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
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
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
Ras homolog(Rho)-associated kinases(ROCKs)belong to the serine-threonine kinase family,which plays a pivotal role in regulating the damage,survival,axon guidance,and regeneration of neurons.ROCKs are also involved in ...Ras homolog(Rho)-associated kinases(ROCKs)belong to the serine-threonine kinase family,which plays a pivotal role in regulating the damage,survival,axon guidance,and regeneration of neurons.ROCKs are also involved in the biological effects of immune cells and glial cells,as well as the development of neurodegenerative disorders such as Alzheimer’s disease,Parkinson’s disease,and multiple sclerosis.Previous studies by us and others confirmed that ROCKs inhibitors attenuated the symptoms and progression of experimental models of the abovementioned neurodegenerative diseases by inhibiting neuroinflammation,regulating immune imbalance,repairing the blood-brain barrier,and promoting nerve repair and myelin regeneration.Fasudil,the first ROCKs inhibitor to be used clinically,has a good therapeutic effect on neurodegenerative diseases.Fasudil increases the activity of neural stem cells and mesenchymal stem cells,thus optimizing cell therapy.This review will systematically describe,for the first time,the effects of abnormal activation of ROCKs on T cells,B cells,microglia,astrocytes,oligodendrocytes,and pericytes in neurodegenerative diseases of the central nervous system,summarize the therapeutic potential of fasudil in several experimental models of neurodegenerative diseases,and clarify the possible cellular and molecular mechanisms of ROCKs inhibition.This review also proposes that fasudil is a novel potential treatment,especially in combination with cell-based therapy.Findings from this review add support for further investigation of ROCKs and its inhibitor fasudil for the treatment of neurodegenerative diseases.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
Sinomenine,a major active ingredient from traditional Chinese medicine Qingfengteng(Sinomenium acutum(Thunb.)Rehd.et Wils.),has been proven to have anti-inflammatory,analgesic,anti-tumor,immunomodulatory and other pha...Sinomenine,a major active ingredient from traditional Chinese medicine Qingfengteng(Sinomenium acutum(Thunb.)Rehd.et Wils.),has been proven to have anti-inflammatory,analgesic,anti-tumor,immunomodulatory and other pharmacological effects,and is clinically used for various inflammatory and autoimmune diseases.However,due to complex molecular mechanisms and pathological characteristics in inflammatory and immune responses,the precise anti-inflammatory and immunological mechanisms of sinomenine are still unclear.This review summarizes the anti-inflammatory and immunoregulatory mechanisms of sinomenine during recent years in rheumatoid arthritis,respiratory system,nervous system,digestive system and organ transplant rejection.The molecular pharmacological mechanisms of sinomenine responsible for anti-inflammatory and immunosuppressive effects were in detail introduced based on 3 aspects including cytokines induction,signal pathways modulation and immune cells function regulation.Moreover,this review also raises some concerns and challenges in future sinomenine study,which will contribute to crucial theoretical and practical significance for in-depth development and utilization of sinomenine as medicinal resource.展开更多
Objective: The aim of our study was to assess the efficacy of regional hyperthermia combined with intrapleural chemotherapy and to evaluate the effect on the immunologic cells and vascular endothelial growth factor (V...Objective: The aim of our study was to assess the efficacy of regional hyperthermia combined with intrapleural chemotherapy and to evaluate the effect on the immunologic cells and vascular endothelial growth factor (VEGF) in patients with malignant pleural effusion. Methods: The 102 patients with malignant pleural effusion were included in this study: 52 patients undergoing regional hyperthermia with intrapleural chemotherapy (HICT), and 50 patients treated with intrapleural chemotherapy (ICT). Chemotherapy was administered into the thoracic cavity weekly through a tube with CDDP (dose = 40 mg/m2), and hyperthermia was performed twice a week for 60 minutes following the ICT. We evaluated the response rates and side-effects after 4 weeks. Before and after the treatment, T cell subsets and NK cells were detected by flow cytometry and VEGF was measured with ELISA kits. Results: Compared HICT to ICT, the overall response rates of the whole group, breast cancers and lung cancers were 80.8% vs 54% (P < 0.01), 86.7% vs 56.3% (P > 0.05) and 78.4% vs 52.9% (P < 0.05) respectively. The ratios of CD4+, CD4+/CD8+ and NK cells increased and the concentration of VEGF decreased more significantly after HICT. Conclusion: We concluded that combined regional hyperthermia with intrapleural chemotherapy could control the malignant pleural effusion effectively with mild toxicity. The levels of the T cell subset, NK cells and VEGF in both blood and effusion changed obviously.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
