BACKGROUND Liver cirrhosis is a progressive hepatic disease whose immunological basis has attracted increasing attention.However,it remains unclear whether a concrete causal association exists between immunocyte pheno...BACKGROUND Liver cirrhosis is a progressive hepatic disease whose immunological basis has attracted increasing attention.However,it remains unclear whether a concrete causal association exists between immunocyte phenotypes and liver cirrhosis.AIM To explore the concrete causal relationships between immunocyte phenotypes and liver cirrhosis through a mendelian randomization(MR)study.METHODS Data on 731 immunocyte phenotypes were obtained from genome-wide assoc-iation studies.Liver cirrhosis data were derived from the Finn Gen dataset,which included 214403 individuals of European ancestry.We used inverse variable weighting as the primary analysis method to assess the causal relationship.Sensitivity analyses were conducted to evaluate heterogeneity and horizontal pleiotropy.RESULTS The MR analysis demonstrated that 11 immune cell phenotypes have a positive association with liver cirrhosis[P<0.05,odds ratio(OR)>1]and that 9 immu-nocyte phenotypes were negatively correlated with liver cirrhosis(P<0.05,OR<1).Liver cirrhosis was positively linked to 9 immune cell phenotypes(P<0.05,OR>1)and negatively linked to 10 immune cell phenotypes(P<0.05;OR<1).None of these associations showed heterogeneity or horizontally pleiotropy(P>0.05).CONCLUSION This bidirectional two-sample MR study demonstrated a concrete causal association between immunocyte phenotypes and liver cirrhosis.These findings offer new directions for the treatment of liver cirrhosis.展开更多
Tertiary lymphoid structures(TLSs)are formations at sites with persistent inflammatory stimulation,including tumors.These ectopic lymphoid organs mainly consist of chemo-attracting B cells,T cells,and supporting dendr...Tertiary lymphoid structures(TLSs)are formations at sites with persistent inflammatory stimulation,including tumors.These ectopic lymphoid organs mainly consist of chemo-attracting B cells,T cells,and supporting dendritic cells(DCs).Mature TLSs exhibit functional organization for the optimal development and collaboration of adaptive immune response,delivering an augmented effect on the tumor microenvironment(TME).The description of the positive correlation between TLSs and tumor prognosis is reliable only under a certain condition involving the localization and maturation of TLSs.Emerging evidence suggests that underlying mechanisms of the anti-tumor effect of TLSs pave the way for novel immunotherapies.Several approaches have been developed to take advantage of intratumoral TLSs,either by combining it with therapeutic agents or by inducing the neogenesis of TLSs.展开更多
The aim of this study is to describe the presence of neuroendocrine(NE) cells (paraneurons), producing biogenic amines and/orpeptidergic hormones, in the female urethra of wild mainmals, by means of histochemical and ...The aim of this study is to describe the presence of neuroendocrine(NE) cells (paraneurons), producing biogenic amines and/orpeptidergic hormones, in the female urethra of wild mainmals, by means of histochemical and double labeling immunofluoresent techniques. 5-Hydroxytrytamine-. chromogranin A-, cholecystokinin- and somatostatin-contain NE cells are present in the urethral epithelium of all the species studied. Paraneurons containing 5-hydrxytryptamine colocalized with chromogranin A or cholecystokinin were also found in all subjects. Such active substances are hypothesized to play a role in the contretion of the urethral musculature, emission of urogenital fluids, and inhibition of endocrine and exocrine secretions.展开更多
