BACKGROUND: Sepsis has become the greatest threat to in-patients, with a mortality of over 25%.The dysfunction of gut barrier, especially the immunological barrier, plays an important role in the development of sepsi...BACKGROUND: Sepsis has become the greatest threat to in-patients, with a mortality of over 25%.The dysfunction of gut barrier, especially the immunological barrier, plays an important role in the development of sepsis. This dysfunction occurs after surgery, but the magnitude of change does not differentiate patients with sepsis from those without sepsis. Increased intestinal permeability before surgery is of no value in predicating sepsis. The present study aimed to observe the changes of intestinal mucosal immunologic barrier in rat models of sepsis induced by cecal ligation and puncture.METHODS: Sixty Sprague-Dawley rats were randomly divided into a sepsis group (n=45) and a control group (n=15). The rats in the sepsis group were subjected to cecal ligation and puncture (CLP), whereas the rats in the control group underwent a sham operation. The ileac mucosa and segments were harvested 3, 6 and 12 hours after CLP, and blood samples were collected. Pathological changes, protein levels of defensin-5 (RD-5) and trefoil factor-3 (TFF3) mRNA, and lymphocytes apoptosis in the intestinal mucosa were determined. In an additional experiment, the gut-origin bacterial DNA in blood was detected.RESULTS: The intestinal mucosa showed marked injury with loss of ileal villi, desquamation of epithelium, detachment of lamina propria, hemorrhage and ulceration in the sepsis group. The expression of TFF3 mRNA and level of RD-5 protein were decreased and the apoptosis of mucosal lymphocyte increased (P〈0.05) in the sepsis group compared with the control group. Significant differences were observed in RD-5 and TFF3 mRNA 3 hours after CLP and they were progressively increased 6 and 12 hours after CLP in the sepsis group compared with the control group (P〈0.05, RD-5 F=11.76, TFF3 F=16.86 and apoptosis F=122.52). In addition, the gut-origin bacterial DNA detected in plasma was positive in the sepsis group.CONCLUSION: The immunological function of the intestinal mucosa was impaired in septic rats and further deteriorated in the course of sepsis.展开更多
BACKGROUND Cirrhosis results from persistent liver injury that leads to liver fibrosis.Immunological factors play important regulatory roles in the development and progression of cirrhosis.Bibliometrics is one of the ...BACKGROUND Cirrhosis results from persistent liver injury that leads to liver fibrosis.Immunological factors play important regulatory roles in the development and progression of cirrhosis.Bibliometrics is one of the most commonly used methods for systematic evaluation of a field of study.To date,there are no bibliometric studies on the role of immunological factors in cirrhosis.AIM To provide a comprehensive overview of the knowledge structure and research hotspots of immunological factors in cirrhosis.METHODS We retrieved publications related to immunological factors in cirrhosis between 2003 to 2022 from the Web of Science Core Collection database on December 7,2022.The search strategy was TS=((Liver Cirrhosis OR hepatic cirrhosis OR liver fibrosis)AND(Immunologic*Factor*OR Immune Factor*OR Immunomodulator*OR Biological Response Modifier*OR Biomodulator*)).Only original articles and reviews were included.A total of 2873 publications were analyzed using indicators of publication and citation metrics,countries,institutes,authors,journals,references,and keywords by CiteSpace and VOSviewer.RESULTS A total of 5104 authors from 1173 institutions across 51 countries published 2873 papers on cirrhosis and immunological factors in 281 journals.In the past 20 years,the increasing number of related annual publications and citations indicates that research on immunological factors in cirrhosis has become the focus of attention and has entered a period of accelerated development.The United States(781/27.18%),China(538/18.73%),and Germany(300/10.44%)were the leading countries in this field.Most of the top 10 authors were from the United States(4)and Germany(3),with Gershwin ME contributing the most related articles(42).World Journal of Gastroenterology was the most productive journal,whereas Hepatology was the most co-cited journal.Current research hotspots regarding immunological factors in cirrhosis include fibrosis,cirrhosis,inflammation,liver fibrosis,expression,hepatocellular carcinoma,activation,primary biliary cirrhosis,disease,and hepatic stellate cells.Burst keywords(e.g.,epidemiology,gut microbiota,and pathways)represent research frontiers that have attracted the interest of researchers in recent years.CONCLUSION This bibliometric study comprehensively summarizes the research developments and directions of immunological factors in cirrhosis,providing new ideas for promoting scientific research and clinical applications.展开更多
Histamine in food has attracted widespread attention due to the potential toxicity and associated health risk.However,its influences on immunological components,especially the function of key immune cells,are still po...Histamine in food has attracted widespread attention due to the potential toxicity and associated health risk.However,its influences on immunological components,especially the function of key immune cells,are still poorly known.In this work,we explored the effects of exogenous histamine on the function of key immune cells such as intestinal epithelial cells,dendritic cells,and T cells.The results showed that histamine could affect the expression of allergy-related genes in CMT93 cells at a high dose of histamine.Moreover,it’s found that histamine could cause an imbalance in the levels of relevant immune factors secreted by dendritic cells and T cells,especially those related to allergy.At the same time,the proportion of MHC class IIpositive dendritic cells and the proportion of T helper 2(Th2)cells in CD4^(+)T cells increased after histamine stimulation.We concluded that the presence of a certain level of histamine in food may affect the expression of allergy-related cytokines,disrupt the balance of the immune homeostasis,and potentially lead to adverse immune reactions.This work demonstrated the importance of including the estimation of histamine’s immune safety in aquatic products rather than merely considering the potential risk of food poisoning.展开更多
