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Maintenance of skeletal integrity requires the coordinated activity of multinucleated bone-resorbing osteoclasts and bone-forming osteoblasts. Osteoclasts form resorption lacunae on bone surfaces in response to cytokines by fusion of precursor cells. Osteoblasts are derived from mesenchymal precursors and lay down new bone in resorption lacunae during bone remodeling. Nuclear factorkappa B (NF-κB) signaling regulates osteoclast and osteoblast formation and is activated in osteoclast precursors in response to the essential osteoclastogenic cytokine, receptor activator of NF-κB ligand (RANKL), which can also control osteoblast formation through RANK-RANKL reverse signaling in osteoblast precursors. RANKL and some pro-inflammatory cytokines, including tumor necrosis factor (TNF), activate NF-κB signaling to positively regulate osteoclast formation and functions. However, these cytokines also limit osteoclast and osteoblast formation through NF-κB signaling molecules, including TNF receptor-associated factors (TRAFs). TRAF6 mediates RANKL-induced osteoclast formation through canonical NF-κB signaling. In contrast, TRAF3 limits RANKL- and TNF-induced osteoclast formation, and it restricts transforming growth factor β (TGFβ)-induced inhibition of osteoblast formation in young and adult mice. During aging, neutrophils expressing TGFβ and C-C chemokine receptor type 5 (CCR5) increase in bone marrow of mice in response to increased NF-κB-induced CC motif chemokine ligand 5 (CCL5) expression by mesenchymal progenitor cells and injection of these neutrophils into young mice decreased bone mass. TGFβ causes degradation of TRAF3, resulting in decreased glycogen synthase kinase-3β/β-catenin-mediated osteoblast formation and age-related osteoporosis in mice. The CCR5 inhibitor, maraviroc, prevented accumulation of TGFβ+/CCR5+ neutrophils in bone marrow and increased bone mass by inhibiting bone resorption and increasing bone formation in aged mice. This paper updates current understanding of how NF-κB signaling is involved in the positive and negative regulation of cytokine-mediated osteoclast and osteoblast formation and activation with a focus on the role of TRAF3 signaling, which can be targeted therapeutically to enhance bone mass.
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Liposomes have made remarkable achievements as drug delivery vehicles in the clinic. Liposomal products mostly benefited from remote drug loading techniques that succeeded in amphipathic and/or ionizable drugs, but seemed impracticable for nonionizable and poorly water-soluble therapeutic agents, thereby impeding extensive promising drugs to hitchhike liposomal vehicles for disease therapy. In this study, a series of weak acid drug derivatives were designed by a simplistic one step synthesis, which could be remotely loaded into liposomes by pH gradient method. Cabazitaxel (CTX) weak acid derivatives were selected to evaluate regarding its safety profiles, pharmacodynamics, and pharmacokinetics. CTX weak acid derivative liposomes were superior to Jevtana® in terms of safety profiles, including systemic toxicity, hematological toxicity, and potential central nerve toxicity. Specifically, it was demonstrated that liposomes had capacity to weaken potential toxicity of CTX on cortex and hippocampus neurons. Significant advantages of CTX weak acid derivative-loaded liposomes were achieved in prostate cancer and metastatic cancer therapy resulting from higher safety and elevated tolerated doses.
