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Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling. Here, we focused on the role of Semaphorin 3A (Sema3A), expressed by sensory nerves, in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement (OTM) model. Firstly, bone formation was activated after the 3rd day of OTM, coinciding with a decrease in sensory nerves and an increase in pain threshold. Sema3A, rather than nerve growth factor (NGF), highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM. Moreover, in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells (hPDLCs) within 24 hours. Furthermore, exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload. Mechanistically, Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway, maintaining mitochondrial dynamics as mitochondrial fusion. Therefore, Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation, both as a pain-sensitive analgesic and a positive regulator for bone formation.
Subject(s)
Humans , Bone Remodeling , Cell Differentiation , Osteogenesis , Semaphorin-3A/pharmacology , Trigeminal Ganglion/metabolismABSTRACT
Objective:To investigate the efficacy and safety of nasal continuous positive airway pressure (NCPAP) combined with inhalation of pulmonary surfactant (PS) using vibrating mesh nebulizers in the treatment of neonatal respiratory distress syndrome (RDS).Methods:A prospective study was performed on premature infants with RDS admitted to the First Affiliated Hospital of Bengbu Medical College between December 2020 and June 2021. They were randomly assigned into vibrating mesh atomization technology group and intubation-surfactant-extubation (INSURE) technology group. The two groups were treated with NCPAP combined with PS. PS in the vibrating mesh atomization technology group was inhaled into the lungs by the new vibrating mesh atomization technology, while PS in the INSURE group was injected into the lungs by endotracheal tube. The pH value, arterial partial pressure of carbon dioxide (PaCO 2), oxygenation index (PaO 2/FiO 2), mechanical ventilation via endotracheal tube (MVET) demand rate, duration of respiratory support, secondary use of PS, complications, and hospital mortality were compared between the two groups. The occurrences of adverse events in the two groups were recorded. Results:A total of 42 preterm infants were finally enrolled, including 20 cases in the vibrating mesh atomization technology group and 22 cases in the INSURE technology group. There were no significant differences in blood gas analysis and PaO 2/FiO 2 before PS administration between the two groups. One hour after PS administration, blood gas analysis and PaO 2/FiO 2 were significantly improved in both groups. Compared with the INSURE technology group, the improvement of PaO 2/FiO 2 was more obvious in the vibrating mesh atomization technology group [mmHg (1 mmHg≈0.133 kPa): 198±34 vs. 173±39, P < 0.05], but no significant difference in pH value or PaCO 2 was found between the two groups. The duration of respiratory support in the vibrating mesh atomization technology group was significantly shorter than that in the INSURE technology group (hours: 96±13 vs. 120±18, P < 0.01), but there was no statistical difference in MVET demand rate [5.0% (1/20) vs. 13.6% (3/22), P > 0.05]. The incidence of periventricular-intraventricular hemorrhage (PVH-IVH) in the vibrating mesh atomization technology group was less than that in the INSURE technology group [0% (0/20) vs. 18.2% (4/22)], but no statistical difference was found ( P > 0.05). No significant differences in the secondary use rate of PS and incidence of bronchopulmonary dysplasia (BPD) or other complications were found between the vibrating mesh atomization technology group and the INSURE technology group [5.0% (1/20) vs. 9.1% (2/22), 5.0% (1/20) vs. 4.5% (1/22), both P > 0.05]. There were no deaths or serious adverse events such as pneumothorax, pulmonary hemorrhage, periventricular leukomalacia (PVL), retinopathy of prematurity (ROP), and necrotizing enterocolitis (NEC) in both groups. Conclusion:Compared with the INSURE technique, NCPAP combined with vibrating mesh atomization technology was also effective and safe in the treatment of RDS, which could significantly improve PaO 2/FiO 2 and shorten the duration of respiratory support. Thus, it was worthy of clinical popularization and application.
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A series of 2-(((5-akly/aryl-1-pyrazol-3-yl)methyl)thio)-5-alkyl-6-(cyclohexylmethyl)-pyrimidin-4(3)-ones were synthesized and their anti-HIV-1 activities were evaluated. Most of these compounds were highly active against wild-type (WT) HIV-1 strain (IIIB) with EC values in the range of 0.0038-0.4759 μmol/L. Among those compounds, had an EC value of 3.8 nmol/L and SI (selectivity index) of up to 25,468 indicating excellent activity against WT HIV-1. anti-HIV-1 activity and resistance profile studies suggested that compounds and displayed potential anti-HIV-1 activity against laboratory adapted strains and primary isolated strains including different subtypes and tropism strains (ECs range from 4.3 to 63.6 nmol/L and 18.9-219.3 nmol/L, respectively). On the other hand, it was observed that those two compounds were less effective with EC values of 2.77 and 4.87 μmol/L for HIV-1A (K103N + Y181C). The activity against reverse transcriptase (RT) was also evaluated for those compounds. Both and obtained sub-micromolar IC values showing their potential in RT inhibition. The pharmacokinetics examination in rats indicated that compound has acceptable pharmacokinetic properties and bioavailability. Preliminary structure-activity relationships and molecular modeling studies were also discussed.