Immune checkpoint inhibitors(ICIs)have significantly improved outcomes for patients with advanced driver-negative non-small cell lung cancer(NSCLC).However,targeted therapy remains the preferred treatment for advanced...Immune checkpoint inhibitors(ICIs)have significantly improved outcomes for patients with advanced driver-negative non-small cell lung cancer(NSCLC).However,targeted therapy remains the preferred treatment for advanced driver-positive NSCLC,including cases with epidermal growth factor receptor(EGFR)mutations.Con-sidering the variability in EGFR-mutant NSCLC,including expression levels of programmed cell death ligand 1(PD-L1),tumor mutation burden(TMB),and other immunological features,the application of immunotherapy in this group is still a subject of investigation.Therefore,we have summarized and analyzed the immunological characteristics and regulatory mechanisms of different EGFR mutations in NSCLC,as well as the current clinical application of immunotherapy in the EGFR-mutant population,to provide a reference for future research.展开更多
IM To investigate the risk factors of esophageal cancer (EC) in urban areas of Xi′an and to determine the association between overexpression of P53 and these risk factors.METHODS All cases (89) and controls (97) we...IM To investigate the risk factors of esophageal cancer (EC) in urban areas of Xi′an and to determine the association between overexpression of P53 and these risk factors.METHODS All cases (89) and controls (97) were permanent residents in urban areas of Xi′an, all cases of primary EC had been histologically confirmed, controls were inpatients with noncancer and nonsmokingrelated disease. Cancer tissues and tissues adjacent to the cancer of 65 cases and 24 available normal esophageal tissues of controls were detected for P53 overexpression by the immunohistochemical method.RESULTS The smoking and familial history of cancer were significantly associated with EC in Xi′an inhabitants. The laboratory assay indicated that P53 positive stain in EC was 500%(34/65) and 61%(4/65) in tissues adjacent to the cancer, but no positive stain was found in normal esophageal tissues of controls. The results showed that P53 overexpression in EC was closely related to smoking and cases with familial history of cancer.CONCLUSION Smoking and familial cancer history were important risk factors for EC, and the alteration of P53 gene may be due to smoking and inheritance factors..展开更多
BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are heterogeneous cell types that suppress T-cell responses in cancer patients and animal models, some MDSC subpopulations are increased in patients with pancrea...BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are heterogeneous cell types that suppress T-cell responses in cancer patients and animal models, some MDSC subpopulations are increased in patients with pancreatic cancer. The present study was to investigate a specific subset of MDSCs in patients with pancreatic cancer and the mechanism of MDSCs increase in these patients. METHODS: Myeloid cells from whole blood were collected from 37 patients with pancreatic cancer, 17 with cholangiocarcinoma, and 47 healthy controls. Four pancreatic cancer cell lines were co- cultured with normal peripheral blood mononudear cells (PBMCs) to test the effect of tumor cells on the conversion of PBMCs to MDSCs. Levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and arginase activity in the plasma of cancer patients were analyzed by enzyme-linked immunosorbent assay. RESULTS: CD14+/CD11b+/HLA-DR MDSCs were increased in patients with pancreatic or bile duct cancer compared with those in healthy controls, and this increase was correlated with clinical cancer stage. Pancreatic cancer cell lines induced PBMCs to MDSCs in a dose-dependent manner. GM-CSF and arginase activity levels were significantly increased in the se rum of patients with pancreatic cancer. CONCLUSIONS: MDSCs were tumor related: tumor cells induced PBMCs to MDSCs in a dose-dependent manner and circulating CD14+/CD11b+/HLA-DR- MDSCs in pancreatic cancer patients were positively correlated with tumor burden. MDSCs might be useful markers for pancreatic cancer detection and progression.展开更多
Insulin-like growth factor binding-protein-7 (IGFBP7) was obtained from our previous colonic adenocarcinoma (CRC) and normal mucosa suppression subtraction hybridization (SSH) cDNA libraries. By RT-PCR and immun...Insulin-like growth factor binding-protein-7 (IGFBP7) was obtained from our previous colonic adenocarcinoma (CRC) and normal mucosa suppression subtraction hybridization (SSH) cDNA libraries. By RT-PCR and immunohistochemistry, we found that IGFBP7 was overexpressed in CRC tissue compared to normal tissue. However, our in vitro experiments performed in 10 CRC cell lines showed that IGFBP7 expressed only in SW480 and Caco2 cell lines, which implied an underlying reversible regulatory mechanism. Using methylation-specific PCR (MSP) and bisulfite sodium PCR (BSP), we found that its expression was associated with DNA hypomethylation of exonl. This was further supported by the in vitro study which showed restored IGFBP7 expression after demethylation agent 5-aza-2'-deoxycytidine treatment. Correlation analysis between IGFBP7 expression and prognosis indicated that overexpression of IGFBP7 in CRC tissue correlated with favourable survival. Investigation of the functional role of IGFBP7 through transfection studies showed that IGFBP7 protein could inhibit growth rate, decrease colony formation activity, and induce apoptosis in RKO and SW620 cells, suggesting it a potential tumor suppressor protein in colorectal carcinogenesis. In conclusion, our study clearly demonstrated that IGFBP7 plays a potential tumor suppressor role against colorectal carcinogenesis and its expression is associated with DNA hypomethylation of exon 1.展开更多
