MCTS1 enhances the proliferation of laryngeal squamous cell carcinoma via promoting OTUD6B-1 mediated LIN28B deubiquitination.

The aberrant upregulation of MCTS1 Re-Initiation and Release Factor (also known as Malignant T-cell-amplified sequence 1, MCTS1) can promote laryngeal squamous cell carcinoma (LSCC). It might act as a binding partner of multiple proteins. In this study, we further explored the expression of potential interaction between MCTS1 and OTU domain-containing protein 6B (OTUD6B) and its influence on the ubiquitination and degradation of OTUD6B's substrate in LSCC. LSCC cell lines AMC-HN-8 and TU177 were utilized for assessing protein-protein interaction, protein degradation and tumor growth in vitro and in vivo. The results showed that MCTS1 interacts with OUTD6B isoform 1 (OTUD6B-1) in the cell lines. Higher OTUD6B-1 expression is associated with significantly shorter progression-free interval in LSCC patients. OTUD6B positively modulated the expression of cyclin D1, cyclin E1 and c-Myc and LSCC cell proliferation in vitro and in vivo. MCTS1 negatively modulated the degradation of LIN28B in G1/S cells, via enhancing OTUD6B-mediated cleaving of K48-branched ubiquitin chains from LIN28B. OTUD6B or LIN28B shRNA weakened MCTS1 overexpression-induced cyclin D1 and c-Myc protein expression and LSCC cell proliferation. In summary, this study revealed that MCTS1 could enhance LSCC proliferation partially via the OTUD6B-LIN28B axis.

Hepatic venous pressure gradient evaluates the Scheuer stage of liver fibrosis by transjugular liver biopsy: a multicenter study.

BACKGROUND: Hepatic venous pressure gradient (HVPG) is the criterion for assessing sinusoidal portal hypertension. Using HVPG to assess the degree of liver fibrosis by transjugular liver biopsy (TJLB) is still being explored, as no data has been shown that portal hypertension may already be present in patients with advanced hepatic fibrosis (Scheuer stage ≥ S3). The objective of this study was to observe whether portal hypertension exists before progressing to cirrhosis (Scheuer stage = S4). METHODS: Fifty patients who underwent TJLB and HVPG were enrolled. The correlation between Scheuer stage and HVPG was analyzed using the Pearson correlation coefficient, and the ROC curve predicted the diagnostic value of HVPG in patients with hepatic fibrosis. RESULTS: The Scheuer stage and HVPG significantly correlated (r = 0.654, p < 0.001). The AUC of HVPG in predicting advanced liver fibrosis was 0.896, and of cirrhosis was 0.810. There were 45 patients with portal hypertension (HVPG> 5 mmHg), 12 with S3, 29 with S4; There were 42 patients with CSPH (HVPG≥ 10 mmHg), 11 with S3, and 29 with S4. CONCLUSION: HVPG is valuable in evaluating the Scheuer stage of liver fibrosis in patients with TJLB. Portal hypertension might already exist before the progression to cirrhosis in some patients.

[Effect of CPAP therapy on dynamic glucose level in OSAHS patients with newly diagnosed T2DM].

