause mortality was similar. However, the best cutoff values of TNT for mortality were different between ICM and NIDCM groups, which were 0.113 ng/mL and 0.048 ng/mL, respectively. CONCLUSION: The TNT level was higher in ICM patient than that in NIDCM patients. TNT was an independent risk factor for in-hospital all-cause mortality for both ICM and NIDCM patients, although the best cutoff value was higher in ICM patients.

Engineering a triple-functional magnetic gel driving mutually-synergistic mild hyperthermia-starvation therapy for osteosarcoma treatment and augmented bone regeneration.

Malignant bone tumors result in high rates of disability and death and are difficult to treat in terms of killing tumors and repairing bone defects. Compared with other hyperthermia strategies, magnetic hyperthermia has become an effective therapy for treating malignant bone tumors due to its lack of depth limitations. However, tumor cells express heat shock protein (HSP) to resist hyperthermia, which reduces its curative effect. Competitive ATP consumption can reduce HSP production; fortunately, the basic principle of starvation therapy by glucose oxidase (GOx) is consuming glucose to control ATP production, thereby restricting HSP generation. We developed a triple-functional magnetic gel (Fe3O4/GOx/MgCO3@PLGA) as a magnetic bone repair hydrogels (MBRs) with liquid‒solid phase transition capability to drive magneto-thermal effects to simultaneously trigger GOx release and inhibit ATP production, reducing HSP expression and thereby achieving synergistic therapy for osteosarcoma treatment. Moreover, magnetic hyperthermia improves the effect of starvation therapy on the hypoxic microenvironment and achieves a reciprocal strengthening therapeutic effect. We further demonstrated that in situ MBRs injection effectively suppressed tumor growth in 143B osteosarcoma tumor-bearing mice and an in-situ bone tumor model in the rabbit tibial plateau. More importantly, our study also showed that liquid MBRs could effectively match bone defects and accelerate their reconstruction via magnesium ion release and enhanced osteogenic differentiation to augment the regeneration of bone defects caused by bone tumors, which generates fresh insight into malignant bone tumor treatment and the acceleration of bone defect repair.

Advanced polymer hydrogels that promote diabetic ulcer healing: mechanisms, classifications, and medical applications.

Diabetic ulcers (DUs) are one of the most serious complications of diabetes mellitus. The application of a functional dressing is a crucial step in DU treatment and is associated with the patient's recovery and prognosis. However, traditional dressings with a simple structure and a single function cannot meet clinical requirements. Therefore, researchers have turned their attention to advanced polymer dressings and hydrogels to solve the therapeutic bottleneck of DU treatment. Hydrogels are a class of gels with a three-dimensional network structure that have good moisturizing properties and permeability and promote autolytic debridement and material exchange. Moreover, hydrogels mimic the natural environment of the extracellular matrix, providing suitable surroundings for cell proliferation. Thus, hydrogels with different mechanical strengths and biological properties have been extensively explored as DU dressing platforms. In this review, we define different types of hydrogels and elaborate the mechanisms by which they repair DUs. Moreover, we summarize the pathological process of DUs and review various additives used for their treatment. Finally, we examine the limitations and obstacles that exist in the development of the clinically relevant applications of these appealing technologies. This review defines different types of hydrogels and carefully elaborate the mechanisms by which they repair diabetic ulcers (DUs), summarizes the pathological process of DUs, and reviews various bioactivators used for their treatment.

Clinical characteristics and 1-year outcomes in hospitalized patients with heart failure with preserved ejection fraction: results from the China Cardiovascular Association Database-Heart Failure Center Registry.