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Objective@#To explore the feasibility of real-time three-dimensional ultrasound Xplane imaging in quantifying left and right atrial diastolic maximal volume (LAVmax, RAVmax) and evaluating cardiac diastolic function in fetuses with cardiac disease in second and later trimesters.@*Methods@#One hundred and forty-four fetuses with abnormal heart morphology at 16-34 weeks of gestational age were included and divided into 3 groups according to the influence of pathological changes on atrial volume: group A with symmetrical left and right atrial volume, group B with decreased left atrial volume and increased right atrial volume and group C with increased left atrial volume and decreased right atrial volume, and the fetus were also divided into 2 groups according to the law of fetal development: the middle pregnancy group (16-27+ 6 weeks) and the late pregnancy group (28-34+ 6 weeks). Using the " Xplane" mode of volume probe, the maximal atrial volume was calculated automatically by tracing method and three-path line method. The correlation between the two methods in quantitative LAVmax was validated by paired sample t test and Pearson correlation analysis. The correlation between LAVmax, RAVmax and gestational age were analyzed by curve fitting. The volumes of bilateral chambers and the average weekly growth rates of E peak, A peak and E/A value of mitral and tricuspid orifices were calculated and compared.@*Results@#There was no significant statistical difference between the maximal volume of the left atrium obtained by the tracing method and the three-diameter line method (P>0.05), and there was high correlation between the two methods in the comparison of the maximal volume of the left atrium (r=0.90, 0.88, 0.85; all P<0.01). The data of group A, B and C showed that LAVmax and RAVmax could increase with the increase of gestational weeks in a certain period of abnormal state, and had a good correlation with them(LAVmax: r=0.78, 0.74, 0.78, all P<0.005; RAVmax: r=0.79, 0.77, 0.78, all P<0.005). The average weekly growth rate of RAVmax showed an advantage in group A, B and C. Especially in group C with reduced right atrium, the growth rate of right atrium was 8.15%, which was higher than that of group B with decreased left atrium by 5.06%. The weekly growth rates of E peak and E/A in tricuspid orifice were also higher than those in mitral orifice. The E peak and E/A values of tricuspid orifice in group C were 4.05% and 0.60%, respectively, higher than those in group B, which were 2.58% and 0.02%. Peak A showed an increase in growth rate in group B and group C with decreased atria, peak A values in group B and group C increased by 4.01% and 2.19%, respectively.@*Conclusions@#The right ventricular dominance of fetal heart can still be reflected in certain stages of disease, and the atrial active systolic may play a regulatory role in the filling of cardiac blood flow. Real-time three-dimensional ultrasound Xplane imaging could be used to quantify the atrial volume of fetuses with abnormal heart morphology in second and later trimesters and to preliminary assess atrial function combined with the changes of atrioventricular valve orifice hemodynamics. Real-time three-dimensional ultrasound Xplane imaging technology has obvious advantages of simple, safe, non-invasive, simultaneous and high repeatability in measuring fetal atrial volume.
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Objective To explore the feasibility of real-time three-dimensional ultrasound Xplane imaging in quantifying left and right atrial diastolic maximal volume (LAVmax,RAVmax) and evaluating cardiac diastolic function in fetuses with cardiac disease in second and later trimesters.Methods One hundred and forty-four fetuses with abnormal heart morphology at 16-34 weeks of gestational age were included and divided into 3 groups according to the influence of pathological changes on atrial volume:group A with symmetrical left and right atrial volume,group B with decreased left atrial volume and increased right atrial volume and group C with increased left atrial volume and decreased right atrial volume,and the fetus were also divided into 2 groups according to the law of fetal development:the middle pregnancy group (16-27+6 weeks) and the late pregnancy group (28-34+6 weeks).Using the "Xplane" mode of volume probe,the maximal atrial volume was calculated automatically by tracing method and three-path line method.The correlation between the two methods in quantitative LAVmax was validated by paired sample t test and Pearson correlation analysis.The correlation between LAVmax,RAVmax and gestational age were analyzed by curve fitting.The volumes of bilateral chambers and the average weekly growth rates of E peak,A peak and E/A value of mitral and tricuspid orifices were calculated and compared.Results There was no significant statistical difference between the maximal volume of the left atrium obtained by the tracing method and the three-diameter line method (P ＞0.05),and there was high correlation between the two methods in the comparison of the maximal volume of the left atrium (r =0.90,0.88,0.85;all P ＜0.01).The data of group A,B and C showed that LAVmax and RAVmax could increase with the increase of gestational weeks in a certain period of abnormal state,and had a good correlation with them(LAVmax:r =0.78,0.74,0.78,all P ＜0.005;RAVmax:r =0.79,0.77,0.78,all P ＜0.005).The average weekly growth rate of RAVmax showed an advantage in group A,B and C.Especially in group C with reduced right atrium,the growth rate of right atrium was 8.15 ％,which was higher than that of group B with decreased left atrium by 5.06％.The weekly growth rates of E peak and E/A in tricuspid orifice were also higher than those in mitral orifice.The E peak and E/A values of tricuspid orifice in group C were 4.05％ and 0.60％,respectively,higher than those in group B,which were 2.58％ and 0.02％.Peak A showed an increase in growth rate in group B and group C with decreased atria,peak A values in group B and group C increased by 4.01 ％ and 2.19％,respectively.Conclusions The right ventricular dominance of fetal heart can still be reflected in certain stages of disease,and the atrial active systolic may play a regulatory role in the filling of cardiac blood flow.Real-time three-dimensional ultrasound Xplane imaging could be used to quantify the atrial volume of fetuses with abnormal heart morphology in second and later trimesters and to preliminary assess atrial function combined with the changes of atrioventricular valve orifice hemodynamics.Real-time three-dimensional ultrasound Xplane imaging technology has obvious advantages of simple,safe,non-invasive,simultaneous and high repeatability in measuring fetal atrial volume.