Transient receptor potential(TRP)channels are one primary type of calcium(Ca^(2+))permeable channels,and those relevant transmembrane and intracellular TRP channels were previously thought to be mainly associated with...Transient receptor potential(TRP)channels are one primary type of calcium(Ca^(2+))permeable channels,and those relevant transmembrane and intracellular TRP channels were previously thought to be mainly associated with the regulation of cardiovascular and neuronal systems.Nowadays,however,accumulating evidence shows that those TRP channels are also responsible for tumorigenesis and progression,inducing tumor invasion and metastasis.However,the overall underlying mechanisms and possible signaling transduction pathways that TRP channels in malignant tumors might still remain elusive.Therefore,in this review,we focus on the linkage between TRP channels and the significant characteristics of tumors such as multi-drug resistance(MDR),metastasis,apoptosis,proliferation,immune surveillance evasion,and the alterations of relevant tumor micro-environment.Moreover,we also have discussed the expression of relevant TRP channels in various forms of cancer and the relevant inhibitors’efficacy.The chemo-sensitivity of the anti-cancer drugs of various acting mechanisms and the potential clinical applications are also presented.Furthermore,it would be enlightening to provide possible novel therapeutic approaches to counteract malignant tumors regarding the intervention of calcium channels of this type.展开更多
Endometriosis(EMS)is a chronic inflammatory and estrogen-dependent gynecological disease characterized by the presence of endometrial tissue outside the uterine cavity.Although it is a benign disease,EMS is tumor-like...Endometriosis(EMS)is a chronic inflammatory and estrogen-dependent gynecological disease characterized by the presence of endometrial tissue outside the uterine cavity.Although it is a benign disease,EMS is tumor-like in several aspects,which include unrestrained growth,decreased apoptosis,and aggressive invasion.EMS involves endocrine disorders and immunological factors.Indoleamine 2,3-dioxygenase(IDO)is an intracellular enzyme that catalyzes the initial and rate-limiting step of the metabolism of tryptophan.IDO is a potential candidate facilitating EMS development.Increased IDO expression in both eutopic and ectopic endometria of women with EMS is biologically important in aspects,which include regulation of endometrial stromal cell function and modulation of adjacent local immunocytes to generate a supportive microenvironment.In turn,the expression of IDO can be regulated by the complex endocrine-immune microenvironment networks in endometrial lesions.Here,we systematically review the roles of IDO in EMS to explore its pathological implications and treatment potential.展开更多
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.
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 National Natural Science Foundation of China, Nos.81473577 (to CGM), 81903596 (to QW), 82004028 (to LJS)China Postdoctoral Science Foundation, No.2020M680912 (to LJS)+2 种基金Open Project of The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education of China,No.2019004 (to CGM)Science and Technology Innovation Project of Shanxi Colleges of China, Nos.2019L0728 (to QW)Cultivation Project of Shanxi Universtity of Chinese Medicine of China, No.2019PY130 (to QW)
文摘Ras homolog(Rho)-associated kinases(ROCKs)belong to the serine-threonine kinase family,which plays a pivotal role in regulating the damage,survival,axon guidance,and regeneration of neurons.ROCKs are also involved in the biological effects of immune cells and glial cells,as well as the development of neurodegenerative disorders such as Alzheimer’s disease,Parkinson’s disease,and multiple sclerosis.Previous studies by us and others confirmed that ROCKs inhibitors attenuated the symptoms and progression of experimental models of the abovementioned neurodegenerative diseases by inhibiting neuroinflammation,regulating immune imbalance,repairing the blood-brain barrier,and promoting nerve repair and myelin regeneration.Fasudil,the first ROCKs inhibitor to be used clinically,has a good therapeutic effect on neurodegenerative diseases.Fasudil increases the activity of neural stem cells and mesenchymal stem cells,thus optimizing cell therapy.This review will systematically describe,for the first time,the effects of abnormal activation of ROCKs on T cells,B cells,microglia,astrocytes,oligodendrocytes,and pericytes in neurodegenerative diseases of the central nervous system,summarize the therapeutic potential of fasudil in several experimental models of neurodegenerative diseases,and clarify the possible cellular and molecular mechanisms of ROCKs inhibition.This review also proposes that fasudil is a novel potential treatment,especially in combination with cell-based therapy.Findings from this review add support for further investigation of ROCKs and its inhibitor fasudil for the treatment of neurodegenerative diseases.
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.
基金This research was funded by National Natural Science Foundation of China(No.81973505)The National Key Research and Development Program of China(No.2019YFC1708902,2019YFC1711000).