To prepare an effective immune preparation to treat hepatitis B, hens were immunized with hepatitis B vaccines, and then anti-HBV egg yolk extraction (anti-HBV EYE) was refined from egg yolk by a dialyzable method. ...To prepare an effective immune preparation to treat hepatitis B, hens were immunized with hepatitis B vaccines, and then anti-HBV egg yolk extraction (anti-HBV EYE) was refined from egg yolk by a dialyzable method. Its chemical characteristics were identified by ultraviolet spectrum, HPLC, Lowry analysis and pharmacopocia-raleted methods. The specific immunological activity was examined by leukocyte adherence inhibition (LAI) in vitro and delayed type hypersensitivity (DTH) in vivo. Anti-HBV EYE was a small dialyzable substance with molecular weight less than 12 kD containing 18 kinds of amino acids. The preparation could obviously inhibit LAI and DTH which was similar to hepatitis B virus-specific transfer factor of pig spleen. However, there were no similar effects observed in the nonspecific transfer factor (NTF) group, control egg yolk extraction (CEYE) group and hepatitis A virus (HAV) group. The results suggested that anti-HBV EYE contained hepatitis B virus-specific transfer factor (STF) and had the antigen-specific cell immune activity similar to PSHBV-TF. The STF obtained from egg yolk of the hens immunized with specific antigen, might be a potential candidate for immunoregulation in hepatitis B prevention and treatment.展开更多
Background and aim: The Krueppel-like transcription factor KLF6 is a novel tumor-suppressor gene. It was inactivated in human prostate cancer and other tumors tissue, as the result of frequent mutation and loss of he...Background and aim: The Krueppel-like transcription factor KLF6 is a novel tumor-suppressor gene. It was inactivated in human prostate cancer and other tumors tissue, as the result of frequent mutation and loss of heterozygosity (LOH). However, there is no data reporting the levels of KLF6 both mRNA and protein in hepatocellular carcinomas (HCCs). We therefore detected mutations and expression of KLF6 in HCC tissues and further observed the effect of it on cell growth in HCC cell lines. Methods: We analyzed the exon-2 ofKLF6 gene by direct DNA sequencing, and detected the expression of KLF6 by RT-PCR and Western blot in 23 HCC tissues and corresponding nontumorous tissues. Loss of growth suppressive effect of the HCC-derived KLF6 mutant was characterized by in vitro growth curves plotted, flow cytometry and Western blotting. Results: KLF6 mutations were found in 2 of 23 HCC tissues and one of mutations was missense. Expression ofKLF6 mRNA or protein was down-regulated in 8 (34.7%) or 9 (39.1%) of 23 HCC tissues. Wild-type KLF6 (wtKLF6) inhibited cellular proliferation and prolonged G1 -S transition by inducing the expression of p21WAF 1 following stable transfection into cultured HepG2 cells, but tumor-derived KLF6 mutant (mKLF6) had no effects. Conclusion: Our findings suggest that KLF6 may be involved in pathogenesis of HCC.展开更多
Purpose: A series of clinical studies have established the safety and efficacy of transcatheter arterial chemoembolization(TACE) with gelatin sponge microparticles(GSMs) in treating hepatocellular carcinoma(HCC). HCC ...Purpose: A series of clinical studies have established the safety and efficacy of transcatheter arterial chemoembolization(TACE) with gelatin sponge microparticles(GSMs) in treating hepatocellular carcinoma(HCC). HCC can lead to obvious necrosis inside tumors, especially larger ones, although it is unclear whether such necrotic tumor tissue can induce favorable immune reactions against the tumor. Myeloid-derived suppressor cells(MDSCs)have immunosuppressive functions and are currently considered a very important cell type affecting tumor immunity. This study observed changes in MDSC frequency in peripheral blood before and after GSM–TACE to evaluate the effect on the immune function of HCC patients.Methods: Eight patients diagnosed with HCC underwent GSM–TACE treatment in the Hepatobiliary Interventional Department of Beijing Tsinghua Chang Gung Hospital, Beijing, China;we followed up with the patients over a period of 30 days post-surgery. We used flow cytometry(FCM) to quantify the frequency of MDSCs in peripheral blood before TACE, 10 days after surgery and 30 days after surgery.Results: MDSC frequency after GSM–TACE had a significant downward trend. Pre-TACE, it was 30.73% ? 11.93%,decreasing to 18.60% ? 11.37% at 10 days after operation. This decrease was not statistically significant(P > 0.05). MDSC frequency was even lower 30 days after TACE(7.63% ? 7.32%) than at 10 days after TACE(P < 0.05), and there was a significant difference compared with pre-TACE(P < 0.001). We evaluated tumor response at 30 days after GSM–TACE according to the Modified Response Evaluation Criteria in Solid Tumors(mRECIST), and all eight patients showed partial response(PR).Conclusion: Our results confirmed that GSM–TACE was beneficial for improving anti-tumor immunity in the treatment of HCC.展开更多
The effects of granulocyte colony-stimulation-factor (G-CSF) on stem cell mobilization and its impact on the amplification of myeloid-derived suppressor cells (MDSCs) of donor mice were ex- amined. A mouse model o...The effects of granulocyte colony-stimulation-factor (G-CSF) on stem cell mobilization and its impact on the amplification of myeloid-derived suppressor cells (MDSCs) of donor mice were ex- amined. A mouse model of stem cell mobilization was established by consecutive subcutaneous injec- tion of 100 μg/kg G-CSF for 5 days. The blood from the donor mice was routinely examined during mobilization. Stem cells and MDSCs were analyzed by flow cytometry. The immunosuppressive mole- cules derived from MDSCs in serum and spleen, including hydrogen dioxide (H202) and nitric oxide (NO), and the activity of nitric oxide synthase (NOS) were determined during the mobilization. Apop- tosis of T lymphocytes was assessed by using Annexin-V/PI. During stem cell mobilization, the number of lymphocytes and white blood cells in the peripheral blood was increased, and peaked on the 4th day. The number of stem cells in G-CSF-treated mice was significantly greater than that in controls (P〈0.01). The expansions of MSDCs were also observed after G-CSF mobilization, with a more notable rate of growth in the peripheral blood than in the spleen. The activity of NOS and the production of NO were increased in the donor mice, and the serum H202 levels were approximately 4-fold greater than the con- trois. Consequently, apoptosis of T lymphocytes was increased and showed a positive correlation with the elevated percentage of MDSCs. It was concluded that G-CSF could provide sufficient peripheral blood stem cells for transplantation. Exogenous administration of G-CSF caused the accumulation of MDSCs in the peripheral blood and the spleen, which could lead to apoptosis ofT lymphocytes and may offer a new strategy for the prevention and treatment of graft versus host disease.展开更多
