IR808@MnO nano-near infrared fluorescent dye's diagnostic value for malignant pleural effusion.

BACKGROUND: Malignant pleural effusion is mostly a complication of advanced malignant tumors. However, the cancer markers such as carbohydrate antigen 125 (CA 125), carbohydrate antigen 15-3 (CA 15-3), carbohydrate antigen 19-9 (CA 19-9), and cytokeratin fragment 21-1 (CYFRA 21-1) have low sensitivity and organ specificity for detecting malignant pleural effusion. RESEARCH QUESTION: Is IR808@MnO nano-near infrared fluorescent dye worthy for the diagnosis in differentiating benign and malignant pleural effusions. STUDY DESIGN AND METHODS: This experiment was carried out to design and characterize the materials for in vitro validation of the new dye in malignant tumor cells in the A549 cell line and in patients with adenocarcinoma pleural effusion. The dye was verified to possess tumor- specific targeting capabilities. Subsequently, a prospective hospital-based observational study was conducted, enrolling 106 patients and excluding 28 patients with unknown diagnoses. All patients underwent histopathological analysis of thoracoscopic biopsies, exfoliative cytological analysis of pleural fluid, and analysis involving the new dye. Statistical analyses were performed using Microsoft Excel, GraphPad Prism, and the R language. RESULTS: The size of IR808@MnO was 136.8 ± 2.9 nm, with peak emission at 808 nm, and it has near-infrared fluorescence properties. Notably, there was a significant difference in fluorescence values between benign and malignant cell lines (p < 0.0001). The malignant cell lines tested comprised CL1-5, A549, MDA-MB-468, U-87MG, MKN-7, and Hela, while benign cell lines were BEAS-2B, HUVEC, HSF, and VE. The most effective duration of action was identified as 30 min at a concentration of 5 µl. This optimal duration of action and concentration were consistent in patients with lung adenocarcinoma accompanied by pleural effusion and 5 µl. Of the 106 patients examined, 28 remained undiagnosed, 39 were diagnosed with malignant pleural effusions, and the remaining 39 with benign pleural effusions. Employing the new IR808@MnO staining method, the sensitivity stood at 74.4%, specificity at 79.5%, a positive predictive value of 69.2%, and a negative predictive value of 82.1%. The area under the ROC curve was recorded as 0.762 (95% CI: 0.652-0.872). The confusion matrix revealed a positive predictive value of 75.7%, a negative predictive value of 75.6%, a false positive rate of 22.5%, and a false negative rate of 26.3%. INTERPRETATION: The IR808@MnO fluorescent probe represents an efficient, sensitive, and user-friendly diagnostic tool for detecting malignant pleural fluid, underscoring its significant potential for clinical adoption.

Disseminated Nocardia Infection in an Old Male Patient with Nephrotic Syndrome.

BACKGROUND: Nocardia infection is a very rare bacterial infection caused by Gram-positive, aerobic nocardia species. However, in recent years, it has become a serious infection in immunocompromised patients. Earlier diagnosis plays a pivotal in the effective treatment of nocardia infection. METHODS: In this study, we reported a 65-year-old male patient with nephrotic syndrome who had disseminated abscesses in the lungs, right lower limb, and right cheek. RESULTS: Bacterial culture from these lesions confirmed the presence of nocardia. Timely administration of sensitive antibiotics resulted in a quick recovery for this patient. CONCLUSIONS: Nocardia infection should be considered in the differential diagnosis of infectious lesions, especially when a patient has multiple abscesses and an underlying disorder in which the immune function of the patient may be compromised.

Causal association of immune effector proteins with sepsis: A Mendelian randomization study.

Sepsis is an infection-induced systemic inflammatory response syndrome. Immune regulation plays a crucial role in sepsis. We looked into the link between immune effector-related proteins and sepsis in this study by using both univariate and multivariate Mendelian randomization (MR) analyses. We accessed and collected data from the Integrative Epidemiology Unit's Open About Sepsis genome-wide association study database. The 6 immune effector-associated proteins each contained 10,534,735 single-nucleotide polymorphisms from 3301 samples. Using the weighted median, MR-Egger, simplex, inverse-variance weighting, and weighted mode methods, univariate MR then investigated the link between complement factor H-related protein-5 (CFHR5), Fc epsilon receptor II (FCER2), granzyme B (GZMB), major histocompatibility complex, class II, DQ alpha (HLA-DQA2), mannose-binding lectin 2 (MBL2), or myeloperoxidase (MPO) and sepsis. In the inverse-variance weighted results, the P values of all 6 immune effector-related proteins were <0.05, suggesting a possible causal relationship between them and sepsis. MBL2 (odds ratio [OR] = 1.046) was a risk factor for sepsis, while the other proteins (FCER2: OR = 0.922; GZMB: OR = 0.908; CFHR5: OR = 0.858; HLA-DQA2: OR = 0.896; MPO: OR = 0.875) were safety factors. By revealing a causal link between sepsis and CFHR5, FCER2, GZMB, HLA-DQA2, MBL2, or MPO, our study offers an essential resource for additional investigations on the subject.

