Therapeutic ultrasound potentiates the anti-nociceptive and anti-inflammatory effects of curcumin to postoperative pain via Sirt1/NF-κB signaling pathway.

Background: Postoperative pain has well defined and is perceived by patients as one of the most obnoxious aspects of surgical pain. The aim of this study was to determine whether the combination of Therapeutic ultrasound (TUS) and Curcumin (CUR) resulted in an enhancement of their pain relieving activities in a rat model of postoperative pain. Methods: We explored the effect of these treatment and their interaction with signal transduction pathways involved in inflammatory. In this study, TUS and CUR alone or in combination were administered prior to or simultaneously with or after the incisional surgery. Results: At the start time of administration, we observed that the TUS plus CUR treatment reduced the mean paw withdrawal threshold more efficiently than CUR alone. Then we demonstrated that TUS potentiates the antinociceptive effect of CUR in a rat model of chronic postoperative pain and that the combination could facilitate the recovery of surgical pain. However, preventive value was not statistically significant when the treatments were given prior to the incisional surgery. We provide evidence that TUS plus CUR administrations were safe and significantly reduced the ED50 compared to treatment with the single CUR treatment in rats. TUS plus CUR administrations decreases incisional surgery induced activation of inflammatory cells and down-regulation of chemokines and proinflammatory cytokines, MCP-1, MIP-1α, IL-1ß, and TNF-α through regulating Sirt1/NF-κB signaling pathway. Conclusions: Taken together, our results indicate that the combinations of TUS and CUR can be more effective in the anti-nociceptive effects than the treatment with CUR alone.

Influence of risk factors on stomal recurrence after total laryngectomy for laryngeal carcinomas: A meta-analysis.

BACKGROUND: Total laryngectomy is preserved for those the most advanced larynx cancer and nonsurgical cases. However, stomal recurrence is frequently occurred and leads to high mortality. Herein, we aimed to determine the risk factors for the stomal recurrence after total laryngectomy (SRAL). METHODS: Databases such as PubMed and EMBASE were comprehensively searched using the keywords "stomal recurrence" and "total laryngectomy." Based on the inclusion and exclusion criteria, qualified studies would be incorporated in this meta-analysis, followed by quality evaluation and data extraction. Risk ratios (RRs) were used. RESULTS: A total of six studies were included in the meta-analysis, and the pooled RRs showed that subglottic location increased the incidence of stomal recurrence most among the four primary locations. Expectedly, advanced tumor stage before the laryngectomy was the risk factor for stomal recurrence, while lymph node metastases showed no difference in this meta-analysis. Further, preoperative tracheostomy increased two times more risk in the stomal recurrence compared with nonpreoperative surgery. CONCLUSIONS: In this study, we proved that subglottic location, advanced tumor stage, especially T4 stage, and preoperative tracheostomy were risk factors for SRAL for larynx cancer. However, many other potential risk factors, such as surgical margins, could not be determined for inadequate records. Hence, more prospective trials should be designed to determine the risk factors for SRAL for larynx cancer.

Curcumin induces G2/M cell cycle arrest and apoptosis of head and neck squamous cell carcinoma in vitro and in vivo through ATM/Chk2/p53-dependent pathway.

Studies have demonstrated that curcumin (CUR) exerts its tumor suppressor function in a variety of human cancers including head and neck squamous cell carcinoma (HNSCC). However, the exact underlying molecular mechanisms remain obscure. Here, we aim to test whether CUR affects ATM/Chk2/p53 signaling pathway, leading to the induction of cell cycle arrest, inhibition of angiogenesis of HNSCC in vitro and in vivo. To this end, we conducted multiple methods such as MTT assay, Invasion assay, Flow cytometry, Western blotting, RT-PCR, and transfection to explore the functions and molecular insights of CUR in HNSCC. We observed that CUR significantly induced apoptosis and cell cycle arrest, inhibited angiogenesis in HNSCC. Mechanistically, we demonstrated that CUR markedly up-regulated ATM expression and subsequently down-regulated HIF-1α expression. Blockage of ATM production totally reversed CUR induced cell cycle arrest as well as anti-angiogenesis in HNSCC. Moreover, our results demonstrated that CUR exerts its antitumor activity through targeting ATM/Chk2/p53 signal pathway. In addition, the results of xenograft experiments in mice were highly consistent with in vitro studies. Collectively, our findings suggest that targeting ATM/Chk2/p53 signal pathway by CUR could be a promising therapeutic approach for HNSCC prevention and therapy.