The leukemia-associated autoinhibitor (LAI-615) derived from murine leukemia L7811 has been investigated intensively in our laboratory. In the following experiments, the partial purification of LA I-615 has been carri...The leukemia-associated autoinhibitor (LAI-615) derived from murine leukemia L7811 has been investigated intensively in our laboratory. In the following experiments, the partial purification of LA I-615 has been carried out in addition to the observation of phenotype variations of L7811 leuke-mic cells. The factor was purified over 1306-fold by sequential fractionation with Sephadex G-150 gel filtration, DEAE-cellulose ion exchange chromato-graphy, and Mono Q-fast protein liquid chromato-graphy. The molecular weight of LAI-615 was 68,000 as estimated by gel filtration. LAI-615 was a protein but not glycosylated, and it was suggested LAI-615 be secreted in an autocrine manner. Im-munocytochemical staining showed that the expression of Lyt2 phenotype of L7811 leukemic cells was often coincident with the secretion of LAI-615. Moreover, the physicochemical characteristics of LAI-615 was similar to that of T suppressor factor. Thus it is concluded that LAI-615 may be one of TsF-like factors.展开更多
Objective:To explore the effect of Kangfuxin solution on inflammatory, immune, oxidative indexes and vascular factorsin patients with ulcerative colitis.Methods: 172 cases of ulcerative colitis from August 2015 to Feb...Objective:To explore the effect of Kangfuxin solution on inflammatory, immune, oxidative indexes and vascular factorsin patients with ulcerative colitis.Methods: 172 cases of ulcerative colitis from August 2015 to February 2017 were selected and divided into control group (n=86) and observation group (n=86) according to random principle, the control group was treated with Mesalazin Enteric-coated Tablets, and the observation group was treated with enema by infusion of rectal drip on the basis of the control group, and the levels of the two groups of inflammatory factors, immune indexes, oxidation indexes and vascular factors were compared.Results: After treatment, the total effective rate of the observation group (88.37%) was significantly higher than that of the control group (73.26%) (P<0.05);the two groups of CRP and TNF-α were significantly lower than those before treatment (P<0.05), and the observation group was significantly lower than that of the control group (P<0.05);the two groups of CD4+, CD4+/CD8+ and SOD increased significantly compared with those before treatment (P<0.05), while CD8+, MDA and LOP were significantly lower than those before treatment (P<0.05), and the CD4+, CD4+/CD8+ and SOD in the observation group were significantly higher than those in the control group (P<0.05), while CD8+, MDA and LOP were significantly lower than those in the control group (P<0.05);The levels of VEGF and PDGF in both groups were significantly higher than those before treatment (P<0.05), and the levels of VEGF and PDG in observation group were significantly higher than those in control group (P<0.05).Conclusions:The combined treatment of Kangfuxin Liquid and mesalazine can significantly improve the clinical efficacy of the patients. The mechanism of its action is related to reducing the inflammatory response and enhancing the immune, antioxidant functionsand vascular factors. It is worthy of further study in clinical.展开更多
Objective: To investigate the correlation of Runt-related transcription factor 2 (RunX2) with proliferation genes, tumor suppressor genes and angiogenesis molecules in colon cancer lesions. Methods: A total of 90 pati...Objective: To investigate the correlation of Runt-related transcription factor 2 (RunX2) with proliferation genes, tumor suppressor genes and angiogenesis molecules in colon cancer lesions. Methods: A total of 90 patients with primary colon cancer were enrolled in colon cancer group, 68 patients with benign colon polyps were enrolled in colon polyps group, the differences in the expression levels of RunX2, proliferation genes, tumor suppressor genes and angiogenesis molecules in the two groups of lesions were compared, and Pearson test was further used to evaluate the correlation of RunX2 expression level with proliferation gene, tumor suppressor gene and angiogenesis molecule expression levels in colon cancer tissues. Results: RunX2 mRNA expression level in the lesions of colon cancer group was higher than that of colon polyps group. Proliferation genes GTPBP4, HOXB7, ZNF331, ADAM17 and HSP60 mRNA expression levels in the lesions of colon cancer group were higher than those of colon polyps group;tumor suppressor genes ATF3, FOXN3, OTUD1 and NDRG2 mRNA expression levels were lower than those of colon polyps group;angiogenesis molecules Musashi 1, NF-κB, RegⅣ and STAT3 mRNA expression levels were higher than those of colon polyps group. RunX2 mRNA expression level in the colon cancer lesions was directly correlated with the expression levels of the above proliferation genes, tumor suppressor genes and angiogenesis molecules. Conclusion: RunX2 expression is abnormally high in colon cancer lesions, the specific expression level is positively correlated with cancer cell proliferation activity and angiogenesis activity, and it is an important molecular target that can lead to the occurrence and development of colon cancer.展开更多
基金This study was supported by the National Natural Science Foundation of Guangdong Province (06021323).
