Tauroursodeoxycholic acid attenuates endoplasmic reticulum stress and protects the liver from chronic intermittent hypoxia induced injury.

Obstructive sleep apnea that characterized by chronic intermittent hypoxia (CIH) has been reported to associate with chronic liver injury. Tauroursodeoxycholic acid (TUDCA) exerts liver-protective effects in various liver diseases. The purpose of this study was to test the hypothesis that TUDCA could protect liver against CIH injury. C57BL/6 mice were subjected to intermittent hypoxia for eight weeks and applied with TUDCA by intraperitoneal injection. The effect of TUDCA on liver histological changes, liver function, oxidative stress, inflammatory response, hepatocyte apoptosis and endoplasmic reticulum (ER) stress were investigated. The results showed that administration of TUDCA attenuated liver pathological changes, reduced serum alanine aminotransferase and aspartate aminotransferase level, suppressed reactive oxygen species activity, decreased tumor necrosis factor-α and interleukin-1ß level and inhibited hepatocyte apoptosis induced by CIH. TUDCA also inhibited CIH-induced ER stress in liver as evidenced by decreased expression of ER chaperone 78 kDa glucose-related protein, unfolded protein response transducers and ER proapoptotic proteins. Altogether, the present study described a liver-protective effect of TUDCA in CIH mice model, and this effect seems at least partly through the inhibition of ER stress.

CT Study of the Arytenoid Cartilage in Patients with Laryngeal Contact Granuloma.

Objective To explore high-resolution computed tomography (HRCT) characteristics of arytenoid cartilage in patients with laryngeal contact granuloma (LCG). Setting Tertiary hospitals. Study Design Individual case-control study. Methods HRCT scans were obtained before treatment from 42 patients with LCG. Similar scans were obtained from 50 patients with glottic laryngeal cancer or vocal cord leukoplakia without vocal process involvement. Results Forty-two male patients with LCG were enrolled in the study. There were 41 patients with unilateral vocal cord lesions, and 1 patient had bilateral lesions. All 50 eligible patients in the laryngeal lesion group were men. There were 39 patients with unilateral lesions, and 11 had bilateral lesions. The rate of arytenoid cartilage sclerosis in the LCG group was 79.07% (34/43) on the lesion side and 7.32% (3/41) on the healthy side. In the laryngeal lesion group, the rate of arytenoid cartilage sclerosis was 13.11% (8/61) on the lesion side and 2.56% (1/39) on the healthy side. The rate of arytenoid cartilage sclerosis on the lesion side of patients with LCG was significantly higher than on the healthy side of patients with LCG and significantly higher than both the healthy and lesion sides of patients with laryngeal lesions ( P < .001). Conclusions Arytenoid cartilage sclerosis was observed on the lesion side in most patients with LCG, and the presence of sclerosis may support the diagnosis of LCG.

Unitary ototoxic gentamicin exposure may not disrupt the function of cochlear outer hair cells in mice.

BACKGROUND: Previous study showed that mild ototoxic exposure could induce a reversible hearing impairment, and the loss and secondary incomplete recovery of cochlear ribbon synapses could be responsible for the hearing loss. However, it remains unclear whether cochlear outer hair cells' (OHCs) functions are affected. OBJECTIVE: To verify whether the function of OHCs are also affected significantly after the ototoxic exposure. METHODS: Mice were injected intraperitoneally with 100 mg/kg concentration of gentamicin daily for 14 days. Distortion Product of Oto-acoustic Emission (DPOAE) was detected at control (pre-treatment), Day 0, day 4, day 7, day 14 and day 28 after the ototoxic exposure, respectively. In addition, the morphology of OHCs was observed by electron microscopy, OHCs has been counted by light microscopy, and the hearing thresholds were detected by auditory brain response (ABR). RESULTS: No significant changes have been found in OHC and OHC stereocilia among the experimental groups (p > .05). Further, no significant changes or loss was found in the morphology of OHCs either. However, we found ABR threshold elevations occurred after ototoxic exposure. CONCLUSIONS: Unitary ototoxic gentamicin exposure may not disrupt the function of cochlear OHCs in mice, regardless of hearing loss identified in this ototoxic exposure.

Association between vitamin D and development of otitis media: A PRISMA-compliant meta-analysis and systematic review.

BACKGROUND: Nutrients related to serum vitamin D level were previously shown to be significantly associated with the risk of many chronic diseases. This study aimed to assess potential relationships between serum vitamin D level and otitis media (OM) risk. METHODS: PubMed, EMBASE, and Cochrane Library databases were searched till Aug 18, 2015 for studies of quantitative OM risk estimates in relation to serum vitamin D level. The odds ratio and weighted mean difference, with 95% confidence intervals (CIs), were used to measure the relationship between serum vitamin D level and OM risk. RESULTS: Of the 89 articles identified by database search, 5 studies reported data of 16,689 individuals were included in our meta-analysis. We noted participants with OM was associated with lower level of plasma vitamin D when compared with patients without OM (weighted mean difference -5.67; 95% CI -8.08 to -3.26, P < 0.001). Furthermore, as compared with control group, serum vitamin D level was not associated with the risk of OM (odds ratio 0.80, 95% CI 0.47-1.38, P = 0.425). Subgroup analyses suggested that participants with acute OM might associate with lower serum vitamin D level. CONCLUSIONS: Plasma vitamin D level might play an important role on the progression of acute OM, whereas no significant impact in patients with chronic OM.