Restoration of secreted frizzled-related protein 1 suppresses growth and increases cisplatin sensitivity in laryngeal carcinoma cells by downregulating NHE1.

It has been documented that secreted frizzled-related protein 1 (SFRP1) is epigenetically silenced in laryngeal carcinoma. However, the function of SFRP1 in laryngeal carcinoma remains elusive. In this study, we performed gain-of-function studies to determine the roles of SFRP1 in laryngeal carcinoma growth, tumorigenesis, and cisplatin resistance. Laryngeal carcinoma cell lines were treated with 5-aza-2'-deoxycytidine (5-aza-dC) and examined for SFRP1 expression. The effects of overexpression of SFRP1 on cell proliferation, colony formation, apoptosis, tumorigenesis, and cisplatin sensitivity were assessed. It was found that 5-aza-dC exposure significantly induced the expression of SFRP1 in both Hep-2 and SNU899 laryngeal carcinoma cells. Ectopic expression of SFRP1 significantly decreased cell proliferation and colony formation in vitro and retarded xenograft tumor growth in vivo. SFRP1-overexpressing Hep-2 cells displayed a higher percentage of apoptosis and enhancement of caspase-3 cleavage, which was coupled with loss of Δψm and increased release of cytochrome c from the mitochondria to the cytosol. Moreover, SFRP1 overexpression sensitized laryngeal carcinoma cells to cisplatin and decreased intracellular pH values. Mechanistically, SFRP1 inhibited the expression of Na+/H+ exchanger 1 (NHE1) and overexpression of NHE1 reversed the suppressive activity of SFRP1 on laryngeal carcinoma cells. In conclusion, we demonstrate that SFRP1 induces mitochondrial apoptosis and increases cisplatin sensitivity in laryngeal carcinoma cells via downregulation of NHE1. Delivery of SFRP1 may offer therapeutic benefits in the treatment of laryngeal carcinoma.

Haplotype analysis of the XRCC1 gene and laryngeal cancer.

OBJECTIVE: Several polymorphisms in DNA repair genes have been extensively studied in association with various human cancers, including laryngeal cancer. The present study aimed to investigate the association between polymorphisms of the XRCC1 gene and laryngeal cancer in a Chinese population. METHODS: Five polymorphisms of the XRCC1 gene (rs3213403, rs1799778, rs1001581, rs3213282, and rs3810378) were genotyped by TaqMan in 234 patients with larynx cancer and 230 age- and sex-matched controls without cancer. RESULTS: The rs3213403, rs1799778, and rs3213282 polymorphisms of XRCC1 were associated with larynx cancer. Haplotype analysis indicated that CCA (odds ratio [OR], 5.707; 95% confidence interval [CI], 3.277-9.938; p<0.001), TGG (OR, 4.344; 95% CI, 2.804-6.732; p<0.001), ACA (OR, 1.615; 95% CI, 1.159-2.250; p=0.004), and GCG (OR, 1.702; 95% CI, 1.164-2.489; p=0.005) were associated with an increased risk for larynx cancer, respectively. However, TGA (OR, 0.518; 95% CI, 0.398-0.673; p<0.001) and ACC (OR, 0.314; 95% CI, 0.215-0.457; p<0.001) were associated with a decreased risk for larynx cancer. CONCLUSIONS: The results indicated that XRCC1 genetic polymorphisms were associated with larynx cancer in a Chinese population.

DNA microarray reveals ZNF195 and SBF1 are potential biomarkers for gemcitabine sensitivity in head and neck squamous cell carcinoma cell lines.

