Unraveling the therapeutic mechanisms of dichloroacetic acid in lung cancer through integrated multi-omics approaches: metabolomics and transcriptomics.

Objective: The aim of this study was to investigate the molecular mechanisms underlying the therapeutic effects of dichloroacetic acid (DCA) in lung cancer by integrating multi-omics approaches, as the current understanding of DCA's role in cancer treatment remains insufficiently elucidated. Methods: We conducted a comprehensive analysis of publicly available RNA-seq and metabolomic datasets and established a subcutaneous xenograft model of lung cancer in BALB/c nude mice (n = 5 per group) treated with DCA (50 mg/kg, administered via intraperitoneal injection). Metabolomic profiling, gene expression analysis, and metabolite-gene interaction pathway analysis were employed to identify key pathways and molecular players involved in the response to DCA treatment. In vivo evaluation of DCA treatment on tumor growth and MIF gene expression was performed in the xenograft model. Results: Metabolomic profiling and gene expression analysis revealed significant alterations in metabolic pathways, including the Warburg effect and citric acid cycle, and identified the MIF gene as a potential therapeutic target in lung cancer. Our analysis indicated that DCA treatment led to a decrease in MIF gene expression and an increase in citric acid levels in the treatment group. Furthermore, we observed a potential interaction between citric acid and the MIF gene, suggesting a novel mechanism underlying the therapeutic effects of DCA in lung cancer. Conclusion: This study underscores the importance of integrated omics approaches in deciphering the complex molecular mechanisms of DCA treatment in lung cancer. The identification of key metabolic pathways and the novel finding of citric acid elevation, together with its interaction with the MIF gene, provide promising directions for the development of targeted therapeutic strategies and improving clinical outcomes for lung cancer patients.

The impact of alfentanil supplementation on the sedation of bronchoscopy: A meta-analysis of randomized controlled trials.

BACKGROUND: The efficacy of alfentanil supplementation for the sedation of bronchoscopy remains controversial. We conduct a systematic review and meta-analysis to explore the influence of alfentanil supplementation on the sedation during bronchoscopy. METHODS: We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through December 2019 for randomized controlled trials (RCTs) assessing the effect of alfentanil supplementation versus placebo for the sedation during bronchoscopy. This meta-analysis is performed using the random-effect model. RESULTS: Five RCTs are included in the meta-analysis. Overall, compared with control group for bronchoscopy, alfentanyl supplementation is associated with significantly reduced coughing scores (Std. MD = -0.55; 95% CI = -0.96 to -0.14; P = 0.009) and dose of propofol (Std. MD = -0.34; 95% CI = -0.64 to -0.04; P = 0.03), but reveals the increase in hypoxemia (RR = 1.56; 95% CI = 1.17 to 2.08; P = 0.002). CONCLUSIONS: Alfentanyl supplementation benefits to reduce coughing scores and dose of propofol for bronchoscopy, but increases the incidence of hypoxemia. The use of alfentanyl supplementation for bronchoscopy should be with caution.

The comparison of fluticasone propionate/formoterol with fluticasone propionate/salmeterol for paediatric asthma: a meta-analysis of randomized controlled trials.

INTRODUCTION: The comparison of fluticasone propionate/formoterol (FP/FORM) with fluticasone propionate/salmeterol (FP/SAL) for paediatric asthma remains controversial. AIM: We conduct a systematic review and meta-analysis to explore the efficacy and safety of FP/FORM versus FP/SAL for paediatric asthma. MATERIAL AND METHODS: We have searched PubMed, Embase, Web of science, EBSCO, and Cochrane library databases through August 2019 for randomized controlled trials (RCTs) assessing the effect of FP/FORM versus FP/SAL for paediatric asthma. This meta-analysis is performed using the random-effects model. RESULTS: Three RCTs are included in the meta-analysis. Overall for paediatric asthma, FP/FORM and FP/SAL demonstrate a comparable influence on FEVj (Std. MD = -0.01; 95% CI: -0.04 to 0.03; p = 0.62), FVC (Std. MD = 0; 95% CI: -0.07 to 0.06; p = 0.87), FEF25 (Std. MD = -1.69; 95% CI: -6.69 to 3.31; p = 0.51), FEF50 (Std. MD = 0.10; 95% CI: -0.12 to 0.33; p = 0.37), FEF75 (Std. MD = 0.01; 95% CI: -0.21 to 0.24; p = 0.91), asthma symptom scores (Std. MD = -0.03; 95% CI: -0.11 to 0.04; p = 0.43), sleep disturbance scores (Std. MD = 0.03; 95% CI: -0.19 to 0.24; p = 0.81) and adverse events (RR = 1.07; 95% CI: 0.83 to 1.38; p = 0.61). CONCLUSIONS: FP/FORM and FP/SAL show a comparable efficacy for paediatric asthma.

Clinical Impact of Metagenomic Next-Generation Sequencing of Bronchoalveolar Lavage in the Diagnosis and Management of Pneumonia: A Multicenter Prospective Observational Study.

