BackgroundLet-7a has been shown to play important roles in nasopharyngeal carcinoma (NPC) cell proliferation and apoptosis, but little is known about the function and mechanism of let-7a in nasopharyngeal carcinoma metastasis. We aimed to investigate the function and mechanism of let-7a in nasopharyngeal carcinoma metastasis and clarified the regulation of high mobility group A2 (HMGA2) by let-7a.MethodsThe expression levels of let-7a and HMGA2 were examined in NPC clinical specimens using quantitative reverse transcription-PCR (RT-qPCR). HMGA2 was confirmed as a target of let-7a through luciferase reporter assays, RT-qPCR, and Western blotting. Furthermore, the roles of let-7a and HMGA2 in regulating NPC cells biological properties including proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) process were analyzed with let-7a mimics and si-HMGA2 transfected cells.ResultsOur study demonstrated that let-7a was downregulated and inversely associated with the clinical stage, T classification and N classification, and HMGA2 was upregulated and directly associated with the clinical stage and N classification in patients with NPC. Moreover, there was an inverse correlation between let-7a expression and HMGA2 expression in NPC patient. In addition, HMGA2 was negatively regulated at the posttranscriptional level by let-7a via a binding site of HMGA2-3′UTR. In addition, synthetic let-7a mimics suppressed NPC cells migration, invasion and EMT process and knockdown of HMGA2 was consistent with the effects of let-7a in NPC cells.ConclusionLet-7a directly downregulates HMGA2 protein expression, which suppress NPC cell migration, invasion and EMT process. Let-7a could serve as a potential diagnostic marker and therapeutic target for NPC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0462-8) contains supplementary material, which is available to authorized users.

Background: Nonspecific low back pain (NLBP) is a common disabling disease that cannot be attributed to a specific, recognizable pathology. The use of acupuncture for NLBP is supported by several guidelines and systematic reviews. However, the efficacy of different acupuncture methods for NLBP management is still debated. This study ranked the effectiveness of acupuncture methods using network meta-analysis to screen out the optimal acupuncture methods and expound the current controversies for their effective application in health policies as well as guiding clinical operations. Methods:The following databases were searched for relevant randomized controlled trials (RCTs) from inception to December 20, 2020: China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals, WANFANG Database, Chinese biomedical literature service system, PubMed, Web of Science, Embase, and Cochrane Library. Relevant registration platforms, including the International Standard Randomised Controlled Trial Number Register (ISRCTN) and Chinese Clinical Trial Registry (ChiCTR), were also searched. Manual retrieval and tracking of references was also performed. Pairwise meta-analysis and Bayesian network meta-analysis using Revman and ADDIS, respectively, were performed and standardized mean differences examined. The primary outcome was visual analog scale (VAS) score and the secondary outcome was Oswestry Disability Index (ODI) score. Safety was defined as the incidence of adverse events. Results: A total of 30 trials with 3196 participants were analyzed; 16.67% of which showed a high risk of bias. The results indicated that fire acupuncture plus manual acupuncture, auricular needling, and electroacupuncture plus warm acupuncture were most effective in reducing VAS score. The most effective interventions for reducing ODI score were manual acupuncture plus conventional medicines, followed by moxibustion and manual acupuncture plus moxibustion. Manual acupuncture plus moxibustion was dominant in the cluster ranking. Acupuncture showed a lower incidence of adverse events (7.70%) than other interventions (conventional medicines, routine care, and placebo; 12.24%). Conclusion:We found that manual acupuncture plus moxibustion is the most effective way to reduce NLBP pain and disability. Acupuncture is safer than other interventions. However, more direct comparative evidence from high-quality, large-sample, multicenter RCTs is needed to validate these findings.

