Recent research has demonstrated that static magnetic fields (SMF) can generate an analgesic effect in different conditions. The present study explored effects of SMF on pain levels and expressions of P2X3 receptors in trigeminal ganglion (TG) in mice after experimental tooth movement (tooth movement induced by springs between teeth). Experiments were performed in male mice (body mass: 25-30g) and divided into SMF+force group, force group, and no force group. Exposure time was over 22h per day. Mouse Grimace Scale was used for evaluating orofacial pain levels during experimental tooth movement at 4h and 1, 3, 7, and 14 days. Meanwhile, expression levels of P2X3 receptors in the TG were evaluated by immunohistochemistry and western blotting at same time points. We finally found that during experimental tooth movement, pain levels of mice peaked at 3 days, and then decreased. While pain levels of mice were reduced in the SMF environment at 4h, 1 and 3 days, there was a significant difference at 1 and 3 days. Meanwhile, under the action of SMF, expression levels of P2X3 receptors in TG were significantly lower at 4h, 3 and 7 days. These results suggest that SMF can reduce pain levels in mice, and down-regulate P2X3 receptors in TG. Bioelectromagnetics. 38:22-30, 2017. (c) 2016 Wiley Periodicals, Inc.
Several imaging modalities have been widely applied for the detection of cancer and its pathological activity in combination with probes capable of improving the contrast between healthy and cancerous tissues. Biocompatible polymeric nanoassemblies have been developed for precise detection of malignant tumors by enhancing the selectivity and sensitivity of the imaging. Exploiting the compartmentalized structure of the nanoassemblies advantageously allows delivering both imaging and therapeutic agents for cancer multifunctional imaging and theranostics, i.e., the combination of therapy and diagnosis tool on a single platform. Thus, nanoassemblies have high potential not only for cancer molecular imaging but also for tracing nanoparticles in biological systems, studying their biological pathways, gathering pathological information, monitoring therapeutic effects, and guiding pinpoint therapies. In this review, polymeric nanoassemblies for optical imaging, magnetic resonance imaging, multifunctional imaging, and image-guided therapy, emphasizing their role in cancer diagnosis and theranostics are highlighted.
Aim: Inflammation plays a role in secondary brain injury after intracerebral hemorrhage (ICH). We aimed to determine the prognostic significance of admission white blood cell (AWC), neutrophil count (ANC), lymphocyte count, monocyte count and neutrophil to lymphocyte ratio (NLR) for 90-day outcome after ICH. Patients & methods: A total of 336 patients with spontaneous ICH were retrospectively investigated. Clinical outcome was assessed by modified Rankin Scale at 90 days. Results: Multivariate analysis showed that higher AWC, ANC, NLR were independently associated with mortality and worse outcome. Moreover, NLR showed a higher predictive ability in mortality than in poor outcome in receiver operating characteristic analysis. Linear regression analyses revealed admission Glasgow Coma Scale score and ICH volume were mostly correlated with these indices. Conclusion: Elevated levels of AWC, ANC and NLR were independently related to poor 90-day outcome after ICH. NLR may be a novel inflammatory biomarker following ICH.
Objectives: Antihypertensive therapy is effective to control blood pressure (BP) and to prevent cardiovascular events, but the further treatment strategies for patients who cannot achieve goal BP with low-dose monotherapy is still under dispute. Our study investigates the effects of high-dose amlodipine and valsartan and their low-dose combination on blood pressure variability (BPV) and pulse wave velocity (PWV) to provide references for clinical medication.
Materials and Methods: This study was a prospective, randomized, parallel, case-controlled trial performed in a medical center. A total of 134 outpatients newly diagnosed with essential hypertension or receiving low-dose monotherapy were enrolled and 119 completed the trial. They were randomized into amlodipine 10 mg group (n = 40), valsartan 160 mg group (n = 38) and amlodipine 5 mg + valsartan 80 mg (n = 41) in a 1:1:1 allocation ratio for a 10-week treatment. Demographic data and laboratory indicators were collected at the randomization and 10 weeks after the treatment. The 24-hour ambulatory BP and brachial-ankle PWV were also monitored.
Results: All therapies reduced systolic and diastolic BP (P < 0.05). The 24-hour systolic BPV was significantly decreased in amlodipine and combination groups (3.55 +/- 2.57, 4.11 +/- 2.20 versus 2.23 +/- 2.54 mm Hg, P < 0.05). The effects on diastolic BPV differed between different treatments. PWV was lowered by 3 antihypertensive schemes; the degree of which from strongest to weakest were valsartan, combination and amlodipine (228.87 +/- 60.41 versus 152.49 +/- 49.25 versus 99.35 +/- 35.57 cm/second, P < 0.01).
Conclusions: All further strategies can effectively control BP. The combination treatment reduces both BPV and PWV noticeably, whereas double-dose amlodipine achieves the greatest BPV decrease and valsartan is best in controlling PWV.
Background: In the Phase III LUX-Lung 3/6 (LL3/LL6) trials in epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma patients, we evaluated feasibility of EGFR mutation detection using circulating cell-free DNA (cfDNA) and prognostic and predictive utility of cfDNA positivity (cfDNA+).
Methods: Paired tumour and blood samples were prospectively collected from randomised patients. Mutations were detected using cfDNA from serum (LL3) or plasma (LL6) by a validated allele-specific quantitative real-time PCR kit.
Results: EGFR mutation detection rates in cfDNA were 28.6% (serum) and 60.5% (plasma). Mutation detection in blood was associated with advanced disease characteristics, including higher performance score, number of metastatic sites and bone/liver metastases, and poorer prognosis. In patients with common EGFR mutations, afatinib improved progression-free survival vs chemotherapy in cfDNA+ (LL3: HR, 0.35; P = 0.0009; LL6: HR, 0.25; P < 0.0001) and cfDNA- (LL3: HR, 0.46; P < 0.0001; LL6: HR, 0.12; P < 0.0001) cohorts. A trend towards overall survival benefit with afatinib was observed in cfDNA+ patients.
