Transcutaneous electrical nerve stimulation for the control of pain during rehabilitation after total knee arthroplasty: A randomized,blinded, placebo-controlled trial

This study evaluated the efficacy of transcutaneous electrical nerve stimulation (TENS) in reducing pain and hyperalgesia and increasing function after total knee arthroplasty (TKA). We hypothesized that participants using TENS during rehabilitation exercises would report significantly lower pain during range-of-motion (ROM) activity and fast walking but not at rest, would have less hyperalgesia, and would have better function than participants receiving placebo-TENS or standard care. We also hypothesized that change in ROM pain would differ based on psychological characteristics (trait anxiety, pain catastrophizing, and depression) and treatment group. This prospective, randomized study used intent-to-treat analyses in 317 participants after primary, unilateral TKA. Assessors, blinded to treatment allocation, measured pain, function (ROM and gait speed), and hyperalgesia (quantitative sensory tests) postoperatively and 6 weeks after surgery. Analgesic intake, anxiety, depression, and pain catastrophizing were also assessed. TENS participants used it 1 to 2 times per day at 42 mA (on average) and had less pain postoperatively during active knee extension (P = .019) and fast walking (P = .006) than standard care participants. TENS and placebo-TENS were not significantly different. TENS participants who scored low on anxiety and pain catastrophizing had a greater reduction in ROM pain at 6 weeks than those who scored high on these factors (P = .002 and P = .03). Both TENS and placebo-TENS participants had less postoperative mechanical hyperalgesia (P = .03–.01) than standard care participants. Supplementing pharmacologic analgesia with TENS during rehabilitation exercises reduces movement pain postoperatively, but a placebo influence exists and the effect is gone by 6 weeks. Patients with low anxiety and pain catastrophizing may benefit most from TENS.     

Up-regulation of urinary-type plasminogen activator correlates with high-risk papillary thyroid carcinoma with BRAFV600E mutation and its possible molecular mechanism

The aim of the present study is to investigate the relationship between urinary-type plasminogen activator (uPA) expression and clinicopathological features in papillary thyroid carcinoma (PTC) and to determine the signal transduction of PTC cells in vitro.PTC tissues from 42 patients were analyzed for the expression of uPA and the BRAF^V600E mutation. BCPAP, a PTC cell line harboring the BRAF^V600E mutation, was used to study MAPK signaling. PCR and direct sequencing were applied to analyze BRAF^V600E mutation status. uPA mRNA expression was measured using a quantitative RT-PCR method, and uPA protein was localized using an immunohistochemical method. The ERK protein status was detected by Western blot analysis.uPA gene expression was significantly increased in PTC tissues as compared to the corresponding non-tumor tissues. Furthermore, the up-regulation of uPA mRNAs was correlated with high-risk clinicopathological features, including extrathyroid invasion, loss of cellular polarity/cohesiveness, and the BRAF^V600E mutation. Marked dephosphorylation of ERK1/2 and down-regulation of uPA expression were detected when BCPAP was treated with a MEK inhibitor, U0126.MEK inhibitors might be a potential treatment strategy for aggressive PTC with BRAF^V600E through inhibition of uPA expression.     

Transferrin-mediated fullerenes nanoparticles as Fe2+-dependent drug vehicles for synergistic anti-tumor efficacy

Artesunate (AS) is an iron-dependent drug, which has been used extensively as anti-malarial drugs worldwide with no obvious side effects. Recently, studies have shown that AS also possess profound cytotoxicity against tumor cells. However, simultaneous delivery of hydrophobic AS and Fe²⁺ into tumor cells remains a major challenge. Herein, we report a new kind of active-targeting preparations which could not only specially target to tumor cells but also synchronously transfer AS and irons into tumor tissue. In this study, hyaluronic acid (HA) was grafted onto fullerene to get a water-soluble biomaterial (HA-C60) with excellent biocompatibility, and then combined with transferrin (Tf) to obtain a multi-functional drug delivery system (HA-C60-Tf) with significant tumor-targeting efficacy and powerful photodynamic therapy capacity. Finally, AS was adsorbed on HA-C60-Tf with a high loading efficacy of 162.4% (weight ratio of AS: HA-C60-Tf). Compared with free AS, remarkably enhanced antitumor efficacy of AS-loaded HA-C60-Tf nanoparticles was realized both in a cultured MCF-7 cells in vitro and in a tumor-bearing murine model in vivo, due to increased intracellular accumulation of AS in tumor and activated mechanism by co-delivery of Tf and AS analogs. Furthermore, with laser irradiation in vivo, the relative tumor volume (V/V₀) of HA-C60-Tf/AS declined by half, from 1.72 ± 0.12 to 0.84 ± 0.07, suggesting a new way with multi-mechanism for tumor treatment was developed.     