文摘BACKGROUND: Sepsis has become the greatest threat to in-patients, with a mortality of over 25%.The dysfunction of gut barrier, especially the immunological barrier, plays an important role in the development of sepsis. This dysfunction occurs after surgery, but the magnitude of change does not differentiate patients with sepsis from those without sepsis. Increased intestinal permeability before surgery is of no value in predicating sepsis. The present study aimed to observe the changes of intestinal mucosal immunologic barrier in rat models of sepsis induced by cecal ligation and puncture.METHODS: Sixty Sprague-Dawley rats were randomly divided into a sepsis group (n=45) and a control group (n=15). The rats in the sepsis group were subjected to cecal ligation and puncture (CLP), whereas the rats in the control group underwent a sham operation. The ileac mucosa and segments were harvested 3, 6 and 12 hours after CLP, and blood samples were collected. Pathological changes, protein levels of defensin-5 (RD-5) and trefoil factor-3 (TFF3) mRNA, and lymphocytes apoptosis in the intestinal mucosa were determined. In an additional experiment, the gut-origin bacterial DNA in blood was detected.RESULTS: The intestinal mucosa showed marked injury with loss of ileal villi, desquamation of epithelium, detachment of lamina propria, hemorrhage and ulceration in the sepsis group. The expression of TFF3 mRNA and level of RD-5 protein were decreased and the apoptosis of mucosal lymphocyte increased (P〈0.05) in the sepsis group compared with the control group. Significant differences were observed in RD-5 and TFF3 mRNA 3 hours after CLP and they were progressively increased 6 and 12 hours after CLP in the sepsis group compared with the control group (P〈0.05, RD-5 F=11.76, TFF3 F=16.86 and apoptosis F=122.52). In addition, the gut-origin bacterial DNA detected in plasma was positive in the sepsis group.CONCLUSION: The immunological function of the intestinal mucosa was impaired in septic rats and further deteriorated in the course of sepsis.
基金the National Multi-Center Clinical Research Project of Peking University First Hospital,No.2022CR57.
文摘BACKGROUND Cirrhosis results from persistent liver injury that leads to liver fibrosis.Immunological factors play important regulatory roles in the development and progression of cirrhosis.Bibliometrics is one of the most commonly used methods for systematic evaluation of a field of study.To date,there are no bibliometric studies on the role of immunological factors in cirrhosis.AIM To provide a comprehensive overview of the knowledge structure and research hotspots of immunological factors in cirrhosis.METHODS We retrieved publications related to immunological factors in cirrhosis between 2003 to 2022 from the Web of Science Core Collection database on December 7,2022.The search strategy was TS=((Liver Cirrhosis OR hepatic cirrhosis OR liver fibrosis)AND(Immunologic*Factor*OR Immune Factor*OR Immunomodulator*OR Biological Response Modifier*OR Biomodulator*)).Only original articles and reviews were included.A total of 2873 publications were analyzed using indicators of publication and citation metrics,countries,institutes,authors,journals,references,and keywords by CiteSpace and VOSviewer.RESULTS A total of 5104 authors from 1173 institutions across 51 countries published 2873 papers on cirrhosis and immunological factors in 281 journals.In the past 20 years,the increasing number of related annual publications and citations indicates that research on immunological factors in cirrhosis has become the focus of attention and has entered a period of accelerated development.The United States(781/27.18%),China(538/18.73%),and Germany(300/10.44%)were the leading countries in this field.Most of the top 10 authors were from the United States(4)and Germany(3),with Gershwin ME contributing the most related articles(42).World Journal of Gastroenterology was the most productive journal,whereas Hepatology was the most co-cited journal.Current research hotspots regarding immunological factors in cirrhosis include fibrosis,cirrhosis,inflammation,liver fibrosis,expression,hepatocellular carcinoma,activation,primary biliary cirrhosis,disease,and hepatic stellate cells.Burst keywords(e.g.,epidemiology,gut microbiota,and pathways)represent research frontiers that have attracted the interest of researchers in recent years.CONCLUSION This bibliometric study comprehensively summarizes the research developments and directions of immunological factors in cirrhosis,providing new ideas for promoting scientific research and clinical applications.