AIM: We aimed to evaluate clinical characteristics and 1-year outcomes in hospitalized patients with heart failure with preserved ejection fraction (HFpEF) from China. Factors associated with outcomes (hospitalization for HF [HHF] and cardiovascular [CV] death) were assessed. METHOD AND RESULTS: Data were from the China Cardiovascular Association (CCA) Database-HF Center Registry. Between January 2017 and June 2021, 41 708 hospitalized HFpEF patients with 1-year follow-up from 481 CCA Database-HF Center certified secondary and tertiary hospitals across overall 31 provinces of mainland China were included in this study. Of study participants (mean age 72.2 years, 49.3% female), 18.2% had HHF in prior 1 year and 55.8% had New York Heart Association class III/IV. Median left ventricular ejection fraction was 59%. Ischaemia (26.6%), infection (14.4%) and arrhythmia (10.5%) were the three most common precipitating factors for index HHF. Nearly 67.4% had ≥3 comorbidities. Hypertension (65.2%), coronary heart disease (60.3%) and atrial fibrillation (41.2%) were the three most common comorbidities. Device and medication therapy non-compliance with current HF guideline recommendation was observed. The 1-year rate of clinical outcomes was 16.4%, the 1-year rate of HHF was 13.6% and CV death was 3.1%. Factors associated with clinical outcomes included HHF in prior 1 year, serum level of sodium <135 mmol/L and N-terminal pro-B-type natriuretic peptide >1800 pg/ml. CONCLUSION: Patients with HFpEF from China were characterized by high comorbid burden and high 1-year risk of HHF and CV death. Immediate efforts are needed to improve HFpEF management in China.

Influence of bone morphology on the mechanobiological stimuli distribution of maxillary anterior labial bone: A biomechanical study.

OBJECTIVE: This study intended to ascertain the dimensional effects of labial bone thickness and height on the mechanobiological stimuli distribution of maxillary anterior labial bone through biomechanical analysis. MATERIAL AND METHODS: Twelve 3D finite element models of an anterior maxillary region with an implant were computer-simulated, including four levels of labial bone thicknesses (2, 1.5, 1.0, and 0.5 mm) and three levels of labial bone heights (normal, reduced by 1/3, reduced by 1/2). A 45° buccolingual oblique load of 100 N was applied to the implant restoration. RESULTS: Equivalent stress and principal strain mainly concentrated on crestal bone around the implant neck. The maximum equivalent stress in bone decreased as labial bone mass decreased, while the maximum principal strain and the displacement of dental implant increased as labial bone mass decreased. No significant difference of these three indicators was observed, when the labial bone thickness changed in the range of 2.0-1.0 mm with sufficient labial bone height. CONCLUSIONS: In terms of biomechanics, the thickness of labial bone plate was recommended ≥1 mm. Sufficient labial bone height was warranted to prevent the stability of the implants from being seriously affected. The labial bone heights were more effective than thicknesses on the mechanobiological stimuli response of the dental implant-bone system. CLINICAL SIGNIFICANCE: For this 3D finite element study, the biomechanical responses under different bone mass conditions were explored, in order to predict the process of bone remodeling and provide valid clinical recommendations for the decision-making process regarding the choices of tissue augmentation for some specific esthetic implantation cases for future clinical applications.

BMP2 immune complexes promote new bone formation by facilitating the direct contact between osteoclasts and osteoblasts.

BMP2 antibody is proposed as a promising replacement for rhBMP2 in bone tissue engineering. Although studies have demonstrated its osteoinductive efficacy, the underlying osteogenic mechanism and adverse reactions of specific BMP2 antibody are not clarified yet, making it difficult to optimize the antibody for future application. By establishing BMP2 immune complexes (BMP2-ICs) ex vivo, we were able to introduce BMP2-ICs directly in vivo and found that BMP2-ICs promoted bone formation while suppressing osteoclastogenesis. However, ex vivo osteoclastogenic assays showed that BMP2-ICs promoted osteoclastogenesis by binding FcγR and activating PLCγ2 phosphorylation. Given that BMP2-ICs react with osteoblast and osteoclast lineage cells by the conjugated BMP2 domain and the Fc domain respectively, we introduced BMP2-ICs into coculture system of the two lineage cells and found that BMP2-ICs promoted osteogenesis while suppressing osteoclastogenesis by facilitating osteoblast-osteoclast contact and activating the EphrinB2-EphB4 signaling. This bidirectional function of BMP2-ICs was reproduced in the cranial bone resorption model, where osteoblast and osteoclast lineage cells co-localized. This study excluded the hidden problem of osteoclast overactivation that usually comes with rhBMP2 and clarified the first evidence of the mechanism of antibody-mediated bone regeneration, suggesting BMP2-ICs may present a promising therapy for bone diseases related with disrupted osteoclast-osteoblast interaction.

