Elderly Patients with Laryngeal and Hypopharyngeal Cancer Undergoing Total Pharyngolaryngectomy with a Radial Forearm, Free Flap-reconstructed Phonation Tube

SummaryBackgroundThe radial forearm, free-flap (RFFF)-reconstructed phonation tube was developed for functional restoration of voice after total pharyngolaryngectomy. We aimed to report the efficacy of RFFF phonation tube after pharyngolaryngectomy with radiotherapy (RT) or concurrent chemoradiation therapy (CCRT) with intensity-modulated radiotherapy (IMRT) for elderly.Materials and methodsTen patients with laryngeal and hypopharyngeal cancer underwent total pharyngolaryngectomy and one-stage reconstruction with an RFFF-accompanied phonation tube, followed by RT or CCRT. Voice restoration was achieved with the RFFF-reconstructed phonation tube. Functional outcomes of phonation and speech were evaluated and scored.ResultsPercentages of stage III and stage IV patients among all participants were 10% and 90%, respectively. The median follow-up time was 31 months (range, 4–67 months). Almost 9 out of 10 (90%) patients experienced phonation efficacy greater than 80%. The maximal phonation time per breath was 70% longer than 3 sec. The graded as mild of wet voice was 90%. Percentage of mild decreased loudness was 60% and that of low and high pitch was 80%. Of the 10 patients, 40% could count more than 10 and 70% could pronounce more than 1 to 5 words per breath. After RT or CCRT, of patients had moderately good to excellent speech intelligibility.ConclusionThe RFFF phonation tube that was used after pharyngolaryngectomy with RT or CCRT with IMRT provided acceptable complications and functional restoration of voice for elderly patients

Ventricular divergence correlates with epicardial wavebreaks and predicts ventricular arrhythmia in isolated rabbit hearts during therapeutic hypothermia

INTRODUCTION: High beat-to-beat morphological variation (divergence) on the ventricular electrogram during programmed ventricular stimulation (PVS) is associated with increased risk of ventricular fibrillation (VF), with unclear mechanisms. We hypothesized that ventricular divergence is associated with epicardial wavebreaks during PVS, and that it predicts VF occurrence. METHOD AND RESULTS: Langendorff-perfused rabbit hearts (n = 10) underwent 30-min therapeutic hypothermia (TH, 30°C), followed by a 20-min treatment with rotigaptide (300 nM), a gap junction modifier. VF inducibility was tested using burst ventricular pacing at the shortest pacing cycle length achieving 1:1 ventricular capture. Pseudo-ECG (p-ECG) and epicardial activation maps were simultaneously recorded for divergence and wavebreaks analysis, respectively. A total of 112 optical and p-ECG recordings (62 at TH, 50 at TH treated with rotigaptide) were analyzed. Adding rotigaptide reduced ventricular divergence, from 0.13±0.10 at TH to 0.09±0.07 (p = 0.018). Similarly, rotigaptide reduced the number of epicardial wavebreaks, from 0.59±0.73 at TH to 0.30±0.49 (p = 0.036). VF inducibility decreased, from 48±31% at TH to 22±32% after rotigaptide infusion (p = 0.032). Linear regression models showed that ventricular divergence correlated with epicardial wavebreaks during TH (p<0.001). CONCLUSION: Ventricular divergence correlated with, and might be predictive of epicardial wavebreaks during PVS at TH. Rotigaptide decreased both the ventricular divergence and epicardial wavebreaks, and reduced the probability of pacing-induced VF during TH

Evaluation of the Effect of Laser Acupuncture and Cupping with Ryodoraku and Visual Analog Scale on Low Back Pain

The purpose of this study was to evaluate the effect of laser acupuncture (LA) and soft cupping on low back pain. In this study, the subjects were randomly assigned to two groups: active group (real LA and soft cupping) and placebo group (sham laser and soft cupping). Visual analog scale (VAS) and Ryodoraku were used to evaluate the effect of treatment on low back pain in this trial. Laser, 40 mW, wavelength 808 nm, pulse rate 20 Hz, was used to irradiate Weizhong (BL40) and Ashi acupoints for 10 minutes. And the Ryodoraku values were measured 2 times, that is, before and 15 minutes after treatment. The results show that there were significant difference between the first day baseline and the fifth day treatment in VAS in the two groups. Therefore, LA combined with soft cupping or only soft cupping was effective on low back pain. However, the Ryodoraku values of Bladder Meridian of the placebo group have been decreased apparently, and didn’t come back to their original values. It means that “cupping” plays the role of “leak or purge” in traditional Chinese medicine (TCM). On the other hand, the Ryodoraku values of Bladder Meridian of the active group have been turned back to almost their original values; “mend or reinforcing” effect is attributed to the laser radiation