基金financially supported by the Key Project of Zhejiang Provincial Natural Science Foundation of China(LZ22C200003)the National Natural Science Foundation of China(32072290)。
文摘Histamine in food has attracted widespread attention due to the potential toxicity and associated health risk.However,its influences on immunological components,especially the function of key immune cells,are still poorly known.In this work,we explored the effects of exogenous histamine on the function of key immune cells such as intestinal epithelial cells,dendritic cells,and T cells.The results showed that histamine could affect the expression of allergy-related genes in CMT93 cells at a high dose of histamine.Moreover,it’s found that histamine could cause an imbalance in the levels of relevant immune factors secreted by dendritic cells and T cells,especially those related to allergy.At the same time,the proportion of MHC class IIpositive dendritic cells and the proportion of T helper 2(Th2)cells in CD4^(+)T cells increased after histamine stimulation.We concluded that the presence of a certain level of histamine in food may affect the expression of allergy-related cytokines,disrupt the balance of the immune homeostasis,and potentially lead to adverse immune reactions.This work demonstrated the importance of including the estimation of histamine’s immune safety in aquatic products rather than merely considering the potential risk of food poisoning.
基金supported by the Natural Science Foundation of Hubei Province of China(grant number:2022CFB114).
文摘Immune checkpoint inhibitors(ICIs)have significantly improved outcomes for patients with advanced driver-negative non-small cell lung cancer(NSCLC).However,targeted therapy remains the preferred treatment for advanced driver-positive NSCLC,including cases with epidermal growth factor receptor(EGFR)mutations.Con-sidering the variability in EGFR-mutant NSCLC,including expression levels of programmed cell death ligand 1(PD-L1),tumor mutation burden(TMB),and other immunological features,the application of immunotherapy in this group is still a subject of investigation.Therefore,we have summarized and analyzed the immunological characteristics and regulatory mechanisms of different EGFR mutations in NSCLC,as well as the current clinical application of immunotherapy in the EGFR-mutant population,to provide a reference for future research.
文摘IM To investigate the risk factors of esophageal cancer (EC) in urban areas of Xi′an and to determine the association between overexpression of P53 and these risk factors.METHODS All cases (89) and controls (97) were permanent residents in urban areas of Xi′an, all cases of primary EC had been histologically confirmed, controls were inpatients with noncancer and nonsmokingrelated disease. Cancer tissues and tissues adjacent to the cancer of 65 cases and 24 available normal esophageal tissues of controls were detected for P53 overexpression by the immunohistochemical method.RESULTS The smoking and familial history of cancer were significantly associated with EC in Xi′an inhabitants. The laboratory assay indicated that P53 positive stain in EC was 500%(34/65) and 61%(4/65) in tissues adjacent to the cancer, but no positive stain was found in normal esophageal tissues of controls. The results showed that P53 overexpression in EC was closely related to smoking and cases with familial history of cancer.CONCLUSION Smoking and familial cancer history were important risk factors for EC, and the alteration of P53 gene may be due to smoking and inheritance factors..
基金supported by grants from the National Natural Science Foundation of China(81071775,81272659,81101621,81160311,81172064,81001068,81272425 and 81101870)National“Eleventh Five-Year”Scientific and Technological Support Projects(2006BAI02A13-402)+1 种基金Key Projects of Science Foundation of Hubei Province(2011CDA030)Research Fund of Young Scholars for the Doctoral Program of Higher Education of China(20110142120014)
文摘BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are heterogeneous cell types that suppress T-cell responses in cancer patients and animal models, some MDSC subpopulations are increased in patients with pancreatic cancer. The present study was to investigate a specific subset of MDSCs in patients with pancreatic cancer and the mechanism of MDSCs increase in these patients. METHODS: Myeloid cells from whole blood were collected from 37 patients with pancreatic cancer, 17 with cholangiocarcinoma, and 47 healthy controls. Four pancreatic cancer cell lines were co- cultured with normal peripheral blood mononudear cells (PBMCs) to test the effect of tumor cells on the conversion of PBMCs to MDSCs. Levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and arginase activity in the plasma of cancer patients were analyzed by enzyme-linked immunosorbent assay. RESULTS: CD14+/CD11b+/HLA-DR MDSCs were increased in patients with pancreatic or bile duct cancer compared with those in healthy controls, and this increase was correlated with clinical cancer stage. Pancreatic cancer cell lines induced PBMCs to MDSCs in a dose-dependent manner. GM-CSF and arginase activity levels were significantly increased in the se rum of patients with pancreatic cancer. CONCLUSIONS: MDSCs were tumor related: tumor cells induced PBMCs to MDSCs in a dose-dependent manner and circulating CD14+/CD11b+/HLA-DR- MDSCs in pancreatic cancer patients were positively correlated with tumor burden. MDSCs might be useful markers for pancreatic cancer detection and progression.
基金Project (Nos. 30200333 and 30570840) supported by the NationalNatural Science Foundation of China
文摘Insulin-like growth factor binding-protein-7 (IGFBP7) was obtained from our previous colonic adenocarcinoma (CRC) and normal mucosa suppression subtraction hybridization (SSH) cDNA libraries. By RT-PCR and immunohistochemistry, we found that IGFBP7 was overexpressed in CRC tissue compared to normal tissue. However, our in vitro experiments performed in 10 CRC cell lines showed that IGFBP7 expressed only in SW480 and Caco2 cell lines, which implied an underlying reversible regulatory mechanism. Using methylation-specific PCR (MSP) and bisulfite sodium PCR (BSP), we found that its expression was associated with DNA hypomethylation of exonl. This was further supported by the in vitro study which showed restored IGFBP7 expression after demethylation agent 5-aza-2'-deoxycytidine treatment. Correlation analysis between IGFBP7 expression and prognosis indicated that overexpression of IGFBP7 in CRC tissue correlated with favourable survival. Investigation of the functional role of IGFBP7 through transfection studies showed that IGFBP7 protein could inhibit growth rate, decrease colony formation activity, and induce apoptosis in RKO and SW620 cells, suggesting it a potential tumor suppressor protein in colorectal carcinogenesis. In conclusion, our study clearly demonstrated that IGFBP7 plays a potential tumor suppressor role against colorectal carcinogenesis and its expression is associated with DNA hypomethylation of exon 1.