Objective: To investigate the effect of acupuncture on high hemagglutination state, blood sugar raising hormone and immunocyte factor levels in type II diabetes patients. Methods: A total of 120 inpatients and outpati...Objective: To investigate the effect of acupuncture on high hemagglutination state, blood sugar raising hormone and immunocyte factor levels in type II diabetes patients. Methods: A total of 120 inpatients and outpatients were randomly divided into acupuncture plus medication group (n=52) and medication group (n=50). In addition, 18 type II diabetes patients formed acupuncture group for comparing their therapeutic effects. Main acupoints used were Pishu (BL 20), Geshu (BL 17), Yishu, Shenshu (BL 23), Zusanli (ST 36), Sanyinjiao (SP 6), etc.. combined with other acupoints according to different sydroms. These acupoints were stimulated by manipulaing the filiform needles with uniform reinforcing and reducing method for 15 min and then stimulated electrically for 15 min with an electroacupuncture therapeutic apparatus. Western medicines used were Glipizide, Dimethyldiguanide Hydrochloride, etc.. The treatment was given once daily, with 10 sessions being a therapeutic course, 2～3 courses altogether. Indexes of external thrombosis length (ETL), platelet agglutination rate (PAgR), fibrinogen (FG), activated partial thromboplastin time (APTT), fasting blood glucose (FBG), prothrombin time(PT), adrenocoticortropic hormone (ACTH), cortisol (CS), growth hormone (GH), glucagon (GL), tumor necrosis factor alpha (TNF α), interleukin 6 (IL 6), insulin (INS) and C peptide (C P) were determined using radioimmunoassay. Results: After 2～3 courses of treatment, both acupuncture group and medication plus acupuncture group could significantly improve high hemagglutination state, lower blood sugar raising hormone level, regulate immunocyte factor level and raise the sensitivity of insulin, which were apparently superior to those of medication group (P<0.05～0.01). Conclusion: Acupuncture therapy can effectively regulate plasma blood sugar raising hormone, immunocyte factor levels, increase the sensitivity of insulin to target cells, resist blood coagulation and improve microcirculation.展开更多
Background:The immune microenvironment(IME)is closely associated with prognosis and therapeutic response of hepatitis B virus-related hepatocellular carcinoma(HBV-HCC).Multi-parametric magnetic resonance imaging(MRI)e...Background:The immune microenvironment(IME)is closely associated with prognosis and therapeutic response of hepatitis B virus-related hepatocellular carcinoma(HBV-HCC).Multi-parametric magnetic resonance imaging(MRI)enables non-invasive assessment of IME and predicts prognosis in HBV-HCC.We aimed to construct an MRI prediction model of the immunocyte-infiltration subtypes and explore its prognostic significance.Methods:HBV-HCC patients at the First Affiliated Hospital of Sun Yat-sen University(Guangzhou,China)with radical surgery(between 1 October and 30 December 2021)were prospectively enrolled.Patients with pathologically proven HCC(between 1 December 2013 and 30 October 2019)were retrospectively enrolled.Pearson correlation analysis was used to examine the relationship between the immunocyte-infiltration counts and MRI parameters.An MRI prediction model of immunocyte-infiltration subtypes was constructed in prospective cohort.Kaplan-Meier survival analysis was used to analyse its prognostic significance in the retrospective cohort.Results:Twenty-four patients were prospectively enrolled to construct the MRI prediction model.Eighty-nine patients were retrospectively enrolled to determine its prognostic significance.MRI parameters(relative enhancement,ratio of the apparent diffusion coefficient value of tumoral region to peritumoral region[rADC],T1 value)correlated significantly with the immunocyte-infiltration counts(leukocytes,T help cells,PD1+Tc cells,B lymphocytes).rADC differed significantly between high and low immunocyte-infiltration groups(1.47±0.36 vs 1.09±0.25,P=0.009).The area under the curve of the MRI model was 0.787(95%confidence interval 0.587-0.987).Based on the MRI model,the recurrence-free time was longer in the high immunocyte-infiltration group than in the low immunocyte-infiltration group(P=0.026).Conclusions:MRI is a non-invasive method for assessing the IME and immunocyte-infiltration subtypes,and predicting prognosis in post-operative HBV-HCC patients.展开更多