OBJECTIVE: To investigate the characteristic of dynamic glucose level in obstructive sleep apnea-hypopnea syndrome (OSAHS) patients with newly diagnosed type 2 diabetes mellitus (T2DM) and to evaluate the effect of continuous positive airway pressure (CPAP) treatment on the glucose level. METHODS: A total of 65 cases of patients with T2DM who were newly diagnosed by oral glucose tolerance test (OGTT) were enrolled from April 2014 to April 2015 in Gansu Provincial Hospital, and divided into simple T2DM group (n=30) and OSAHS with T2DM group (n=35) according to aponea-hypopnea index (AHI) which was monitored by polysomnography (PSG). Their general clinical data were collected, and glucose level of different periods was monitored by continuous glucose moitoring system (CGMS). Changes of glucose level were compared between two groups before and after CPAP treatment. RESULTS: Age, gender proportion, BMI, smoking and drinking history, glycosylated hemoglobin (HbA1c) and blood lipid profile had no significantly difference between two groups. Longer neck circumstance and higher waist-hip ration (WHR), higher systolic blood pressure and diastolic blood pressure, higher fasting plasma glucose (FPG) [(9.4 ± 3.2) vs (7.3 ± 2.1) mmol/L, P=0.028] and fasting insulin (FINS) [(19.2 ± 8.7) vs (11.1 ± 4.7) mU/L, P=0.044] level, more serious homeostasis model assessment insulin resistance (HOMA-IR) were found in OSAHS patients with T2DM when compared to patients in simple T2DM group. The average dynamic glucose level of 24 hours, daytime, nocturnal and sleep time in OSAHS with T2DM group were higher than that in the simple T2DM group (all P<0.05). The alarming times when the average dynamic glucose level of nocturnal time was more than 0.1 mmol·L⁻¹·min⁻¹ in T2DM with OSAHS was more than that in control group (P=0.001). After treatment of CPAP, the level of AHI [(5.9 ± 3.6) vs (56.7 ± 11.4) times/h, P<0.001], average dynamic glucose level of 24 hours, day, nocturnal and sleep time were obviously decreased (all P<0.05); lowest saturation oxygen (LSpO2) was significantly increased [(92.3 ± 3.7)% vs (81.5 ± 20.2)%, P<0.001]; the alarming times and HOMA-IR were obviously decreased (P=0.019, 0.043). According to multiple linear regression analysis, the AHI (ß=0.736, P<0.001) in OSAHS with T2DM group was positively related to the average dynamic glucose level during sleep time, but the LSpO2(ß=-0.889, P<0.001) was negatively correlated. CONCLUSIONS: OSAHS patients with newly diagnosed T2DM have higher glucose level than that in simple T2DM patients, and CPAP therapy can obviously decrease the glucose level in newly diagnosed T2DM patients with OSAHS. AHI and LSpO2may influence the average dynamic glucose level during sleep time.

[The clinical significance and changes of serum tumor necrosis factor and plasma endothelium in patients with OSAHS associated Type 2 diabetes mellites].

OBJECTIVE: To investigate the significance of tumor necrosis factor-alpha (TNF-α) and plasma endothelium (ET) in pathophysiologic process of patients with obstructive sleep apnea hypopnea syndrome(OSAHS) with type 2 diabetes mellitus (T2DM). METHOD: All observed subjects were divided into 4 groups. A number of 80 patients with OSAHS, 65 cases of OSAHS with T2DM patients, 20 patients with T2DM, and 32 cases of healthy control group were observed in this study. The serum levels of TNF-α and ET were detected by double antibody sandwich ELISA, the content of TNF-α and ET were compared between OSAHS group and OSAHS + T2DM group. It were also compared before and after treatment of CPAP or surgery. RESULT: TNF-α level is higher in OSAHS+T2DM group than that in the OSAHS group, T2DM group and the control group (P < 0.05); TNF-α level in OSAHS group and the T2DM group are higher than that in the control group (P < 0.05), but there was no difference in TNF-α level between the OSAHS group and the T2DM group. There was also no difference in ET level of the four groups. There were significant differences of TNF-α before and after treatment of CPAP or surgery in OSAHS group and OSAHS+T2DM group (P < 0.05). But there was no significant differences of ET before and after treatment of CPAP or surgery in the OSAHS+T2DM group (P > 0.05). CONCLUSION: TNF-α may be involved in the development of OSAHS and T2DM, while ET may have little effect on the occurrence and development of OSAHS and T2DM.

Nocturnal Hypoxemia Causes Hyperglycemia in Patients With Obstructive Sleep Apnea and Type 2 Diabetes Mellitus.

