Regulation of microRNA-126 on the polarization of human macrophages stimulated by Porphyromonas gingivalis lipopolysaccharide / 中华口腔医学杂志

Objective: To study the effect of microRNA-126 (miR-126) on the polarization of human monocyte-derived macrophages stimulated by Porphyromonas gingivalis (Pg) lipopolysaccharide (LPS). Methods: Macrophages derived from human myeloid leukemia mononuclear cells were stimulated by Pg-LPS (5 mg/L) and by Pg-LPS (5 mg/L) after 24 h-transfection of miR-126 mimic or negative control RNA for 48 h, respectively. Real-time quantitative-PCR (qRT-PCR), enzyme-linked immunosorbent assay (ELISA) and Western blotting were conducted to detect the changes in miR-126, pro-inflammatory factor tumor necrosis factor-α (TNF-α), anti-inflammatory factors interleukin-10 (IL-10), inducible nitric oxide synthase (iNOS), arginase-1 (Arg-1) and M1 polarization-related pathways such as nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Results: Compared with non-LPS stimulation group (TNF-α: 1.000±0.020, iNOS: 1.125±0.064, miR-126: 1.004±0.113, IL-10: 1.003±0.053, Arg-1: 1.130±0.061), the mRNA levels of TNF-α (3.105±0.278) and iNOS (4.296±0.003) increased significantly (t=6.53, P=0.003; t=42.63, P<0.001, respectively), while miR-126, IL-10 and Arg-1 expressions (0.451±0.038, 0.545±0.004 and 0.253±0.017) decreased significantly (t=7.95, P=0.001; t=7.36, P=0.002; t=11.94, P<0.001, respectively) after Pg-LPS stimulated by human-derived macrophages for 48 h. The protein expression of iNOS, TNF-α, Arg-1 and IL-10 were consistent at mRNA levels. Meanwhile, the expressions of phospho-NF-κB p65 (p-p65), phospho-extracellular signal-regulated kinase (p-ERK) and phospho-p38 MAPK (p-p38) increased significantly, while the expression of Arg-1 decreased significantly. Compared with the negative controls (scramble RNA) (TNF-α: 1.141±0.197, iNOS: 1.173±0.115, IL-10: 1.032±0.138, Arg-1: 0.933±0.044), the mRNA levels of TNF-α (0.342±0.022) and iNOS (0.588±0.085) expressions significantly decreased (t=5.35, P=0.006; t=5.05, P=0.007), while IL-10 (1.786±0.221) and Arg-1 expressions (2.152±0.229) significantly increased (t=3.71, P=0.021; t=6.21, P=0.003) after Pg-LPS stimulation with miR-126 mimic transfection. The relative protein expressions of iNOS, p-p65, p-ERK and p-p38 significantly decreased (t=13.00, P<0.001; t=6.98, P=0.002; t=10.86, P<0.001; t=8.32, P=0.001), while the protein level of Arg-1 significantly increased (t=12.08, P<0.001). Conclusions: Pg-LPS could promote M1 polarization of macrophages. miR-126 might inhibit the effect of Pg-LPS on the M1 polarization of macrophages through down-regulating NF-κB and MAPK signaling pathways.

Effectiveness and safety of idarucizumab in the management of perioperative complications of atrial fibrillation catheter ablation in atrial fibrillation patients under dabigatran therapy / 中华心血管病杂志

