In the past,there has been considerable focus on a host of drugs and chemicals that may produce colonic toxicity.Now,a variety of new biological monoclonal antibody agents,usually administered by infusion,have appeare...In the past,there has been considerable focus on a host of drugs and chemicals that may produce colonic toxicity.Now,a variety of new biological monoclonal antibody agents,usually administered by infusion,have appeared in the clinical realm over the last decade or so to treat different chronic inflammatory or malignant disorders.For some of these agents,adverse effects have been documented,including apparently new forms of immune-mediated inflammatory bowel disease.In some,only limited symptoms have been recorded,but in others,severe colitis with serious complications,such as bowel perforation has been recorded.In others,adverse effects may have a direct vascular or ischemic basis,while other intestinal effects may be related to a superimposed infection.Some new onset cases of ulcerative colitis or Crohn's disease may also be attributed to the same agents used to treat these diseases,or be responsible for disease exacerbation.Dramatic and well documented side effects have been observed with ipilimumab,a humanized monoclonal antibody developed to reduce and overcome cytotoxic T-lymphocyte antigen 4,a key negative feedback regulator of the T-cell anti-tumor response.This agent has frequently been used in the treatment of different malignancies,notably,malignant melanoma.Side effects with this agent occur in up to 40% and these are believed to be largely immune-mediated.One of these is a form of enterocolitis that may be severe,and occa-sionally,fatal.Other agents include rituximab(an antiCD20 monoclonal antibody),bevacizumab(a monoclonal antibody against the vascular endothelial growth factor) and anti-tumor necrosis factor agents,including infliximab,adalimumab and etanercept.展开更多
Objective To compare effects of combined acupuncture and general anesthesia （CAGA） and general anesthesia （GA） on immune function in patients of laparoscopic cholecystectomy （LC） in peri-operative period. Method...Objective To compare effects of combined acupuncture and general anesthesia （CAGA） and general anesthesia （GA） on immune function in patients of laparoscopic cholecystectomy （LC） in peri-operative period. Methods Thirty-nine cases undergoing LC were randomly divided into a CAGA group and a GA group. The CAGA group was treated with electroacupuncture at Hegu （合谷- LI 4）, Neiguan （内关PC 6）, Zusanli （足三里ST 36） and Yanglingquan （阳陵泉 GB 34） for 15-30 minutes followed by the general anesthesia, and the continuous electroacupuncture stimulation was given till the operation finished. The GA group was treated with simple general anesthesia. Changes of T cell subsets, tumor necrosis factor-alpha （TNF-α） and interleukin-6 （IL-6） were observed before anesthesia induction, and 2 hours, 1st and 3 rd day after operation, and the adverse reaction after operation was recorded. Results At 2 hours after operation, the percentages of CD3 and CDs in both groups were significantly lower than those before anesthesia induction （all P〈0.05）, and the percentage of CD4 in the GA group decreased significantly （P〈0.05）, while the percentage of CD： did not significantly change and CD4/CD8 increased significantly in the CAGA group （P〈0.05）. At 3 days after operation, the level of TNF-α in the ACGA group decreased significantly as compared with that before anesthesia induction （P〈0.05）. The cases with nausea after operation in the CAGA group were significantly less than those in the GA group （P〈0.05）. Conclusion Acupuncture combined with general anesthesia has a little effect on immune function in patients of LC with less adverse reactions.展开更多