BACKGROUND: Our purpose was to investigate the relationship between oxygen saturation (SpO2) and dynamic interstitial glucose level (IGL) in patients with obstructive sleep apnea (OSA) along with type 2 diabetes mellitus (T2DM), and to investigate the potential mechanisms thereof. MATERIALS AND METHODS: A total of 130 patients with OSA and T2DM underwent polysomnography and oral glucose tolerance tests at the Sleep Medicine Center. Using the lowest (L) SpO2% tested, patients were divided into mild, moderate and severe LSpO2 groups. Polysomnography and continuous glucose monitoring systems were used to analyze the altered pattern of SpO2 and dynamic IGL in the 3 groups. RESULTS: LSpO2 during sleep in patients with OSA and T2DM stimulated an increase in IGL. The moderate and severe levels were represented by IGL45 and IGL30, respectively. The average nocturnal and peak IGL after LSpO2 in the severe group were significantly higher than in the mild and moderate groups. Stepwise multiple regression analysis showed that the body mass index (ß = 0.301, P < 0.001), homeostatic model assessment of insulin resistance (ß = 0.260, P < 0.001), apnea-hypopnea index (ß = 0.309, P < 0.001), average SpO2 (ß = -0.423, P = 0.008), LSpO2 (ß = -0.369, P < 0.001) and microarousal index (ß = 0.335, P = 0.044) were probably related to nocturnal IGL in patients with OSA along with T2DM. CONCLUSIONS: Severe and moderate OSA with T2DM is marked by a delayed IGL peak following LSpO2. Nocturnal hypoxemia causes hyperglycemia in patients with OSA along with T2DM.

[The curative effect analysis of continuous positive airway pressure combined with modified oral appliance in the treatment of severe OSAHS].

OBJECTIVE: To evaluate the curative effect of continuous positive airway pressure(CPAP) combined with modified oral appliance (MOA) in the treatment of severe OSAHS. METHOD: The research chose 120 male patients with severe OSAHS. They were treated with CPAP and MOA (30 cases), CPAP (30 cases), and MOA (30 cases) respectively. At the same time, the rest 30 cases without any treatment were in control group (matching factors: age, gender, IBM). After 3 months treatment, the characteristics of PSG and respiratory machine wear condition were observated in four groups. RESULT: The ESS score in CPAP and MOA group was significantly lower than that in other groups (P < 0.05); After 3 months treatment, the AHI, awake index (AI), and Ni (non-rapid eyemovement sleep1, N1) and N2 (non-rapid eye movement sleep2, N2) period of total sleep time (TST) percentage in CPAP assisted MOA group and CPAP group were significantly lower than that in MOA group and control group (P < 0.05); Sleep efficiency, ESS score, average blood oxygen saturation (MSaO2), the lowest oxygen saturation (LSaO2), slow wave sleep phases (SWS) and rapid eyemovement sleep (REM) accounted for the proportion of TST increased significantly (P < 0.05); There was no significant difference between CPAP assisted MOA group and CPAP group in AHI, MSaO2, AI, sleep efficiency, N1, N2, SWS and REM percentage of TST and ESS score. The LSaO2 and average machine time in CPAP assisted MOA group were significantly greater than that in CPAP group (P < 0.05), but 90% pressure and average air leakage were significantly lower in the CPAP group (P < 0.05) CONCLUSION: The curative effect of CPCR combined with modified oral appliance was better than CPCR or MOA alone in the treatment of severe OSAHS.

[The clinical effect observation for surgery of nose and pharyngeal auxiliary oral appliance in severe OSAHS].

OBJECTIVE: To investigate the therapeutic effects of oral modified device combined with nasopharyngeal enlargement surgery and evaluate the oral modified device' s adjuvant therapy meaning in severe OSAHS patients after surgery treatment. METHOD: 46 cases with severe OSAHS were diagnosed by PSG according to AHI and the lowest arterial oxygen saturation (LSaO2). We performed the nasal or pharyngeal cavity expansion surgery for them according to the pathological change part correspondingly. Then all subjects were divided into combined group (n=26) and surgery alone group (n=20) according to their personal willingness. We monitored the PSG for all subjects aftter 2 weeks and 3 months respectively, then we calculate the diversity between the two group or intragroup change on the basis of the AHI, LAT, LSaO2, mean arterial oxygen saturation (MSaO2) and sleep structures recorded by PSG. At the same time, we collected the subjective sensations by questionnaire. RESULT: The AHI and LAT in combined group were significantly lower and LSaO2 was significantly higher than these in surgery alone group(P<0. 05), and it's no difference in MSO2 between the two groups (P>0. 05). The N 1% was more shorter and the N2% and N3% were more longer after nasal or pharyngeal operation compared with pre-operative states in both groups(P<. 05), but we didn't find difference in REM%(P>. 05). The data of PSG also showed that the shallow sleep proportion was more shorter and the slow wave sleep proportion was more longer in combined group compared with surgery alone group. The subjective sensations results also showed significantly alleviated in combined group, such as mental state, daytime sleepiness and physical strength. The efficiency ratio of treatment was 85. 0% and 92. 3% in surgery alone group and combined group respectively. CONCLUSION: Nasal and pharyngeal cavity enlargement surgery combined with oral modified device is a more effective treatment in patients with severe OSAHS, and it is meaningful for the long-term curative effect of surgery to prevent relapse and improve.