FOXQ1 is overexpressed in laryngeal carcinoma and affects cell growth, cell cycle progression and cell invasion.

Forkhead box Q1 (FOXQ1) is a forkhead transcription factor that is involved in numerous biological processes and has been shown to participate in tumorigenesis. However, the clinical significance of the expression of this protein in laryngeal carcinoma, and the mechanisms underlying its regulation in this disease remain unclear. The aim of present study was to measure the expression of FOXQ1 in laryngeal carcinoma, and to examine its effect on tumorigenesis. In the present study, reverse transcription-quantitative polymerase chain reaction and western blotting were employed to measure FOXQ1 expression in laryngeal carcinoma tissue samples, small interfering RNA specific to FOXQ1, was transfected into Hep2 cells and its effect on cell proliferation, cell cycle progression and cell migration was examined, using a CCK-8 assay, flow cytometry and a transwell migration assay, respectively. The results showed overexpression of FOXQ1 mRNA and protein in laryngeal cancer tissue samples. Inhibition of FOXQ1 suppressed cell growth and invasion, and arrested cells in the G0/G1 phase. Overexpression of FOXQ1 is associated with the development of laryngeal carcinoma and may enhance tumorigenesis through its effects on cell proliferation, cell cycle progression and cell migration.

MicroRNA-126 modulates the tumor microenvironment by targeting calmodulin-regulated spectrin-associated protein 1 (Camsap1).

Plasma miRNAs have been reported as biomarkers for various diseases. In this study, we investigated whether plasma concentrations of miR-126 may be useful as biomarkers for laryngeal squamous cell carcinoma (LSCC). We examined the function and mechanism of miR-126 in LSCC by using cell biology and molecular pathology techniques such as western blotting, quantitative PCR, IHC and IF. The expression of Camsap1 mRNA and protein is higher in cancer tissues compared to that in normal tissues. Both miR-126 and Camsap1 were related with the prognosis of LSCC patients. We found that miR-126 was able to inhibit LSCC partly by suppressing Camsap1 expression. In addition, Camsap1 expression induced microtubule formation and aggregation. This mechanism possibly explains why loss of miR-126 is frequently associated with tumor metastasis.

[Clinical analysis of 14 cases with nasal respiratory enithelial adenomatoid hamartom].

OBJECTIVE: To describe and analyze the clinical features of nasal respiratory epithelial adenomatoid hamartom and improve the levels of diagnosis and treatment. METHOD: Fourteen cases of nasal respiratory epithelial adenomatoid hamartom confirmed by pathology were collected and analyzed. RESULT: In 14 cases, primary complaint of Hyposmia(or Anosmia)and nasal obstruction were occured in 13 and 11 cases respectively. Four cases had past history of endoscopic sinus surgery because of the diagnosis of nasal polyps. Polypoid neoplasms could be seen in the bilateral olfactory clefts. Sinus CT showed soft tissue shadows in bilateral nasal cavity and mucous membrane thickening in different sinus. Endoscopic sinus surgery were utilized to eliminate focus in all cases. All cases weren t recurred after 2-20 months' following-up visitings. CONCLUSION: Nasal respiratory epithelial adenomatoid hamartom is so rare that clinical and pathological doctors have limited knowledge of it. It has its own characteristics from the clinical symptoms, signs to sinus CT although they are nonspecific. So we should improve the understanding about it to avoid misdiagnosis or missed diagnosis.

[The necessity of post-maneuver postural restriction in treating benign paroxysmal positional vertigo].

OBJECTIVE: To evaluate the necessity of postural restrictions after repositioning maneuvers in posterior canal benign paroxysmal positional vertigo (BPPV). METHOD: Sixty-eight consecutive patients diagnosed of posterior canal BPPV with a positive Dix-Hallpike test. Thirty-two patients were instructed to follow postural restrictions after repositioning maneuvers, and 36 patients did not receive any postural restriction after treatment. All the patients were reevaluated at 1 week and 3 months later respectively. RESULT: There was no statistical difference in number of maneuvers needed to resolve symptoms between two groups. CONCLUSION: Epley maneuver is effective to treat patients with posterior canal BPPV, and postural restrictions does not improved the efficacy. Above all, we do not recommend any postural restrictions to patients with posterior canal BPPV.

The neuronal responses to repetitive acoustic pulses in different fields of the auditory cortex of awake rats.