Background:Primary liver cancer poses a significant global health burden,with projections indicating a surpassing of one million cases by 2025.Cuproptosis,a copper-dependent mechanism of cell death,plays a crucial rol...Background:Primary liver cancer poses a significant global health burden,with projections indicating a surpassing of one million cases by 2025.Cuproptosis,a copper-dependent mechanism of cell death,plays a crucial role in the pathogenesis,progression,and prognosis of various cancers,including hepatocellular carcinoma(HCC).Purpose:This study aimed to develop a prognostic model for HCC based on cuproptosis-related genes,utilizing clinical data and gene expression profiles from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases.Materials and Methods:Clinical features and gene expression data of HCC patients were collected from publicly available databases.Patients from TCGA were randomly divided into training and testing sets,and Lasso Cox regression was applied to develop a predictive model using cuproptosis-related genes.Results:The analysis identified Copper Metabolism Domain Containing 1(COMMD1)as a potential prognostic marker for HCC,with deletion of this gene impacting disease progression.Cellular functional experiments validated the role of COMMD1 in HCC.Conclusions:COMMD1 emerges as a promising candidate for HCC treatment,with implications for prognosis prediction and therapeutic targeting.展开更多
Cancer-induced bone pain(CIBP)is a type of ongoing or breakthrough pain caused by a primary bone tumor or bone metastasis.CIBP constitutes a specific pain state with distinct characteristics;however,it shares similari...Cancer-induced bone pain(CIBP)is a type of ongoing or breakthrough pain caused by a primary bone tumor or bone metastasis.CIBP constitutes a specific pain state with distinct characteristics;however,it shares similarities with inflammatory and neuropathic pain.At present,although various therapies have been developed for this condition,complete relief from CIBP in patients with cancer is yet to be achieved.Hence,it is urgent to study the mechanism underlying CIBP to develop efficient analgesic drugs.Herein,we focused on the peripheral mechanism associated with the initiation of CIBP,which involves tissue injury in the bone and changes in the tumor microenvironment(TME)and dorsal root ganglion.The nerve–cancer and cancer–immunocyte cross-talk in the TME creates circumstances that promote tumor growth and metastasis,ultimately leading to CIBP.The peripheral mechanism of CIBP and current treatments as well as potential therapeutic targets are discussed in this review.展开更多
目的应用孟德尔随机化(Mendelian randomization,MR)技术探究免疫细胞特征与细菌性肺炎之间的相关性。方法选取已知731种免疫细胞特征,从全基因组关联研究(genome-wide association study,GWAS)开放数据库获取数据,使用双样本MR方法揭...目的应用孟德尔随机化(Mendelian randomization,MR)技术探究免疫细胞特征与细菌性肺炎之间的相关性。方法选取已知731种免疫细胞特征,从全基因组关联研究(genome-wide association study,GWAS)开放数据库获取数据,使用双样本MR方法揭示免疫细胞特征是否对细菌性肺炎发生风险具有直接影响。两样本MR分析主要采用逆方差加权法(inverse variance weighting,IVW),根据效应指标优势比(OR)和95%置信区间(CI)评估结果,并进行敏感性分析,包括但不限于结果的稳健性验证、潜在的异质性检验以及多效性检验等确保最终结论的科学性及准确性。为避免反向因果关系,将细菌性肺炎作为暴露因素,筛选的六种免疫细胞特征作为结局事件,进行反向MR分析。结果通过MR分析识别出CD33^(-)HLA-DR^(+)髓样细胞、CD86^(+)树突状细胞、CD39^(+)调节性T细胞、HLA-DR^(+)自然杀伤细胞、CD14^(+)CD16^(+)单核细胞及程序性死亡配体1(PD-L1)单核细胞等六种检验效能P<0.01的免疫细胞特征与细菌性肺炎风险存在因果关联。反向MR结果未发现细菌性肺炎与上述六种免疫细胞特征存在因果关系。结论本研究揭示了遗传因素在免疫细胞特征及功能与细菌性肺炎发病风险之间的关系,筛选并鉴定了多种与细菌性肺炎存在显著联系的免疫细胞特征。展开更多
基金the National Natural Science Foundation of China,No.82270649.
文摘BACKGROUND Liver cirrhosis is a progressive hepatic disease whose immunological basis has attracted increasing attention.However,it remains unclear whether a concrete causal association exists between immunocyte phenotypes and liver cirrhosis.AIM To explore the concrete causal relationships between immunocyte phenotypes and liver cirrhosis through a mendelian randomization(MR)study.METHODS Data on 731 immunocyte phenotypes were obtained from genome-wide assoc-iation studies.Liver cirrhosis data were derived from the Finn Gen dataset,which included 214403 individuals of European ancestry.We used inverse variable weighting as the primary analysis method to assess the causal relationship.Sensitivity analyses were conducted to evaluate heterogeneity and horizontal pleiotropy.RESULTS The MR analysis demonstrated that 11 immune cell phenotypes have a positive association with liver cirrhosis[P<0.05,odds ratio(OR)>1]and that 9 immu-nocyte phenotypes were negatively correlated with liver cirrhosis(P<0.05,OR<1).Liver cirrhosis was positively linked to 9 immune cell phenotypes(P<0.05,OR>1)and negatively linked to 10 immune cell phenotypes(P<0.05;OR<1).None of these associations showed heterogeneity or horizontally pleiotropy(P>0.05).CONCLUSION This bidirectional two-sample MR study demonstrated a concrete causal association between immunocyte phenotypes and liver cirrhosis.These findings offer new directions for the treatment of liver cirrhosis.
