Chronic pain exacerbates memory impairment and pathology of Aß and tau by upregulating IL-1ß and p-65 signaling in a mouse model of Alzheimer's disease.

BACKGROUND: Chronic pain is linked to cognitive impairment; however, the underlying mechanisms remain unclear. In the present study, we examined these mechanisms in a well-established mouse model of Alzheimer's disease (AD). METHODS: Neuropathic pain was modeled in 5-month-old transgenic APPswe/PS1dE9 (APP/PS1) mice by partial ligation of the sciatic nerve on the left side, and chronic inflammatory pain was modeled in another group of APP/PS1 mice by injecting them with complete Freund's adjuvant on the plantar surface of the left hind paw. Six weeks after molding, the animals were tested to assess pain threshold (von Frey filament), learning, memory (novel object recognition, Morris water maze, Y-maze, and passive avoidance), and depression-like symptoms (sucrose preference, tail suspension, and forced swimming). After behavioral testing, mice were sacrificed and the levels of p65, amyloid-ß (residues 1-42) and phospho-tau in the hippocampus and cerebral cortex were assayed using western blotting, while interleukin (IL)-1ß levels were measured by enzyme-linked immunosorbent assay. RESULTS: Animals subjected to either type of chronic pain showed lower pain thresholds, more severe deficits in learning and memory, and stronger depression-like symptoms than the corresponding control animals. Either type of chronic pain was associated with upregulation of p65, amyloid-ß (1-42), and IL-1ß in the hippocampus and cerebral cortex, as well as higher levels of phosphorylated tau. CONCLUSIONS: Chronic pain may exacerbate cognitive deficits and depression-like symptoms in APP/PS1 mice by worsening pathology related to amyloid-ß and tau and by upregulating signaling involving IL-1ß and p65.

Suppression of nuclear factor-kappa B and mitogen-activated protein kinase signalling pathways by goshonoside-F5 extracted from Rubi Fructus.

Rubi Fructus, a traditional Chinese medicine, was considered as an anti-inflammatory agent in folk medicine. In the present study, we investigated the signalling pathways involved in the anti-inflammatory effects of goshonoside-F5 (GF5), isolated from Rubi Fructus, in peritoneal macrophages and examined its therapeutic effect in a mouse endotoxic shock model. GF5 decreased NO and PGE2 production in LPS-stimulated macrophages (IC50=3.84 and 3.16µM). This effect involved the suppression of NOS-2 and COX-2 gene expression at the transcriptional level. Examination of the effects of GF5 on NF-κB signalling demonstrated that it inhibits the phosphorylation of IκB-α and IκB-ß, blocking their degradation and the nuclear translocation of the NF-κB p65 subunit. Moreover, inhibition of MAPK signalling was also observed, and phosphorylation of p38 and JNK was suppressed in the presence of GF5. Inflammatory cytokines, including IL-6 and TNF-α, were down-regulated by this compound after activation with LPS (IC50=17.04 and 4.09µM). Additionally, GF5 (30 and 90mg/kg, i.p.) significantly reduced the circulating cytokine levels (IL-6 and TNF-α) and increased survival in a mouse model of endotoxemia. These results show that GF5 significantly inhibits the pro-inflammatory response induced by LPS, both in vitro and in vivo. Our results provide a strong pharmacological basis for further understanding the potential therapeutic role of GF5 in inflammatory disease and shed new light on the bioactivity of ent-labdane diterpene glucoside.

[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.

Risk factors for adverse outcome in low rectal cancer.

AIM: To demonstrate the oncologic outcomes of low rectal cancer and to clarify the risk factors for survival, focusing particularly on the type of surgery performed. METHODS: Data from patients with low rectal carcinomas who underwent surgery, either sphincter-preserving surgery (SPS) or abdominoperineal resection (APR), at The First Affiliated Hospital of Sun Yat-sen University in China from August 1994 to December 2005 were retrospectively analyzed. RESULTS: Of 331 patients with low rectal cancer, 159 (48.0%) were treated with SPS. A higher incidence of positive resection margins and a higher 5-year cumulative local recurrence rate (14.7% vs 6.8%, P = 0.041) were observed in patients after APR compared to SPS. The five-year overall survival (OS) was 54.6% after APR and 66.8% after SPS (P = 0.018), and the 5-year disease-free survival (DFS) was 52.9% after APR and 65.5% after SPS (P = 0.013). In multivariate analysis, poor OS and DFS were significantly related to positive resection margins, pT3-4, and pTNM III-IV but not to the type of surgery. CONCLUSION: Despite a higher rate of positive resection margins after APR, the type of surgery was not identified as an independent risk factor for survival.