Ifosfamide has been used in neoadjuvant chemotherapy since the mid-1980s. Although several studies have been conducted, the results remain controversial. Randomized controlled trials have an improved balance of confounding factors and reliable results. Thus, we performed a meta-analysis based on randomized controlled trials to gather more evidence of the effect of ifosfamide on neoadjuvant chemotherapy for patients with osteosarcoma of the extremity. An electronic search was conducted via the Internet retrieval system to identify eligible trials until September 2014. Odds ratios (ORs) and 95 % confidence interval (CI) were calculated to compare the results of ifosfamide and ifosfamide-free therapies. Four trials with a total of 1,378 patients were eligible for our meta-analysis. Overall, compared with neoadjuvant chemotherapy without ifosfamide, the use of ifosfamide had no advantage in terms of histological response to chemotherapy (cHR; OR 1.36; 95 % CI 0.90-2.03, P = 0.140), 5-year event-free survival (EFS; OR 1.16; 95 % CI 0.789-1.75, P = 0.464), and 5-year overall survival (OS; OR 1.06; 95 % CI 0.70-1.59, P = 0.794). However, improvement was noted in the rate of limb salvage (OR 4.06; 95 % CI 2.04-8.10, P < 0.001). Neoadjuvant chemotherapy with ifosfamide for patients with extremity osteosarcoma might not increase the cHR and exhibited no significant effect on either EFS or OS. However, ifosfamide therapy could significantly increase the rate of limb salvage for osteosarcoma of the extremity, which suggests that the preoperative use of ifosfamide could increase the success rate of limb salvage operation.

Lung cancer has the highest morbidity rate (11.6%) and mortality rate (18.4%) among all current tumors. The morbidity rate in China accounts for approximately one-third, and it is still rising. Nonsmall cell lung cancer is the most common type of lung cancer, accounting for 80%–85% of all lung cancers, and approximately 57% of patients with advanced nonsmall cell lung cancer have distant metastases at the time of diagnosis. To explore the expression changes in microRNA-184 (miR-184) and its clinical value in serum exosomes of patients with nonsmall cell lung cancer (NSCLC). This study adopted a case-control study method, selecting 88 patients (NSCLC group) from June 2015 to June 2017 in our hospital who are confirmed to have NSCLC by fiber-optic bronchoscopy, and 90 patients who are confirmed to have benign lung diseases by pathological examination during the same period (control group). Fluorescence quantitative PCR technology is used to detect the levels of miR-184 in serum exosomes of the two groups, and the differences in the levels of miR-184 in serum exosomes of NSCLC patients with different pathological characteristics are analyzed. According to the results of the 3-year follow-up, the miR-184 levels in serum exosomes of NSCLC patients are grouped and compared. The expression level of miR-184 in serum exosomes in the NSCLC group is significantly higher than that in the control group, and the difference between the two groups is statistically significant ( p  < 0.05). The ROC curve is drawn with the expression level of miR-184 in serum exosomes of the two groups of patients. The results showed that the area under the ROC curve for the differential diagnosis of NSCLC and benign lung tumors with the expression level of miR-184 in serum exosomes is 0.927, and the sensitivity is 87.61%, while the specificity is 84.02%. The expression levels of miR-184 in serum exosomes of NSCLC patients with different pathological characteristics, in different TNM stages [(I+II) vs. (III+IV)], lymph node metastasis (yes vs. no), and different degrees of differentiation [(High + Medium) vs. Poorly differentiated] are compared and showed statistical significance ( p  < 0.05). In 88 NSCLC patients, after 3 years of follow-up, 33 survived, and 55 died, with a survival rate of 37.50%. The expression of miR-184 in serum exosomes of the 33 surviving patients is significantly lower than that of the nonsurviving group ( p  < 0.05). The expression level of miR-184 in serum exosomes of NSCLC patients is significantly increased, which has a certain value for the differential diagnosis of the nature of benign and malignant lung diseases and is closely related to the prognosis of patients.

The epithelial-mesenchymal transition (EMT) is a phenotype transdifferentiation of epithelial into mesenchymal cells and contributes to pulmonary fibrotic disease. SMAD-dependent pathway has been reported to play a key role in the multiple fibrotic diseases. We hypothesized that TGF-β/SMAD signaling could cross-interact with BMP/SMAD signaling pathways in silica-induced EMT in A549 cells. We investigated that the ability of silica-induced EMT in A549 cells, and this process was significantly inhibited by SB431542 through up-regulation of Vimentin, α-SMA and collagen type I expression and down-regulation of E-cadherin expression. Whereas BMP/SMAD inhibition using LDN193189 enhanced EMT. In addition, we also demonstrated that SB431542 could enhance BMP/SMAD signaling pathways in silica-induced EMT and vice versa. Therefore, our study provides evidence that the TGF-β/SMAD pathway was a crucial regulator in silica-induced EMT and that SB431542 could prevent the EMT. More importantly, we have identified that the interplay of TGF-β/SMAD and BMP/SMAD pathways in silica-induced EMT in A549 cells.