ObjectiveTo understand the current progress of programmed cell death in the pathogenesis of acute pancreatitis, and to provide reference for the pathogenesis and treatment of acute pancreatitis.MethodThe research progress of acute pancreatitis and programmed cell death in recent years was reviewed by reading relevant literatures at home and abroad in recent years.ResultsProgrammed cell death was defined as controlled cell death performed by intracellular procedures, including apoptosis, autophagy, programmed necrosis, and coronation. The pattern of death of pancreatic acinar cells mainly includes apoptosis and programmed necrosis. Although the pathogenesis of acute pancreatitis had not yet been fully clarified, it was known that through the study of programmed cell death, it could help us to understand the pathogenesis and pathogenesis of acute pancreatitis and provide more effective treatment methods.ConclusionsProgrammed cell death is very important for acute pancreatitis. The mechanism of programmed cell death in acute pancreatitis is necessary for the treatment and prevention of it.
Lung cancer is the most frequent cancer and the leading cause of cancer death all around the world. Anti-programmed cell death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) therapies have significantly improved the outcomes of non-small cell lung cancer (NSCLC) patients in recent years. However, the objective response rate in non-screened patients is only about 20%. It is very important to screen out the potential patients suitable for immunotherapy. Immunohistochemical staining of tumor tissue biopsies with PD-L1 antibodies can predict the therapeutic response to immunotherapy to some extent, but it still has some limitations. Recently some clinical studies have shown that PD-L1 expression in circulating tumor cells (CTC-PD-L1) is a potential independent biomarker and may provide important information for immunotherapy in NSCLC. This article will review technology for CTC-PD-L1 detection and the predictive value of CTC-PD-L1 for immunotherapy in NSCLC and review the latest clinical research progress.
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. Although surgery can cure some early-stage resectable patients, the postoperative recurrence rate remains as high as 30%-55%. Perioperative immune checkpoint inhibitor (ICI) therapy, which includes "neoadjuvant" therapy before surgery and "adjuvant" therapy after surgery, has significantly improved survival outcomes in resectable NSCLC patients. Large clinical studies, such as CheckMate 816, have demonstrated the superiority of neoadjuvant ICIs combined with chemotherapy in increasing the pathological complete response rate (pCR) and prolonging event-free survival (EFS). However, even with these advanced treatments, some patients do not achieve long-term benefits and experience early recurrence. This paper reviews the latest research progress of perioperative ICIs in NSCLC treatment, particularly the effectiveness of neoadjuvant chemoimmunotherapy in improving pCR and extending EFS. It further explores the recurrence patterns, resistance mechanisms, and potential biomarkers in NSCLC patients after neoadjuvant immunotherapy. By integrating basic research and clinical data, we analyze the mechanisms of early recurrence following perioperative immunotherapy and discuss future research directions and therapeutic strategies, providing new insights into precision treatment and recurrence prevention for NSCLC patients.
Objective To systematically evaluate the efficacy and safety of a combination regimen of PD-1/PD-L1 immune checkpoint inhibitors in the first-line treatment of advanced non-small cell lung cancer. Methods Randomized controlled trials (RCTs) of PD-1/PD-L1 inhibitor combination regimen in the first-line treatment of advanced non-squamous NSCLC were systematically retrieved from the Chinese and English electronic databases from inception to September 2023. The combination regimen includes PD-1/PD-L1 inhibitor+chemotherapy, PD-1/PD-L1 inhibitor+chemotherapy+anti-angiogenic agents (bevacizumab), and PD-1/PD-L1 inhibitor+CTLA4 inhibitor (ipilimumab). The network meta-analysis was performed using StataMP16.0 and R4.2.0 software. ResultsA total of 13 RCTs were collected, including 7 764 patients. In terms of effectiveness, compared with chemotherapy, several regimens improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Among them, toripalimab (Tor) plus chemotherapy (CT) may be associated with the best OS, and nivolumab plus bevacizumab and chemotherapy (Niv+Bev+CT) may provide the best PFS. Pembrolizumab (Pem) combined with CT was associated with the best treatment regimen for improving ORR. In terms of safety, except sintilimab (Sin) and Pem, the incidence of grade≥3 adverse events of all treatment regimens was significantly higher than that of chemotherapy (P<0.05). The incidence of AEs≥3 grade in Cam+CT was higher than that in Sin+CT (OR=0.44, 95%CI 0.25-0.80) and Pem+CT (OR=0.52, 95%CI 0.31-0.88). And the incidence of ≥3grade AEs in Atezolizumab (Ate) +Bev+CT (OR=2.32, 95%CI 1.14-4.71; OR=1.97, 95%CI 1.02-3.79) was also higher than that in Sin+CT and Pem+CT (P<0.05). Conclusion In non-squamous NSCLC patients, PD-1 inhibitor combined with chemotherapy can bring more benefits to advanced NSCLC patients than chemotherapy alone.