Procyanidin B2 Suppresses Lipopolysaccharides-Induced Inflammation and Apoptosis in Human Type II Alveolar Epithelial Cells and Lung Fibroblasts.

Acute lung injury (ALI) is characterized by acute lung inflammation and apoptosis of alveolar epithelial cells (AECs) with a high morbidity and mortality. Procyanidin B2 (PCB2) is a naturally occurring flavonoid with anti-inflammatory activity. Our previous study demonstrated that PCB2 inhibited NLRP3 inflammasome signaling and ameliorated paraquat-induced ALI in rat, indicating the protective role of PCB2. As lipopolysaccharide (LPS) induced acute cell injury and dysfunction, we continued to evaluate the protective effects of PCB2 using LPS-treated human AECs and lung fibroblasts (LFs) model. We tested the effects of PCB2 on cell permeability, viability, apoptosis, nuclear factor-kappaB (NF-κB) activation, NLRP3 inflammasome activation, and proinflammatory cytokines production in LPS-treated human AECs and LFs. PCB2 prevented LPS-induced cell apoptosis, and increased the cell viability in LPS-treated human AECs and LFs. PCB2 inhibited LPS-induced Bax and active caspase-3 expression, and promoted Bcl-2 expression. PCB2 prevented LPS-induced tumor necrosis factor-α, interleukin-1ß expression, NF-κB activation, and NLRP3 inflammasome activation. PCB2 suppressed LPS-induced inflammation and apoptosis in human AECs and LFs by inhibiting NF-κB and NLRP3 inflammasome.

Abnormal Static and Dynamic Local-Neural Activity in COPD and Its Relationship With Pulmonary Function and Cognitive Impairments.

Patients with chronic obstructive pulmonary disease (COPD) are characterized by attenuated pulmonary function and are frequently reported with cognitive impairments, especially memory impairments. The mechanism underlying the memory impairments still remains unclear. We applied resting-state functional magnetic resonance imaging (RS-fMRI) to compare the brain local activities with static and dynamic amplitude of low-frequency fluctuations (sALFF, dALFF) among patients with COPD (n = 32) and healthy controls (HC, n = 30). Compared with HC, COPD patients exhibited decreased sALFF in the right basal ganglia and increased dALFF in the bilateral parahippocampal/hippocampal gyrus. The reduced the left basal ganglia was associated with lower oxygen partial pressure. Besides, the increased dALFF in the left hippocampal/parahippocampal cortex was associated with poor semantic-memory performance and the increased dALFF in the left hippocampal/parahippocampal cortex was associated the forced vital capacity. The present study revealed the abnormal static and dynamic local-neural activities in the basal ganglia and parahippocampal/hippocampal cortex in COPD patient and its relationship with poor lung function and semantic-memory impairments.

Procyanidin B2 protects rats from paraquat-induced acute lung injury by inhibiting NLRP3 inflammasome activation.

Paraquat is a commonly used heterocyclic herbicide and has high toxicity by causing acute lung injury. There is no effective treatment for paraquat poisoning. We evaluated the effects of procyanidin B2, a natural dietary phytochemical, on paraquat-induced lung injury in rats. Paraquat was used to induce acute lung injury of rats, which were administered with procyanidin B2. The lung injury was evaluated by measuring the lung/body weight ratio, the histology and PMNs count. The oxidative stress was assessed by detecting ROS-mediated indices in the BALF. The expression of IL-1ß and IL-18 were detected by RT-PCR and ELISA. The levels of NLRP3 inflammasome components including NLRP3, ASC and caspase-1 were detected by western blot. The lung injury in the paraquat-induced models in NLRP3 gene silenced animals was compared with the same lung injury model treated with procyanidin B2. Administration of procyanidin B2 significantly reduced paraquat-induced lung injury with lower BALF PMNs count, MPO activity, MDA level and elevated SOD activity. Procyanidin B2 suppressed expression of IL-1ß and IL-18 at both RNA and protein levels, similar to the NLRP3 gene silenced rats. Compared to paraquat-induced group, procyanidin B2 showed remarkably decreased NLRP3, ASC and caspase-1 signals in the lung tissues in a dose-dependent manner. Procyanidin B2 significantly suppressed the activation of NLRP3 inflammasome in the lung tissue induced by paraquat in the rat model. This finding revealed a novel mechanism by which procyanidin B2 exerts anti-inflammatory effects and their clinical benefits in health.

[Effects of EGFR-TKIs on sequential pemetrexed
for advanced pulmonary adenocarcinoma].