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OBJECTIVE:To investigate the effects of aerosol inhalation of ambroxol combined with gentamicin on postopera-tive related indexes of esophageal cancer patients. METHODS:60 patients underwent esophageal cancer operation were retrospec-tive analyzed and divided into control group(30 cases)and observation group(30 cases)according to drug use. Three days before surgery,control group was given 5% Glucose injection 250 mL intravenously,twice a day;observation group was given Ambrox-ol hydrochloride injection 50 mL added into 5% Glucose injection 250 mL intravenously,twice a day. After operation,both groups were given anti-inflammatory and analgesic drugs. Control group was additionally given aerosol inhalation of Gentamicin sulfate in-jection 80000 units added into 0.9% Sodium chloride injection 20 mL,4 times a day. Observation group was additionally given aerosol inhalation of Ambroxol hydrochloride injection 10 mL added into 0.9% Sodium chloride injection 20 mL,4 times a day, on the basis of control group. Both groups were treated for 5 days. The occurrence of postoperative pulmonary complications were compared between 2 groups. The levels of CRP,TNF-α,PaO2,SaO2,oxygenation index (PaO2/FiO2),the occurrence of ADR were observed before and after operation. RESULTS:The total incidence of postoperative pulmonary complications in observation group was significantly lower than control group,with statistical significance(P0.05). After operation,the levels of CRP and TNF-α in 2 groups were significantly lower than before operation;the observation group was significantly lower than the control group. PaO2,SaO2 and PaO2/FiO2 of 2 groups were sig-nificantly higher than before operation;the observation group was significantly higher than the control group,with statistical significance (P<0.05). No obvious ADR was found in 2groups during medication. CONCLUSIONS:The aerosol inhalation of ambroxol combined with gentamicin can reduce postopera-tive inflammatory factors of esophageal cancer patients,and promotes the recovery of respiratory function without increasing the in-cidence of ADR.
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Objective To analyze the rules of acupoint selection in treating knee osteoarthritis with acupuncture and moxibustion therapy based on data mining; To provide references for clinical treatment.MethodsArticles about treating knee osteoarthritis with acupuncture and moxibustion were retrived from China National Knowledge Infrastructure (CNKI), Wanfang academic periodical full-text database, Chinese Journal Full-text Database (VIP) and SinoMed in China from Jan. 1st 2006 to Jan. 1st 2016. The database of acupuncture and moxibustion prescription was set up. The Apriori association rules, system cluster analysis and factor analysis were adopted in order to analyze the rules of acupoint selection for knee osteoarthritis.ResultsTotally 190 articles were included, covering 228 acupuncture- moxibustion prescriptions, 65 acupoints and the total frequency for 1736 times. The usual acupoints in the lower limbs were Dubi (ST35), Neixiyan (EX-LE 4), and Yanglingquan (GB34). The main maridians were Stomach Meridian of Foot-Yangming, Spleen Meridian of Foot-Taiyin, and Gallbladder Meridian of Foot-Shaoyang, accounting to for 1626 times (93.66%). Cluster analysis achieved other four groups of acupoint selection based on syndrome differentiation.ConclusionLocal acupoints and dialectical point selection were important principle in treating knee osteoarthritis combined with acupoint selection based on syndrome differentiation.