[Clinical study on efficacy of nasal surgical expansion as a basic operation in treatment of patients with OSAHS].

OBJECTIVE: To observe the clinical effect of nasal surgical expansion as basical surgical treatment of patients with OSAHS. METHOD: A total of 320 patients with OSAHS were retrospectively analyzed. The patient was diagnosed by PSG. The electronic nasopharyngolarygnoscope exam airway CT, and MRI were applied to determining the nasal plane block. According to the concrete reasons, the nasal endoscopic nasal septum corrective surgery and open surgery were carried out, respectively. Nasal sinus neoplasm resection of off shoring, inferior turbinate fracture surgery or inferior turbinate back-end 1/3 line expansion and low temperature plasma ablation of nasal surgery, respectively. Pittsburgh sleep quality index (PSQI), snore outcome survey (SOS), epworth sleepiness score (ESS), the lowest arterial oxygen saturation (LSaO2) and AHI, time and ratio of slow wave sleep (SWS) stage and rapid eye movement (REM) stage were applied to comparing the curative effect between pre-operation and post-operation periods. RESULT: Snoring, sleep apnea, subjective mental symptoms of all patients with OSAHS were improved after operation; PSQI, SOS and ESS score were improved compared to pretreatment (P < 0.05); according to the 2009 OSAHS diagnosis and curative effect evaluation standard, 38 cases cured, 189 cases had obvious effect, 93 cases effective, and the total effective rate was 100%; there was statistical difference between the pre-operative period and 6 months post-operative in PSQI, SOS and ESS, LSaO2, AHI and proportion of REM (P < 0.05); sleep structure was improved, time and proportion of SWS were increased after the operation (P < 0.05). CONCLUSION: Solving the problem of nasal airway obstruction is the first step in surgical treatment of patients with OSAHS.

[The changes and significance of IL-6 levels in patients with OSAHS associated Type 2 diabetes Mellites].

OBJECTIVE: To explore the changes of serum interleukin-6 (IL-6) level in patients with obstructive sleep apnea hypopnea syndrome (OSAHS) and OSAHS associated type 2 diabetes mellitus (T2DM) and their significance. METHOD: All observed subjects were divided into 3 groups: 20 cases of normal subjects, 35 cases of simple OSAHS patients, 48 cases of OSAHS associated T2DM patients, IL-6 concentrations of serum were measured by the enzyme-linked immunosorbent. RESULT: IL-6 level was higher in the group of OSAHS with T2DM than the group of OSAHS and the healthy control group (P < 0.05); IL-6 level was higher in the simple OSAHS group than the healthy controls. CONCLUSION: IL-6 and other inflammatory factors may involved pathological physiological process in OSAHS patients sugar metabolic abnormalities; and is associated with the development of OSAHS associated with type 2 diabetes.

Electrical signals guided entrapment and controlled release of antibiotics on titanium surface.

Electrical signals are used to trigger the entrapment and release of antibiotics on the surface of titanium plate. The entrapment of antibiotics relies on the electrochemically induced pH gradient generated at the titanium surface that allows the gelation of an aminopolysaccharide chitosan and codeposition of vancomycin, a common antibiotic, within chitosan gel. The release of vancomycin is controlled by an anodic signal imposed to the titanium plate that causes a pH decrease and erosion of chitosan gel. We show that the on demand entrapment and release of vancomycin at the surface of titanium plate is fundamentally altered and controlled by voltage. We expect that this rapid, mild and facile electrochemical process for antibiotics loading and release will find applications in controlled drug release from titanium implants.