BACKGROUND:Distraction osteogenesis is one of the most important tissue engineering technologies. However, the exact signaling pathway controling mesenchymal stem cel-osteoblast lineage (MSC-OB) migration during distraction osteogenesis has not yet been elucidated. More efforts should be paid to make a ful understanding of the mechanism on MSC-OB lineage migration, which can improve the clinical efficacy of distraction osteogenesis.
OBJECTIVE:To evaluate the effects of mechanical stretch on the ability of MSC-OB mobility and expression of mammalian target of rapamycin (mTOR) signaling pathway as wel as matrix metaloproteinases (MMPs) in MSC-OB, and to make clear the mechanism by which controls MSC-OB migration during distraction osteogenesis.
METHODS:Twelve Sprague-Dawley rats were randomized into two groups: experimental group (n=6), anin vivo rat mandibular distraction osteogenesis model was established on the right side of rats; non-stretch group (n=6), only the mandibular resection was done but with no distraction osteogenesis. Immunohistochemical staining was used to detect phosphorylated mTOR expression in new osteotylus at 15 days after operation. In addition, an in vitro cel stretch model was made in the mandibular mesenchymal stem cels from healthy Sprague-Dawley rats under resting tension force (6%, 4 hours); no distraction was done in control group. The ability of MSC-OB mobility, the expression of mTOR, Raptor, p70S6K and MMPs were evaluated using experiment methods including immunohistochemistry staining, real-time PCR and scratch assay.
RESULTS AND CONCLUSION: The expression of phosphorylated mTOR in MSC-OB was upregulated in the mandibular bone calus of the stretch group than the non-stretch group (P < 0.05). In thein vitro experiments, MSC-OB applied with mechanical stretch (6%, 4 hours) showed elevated gene expression levels of mTOR, Raptor, p70S6K, MMP-2, MMP-9 and MMP-13 compared with the control group (0%, 4 hours). Meanwhile, MSC-OB in the experiment group (6%, 4 hours) showed a greater ability of mobility, as demonstrated by a farther distance after 48 hours of observation (P < 0.05). The present study suggests that the enhancement of MSC-OB mobility correlates with increase of the gene expression of MMPs and mTOR signaling pathway. Mechanical stretch may promote MSC-OB migration through activation of mTOR/MMPs signaling pathway.

BACKGROUND: Over the last 10-20 years, international guidelines and consensus statements for the management of common allergic diseases (e.g. allergic rhinitis and asthma) have been developed and disseminated worldwide. However, their impact on knowledge and standard of clinical practice among primary care physicians and specialists is unknown. OBJECTIVE: To investigate need for an improvement in the dissemination of international guidelines for the diagnosis and management of allergic rhinitis. METHODS: Seven medical students who attended 3-day 1st International Basic Allergy Course (2010) took down all questions raised during the entire course. A systemic analysis of these questions was performed to identify areas for improvement in diagnosis and management of allergic diseases mainly in the Association of Southeast Asian Nations (ASEAN) region. RESULTS: 268 participants, 143 males and 125 females, comprising Ear, Nose and Throat (ENT) specialists (n = 106) and trainees (n = 34), general practitioners (n = 87), and other healthcare professionals (n = 41) attended the course. Of the 103 questions recorded, 59 were regarding treatment modalities in allergy practice such as immunotherapy (n = 38), pharmacologics (n = 15), nasal surgery (n = 2), and others (n = 4). 41 questions (39.8%) have answers based in the Allergic Rhinitis and its Impact on Asthma guidelines (2001 and 2008). Certain questions were selected for further analysis because they appeared to be (a) more commonly asked (e.g. immunotherapy) or (b) were deemed to be challenging or, even controversial (e.g. food allergy and differential diagnosis between vasovagal and anaphylaxis reaction), as the recommendations in current international guidelines were less well-defined. CONCLUSION: Our study identified several problems that, if tackled, could help minimize confusion and provide better care for patients suffering from allergic diseases especially in the ASEAN region.
Anaphylaxis ; Asian Continental Ancestry Group ; Asthma ; Consensus ; Delivery of Health Care ; Diagnosis ; Diagnosis, Differential ; Ear ; Female ; Food Hypersensitivity ; General Practitioners ; Humans ; Hypersensitivity ; Immunotherapy ; Male ; Nasal Surgical Procedures ; Nose ; Pharynx ; Physicians, Primary Care ; Rhinitis, Allergic ; Specialization ; Students, Medical