基金supported by the Zhejiang Provincial Key Project of Research and Development(No.2019C03043)the National Natural Science Foundation of China(Nos.32030035,31870874,32000623,and 32100693)the Zhejiang Provincial Natural Science Foundation(No.LZ21C080001)of China。
文摘Tertiary lymphoid structures(TLSs)are formations at sites with persistent inflammatory stimulation,including tumors.These ectopic lymphoid organs mainly consist of chemo-attracting B cells,T cells,and supporting dendritic cells(DCs).Mature TLSs exhibit functional organization for the optimal development and collaboration of adaptive immune response,delivering an augmented effect on the tumor microenvironment(TME).The description of the positive correlation between TLSs and tumor prognosis is reliable only under a certain condition involving the localization and maturation of TLSs.Emerging evidence suggests that underlying mechanisms of the anti-tumor effect of TLSs pave the way for novel immunotherapies.Several approaches have been developed to take advantage of intratumoral TLSs,either by combining it with therapeutic agents or by inducing the neogenesis of TLSs.
文摘The aim of this study is to describe the presence of neuroendocrine(NE) cells (paraneurons), producing biogenic amines and/orpeptidergic hormones, in the female urethra of wild mainmals, by means of histochemical and double labeling immunofluoresent techniques. 5-Hydroxytrytamine-. chromogranin A-, cholecystokinin- and somatostatin-contain NE cells are present in the urethral epithelium of all the species studied. Paraneurons containing 5-hydrxytryptamine colocalized with chromogranin A or cholecystokinin were also found in all subjects. Such active substances are hypothesized to play a role in the contretion of the urethral musculature, emission of urogenital fluids, and inhibition of endocrine and exocrine secretions.
文摘Objective: To investigate the effect of acupuncture on high hemagglutination state, blood sugar raising hormone and immunocyte factor levels in type II diabetes patients. Methods: A total of 120 inpatients and outpatients were randomly divided into acupuncture plus medication group (n=52) and medication group (n=50). In addition, 18 type II diabetes patients formed acupuncture group for comparing their therapeutic effects. Main acupoints used were Pishu (BL 20), Geshu (BL 17), Yishu, Shenshu (BL 23), Zusanli (ST 36), Sanyinjiao (SP 6), etc.. combined with other acupoints according to different sydroms. These acupoints were stimulated by manipulaing the filiform needles with uniform reinforcing and reducing method for 15 min and then stimulated electrically for 15 min with an electroacupuncture therapeutic apparatus. Western medicines used were Glipizide, Dimethyldiguanide Hydrochloride, etc.. The treatment was given once daily, with 10 sessions being a therapeutic course, 2～3 courses altogether. Indexes of external thrombosis length (ETL), platelet agglutination rate (PAgR), fibrinogen (FG), activated partial thromboplastin time (APTT), fasting blood glucose (FBG), prothrombin time(PT), adrenocoticortropic hormone (ACTH), cortisol (CS), growth hormone (GH), glucagon (GL), tumor necrosis factor alpha (TNF α), interleukin 6 (IL 6), insulin (INS) and C peptide (C P) were determined using radioimmunoassay. Results: After 2～3 courses of treatment, both acupuncture group and medication plus acupuncture group could significantly improve high hemagglutination state, lower blood sugar raising hormone level, regulate immunocyte factor level and raise the sensitivity of insulin, which were apparently superior to those of medication group (P<0.05～0.01). Conclusion: Acupuncture therapy can effectively regulate plasma blood sugar raising hormone, immunocyte factor levels, increase the sensitivity of insulin to target cells, resist blood coagulation and improve microcirculation.
