Characteristics of Tongue Pressure Measured by Novel Multisite Flexible Sensors in Nasopharyngeal Carcinoma Patients With Dysphagia.

OBJECTIVE: To explore characteristics of tongue pressure changes in nasopharyngeal carcinoma (NPC) patients with dysphagia after radiotherapy using a novel system with multisite flexible sensors. DESIGN: Prospective observational study. SETTING: Inpatient rehabilitation centers and community dwellings. PARTICIPANTS: Nineteen patients with dysphagia after radiotherapy for NPC and 19 healthy participants were recruited for this study (N=38). INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: A new 9-site (3 × 3) flexible tongue pressure sensor was used to measure tongue-to-palate pressure across different parts of the tongue. The oral tongue was divided into 3 parts: anterior tongue region (TAR), central tongue region (TCR), and posterior tongue region (TPR); 3 sensors were placed on each part. The mean tongue pressure and endurance time at the 3 sites in the TAR, TCR, and TPR were analyzed. The ratios of the mean TAR, TCR, and TPR values were calculated. RESULTS: Pressures of TAR, TCR, and TPR in NPC patients with dysphagia were significantly lower than those in healthy participants (P<.05). The pressure in TPR decreased most significantly, followed by that in TCR. The endurance times of TAR and TCR were longer than those of healthy participants (P<.05). The endurance time of TPR was not significantly different between the patients and healthy participants (P>.05). Ratios of pressure between TAR and TCR and TAR and TPR in patients were lower than that in healthy participants (P<.05). There was no significant difference in the TCR to TPR pressure ratio between patients and healthy participants (P>.05). CONCLUSIONS: Tongue pressure significantly decreased in NPC patients with dysphagia, and the drop in pressure was most pronounced in the TPR area. The results of our study indicate that we should pay attention to the pressure training of the TPR during treatments. The endurance time of the TAR and TCR increased significantly, which may be due to bolus transport compensation. Therefore, clinical rehabilitation strategies should aim to increase the endurance time training in NPC patients after radiotherapy to help increase the effectiveness of the swallowing process in patients.

Analgesic Effect of Perineural Injection of BoNT/A on Neuropathic Pain Induced by Chronic Constriction Injury of Sciatic Nerve in Rats.

This study was designed to investigate the analgesic effect of perineural injection of BoNT/A on neuropathic pain induced by sciatic nerve chronic constriction injury (CCI) and possible mechanisms. SD rats were randomly divided into Sham group, CCI group and BoNT/A group. Paw mechanical withdrawal threshold (pMWT) and paw thermal withdrawal latency (pTWL) of each group were detected at different time points after surgery. The expression of myelin markers, autophagy markers and NLRP3 inflammasome-related molecules in injured sciatic nerves were examined at 12 days after surgery. Moreover, C-fiber evoked potential in spinal dorsal horn was recorded. The expression of SNAP-25, neuroinflammation and synaptic plasticity in spinal dorsal horn of each group were examined. Then rats treated with BoNT/A were randomly divided into DMSO group and Wnt agonist group to further explore the regulatory effect of BoNT/A on Wnt pathway. We found that pMWT and pTWL of ipsilateral paw were significantly decreased in CCI group compared with Sham group, which could be improved by perineural injection of BoNT/A at days 7, 9 and 12 after surgery. The peripheral analgesic mechanisms of perineural injection of BoNT/A might be related to the protective effect on myelin sheath by inhibiting NLRP3 inflammasome and promoting autophagy flow, while the central analgesic mechanisms might be associated with inhibition of neuroinflammation and synaptic plasticity in spinal dorsal horn due to inhibiting SNAP-25 and Wnt pathway. As a new route of administration, perineural injection of BoNT/A can relieve CCI induced neuropathic pain probably via both peripheral and central analgesic mechanisms.

The Biomechanical Characteristics of Swallowing in Tracheostomized Patients with Aspiration following Acquired Brain Injury: A Cross-Sectional Study.