OBJECTIVE:To investigate the clinical effects of Weining Granules on gastric precancerous lesions(GPLs).METHODS:120 patients with GPLs were randomly assigned in a 1:1 ratio to receive Weining Granules(trial group) or ...OBJECTIVE:To investigate the clinical effects of Weining Granules on gastric precancerous lesions(GPLs).METHODS:120 patients with GPLs were randomly assigned in a 1:1 ratio to receive Weining Granules(trial group) or the comparator Weifuchun tablets(control group) for 6 months.Outcomes were compared between the two groups including:overall response;gastroscopically-determined response;pathologically-confirmed response;eradication of Helicobacter pylori(HP);microvessel density(MVD) in the gastric mucosa;expression of vascular endothelial growth factor(VEGF);interleukin 2(IL-2);interleukin 6(IL-6);T lymphocyte subsets;immunoglobulins;symptom scores;quality of life(QOL);and adverse reactions.RESULTS:Patients in the trial group had a significantly higher(P<0.05) overall response rate(81.7%) as compared with those in the control group(63.3%).Relative to treatment with Weifuchun tablets treatment with Weining Granules resulted in a significant improvement(P<0.05) in the scores for gastric pain,distension and stuffiness in the hypochondrium,and anorexia.As compared with the tablets the Granules were associated with a significantly higher overall gastroscopically-determined response rate(78.3%;P<0.05).Pathological examination of tissue samples indicated that 61.7% of patients receiving the granules were cured with an overall response rate of 75.5%;these rates were significantly higher than in the control group(P<0.05).In comparison with patients receiving the tablets,those given the granules were significantly more likely to have their HP eradicated(75.0% vs.51.4%;P<0.05).Improvements in MVD,VEGF,CD4+,CD4+/CD8+,IL-2,IL-6 and IgG were significantly greater with the Weining Granules than with the Weifuchun tablets(P<0.05 or P<0.01).After follow-up of 1 year,17.5% of patients in the trial group relapsed as compared with 39.5% in the control group(P<0.05).Relative to the control group,the trial group showed significantly greater improvements in physical,psychological and social relationships,and in environmental domains(P<0.05 or P<0.01).No significant adverse reactions were observed during treatment.CONCLUSION:The Weining Granules appear to be effective in improving the gastric precancerous state and the main symptoms,in inhibiting angiogenesis,enhancing immune function and QOL,and in reducing 1-year relapses.In addition,this preparation seems to be associated with a low risk of adverse events,making it a safe and efficacious option for the treatment of GPLs.展开更多
Objective: To observe the relations among expression of interleukin 2 (IL 2) in spleen lymphocytes, DNA binding activity of nuclear factor of activated T cells (NFAT) and expression of the partly family members C Fos,...Objective: To observe the relations among expression of interleukin 2 (IL 2) in spleen lymphocytes, DNA binding activity of nuclear factor of activated T cells (NFAT) and expression of the partly family members C Fos, C Jun after trauma. Methods: A murine closed trauma model was used, animals were sacrificed 6, 12 hours and 1, 4, 7, 10, 14 days, respectively after injury. Spleen lymphocytes were isolated from injured mice and stimulated with concanavalin A. The culture supernatants were harvested and assayed for IL 2 activity. Total RNA was extracted from spleen lymphocytes and assayed for IL 2 mRNA. Nuclear protein was extracted, and the DNA binding activity of NFAT was measured using an electrophoretic mobility shift assay (EMSA), the expressions of C Fos, C Jun protein determined by Western blot analysis. Results: The expressions of IL 2 activity and IL 2 mRNA in spleen lymphocytes were decreased in injured mice compared with those in control mice, and the most obvious decrease appeared on the 4th day after injury. The DNA binding activity of NFAT decreased gradually and reached the minimum that was only 41% of the control on the 4th day after injury, which was closely associated with the decline of IL 2 activity and IL 2 mRNA. An decrease in the expression of C Fos on the 1st and 4th day after injury, trauma had no significant effect on the C Jun expression. Conclusions: These results suggest that the inhibition of IL 2 expression is partly due to the impairment in the activation of NFAT in injured mice; and the decline in the DNA binding activity of NFAT is partly due to trauma block in the C Fos expression.展开更多
