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.

ObjectiveTo establish a method for content determination of total iridoid compounds and baldrinal and 11-ethoxyviburtinal from Valerianae Jatamansi Rhizoma et Radix; To determine the contents of total iridoid compounds and baldrinal and 11-ethoxyviburtinal in Valerianae Jatamansi Rhizoma et Radix from three medicinal origins.Methods UV spectrophotometry was applied, 11-ethoxyviburtinal (cyclopentane-pyran-7-formaldehyde, 4-ethoxy methyl) was set as the reference substance, and the content of total iridoid compounds was determined at 288 nm. HPLC method was used to simultaneously determine the contents of baldrinal and 11-ethoxyviburtinal. The HPLC analysis was performed on a Phenomenex Luna C18 column (250 mm×4.6 mm, 5μm). The mobile phase was composed of acetonitrile-water in gradient elution at a flow rate of 0.95 mL/min. The detection wavelength was 288 nm and the column temperature was 30℃.Results The total iridoid compounds, baldrinal and 11-ethoxyviburtinal were in good linearity within the ranges of 2.088–14.616μg/μL, 74.88–224.64μg, and 41.6–249.6μg, respectively. This method was precise, and with good repeatability, stability and recovery rate.Conclusion The method is accurate, simple, rapid, which can be used for the quality control of Valerianae Jatamansi Rhizoma et Radix.

Acetaminophen(AAP)-induced hepatic injury is one of the common causes of drug-induced hepatic injury.Up to date,the mechanisms of AAP-induced hepatic injury are still incompletely understood.Recent advances suggest that reactive metabolite formation,glutathione depletion,alkylation of proteins,especially mitochondrial proteins and peroxynitrite formation are critical initiating events for the toxicity.This review will focus on more recent advances in mitochondrial dysfunction after AAP overdose.Additional,oxidative stress and inflammatory mediators are also important for the overall outcome.