Association between number of dissected lymph nodes and survival in patients undergoing resection for clinical stage IA pure solid lung adenocarcinoma: a retrospective analysis.

BACKGROUND: Lymph node dissection is essential for staging of pure solid lung adenocarcinoma and selection of treatment after surgical resection, particularly for stage I disease since the rate of lymph node metastasis can vary from 0 to 23.7%. METHODS: We retrospectively screened all adult patients (18 years of age or older) who underwent lobectomy for pure solid cT1N0M0 lung adenocarcinoma between January 2015 and December 2017 at our center. Cox proportional hazard regression was used to assess the association between the number of dissected lymph nodes and recurrence-free survival (RFS) and to determine the optimal number of dissected lymph nodes. RESULTS: The final analysis included 458 patients (age: 60.26 ± 8.07 years; 241 women). RFS increased linearly with an increasing number of dissected lymph nodes at a range between 0 and 9. Kaplan-Meier analysis revealed significantly longer RFS in patients with ≥ 9 vs. <9 dissected lymph nodes. In subgroup analysis, ≥ 9 dissected lymph nodes was not only associated with longer RFS in patients without lymph node metastasis (n = 332) but also in patients with metastasis (n = 126). In multivariate Cox proportional hazard regression, ≥ 9 dissected lymph nodes was independently associated with longer RFS (hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.26 to 0.73; P = 0.002). CONCLUSIONS: ≥9 Dissected lymph nodes was associated with longer RFS; accordingly, we recommend dissecting 9 lymph nodes in patients undergoing lobectomy for stage IA pure solid lung adenocarcinoma.

Adjuvant EGFR-TKI therapy in resected EGFR-mutation positive non-small cell lung cancer: A real-world study.

Background: Although several clinical studies have laid the foundation for the adjuvant application of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), some questions remain unresolved. This real-world study aimed to address questions such as the effect of adjuvant chemotherapy prior to adjuvant EGFR-TKI therapy on survival outcomes, and the duration of adjuvant EGFR-TKI therapy, etc. Methods: Between October 2005 and October 2020, 227 consecutive patients with non-small cell lung cancer (NSCLC) who underwent complete pulmonary resections were included in this retrospective study. Patients received postoperative adjuvant chemotherapy followed by EGFR-TKI or adjuvant EGFR-TKI monotherapy. The disease-free survival (DFS) and overall survival (OS) were evaluated. Results: Of the total 227 patients, 55 (24.2%) patients underwent 3-4 cycles of chemotherapy prior to receiving adjuvant EGFR-TKI therapy. The 5-year DFS rate was 67.8%, while the 5-year OS rate was 76.4%. The stages were significantly associated with both DFS (P<0.001) and OS (P<0.001), while no significant differences were observed in the DFS (P=0.093) and OS (P=0.399) between the adjuvant chemotherapy followed by EGFR-TKI and adjuvant EGFR-TKI monotherapy groups. A longer duration of EGFR-TKI therapy was associated with better DFS (P<0.001) and OS (P<0.001) benefit. Additionally, pTNM stage and duration of EGFR-TKI therapy were considered independent prognostic factors for long-term survival (All P<0.05). Conclusions: This study supports the use of EGFR-TKI as a postoperative adjuvant treatment for patients with stage II-IIIA EGFR-mutation positive NSCLC. Additionally, patients with stage I who had pathological risk factors were also suitable for receiving adjuvant EGFR-TKI therapy. Postoperative EGFR-TKI based, chemotherapy-free adjuvant regimen may be a potential therapeutic option for patients with EGFR-mutation positive NSCLC.

Morin exerts protective effects on encephalopathy and sepsis-associated cognitive functions in a murine sepsis model.

Sepsis-associated encephalopathy (SAE) often leads to cognitive impairments in the rest life of septic survivors. The potential pathological changes of SAE are complicated and have not been fully understood. Morin, a flavone compound exhibiting neuroprotective activity and anti-inflammation effect, was employed to treat with CLP-induced septic mice in our study. The data from a novel object recognition test and tail suspension test indicated that morin treatment reversed cognitive dysfunction and relieved depressive-like behaviors in septic mice. Morin down-regulated the expressions of IL-6, MCP-1, TNF-α and IL-10 in serum and diminished microglia activation in septic mice. Additionally, Western blot results showed that morin reduced the phosphokinase GSK3ß activity and elevated the phosphatase PP2A activity, which led to lower tau phosphorylation. Morin reduced Aß deposition and protected the synapse integrity, which might be the possible mechanism of protecting cognitive functions in septic mice. In conclusion, we identified that morin exerted anti-inflammation and anti-neurodegeneration effects in septic mice, and prevented further cognitive impairments.

Caspase-1 inhibitor exerts brain-protective effects against sepsis-associated encephalopathy and cognitive impairments in a mouse model of sepsis.

Sepsis-associated encephalopathy (SAE) manifested clinically in acute and long-term cognitive impairments and associated with increased morbidity and mortality worldwide. The potential pathological changes of SAE are complex and remain to be elucidated. Pyroptosis, a novel programmed cell death, is executed by caspase-1-cleaved GSDMD N-terminal (GSDMD-NT) and we investigated it in peripheral blood immunocytes of septic patients previously. Here, a caspase-1 inhibitor VX765 was treated with CLP-induced septic mice. Novel object recognition test indicated that VX765 treatment reversed cognitive dysfunction in septic mice. Elevated plus maze, tail suspension test and open field test revealed that depressive-like behaviors of septic mice were relieved. Inhibited caspase-1 suppressed the expressions of GSDMD and its cleavage form GSDMD-NT, and reduced pyroptosis in brain at day 1 and day 7 after sepsis. Meantime, inhibited caspase-1 mitigated the expressions of IL-1ß, MCP-1 and TNF-α in serum and brain, diminished microglia activation in septic mice, and reduced sepsis-induced brain-blood barrier disruption and ultrastructure damages in brain as well. Inhibited caspase-1 protected the synapse plasticity and preserved long-term potential, which may be the possible mechanism of cognitive functions protective effects of septic mice. In conclusion, caspase-1 inhibition exerts brain-protective effects against SAE and cognitive impairments in a mouse model of sepsis.