Objectives: Investigate the biomechanical characteristics in tracheostomized patients with aspiration following acquired brain injury (ABI) and further explore the relationship between the biomechanical characteristics and aspiration. Methods: This is a single-center cross-sectional study. The tracheostomized patients with aspiration following ABI and age-matched healthy controls were recruited. The biomechanical characteristics, including velopharynx (VP) maximal pressure, tongue base (TB) maximal pressure, upper esophageal sphincter (UES) residual pressure, UES relaxation duration, and subglottic pressure, were examined by high-resolution manometry and computational fluid dynamics simulation analysis. The penetration−aspiration scale (PAS) score was evaluated by a videofluoroscopic swallowing study. Results: Fifteen healthy subjects and fifteen tracheostomized patients with aspiration following ABI were included. The decreased VP maximal pressure, increased UES residual pressure, and shortened UES relaxation duration were found in the patient group compared with the control group (p < 0.05). Furthermore, the subglottic pressure significantly decreased in patients (p < 0.05), while no significant difference was found in TB maximal pressure between groups (p > 0.05). In addition, in the patient group, VP maximal pressure (rs = −0.439; p = 0.015), UES relaxation duration (rs = −0.532; p = 0.002), and the subglottic pressure (rs = −0.775; p < 0.001) were negatively correlated with the PAS score, while UES residual pressure (rs = 0.807; p < 0.001) was positively correlated with the PAS score (p < 0.05), the correlation between TB maximal pressure and PAS score (rs = −0.315; p = 0.090) did not reach statistical significance. Conclusions: The biomechanical characteristics in tracheostomized patients with aspiration following ABI might manifest as decreased VP maximal pressure and subglottic pressure, increased UES residual pressure, and shortened UES relaxation duration, in which VP maximal pressure, UES relaxation duration, subglottic pressure, and UES residual pressure were correlated with aspiration.

[Clinical effect of ultrasound combined with anatomy-measure guidance botulinum toxin type A injection in poststroke patients with spasticity].

OBJECTIVE: To evaluate the clinical efficacies of botulinum toxin type A (BTX-A) injection under ultrasonic guidance and body surface positioning in poststroke patients with lower extremities spasticity. METHODS: From January 2009 to January 2011, a total of 18 patients with stroke-related spasticity in lower extremities were recruited at Third Affiliated Hospital of Sun Yat-sen University. Under the guide of color Doppler ultrasound and body surface positioning, BTX-A was injected into multi-points of muscles. The outcome after BTX-A injection was assessed by modified Ashworth scale (MAS), passive range of movement (PROM), 10-meter walking test (10 MWT) and Berg balance scale (BBS). Assessments were performed at baseline, Day 3, Weeks 1, 2, 4 and 12 post-injection respectively. RESULTS: Compared the scores of MAS (MAS(pre-treatment) 2.6 ± 0.5, MAS(post-treatment) 1.9 ± 0.2 - 1.1 ± 0.3 score), PROM (PROM(pre-treatment) 7.2 ± 2.4°, PROM(post-treatment) 12.3 ± 2.0 - 18.6 ± 2.2°) between baseline and follow-up at Weeks 1, 2, 4 and 12 post-treatment, there were significant statistical differences (P < 0.05).10 MW (10 MWT(pre-treatment) 55.1 ± 5.2 s, 10 MWT(post-treatment) 48.6 ± 4.2 - 42.9 ± 3.8 s) and BBS (BBS(pre-treatment) 34.7 ± 5.1, BBS(post-treatment) 39.9 ± 4.9 - 45.8 ± 2.1 score) improved greatly at Weeks 2, 4 and 12 post-treatment. CONCLUSION: Ultrasonic guidance and body surface positioning is an accurate positioning modality of using BTX-A for treating the spasticity of lower extremities.

Honatisine, a novel diterpenoid alkaloid, and six known alkaloids from Delphinium honanense and their cytotoxic activity.

A novel diterpene alkaloid named honatisine (1) has been isolated from the whole plants of Delphinium honanense, along with six known alkaloids, siwanine E (2), isoatisine (3), atisine (4), delcorinine (5), uraphine (6), and nordhagenine A (7). Their structures were deduced on the basis of their spectral data. All of them were evaluated by a SRB assay for their cytotoxicity, and compound 1 showed a significant cytotoxic activity (IC(50) =3.16 µM) against the MCF-7 cell line.