Gemcitabine is a potential chemotherapy drug for treatment of head and neck squamous cell carcinoma (HNSCC), however, the poor or partial response of HNSCC patients to gemcitabine demonstrated the urgent need for gemcitabine biomarkers to improve the therapy. In present work, 10 HNSCC cell lines were employed to figure out the biomarkers for gemcitabine sensitivity. The sensitivities of these 10 cell lines to gemcitabine and the basal expression of these cell lines was investigated, the correlation between gemcitabine response (IC50 dose) and gene expression was investigated by Pearson correlation and FDR estimation. The top seven positive genes responsible for gemcitabine sensitivity were validated by qPCR in these 10 HNSCC cell lines, while only two genes (SBF1 and ZNF195) were expression-correlated to gemcitabine response. Furthermore, ZNF195 expression was closely associated with gemcitabine sensitivity in the subsequent independent validation in cell lines from various types of cancer. Our work might provide potential biomarkers for gemcitabine sensitivity in HNSCC and various type of cancer.

[Application research on RBH perceptual evaluation of voice disorders].

OBJECTIVE: To investigate the reliability of RBH perceptual evaluation system, and the correlation between its perceptual and acoustic parameters inorder to providing the evidence for clinic practice. METHODS: The voice samples were collected from 100 patients with variable dysphonia and 15 normal people. According to the R, B, H parameters of the RBH system,voice samples were rated on 4-point scale from 0 to 3. The interrater agreement and intrarater reliability were tested. The differences of the acoustic parameters between adjacent ranks in the perceptual parameters were investigated. The correlation between perceptual parameters and acoustic parameters were also studied. RESULTS: The interrater agreement and intrarater reliability were good. Intrarater reliability was varying from 0.428 to 0.608 using Kappa coefficient; intraclass correlation coefficients for interrater agreement were 0.741-0.797 and 0.689-0.762 in the twice perceptual assessments. The differences of the acoustic parameters between adjacent ranks in the perceptual parameters (R, B, H) were significant (P < 0.05). The perceptual parameters (R, B, H) were significantly correlated with the acoustic parameters (Jitter, Shimmer, HNR, MPT and DSI, with r varying from 0.360 to 0.551 or from -0.472 to -0.620, P < 0.01). CONCLUSION: The reliability of RBH perceptual evaluation system is good; its 4-point scale is acceptable; the perceptual parameters are correlated with the acoustic parameters; the RBH system has broad prospects in clinic practice.

[Chemical constituents from Lyophyllum decastes].

The chemical constituents from the fruiting bodies of Lyophyllum decastes (Fr.) Singer were studied in this paper. Thirteen compounds were isolated and purified by column chromatographies on silica gel and Sephadex LH-20. Their structures were identified by MS and NMR data analysis as adenosine (1), 2R, 3S, 4S, 8E)-2-[(2'R)-2-hydroxyheneicosanoylamino]-8-octadecene-1, 3, 4-triol (2), (2R, 3S, 4S, 8E)-2-[(2'R)-2-hydroxypentacosanoylamino]-8-octadecene-1, 3, 4-triol (3), nicotinic acid (4), (4E, 8E) -2-N-2-hydroxytetracosanoyl-1-O-beta-D-glycopyranosyl-9-methyl-4, 8-sphingadienine (5), D-mannitol (6), ergosteryl-3-O-beta-D-glucopyranoside (7), tuberoside (8), (2R, 3S, 4S, 8E)-2-[(2'R)-2-hydroxybehenoylamino]-8-octadecene-1, 3, 4-triol (9),(2R, 3S, 4S, 8E)-2-[(2'R) -2-hydroxytricosanoylamino] -8-octadecene-1, 3, 4-triol (10), (22E, 24R)-ergosta-7, 22-dien-3beta, 5alpha, 6beta-triol (11), (22E, 24R)-ergosta-5, 7, 22-trien-3beta-ol (12), and 5alpha, 8alpha-epidiory-(22E, 24R)-ergosta-6, 22-dien-3beta-ol (13), respectively. All the above compounds are first obtained from the mushroom and compounds 2-10 are reported to be obtained from the Lyophyllum for the first time.

Zinc sulfate therapy of vocal process granuloma.