Conclusions: Plasma cfDNA is a promising alternative to biopsy for EGFR testing. Detectable mutation in blood was associated with more advanced disease and poorer prognosis. Afatinib improved outcomes in EGFR mutation-positive patients regardless of blood mutation status.
At present, there is no specific anti-metastasis drug in HCC treatment. Drugs used for primary HCC tumors and tumor metastasis are very similar, among which cytotoxic drugs are prevalent, such as cisplatin, doxorubicin and 5-FU. The EGFR pathway plays an important role in promoting hepatocellular carcinoma (HCC) metastasis. Hence, development of non-toxic anti-metastasis drugs, such as EGFR or downstream pathways inhibitors, is of great importance. In our present study, we found non-toxic dose of liposomal honokiol (LH) could inhibit the HCC metastasis by destabilizing EGFR and inhibiting the downstream pathways. Non-toxic dose of LH significantly inhibited the motility, migration and lamellipodia formation of HepG2 cells in vitro and decreased extravasation of HepG2 cells in a novel metastasis model of transgenic zebrafish. In two lung metastasis models (HepG2 and B16F10) and a spontaneous metastasis model of HepG2 cells, LH remarkably inhibited pulmonary metastasis and regional lymph nodes metastasis without obvious toxicity. Further study showed that destabilizing EGFR and inhibiting the downstream pathways were the main mechanisms of non-toxic dose of LH on metastasis inhibition. Our results provide the preclinical rationale and the underlying mechanisms of LH to suppress HCC metastasis, implicating LH as a potential therapeutic agent to block HCC metastasis without severe side effects.
The aims of this study are to characterize the biological disease-modifying antirheumatic drug (bDMARD) usage patterns in real-life and examine the remission rate of rheumatoid arthritis (RA) patients receiving bDMARDs in routine clinical practice in China. Consenting RA patients (18 years) from 15 teaching hospitals and receiving marketed bDMARDs were included. In total, 802 patients (81.3 % women, 49.0 +/- 13.9 years) were included; 89.5 % were receiving a combination of bDMARDs and conventional synthetic DMARDs (csDMARDS), whereas 10.5 % were receiving bDMARD monotherapy. Etanercept (including EnbrelA (R) and local brand Yi Sai PuA (R) and QiangkeA (R)), tocilizumab, adalimumab, and infliximab were used by 66.6 %, 17.0 %, 7.5 %, and 6.6 % patients, respectively. Etanercept was used at a mean weekly dose of 38.2 +/- 15.6 mg for 25.5 +/- 47.0 weeks and tocilizumab at 94.5 +/- 21.9 mg for 4.7 +/- 7.5 weeks. Overall rate of remission was 12.6 %, 5.4 % , and 3.5 % based on DAS28, CDAI, and SDAI scores, respectively. Compared with patients receiving bDMARDs for < 3 months, those receiving bDMARDs for 3 months exhibited significantly lower DAS28 scores (p < 0.0001), and a significantly higher proportion of patients who received bDMARDs for 12 months achieved the treatment goal (remission or low disease activity, 62.5 % vs. 18.3 %, p < 0.0001). Patients receiving combination therapy with csDMARDs exhibited lower DAS28 scores than patients receiving bDMARD monotherapy (4.3 vs. 4.8, p = 0.011). This large-scale real-world study showed that bDMARD usage patterns in routine clinical practice in China were in accordance with international guidelines for RA management despite the short treatment duration. Longer duration of bDMARD usage and combination therapy showed a favored outcome of RA.
Background and Aim: A matched-pair comparison was performed to compare the efficacy and safety of sublobar resection versus radiotherapy for high-risk elderly patients with Stage I non-small cell lung cancer (NSCLC).
Patients and Methods: We searched the Cochrane Library, MEDLINE, CENTRAL, EMBASE and manual searches. The meta-analysis was performed to compare overall survival, pattern of failure, and toxicity among the homogeneous studies. Subdivided analyses were also performed.
Results: Sixteen studies containing 11540 patients were included in the meta-analysis. Among these studies, 9 were propensity-score matched (PSM) cohort studies, and 7 were cohort studies. Sublobar resection, compared with radiotherapy (either conventional fraction radiation therapy or stereotactic body radiation therapy), significantly improved the overall survival regardless in both PSM and non-PSM analyses (all p < 0.05). However, the difference in the pattern of failure and toxicity were not significant (all p > 0.05).
Conclusions: Sublobar resection was associated with improved outcomes in high-risk elderly patients with Stage I NSCLC, which supports the need to compare both treatments in large prospective, randomized, controlled clinical trials.
Deferoxamine (DFO), an iron chelator, is commonly used to remove excess iron from the body. DFO has also been demonstrated to have anti-tumor effect. However, there is no available report on the effect of deferoxamine on mesenchymal stromal cells (MSCs). In this study, we first isolated tumor-associated MSCs (TAMSCs) from EG-7 tumors, which were positive for CD29, CD44, CD73, CD90 and CD105. Ex vivo cultured stem cells derived from tumor and bone marrow compartment were exposed to DFO. We demonstrated that DFO had growth-arresting and apoptosis-inducing effect on TAMSCs and bone marrow MSCs (BMMSCs). DFO also influenced the expression pattern of adhesion molecule VCAM-1 on both TAMSCs and BMMSCs. Notwithstanding its widespread use, our results here warrants caution in the application of DFO, and also highlights the need for careful evaluation of the bone marrow compartment in patients receiving DFO treatment. (C) 2016 Elsevier B.V. All rights reserved.
