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Background The elderly are at high risk for acute pulmonary embolism (APE) , and the difficulty of early identification and diagnosis of APE in the elderly has made the active search for an optimal prediction method for elderly patients with suspected APE a medical problem that must be faced. Objective To investigate the predictive value of the 4-level Clinical Pretest Probability Score (4PEPS) for pulmonary embolism (PE) in elderly patients with suspected APE. Methods Basic information and related clinical data were collected from elderly (age≥60 years) hospitalized patients who completed spiral CT pulmonary arteriography (CTPA) examinations in the Third Affiliated Hospital of Zunyi Medical University from 2017 to 2021. The study subjects were divided into the APE group and non-APE group according to the CTPA criteria for the diagnosis of PE in 2018 Guidelines for the Diagnosis, Treatment and Prevention of Pulmonary Thromboembolism. The 4PEPS, Standard algorithm, age-adjusted D-dimer (AADD) algorithm, YEARS algorithm and pulmonary embolism graduated D-dimer (PEGeD) algorithm were used to predict the APE of the study subjects, respectively, who were divided into the positive and negative groups, and the number of true positives, true negatives, false positives and false negatives of each prediction method was counted. The efficacy evaluation indexes of the five prediction method were calculated and their prediction values were compared. Results Among 1 193 elderly hospitalized patients who completed CTPA examination, 608 (50.96%) were male and 585 (49.04%) were female, with a median age of 74 (68, 81) years; 323 (27.07%) were APE patients and 870 (72.93%) were non-APE patients; there was no statistically significant difference between elderly APE patients and elderly non-APE patients in terms of gender and age (P>0.05) . 4PEPS, AADD algorithm, Standard algorithm, YEARS algorithm and PEGeD algorithm for elderly patients with suspected APE had a sensitivity of 95.05%, 97.83%, 98.76%, 97.21%, 97.83%, the specificity of 31.84%, 18.16%, 12.87%, 22.41%, 22.41%, the correctness of 48.95%, 39.73%, 36.13%, 42.67%, 42.83%, Youden index of 0.27, 0.16, 0.12, 0.20, 0.20. The net reclassification improvement (NRI) of 4PEPS, Standard algorithm, YEARS algorithm and PEGeD algorithm compared to AADD algorithm were 0.218, -0.087, 0.073, and 0.085, the difference of the NRI of 4PEPS compared to AADD algorithm was statistically significant (P

Objective To investigate the effect of endotracheal suctioning method using suctioning sputum with suctioning salivary tube in patients with craniocerebral injury undergoing tracheotomy. Methods A randomized controlled trial was conducted in 106 patients with traumatic brain injury after tracheotomy who met the inclusion criteria. According to the random number table method, they were divided into two groups, with 53 cases in each group. The experimental group was treated with endotracheal suctioning method using sputum suction tube combined with sputum suction tube, while the control group was treated with routine sputum suction method using sputum suction tube . The secretion severity grade under electronic laryngoscope swallowing function assessment (FEES) before and after sputum aspiration was compared between the two groups. The number of sputum aspiration, blood oxygen saturation and heart rate changes at 1 minute before and after sputum aspiration were observed in the two groups at 1, 3 and 7 days after admission. The mucosal damage under electronic hose bronchoscopy was observed in the two groups at 1, 3 and 7 days after admission. Results The severity of FEES was significantly lower in the experimental group than in the control group (P