ObjectiveTo summarize the mechanism of action of programmed cell death protein 1 (PD-1)/programmed cell death ligand-1 (PD-L1) inhibitors, the application in breast cancer in recent years and the advances in the study of their bio-markers of effects. MethodRelevant literatures on PD-1/PD-L1 inhibitors and the study in the field of breast cancer were reviewed and summarized.ResultsIn recent years, the monotherapy of immune checkpoint inhibitors represented by PD-1/PD-L1 inhibitors or in combination with other therapies had brought new hope for patients with breast cancer especially triple-negative breast cancer (TNBC). However, only a small number of patients could benefit from breast cancer immunotherapy. The current researchers think that the efficacy of these drugs is related to PD-L1 expression in tumor tissue, tumor mutation burden (TMB), high level of microsatellite instability (MSI-H) and deficient mismatch repair (dMMR).ConclusionBreast cancer can benefit from the immunotherapy of PD-1/PD-L1 inhibitors, but formulating personalized medicine model, finding biomarkers that can predict efficacy and selecting patients with breast cancer who can benefit from it for targeted therapy are the new requirements in the new era of breast cancer immunotherapy.
ObjectiveTo explore the short-term efficacy and safety of pembrolizumab combined with chemotherapy in the neoadjuvant treatment of non-small cell lung cancer. MethodsThe clinical data of 11 male patients with non-small cell lung cancer who underwent pembrolizumab combined with neoadjuvant chemotherapy in the Department of Thoracic Surgery, the First Affiliated Hospital of Xi'an Jiaotong University from December 2019 to June 2021 were retrospectively analyzed. The average age of the patients was 52.0-79.0 (62.0±6.9) years. The imaging data and pathological changes before and after neoadjuvant treatment were compared, and adverse reactions during neoadjuvant treatment were recorded. Objective remission rate (ORR) and main pathological remission rate (MPR) and pathological complete remission rate (pCR) were the main observation endpoints. ResultsAfter preoperative neoadjuvant therapy with pembrolizumab combined with platinum or paclitaxel, all patients successfully underwent thoracoscopic radical resection of lung cancer. The ORR was 72.7%, and the MPR was 81.8%. Among them, 45.5% of patients achieved pCR. The main adverse reactions were hypoalbuminemia, decreased appetite and nausea. The mortality rate within 30 days after surgery was 0, and no tumor metastasis was observed. ConclusionPembrolizumab combined with neoadjuvant chemotherapy is safe and feasible to treat non-small cell lung cancer, and the short-term efficacy is beneficial.
Objective To analyze the predictive value of serum copeptin, pentraxin 3 (PTX3), and soluble programmed cell death ligand 1 (sPD-L1) for poor prognosis in children with neonatal purulent meningitis. Methods Children with neonatal purulent meningitis admitted to the Department of Pediatrics, the Second Hospital of Handan between September 2020 and February 2023 were selected. According to the Gesell developmental scale score, the children were separated into a good prognosis group and a poor prognosis group. The correlation between serum levels of copeptin, PTX3, sPD-L1 and the prognosis of neonatal purulent meningitis were analyzed using Spearman correlation coefficient. The correlation of serum levels of copeptin, PTX3, and sPD-L1 with white blood cell count (WBC) and procalcitonin (PCT) were analyzed using Pearson correlation analysis. The area under the curve (AUC) of serum copeptin, PTX3, and sPD-L1 in predicting the prognosis of neonatal purulent meningitis were obtained by plotting the receiver operator characteristic curve. The factors affecting the prognosis of neonatal purulent meningitis were analyzed using multiple logistic regression analysis. Results A total of 107 children were included. Among them, 79 cases had good prognosis and 28 cases had poor prognosis. The serum levels of copeptin, PTX3, sPD-L1, WBC and PCT in the poor prognosis group were obviously higher than those in the good prognosis group (P<0.05). The levels of serum copeptin, PTX3, and sPD-L1 were positively correlated with the prognosis, WBC, and PCT of neonatal purulent meningitis (P<0.05). The results of logistic regression analysis showed that copeptin, PTX3, and sPD-L1 were risk factors affecting the prognosis of neonatal purulent meningitis (P<0.05). The AUC for predicting the prognosis of neonatal purulent meningitis with the combination of serum copeptin, PTX3, and sPD-L1 was 0.976, and the combined predictive value of the three was better than predicting separately (P<0.05). Conclusions Copeptin, PTX3, and sPD-L1 are abnormally upregulated in the serum of children with poor prognosis of neonatal purulent meningitis. The combination of the three can improve the predictive value for poor prognosis of neonatal purulent meningitis.
