Prognostic value of lymph node metastasis in patients with T1-stage colorectal cancer from multiple centers in China

AIM To explore the features and prognostic value of lymph node metastasis in patients with T1-stage colorectal cancer(CRC).METHODS In all,321 cases of T1-stage CRC were selected from 10132 patients with CRC who received surgical therapy in six large-scale hospitals in China and were retrospectively analyzed. Univariate and multivariate analyses were performed to analyze the risk factors for lymphatic metastasis. A survival analysis was then performed to analyze the prognostic value of lymph node metastasis.RESULTS The occurrence rate of T1 stage was 3.17%(321/10132);of these patients,the lymph node metastasis rate was 8.41%(27/321),and the non-lymph node metastasis rate was 91.59%(294/321). Univariate analysis showed that preoperative serum CEA,preoperative serum CA199,preoperative serum CA724,vascular invasion,and degree of differentiation were associated with lymph node metastasis in T1-stage CRC(P < 0.05 for all). Multivariate analysis indicated that preoperative serum CA724,vascular invasion,and degree of differentiation were closely related to lymph node metastasis(P < 0.05 for all). Log-rank survival analysis showed that age,preoperative serum CEA,preoperative serum CA199,vascular invasion,degree of differentiation,and lymph node metastasis(χ2 = 24.180,P < 0.001) were predictors of 5-year overall survival(OS)(P < 0.05 for all). COX regression analysis demonstrated that preoperative serum CA199 and lymph node metastasis(HR = 5.117;P < 0.05;95%CI: 0.058-0.815) were independent prognostic indicators of 5-year OS in patients with T1-stage CRC(P < 0.05 for both). CONCLUSION The morbidity of T1-stage CRC was 3.17% for all CRC cases. Preoperative serum CA724,vascular invasion,and degree of differentiation are independent risk factors for lymph node metastasis. Lymph node metastasis is an independent prognostic factor for OS in patients with T1-stage CRC.

Intranasal delivery of replicating mRNA encoding neutralizing antibody against SARS-CoV-2 infection in mice

The lung is the prophylaxis target against SARS-CoV-2 infection,and neutralizing antibodies are a leading class of biological products against various infectious viral pathogen.In this study,we develop a safe and cost-effective platform to express neutralizing antibody in the lung with replicating mRNA basing on alphavirus replicon particle(VRP)delivery system,to prevent SARS-CoV-2 infections.First,a modified VEEV replicon with two subgenomic(sg)promoters was engineered to translate the light and heavy chains of antibody simultaneously,for expression and assembly of neutralizing anti-SARS-CoV-2 antibody CB6.Second,the feasibility and protective efficacy of replicating mRNA against SARS-CoV-2 infection were demonstrated through both in vitro and in vivo assays.The lung target delivery with the help of VRP system resulted in efficiently block SARS-CoV-2 infection with reducing viral titer and less tissue damage in the lung of mice.Overall,our data suggests that expressing neutralizing antibodies in the lungs with the help of self-replicating mRNA could potentially be a promising prophylaxis approach against SARS-CoV-2 infection.