Characterization of the complete chloroplast genome of Lonicera similis (Caprifoliaceae).

The complete chloroplast genome of Lonicera similis Hemsl. has been characterized by reference-based assembly using Illumina paired-end data. The circular complete cp genome is 155,463 bp in length, containing a large single copy (LSC) region of 89,282 bp, a small single copy (SSC) region of 18,661 bp, which are separated by a pair of inverted repeat (IR) regions of 23,760 bp. A total of 129 genes were predicted from the cp genome, including 83 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Phylogenetic analysis reveals that L. similis is more closely related to Lonicera japonica Thunb. and Lonicera dasystyla Rehd. Our result will provide a reference for the phylogenetic relationship, plant identification and resource development and utilization of Lonicera species.

Ultrasound-Guided Nerve Hydrodissection With 5% Dextrose 4 Weeks After Steroid Injection in Treatment of Carpal Tunnel Syndrome: A Retrospective Study.

OBJECTIVE: To investigate the efficacy and safety of ultrasound-guided nerve hydrodissection (HD) with 5% dextrose (D5W) as add-on therapy after corticosteroid injection in carpal tunnel syndrome (CTS), and provide a novel strategy. METHODS: In this retrospective study, patients with CTS who received ultrasound-guided nerve HD with D5W as add-on therapy after corticosteroid injection (combination group) were enrolled. Patients who received corticosteroid injection without add-on therapy (steroid group) were recruited as the control group. Ultrasound-guided nerve HD with D5W was performed 4 weeks after corticosteroid injection. Treatment effectiveness were assessed by visual analog scale (VAS) and Boston Carpal Tunnel Syndrome Questionnaire (BCTQ). The assessment was performed at baseline and 4, 8, and 12 weeks after corticosteroid injection. In addition, adverse events were recorded in this study. RESULTS: A total of 49 patients and 62 wrists meeting the criteria were included, with 24 patients and 31 wrists in the steroid group and 25 patients and 31 wrists in the combination group. Compared with baseline data, both groups showed greater improvement in VAS, BCTQs (BCTQ severity), and BCTQf (BCTQ function) at 4, 8, and 12 weeks follow-up. VAS, BCTQs, and BCTQf scores at baseline and week 4 were comparable between steroid group and combination group. Compared with steroid group, combination group exhibited a significant reduction in VAS, BCTQs, and BCTQf at 8- and 12-week follow-up (P ≤ 0.01). No adverse event occurred in any group. CONCLUSIONS: Our results showed that ultrasound-guided nerve HD with D5W as add-on therapy after corticosteroid injection was efficacious and safe in CTS, and combination therapy is more beneficial than corticosteroid monotherapy in the improvement of symptoms and function at 8- and 12-week follow-up.

Correction to: Promoter hypomethylation mediated upregulation of MicroRNA-10b-3p targets FOXO3 to promote the progression of esophageal squamous cell carcinoma (ESCC).

In the original publication of this manuscript [1], Fig. 6 contains a repeated image in error (the left image of 'Migration' and the left image of 'Invasion').

miR-4317 suppresses non-small cell lung cancer (NSCLC) by targeting fibroblast growth factor 9 (FGF9) and cyclin D2 (CCND2).