文摘Sinomenine,a major active ingredient from traditional Chinese medicine Qingfengteng(Sinomenium acutum(Thunb.)Rehd.et Wils.),has been proven to have anti-inflammatory,analgesic,anti-tumor,immunomodulatory and other pharmacological effects,and is clinically used for various inflammatory and autoimmune diseases.However,due to complex molecular mechanisms and pathological characteristics in inflammatory and immune responses,the precise anti-inflammatory and immunological mechanisms of sinomenine are still unclear.This review summarizes the anti-inflammatory and immunoregulatory mechanisms of sinomenine during recent years in rheumatoid arthritis,respiratory system,nervous system,digestive system and organ transplant rejection.The molecular pharmacological mechanisms of sinomenine responsible for anti-inflammatory and immunosuppressive effects were in detail introduced based on 3 aspects including cytokines induction,signal pathways modulation and immune cells function regulation.Moreover,this review also raises some concerns and challenges in future sinomenine study,which will contribute to crucial theoretical and practical significance for in-depth development and utilization of sinomenine as medicinal resource.
文摘Objective: The aim of our study was to assess the efficacy of regional hyperthermia combined with intrapleural chemotherapy and to evaluate the effect on the immunologic cells and vascular endothelial growth factor (VEGF) in patients with malignant pleural effusion. Methods: The 102 patients with malignant pleural effusion were included in this study: 52 patients undergoing regional hyperthermia with intrapleural chemotherapy (HICT), and 50 patients treated with intrapleural chemotherapy (ICT). Chemotherapy was administered into the thoracic cavity weekly through a tube with CDDP (dose = 40 mg/m2), and hyperthermia was performed twice a week for 60 minutes following the ICT. We evaluated the response rates and side-effects after 4 weeks. Before and after the treatment, T cell subsets and NK cells were detected by flow cytometry and VEGF was measured with ELISA kits. Results: Compared HICT to ICT, the overall response rates of the whole group, breast cancers and lung cancers were 80.8% vs 54% (P < 0.01), 86.7% vs 56.3% (P > 0.05) and 78.4% vs 52.9% (P < 0.05) respectively. The ratios of CD4+, CD4+/CD8+ and NK cells increased and the concentration of VEGF decreased more significantly after HICT. Conclusion: We concluded that combined regional hyperthermia with intrapleural chemotherapy could control the malignant pleural effusion effectively with mild toxicity. The levels of the T cell subset, NK cells and VEGF in both blood and effusion changed obviously.
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.
基金This work was supported by the National Natural Science Foundation of China(No.81930102 to Bo Yang)the National Natural Science Foundation of China(No.81773754 to Ling Ding).
文摘Transient receptor potential(TRP)channels are one primary type of calcium(Ca^(2+))permeable channels,and those relevant transmembrane and intracellular TRP channels were previously thought to be mainly associated with the regulation of cardiovascular and neuronal systems.Nowadays,however,accumulating evidence shows that those TRP channels are also responsible for tumorigenesis and progression,inducing tumor invasion and metastasis.However,the overall underlying mechanisms and possible signaling transduction pathways that TRP channels in malignant tumors might still remain elusive.Therefore,in this review,we focus on the linkage between TRP channels and the significant characteristics of tumors such as multi-drug resistance(MDR),metastasis,apoptosis,proliferation,immune surveillance evasion,and the alterations of relevant tumor micro-environment.Moreover,we also have discussed the expression of relevant TRP channels in various forms of cancer and the relevant inhibitors’efficacy.The chemo-sensitivity of the anti-cancer drugs of various acting mechanisms and the potential clinical applications are also presented.Furthermore,it would be enlightening to provide possible novel therapeutic approaches to counteract malignant tumors regarding the intervention of calcium channels of this type.
基金This study was supported by the Major Research Program of National Natural Science Foundation of China(No.91542108,81471513,and 31671200)the Shanghai Rising-Star Program 16QA1400800+1 种基金the Innovation-oriented Science and Technology Grant from National Population and Family Planning Commission Key Laboratory of Reproduction Regulation(CX2017-2)the Program for Zhuoxue of Fudan University,China.
文摘Endometriosis(EMS)is a chronic inflammatory and estrogen-dependent gynecological disease characterized by the presence of endometrial tissue outside the uterine cavity.Although it is a benign disease,EMS is tumor-like in several aspects,which include unrestrained growth,decreased apoptosis,and aggressive invasion.EMS involves endocrine disorders and immunological factors.Indoleamine 2,3-dioxygenase(IDO)is an intracellular enzyme that catalyzes the initial and rate-limiting step of the metabolism of tryptophan.IDO is a potential candidate facilitating EMS development.Increased IDO expression in both eutopic and ectopic endometria of women with EMS is biologically important in aspects,which include regulation of endometrial stromal cell function and modulation of adjacent local immunocytes to generate a supportive microenvironment.In turn,the expression of IDO can be regulated by the complex endocrine-immune microenvironment networks in endometrial lesions.Here,we systematically review the roles of IDO in EMS to explore its pathological implications and treatment potential.