Objective To screen the specific cytokines of tuberculous pleural effusion(plTB)by using liquid array technique to establish a diagnostic model and discuss its application value.Methods A total of 86 patients with plTB(plTB group)were included,including 41 patients in the confirmed plTB group and 45 patients in the clinically diagnosed plTB group.There were 42 other patients with pleural effusion in the control group.Seventeen cytokines in pleural effusion were analyzed by liquid array technology.Interleukin(IL)-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-9,IL-10,gamma-interferon-induced protein 10(IP-10),IL-15,IL-17F,IL-27,tumor necrosis factor(TNF)-α,monocyte chemotactic protein-1(MCP-1),the expression levels of macrophage inflammatory protein-3a(MIP-3α),macrophage colony-stimulating factor(M-CSF)and β-interferon(IFN-β)were detected.Difference factors between the confirmed plTB group and the control group were screened,and the receiver operating characteristic(ROC)curve was drawn in the confirmed plTB patients.IP-10,IL-27 and MCP-1 with AUC>0.850 and specificity>80%were combined to diagnose plTB,and were compared with adenylate deaminase(ADA)and T-SPOT.TB in pleural effusion to evaluate the diagnostic efficacy.Results The levels of IL-2,IP-10,IL-27,TNF-α and MCP-1 were higher in the confirmed plTB group than those in the control group(P＜0.05).The sensitivity and specificity of IP-10,IL-27 and MCP-1 in the diagnosis of plTB were 87.8%and 81.0%.The sensitivity of three-factor combined diagnosis in 45 patients with plTB was still as high as 86.7%,and there was no significant difference in sensitivity compared with that in the diagnosed plTB group(P＞0.05).In the plTB group,the sensitivity of IP-10,IL-27 and MCP-1 combined detection was 87.2%,which was higher than that of T-SPOT.TB(81.4%)and ADA(54.7%).Conclusion The application of liquid array technology to the joint detection of pleural effusion IP-10,IL-27 and MCP-1 can provide help for the diagnosis of plTB.

Objective:To observe the characteristics of the phagocytosis and bactericidal function of multidrug-resistant Mycobacterium tuberculosis(MDR- Mtb)-infected macrophage model, and the changes of the immune response and metabolic function in the process of phagocytosis and bactericidal function, aiming to provide reference for studying the role and mechanism of macrophages in the occurrence and development of multidrug-resistant tuberculosis(MDR-TB). Methods:We established MDR- Mtb and H37Rv-infected macrophage models, and used the colony-forming unit (CFU), Magnetic Luminex ? Assay and Cholesterol Assay kit to observe the effects on phagocytosis and bactericidal function, the secretion of Th1(IL-12/23 p40, IL-27 and TNF-α) and Th2 cytokines (IL-6 and IL-10) and cholesterol metabolism. The data were analyzed by SPSS25.0 software. The data were expressed as Mean± SD and analyzed by t test or F test. P<0.05 was considered statistically significant. Results:(1) After MDR- Mtb-infected macrophages, the intracellular CFU gradually increased and reached the highest at 24 h, while the extracellular CFU gradually decreased and reached the lowest at 24 h. The intracellular CFU at 48 h was lower than that at 24 h, while the extracellular CFU was higher than that at 24 h ( P<0.05). Both intracellular and extracellular CFU at 48 h were close to those at 4 h ( P>0.05). The intracellular CFU was lower than the H37Rv group at 8-48 h, while the extracellular CFU was higher than the H37Rv group ( P<0.05). (2) The level of IL-12/23 p40, IL-27, TNF-α, IL-6 and IL-10 of MDR-TB group were higher than those of blank group ( P<0.05), but the level of TNF-α and IL-6 at 24 h and 48 h were higher than that at 4 h ( P<0.05). IL-12/23 p40 and TNF-α at 48 h and IL-6 at 24 h were lower than those of the H37Rv group, while IL-27 at 48 h was higher than that of the H37Rv group ( P<0.05). (3) The levels of cholesterol of MDR-TB group at 24 h and 48 h were lower than those of 4 h and blank group ( P<0.05), but the level of cholesterol was similar to the H37Rv group at any time ( P>0.05). (4) TNF-α reached the highest when the intracellular CFU reached the highest at 24 h, and IL-6 reached the highest when the intracellular CFU decreased at 48 h. With the decreasing of cholesterol expression, the intracellular CFU increased and then decreased. Conclusions:MDR- Mtb could induce the phagocytosis and bactericidal function of macrophages, increase the expression of Th1 and Th2 cytokines and promote the utilization and consumption of cholesterol, but this function was weaker than that of H37Rv strain.

Pulmonary hypertension (PH) is an extremely malignant pulmonary vascular disease of unknown etiology. ADAR1 is an RNA editing enzyme that converts adenosine in RNA to inosine, thereby affecting RNA expression. However, the role of ADAR1 in PH development remains unclear. In the present study, we investigated the biological role and molecular mechanism of ADAR1 in PH pulmonary vascular remodeling. Overexpression of ADAR1 aggravated PH progression and promoted the proliferation of pulmonary artery smooth muscle cells (PASMCs). Conversely, inhibition of ADAR1 produced opposite effects. High-throughput whole transcriptome sequencing showed that ADAR1 was an important regulator of circRNAs in PH. CircCDK17 level was significantly lowered in the serum of PH patients. The effects of ADAR1 on cell cycle progression and proliferation were mediated by circCDK17. ADAR1 affects the stability of circCDK17 by mediating A-to-I modification at the A5 and A293 sites of circCDK17 to prevent it from m1A modification. We demonstrate for the first time that ADAR1 contributes to the PH development, at least partially, through m1A modification of circCDK17 and the subsequent PASMCs proliferation. Our study provides a novel therapeutic strategy for treatment of PH and the evidence for circCDK17 as a potential novel marker for the diagnosis of this disease.