Alteration of m6A RNA Methylation in Heart Failure With Preserved Ejection Fraction.

Background: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous disease, in which its pathogenesis is very complex and far from defined. Here, we explored the N6-methyladenosine (m6A) RNA methylation alteration in patients with HFpEF and mouse model of HFpEF. Methods: In this case-control study, peripheral blood mononuclear cells (PBMCs) were separated from peripheral blood samples obtained from 16 HFpEF patients and 24 healthy controls. The change of m6A regulators was detected by quantitative real-time PCR (RT-PCR). A "two-hit" mouse model of HFpEF was induced by a high-fat diet and drinking water with 0.5 g/L of N ω-nitro-l-arginine methyl ester (L-NAME). MeRIP-seq was used to map transcriptome-wide m6A in control mice and HFpEF mice, and the gene expression was high-throughput detected by RNA-seq. Results: The expression of m6A writers METTL3, METTL4, and KIAA1429; m6A eraser FTO; and reader YTHDF2 was up-regulated in HFpEF patients, compared with health controls. Furthermore, the expression of FTO was also elevated in HFpEF mice. A total of 661 m6A peaks were significantly changed by MeRIP-seq. Gene Ontology (GO) analysis revealed that protein folding, ubiquitin-dependent ERAD pathway, and positive regulation of RNA polymerase II were the three most significantly altered biological processes in HFpEF. The pathways including proteasome, protein processing in the endoplasmic reticulum, and PI3K-Akt signaling pathway were significantly changed in HFpEF by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Conclusions: The expression pattern of m6A regulators and m6A landscape is changed in HFpEF. This uncovers a new transcription-independent mechanism of translation regulation. Therefore, our data suggest that the modulation of epitranscriptomic processes, such as m6A methylation, might be an interesting target for therapeutic interventions.

Sensory denervation increases potential of bisphosphonates to induce osteonecrosis via disproportionate expression of calcitonin gene-related peptide and substance P.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious side effect of systematic administration of bisphosphonates (BPs). Sensory innervation is crucial for bone healing. We established inferior alveolar nerve injury (IANI) and inferior alveolar nerve transection (IANT) models characterized by disorganized periosteum, increased osteoclasts, and unbalanced neuropeptide expression. Zoledronate injection disrupted neuropeptide expression in the IANI and IANT models by decreasing calcitonin gene-related peptide (CGRP) and increasing substance P (SP); associated with this, BRONJ prevalence was significantly higher in the IANT model, followed by the IANI model and the sham control. CGRP treatment significantly reduced BRONJ occurrence, whereas SP administration had the opposite effect. In vitro, RAW 264.7 cells were treated with BPs and then CGRP and/or SP to study changes in zoledronate toxicity; combined application of CGRP and SP decreased zoledronate toxicity, whereas CGRP or SP applied alone showed no effects. These results demonstrate that sensory denervation facilitates the occurrence of BRONJ and that CGRP used therapeutically may prevent BRONJ progression, provided that SP is also present. Further studies are necessary to determine the optimal ratio of CGRP to SP for promoting bone healing and to uncover the mechanism by which CGRP and SP cooperate.

The sialylation profile of IgG determines the efficiency of antibody directed osteogenic differentiation of iMSCs by modulating local immune responses and osteoclastogenesis.

