Triple-negative breast cancer(TNBC)is a highly aggressive and prognostically unfavorable subtype.Tertiary lymphoid structure(TLS)within the tumor microenvironment,comprising dendritic cells,B cells,T cells,and other immune cells,modulate the tumor immune response.The heterogeneity of TLS in TNBC,such as density,structural maturity,and molecular expression patterns,affects the tumor immune microenvironment and,consequently,treatment responses and clinical outcomes.Studies indicate a positive correlation between the density and maturity of TLS and the pathological complete response(pCR)of TNBC patients,with TLS enhancing the quantity of tumor-infiltrating immune cells and improving anti-tumor immune responses,thereby increasing sensitivity to chemotherapy and immunotherapy.Recent research has found that mature TLS are associated with effective immune responses,becoming significant predictors of treatment response.The combination of TLS with immune checkpoint inhibitors has shown promising prospects.Research demonstrates that promoting the formation or enhancing the functionality of TLS can improve anti-tumor immune effects and enhance treatment outcomes for TNBC patients.Targeting TLS may reduce immune evasion and increase the sensitivity to immunotherapy.However,clinical application of TLS still faces challenges,particularly the impact of their heterogeneity on treatment response.Current assessment methods for TLS are not standardized,lacking a uniform standard and diagnostic system,which limits their widespread application.Future research should focus on resolving these issues by developing standardized assessment tools and further exploring the role of TLS in immune escape and resistance mechanisms.This review aimed to summarize and analyze the existing research progress on TLS in TNBC,in order to provide new ideas for the development of personalized immunotherapy strategies.

Triple-negative breast cancer(TNBC)is a highly aggressive and prognostically unfavorable subtype.Tertiary lymphoid structure(TLS)within the tumor microenvironment,comprising dendritic cells,B cells,T cells,and other immune cells,modulate the tumor immune response.The heterogeneity of TLS in TNBC,such as density,structural maturity,and molecular expression patterns,affects the tumor immune microenvironment and,consequently,treatment responses and clinical outcomes.Studies indicate a positive correlation between the density and maturity of TLS and the pathological complete response(pCR)of TNBC patients,with TLS enhancing the quantity of tumor-infiltrating immune cells and improving anti-tumor immune responses,thereby increasing sensitivity to chemotherapy and immunotherapy.Recent research has found that mature TLS are associated with effective immune responses,becoming significant predictors of treatment response.The combination of TLS with immune checkpoint inhibitors has shown promising prospects.Research demonstrates that promoting the formation or enhancing the functionality of TLS can improve anti-tumor immune effects and enhance treatment outcomes for TNBC patients.Targeting TLS may reduce immune evasion and increase the sensitivity to immunotherapy.However,clinical application of TLS still faces challenges,particularly the impact of their heterogeneity on treatment response.Current assessment methods for TLS are not standardized,lacking a uniform standard and diagnostic system,which limits their widespread application.Future research should focus on resolving these issues by developing standardized assessment tools and further exploring the role of TLS in immune escape and resistance mechanisms.This review aimed to summarize and analyze the existing research progress on TLS in TNBC,in order to provide new ideas for the development of personalized immunotherapy strategies.

Objective To investigate the effect of resveratrol (Res) on temozolomide (TEM) against gliomas in vivo.Methods Human glioma cell line T98G was transplanted into BALB/C-nu female nude mice to establish orthotopic human glioma cell transplanted models.Five d after modeling,the 48 successfully modeled nude mice were randomly divided into solvent control group,Res group,TEM group,combination drug group,Wnt signaling pathway agonist group,and Wnt signaling pathway inhibitor group(n=8);and dimethyl sulfoxide (10 mg/kg),Res (10 mg/kg),TEM (25 mg/kg),Res (10mg/kg+TEM (25 mg/kg),Res (10 mg/kg)+TEM (25 mg/kg)+lithium chloride (2 mg/kg),and Res (10mg/kg)+TEM (25 mg/kg)+IWR-1 (5 mg/kg) were given,respectively,once/d for 30 d.During the administration,the survival status of nude mice in each group was continuously observed,tumor volume was measured by MR imaging every 5 d.Thirty d after administration,TUNEL was used to detect the apoptosis of tumor cells,and immunofluorescence was used to detect the immunofluorescent intensity of O6-methylguanine-DNA methyltransferase (MGMT) and β-catenin in the tumor tissues.Western blotting was used to detect the protein expression levels of Wnt signaling pathway-related proteins (Wnt2,and β-catenin),MGMT,and glycogen synthase kinase 3β (GSK3β).Results As compared with the TEM group,the combination drug group and Wnt signaling pathway inhibitor group had significantly decreased tumor volumes 20,25,30,and 35 d after modeling (/P＜0.05);as compared with the combination drug group,the Wnt signaling pathway inhibitor group had significantly decreased tumor volumes while Wnt signaling pathway agonist group had significantly increased tumor volumes 20,25,30,and 35 d after modeling (P＜0.05).TUNEL showed that the apoptosis rate of tumor cells in the combination drug group and Wnt signaling pathway inhibitor group was significantly increased as compared with that in the temozolomide group (P＜0.05);as compared with that in the TEM group,the apoptosis rate of tumor cells in the Wnt signaling pathway inhibitor group was significantly increased while that in the Wnt signaling pathway agonist group was statistically decreased (P＜0.05).Western blotting results showed that as compared with those in the combination drug group,the protein expression levels ofWnt2,β-catenin,and MGMT in the Wnt signaling pathway inhibitor group were significantly reduced,and GSK-3β protein expression level was significantly increased;while the protein expression levels of Wnt2,[β-catenin,and MGMT in the Wnt signaling pathway agonist group were significantly increased,and GSK-3β protein expression level was significantly decreased (P＜0.05).Conclusion Res inhibits Wnt signaling pathway by reducing expressions of Wnt2 and β-catenin,leading to decrease in MGMT expression,thereby enhancing the anti-glioma effect of TEM.

