BACKGROUND:Although cancer stem cells (CSCs) contribute to tumorigenesis, progression, and drug resistance, stemness-based classification and prognostic signatures of lung squamous cell carcinoma (LUSC) remain unclarified. This study attempted to identify stemness-based subtypes and develop a prognostic risk model for LUSC.METHODS:Based on RNA-seq data from The Cancer Genome Atlas (TCGA), Gene-Expression Omnibus (GEO) and Progenitor Cell Biology Consortium (PCBC), mRNA expression-based stemness index (mRNAsi) was calculated by one-class logistic regression (OCLR) algorithm. A weighted gene coexpression network (WGCNA) was employed to identify stemness subtypes. Differences in mutation, clinical characteristics, immune cell infiltration, and antitumor therapy responses were determined. We constructed a prognostic risk model, followed by validations in GEO cohort, pan-cancer and immunotherapy datasets.RESULTS:LUSC patients with subtype C2 had a better prognosis, manifested by higher mRNAsi, higher tumor protein 53 (TP53) and Titin (TTN) mutation frequencies, lower immune scores and decreased immune checkpoints. Patients with subtype C2 were more sensitive to Imatinib, Pyrimethamine, and Paclitaxel therapy, whereas those with subtype C1 were more sensitive to Sunitinib, Saracatinib, and Dasatinib. Moreover, we constructed stemness-based signatures using seven genes (BMI1, CCDC51, CTNS, EIF1AX, FAM43A, THBD, and TRIM68) and found high-risk patients had a poorer prognosis in the TCGA cohort. Similar results were found in the GEO cohort. We verified the good performance of risk scores in prognosis prediction and therapy responses.CONCLUSION:The stemness-based subtypes shed novel insights into the potential roles of LUSC-stemness in tumor heterogeneity, and our prognostic signatures offer a promising tool for prognosis prediction and guide therapeutic decisions in LUSC.
Objective The purpose of this review was to collate evidence on the prognostic ability of the geriatric nutritional risk index (GNRI) for predicting overall survival (OS) and disease-free survival (DFS) in non-small cell lung cancer (NSCLC). Methods The datasets of PubMed, Scopus, Embase, CENTRAL, and Google Scholar were searched up to 24 May 2022 for English-language studies reporting the association between GNRI and OS or DFS in NSCLC patients. Results Eleven studies with 2865 patients were included. We noted that low GNRI was a significant predictor of poor OS (HR: 1.96 95% CI 1.66, 2.30 I-2 = 0% p < 0.00001) and poor DFS (HR: 1.74 95% CI: 1.36, 2.23 I-2 = 34% p < 0.0001) in NSCLC patients. The results did not change on sensitivity analysis. There was no evidence of publication bias. Most results were significant on subgroup analysis based on study location, tumor stage, therapy type, sample size, and GNRI cut-off. Conclusion Data indicate that GNRI has good prognostic ability in patients with NSCLC. Individuals with low GNRI are at an increased risk of poor OS and DFS. GNRI could be incorporated as a simple, easy-to-use tool for the initial stratification of patients thereby allowing focused treatment plans.
Background: Acute respiratory distress syndrome is regarded as a formidable clinical challenge due to its high prevalence and mortality. The treatment of acute respiratory distress syndrome is very complex and difficult. As an adjuvant therapy, the antioxidant N-acetylcysteine has been investigated for several years but the benefit is controversial. Objectives: We performed the systematic review and meta-analysis of randomized controlled trials to evaluate the efficacy of N-acetylcysteine on patients with acute respiratory distress syndrome. Methods: We searched PubMed, CENTRAL, and CBM databases. Randomized controlled trials comparing the effects of N-acetylcysteine and control were included. Overall mortality was the primary outcome; length of intensive care unit stay, duration of mechanical ventilation, glutathione levels, and PaO2/FiO2 were the secondary outcomes. Results: Eight trials with a total of 289 patients were included. Compared to the control group, the N-acetylcysteine group did not lower the overall mortality (risk ratio: 0.83; 95% confidence interval: 0.62 to 1.11; P = 0.21; I2 = 0%). However, N-acetylcysteine significantly shortened intensive care unit stay in the random-effects model (mean difference: –4.47 days; 95% confidence interval: –8.79 to −0.14; P = 0.04; I2 = 46%). Due to substantial heterogeneity and limited number of studies, the data of duration of mechanical ventilation, glutathione levels, and PaO2/FiO2 could not be pooled in the meta-analysis. Conclusion: N-acetylcysteine is ineffective in reducing mortality but beneficial for intensive care unit stay. Nonetheless, the effectiveness of N-acetylcysteine for acute respiratory distress syndrome is limited and further research is required before strong recommendations can be made.