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Objective:To evaluate the literature quality of randomized controlled trials of acupuncture plus rehabilitation for post-stroke limb spasm in the recent ten years in China. Methods:By searching four databases of China National Knowledge Internet (CNKI), Wanfang Academic Journal Full-text Database (Wanfang), Chongqing VIP Database (CQVIP) and Chinese Biomedical Literature Database (CBM), randomized controlled trial (RCT) of acupuncture plus rehabilitation for the treatment of post-stroke limb spasm were screened and selected. In accordance with 2010 edition of the consolidated standards of reporting trials (CONSORT) and standards for reporting interventions in clinical trials of acupuncture (STRICTA), the quality evaluation was processed for RCT documents. Results:Finally, 50 documents were selected. The issues of titles, sample size calculation, application of randomization and blind method, subject’s procedure, conclusion and estimated value, explanation of trial limitation, auxiliary intervention measures and therapeutic plans, and background of therapists exist in most documents. Conclusion:Currently, RCT documents about acupuncture plus rehabilitation for the treatment of post-stroke limb spasm are generally of low quality. In the future, it is necessary to standardize the reports of the clinical trials based upon CONSORT and STRICTA, in order to enhance the document quality.
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A polydimethylsiloxane ( PDMS )/glass microfluidic chip consisting of a three-layer sandwich structure and three-parallel micro-electrode system was fabricated for the separation of polystyrene microspheres according to the particle size in high conductive solution by electric field produced by alternating current. The principle of electrokinetics of microspheres directional movement was investigated. The results showed that, when the applied voltage was 14 V at 100 kHz, the separation efficiency of 10 and 25 μm polystyrene microspheres was the best. Similarly, with a voltage of 10 V at 2 MHz, the separation efficiency of 5 and 25 μm polystyrene microspheres could achieve the highest value. Meanwhile, the voltage of 11 V at 1 MHz was suitable for the separation of 5 , 10 and 25 μm polystyrene microspheres with the separation efficiency of over 90%. At the same time, the formation of the laminar region in the middle of the electrode gap was the key role of microsphere separation.
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Osteoclasts are multinucleated cells formed mainly on bone surfaces in response to cytokines by fusion of bone marrow-derived myeloid lineage precursors that circulate in the blood. Major advances in understanding of the molecular mechanisms regulating osteoclast formation and functions have been made in the past 20 years since the discovery that their formation requires nuclear factor-kappa B (NF-kappaB) signaling and that this is activated in response to the essential osteoclastogenic cytokine, receptor activator of NF-kappaB ligand (RANKL), which also controls osteoclast activation to resorb (degrade) bone. These studies have revealed that RANKL and some pro-inflammatory cytokines, including tumor necrosis factor, activate NF-kappaB and downstream signaling, including c-Fos and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), and inhibition of repressors of NFATc1 signaling, to positively regulate osteoclast formation and functions. However, these cytokines also activate NF-kappaB signaling that can limit osteoclast formation through the NF-kappaB signaling proteins, TRAF3 and p100, and the suppressors of c-Fos/NFATc1 signaling, IRF8, and RBP-J. This paper reviews current understanding of how NF-kappaB signaling is involved in the positive and negative regulation of cytokine-mediated osteoclast formation and activation.
Subject(s)
Cytokines , NF-kappa B , NFATC Transcription Factors , Osteoclasts , RANK Ligand , Receptor Activator of Nuclear Factor-kappa B , TNF Receptor-Associated Factor 3 , Tumor Necrosis Factor-alphaABSTRACT
Objective To study the effect of assessment criteria for thoracic surgery health education in the health education to patients undergoing thoracic surgeries.Methods One hundred and forty patients undergoing selective surgeries were evenly divided by their registration sequence into the control and experiment groups:The former received routine health education and the latter the health education based on thoracic surgery health education criteria.The effects of the health education were assessed by self-designed recognition evaluation criteria for thoracic surgery health education.Results The experiment group was significantly better than the control in terms of health-related knowledge,health belief and health behaviors,except operative approach,anesthesia method and intraoperative medication(all P<0.05).Conclusions The assessment criteria for thoracic surgery health education are helpful for the nurses to perform health education purposefully and pertinently.The criteria are also applicable clinically for the nursing administers to carry out health education assessment.