Objective: To investigate the efficacy and safety of idarucizumab in the treatment of perioperative cardiac tamponade and thromboembolic events during catheter ablation in atrial fibrillation (AF) patients under dabigatran therapy. Methods: This study was a retrospective analysis enrolling patients under dabigatran therapy, who underwent catheter ablation for AF at Beijing Anzhen Hospital from January 2019 to December 2020 and developed perioperative cardiac tamponade or acute ischemic stroke (AIS) and received idarucizumab to reverse the anticoagulant effect of dabigatran. Patients' age, sex, renal function, coagulation test and safety events at 30 d after idarucizumab administration were collected and analyzed. The clinical presentation and prognosis were also analyzed. Results: A total of 7 patients were included, 2 (2/7) were male, mean age was (66.3±11.2) years, serum creatinine level was (66.3±13.6) μmol/L, estimated glomerular filtration rate was (89.4±11.2) ml·min-1·1.73 m-2, CHA2DS2-VASc and HAS-BLED scores were (3.2±1.9) and (1.3±1.3), respectively. Five patients (5/7) developed cardiac tamponade during the perioperative period and the time interval to the last dose of dabigatran was (6.3±2.6) h. Idarucizumab was given at (36.4±16.7) min after the definitive diagnosis of cardiac tamponade. A significant decrease of activated partial thromboplastin time was achieved after idarucizumab administration in all five cases. Pericardial puncture and drainage were applied to all patients (5/5) with cardiac tamponade, the drainage volume was (1 037.0±846.9) ml, the retention time of pericardial drainage catheter was (27.9±13.9) h, and the recovery time of anticoagulation was (28.4±13.2) h. One patient (1/5) underwent thoracotomy for hemostasis due to excessive blood loss with the aim of ensuring complete hemostasis. Bleeding occurred in 1 patient (1/5) after the first restart of anticoagulation. AIS occurred in 2 patients (2/7) after operation. One case (1/2) received intravenous thrombolysis after receiving 5.0 g idarucizumab, no hemorrhagic transformation was observed, and the recovery process was satisfactory. Another patient in this group experienced significantly prolonged onset time and 5.0 g idarucizumab was applied before intravascular thrombectomy, there was no bleeding complication in this patient after thrombectomy. At the time of discharge, the consciousness was not significantly improved, and the muscle strength of the right lower limb was recovered somehow compared with that before operation. No hypersensitivity reactions or thrombotic events occurred in these patients within 30 days of the administration of idarucizumab. Conclusion: In AF catheter ablation-associated cardiac tamponade and AIS, idarucizumab is safe and effective in rapidly reversing the anticoagulant effect of dabigatran, use of thrombectomy saves valuable time for timely hemostasis and improvement of cerebral blood circulation.

Salvianolic acid B decreases interleukin-1β-induced colitis recurrence in mice / 中华医学杂志(英文版)

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-1β (IL-1β) was injected intraperitoneally to induce colitis recurrence.@*RESULTS@#Compared with sham control, cell apoptosis in colitis group was increased from 100.85 ± 3.46% to 162.89 ± 11.45% (P = 0.0038), and TJ dysfunction marker myosin light chain kinase (MLCK) was also significantly increased from 99.70 ± 9.29% to 296.23 ± 30.78% (P = 0.0025). The increased cell apoptosis was reversed by both SASP (125.99 ± 8.45% vs. 162.89 ± 11.45%, P = 0.0059) and Sal B (104.27 ± 6.09% vs. 162.89 ± 11.45%, P = 0.0044). High MLCK expression in colitis group was reversed by Sal B (182.44 ± 89.42% vs. 296.23 ± 30.78%, P = 0.0028) but not influenced by SASP (285.23 ± 41.04% vs. 296.23 ± 30.78%, P > 0.05). The recurrence rate induced by recombinant human IL-1β 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.

Effects of titanium implant surface modification on macrophage polarization and osteogenesis / 中国组织工程研究

BACKGROUND: A single use of bone-forming cells to evaluate the biological properties of titanium implant materials cannot meet the demands of early and long-term stable osseointegration. In order to fulfill the objective mentioned above, it is necessary to understand the interaction between implant and body at the interface of implantation. It is also urgent to consider the invaluable function of immunological factors including macrophage, so as to guide the implant surface modification. OBJECTIVE: To review the influence of physical, chemical and biological surface modifications of implants on the macrophage polarization and osteogenesis.METHODS: The first author conducted a computer-based retrieval of PubMed, Springerlink, Web of Science, ScienceDirect, CNKI, CqVip and WanFang databases for relevant articles published from January 2010 to December 2017. The key words were "titanium, implant, macrophage, polarization, osteogenesis" in English and Chinese, respectively. RESULTS AND CONCLUSION: Macrophages represent the first and the most abundant cells in contact with these implant materials and act as main effector cells in the intrinsic immune response. Surface modifications of implants play an important role in osseintegration by a M1"tissue-inflammatory" polarization or M2 "wound-healing" activation. Furthermore, implant surface modification also affects the osteoinductive ability of macrophage. Future research intends to explain the bone healing mechanism between implant and host tissues from the immunological aspect and develop new-type titanium implants. New surface modification methods of implants, which could induce osteogenesis and acquire bone coupling and homeostasis, will be developed to fulfill early-and long-term stable osseointegration.

