Objective The aim of the study was to investigate the prognostic value of the preoperative peripheral neutrophil-to-lymphocyte ratio （NLR） in patients with hepatocellular cancer （HCC） and cirrhosis after hepa- tec...Objective The aim of the study was to investigate the prognostic value of the preoperative peripheral neutrophil-to-lymphocyte ratio （NLR） in patients with hepatocellular cancer （HCC） and cirrhosis after hepa- tectomy. Methods This retrospective study included 321 patients with HCC who underwent resection. The NLR was calculated using the neutrophil and lymphocyte counts in routine preoperative blood tests. Receiver operating characteristic curve analysis was performed to select the most appropriate NLR cutoff value. The preoperative NLR, patient demographics, and clinical and pathological data, including disease-free survival （DFS） and overall survival （OS）, were analyzed. Results The NLR was correlated with alpha-fetoprotein levels （X2 = 5.876, P = 0.015）, tumor size （X2 = 32.046, P 〈 0.001）, portal vein tumor thrombus （PVTT; x2 = 4.930, P = 0.026）, tumor encapsulation （x2 = 7.243, P = 0.007）, and recurrence （x2 = 7.717, P = 0.005）. Multivariate analyses illustrated that the number of tumors, PVTT, tumor size, and the NLR were independent factors for predicting DFS and OS. in patients with HCC and cirrhosis, but not among those without cirrhosis, a larger NLR predicted poorer postoperative DFS and OS （both P 〈 0.001）. Conclusion As a simple, effective independent predictor for patients with HCC, the preoperative NLR plays an important role in accurately predicting the postoperative outcomes of patients with HCC and cir- rhosis, but not those of patients without cirrhosis.展开更多
T follicular helper(Tfh)cells specialize in facilitating germinal center B-cell activation and high-affinity antibody generation,which are crucial in humoral immune responses.However,aberrant control of Tfh cells also...T follicular helper(Tfh)cells specialize in facilitating germinal center B-cell activation and high-affinity antibody generation,which are crucial in humoral immune responses.However,aberrant control of Tfh cells also contributes to the generation of self-reactive autoantibodies and promotes autoimmune diseases such as systemic lupus erythematosus(SLE).The mechanisms that control proper Tfh expansion remain unclear.Here,we show that farnesoid X receptor(FXR)is relatively upregulated in Tfh cells.Genetic deletion of Fxr restrains Tfh expansion both at steady state and in pristane-induced lupus.As a consequence of these defects,mice lacking Fxr manifested GC dysfunction and decreased plasma cell and autoantibody production,which alleviated nephritis progression in pristane-induced lupus.Mechanistically,FXR intrinsically regulates cholesterol homeostasis in Tfh cells,which subsequently controls Tfh cell proliferation.Preclinical treatment of wild-type(WT)mice with the clinically approved drug ursodeoxycholic acid(UDCA)to reduce FXR signaling mitigated lupus disease progression by repressing Tfh expansion,the GC reaction and autoantibody production.These findings provide a rationale for exploring FXR as a potential therapeutic target for SLE.展开更多
基金Supported by grants from the National Natural Science Foundation of China(No.81201918)the Science and Technology Project of Guangdong Province(No.2012B031800099)+1 种基金the Doctorial Fellowship of Higher Education of China(No.200805581172)the Scientific Research Foundation for Returned Overseas Chinese Scholars and the State Education Ministry(No.311,in 2015)
文摘Objective The aim of the study was to investigate the prognostic value of the preoperative peripheral neutrophil-to-lymphocyte ratio （NLR） in patients with hepatocellular cancer （HCC） and cirrhosis after hepa- tectomy. Methods This retrospective study included 321 patients with HCC who underwent resection. The NLR was calculated using the neutrophil and lymphocyte counts in routine preoperative blood tests. Receiver operating characteristic curve analysis was performed to select the most appropriate NLR cutoff value. The preoperative NLR, patient demographics, and clinical and pathological data, including disease-free survival （DFS） and overall survival （OS）, were analyzed. Results The NLR was correlated with alpha-fetoprotein levels （X2 = 5.876, P = 0.015）, tumor size （X2 = 32.046, P 〈 0.001）, portal vein tumor thrombus （PVTT; x2 = 4.930, P = 0.026）, tumor encapsulation （x2 = 7.243, P = 0.007）, and recurrence （x2 = 7.717, P = 0.005）. Multivariate analyses illustrated that the number of tumors, PVTT, tumor size, and the NLR were independent factors for predicting DFS and OS. in patients with HCC and cirrhosis, but not among those without cirrhosis, a larger NLR predicted poorer postoperative DFS and OS （both P 〈 0.001）. Conclusion As a simple, effective independent predictor for patients with HCC, the preoperative NLR plays an important role in accurately predicting the postoperative outcomes of patients with HCC and cir- rhosis, but not those of patients without cirrhosis.
基金supported by the National Natural Science Foundation of China(82271866,82471853 and 82402127)the Guangzhou Key Research and Development Program(02A004999000186)the Guangdong Basic and Applied Basic Research Foundation(2024B1515020039,2021A1515011451,2017B030314120 and 202201011028).
文摘T follicular helper(Tfh)cells specialize in facilitating germinal center B-cell activation and high-affinity antibody generation,which are crucial in humoral immune responses.However,aberrant control of Tfh cells also contributes to the generation of self-reactive autoantibodies and promotes autoimmune diseases such as systemic lupus erythematosus(SLE).The mechanisms that control proper Tfh expansion remain unclear.Here,we show that farnesoid X receptor(FXR)is relatively upregulated in Tfh cells.Genetic deletion of Fxr restrains Tfh expansion both at steady state and in pristane-induced lupus.As a consequence of these defects,mice lacking Fxr manifested GC dysfunction and decreased plasma cell and autoantibody production,which alleviated nephritis progression in pristane-induced lupus.Mechanistically,FXR intrinsically regulates cholesterol homeostasis in Tfh cells,which subsequently controls Tfh cell proliferation.Preclinical treatment of wild-type(WT)mice with the clinically approved drug ursodeoxycholic acid(UDCA)to reduce FXR signaling mitigated lupus disease progression by repressing Tfh expansion,the GC reaction and autoantibody production.These findings provide a rationale for exploring FXR as a potential therapeutic target for SLE.