基金funded by the National Natural Science Foundation of China[no.82271958,no.81971684].
文摘Background:The immune microenvironment(IME)is closely associated with prognosis and therapeutic response of hepatitis B virus-related hepatocellular carcinoma(HBV-HCC).Multi-parametric magnetic resonance imaging(MRI)enables non-invasive assessment of IME and predicts prognosis in HBV-HCC.We aimed to construct an MRI prediction model of the immunocyte-infiltration subtypes and explore its prognostic significance.Methods:HBV-HCC patients at the First Affiliated Hospital of Sun Yat-sen University(Guangzhou,China)with radical surgery(between 1 October and 30 December 2021)were prospectively enrolled.Patients with pathologically proven HCC(between 1 December 2013 and 30 October 2019)were retrospectively enrolled.Pearson correlation analysis was used to examine the relationship between the immunocyte-infiltration counts and MRI parameters.An MRI prediction model of immunocyte-infiltration subtypes was constructed in prospective cohort.Kaplan-Meier survival analysis was used to analyse its prognostic significance in the retrospective cohort.Results:Twenty-four patients were prospectively enrolled to construct the MRI prediction model.Eighty-nine patients were retrospectively enrolled to determine its prognostic significance.MRI parameters(relative enhancement,ratio of the apparent diffusion coefficient value of tumoral region to peritumoral region[rADC],T1 value)correlated significantly with the immunocyte-infiltration counts(leukocytes,T help cells,PD1+Tc cells,B lymphocytes).rADC differed significantly between high and low immunocyte-infiltration groups(1.47±0.36 vs 1.09±0.25,P=0.009).The area under the curve of the MRI model was 0.787(95%confidence interval 0.587-0.987).Based on the MRI model,the recurrence-free time was longer in the high immunocyte-infiltration group than in the low immunocyte-infiltration group(P=0.026).Conclusions:MRI is a non-invasive method for assessing the IME and immunocyte-infiltration subtypes,and predicting prognosis in post-operative HBV-HCC patients.
文摘Background:Primary liver cancer poses a significant global health burden,with projections indicating a surpassing of one million cases by 2025.Cuproptosis,a copper-dependent mechanism of cell death,plays a crucial role in the pathogenesis,progression,and prognosis of various cancers,including hepatocellular carcinoma(HCC).Purpose:This study aimed to develop a prognostic model for HCC based on cuproptosis-related genes,utilizing clinical data and gene expression profiles from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases.Materials and Methods:Clinical features and gene expression data of HCC patients were collected from publicly available databases.Patients from TCGA were randomly divided into training and testing sets,and Lasso Cox regression was applied to develop a predictive model using cuproptosis-related genes.Results:The analysis identified Copper Metabolism Domain Containing 1(COMMD1)as a potential prognostic marker for HCC,with deletion of this gene impacting disease progression.Cellular functional experiments validated the role of COMMD1 in HCC.Conclusions:COMMD1 emerges as a promising candidate for HCC treatment,with implications for prognosis prediction and therapeutic targeting.
基金supported by the Zhongshan-Fudan Joint Innovation Center,Zhongshan,Guangdong Province,China(528437)the National Natural Science Foundation of China(82271258,82271248,82204830,81971056)+1 种基金Innovative Research Team of High-level Local Universities in Shanghai,Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)ZJ Lab,Shanghai Center for Brain Science and Brain-Inspired Technology.
文摘Cancer-induced bone pain(CIBP)is a type of ongoing or breakthrough pain caused by a primary bone tumor or bone metastasis.CIBP constitutes a specific pain state with distinct characteristics;however,it shares similarities with inflammatory and neuropathic pain.At present,although various therapies have been developed for this condition,complete relief from CIBP in patients with cancer is yet to be achieved.Hence,it is urgent to study the mechanism underlying CIBP to develop efficient analgesic drugs.Herein,we focused on the peripheral mechanism associated with the initiation of CIBP,which involves tissue injury in the bone and changes in the tumor microenvironment(TME)and dorsal root ganglion.The nerve–cancer and cancer–immunocyte cross-talk in the TME creates circumstances that promote tumor growth and metastasis,ultimately leading to CIBP.The peripheral mechanism of CIBP and current treatments as well as potential therapeutic targets are discussed in this review.