Extent of Lung Involvement and Serum Cryptococcal Antigen Test in Non-Human Immunodeficiency Virus Adult Patients with Pulmonary Cryptococcosis / 中华医学杂志(英文版)

<p><b>Background</b>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.</p><p><b>Methods</b>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.</p><p><b>Results</b>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 (χ = 40.34, P < 0.001; OR = 39.87).</p><p><b>Conclusions</b>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.</p>

Effect of orofacial inflammatory pain on p38 mitogen-activated protein kinase activation in trigeminal caudal nucleus of rats / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To evaluate the potential role of p38 mitogen-activated protein kinase (MAPK) in the orofacial inflammatory pain.</p><p><b>METHODS</b>SD rats received subcutaneous injection of 2.5% formalin 50 µl in the left vibrissa pad to establish the inflammatory pain model. The rats were grouped into the control group, the formalin group (FOR group), the formalin + saline group (FOR + NS group) and the formalin + SB203580 group (FOR + SB group). SB203580 or saline was inserted into the rat's cisterna magna 20 minutes prior to the formalin injection, then the behavioral changes were tested. The immunofluorescence staining and Western blotting analysis were performed to examine c-fos, p38MAPK and phosphorylated p38 (p-p38) activity in Vc at 20, 60, 120, 180 minutes after formalin injection.</p><p><b>RESULTS</b>p38MAPK was constitutively expressed in Vc (P > 0.05) and p38MAPK was activated following formalin injection.Compared with the control group at 20 min (0.12 ± 0.01), the level of p-p38 in FOR group (0.66 ± 0.04) and FOR + NS group (0.64 ± 0.04) increased significantly (P < 0.001). The expression of p-p38 peaked at 20 minutes, and then declined in each group. Intracisterna magna pretreatment of p38MAPK inhibitor SB203580 resulted in potent attenuation of phase II of pain behavior (P < 0.05), while the expression of c-fos was also inhibited, especially at the point of 120 min (P < 0.01).</p><p><b>CONCLUSIONS</b>Activation of p38 mitogen-activated protein kinase played a major role in the development of orofacial inflammatory pain and it was verified by the experimental result that p38MAPK inhibitor SB203580 inhibited the formalin-induced orofacial pain.</p>

Regulation of epithelial sodium channel α-subunit expression by adenosine receptor A₂a in alveolar epithelial cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The amiloride-sensitive epithelial sodium channel α-subunit (α-ENaC) is an important factor for alveolar fluid clearance during acute lung injury. The relationship between adenosine receptor A(2a) (A(2a)AR) expressed in alveolar epithelial cells and α-ENaC is poorly understood. We targeted the A(2a)AR in this study to investigate its role in the expression of α-ENaC and in acute lung injury.</p><p><b>METHODS</b>A549 cells were incubated with different concentrations of A(2a)AR agonist CGS-21680 and with 100 µmol/L CGS-21680 for various times. Rats were treated with lipopolysaccharide (LPS) after CGS-21680 was injected. Animals were sacrificed and tissue was harvested for evaluation of lung injury by analysis of the lung wet-to-dry weight ratio, lung permeability and myeloperoxidase activity. RT-PCR and Western blotting were used to determine the mRNA and protein expression levels of α-ENaC in A549 cells and alveolar type II epithelial cells.</p><p><b>RESULTS</b>Both mRNA and protein levels of α-ENaC were markedly higher from 4 hours to 24 hours after exposure to 100 µmol/L CGS-21680. There were significant changes from 0.1 µmol/L to 100 µmol/L CGS-21680, with a positive correlation between increased concentrations of CGS-21680 and expression of α-ENaC. Treatment with CGS-21680 during LPS induced lung injury protected the lung and promoted α-ENaC expression in the alveolar epithelial cells.</p><p><b>CONCLUSION</b>Activation of A(2a)AR has a protective effect during the lung injury, which may be beneficial to the prognosis of acute lung injury.</p>