Objective To investigate the necessity of further surgery for patients with locally advanced esophageal squamous cell carcinoma following treatment with the programmed cell death-1 (PD-1) inhibitor combined with chemotherapy, and to assess its impact on survival. MethodsPatients with stage ⅡA to ⅢB esophageal squamous cell carcinoma who received immunotherapy combined with chemotherapy at our hospital from January 2020 to June 2022 were selected for this study. Based on whether they underwent surgery after receiving PD-1 inhibitor combined with chemotherapy, patients were divided into a surgery group and a non-surgery group. We compared the general clinical data, side effects, clinical complete response rates, progression-free survival (PFS), and overall survival (OS) between the two groups. Results A total of 58 patients were included in the study, comprising 45 males and 13 females, with an average age of (65.5±6.9) years. There were no statistical differences in general clinical data or adverse reactions between the two groups. Univariate analysis revealed that the objective response rate and surgery were significantly associated with PFS (P<0.05). Binary logistic regression analysis showed that surgery was the only independent risk factor for PFS (P=0.003). Kaplan-Meier survival analysis showed that the PFS and OS in the surgery group were significantly higher than those in the non-surgery group (HR=0.13, 95%CI 0.036 to 0.520, P＜0.001; HR=0.17, 95%CI 0.045 to 0.680, P=0.004). ConclusionAfter treatment with the PD-1 inhibitor combined with chemotherapy, patients with locally advanced esophageal squamous cell carcinoma still require surgical intervention to achieve improved PFS and OS.
Objective To summarize the effect of lenvatinib + transarterial chemoembolization (TACE) + programmed cell death protein-1 (PD-1) antibody in the treatment of hepatocellular carcinoma with main portal vein tumor thrombus and cavernous transformation. Methods In this study, we reported the clinical data of four patients with hepatocellular carcinoma with main portal vein tumor thrombus and cavernous transformation who received conversion therapy with lenvatinib combined with TACE and PD-1 antibody in West China Hospital. Results Among the four patients, two patients achieved complete response and two achieved partial response; tumor markers were significantly decreased after combination treatment. However, all four patients failed to undergo hepatectomy. ConclusionsLenvatinib + TACE + PD-1 antibody is effective for hepatocellular carcinoma with main portal vein tumor thrombus and cavernous transformation. However, there are still many problems worthy of further discussion.
ObjectiveTo screen long non-coding RNAs (lncRNAs) relevant to programmed cell death (PCD) and construct a nomogram model predicting prognosis of hepatocellular carcinoma (HCC). MethodsThe HCC patients selected from The Cancer Genome Atlas (TCGA) were randomly divided into training set and validation set according to 1∶1 sampling. The lncRNAs relevant to PCD were screened by Pearson correlation analysis, and which associated with overall survival in the training set were screened by univariate Cox proportional hazards regression (abbreviation as “Cox regression”), and then multivariate Cox regression was further used to analyze the prognostic risk factors of HCC patients, and the risk score function model was constructed. According to the median risk score of HCC patients in the training set, the HCC patients in each set were assigned into a high-risk and low-risk, and then the Kaplan-Meier method was used to draw the overall survival curve, and the log-rank test was used to compare the survival between the HCC patients with high-risk and low-risk. At the same time, the area under receiver operating characteristic curve (AUC) was used to evaluate the value of the risk score function model in predicting the 1-, 3-, and 5-year overall survival rates of HCC patients in the training set, validation set, and integral set. Then the nomogram was constructed based on the risk score function model and factors validated in clinic, and its predictive ability for the prognosis of HCC patients was evaluated. ResultsA total of 374 patients with HCC were downloaded from the TCGA, of which 342 had complete clinicopathologic data, including 171 in the training set and 171 in the validation set. Finally, 8 lncRNAs genes relevant to prognosis (AC099850.3, LINC00942, AC040970.1, AC022613.1, AC009403.1, AL355974.2, AC015908.3, AC009283.1) were screened out, and the prognostic risk score function model was established as follows: prognostic risk score=exp1×β1+exp2×β2...+expi×βi (expi was the expression level of target lncRNA, βi was the coefficient of multivariate Cox regression analysis of target lncRNA). According to this prognostic risk score function model, the median risk score was 0.89 in the training set. The patients with low-risk and high-risk were 86 and 85, 86 and 85, 172 and 170 in the training set, validation set, and integral set, respectively. The overall survival curves of HCC patients with low-risk drawn by Kaplan-Meier method were better than those of the HCC patients with high-risk in the training set, validation set, and integral set (P<0.001). The AUCs of the prognostic risk score function model for predicting the 1-, 3-, and 5-year overall survival rates in the training set were 0.814, 0.768, and 0.811, respectively, in the validation set were 0.799, 0.684, and 0.748, respectively, and in the integral set were 0.807, 0.732, and 0.784, respectively. The multivariate Cox regression analysis showed that the prognostic risk score function model was a risk factor affecting the overall survival of patients with HCC [<0.89 points as a reference, RR=1.217, 95%CI (1.151, 1.286), P<0.001]. The AUC (95%CI) of the prognostic risk score function model for predicting the overall survival rate of HCC patients was 0.822 (0.796, 0.873). The AUCs of the nomogram constructed by the prognostic risk score function model in combination with clinicopathologic factors to predict the 1-, 3-, and 5-year overall survival rates were 0.843, 0.839, and 0.834. The calibration curves of the nomogram of 1-, 3-, and 5-year overall survival rates in the training set were close to ideal curve, suggesting that the predicted overall survival rate by the nomogram was more consistent with the actual overall survival rate. ConclusionThe prognostic risk score function model constructed by the lncRNAs relevant to PCD in this study may be a potential marker of prognosis of the patients with HCC, and the nomogram constructed by this model is more effective in predicting the prognosis (overall survival) of patients with HCC.