Vocal process granuloma is a benign lesion that occurs on the arytenoid cartilage. It tends to recur locally, and there is a great diversity of methods to treat it. Here, we reviewed the effects of zinc sulfate therapy program in 16 patients with vocal process granulomas. Eleven patients had a history of trauma or laryngeal intubation and five patients had unknown origin. Eleven had recurrence after one to three failed surgeries, and the others had no prior treatment. Symptoms included hoarseness, sore throat, lump sensation in the throat and cough that apparently improved. The granulomas did not recur for at least 1 year. No complications occurred. For vocal process granuloma, zinc sulfate therapy is good either as an initial or compensatory treatment.

[Surgical management and reconstruction of petrous internal carotid artery involved in malignant tumors of lateral skull base].

OBJECTIVE: To investigate the feasibility of reconstruction of internal carotid artery after ablation of malignant tumors in lateral skull base. METHODS: Four male patients with malignant tumors in lateral skull base involved internal carotid artery underwent surgical treatment during Jan 2006 to Jan 2009 were retrospectively analyzed. MRI, CT and DSA were performed in all patients and showed that petrous internal carotid arteries (PICAs) were invaded, with luminal narrow. After radical dissection of tumors and the invaded PICAs, saphenous veins were used to reconstruct the PICAs. All cases were applied with postoperative concomitant radiochemotherapy. Three cases underwent total resection of temporal bone and one case underwent sub-total resection of temporal bone. Retrusion of facial nerve was performed in one case and reconstruction of facial nerve in three cases; Resection of sigmoid sinus and jugular foramen was performed in three cases. Resection and repair of meninges were performed in three cases. Free abdominal rectus and latissimus dorsi muscle myocutaneous flaps were used to repair the defect of lateral skull base and the flaps were well survived. RESULTS: No significant neurovascular complications occurred in the patients. Postoperative DSA showed that the reconstructed PICAs were in well conditions. Follow up showed two patients survived tumor-free for five years, one patient had recurrence three years after operation and survived with tumor, and one patient died of recurrence one year after operation. CONCLUSIONS: Reconstruction of PICA by saphenous vein offered the possibility of radical resection of malignant tumors in lateral skull base involved PICAs.

[Hair cells apoptosis and the activation of P53 protein in intensive impulse noise induced cochlear lesion].

OBJECTIVE: To explore the pattern of hair cell injury and expression of P53 apoptosis protein in intensive impulse noise injured cochlear hair cells in guinea pigs. METHODS: Twelve adult guinea pigs were exposed to a series of 40 pairs of impulse noise (2 second intervals) at the intensity of 168 dB (SPL). Animals were terminated at 3, 6 and 12 hours after noise exposure, respectively. Cochlear surface preparations were performed with a double staining of FITC-conjugated phalloidin and propidium iodide for the observations of the stereocilia and the nucleus. P53 immunochemical staining was also performed 12 hours post-noise exposure to observe if there was expression of p53 protein in injured hair cells. Results Three hours after noise exposure, the outer hair cells at the end of basal turn and beginning of second turn were destroyed first with a character of nuclear condensation. Six hours post-noise exposure, many hair cells in the center of damage region had nuclear fragmentations, and the damaging area expanded towards to basal turn and apical turn. Twelve hours after noise exposure, the nucleus in most outer hair cells and inner hair cells at the region of damage center were missing. The nuclear condensation and fragmentation were appeared in hair cells in both sides of the center region of degeneration. P53 immunoreactive products were also found in damaged hair cells, not only in the central damage area, but also in the basal turn and the third turn. CONCLUSIONS: Intensive impulse noise resulted in apoptosis of cochlear hair cells that initiated between the end of basal turn and the beginning of second turn. Hair cell degeneration spread to basal and third turn along the basilar membrane. P53 may play an important role in impulse noise induced-hair cell apoptosis.

[Sternum-hyoid muscle transposition and arytenoid adduction for unilateral vocal cord paralysis].