Nonalcoholic fatty liver disease (NAFLD) has become the most important liver disease in the world and its prevalence rate still tends to increase. However, there are still no effective drugs so far. The complex and dynamic interactions between multiple effects/mediators in the pathophysiology of NAFLD provide new insights and help with stratification and redefinition of clinical phenotypes and evaluation of disease susceptibility and multiplicity of progression. They may also provide new targets for future treatment. Therefore, research on the pathophysiology of NAFLD is imperative. Alcoholic liver disease is a great harm to health and an important cause of end-stage liver disease. Some progress has been made in the research on alcoholic liver disease around the world in 2016. This article reviews the research advances in alcoholic liver disease in 2016 from the aspects of epidemiology, pathogenesis, diagnostic and therapeutic methods, and prognosis.

OBJECTIVE:To screen antioxidant active components of Schisandra chinensis. METHODS:The orthogonal test was adopted to optimize extraction technology using DPPH free radical scavenging activity(IC50)as index and ethanol volume frac-tion,material-liquid ratio and extraction time as factors,and the verification test were made. The fractions(SC-0,SC-10,SC-30, SC-50,SC-70,SC-95) were made by extracting and purifying S. chinensis with macroporous resin with water and 10%,30%, 50%,70%and 95%ethanol. With IC50 and total antioxidant capacity(determined by ABTS method)as indexes(vitamin C as pos-itive control),the antioxidant active components of S. chinensis were optimized. The contents of 5 kinds of lignan in different posi-tions of S. chinensis were determined by HPLC. RESULTS:The optimal extraction condition of S. chinensis was as follows as 60% ethanol,material-liquid ratio of 1∶14,extracting for 2.0 h. The average IC50 of DPPH free radical scavenging activity was 23.81 mg/ml(RSD=0.52%,n=3)in verification test. SC-0 did not have antioxidant abilities. DPPH free radical scavenging activi-ty of those components (ie. the IC50 value from low to high) were in the following order of positive control>SC-50>SC-30>SC-95>SC-70>SC-10;total antioxidant ability of them were in the following order of SC-50>positive control>SC-30>SC-70>SC-95>SC-10;the contents of 5 types of lignan in different components were in the following order of SC-70>SC-50>SC-95>SC-30. CONCLUSIONS:The antioxidant active component of S. chinensis is 50%ethanol eluate.

OBJECTIVE:To screen decolorizing agents suitable for the extracts from the fruit and stem of Schisandra chinen-sis. METHODS:HPLC was adopted to determine the contents of 4 kinds of lignans(schizandrin,schisandrol B,deoxyschizandrin and γ-schizandrin) in the extract solution from the fruit and stem of S. chinensis which was treated with 8 kinds of decolorizing agents (activated clay,activated carbon,diatomite,calcium bentonite,kaolin,activated aluminium oxide,magnesium oxide,at-tapulgite clay),and the decolourization rates of the samples of the fruit and stem of S. chinensis and the retention rates of lignans in such samples were calculated respectively. RESULTS:The above-mentioned decolorizing agents were arranged in order as fol-lows respectively based on the decolourization effects on the extract solution from the fruit and stem of S. chinensis:attapulgite clay>activated carbon>activated aluminium oxide>kaolin>magnesium oxide>diatomite>calcium bentonite>activated clay,and activated carbon>diatomite>attapulgite clay>magnesium oxide>kaolin>activated aluminium oxide>activated clay>calcium ben-tonite. The attapulgite clay and activated carbon have the best decolourization effects on the extracts from the fruit and stem of S. chinensis,with the decolourization rates of 60.47% and 69.24% respectively,and the retention rates of schizandrin,schisandrol B,deoxyschizandrin and γ-schizandrin were 77.43%,77.73%,77.07%,77.53%,and 72.18%,70.17%,70.32%,70.28%,re-spectively. CONCLUSIONS:Among the 8 decolorizing agents,attapulgite clay and activated carbon have the best decolourization effects on the extract solution from the fruit and stem of S. chinensis.