BACKGROUND: Non-small cell lung cancer (NSCLC) is a leading cause of death worldwide. MicroRNAs (miRNAs) have been indicated as crucial actors in cancer biology. Accumulating evidence suggests that miRNAs can be used as diagnostic and prognostic markers for NSCLC. METHODS: The purpose of this study was to characterize and identify the novel biomarker miR-4317 and its targets in NSCLC. The expression of miR-4317 was analyzed by in situ hybridization (ISH) and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The effect of miR-4317 on proliferation was evaluated through 3-4,5-dimethylthiazol-2-yl-5-3-carboxymethoxyphenyl-2-4-sulfophenyl-2H-tetrazolium (MTS) and colony formation assays, and cell migration and invasion were evaluated through transwell assays. The expression of target proteins and downstream molecules was analyzed by qRT-PCR and western blot. Dual-luciferase reporter assay was used to assess the target genes of miR4317 in NSCLC cells. RESULTS: Our results demonstrated that miR-4317 was downregulated in NSCLC tissues and serum, particularly in lymph node metastasis and advanced clinical stage tissues. Kaplan-Meier survival analysis showed that NSCLC patients with high expression of miR-4317 exhibited better overall survival (OS). Enhanced expression of miR-4317 significantly inhibited proliferation, colony formation, migration and invasion, and hampered cycles of NSCLC cell lines in vitro. Our results suggested that miR-4317 functions by directly targeting fibroblast growth factor 9 (FGF9) and cyclin D2 (CCND2). In concordance with in vitro studies, mouse xenograft, lung, and brain metastatic studies validated that miR-4317 functions as a potent suppressor miRNA of NSCLC in vivo. Systemically delivered agomiR-4317 reduced tumor growth and inhibited FGF9 and CCND2 protein expression. Reintroduction of FGF9 and CCND2 attenuated miR-4317-mediated suppression of migration and invasion in NSCLC. CONCLUSIONS: Our results indicate that miR-4317 can reduce NSCLC cell growth and metastasis by targeting FGF9 and CCND2. These findings provide new evidence of miR-4317 as a potential non-invasive biomarker and therapeutic target for NSCLC.

Promoter hypomethylation mediated upregulation of MicroRNA-10b-3p targets FOXO3 to promote the progression of esophageal squamous cell carcinoma (ESCC).

BACKGROUND: Esophageal cancer is a high incident cancer worldwide with poor survival and limited therapeutic options. Alterations of microRNAs are common in cancers, and many of these micro RNAs are potential therapeutic and diagnostic targets to treat these cancers. miR-10b-3p located in chromosome region 2q31.1, and its expression is frequently increased in esophageal squamous cell carcinoma (ESCC). However, the biological functions, clinical significance and therapeutic implications of miR-10b-3p in ESCC remain unclear. METHODS: The expression levels of miR-10b-3p in ESCC specimens were analyzed by in situ hybridization (ISH) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays. Ectopic overexpression of miR-10b-3p in ESCC cells, mouse xenograft model, and metastasis model were used to evaluate the effects of miR-10b-3p on proliferation, and migration of cancer cells. Luciferase reporter assay and Western blot were performed to validate the potential targets of miR-10b-3p after the preliminary screening by computer-aided microarray analysis. RESULTS: We found that miR-10b-3p expression levels were significantly upregulated in the tumor tissues and serum samples of patients with ESCC. The expression levels of miR-10b-3p in both tumor tissues and serum samples were inversely associated with lymph node metastasis and clinical stages. We identified the expression level of miR-10b-3p in ESCC cancer samples as an independent prognostic marker of the overall survival rates of ESCC patients. We found more frequent hypomethylation of the CpG sites located upstream of the miR-10b-3p gene in the ESCC tissues compared with in the adjacent normal tissues, and the DNA methylation status of miR-10b-3p promoter region inversely correlated with the expression levels of miR-10b-3p. Ectopic overexpression of miR-10b-3p promoted cell proliferation, colony formation, migration and invasion in ESCC. While knockdown of miR-10b-3p had the opposite effects, particularly in promoting apoptosis. Mouse xenograft model confirmed that miR-10b-3p functions as a potent oncogenic miRNA in ESCC, which also promoting ESCC metastasis. Mechanistically, we found miR-10b-3p regulated FOXO3 expression by directly binding to the 3'-untranslated region. And systemic delivery of miR-10b-3p antagomir reduced tumor growth and inhibit FOXO3 protein expression in nude mice. CONCLUSIONS: Collectively, our findings suggested upregulated expression of miR-10b-3p caused by promoter hypomethylation contributed to the progression of ESCC; Thus, miR-10b-3p is a potentially effective biomarker for ESCC that could have further therapeutic implications.

Correlation between Pathological Characteristics and Young's Modulus Value of Spastic Gastrocnemius in a Spinal Cord Injury Rat Model.