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Objective To investigate the expression of human β defensin-2(hβD-2)in the eutopic and ectopic endometrial tissue in patients with adenomyosis and in women with normal endometrium.Methods Twenty-five hysteromyoma patients with adenomyosis(AM) and 25 hysteromyoma patients without endometriosis (EMS) were selected and divided into three groups:AM ectopic endometrium group,AM eutopic endometrium group and control group( endometrial tissue in patients with hysteromyoma).The level of mRNA expressions of hβD-2,interleukin-1β ( IL-1β ),interleukin-6 ( IL-6 ) and tumor necrosis factor-α (TNF-α) was investigated quantitatively using Real Time PCR (RT-PCR) and the corresponding protein level was detected by immunohistochemistry.Results Comparing the expression of hβD-2,IL-1β,IL-6,TNF-α genes among the three groups,there was no significant difference between ectopic endometrium group and eutopic endometrium group and there was also no significant difference between eutopic endometrium group and the control group.( P ＞ 0.05 ).The expression of hβD-2 and IL-1β were 0.0320 (0.0095 ～ 0.0690 ) and 0.0427 ( 0.0038 ～ 0.0975 ) in the ectopic endometrium group,and they were 0.0034(0.0025 ～0.0424) and 0.0080(0.0040 ～0.0251 ) in the control group,respectively.They were both significantly higher in ectopic endometrium group than in the control group (P ＜ 0.05 ).In the ectopic endometrium group hβD-2 expression was positively correlated with the level of TNF-α ( r =0.857,P =0.014 ),and it had no correlation with both IL-1β and IL-6 ( r =0.750,P =0.052 ; r =0.464,P =0.464; respectively)Conclusion HβD-2 might not play an important role in the formation of adenomyosis.It may be related to no significant up-regulation of inflammatory factors in ectopic lesion tissue.
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The influence of temperature, chloride ions and sulfide ions on the anticorrosion behavior of 316L stainless steel in simulated cooling water was studied by electrochemical impedance spectroscopy and anodic polarization curves. The results show that the film resistance increases with the solution temperature but decreases after 8 days' immersion, which indicates that the film formed at higher temperature has inferior anticorrosion behavior; Chloride ions and sulfide ions have remarkable effects on the electrochemical property of 316L stainless steel in simulated cooling water and the pitting potential declines with the concentration of chloride ions; the passivation current has no obvious effect; the rise of the concentration of sulfide ions obviously increases the passivation current, but the pitting potential changes little, which indicates that the two types of ions may have different effects on destructing passive film of stainless steel. The critical concentration of chloride ions causing anodic potential curve's change in simulated cooling water is 250 mg/L for 316 L stainless. The effect of sulfide ions on the corrosion resistance behavior of stainless steel is increasing the passivation current density Ip. The addition of 6mg/L sulfide ions to the solution makes Ip of 316 L increase by 0.5 times.
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Objective: To study the effect of organizational justice,organizational support,organizational commitment,role stress on job burnout.Methods: A total of 361 employees were evaluated for their job burnout,organizational justice,organizational support,role stress and organizational commitment.And the LISREL model was built based on the data.Results: The role stress,organizational commitment and organizational justice were the important forecast variables to job burnout.Role stress and organizational commitment mainly produced direct effect to job burnout,but organizational justice mostly produced indirect effect to job burnout by organizational commitment.Furthermore,It was also found that organizational support played an intermediate role organizational justice,role stress and organizational commitment.Conclusion: Organizational justice,organizational support,organizational commitment and role stress have different level of effects on job burnout.