Antibody-mediated osseous regeneration (AMOR) has been proved as a promising strategy for osteogenic differentiation of induced pluripotent stem cells derived MSCs (iMSCs). The key characteristic of antibody that determines the AMOR potential is largely unknown. The glycosylation profile of immunoglobulin G (IgG) represents a key checkpoint that determines its effector functions. Herein, we modified the sialylation profile of BMP2 antibodies to investigate the effects of glycosylation on antibody-mediated osteogenic differentiation of iMSCs. We found that over-sialylated BMP2 antibodies stimulated the highest amount of new bone while those non- or low-sialylated led to bone porosity and collapse. The immune response aroused by BMP2 immune complexes (BMP2-ICs) was intensified by desialylation, which contributed to an environment that favored osteoclastogenesis while inhibited osteoblastogenesis. In vitro study further demonstrated that the osteogenic potential of BMP2-ICs was not significantly affected by the degree of sialylation. On the other hand, BMP2-ICs could stimulate osteoclastogenesis by binding FcγRs on preosteoclasts directly, which was significantly intensified by desialylation and attenuated by over-sialylation. Bone defects implanted with alginate microbeads loaded with iMSCs and over-sialylated antibodies showed more bone formation than those sites with non- or low sialylated antibodies. Taken together, our study demonstrated that sialylation profile is one of the traits that decide the AMOR potential of BMP2 antibodies. Enhancement of sialylation may be a promising strategy to optimize antibody for iMSCs application in bone tissue engineering. STATEMENT OF SIGNIFICANCE: Antibody-mediated osseous regeneration (AMOR) is a promising strategy for bone tissue engineering that takes advantage of the specific reactivity of antibodies to sequester endogenous BMP2 and present it to osteoprogenitor cells. We previously demonstrated that BMP2 immune complex can drive iPSCs derived MSCs to osteogenic lineage. In this study, we analyze the effects of glycosylation profile on antibody directed osteogenic differentiation of iMSCs because glycosylation profile represents a key checkpoint that determines the effector functions of antibodies, and it is susceptible to variations in different clones. The results showed that sialylation profile is one of the traits that decides the AMOR potential of BMP2 antibody, and the enhancement of sialylation maybe a promising strategy to optimize antibodies for AMOR.

Prognostic value of sST2 in patients with heart failure with reduced, mid-range and preserved ejection fraction.

BACKGROUNDS: Prognostic value of soluble suppression of tumorigenecity (sST2), a novel circulating biomarker for myocardial fibrosis, remains elusive in the heart failure patients with preserved ejection fraction (HFpEF). METHODS: 405 consecutive patients with heart failure (HF) were enrolled prospectively, and were grouped into HF with reduced ejection fraction (HFrEF, N = 215), HF with mid-range ejection fraction (HFmrEF, N = 80) and HFpEF (N = 110). The primary endpoint was the composite endpoint of all-cause death and HF rehospitalization. RESULTS: After a median of 12 months, 139 patients reached the primary endpoint, with 57 patients died and 82 patients rehospitalized. Multivariate analysis confirmed that sST2 was an independent risk factor of the primary endpoint for all HF patients [hazard ratio (HR) 2.35, 95% confidence interval (CI) 1.30-4.22, P = 0.004]. Predicting efficacy of sST2 on outcomes was higher for HFpEF (HR 6.48, 95%CI 1.89-22.21, P = 0.003) as compared to HFrEF (HR 3.21, 95% CI 1.67-6.19, P = 0.000). But the association between sST2 and outcomes in HFmrEF is not statistical (HR 3.38, 95%CI 0.82-13.86, P = 0.091). The combined use of sST2 and N terminal pro B type natriuretic peptide (NT-proBNP) could improve the prognostic value compared to using NT-proBNP alone in HFrEF (AUC = 0.794 vs. 0.752, P = 0.034). CONCLUSION: Higher baseline sST2 levels are associated with increased risk of all-cause death and HF rehospitalization in patients with HF independent of ejection fraction. The combined use of sST2 and NT-proBNP could improve the prognostic value than using these two values alone, especially for HFrEF patients.

Histone hyperacetylation mediates enhanced IL-1ß production in LPS/IFN-γ-stimulated macrophages.

