To develop a prognostic model for neoadjuvant immunochemotherapy efficacy in esophageal squamous cell carcinoma by analyzing the immune microenvironment.

Objective: The choice of neoadjuvant therapy for esophageal squamous cell carcinoma (ESCC) is controversial. This study aims to provide a basis for clinical treatment selection by establishing a predictive model for the efficacy of neoadjuvant immunochemotherapy (NICT). Methods: A retrospective analysis of 30 patients was conducted, divided into Response and Non-response groups based on whether they achieved major pathological remission (MPR). Differences in genes and immune microenvironment between the two groups were analyzed through next-generation sequencing (NGS) and multiplex immunofluorescence (mIF). Variables most closely related to therapeutic efficacy were selected through LASSO regression and ROC curves to establish a predictive model. An additional 48 patients were prospectively collected as a validation set to verify the model's effectiveness. Results: NGS suggested seven differential genes (ATM, ATR, BIVM-ERCC5, MAP3K1, PRG, RBM10, and TSHR) between the two groups (P < 0.05). mIF indicated significant differences in the quantity and location of CD3+, PD-L1+, CD3+PD-L1+, CD4+PD-1+, CD4+LAG-3+, CD8+LAG-3+, LAG-3+ between the two groups before treatment (P < 0.05). Dynamic mIF analysis also indicated that CD3+, CD8+, and CD20+ all increased after treatment in both groups, with a more significant increase in CD8+ and CD20+ in the Response group (P < 0.05), and a more significant decrease in PD-L1+ (P < 0.05). The three variables most closely related to therapeutic efficacy were selected through LASSO regression and ROC curves: Tumor area PD-L1+ (AUC= 0.881), CD3+PD-L1+ (AUC= 0.833), and CD3+ (AUC= 0.826), and a predictive model was established. The model showed high performance in both the training set (AUC= 0.938) and the validation set (AUC= 0.832). Compared to the traditional CPS scoring criteria, the model showed significant improvements in accuracy (83.3% vs 70.8%), sensitivity (0.625 vs 0.312), and specificity (0.937 vs 0.906). Conclusion: NICT treatment may exert anti-tumor effects by enriching immune cells and activating exhausted T cells. Tumor area CD3+, PD-L1+, and CD3+PD-L1+ are closely related to therapeutic efficacy. The model containing these three variables can accurately predict treatment outcomes, providing a reliable basis for the selection of neoadjuvant treatment plans.

Role of intrapulmonary expression of MIF mRNA in acute lung injury of rats with acute necrotizing pancreatitis / 中华胰腺病杂志

Objective To investigate the relationship between the expression of MIF mRNA and TNF-α in the lung tissue of rats with acute necrotizing pancreatitis (ANP) and explore their mechanism of action in acute lung injury during the course of ANP. Methods A total of 40 Sprague-Dawley rats were randomly divided into four groups (n = 10 in each group) : the sham operation (SO) group, ANP 3h group, 6h group, 12h group. The model of ANP was induced by retrograde injection of 5% sodium tanrocholate (0. 1 ml/100 g) into the biliary and pancreatic duct. The level of serum amylase was determined;pancreatic and lung tissues were harvested for pathological examination, and wet/dry weight ratios were estimated. Intrapulmonary expression of MIF mRNA was assayed by semi-quantitative RT-PCR. TNF-α in pulmonary homogenate was measured by immunoradiometric assay. Results Serum amylase, wet/dry weight ratios of pancreatic and lung tissues all significantly increased, and pathological injuries aggravated with time in ANP groups. Levels of TNF-α in ANP 3h, 6h, 12h group were (0.69 ± 0. 107) ng/ml, (1.64 ± 0. 10) ng/ml and (0.92 ± 0.11) ng/ml, and expression of MIF mRNA were 1.97±0.09, 2.55±0.23, 3.29±0.26, which were significantly higher than those in control group [(0. 19±0.06)ng/ml, 1.21±0.34, P<0.01]. lntrapulmonary expression of MIF mRNA was positively associated with lung pathological injuries, wet/dry weight ratio, and TNF-α(r = 0. 637, r = 0.684, r = 0.858, P < 0.01). Intrapulmonary levels of TNF-α was positively associated with lung pathological injuries, wet/dry weight ratio (r=0.540, r=0.421, P<0.01). Conclusions MIF mRNA was over- expressed and level of TNF-α was significantly increased in pulmonary tissue in rats with ANP, and this may be one of the mechanisms in the pathogenesis of lung injury in ANP.