Corrosion resistance of a new Ti-12.5Zr-3Nb-2.5Sn alloy / 中华口腔医学杂志

<p><b>OBJECTIVE</b>to evaluate the corrosion resistance of a new titanium alloy for dental restoration in artificial saliva.</p><p><b>METHODS</b>in simulated oral environment, the electrochemical behavior of a new titanium alloy (Ti-12.5Zr-3Nb-2.5Sn) for dental restoration based on the d-electron alloy design method with high elastic modulus, high mechanical and good biological safety properties was investigated together with that of Ti-6Al-4V and TA2 as control groups. The anodic polarization curve and polarization resistance of these alloys were analyzed and the element release of Ti-12.5Zr-3Nb-2.5Sn and Ti-6Al-4V alloy after immersion in artificial saliva for 1, 2, 3, 5, 7, 15 d were measured.</p><p><b>RESULTS</b>polarization curve indicated that Ti-6Al-4V alloy had lower breakdown potential (0.8 V) than Ti-12.5Zr-3Nb-2.5Sn alloy did (> 2.5 V). Ti-6Al-4V alloy showed higher passivation current density (1.45 × 10(-4) - 1.09 × 10(-3) A/cm(2)) than Ti-12.5Zr-3Nb-2.5Sn alloy (3.32 × 10(-6) - 3.46 × 10(-5) A/cm(2)) and TA2(5.03 × 10(-6) - 2.65 × 10(-5) A/cm(2)) did. Polarization resistance results showed that polarization resistance volume of TA2, Ti-12.5Zr-3Nb-2.5Sn alloy and Ti-6Al-4V alloy were 371.0, 252.0, and 60.1 kΩ×cm(2) respectively. With the increasing of dipping time in artificial saliva, the ion release of Ti-12.5Zr-3Nb-2.5Sn alloy and Ti-6Al-4V alloy increased to different degrees. Ti-6Al-4V alloy always showed more ion release than Ti-12.5Zr-3Nb-2.5Sn alloy did in the experiment.</p><p><b>CONCLUSIONS</b>data from this study indicated that Ti-12.5Zr-3Nb-2.5Sn alloy, as a dental restoration material, had good corrosion resistance in artificial saliva.</p>

Effect of different heat treatment on mechanical properties and microstructure of laser welding CoCr-NiCr dissimilar alloys / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To evaluate the effect of heat treatment and porcelain-fused-to-metal (PFM) processing on mechanical properties and microstructure of laser welding CoCr-NiCr dissimilar alloys.</p><p><b>METHODS</b>Samples of CoCr-NiCr dissimilar alloys with 0.5 mm thickness were laser-welded single-side under the setting parameters of 280 V, 10 ms pulse duration. After being welded, samples were randomly assigned to three groups, 10 each. Group1 and 2 received heat treatment and PFM processing, respectively. Group 3 was control group without any treatment. Tensile strength, microstructure and element distribution of samples in the three groups were tested and observed using tensile test, metallographic examinations, scanning electron microscope (SEM), and energy dispersive spectroscopy (EDS) analysis.</p><p><b>RESULTS</b>After heat treatment and PFM processing, tensile strength of the samples were (537.15 +/- 43.91) MPa and (534.58 +/- 48.47) MPa respectively, and elongation rates in Group 1 and 2 were (7.65 +/- 0.73)% and (7.40 +/- 0.45)%. Ductile structure can be found on tensile fracture surface of samples and it was more obvious in heat treatment group than in PFM group. The results of EDS analysis indicated that certain CoCr alloy diffused towards fusion zone and NiCr side after heat treatment and PFM processing. Compared with PFM processing group, the diffusion in the heat treatment group was more obvious.</p><p><b>CONCLUSIONS</b>Heat treatment and PFM processing can improve the mechanical properties and microstructure of welded CoCr-NiCr dissimilar alloy to a certain degree. The improvements are more obvious with heat treatment than with porcelain treatment.</p>