Under the condition of lipopolysaccharide (LPS)/interferon (IFN)-γ activation, macrophage metabolism is converted from oxidative phosphorylation to glycolysis. In the present work, we analysed whether glycolysis could affect interleukin (IL)-1ß expression through altering histone acetylation levels in mouse bone marrow-derived macrophages. Immunocytochemistry and Western blot analysis are used to characterize histone acetylation in macrophages stimulated by LPS/IFN-γ. Real-time polymerase chain reaction and enzyme-linked immunosorbent assay were used to determine IL-1ß production. The metabolism of macrophages was monitored in real-time by the Seahorse test. Our results showed that glycolytic metabolism could enhance histone acetylation and promote IL-1ß production in LPS/IFN-γ-activated macrophages. Moreover, increased production of IL-1ß by glycolysis was mediated through enhanced H3K9 acetylation. Importantly, it was found that a high dose of histone deacetylase inhibitor could also significantly increase the expression of IL-1ß in the absence of glycolytic metabolism. In conclusion, this study demonstrates that glycolytic metabolism could regulate IL-1ß expression by increasing histone acetylation levels in LPS/IFN-γ-stimulated macrophages.

Application of problem-based learning and case-based learning integrated method in the teaching of maxillary sinus floor augmentation in implant dentistry.

BACKGROUND: Teaching of maxillary sinus floor augmentation (MSFA) is challenging for dental educators due to the varied sinus anatomy and high rate of complications. The method integrating problem-based learning and case-based learning (PBL-CBL method) may be more effective than the traditional teacher-centered method. The aim is to evaluate the efficacy of the PBL-CBL method in teaching MSFA. MATERIALS & METHODS: Ninety-two students who received training between 2015 and 2017 at the Department of Implant Dentistry were divided randomly into an experimental group and a control group. Students in the experimental group were trained using the PBL-CBL method, while those in the control group were trained using the traditional teacher-centered method. After three months of training, a survey of the students' opinions about the corresponding teaching method was carried out through a feedback questionnaire. A theory test was used to investigate the level of MSFA knowledge among the students. A case analysis was designed to test whether the students can apply the knowledge in solving new problems. RESULTS: Compared with the control method, the PBL-CBL method resulted in higher scores in both the theory test and the case analysis, and obtained a higher rate of satisfaction among the students. The difference in scores between the two methods were statistically significant (P < 0.01). CONCLUSION: The PBL-CBL method resulted in better results regarding acquisition of academic knowledge, ability in case analysis and student satisfaction compared with the teacher-centered method. It may be a promising mode for teaching complex surgical techniques in implant dentistry and other dental fields.

Comprehensive metabolic profiles of seminal plasma with different forms of male infertility and their correlation with sperm parameters.

Metabolomics measurements of seminal plasma are widely used in diagnosis and finding of molecular mechanisms of male infertility. However, so far the limitation of metabolome coverage of analytical methods hinders comprehensive metabolite biomarker finding. Moreover, the widely used case-control comparison is not enough to unveil the detailed correlations of the metabolic changes with different sperm abnormalities. In this work, we aimed to have comprehensive metabolic profiling of seminal plasma to find the metabolomics difference between healthy controls and infertility case samples with different semen abnormities by liquid chromatography-mass spectrometry (LC-MS) detection with previously established new sample preparation procedure. Among 624 detected metabolite features, 63 potential biomarkers in various metabolite classes were found for infertility in seminal plasma by multivariate analysis. Interestingly, different infertility forms have different potential biomarkers with few in common, and most of potential biomarkers were found in oligo-astheno-teratospermia samples. To further find the association of the metabolomic changes with specific sperm abnormality, sperm parameters including sperm concentration, sperm deformity rate and sperm motility were also collected, and multivariate linear regression was used to find correlations between sperm parameters and potential biomarkers. Finally, levels of 17 metabolites were found to be significantly correlated with sperm parameters. Most of correlations agreed with previously reported mechanisms of infertility, such as correlation of acylcarnitines with sperm concentration and sperm deformity, and correlation of some antioxidants with sperm deformity rate and sperm motility. Some correlations were reported for the first time, such as negative correlations of isopentenyl pyrophosphate, 2-phosphoglyceric acid and γ-glutamyl-Se-methylselenocysteine with sperm deformity rate, and negative correlation of creatine riboside with sperm concentration. All the potential biomarkers were involved in 14 metabolic pathways playing important role in energy production, antioxidation, hormone regulation and sperm membrane. These results proved previously reported molecular mechanism (such as oxidative stress and energy production) and also gave new possible clues to the pathology of male infertility, which will benefit future etiology, diagnosis and treatment of male infertility.