Colorectal cancer is one of the most prevalent malignant tumors in the digestive system globally,with both its incidence and mortality showing an upward trend.In recent years,immunother-apy has become a research focus in the prognosis of CRC.Different states of tumor-infiltrating lym-phocytes(TILs)in patients have distinct impacts on tumor progression.The diversity of TILs and their interactions among cells reflect the complex relationship between tumors and the immune system.Patients with mismatch repair-deficient and microsatellite instability-high(dMMR/MSI-H)molecular phenotypes exhibit higher levels of TILs.Moreover,immune checkpoint inhibitors(ICIs),which are relevant targeted drugs for immune checkpoint blockade,also demonstrate a higher response rate in colorectal cancer patients with dMMR/MSI-H molecular phenotypes.This article reviewed the basic characteristics and prognostic value of TILs,as well as the relationship between dMMR/MSI-H and the immunological characteristics of colorectal cancer patients.

Objective To study the effect of Honokiol(HKL)on pulmonary microvascular endothelial cells in lipopolysaccharide(LPS)-induced acute respiratory distress syndrome(ARDS)and its potential mechanism.Methods Mouse lung microvascular endothelial cells(PMVECs)were cultured with DMEM+10％FBS in a six-well plate and divided into control(Con)group 1,Honokiol(HKL)group 1,LPS treated(LPS)group 1,and LPS+HKL treatment(HKL+LPS)group 1.The levels of malondialdehyde(MDA)and reactive oxygen species(ROS)in cell lysates were determined by lipid peroxidation assay kit and H2DCF-DA,respectively.TUNEL/DAPI double staining was used to detect apoptosis.Cell junctions were visualized via VE-cadherin/DAPI and Claudin-5/DAPI double staining.Western blot was used to detect caspase-3,cleaved caspase-3,Sirt3,SOD2,and acetylated SOD2(Ac-SOD2)expression.Thirty-two mice were randomly divided into control(Con)group 2,Honokiol(HKL)group 2,LPS treated(LPS)group 2,and LPS+HKL treatment(HKL+LPS)group 2.Hematoxylin and eosin(HE)staining was used to observe pathological changes to the lung tissue.Results HKL pretreatment significantly reversed the LPS-induced increase in ROS and MDA levels(P＜0.05),SOD2 acetylation and Sirt3 down-regulation(P＜0.05).TUNEL and caspase analysis showed that HKL protected against the apoptosis of PMVECs induced by LPS.VE-cadherin fluorescence staining demonstrated that HKL pretreatment prevented LPS from disrupting cell adhesion junctions.Claudin-5 fluorescence staining showed that HKL pretreatment prevented LPS from disrupting the tight junctions between cells.In the animal experiments,HE staining showed that HKL significantly inhibited the typical pathological changes of ARDS in the lung tissue of mice in the LPS group.Conclusions HKL can significantly inhibit the LPS-induced oxidative stress,apoptosis,and cell-connection breakdown of PMVECs,thereby alleviating ARDS symptoms.

Objective Some colorectal cancer patients still face high recurrence rates and poor prognoses even after they have undergone the surgical treatment of radical resection.Identifying potential biochemical markers and therapeutic targets for the prognostic evaluation of patients undergoing radical resection of colorectal cancer is crucial for improving their clinical outcomes.Recently,it has been reported that the T cell immunoglobulin and mucin domain protein 3(Tim-3)and its ligand galactose lectin 9(galectin-9)play crucial roles in immune dysfunction caused by various tumors,such as colorectal cancer.However,their expressions,biological functions,and prognostic value in colorectal cancer are still unclear.This study aims to investigate the relationship between Tim-3 and galectin-9 expression levels and the clinicopathological characteristics and prognosis of patients undergoing radical resection of colorectal cancer.Methods A total of 171 patients who underwent radical resection of colorectal cancer at Chengdu Fifth People's Hospital between February 2018 and March 2019 were selected.Immunohistochemistry was performed to assess the expression levels of Tim-3 and galectin-9 in the cancer tissue samples and the paracancerous tissue samples of the patients.The relationship between Tim-3 and galectin-9 expression levels and the baseline clinical parameters of the patients was analyzed accordingly.Kaplan-Meier analysis was performed to assess the association between Tim-3 and galectin-9 expression levels and the relapse-free survival(RFS)and the overall survival(OS)of colorectal cancer patients.Cox regression analysis was conducted to identify factors associated with adverse prognosis in the patients.Results The immunohistochemical results showed that the high expression levels of Tim-3 and galectin-9 were observed in 70.18%(120/171)and 32.16%(55/171),respectively,of the colorectal cancer tissues,whereas the low expression levels were 29.82%(51/171)and 67.84%(116/171),respectively.Furthermore,the expression score of Tim-3 was significantly higher in colorectal cancer tissues than that in the paracancerous tissues,while the expression score of galectin-9 was lower than that in the paracancerous tissues(P＜0.05).Further analysis revealed that the expression of Tim-3 and galectin-9 was associated with the depth of tumor infiltration,vascular infiltration,and clinical staging(P＜0.05).During the follow-up period of 14-63 months,7 out of 171 patients were lost to follow-up.Among the remaining patients,49 and 112 cases presented abnormally low expression of Tim-3 and galectin-9,respectively,whereas 115 and 52 cases presented high expression of Tim-3 and galectin-9,respectively.Kaplan-Meier survival analysis demonstrated that patients with high Tim-3 expression in colorectal cancer tissues had significantly lower RFS and OS than those with low expression did(RFS:log-rank=22.66,P＜0.001;OS:log-rank=19.71,P＜0.001).Conversely,patients with low galectin-9 expression had significantly lower RFS and OS than those with high expression did(RFS:log-rank=19.45,P＜0.001;OS:log-rank=22.24,P＜0.001).Cox multivariate analysis indicated that TNM stage Ⅲ(HR=2.26,95%CI:1.20-5.68),high expression of Tim-3(HR=0.80,95%CI:0.33-0.91),and low expression of galectin-9(HR=1.80,95%CI:1.33-4.70)were independent risk factors affecting RFS and OS in patients(P＜0.05).Conclusion Aberrant expression of Tim-3 and galectin-9 is observed in colorectal cancer tissues.High expression of Tim-3 and low expression of galectin-9 are closely associated with adverse clinico-pathological characteristics and prognosis.They are identified as independent influencing factors that may trigger adverse prognostic events in patients.These findings suggest that Tim-3 and galectin-9 have potential as new therapeutic targets and clinical indicators.