Cortical representation of time-varying features of acoustic signals is a fundamental issue of acoustic processing remaining unresolved. The rat is a widely used animal model for auditory cortical processing. Though some electrophysiological studies have investigated the neural responses to temporal repetitive sounds in the auditory cortex (AC) of rats, most of them were conducted under anesthetized condition. Recently, it has been shown that anesthesia could significantly alter the temporal patterns of neural response. For this reason, we systematically examined the single-unit neural responses to click-trains in the core region of rat AC under awake condition. Consistent with the reports on anesthetized rats, we confirmed the existence of characteristic tonotopic organizations, which were used to divide the AC into anterior auditory field (AAF), primary auditory cortex (A1) and posterior auditory field (PAF). We further found that the neuron's capability to synchronize to the temporal repetitive stimuli progressively decreased along the anterior-to-posterior direction of AC. The median of maximum synchronization rate was 64, 32 and 16 Hz in AAF, A1 and PAF, respectively. On the other hand, the percentage of neurons, which showed non-synchronized responses and could represent the stimulus repetition rate by the mean firing rate, increased from 7% in AAF and A1 to 20% in PAF. These results suggest that the temporal resolution of acoustic processing gradually increases from the anterior to posterior part of AC, and thus there may be a hierarchical stream along this direction of rat AC.

Ginsenoside Rd attenuates beta-amyloid-induced tau phosphorylation by altering the functional balance of glycogen synthase kinase 3beta and protein phosphatase 2A.

Neurofibrillary tangles are aggregates of hyperphosphorylated tau that are one of the pathological hallmarks of Alzheimer's disease (AD). Tau phosphorylation is regulated by a balance of kinase and phosphatase activities. Our previous study has demonstrated that ginsenoside Rd, one of the principal active ingredients of Pana notoginseng, inhibits okadaic acid-induced tau phosphorylation in vivo and in vitro, but the underlying mechanism(s) is unknown. In this study, we showed that ginsenoside Rd pretreatment inhibited tau phosphorylation at multiple sites in beta-amyloid (Aß)-treated cultured cortical neurons, and in vivo in both a rat and transgenic mouse model. Ginsenoside Rd not only reduced Aß-induced increased expression of glycogen synthase kinase 3beta (GSK-3ß), the most important kinase involved in tau phosphorylation, but also inhibited its activity by enhancing and attenuating its phosphorylation at Ser9 and Tyr216, respectively. Moreover, ginsenoside Rd enhanced the activity of protein phosphatase 2A (PP-2A), a key phosphatase involved in tau dephosphorylation. Finally, an in vitro biochemical assay revealed that ginsenoside Rd directly affected GSK-3ß and PP-2A activities. Thus, our findings provide the first evidence that ginsenoside Rd attenuates Aß-induced pathological tau phosphorylation by altering the functional balance of GSK-3ß and PP-2A.

MicroRNA expression and its detection in human supraglottic laryngeal squamous cell carcinoma.

Laryngeal squamous cell carcinoma (LSCC) is one of the most common head and neck malignancies with a poor prognosis. The aim of this study was to detect the expression of microRNAs (miRNAs) in supraglottic LSCC and attached normal mucosa using microarray assay, and explore the role of miRNAs in supraglottic LSCC. Fresh-frozen samples of five supraglottic LSCC and attached normal mucosa were obtained, and their various endogenous miRNAs were screened by microarray. miRNAs of interest were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) in 48 supraglottic LSCC tumors and 10 normal mucosa tissues. In total, 38 miRNAs were differentially expressed in supraglottic LSCC, with 22 miRNAs being upregulated and 16 downregulated. Of the six miRNAs selected for qRT-PCR, miR-375, miR-139-3P, miR-1290 and miR-106b were differentially expressed in supraglottic LSCC with and without lymphatic metastasis.

[The rule of lymphatic formation and the relationship between lymphatic formation and clinical pathological factors in supraglottic carcinoma].

OBJECTIVE: To investigate the rule of lymphatic formation and the relationship between lymphatic formation and clinical pathological factors in supraglottic carcinoma. METHOD: Immunohistochemistry method and automatic image analysis technique were applied to observe the lymphatic quantity and state in central carcinoma tissue, join tissue and normal larynx mucosa of supraglottic carcinoma. Analyze the rule and the correlation between lymphatic formation and T stage, differentiation, lymph metastasis. RESULT: The lumen-lymphatic formation was not seen in central carcinoma tissue. There are little lymphatic in normal larynx mucosa whereas many lymphatic formation in join area. The lymphatic density in join tissue is correlated with T stage, differentiation and lymph metastasis: T(1-2) lower than T(3-4) and the difference is significant (P<0.01); The difference between high and middle differentiation is insignificant (P=0.212); High-middle differentiation lower than low differentiation and the difference is significant; No lower than N+ and the difference is significant (P<0.01). CONCLUSION: In join area, there are lymphatic formation both in carcinoma area and para-tumor area. Tumor cell can go to lymph nodes via this pathway. This conclusion provides theoretical basis for clinical utility of the anti-tumor medicines which inhibitable lymphatic formation. It can help surgeons forecast prognosis and select more effective treatment method to observe join lymphatic vessel quantity.