Rapid and accurate pathogen identification is necessary for appropriate treatment of pneumonia. Here, we describe the use of shotgun metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage for pathogen identification in pneumonia in a large-scale multicenter prospective study with 159 patients enrolled. The results of mNGS were compared with standard methods including culture, staining, and targeted PCR, and the clinical impact of mNGS was evaluated. A positive impact was defined by a definitive diagnosis made using the mNGS results, or change of management because of the mNGS results, leading to a favorable clinical outcome. Overall, mNGS identified more organisms than standard methods (117 versus 72), detected 17 pathogens that consistently were missed in all cases by standard methods, and had an overall positive clinical impact in 40.3% (64 of 159) of cases. mNGS was especially useful in identification of fastidious and atypical organisms causing pneumonia, contributing to detection of definitive pathogens in 45 (28.3%) cases in which standard results were either negative or insufficient. mNGS also helped reassure antibiotic de-escalation in 19 (11.9%) cases. Overall, mNGS led to a change of treatment in 59 (37.1%) cases, including antibiotic de-escalation in 40 (25.2%) cases. This study showed the significant value of mNGS of bronchoalveolar lavage for improving the diagnosis of pneumonia and contributing to better patient care.

Efficacy and Safety of Vitamin D Supplementation for Pulmonary Tuberculosis: A Systematic Review and Meta-analysis.

BACKGROUND: Vitamin D might be promising to serve as an adjunctive therapy for pulmonary tuberculosis (TB). However, the results remained controversial. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of vitamin D in patients with pulmonary TB. METHODS: Medline, SCOPUS, Google Scholar, EMBASE, Springer, and Science Direct were searched electronically from inception to Oct 2016. Randomized controlled trials (RCTs) and controlled clinical trials (CCTs) assessing the effect of vitamin D plus anti-tuberculosis treatment (ATT) versus placebo plus ATT on the treatment of pulmonary TB were included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. Data were analyzed using RevMan 5.3 software. RESULTS: Five studies were included in this meta-analysis. Overall, compared with placebo intervention, vitamin D supplementation was found to have no significant effect on sputum smear negative conversion rates (RR=0.99; 95% CI=0.91 to 1.07; P=0.77), BMI (MD=0.11; 95% CI=-0.85 to 1.07; P=0.82) and ESR (MD=-2.29; 95% CI=-8.87 to 4.30; P=0.50). CONCLUSION: Vitamin D supplementation showed no influence on the improvement of sputum smear-negative conversion rates and BMI, as well as the decrease in ESR.

The influence of esmolol on septic shock and sepsis: A meta-analysis of randomized controlled studies.

BACKGROUND: Esmolol may have some potential in treating septic shock and sepsis. However, the results remain controversial. We conduct a systematic review and meta-analysis to explore the efficacy of esmolol in patients with septic shock and sepsis. METHODS: PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases are systematically searched. Randomized controlled trials (RCTs) assessing the efficacy of esmolol for septic shock and sepsis are included. Two investigators independently search articles, extract data, and assess the quality of included studies. Meta-analysis is performed using the random-effect model. RESULTS: Five RCTs are included in the meta-analysis. Overall, compared with control intervention in septic patients, esmolol intervention is found to significantly increase survival rate (risk ratio (RR)=2.06; 95% confidence interval (CI)=1.52 to 2.79; P=0.006), decrease heart rate (Standard Mean difference (Std. MD)=-2.43; 95% CI=-4.13 to -0.72; P=0.005) and TnI (Std. MD=-1.91; 95% CI=-2.39 to -1.43; P<0.00001), but has no significant impact on mean arterial pressure (MAP) (Std. MD=0.11; 95% CI=-0.21 to 0.44; P=0.49), central venous pressure (CVP) (Std. MD=-0.11; 95% CI=-0.50 to 0.28; P=0.58) and central venous oxygen saturation (ScvO2) (Std. MD=1.87; 95% CI=-1.53 to 5.26; P=0.28). CONCLUSIONS: Esmolol treatment may be able to improve survival rate, and reduce heart rate and TnI, but has no influence on MAP, CVP and ScvO2 in patients with septic shock and sepsis.

Adjunctive therapy with V-5 Immunitor (V5) for the treatment of tuberculosis patients: a meta-analysis.

OBJECTIVE: To evaluate the effectiveness and safety of V-5 immunitor (V5) added to chemotherapy of tuberculosis (TB) patients. METHODS: The databases Medline, Embase, Biosis, Cochrane Central Register of Controlled Trials, SCI, CBM, VIP and CNKI were searched. Randomized controlled trials (RCT) and controlled clinical trials (CCT) of V5 immunitor with or without a placebo-control as adjuvant therapy in the chemotherapy of TB patients were included. Two reviewers independently performed data extraction and quality assessment. Data were analyzed using RevMan 5.3 software by The Cochrane Collaboration. RESULTS: Four studies were included. At the end of the follow-up period, pooled RR (Risk Ratio) and its 95% CI of sputum smear conversion rate were 4.91 (3.32, 7.28) in drug-sensitive, drug-resistant TB patients or HIV-TB co-infection patients. When analyzing inflammation biomarkers including ESR and leukocyte accounts, pooled mean difference and its 95% CI of ESR and leukocyte accounts were -7.62 (-9.55, -5.68) and -2.13 (-2.58, -1.68), respectively. As to body weight, pooled mean difference and its 95% CI were 0.96 (-1.13, 3.05) in TB patients. Two clinical trials were included for analyzing temperature after using V5 immunitor, pooled mean difference and its 95% CI were -0.34 (-0.46, -0.22) in TB patients. These results suggested that V5 immunitor holds important promise in improving sputum conversion to AFB- and inhibiting inflammatory reaction in TB patients, but showed no significant promotion to the increase in body weight based on this meta-analysis. Compared with the control group, V5 immunitor may have some potential in decreasing the temperature of TB patients. No systemic adverse events were reported. CONCLUSION: Added to chemotherapy, V5 immunitor seems to be helpful in the treatment of TB patients in terms of improving sputum conversion and reducing inflammatory reactions.