BACKGROUND AND OBJECTIVE: Pemetrexed and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) were used in patients with EGFR mutation to determine their effects. This study analyzed the influence of EGFR-TKIs on pemetrexed by observing the clinical efficacy and toxicity of pemetrexed following responses to EGFR-TKIs. METHODS: Pulmonary adenocarcinoma patients were divided into EGFR-TKIs and no-EGFR-TKI groups according to the targeted therapy. All patients received pemetrexed (500 mg/m2) as second (or higher)-line treatment. The Response Evaluation Criteria in Solid Tumors (version 1.0) were used to evaluate the response to pemetrexed. Adverse events were classified based on version 4.0 of the National Cancer Institute Common Toxicity Criteria. RESULTS: There were 57 patients in the EGFR-TKIs group and 56 in the no-EGFR-TKIs group. The disease control rates (DCRs) were 77.2% and 67.9% (P=0.367). The progression free survival (PFS) periods were 5.95 and 3.55 months (P=0.535). The overall survival (OS) periods were 10.10 and 8.24 months (P=0.432). However, these values were not statistically significant. The common toxicities of pemetrexed were hematologic and gastrointestinal (grades I and II). Two patients in the EGFR-TKIs group discontinued pemetrexed because of severe toxicities, which were not observed in the no-EGFR-TKIs group. Both groups had one patient who reduced dosage because of myelosuppression (grade IV). There were five and nine patients in the EGFR-TKIs and no-EGFR-TKIs groups, respectively, who delayed therapy not because of severe toxicities but due to subjective factors. CONCLUSION: The DCRs, PFS periods, and OS periods of the patients administered with pemetrexed following EGFR-TKIs were better than those of the EGFR-TKIs group, but the differences were not statistically significant. Therefore, sequential pemetrexed administration caused negligible toxicities and can be used in adenocarcinoma therapy following responses to EGFR-TKIs.

[Preliminary results of metabolite in serum and urine of lung cancer patients detected by metabolomics].

BACKGROUND AND OBJECTIVE: Lung cancer is one of the most common cancers worldwide. Thus far, good tumor markers for diagnosing this disease have not been found. Therefore, the discovery of novel biomarkers through the application of new methods has become a hotspot in lung cancer research. The aim of this study is to analyze low-molecular-weight metabolites in the serum and urine samples of lung cancer patients and patients with other lung diseases through metabolomics and to explore potential tumor markers further. METHODS: Both serum and urine samples from 19 lung cancer patients and 15 patients with other lung diseases were subjected to metabolomic analysis using gas chromatography mass spectrometry. Orthogonal to partial least squares discriminant analysis was performed for modeling. Two sample t-test was used to identify differences in metabolite concentrations. RESULTS: A total of 57 metabolites were found in the serum, and 38 metabolites were found in the urine. Multivariate statistical analysis yielded a significant distinction in the metabolic profiles between lung cancer patients and patients with other lung diseases. The t-test results indicated a total of 13 metabolites in the serum and 7 metabolites in the urine with statistically significant differences. CONCLUSIONS: Metabolomics is useful in discriminating between lung cancer and other lung diseases. As a novel approach, it has potential in the diagnosis of lung cancer at molecular level.

[Pemetrexed alone versus pemetrexed combined with oxaliplatin as salvage therapy in stage IV lung adenocarcinoma].

BACKGROUND AND OBJECTIVE: At present, there is no standard salvage treatment strategies for lung cancer. The aim of this study is to compare the efficacies and safeties of pemetrexed alone with pemetrexed combined with oxaliplatin as salvage therapy in stage IV lung adenocarcinoma to provide evidences for combination therapy. METHODS: From January 2009 to February 2011, 83 patients with stage IV lung adenocarcinoma received pemetrexed alone (single agent arm, n=47) or pemetrexed combined with oxaliplatin (combination arm, n=36) as salvage therapy. All 83 patients had performance status (PS) scores of 0-2. RESULTS: Eighty-one patients were included in the final analysis. The median progression-free survival (PFS) in the single agent arm was 3.6 months versus 4.1 months in the combination arm (P=0.268). The objective response rate (ORR) was 6.5% versus 20% (P=0.092), and the disease control rate (DCR) was 56.5% versus 65.7% (P=0.493), respectively. The response rates of the hematological and gastrointestinal toxicities in the single agent and combination arms were 33.9% versus 47.2% (P=0.460) and 21.2% versus 25.0% (P=0.213), respectively. CONCLUSIONS: For salvage therapy, pemetrexed combined with oxaliplatin is tolerable in stage IV lung adenocarcinoma patients with good PS scores. Compared with pemetrexed alone, pemetrexed combined with oxaliplatin therapy showed higher response rate, but did not significantly prolong the PFS.