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Objective:To systematically review the association between P2Y12 genetic polymorphisms and the clinical safety of clopidogrel in the patients with cardiovascular and cerebrovascular diseases. Methods:Retrieved from MEDLINE,Embase,CNKI,Si-noMed and Wanfang Database (from January 1995 to December 2016),array researches about the association between P2Y12 genetic polymorphisms and the clinical safety of clopidogrel were collected including the studies of patients taking clopidogrel with cardiovascu-lar and cerebrovascular diseases and excluding animal experimental studies. The bias of recruited studies was assessed and meta-analy-sis was performed by RevMan 5.1 software. Results:Totally 10 array researches(3 in English and 7 in Chinese) were enrolled invol-ving 5 223 patients. There were no statistical differences between T allele gene carriers and CC genetype patients of C34T in the inci-dence of adverse cardiovascular events (RR=0.95,95% CI:0.82-1.09,P=0.46). The incidence of adverse cardiovascular events in T allele gene carriers of G52T was higher than that in GG genetype patients(RR=1.99,95% CI:1.63-2.44,P<0.000 01). The incidence of clopidogrel resistance in T allele gene carriers of C34T was higher than that in CC genetype patients(RR=2.02,95% CI:1.37-2.96,P=0.000 4). The incidence of clopidogrel resistance in T allele gene carriers of G52T was higher than that in GG gene-type patients (RR=1.56,95% CI:1.04-2.34,P=0.03). There was no statistical difference in the risk of clopidogrel resistance be-tween C allele gene carriers of i-T744c and T allele gene no-carriers(RR=0.99,95% CI:0.78-1.25,P=0.92). Conclusion:T al-lele gene carriers of C34T might be a risk factor of the occurrence of clopidogrel resistance,T allele gene carriers of G52T might be a risk factor of the occurrence of cardiovascular events and clopidogrel resistance,and C allele gene carriers of i-T744c might not increase the danger of the occurrence of clopidogrel resistance.
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OBJECTIVE:To systematically review the effect of ticagrelor versus prasugrel on platelet reactivity,and provide evi-dence-based reference for clinical treatment. METHODS:Retrieved from PubMed,CJFD and Wanfang Database,randomized con-trolled trials(RCT)about the effect of ticagrelor versus prasugrel on platelet reactivity were collected. Meta-analysis was performed by using Rev Man software after data extract and quality evaluation by Cochrane 5.1.0. RESULTS:Totally 17 RCTs were enrolled,involv-ing 2 757 patients. Results of Meta-analysis showed,regardless of Verity Now(VN)detection method [MD=15.43,95%CI(-0.39, 31.25),P=0.06] or vasodilator stimulus phosphoprotein(VASP)detection method [MD=-3.04,95%CI(-8.98,2.90),P=0.32], ticagrelor and prasugrel had the same effects on platelet reactivity under loading dose,the differences were not statistically significant;regardless of VN detection method [MD=-48.94,95%CI(-58.04,-39.84),P<0.001] or VASP detection method [MD=-14.32, 95%CI(-20.45,-8.20),P<0.001],the effects of ticagrelor were better than prasugrel on platelet reactivity under maintenance dose,the differences were statistically significant. CONCLUSIONS:At the loading dose,there was no difference between ticagrelor and prasugrel,but ticagrelor has more benefits than prasugrel under maintenance dose.
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OBJECTIVE:To systematically review the effect of organic cation transporter 2 [(OCT2)808G>T] gene polymor-phism on the metformin hydrochloride pharmacokinetics in vivo,and to provide evidence-based reference for clinical medication. METHODS:Retrieved from PubMed,EMBase,Foreign Medical Journey Service,CJFD,VIP database and Wanfang database,re-lated studies about the effect of (OCT2)808G>T gene polymorphism on the metformin hydrochloride pharmacokinetics in vivo were collected,and Meta-analysis was performed by using Rev Man 5.1 statistics software. RESULTS:A total of 5 retrospective studies were included,involving 172 patients. The result of gene type was type GT,type TT and type GG. Results of Meta-analysis showed,compared with type GT volunteers,type TT could prolong the half-time period of metformin hydrochloride;compared with type TT,type GG could increase the peak concentration. However,(OCT2)808G>T gene polymorphism had no effects on the renal clearance rate,creatinine clearance rate and area under the drug-time curve. CONCLUSIONS:(OCT2)808G>T gene poly-morphism has certain effect on the half-time period and peak concentration of metformin hydrochloride in vivo of health volunteer, and has no effect on the renal clearance rate,creatinine clearance rate and area under the drug-time curve. Due to the limit of re-search methodological quality,large-scale and high quality studies are required for further validation of the conclusions.
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Objective To explore the application of the automatic bone age assessment of BoneXpert software in Children and adolescent of China (Shanghai).Methods Left hand and wrist radiographs of 434 cases of children from trauma (264 boys and 170 girls) were obtained from Jan.2010 to Dec.2013.Bone age was assessed by BoneXpert software and 40 radiographs were randomly chosen and re-evaluated after a week.Results Seven images were rejected by BoneXpert,so the efficiency of the software was 98.4％ and it takes only 14.5 s for every image.Sample assessments by two times are exactly the same.As to BoneXpert software,there were statistical differences between bone age and chronological age in 8 groups:7,8,9,11 years old boys and 2,3,9,11 years old girls(P ＜ 0.05) out of 26 groups,and the average difference was about 1 s.The following modifications suggested that 0.57,0.79,0.93,-0.38 and-0.22,0.30,0.37,0.59 years could be added respectively for the groups of boys aged 7,8,9,11 and girls aged 2,3,9,11 years old according to their average differences between the bone age and the chronological age.Conclusions The BoneXpert method for automated determination of skeletal maturity which evaluates bone age objectively and quickly can be applied clinically after slight adjustment in some age groups.BoneXpert software is 100 percent automatic and could eliminate the subjective evaluation inaccuracy.