Clonal suppression induced by CD4+ CD25+ regulatory T cells is one of the principal factors to evoke the immune tolerance in tumor. Through the activation of CD4+ CD25+ regulatory T cells, the indoleamine 2,3-dioxygenase (IDO) reduces the immune response in tumor micro-environment of various systems , and induces the formation of host immune tolerance. IDO inhibitor 1-MT is expected to become a new target for cancer treatment.

ObjectiveTo investigate the inhibitory effect of 1-methyl-tryptophan (1-MT) on transplanted hepatocellular carcinoma in mice.MethodsHuman hepatocellular carcinoma subcutaneous tumor models were established in mice,and the mice were divided into hepG2 group,empty plasmid group,indoleamine 2,3-dioxygenase (IDO) saline group,IDO) 5-fluoropyrimidine (5-FU) group,IDO 1-MT group,and the group combining IDO 1-MT with 5-FU treatment (n=8 in each group).The tumor growth,tumor volume and pathological examination were observed and the expression of IDO in tumor tissues was determined by immunohistochemistry.ResultsCompared with hepG2 and the empty vector saline groups,IDO saline group had bigger tumor,faster growth,and the differences were statistically significant (P＜0.05).Compared with IDO saline group,5-FU group,1-MT group and combination treatment groups showed smaller tumor volume and weight,and the tumor inhibitory rates were 86.54％,79.95％,94.46％,respectively.There were significant differences between these groups (P＜0.05).However,there were no significant differences in tumor volumes between 5-FU group and 1-MT group (P＞0.05).HE pathological observation of ceils in each treatment group showed reduced density,increased necrotic area and significant decrease in peripheral blood alpha-fetoprotein (P＜0.05).ConclusionsIDO can promote the growth of liver cancer cells involved in immune escape.1-MT can inhibit the transplanted tumor growth in mice,and therefore may enhance the chemotherapeutic efficacy.

Objective To explore the current status and potential subtypes of frailty among family caregivers of patients with dementia,and to analyze the related influencing factors of different subtypes.Methods Dementia patients and their family caregivers in 8 community health service centers in Shanghai from June to October 2023 were recruited by convenience sampling.General information questionnaire,Tilburg Frailty Indicator(TFI),Pittsburgh Sleep Quality Index(PSQI),Self-Rating Depression Scale(SDS),Zarit Caregiver Burden Interview(ZBI),and Connor-Davidson Resilience Scale(CD-RISC)were conducted for investigation.Latent profile analysis was used to explore the potential subtypes of frailty among family caregivers of patients with dementia.The influencing factors associated with the potential subtypes were identified by univariate analysis and multivariate Logistic regression analysis.Results A total of 470 family caregivers of patients with dementia were surveyed,and 46.17％of them suffered from frailty.Frailty among family caregivers of patients with dementia can be classified into 3 potential subtypes:comprehensive-low frailty subtype(70.64％),psychosocial-medium frailty subtype(19.57％),and physical-high frailty subtype(9.79％).Family caregivers of patients with dementia who had poor sleep quality and suffered from 2 or more chronic diseases were more likely to be classified into the physical-high frailty subtype(P＜0.05).Family caregivers of patients with dementia who had higher levels of depression,lower mastery levels of caregiving knowledge and skills and spousal caregivers were more likely to be classified into the psychosocial-medium frailty subtype(P＜0.05).Family caregivers of patients with dementia who had higher levels of resilience were more likely to be classified into the comprehensive-low frailty subtype(P＜0.05).Conclusion The incidence of frailty among family caregivers of patients with dementia is at a high level with significant heterogeneity.It is suggested that medical staff should pay attention to the frailty of family caregivers,with a focus on family caregivers in the psychosocial-medium frailty subtype or physical-high frailty subtype,and take timely and targeted interventions according to the characteristics and influencing factors of different subtypes,so as to prevent or delay the occurrence and development of frailty.

Background and purpose:Despite the significant advancements that have been made in the treatment of gastric cancer,there are still problems such as poor prognosis and low five-year survival rate in advanced gastric cancer.Therefore,exploring effective treatment options remains a key focus of clinical research.As a new type of immune checkpoint inhibitor,the clinical efficacy and safety of pembrolizumab still need to be confirmed by extensive research.Therefore,this study conducted regression analysis of the effect of pembrolizumab combined with XELOX regimen in the treatment of advanced gastric cancer,providing a reference for clinical treatment.Methods:Clinical data of patients with advanced gastric cancer who were admitted to Shanxi Province Cancer Hospital from March 2020 to August 2022 were retrospectively collected.Inclusion criteria:patients with HER2-negative,untreated advanced gastric cancer or adenocarcinoma of the esophagogastric junction,confirmed by clinical histopathological examination and meeting relevant diagnostic criteria;TNM stage Ⅳ;age≥20 years;expected survival≥6 months;no severe organ damage before treatment;Karnofsky score＞60;patients with complete clinical data.Exclusion criteria:patients with concurrent major organ dysfunction;hypothyroidism or hyperthyroidism;blood or coagulation disorders;autoimmune diseases;lactating or pregnant women;individuals with mental illnesses or a history of mental illness;those with concurrent other malignancies;those with severe liver or kidney dysfunction;patients with incomplete clinical data.Based on the inclusion and exclusion criteria,91 patients with advanced gastric cancer were selected.Among them,45 received XELOX regimen treatment(control group),and 46 received pembrolizumab combined with XELOX regimen treatment(observation group).After establishing the database,one patient in the observation group was found to have logical errors in their treatment information and was therefore excluded.Ultimately,90 patients were included in the study,with 45 in each of the control and observation groups.The efficacy,median overall survival(OS),median progression-free survival(PFS),toxic side effects,improvement in quality of life,and levels of carcinoembryonic antigen(CEA),carbohydrate antigen 19-9(CA19-9),Escherichia coli,Bifidobacterium and Lactobacillus before and after treatment were compared between the two groups.This study was approved by the ethics committee of Shanxi Province Cancer Hospital(ethics number:KY2023081).Results:After treatment,the proportion of progressive disease(PD)in the observation group was 20.0%(9/45),which was lower than that in the control group(40.0%,18/45).However,there was no significant difference between the two groups in proportion of stable disease(SD),complete response(CR)and partial response(PR)(P＞0.05).The improvement rate of quality of life in the observation group after treatment was 60.0%(27/45),which was higher than that in the control group,with a rate of 37.8%(17/45)(P＜0.05).The median OS and PFS in the observation group were longer compared with the control group(P＜0.05).After treatment,the levels of CEA and CA19-9 in peripheral blood of the observation group were lower compared with the control group(P＜0.05).After treatment,the number of Escherichia coli was lower in the observation group than in the control group,while the numbers of Bifidobacterium and Lactobacillus were higher(P＜0.05).There was no significant difference in the incidence of nausea and vomiting,diarrhea,leukopenia,rash,liver function damage between the two groups(P＞0.05).Conclusion:The combination of pembrolizumab and XELOX regimen can regulate the expression levels of tumor markers in patients with advanced gastric cancer,prevent disease progression,improve patient quality of life,and help maintain intestinal microecology balance.