OBJECTIVE: To explore the therapeutic effect of sternum-hyoid muscle transposition and arytenoid adduction for unilateral vocal cord paralysis (UVCP). METHODS: Included in this study were 19 patients with UVCP lasted for 12 months to 15 years. The surgical technique was as follows. The thyroid cartilage was engaged with a skin hook and gently rotated anteriorly. The lateral-inferior corner of the thyroid cartilage was exposed and the muscular process of the arytenoid was identified. Then, the thyroid lamina on the involved side was parasagittally separated 5 mm off the midline. The inner perichondrium was carefully freed from the overlying thyroid cartilage. The lamina was retracted laterally, and a 3-0 prolene suture was placed through the muscular process and tied to the cricoid cartilage at the origin of the lateral cricoarytenoid muscle. A bipedicled strap muscle flap was then transposed into the space between the lamina and the inner perichondrium. Pre- and postoperative voice evaluations measured mean fundamental frequency, jitter, shimmer, harmonic ratio and maximal phonation time, as well as assessments of voice quality. RESULTS: Vocal improvement was obtained in 100% (19 of 19) of patients. Immediately after the operation, the ingression could be observed in vocal cord membrane and vocal process, vocal cord volume was amplified. There was a significant difference (P < 0.05) in all parameters (fundamental frequency, jitter, shimmer, harmonic ratio and maximal phonation time) between pre- and postoperative voice evaluations measured mean. There was no significant difference (P > 0.05) in voice evaluations measured mean between 2 months and 12 months after operation in all patients. No major complications were noted in any patient. CONCLUSION: Sternum-hyoid muscle transposition and arytenoid adduction for unilateral vocal cord paralysis is simple and convenient, no immune rejection, and the long-term result is stable.

[Correlation between myogenin and transforming growth factor-beta1 expression in long-term human denervated posterior cricoarytenoid muscles].

OBJECTIVE: To investigate the protein expression of myogenin, a mark of muscle regeneration, and TGF-beta1, an important factor of myelofibrosis, in long-term denervated posterior cricoarytenoid muscles (PCAMs) in order to find the appropriate time point of reinnervation in long-term denervated PCAMs. METHODS: Thirty-eight patients with vocal paralysis were divided into four groups, the 0.5-year denervation group, the 1-year denervation group, the 2-year denervation group and the over 3-year denervation group. Twelve normal adults served as a control group. The change in expression of related factors such as myogenin and TGF-beta1 were observed using immunofluorescence stain and Western blot. RESULTS: Immunostaining with antibody against myogenin showed no staining in innervated, however, by 0.5-year of muscle denervation, there was a significant accumulation of myogenin protein in myonuclei. There was a peak in expression of myogenin in 1-year denervated muscles. After 2 years of denervation, expression of myogenin protein in myonuclei was decreased, but after 3 years of denervation, no expression of myogenin protein in myonuclei was found. TGF-beta1 showed no staining in innervated, however, by 0.5-year and 1-year of muscle denervation there was a significant accumulation of TGF-beta1 protein in endochylema of myofiber, After 2 years of denervation, expression of TGF-beta1 protein in endochylema of myofiber was decreased, but after 3 years of denervation, no expression of TGF-beta1 protein in endochylema could be found. In Western blot, the change in protein expression of myogenin was observed 7.12-fold (F = 332.205, P < 0.001) increase from 0.5-year denervated muscles to innervated muscles, 15.58-fold (P < 0.001) increase from 1-year denervated muscles to innervated muscles, 6.50-fold (P < 0.001) increase from 2-years denervated muscles to innervated muscles (P < 0.001). After 3 years, the protein expression of myogenin decreased, 1.12-fold to innervated muscles. The change in protein expression of TGF-beta1 was observed 4.80-fold (F = 106.192, P < 0.001) increase from 0.5-year denervated muscles to innervated muscles, 10.59-fold (P < 0.001) increase from 1-year denervated muscles to innervated muscles, 6.01-fold (P < 0.001) increase from 2-years denervated muscles to innervated muscles(P < 0.001). After 3 years, the protein expression of TGF-beta1 decreased 1.20-fold to innervated muscles. There was significant positive correlation between expression of myogenin and TGF-beta1 in long-term denervated PCAMs. CONCLUSIONS: The change in expression of myogenin and TGF-beta1 indicated that there was a good muscles regeneration and a high amplitude of myelofibrosis within 2 years.