文摘To prepare an effective immune preparation to treat hepatitis B, hens were immunized with hepatitis B vaccines, and then anti-HBV egg yolk extraction (anti-HBV EYE) was refined from egg yolk by a dialyzable method. Its chemical characteristics were identified by ultraviolet spectrum, HPLC, Lowry analysis and pharmacopocia-raleted methods. The specific immunological activity was examined by leukocyte adherence inhibition (LAI) in vitro and delayed type hypersensitivity (DTH) in vivo. Anti-HBV EYE was a small dialyzable substance with molecular weight less than 12 kD containing 18 kinds of amino acids. The preparation could obviously inhibit LAI and DTH which was similar to hepatitis B virus-specific transfer factor of pig spleen. However, there were no similar effects observed in the nonspecific transfer factor (NTF) group, control egg yolk extraction (CEYE) group and hepatitis A virus (HAV) group. The results suggested that anti-HBV EYE contained hepatitis B virus-specific transfer factor (STF) and had the antigen-specific cell immune activity similar to PSHBV-TF. The STF obtained from egg yolk of the hens immunized with specific antigen, might be a potential candidate for immunoregulation in hepatitis B prevention and treatment.
文摘Background and aim: The Krueppel-like transcription factor KLF6 is a novel tumor-suppressor gene. It was inactivated in human prostate cancer and other tumors tissue, as the result of frequent mutation and loss of heterozygosity (LOH). However, there is no data reporting the levels of KLF6 both mRNA and protein in hepatocellular carcinomas (HCCs). We therefore detected mutations and expression of KLF6 in HCC tissues and further observed the effect of it on cell growth in HCC cell lines. Methods: We analyzed the exon-2 ofKLF6 gene by direct DNA sequencing, and detected the expression of KLF6 by RT-PCR and Western blot in 23 HCC tissues and corresponding nontumorous tissues. Loss of growth suppressive effect of the HCC-derived KLF6 mutant was characterized by in vitro growth curves plotted, flow cytometry and Western blotting. Results: KLF6 mutations were found in 2 of 23 HCC tissues and one of mutations was missense. Expression ofKLF6 mRNA or protein was down-regulated in 8 (34.7%) or 9 (39.1%) of 23 HCC tissues. Wild-type KLF6 (wtKLF6) inhibited cellular proliferation and prolonged G1 -S transition by inducing the expression of p21WAF 1 following stable transfection into cultured HepG2 cells, but tumor-derived KLF6 mutant (mKLF6) had no effects. Conclusion: Our findings suggest that KLF6 may be involved in pathogenesis of HCC.
基金Supported by a grant from National Natural Science Foundation of China(grant number 81571783)National Major Project for Infectious Diseases of China(2017ZX100203205005)
文摘Purpose: A series of clinical studies have established the safety and efficacy of transcatheter arterial chemoembolization(TACE) with gelatin sponge microparticles(GSMs) in treating hepatocellular carcinoma(HCC). HCC can lead to obvious necrosis inside tumors, especially larger ones, although it is unclear whether such necrotic tumor tissue can induce favorable immune reactions against the tumor. Myeloid-derived suppressor cells(MDSCs)have immunosuppressive functions and are currently considered a very important cell type affecting tumor immunity. This study observed changes in MDSC frequency in peripheral blood before and after GSM–TACE to evaluate the effect on the immune function of HCC patients.Methods: Eight patients diagnosed with HCC underwent GSM–TACE treatment in the Hepatobiliary Interventional Department of Beijing Tsinghua Chang Gung Hospital, Beijing, China;we followed up with the patients over a period of 30 days post-surgery. We used flow cytometry(FCM) to quantify the frequency of MDSCs in peripheral blood before TACE, 10 days after surgery and 30 days after surgery.Results: MDSC frequency after GSM–TACE had a significant downward trend. Pre-TACE, it was 30.73% ? 11.93%,decreasing to 18.60% ? 11.37% at 10 days after operation. This decrease was not statistically significant(P > 0.05). MDSC frequency was even lower 30 days after TACE(7.63% ? 7.32%) than at 10 days after TACE(P < 0.05), and there was a significant difference compared with pre-TACE(P < 0.001). We evaluated tumor response at 30 days after GSM–TACE according to the Modified Response Evaluation Criteria in Solid Tumors(mRECIST), and all eight patients showed partial response(PR).Conclusion: Our results confirmed that GSM–TACE was beneficial for improving anti-tumor immunity in the treatment of HCC.