The goal of the present study were (1) to investigate the pathological characteristics of gastrocnemius muscle (GM) and quantitatively assess GM tissue stiffness in rat models with spinal cord injury (SCI) and (2) to explore the correlation between pathological characteristics changes and Young's modulus value of GM. 24 Sprague Dawley male rats were allocated into normal control groups and SCI model subgroups, respectively. GM stiffness was assessed with shear wave sonoelastography technology. All GMs were further analyzed by pathological examinations. GM weights were decreased, the ratio of type I fibers was decreased, and the ratio of type II fibers was increased in the GM in the model group. MyHC-I was decreased, while MyHC-II was increased according to the electrophoretic analysis in model subgroups. The elastic modulus value of GM was increased in the model group. A significant negative correlation was found between Young's modulus value of GM and the ratio of type I fibers of GM in model subgroup. Our studies showed that the stiffness of GM is correlated with pathological characteristics during the initial stages of SCI in rats. We also identified shear wave sonoelastography technology as a useful tool to assess GM stiffness in SCI rat models.

Evaluation of clinical outcomes of patients with post-stroke wrist and finger spasticity after ultrasonography-guided BTX-A injection and rehabilitation training.

OBJECTIVE: Using ultrasonography (US) to guide botulinum toxin type A (BTX-A) injection in patients with post-stroke wrist and finger flexor muscle spasticity and assessing clinical outcomes after the injection and rehabilitation intervention. METHODS: Twenty-three patients with wrist and finger spasticity after stroke were recruited in this study from May 2012 to May 2013. Under US guidance, the proper dose (250 U) of BTX-A was injected into each spastic muscle at two injection sites. Then, conventional rehabilitation training started next day after BTX-A injection. The degree of spasticity was assessed by modified Ashworth scale (MAS) and wrist and finger motor function by active rang of movement (AROM), and Fugl-Meyer assessment (FMA) at the baseline, 1, 2, 4 and 12 weeks after BTX-A injection. RESULTS: Significant decreases (p < 0.02) in the MAS scores of both the finger flexor muscle tone and wrist flexor muscle tone measured at 1, 2, 4, and 12 weeks after the BTX-A injection were found in comparison with the baseline scores. Compared with the baseline, the AROM values of the wrist and finger extensions and the FMA scores of the wrist and hand significantly increased (p < 0.02) at 2, 4 and 12 weeks after the BTX-A injection. CONCLUSIONS: US-guided BTX-A injection combined with rehabilitation exercise decrease spasticity of the wrist and finger flexor muscles and improve their motor function in stroke patients up to 12 weeks following BTX-A injection.

[Studies on chemical constituents of Clerodendrum bungei].

OBJECTIVE: To study the constituents from Clerodendrum bungei. METHOD: The constituents were isolated and purified with chromatographic methods, and identified by NMR, MS and IR. RESULT: Five compounds were isolated, beta-sitosterol (1), taraxerol (2), glochidone (3), glochidonol (4), glochidiol (5). CONCLUSION: Compounds (3), (4) and (5) were isolated for the first time from C. bungei.

[Studies on chemical constituents in leafs of Clerodendron fragrans].

OBJECTIVE: To separate and identify the constituents from Clerodendron fragrans. METHOD: The constituents were isolated and purified with chromatographic methods, identified by NMR, MS, IR. RESULT: Beta-sitosterol (1), clerosterol (2), daucosterol (3), caffeic acid (4), kaempferol (5), 5,4'-dihydroxy-kaempferol-7-O-beta-rutinoside (6), acteoside (7) and leucoseceptoside A (8), were isolated and identified. CONCLUSION: Compound 7 and 8 were identified for the first time from Clerodendron fragrans.

Chemical constituents from Delphinium chrysotrichum and their biological activity.

A new diterpene alkaloid named delphatisine C (1) has been isolated from aerial parts of Delphinium chrysotrichum along with three known norditerpenoid alkaloids delpheline (2), delbrunine (3), and delectinine (4). Their structures were characterized on the basis of their spectral data. All of them were determined by SRB assay for their cytotoxicity, and compound (1) showed significant cytotoxic activities (IC(50)=2.36 µmol/L) against the A549 cell line.