Interaction—A missing piece of the jigsaw in interpreter-mediated medical consultation models

In 2015, at the International Conference on Communication in Healthcare in New Orleans, USA, we formed a symposium panel to discuss and debate how interdisciplinary research can inform interpreter-mediated medical consultation training. In all our work, a recurring theme is not just the strengths but also the shortcomings of the guidelines proposed in the textbooks and widely used in medical education. This paper is an account of our multidisciplinary reflections on a prominent issue of the lack of attention to interaction in communications, which shed light on the limitations of these guidelines and clinical communication models. We propose that an international network be established for all stakeholders to foster interprofessional and interdisciplinary collaboration for research and clinical interventions, and to inform training and policy making.     

Preoperative high-dose chemotherapy with peripheral blood stem cell support as a primary management of locally advanced breast cancer

Locally advanced breast cancer (LABC) has a poor prognosis with a high risk of local recurrence and distant metastasis. Preoperative combined chemotherapy with or without granulocyte colony-stimulating factor (G-CSF) support does not improve the long-term survival rate. In our report, two patients with LABC received preoperative high-dose chemotherapy with peripheral blood stem cell support (HDC/PBSCs). Prior to high-dose chemotherapy with peripheral blood stem cell support, they both received induction chemotherapy of cyclophosphamide, epirubicin and 5-fluorouracil (FEC) for two cycles which resulted in a partial response. PBSC mobilization and collection were carried out following the second cycle of induction chemotherapy followed by G-CSF. High-dose cyclophosphamide (2500 mg/m2), carboplatin (600 mg/m2) and etoposide (600 mg/m2) were administered with PBSC support. A radical mastectomy was performed followed by adjuvant chemotherapy with FEC regimen for four cycles, followed by local irradiation, and endocrine therapy with tamoxifen. Both patients achieved a remarkable response in the primary lesion after HDC/PBSCs and tolerated the whole treatment well. Preoperative HDC/PBSCs as a new strategy in the treatment of LABC seems practical but it needs to be studied more deeply.     

沙利度胺调控PD-L1抑制HT-29结肠癌细胞的作用及机制研究

目的：探讨沙利度胺对HT-29结肠癌细胞的抑制作用及其机制。方法：CCK-8检测沙利度胺对HT-29结肠癌细胞增殖的作用;流式细胞术检测沙利度胺对HT-29结肠癌细胞凋亡的作用和对HT-29结肠癌细胞PD-L1表达的作用;Western Blot检测沙利度胺对HT-29结肠癌细胞c-Myc、STAT3、HIF-1蛋白表达的影响。结果：沙利度胺各浓度（40、80、160、320 μmol·L-1）明显抑制HT-29结肠癌细胞的增殖;沙利度胺各浓度（20、40、80 μmol·L-1）明显促进HT-29结肠癌细胞的凋亡,明显减少HT-29结肠癌细胞表面PD-L1的表达,明显减少HT-29结肠癌细胞c-Myc、STAT3、HIF-1蛋白的表达。结论：沙利度胺对HT-29结肠癌细胞具有抑制作用,其机制可能与减少PD-L1表达及抑制癌细胞上游c-Myc、STAT3、HIF-1信号分子表达有关。     

沙利度胺调控PD-L1抑制HT-29结肠癌细胞的作用及机制研究

目的：探讨沙利度胺对HT-29结肠癌细胞的抑制作用及其机制。方法：CCK-8检测沙利度胺对HT-29结肠癌细胞增殖的作用;流式细胞术检测沙利度胺对HT-29结肠癌细胞凋亡的作用和对HT-29结肠癌细胞PD-L1表达的作用;Western Blot检测沙利度胺对HT-29结肠癌细胞c-Myc、STAT3、HIF-1蛋白表达的影响。结果：沙利度胺各浓度（40、80、160、320 μmol·L-1）明显抑制HT-29结肠癌细胞的增殖;沙利度胺各浓度（20、40、80 μmol·L-1）明显促进HT-29结肠癌细胞的凋亡,明显减少HT-29结肠癌细胞表面PD-L1的表达,明显减少HT-29结肠癌细胞c-Myc、STAT3、HIF-1蛋白的表达。结论：沙利度胺对HT-29结肠癌细胞具有抑制作用,其机制可能与减少PD-L1表达及抑制癌细胞上游c-Myc、STAT3、HIF-1信号分子表达有关。