Colorectal cancer(CRC)remains one of the major causes of death worldwide,despite steady improvement in early detection and overall survival over the past decade.Current treatment paradigms,with chemotherapy and biolog...Colorectal cancer(CRC)remains one of the major causes of death worldwide,despite steady improvement in early detection and overall survival over the past decade.Current treatment paradigms,with chemotherapy and biologics,appear to have reached their maximum benefit.Immunotherapy,especially with checkpoint inhibitors,has shown considerable clinical benefit in various cancers,including mismatch-repair-deficient CRC.This has led to the planning and initiation of several clinical trials evaluating novel immunotherapy agents—as single agents,combinations and in conjunction with chemotherapy—in patients with CRC.This article reviews biological and preclinical data for checkpoint inhibitors and discusses various immunotherapy trials in CRC,as well as current efforts in CRC immunotherapy.展开更多
文摘In the past,there has been considerable focus on a host of drugs and chemicals that may produce colonic toxicity.Now,a variety of new biological monoclonal antibody agents,usually administered by infusion,have appeared in the clinical realm over the last decade or so to treat different chronic inflammatory or malignant disorders.For some of these agents,adverse effects have been documented,including apparently new forms of immune-mediated inflammatory bowel disease.In some,only limited symptoms have been recorded,but in others,severe colitis with serious complications,such as bowel perforation has been recorded.In others,adverse effects may have a direct vascular or ischemic basis,while other intestinal effects may be related to a superimposed infection.Some new onset cases of ulcerative colitis or Crohn's disease may also be attributed to the same agents used to treat these diseases,or be responsible for disease exacerbation.Dramatic and well documented side effects have been observed with ipilimumab,a humanized monoclonal antibody developed to reduce and overcome cytotoxic T-lymphocyte antigen 4,a key negative feedback regulator of the T-cell anti-tumor response.This agent has frequently been used in the treatment of different malignancies,notably,malignant melanoma.Side effects with this agent occur in up to 40% and these are believed to be largely immune-mediated.One of these is a form of enterocolitis that may be severe,and occa-sionally,fatal.Other agents include rituximab(an antiCD20 monoclonal antibody),bevacizumab(a monoclonal antibody against the vascular endothelial growth factor) and anti-tumor necrosis factor agents,including infliximab,adalimumab and etanercept.
基金Supported by National Natural Scientif ic Foundation: 30772832
文摘Objective To compare effects of combined acupuncture and general anesthesia （CAGA） and general anesthesia （GA） on immune function in patients of laparoscopic cholecystectomy （LC） in peri-operative period. Methods Thirty-nine cases undergoing LC were randomly divided into a CAGA group and a GA group. The CAGA group was treated with electroacupuncture at Hegu （合谷- LI 4）, Neiguan （内关PC 6）, Zusanli （足三里ST 36） and Yanglingquan （阳陵泉 GB 34） for 15-30 minutes followed by the general anesthesia, and the continuous electroacupuncture stimulation was given till the operation finished. The GA group was treated with simple general anesthesia. Changes of T cell subsets, tumor necrosis factor-alpha （TNF-α） and interleukin-6 （IL-6） were observed before anesthesia induction, and 2 hours, 1st and 3 rd day after operation, and the adverse reaction after operation was recorded. Results At 2 hours after operation, the percentages of CD3 and CDs in both groups were significantly lower than those before anesthesia induction （all P〈0.05）, and the percentage of CD4 in the GA group decreased significantly （P〈0.05）, while the percentage of CD： did not significantly change and CD4/CD8 increased significantly in the CAGA group （P〈0.05）. At 3 days after operation, the level of TNF-α in the ACGA group decreased significantly as compared with that before anesthesia induction （P〈0.05）. The cases with nausea after operation in the CAGA group were significantly less than those in the GA group （P〈0.05）. Conclusion Acupuncture combined with general anesthesia has a little effect on immune function in patients of LC with less adverse reactions.