Expression of PRDX6 Correlates with Migration and Invasiveness of Colorectal Cancer Cells

Background/Aims: Colorectal cancer (CRC) is the third most common type of cancer and the second leading cause of cancer-related deaths worldwide. PRDXs are antioxidant enzymes that play an important role in cell differentiation, proliferation and apoptosis and have diverse functions in malignancy development. However, the mechanism of aberrant overexpression of PRDX6 in CRC remains unclear. Methods: Boyden chamber assay, flow cytometry and a lentiviral shRNA targeting PRDX6 and transient transfection with pCMV-6-PRDX6 plasmid were used to examine the role of PRDX6 in the proliferation capacity and invasiveness of CRC cells. Immunohistochemistry (IHC) with tissue array containing 40 paraffin- embedded CRC tissue specimens and Western blot assays were used to detect target proteins. Results: PRDX6 was significantly up-expressed in different comparisons of metastasis of colorectal adenomas in node-positive CRC (P = 0.03). In in vitro HCT-116, PRDX6 silencing markedly suppressed CRC cell migration and invasiveness while also inducing cell cycle arrest as well as the generation of reactive oxygen species (ROS); specific overexpression of PRDX6 had the opposite effect. Mechanistically, the PRDX6 inactivation displayed decreased levels of PRDX6, N-cadherin, β-catenin, Vimentin, Slug, Snail and Twist-1 through the activation of the PI3K/ AKT/p38/p50 pathways, but they were also significantly inhibited by PRDX6 transfectants. There was also increased transcriptional activation of dimethylation of histone H3 lysine 4 (H3K4me3) of PRDX6 promoter via the activation of the PI3K/Akt/NFkB pathways. Conclusion: Our findings demonstrated that PRDX6 expression plays a characteristic growth-promoting role in CRC metastasis. This study suggests that PRDX6 may serve as a biomarker of node-positive status and may have a role as an important endogenous regulator of cancer cell tumorigenicity in CRC. PRDX6 may also be an effective therapeutic target

A Standardized Wedelia chinensis Extract Overcomes the Feedback Activation of HER2/3 Signaling upon Androgen-Ablation in Prostate Cancer

Crosstalk between the androgen receptor (AR) and other signaling pathways in prostate cancer (PCa) severely affects the therapeutic outcome of hormonal therapy. Although anti-androgen therapy prolongs overall survival in PCa patients, resistance rapidly develops and is often associated with increased AR expression and upregulation of the HER2/3-AKT signaling pathway. However, single agent therapy targeting AR, HER2/3 or AKT usually fails due to the reciprocal feedback loop. Previously, we reported that wedelolactone, apigenin, and luteolin are the active compounds in Wedelia chinensis herbal extract, and act synergistically to inhibit the AR activity in PCa. Here, we further demonstrated that an herbal extract of W. chinensis (WCE) effectively disrupted the AR, HER2/3, and AKT signaling networks and therefore enhanced the therapeutic efficacy of androgen ablation in PCa. Furthermore, WCE remained effective in suppressing AR and HER2/3 signaling in an in vivo adapted castration-resistant PCa (CRPC) LNCaP cell model that was insensitive to androgen withdrawal and second-line antiandrogen, enzalutamide. This study provides preclinical evidence that the use of a defined, single plant-derived extract can augment the therapeutic efficacy of castration with significantly prolonged progression-free survival. These data also establish a solid basis for using WCE as a candidate agent in clinical studies

A cytoplasmic RNA virus generates functional viral small RNAs and regulates viral IRES activity in mammalian cells

The roles of virus-derived small RNAs (vsRNAs) have been studied in plants and insects. However, the generation and function of small RNAs from cytoplasmic RNA viruses in mammalian cells remain unexplored. This study describes four vsRNAs that were detected in enterovirus 71-infected cells using next-generation sequencing and northern blots. Viral infection produced substantial levels (\u3e105 copy numbers per cell) of vsRNA1, one of the four vsRNAs. We also demonstrated that Dicer is involved in vsRNA1 generation in infected cells. vsRNA1 overexpression inhibited viral translation and internal ribosomal entry site (IRES) activity in infected cells. Conversely, blocking vsRNA1 enhanced viral yield and viral protein synthesis. We also present evidence that vsRNA1 targets stem-loop II of the viral 5′ untranslated region and inhibits the activity of the IRES through this sequence-specific targeting. Our study demonstrates the ability of a cytoplasmic RNA virus to generate functional vsRNA in mammalian cells. In addition, we also demonstrate a potential novel mechanism for a positive-stranded RNA virus to regulate viral translation: generating a vsRNA that targets the IRES