As a kind of proteolytic enzyme extracted from earthworms, lumbrokinase has been used as an antithrombotic drug clinically. Nevertheless, its potential in anti-cancer, especially in anti-non-small cell lung cancer (NSCLC), as a single form of treatment or in combination with other therapies, is still poorly understood. In this study, we explored the anti-tumor role and the responsive molecular mechanisms of lumbrokinase in suppressing tumor angiogenesis and chemoresistance development in NSCLC and its clinical potential in combination with bevacizumab and chemotherapeutics. Lumbrokinase was found to inhibit cell proliferation in a concentration-dependent manner and caused metastasis suppression and apoptosis induction to varying degrees in NSCLC cells. Lumbrokinase enhanced the anti-angiogenesis efficiency of bevacizumab by down-regulating BPTF expression, decreasing its anchoring at the VEGF promoter region and subsequent VEGF expression and secretion. Furthermore, lumbrokinase treatment reduced IC50 values of chemotherapeutics and improved their cytotoxicity in parental and chemo-resistant NSCLC cells via inactivating the NF-κB pathway, inhibiting the expression of COX-2 and subsequent secretion of PGE2. LPS-induced NF-κB activation reversed its inhibition on NSCLC cell proliferation and its synergy with chemotherapeutic cytotoxicity, while COX-2 inhibitor celecoxib treatment boosted such effects. Lumbrokinase combined with bevacizumab, paclitaxel, or vincristine inhibited the xenograft growth of NSCLC cells in mice more significantly than a single treatment. In conclusion, lumbrokinase inhibited NSCLC survival and sensitized NSCLC cells to bevacizumab or chemotherapeutics treatment by targeted down-regulation of BPTF/VEGF signaling and inactivation of NF-κB/COX-2 signaling, respectively. The combinational applications of lumbrokinase with bevacizumab or chemotherapeutics are expected to be developed as promising candidate therapeutic strategies to improve the efficacy of the original monotherapy in anti-NSCLC. [ABSTRACT FROM AUTHOR]

BPTF, a subunit of NURF, is well known to be involved in the development of eukaryotic cell, but little is known about its roles in cancers, especially in non-small-cell lung cancer (NSCLC). Here we showed that BPTF was specifically overexpressed in NSCLC cell lines and lung adenocarcinoma tissues. Knockdown of BPTF by siRNA significantly inhibited cell proliferation, induced cell apoptosis and arrested cell cycle progress from G1 to S phase. We also found that BPTF knockdown downregulated the expression of the phosphorylated Erk1/2, PI3K and Akt proteins and induced the cleavage of caspase-8, caspase-7 and PARP proteins, thereby inhibiting the MAPK and PI3K/AKT signaling and activating apoptotic pathway. BPTF knockdown by siRNA also upregulated the cell cycle inhibitors such as p21 and p18 but inhibited the expression of cyclin D, phospho-Rb and phospho-cdc2 in lung cancer cells. Moreover, BPTF knockdown by its specific shRNA inhibited lung cancer growth in vivo in the xenografts of A549 cells accompanied by the suppression of VEGF, p-Erk and p-Akt expression. Immunohistochemical assay for tumor tissue microarrays of lung tumor tissues showed that BPTF overexpression predicted a poor prognosis in the patients with lung adenocarcinomas. Therefore, our data indicate that BPTF plays an essential role in cell growth and survival by targeting multiply signaling pathways in human lung cancers.

Cyclooxygenase-2 (COX-2) plays an important role in lung cancer development and progression. Using streptavidin-agarose pulldown and proteomics assay, we identified and validated Ku80, a dimer of Ku participating in the repair of broken DNA double strands, as a new binding protein of the COX-2 gene promoter. Overexpression of Ku80 up-regulated COX-2 promoter activation and COX-2 expression in lung cancer cells. Silencing of Ku80 by siRNA down-regulated COX-2 expression and inhibited tumor cell growth in vitro and in a xenograft mouse model. Ku80 knockdown suppressed phosphorylation of ERK, resulting in an inactivation of the MAPK pathway. Moreover, CBP, a transcription co-activator, interacted with and acetylated Ku80 to co-regulate the activation of COX-2 promoter. Overexpression of CBP increased Ku80 acetylation, thereby promoting COX-2 expression and cell growth. Suppression of CBP by a CBP-specific inhibitor or siRNA inhibited COX-2 expression as well as tumor cell growth. Tissue microarray immunohistochemical analysis of lung adenocarcinomas revealed a strong positive correlation between levels of Ku80 and COX-2 and clinicopathologic variables. Overexpression of Ku80 was associated with poor prognosis in patients with lung cancers. We conclude that Ku80 promotes COX-2 expression and tumor growth and is a potential therapeutic target in lung cancer.