Dihydromyricetin Alleviates Sepsis-Induced Acute Lung Injury through Inhibiting NLRP3 Inflammasome-Dependent Pyroptosis in Mice Model.

Increasing evidence demonstrates that pyroptosis, pro-inflammatory programmed cell death, is linked to acute lung injury (ALI). Dihydromyricetin (DHM) has been reported to exert anti-inflammatory effects by inhibiting NLRP3 inflammasome activation in vascular endothelial cells. However, the effects of DHM on NLRP3 inflammasome-induced pyroptosis in ALI remain elusive. In the present study, male BALB/c mice were subjected to cecal ligation and puncture (CLP), and DHM (50, 100, 150 mg/kg) was orally administered (once per day, for 3 days) 2 h after CLP. After 72 h, lung histopathology was examined, and the wet/dry (W/D) ratio, inflammatory infiltration, total protein concentration, total cell, and neutrophil counts were detected. Myeloperoxidase (MPO), interleukin (IL)-6, TNF-α, IL-1ß, and IL-18 levels in bronchoalveolar lavage fluid (BALF) were measured by ELISA. Additionally, the expression of NLRP3 signaling pathway proteins were detected by Western blotting. The results revealed that in BALF, DHM (150 mg/kg) treatment significantly reduced the CLP-induced lung histopathological injury, inflammatory cell infiltration, total cell and neutrophil number, and total protein and albumin concentration. DHM treatment significantly inhibited the CLP-induced NLRP3 inflammasome pathway (NLRP3, ASC, caspase-1, gasdermin D (Gsdmd), IL-1ß, and IL-18). In conclusion, these results demonstrate that DHM protects against CLP-induced ALI by inhibiting NLRP3 inflammasome activation and subsequent pyroptosis.

Early plasma monocyte chemoattractant protein 1 predicts the development of sepsis in trauma patients: A prospective observational study.

Monocyte chemoattractant protein 1 (MCP-1) is an initiating cytokine of the inflammatory cascade. Extracellular MCP-1 exhibits pro-inflammatory characteristic and plays a central pathogenic role in critical illness. The purpose of the study was to identify the association between plasma MCP-1 levels and the development of sepsis after severe trauma.The plasma levels of MCP-1 in severe trauma patients were measured by a quantitative enzyme-linked immune sorbent assay and the dynamic release patterns were recorded at three time points during seven days post-trauma. The related factors of prognosis were compared between sepsis and non-sepsis groups and analyzed using multivariate logistic regression analysis. We also used receiver operating characteristic (ROC) curves to assess the values of different variables in predicting sepsis.A total of 72 patients who met criteria indicative of severe trauma (72.22% of male; mean age, 49.40 ±â€Š14.29 years) were enrolled. Plasma MCP-1 concentrations significantly increased on post-trauma day 1 and that this increase was significantly correlated with the Injury Severity Score (ISS) and interleukin-6 (IL-6). Multivariate logistic regression analysis showed that early MCP-1, ISS, and IL-6 were independent risk factors for sepsis in severe trauma patients. Incorporation of the early MCP-1 into the ISS can increase the discriminative performance for predicting development of sepsis.Early plasma MCP-1 concentrations can be used to assess the severity of trauma and is correlated with the development of sepsis after severe trauma. The addition of the early MCP-1 levels to the ISS significantly improves its ability to predict development of sepsis.

Caspase-1-dependent pyroptosis of peripheral blood mononuclear cells predicts the development of sepsis in severe trauma patients: A prospective observational study.

Pyroptosis plays a pivotal role in sepsis and septic shock in animal studies. However, its clinical significance in pathological conditions has not been well elucidated. This study aimed to evaluate the correlation between the percentage of pyroptotic peripheral blood mononuclear cells (PBMCs) and the clinical index and to investigate the relationship between PBMCs pyroptosis and the development of sepsis in trauma patients.This prospective study was conducted from October 2016 to May 2017 in a comprehensive trauma center. Sixty trauma patients and 10 healthy controls were enrolled. Peripheral blood samples were collected from the patients within 24 hours after injury. The percentages of pyroptotic and apoptotic PBMCs were measured using flow cytometry, and plasma levels of cytokines were evaluated using flow cytometric analysis with a human inflammation 13-plex panel.Trauma patients who developed sepsis had higher percentages of pyroptotic and apoptotic PBMCs at admission. Patients who developed sepsis (n = 33) had higher interleukin (IL)-6, IL-18, and monocyte chemotactic protein-1 (MCP-1) concentrations at admission than patients (n = 27) who did not develop sepsis. The percentage of PBMCs pyroptosis was significantly correlated with injury severity score (ISS), acute physiology and chronic health evaluation (APACHE) II score, IL-10, IL-18, and MCP-1 levels in trauma patients. PBMCs pyroptosis is a better biomarker in predicting the development of sepsis after trauma.This study indicates that the percentage of pyroptotic PBMCs increases during the early phase of trauma and that this increase is significantly correlated with the severity and state of inflammation in trauma patients. PBMCs pyroptosis is a potential marker for predicting the development of sepsis after trauma.