基金supported by grants from Department of Health of Hubei Province(No.JX5B07)Department of Health of Wuhan(No.WX09B02)
文摘The effects of granulocyte colony-stimulation-factor (G-CSF) on stem cell mobilization and its impact on the amplification of myeloid-derived suppressor cells (MDSCs) of donor mice were ex- amined. A mouse model of stem cell mobilization was established by consecutive subcutaneous injec- tion of 100 μg/kg G-CSF for 5 days. The blood from the donor mice was routinely examined during mobilization. Stem cells and MDSCs were analyzed by flow cytometry. The immunosuppressive mole- cules derived from MDSCs in serum and spleen, including hydrogen dioxide (H202) and nitric oxide (NO), and the activity of nitric oxide synthase (NOS) were determined during the mobilization. Apop- tosis of T lymphocytes was assessed by using Annexin-V/PI. During stem cell mobilization, the number of lymphocytes and white blood cells in the peripheral blood was increased, and peaked on the 4th day. The number of stem cells in G-CSF-treated mice was significantly greater than that in controls (P〈0.01). The expansions of MSDCs were also observed after G-CSF mobilization, with a more notable rate of growth in the peripheral blood than in the spleen. The activity of NOS and the production of NO were increased in the donor mice, and the serum H202 levels were approximately 4-fold greater than the con- trois. Consequently, apoptosis of T lymphocytes was increased and showed a positive correlation with the elevated percentage of MDSCs. It was concluded that G-CSF could provide sufficient peripheral blood stem cells for transplantation. Exogenous administration of G-CSF caused the accumulation of MDSCs in the peripheral blood and the spleen, which could lead to apoptosis ofT lymphocytes and may offer a new strategy for the prevention and treatment of graft versus host disease.
文摘The leukemia-associated autoinhibitor (LAI-615) derived from murine leukemia L7811 has been investigated intensively in our laboratory. In the following experiments, the partial purification of LA I-615 has been carried out in addition to the observation of phenotype variations of L7811 leuke-mic cells. The factor was purified over 1306-fold by sequential fractionation with Sephadex G-150 gel filtration, DEAE-cellulose ion exchange chromato-graphy, and Mono Q-fast protein liquid chromato-graphy. The molecular weight of LAI-615 was 68,000 as estimated by gel filtration. LAI-615 was a protein but not glycosylated, and it was suggested LAI-615 be secreted in an autocrine manner. Im-munocytochemical staining showed that the expression of Lyt2 phenotype of L7811 leukemic cells was often coincident with the secretion of LAI-615. Moreover, the physicochemical characteristics of LAI-615 was similar to that of T suppressor factor. Thus it is concluded that LAI-615 may be one of TsF-like factors.
文摘Objective:To explore the effect of Kangfuxin solution on inflammatory, immune, oxidative indexes and vascular factorsin patients with ulcerative colitis.Methods: 172 cases of ulcerative colitis from August 2015 to February 2017 were selected and divided into control group (n=86) and observation group (n=86) according to random principle, the control group was treated with Mesalazin Enteric-coated Tablets, and the observation group was treated with enema by infusion of rectal drip on the basis of the control group, and the levels of the two groups of inflammatory factors, immune indexes, oxidation indexes and vascular factors were compared.Results: After treatment, the total effective rate of the observation group (88.37%) was significantly higher than that of the control group (73.26%) (P<0.05);the two groups of CRP and TNF-α were significantly lower than those before treatment (P<0.05), and the observation group was significantly lower than that of the control group (P<0.05);the two groups of CD4+, CD4+/CD8+ and SOD increased significantly compared with those before treatment (P<0.05), while CD8+, MDA and LOP were significantly lower than those before treatment (P<0.05), and the CD4+, CD4+/CD8+ and SOD in the observation group were significantly higher than those in the control group (P<0.05), while CD8+, MDA and LOP were significantly lower than those in the control group (P<0.05);The levels of VEGF and PDGF in both groups were significantly higher than those before treatment (P<0.05), and the levels of VEGF and PDG in observation group were significantly higher than those in control group (P<0.05).Conclusions:The combined treatment of Kangfuxin Liquid and mesalazine can significantly improve the clinical efficacy of the patients. The mechanism of its action is related to reducing the inflammatory response and enhancing the immune, antioxidant functionsand vascular factors. It is worthy of further study in clinical.
文摘Objective: To investigate the correlation of Runt-related transcription factor 2 (RunX2) with proliferation genes, tumor suppressor genes and angiogenesis molecules in colon cancer lesions. Methods: A total of 90 patients with primary colon cancer were enrolled in colon cancer group, 68 patients with benign colon polyps were enrolled in colon polyps group, the differences in the expression levels of RunX2, proliferation genes, tumor suppressor genes and angiogenesis molecules in the two groups of lesions were compared, and Pearson test was further used to evaluate the correlation of RunX2 expression level with proliferation gene, tumor suppressor gene and angiogenesis molecule expression levels in colon cancer tissues. Results: RunX2 mRNA expression level in the lesions of colon cancer group was higher than that of colon polyps group. Proliferation genes GTPBP4, HOXB7, ZNF331, ADAM17 and HSP60 mRNA expression levels in the lesions of colon cancer group were higher than those of colon polyps group;tumor suppressor genes ATF3, FOXN3, OTUD1 and NDRG2 mRNA expression levels were lower than those of colon polyps group;angiogenesis molecules Musashi 1, NF-κB, RegⅣ and STAT3 mRNA expression levels were higher than those of colon polyps group. RunX2 mRNA expression level in the colon cancer lesions was directly correlated with the expression levels of the above proliferation genes, tumor suppressor genes and angiogenesis molecules. Conclusion: RunX2 expression is abnormally high in colon cancer lesions, the specific expression level is positively correlated with cancer cell proliferation activity and angiogenesis activity, and it is an important molecular target that can lead to the occurrence and development of colon cancer.