OBJECTIVETo observe the expression of caspase-3 in the kidney of a rat model of renal tubular damage induced by endotoxin and hypoxia and explore the mechanism of renal tubular damage.

METHODSTen rats were anesthetized with artificial ventilation and received 2 mg/kg lipopolysaccharide (LPS) injection through the penile vein. The FiO2 was reduced 90 min later from 21% to 5%, and the ventilation was withdrawn after another 90 min. Immediately after ventilation withdrawal, the kidney of the rats were obtained for immunocytochemistry and HE staining.

RESULTSHE staining showed obvious hyperemia in most of the glomeruli, mild swelling of the endothelial and mesangial cells, severe swelling and turbidity in the proximal tubular epithelial cells without obvious changes in most of the distal proximal tubules. A small portion of the interstitial epithelial cells showed swelling and turbidity, and the entire renal interstitium appeared hyperemic but without inflammatory cell infiltration. Immunocytochemistry detected the presence of caspase-3 in the cytoplasm, and most of the distal renal tubule cells were positive for caspase-3, while only occasional cells showed caspase-3 positivity in the proximal tubular epithelial cells. Most of the proximal tubular epithelial and glomerulus cells were negative for caspase-3.

CONCLUSIONSEndotoxin and hypoxia can induce renal damage, particularly in the proximal renal tubule cells, and the distal tubular epithelial cells sustain relatively light damage. Caspase-3 is strongly expressed in the distal renal tubular cells, suggesting that in renal tubular damage induced by endotoxin and hypoxia, cell degeneration, necrosis and apoptosis coexist in the tubular epithelial cells; degeneration and necrosis occur primarily in the proximal tubular epithelial cells, while apoptosis is obvious in the distal renal cells.

Animals ; Caspase 3 ; genetics ; metabolism ; Hypoxia ; chemically induced ; Kidney ; metabolism ; Kidney Tubules ; metabolism ; pathology ; Lipopolysaccharides ; Male ; Rats ; Rats, Sprague-Dawley

Objective: To evaluate the effect of depth of remission of induction chemotherapy on the overall prognosis of limited stage small cell lung cancer (L-SCLC). Methods: The study was a retrospective, L-SCLC patients who contained complete imaging data and underwent consecutive standardized treatments at the Department of Thoracic Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University between January 2013 and June 2021 were included. To delineate the volume of tumor before and after induction chemotherapy and to calculate the depth of remission caused by the induced chemotherapy. The time receiver operating characteristic (timeROC) method was used to determine the optimal predictors for prognosis, multi-factor analysis using Cox risk proportional model. Results: A total of 104 patients were included in this study. The median PFS and OS of this cohort were 13.7 months and 20.9 months, respectively. It was observed by timeROC analysis that residual tumor volume after induction chemotherapy had the optimal predictive value of PFS at 1 year (AUC=0.86, 95% CI: 0.78~0.94) and OS at 2 years (AUC=0.76, 95% CI: 0.65~0.87). Multivariate analysis showed residual tumor volume after induction chemotherapy was the independent prognostic factor to PFS (HR=1.006, 95% CI: 1.003~1.009, P<0.01) and OS (HR=1.009, 95% CI: 1.005~1.012, P<0.001). For those whose residual tumor volume remitted to less than 10 cm(3) after induction chemotherapy, the favorable long-term outcomes could be achieved, regardless of their initial tumor load. Conclusion: The depth of remission of induction chemotherapy could be a promising prognostic predictor to the L-SCLC and provide the individualized treatment guidance.
Humans ; Small Cell Lung Carcinoma/pathology* ; Lung Neoplasms/pathology* ; Induction Chemotherapy ; Retrospective Studies ; Neoplasm, Residual ; Prognosis