[Combination of genioglossus advancement by non-trephine technic with uvulopalatopharyngoplasty for treatment of obstructive sleep apnea-hypopnea syndrome].

OBJECTIVE: To evaluate the efficacy and reliability of genioglossus advancement and hyoid suspension with non-trephine technic (GAHM) and uvulopalatopharyngoplasty (UPPP) for surgical obstructive sleep apnea-hypopnea syndrome treatment. METHODS: Twenty-six patients (4 female and 22 male) were classified as moderate and severe cases in terms of apnea hypopnea index (AHI) and Friedman classification in the present study. All cases patients underwent genioglossus advancement and hyoid suspension with non-trephine technic Uvulopalatopharyngoplasty UPPP. Pre- and postoperative polysomnography and Epworth sleepiness scale were performed to assess the therapeutic outcomes. RESULTS: The whole operation time ranged from 120-180 minutes. The average amount of bleeding in genioglossus advancement was about 50-100 ml. There were no severe complications during and after the operation. All the cases were followed up to one year. After surgery, AHI was decreased in both group cases, (42.9 +/- 6.6 vs 16.2 +/- 5.7) in the severe group, and 21.3 +/- 4.4 vs 11.3 +/- 5.2 (x(-) +/- s) in the moderate group. With success defined as AHI decreased by more than 50 per cent after surgery, the total success rate in moderate and severe group was 83.3% and 91.7%, respectively (P < 0.01). Furthermore, the success rate of the moderate group was higher than those of the severe group (P < 0.01). CONCLUSION: GAHM combined with UPPP may be beneficial for the moderate and severe OSAHS patients with oropharyngeal and hypopharyngeal obstruction.

[Glottic measurement and vocal evaluation after three surgical techniques in the treatment of bilateral vocal cord paralysis].

OBJECTIVE: To evaluate postoperative glottic area and vocal quality of three various surgical techniques for treating bilateral vocal cord paralysis, including laser arytenoidectomy (Group A, 24 cases), reinnervation of the posterior cricoarytenoid muscle by phrenic nerve (Group B, 9 cases) and arytenoidectomy accompanying lateral cordopexy by extralaryngeal approach (Woodman's procedure, Group C, 13 cases). METHODS: 46 cases suffered from bilateral recurrent laryngeal nerve injury were included in our study. The pre-postoperative glottic measurement and vocal acoustic parameters were analyzed. RESULTS: The decannulated cases in group A and group B and group C were 22, 8, 13 respectively. The post-operative mean maximal glottic area was (47.2 +/- 7.4) mm2, (78.3 +/- 16.0) mm2, (48.1 +/- 6.5) mm2 respectively. Group B cases glottic area was larger than that of group A and group C (t value were 4.46 and 3.85, P value were 0.000 and 0.001). No significant difference was found between group A and group C (t = 1.68, P = 0.101). After surgery, in group A, 17 cases voice quality was the same compared with that of before surgery, and 7 cases voice quality had become worse; In group B, the voice quality had become better in 5 cases, completely recovered in 1 case, and had not change in 3 cases; In group C, the voice quality had become deteriorated in 10 cases and no change in 3 cases. And in group B, ipsilateral diaphragm paralysis in 9 cases after surgery, whose vital capacity and forced vital capacity had decreased to 72%-84%, 76%-84% of that before the surgery respectively; and the diaphragm mobility had recovered by 35%-76% respectively, while vital capacity and forced vital capacity had become 93%-97%, 91%-98% of that before the surgery. In Group B, all cases' pulmonary function was normal half a year postoperatively. CONCLUSIONS: Reinnervation of the posterior cricoarytenoid muscle by phrenic nerve seems to be best procedure with better post-operative voice and larger glottic area. Although the sufficient airway for decannulation can be acquired in Group A and Group C, but most of patients in Group A had pre-operative vocal level and badly abnormal in Group C.