[Parathyroid hormone-related protein aggravates nonalcoholic fatty liver disease induced by methionine choline-deficient diet in mice].

OBJECTIVE: To study the effect of parathyroid hormone-related protein (PTHrP) on nonalcoholic fatty liver disease (NAFLD) induced by methionine choline-deficient diet (MCD) in mice. METHODS: Twelve male C57BL/6J mice were randomized into blank control group, vehicle group and PTHrP group (n=4). The mice in vehicle group and PTHrP group received injections of a control adeno-associated virus (AAV) vector and an AVV vector carrying PTHrP (AAV-PTHrP) gene, respectively, followed one week later by MCD feeding for 3 weeks; the mice in the blank control were fed a normal diet for 4 weeks. Body weight changes of the mice were monitored during the experiment. At the end of the experiment, liver tissues were harvested from the mice for histological analysis using HE staining, oil red O staining, and Sirius red staining. The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride, and free fatty acids (FFAs) in the liver and serum were detected to assess hepatic impairment and lipid metabolism of the mice. Cell models of NAFLD were established in mouse and human normal liver cells by treatment with 250 µmol/L FFAs for 24 h, and the effect of AAV-PTHrP on lipid deposition and viability of the cells were tested using Oil Red O and Nile red staining and CCK8 assay. RESULTS: Treatment with AAV-PTHrP, as compared with the control AVV vector, caused more rapid reduction of body weight in mice with MCD feeding and significantly increased the levels of AST (P < 0.05), ALT (P < 0.05), triglyceride (P < 0.01) and FFA (P < 0.05) in the liver and the scores of NAS (P < 0.01) and SAF (P < 0.05). HE and Oil red O staining of the liver tissue revealed obvious lipid deposition after MCD feeding, which was more serious in PTHrP group. In the cell experiment, FFAs induced steatosis in both mouse and human hepatocytes, and treatment with PTHrP increased the accumulation of lipid droplets and lowered the viability of the cell model of NAFLD (P < 0.01 or 0.05). CONCLUSION: PTHrP may aggravate MCD-induced NAFLD in mice by promoting the deposition of lipid droplets in the hepatocytes.

[The morphology and resilience change of upper airway in patients with OSAHS: A MSCT study].

Objective:To analyse the morphology and resilience of upper airway in patients with OSAHS using 128-slice MSCT. Method:CT imaging of the upper airway in 49 patients with OSAHS was acquired in two respiratory status (quiet respiration and Müller maneuver). The two-dimensional measurements of retropalatal and retroglossal regions, airway volume, and airway resilience were measured in patients with severe OSAHS and non-severe OSAHS. And the results were compared between those two groups. Result:① The following measurements during Müller maneuver were smaller than those during quiet respiration: the smallest cross section area of retropalatal and retroglossal region, the anteroposterior diameters(AP) and lateral diameters(L) of retropalatal region, L of retroglossal region, volume and average volume of upper airway and retropalatal area（P<0.01）.②The pharyngeal wall resilience of retropalata region was larger than those of retroglossal region in patients with severe OSAHS. The total resilience of retropalatal was larger than that of retroglossal region in patients with non-severe OSAHS. The pharyngeal wall resilience between severe and non-severe OSAHS had no significant difference. ③ L of retropalatal and retroglossal region, and average area of retropalatal region, were smaller in patients with severe OSAHS than those with non-severe OSAHS during Müller maneuver（P<0.05）.④ The cross-section of upper airway tend to be horizontal oval in retropalatal regions, and vertical oval in retroglossal regions. Conclusion:128-slice MSCT scan can achieve both positioning and quantitative analysis of the morphology and resilience changes of the upper airway in patients with OSAHS.

MTBDRplus results correlate with treatment outcome in previously treated tuberculosis patients.

BACKGROUND: Although MTBDRplus is validated for the detection of multidrug-resistant tuberculosis (MDR-TB), its role in the assessment of treatment outcome is less clear. We evaluated the association of MTBDRplus results with treatment outcome in new and previously treated patients in an endemic setting in China and determined factors associated with poor treatment outcomes. METHODS: We prospectively enrolled 298 smear-positive pulmonary TB patients who received the World Health Organization recommended initial treatment regimen or retreatment regimen. MTBDRplus was compared with conventional drug susceptibility testing and DNA sequencing for the detection of MDR-TB. Treatment responses were monitored using sputum smear, culture and chest radiography. RESULTS: MTBDRplus successfully identified all MDR-TB and had good concordance with sequencing. MDR-TB rates were low among new patients (4/187, 2.1%), but high in previously treated patients (12/28, 42.9%); 65.2% (15/23) of previously treated cases and 17.1% (27/158) of new cases were unsuccessfully treated (P < 0.001). Seven of eight (87.5%) previously treated MDR-TB patients failed the retreatment regimen. In addition to drug resistance, sputum smear positivity at week 8 and cavitation are associated with treatment failure. CONCLUSION: Not only did MTBDRplus correctly identify all MDR-TB cases, MTBDRplus results are also associated with treatment outcomes in previously treated patients. The retreatment regimen should no longer be used; treatment should be guided by molecular testing.

Evaluation of the GenoType® MTBDRplus assay and identification of a rare mutation for improving MDR-TB detection.

OBJECTIVE: To assess the new GenoType® MTBDRplus assay for the rapid detection of multidrug-resistant tuberculosis (MDR-TB) in comparison with DNA sequencing to identify drug resistance mutation profiles in China. DESIGN: Using MTBDRplus, drug susceptibility testing (DST) and DNA sequencing, 237 Mycobacterium tuberculosis strains were tested. RESULTS: The sensitivity of MTBDRplus was 75.0% (126/168) for isoniazid (INH) resistant strains, and 93.5% (157/168) for rifampicin (RMP) resistant strains. It correlated well with sequencing, with 94.9% and 99.6% agreement for each strain category and 100% specificity for all categories. The two most common rpoB mutations were S531L (53.6%, 90/168) and D516G (17.3%, 29/168) in RMP-resistant strains. INH resistance was dominated by the katG 315 locus (S to T, N, R, I) mutation (73.7%, 124/168), and a rare katG mutation, S315N (6.5%, 11/168), not covered by MTBDRplus was identified. The mutation combination inhA-15/inhA-8 and katG315 (34 strains) was characteristically displayed in MDR-TB strains (23.5%), but not in INH-monoresistant strains. CONCLUSIONS: Although Genotype MTBDRplus is a rapid and reliable molecular test for detecting MDR-TB, a significant proportion of strains in China contain a rare katG S315N mutation that would be missed by the assay. Further improvements may be achieved by incorporating this mutation into the assay to increase sensitivity in detecting INH resistance in China.