miR-145 as a Potential Biomarker and Therapeutic Target in Patients with Non-Small Cell Lung Cancer.

Our previous study found that miR-145 was downregulated in non-small cell lung cancer (NSCLC) tissues and that it could inhibit the cell proliferation in transfected NSCLC cells. In this study, we found that miR-145 was downregulated in NSCLC plasma samples compared to healthy controls. A receiver operating characteristic curve analysis indicated that plasma miR-145 expression was correlated with NSCLC in patient samples. We further revealed that the transfection of miR-145 inhibited the proliferation, migration, and invasion of NSCLC cells. Most importantly, miR-145 significantly delayed the tumor growth in a mouse model of NSCLC. We further identified GOLM1 and RTKN as the direct targets of miR-145. A cohort of paired tumors and adjacent non-malignant lung tissues from NSCLC patients was used to confirm the downregulated expression and diagnostic value of miR-145. The results were highly consistent between our plasma and tissue cohorts, confirming the clinical value of miR-145 in different sample groups. In addition, we also validated the expressions of miR-145, GOLM1, and RTKN using the TCGA database. Our findings suggested that miR-145 is a regulator of NSCLC and it plays an important role in NSCLC progression. This microRNA and its gene targets may serve as potential biomarkers and novel molecular therapeutic targets in NSCLC patients.

Effects of diabetes mellitus on the clinical presentation and treatment response in tuberculosis.

BACKGROUND AND OBJECTIVE: With the colliding global epidemics of diabetes mellitus (DM) and tuberculosis (TB), we studied the effects of DM on the presentation of TB and its response to treatment. METHODS: Consecutive TB patients from 2006 to 2010 in a territory-wide treatment programme offering 9-month extended treatment for TB patients with DM were examined and followed up prospectively to assess their treatment response. Successful treatment completers were tracked through the TB registry and death registry for relapse, death or till 31 December 2014, whichever was the earliest. RESULTS: DM was independently associated with more chest symptoms (adjusted OR (AOR): 1.13) and systemic symptoms (AOR: 1.30) but less with other site-specific symptoms (AOR: 0.58) at TB presentation. There was more frequent pulmonary involvement (AOR: 1.69), with more extensive lung lesion (AOR: 1.25), lung cavity (AOR: 2.00) and positive sputum smear (AOR: 1.83) and culture (AOR: 1.38), but no difference in the proportion of retreatment cases or isoniazid and/or rifampicin resistance. After treatment initiation, there was higher overall incidence (AOR: 1.38) of adverse effects (mainly gastrointestinal symptoms, renal impairment and peripheral neuropathy but less fever and skin hypersensitivity reactions), more smear non-conversion (AOR: 1.59) and culture non-conversion (AOR: 1.40) at 2 months, and lower combined cure/treatment completion rate at 12 months (AOR: 0.79), but no difference in the relapse rate after having successfully completed treatment. CONCLUSION: DM adversely affected the clinical presentation and treatment response of TB, but there was no difference in the drug resistance and relapse rates.

The hemodynamic characteristics of severe chronic lung disease referred for lung transplantation.

Severe pulmonary hypertension (PH) is not common even in patients with severe chronic lung disease (CLD) but data on hemodynamic characteristics among patients with severe CLD is scarce. All adult patients who had right heart catheterization for lung transplant assessment for severe CLD in the only lung transplant service and for PAH management in the only tertiary pulmonary hypertension service in Hong Kong from 2010 to 2020 were included and classified into CLD group and PAH group. Patient characteristics and hemodynamic parameters were analyzed. There were 153 patients included with 106 patients in the CLD group and 47 in the PAH group. There were only 19.8% of the patients in the CLD group had severe pulmonary hypertension. Patients in the CLD group had significantly lower systolic pulmonary arterial pressure (PAPs), lower mean pulmonary arterial pressure (PAPm), higher cardiac index, and lower PVR when compared with the PAH group (p < 0.001). The area under curve (AUC) of PAPs, PAPm, and PVR were excellent, 0.973, 0.970, and 0.938, respectively for discrimination between CLD and PAH on receiver operator characteristics curve analysis. Optimal cutoff values were 55.5 mmHg, 35.5 mmHg, and 6.1 Wood Units for PAPs, PAPm, and PVR with Youden Index 0.85, 0.80, and 0.82, respectively. There were distinct hemodynamic characteristics between the CLD group and the PAH group. Systolic pulmonary arterial pressure, mean pulmonary arterial pressure, and pulmonary vascular resistance are useful to discriminate between the phenotype of severe CLD and PAH.

Severe acute respiratory syndrome: radiographic evaluation and clinical outcome measures.

PURPOSE: To evaluate the relationship among chest radiographs, oxygen supplementation requirement, and treatment response in severe acute respiratory syndrome (SARS). MATERIALS AND METHODS: Forty patients (20 women, 20 men; mean age, 42.90 years +/- 14.01 [SD]; median age, 41.5 years; age range, 25-82 years) with SARS were evaluated. Daily chest radiographs were graded according to percentage of lung involvement during 20.15 days +/- 5.56 (median, 20 days; range, 14-38 days). Times between symptoms and treatment and time to reach maximal radiographic score from admission and treatment day were determined. Daily oxygen saturation (Sao2) and oxygen supplementation including mechanically assisted ventilation were recorded. Treatment response was defined as good, fair, and poor. Patterns of radiographic opacity at admission and at maximal radiographic score were noted. Differences in radiographic and clinical parameters with respect to oxygen supplementation and treatment response were respectively evaluated with Mann-Whitney and Kruskal-Wallis tests. RESULTS: Larger maximal radiographic scores, lower Sao2 at maximal radiographic change, longer time from treatment to maximal radiographic score (P <.01), and diffuse consolidation at maximal radiographic score were associated with oxygen supplementation. Parameters that influenced treatment response were time from symptom onset to treatment day (P =.003), time from admission to treatment day (P <.001), time to maximal radiographic score from treatment day (P =.001), maximal radiographic score (P =.009), Sao2 at maximal radiographic score (P =.13), and treatment radiographic score (P =.03). Fair responders had shorter time between admission and treatment than did either good (P <.001) or poor responders (P =.002) and shorter time between symptoms and treatment (P <.001) and lower treatment radiographic score (P =.012) than did good responders. Good (82%), poor (36%), and fair (33%) responders developed maximal chest radiographic scores within 4 days of treatment (P =.008). Radiographic patterns at both admission and maximal radiographic score did not influence treatment response. CONCLUSION: There are significant relationships among radiographic parameters, oxygen supplementation, and treatment response, and these relationships appear to be clinically useful in the treatment of SARS.