[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.

Clinical features and risk factors for primary surgery in 205 patients with Crohn's disease: analysis of a South China cohort.

BACKGROUND: The frequency of Crohn's disease in China is increasing, but few reports are available on clinical features, phenotypes according to the Montreal classification, or risk factors for surgery in mainland China. OBJECTIVE: This study aimed to assess clinical presentation, phenotypes according to the Montreal classification, and potential risk factors for initial surgery in patients with Crohn's disease in southern China. DESIGN: This was an observational study designed as a retrospective analysis of a historical cohort. SETTINGS: The study was conducted at a tertiary referral hospital, Guangzhou, China. PATIENTS: Medical records of 212 consecutive patients with Crohn's disease were reviewed; data from 205 patients who met inclusion criteria were analyzed. MAIN OUTCOME MEASURES: The value of age, location, and behavior of disease according to the Montreal system, smoking behavior, and other clinical variables as potential risk factors in predicting the requirement for initial surgery was assessed by use of Cox regression analysis. RESULTS: A total of 205 patients were studied. Abdominal pain (181 patients, 88.3%) was the most common clinical presentation. At the time of diagnosis, age was between 17 and 40 years in 145 patients (70.7%). The Montreal classification of disease location was L3 (ileocolonic) in 114 patients (55.6%), disease behavior was classified as inflammatory in 133 patients (64.9%). During the course of their disease (median, 4 years; range, 1-21 years), 79 patients (38.5%) required bowel resection. Kaplan-Meier analysis showed that the overall cumulative rate of primary bowel surgery was 17.6% at 1 year after onset of symptoms, 20.3% at 2 years, 35.2% at 5 years, and 58.3% at 10 years. In our final Cox model, stricturing (HR, 3.67; 95% CI, 2.14-6.29; P < .001), penetrating behavior (HR, 4.60; 95% CI, 2.58-8.22; P < .001), and smoking habit (HR, 2.02; 95% CI, 1.15-3.53; P = .014) were significantly associated with an increased risk for bowel resection. LIMITATIONS: The study was limited by its retrospective nature. CONCLUSIONS: In Chinese patients with Crohn's disease, abdominal pain is the most common clinical presentation, and the most common phenotypes are age 17 to 40 years at diagnosis, ileocolonic disease location, and inflammatory disease behavior. More than one-third of patients require surgery at a median of 4 years after onset of symptoms. Stricturing, penetrating disease, and smoking are associated with an increased risk of requiring bowel resection.

[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.

[Role of different ligation of the inferior mesenteric artery in sigmoid colon or rectal cancer surgery: a meta-analysis].

OBJECTIVE: To evaluate the effect of different ligation of the inferior mesenteric artery in sigmoid colon or rectal cancer surgery on 5-year overall survival rate and operative mortality. METHODS: The results of several literatures from different countries on high or low ligation of the inferior mesenteric artery and prognosis were analyzed using meta-analysis. RESULTS: Seven studies were included. The 5-year overall survival rate was compared between low and high ligation. The odd ratio (OR) for 5-year survival was 0.87 (95% CI=0.76-0.98, P=0.02), and the OR for perioperative mortality was 1.28 (95% CI=0.94-1.75, P=0.19). CONCLUSIONS: High ligation of the inferior mesenteric artery may improve 5-year overall survival rate. Perioperative mortality may not be influenced by the level of ligation.

[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.

[Display of different injuries of recurrent laryngeal nerve in laryngeal electromyography].

OBJECTIVE: To study the display of different types injuries of recurrent laryngeal nerve (RLN) in laryngeal electromyography (LEMG). METHODS: LEMGs of one hundred and forty-seven patients (147 sides) with traumatic unilateral vocal cord paralysis (UVCP) were studied. After LEMGs, the RLNs exploration operations were performed. The condition of RLNs injury and laryngeal muscles was observed and recorded during the operation. RESULTS: The severe injuries of RLNs were found during operation. The types of injuries were listed as ligation (58 cases), adhesion (28 cases) and cut (61 cases). The waveform morphology of LEMG was recorded less in the patients with the RLNs cut than that in the patients with the RLN ligation or adhesion, respectively. 75.4% RLNs cut showed spontaneous waveform while 96.4% RLNs adhesion and 94.8% RLNs ligation. When the RLN was cut off, single pattern was showed oftener. When the RLN was adhered or ligated, mixed pattern was showed oftener. 92.9% RLN adhesion showed misdirect-regeneration-potentials while 70.7% RLN ligation and 24.6% RLN cut. There were significant difference between two types, but the compound muscular active potential (CMAP) amplitude wasn't significantly different. Evoked amplitude could be recorded in 91.4% patients with ligation and its amplitude was (23.6 +/- 8.1)%, in 85.7% patients with adhesion and its amplitude (16.3 +/- 5.2)%, in 29.5% patients with cut and its amplitude (2.6 +/- 4.2)%. CONCLUSIONS: The display of different injuries of RLN in LEMG presents significant difference. If RLN was cut off, the CMAP might be recorded in most cases. The clinical injury of RLN often is followed by sub-clinic reinnervation.