Objective To evaluate the efficacy and the safety of Ulinastatin in treatment of severe acute pancreatitis.Methods A systematic review of randomized controlled trials (RCT) of Ulinastatin treatmen for severe acute pancreatitis was performed.The databases included Cochrane library controlled clinical trials database,PUBMED,EMBASE,China Biology Medicine disc,Wanfang Data were searched to date.Retrieval words were acute pancreatitis and Ulinastatin.Statistical processing using Review Manager 5.3 software provided by the Cochrane collaboration network.Results A total of 33 trials involving 1 786 patients were included,and all patients of the trials were not followed up at the end of the treatment.In the trials of Ulinastatin plus routine treatment vs routine treatment or placebo plus routine treatment,and 5 trials reported the fatality rate.Meta-analysis showed that the mortality rate in Ulinastatin group was lower than that in control group(RR =0.29,95%CI:0.17-0.52,P < 0.01),and 16 trials used the total efficiency of treatment as outcome criteria.Meta-analysis results showed the total effective rate in the Ulinastatin group was significantly higher than that in control grouIn the trials of Ulinastatin plus routine treatment vs octreotide plus routine treatment,9 trials used the total efficiency of treatment as outcome criteria.Meta-analysis results showed there was no statistically significant difference in total effective rate between Ulinastatin group and octreotide group.Conclusions Ulinastatin treatment was superior to conventional therapy in improving the short-term clinical efficacy of severe acute pancreatitis,and the mortality rate was lower than that in conventional treatment.But no obvious advantage was found in ulinastatin treatment compared with octreotide treatment.
报道1例初诊为不稳定性心绞痛的老年抑郁症患者的诊治经过,分析双心医学在抑郁症患者中的应用.
通过1例以活动后胸闷为主要临床表现的酒精性心肌病患者的临床讨论,分析对于该类患者的全科管理理念以及良好生活习惯的重要意义.
Background The number of immunocompromised patients has increased in recent years. Acute respiratory failure is a common complication leading to intensive care unit (ICU) admission and high mortality among such patients. The use of non-invasive ventilation (NIV) or oxygen therapy among these patients remains controversial, according to the inconsistent results of several randomised clinical trials (RCTs). This meta-analysis aims to evaluate whether NIV or oxygen therapy is the more appropriate initial oxygenation strategy for the immunocompromised patients with acute respiratory failure. Method We will search all the RCTs that compared the efficacy of NIV and oxygen therapy on immunocompromised adult patients with acute hypoxaemic respiratory failure on the major databases (Cochrane Library, MEDLINE, EMBASE, Web of Science and others), conference proceedings and grey literature. Eligible RCTs will be included in accordance with the pre-specified eligibility criteria. The risk of bias will be assessed using the Cochrane Collaboration criteria and the quality of evidence will be assessed with the Grading of Recommendations Assessment, Development and Evaluation system. Data will be extracted with a standardised form and analysed using RevMan V.5.3 analyses software. Heterogeneity will be assessed using I 2 statistic and the source of which will be investigated. Publication bias will be identified with the funnel plot. Ethics and dissemination Ethical approval is not required since it is not carried out in humans. The systematic review will be published in peer-reviewed journals and disseminated extensively through conferences.
Background Acute respiratory failure (ARF) is still one of the most severe complications in immunocompromised patients. Our previous systematic review showed noninvasive mechanical ventilation (NIV) reduced mortality, length of hospitalization and ICU stay in AIDS/hematological malignancy patients with relatively less severe ARF, compared to invasive mechanical ventilation (IMV). However, this systematic review was based on 13 observational studies and the quality of evidence was low to moderate. The efficacy of NIV in more severe ARF and in patients with other causes of immunodeficiency is still unclear. We aim to determine the efficacy of the initial ventilation strategy in managing ARF in immunocompromised patients stratified by different disease severity and causes of immunodeficiency, and explore predictors for failure of NIV. Methods and analysis The VENIM is a multicentre randomized controlled trial (RCT) comparing the effects of NIV compared with IMV in adult immunocompromised patients with severe hypoxemic ARF. Patients who meet the indications for both forms of ventilatory support will be included. Primary outcome will be 30-day all-cause mortality. Secondary outcomes will include in-hospital mortality, length of stay in hospital, improvement of oxygenation, nosocomial infections, seven-day organ failure, adverse events of intervention, et al. Subgroups with different disease severity and causes of immunodeficiency will also be analyzed. Discussion VENIM is the first randomized controlled trial aiming at assessing the efficacy of initial ventilation strategy in treating moderate and severe acute respiratory failure in immunocompromised patients. The result of this RCT may help doctors with their ventilation decisions. Trial registration ClinicalTrials.gov NCT02983851 . Registered 2 September 2016.