[Nerve exploration and decompression for traumatic recurrent laryngeal nerve injuries induced by thyroid gland surgery].

OBJECTIVE: To show the findings of recurrent laryngeal nerve injury exploration and find out therapeutic effects, indications and timing of nerve decompression for traumatic recurrent laryngeal nerve injury induced by thyroid gland surgery. METHODS: In this study there were 87 patients with recurrent laryngeal nerve injury, including 65 for nerve exploration and 22 for nonsurgical treatment. During nerve exploration, the types, severity of laryngeal nerve injuries and laryngeal muscular mass were studied. Nerve decompression was performed in these 14 patients whose compressing sutures or compression due to cicatricial hypertrophy were received nerve decompression. RESULTS: Injuries caused by thyroid gland operations mostly are of suture ligation (43%) and nerve severance (48%); simple scar compression was found only in 6 cases (9%). Atrophy of the laryngeal muscles was not very serious in patients with a course less than 6 months. In 10 patients with a course less than three months, nerve decompression restored normal functional abductor and abductor motion of the vocal cord in 9 patients and had no effects in one. Although functional motion of vocal cord was not seen in one case with a course less than 3 months and 4 cases between 3 and 5 months, the mass and tension of the reinnervated vocal cord became much the same as the contralateral normal vocal cord, thus resuming symmetric vibration of the vocal cords and physiological phonation. Although nonsurgical treatment improved severe hoarseness, it didn't restore normal functional motion of the vocal cord and normal voice. CONCLUSIONS: Nerve exploration showed a primary rule for recurrent laryngeal nerve injury induced by thyroid gland surgery. Early and mid-stage recurrent laryngeal nerve exploration and decompression may restore normal motion of the glottis, and it suggested laryngeal delayed reinnervation may help patients with a course more than 6 months.

[Comprehensive prognostic value of spontaneous and evoked electromyography in laryngeal paralysis].

OBJECTIVE: To determine the comprehensive prognostic value of spontaneous and evoked electromyography (EMG) in laryngeal paralysis. METHODS: The characteristics of laryngeal EMG of 91 cases with unilateral vocal cord paralysis (VCP) after thyroid surgery were assessed. All cases were divided into four groups according to the interval of laryngeal EMG after onset, which were group one (2 months shorter, n = 13), group two (2 to 4 months, n = 23), group three (4 to 6 months, n = 36), group four (6 months longer, n = 19). The waveform morphology and the amplitude of laryngeal EMG and the highest evoked compound muscular active potential (CMAP) of thyroarytenoid muscles were examined and analyzed during voluntary tasks. The potential amplitude was showed by the percentage of that of the healthy lateral. The criterion of evaluation on evoked potential was attained by calculating statistical confidence interval. RESULTS: The highest evoked CMAP in group one was significantly lower than that of the others (P < 0.05), but no significant difference was observed between group two and group three (P > 0.05), so group two and group three were analyzed together. There were 2 recovered cases and 11 unrecovered cases in group one. On the basis of this criterion that a positive prognosis for laryngeal recovery was indicated when the evoked CMAP presented and there was no misdirect generated potential, correct prognostic rate was 92% (12/13). There were 11 recovered cases and 48 unrecovered cases in group two and three. The highest evoked CMAP was much higher in the recovered than in the unrecovered, significant difference was observed between them (P < 0.001). On the basis of the criterion that a positive prognosis for laryngeal recovery was indicated when the highest evoked CMAP was higher than 26. 4%, correct prognostic rate was 90% (53/59). On the basis of the criterion that a positive prognosis for laryngeal recovery was indicated when there was no misdirect generated potential and the highest evoked CMAP was higher than 26.4%, correct prognostic rate was 93% (55/59). When the interval from onset to laryngeal EMG recovering was longer than 6 months, none of these patients had return of vocal cord mobility whatever were the outcomes of laryngeal EMG. CONCLUSIONS: Correct prognostic rate can be improved if the prognosis of VCP in different courses is judged respectively by analyzing comprehensively spontaneous and evoked EMG.