基金Supported by the National Natural Science Foundation of China(No.81160433)Guangxi Traditional Chinese Medicine Administration Foundation(No.GZYZ-10-18)
文摘OBJECTIVE:To investigate the clinical effects of Weining Granules on gastric precancerous lesions(GPLs).METHODS:120 patients with GPLs were randomly assigned in a 1:1 ratio to receive Weining Granules(trial group) or the comparator Weifuchun tablets(control group) for 6 months.Outcomes were compared between the two groups including:overall response;gastroscopically-determined response;pathologically-confirmed response;eradication of Helicobacter pylori(HP);microvessel density(MVD) in the gastric mucosa;expression of vascular endothelial growth factor(VEGF);interleukin 2(IL-2);interleukin 6(IL-6);T lymphocyte subsets;immunoglobulins;symptom scores;quality of life(QOL);and adverse reactions.RESULTS:Patients in the trial group had a significantly higher(P<0.05) overall response rate(81.7%) as compared with those in the control group(63.3%).Relative to treatment with Weifuchun tablets treatment with Weining Granules resulted in a significant improvement(P<0.05) in the scores for gastric pain,distension and stuffiness in the hypochondrium,and anorexia.As compared with the tablets the Granules were associated with a significantly higher overall gastroscopically-determined response rate(78.3%;P<0.05).Pathological examination of tissue samples indicated that 61.7% of patients receiving the granules were cured with an overall response rate of 75.5%;these rates were significantly higher than in the control group(P<0.05).In comparison with patients receiving the tablets,those given the granules were significantly more likely to have their HP eradicated(75.0% vs.51.4%;P<0.05).Improvements in MVD,VEGF,CD4+,CD4+/CD8+,IL-2,IL-6 and IgG were significantly greater with the Weining Granules than with the Weifuchun tablets(P<0.05 or P<0.01).After follow-up of 1 year,17.5% of patients in the trial group relapsed as compared with 39.5% in the control group(P<0.05).Relative to the control group,the trial group showed significantly greater improvements in physical,psychological and social relationships,and in environmental domains(P<0.05 or P<0.01).No significant adverse reactions were observed during treatment.CONCLUSION:The Weining Granules appear to be effective in improving the gastric precancerous state and the main symptoms,in inhibiting angiogenesis,enhancing immune function and QOL,and in reducing 1-year relapses.In addition,this preparation seems to be associated with a low risk of adverse events,making it a safe and efficacious option for the treatment of GPLs.
文摘Objective: To observe the relations among expression of interleukin 2 (IL 2) in spleen lymphocytes, DNA binding activity of nuclear factor of activated T cells (NFAT) and expression of the partly family members C Fos, C Jun after trauma. Methods: A murine closed trauma model was used, animals were sacrificed 6, 12 hours and 1, 4, 7, 10, 14 days, respectively after injury. Spleen lymphocytes were isolated from injured mice and stimulated with concanavalin A. The culture supernatants were harvested and assayed for IL 2 activity. Total RNA was extracted from spleen lymphocytes and assayed for IL 2 mRNA. Nuclear protein was extracted, and the DNA binding activity of NFAT was measured using an electrophoretic mobility shift assay (EMSA), the expressions of C Fos, C Jun protein determined by Western blot analysis. Results: The expressions of IL 2 activity and IL 2 mRNA in spleen lymphocytes were decreased in injured mice compared with those in control mice, and the most obvious decrease appeared on the 4th day after injury. The DNA binding activity of NFAT decreased gradually and reached the minimum that was only 41% of the control on the 4th day after injury, which was closely associated with the decline of IL 2 activity and IL 2 mRNA. An decrease in the expression of C Fos on the 1st and 4th day after injury, trauma had no significant effect on the C Jun expression. Conclusions: These results suggest that the inhibition of IL 2 expression is partly due to the impairment in the activation of NFAT in injured mice; and the decline in the DNA binding activity of NFAT is partly due to trauma block in the C Fos expression.
文摘Colorectal cancer(CRC)remains one of the major causes of death worldwide,despite steady improvement in early detection and overall survival over the past decade.Current treatment paradigms,with chemotherapy and biologics,appear to have reached their maximum benefit.Immunotherapy,especially with checkpoint inhibitors,has shown considerable clinical benefit in various cancers,including mismatch-repair-deficient CRC.This has led to the planning and initiation of several clinical trials evaluating novel immunotherapy agents—as single agents,combinations and in conjunction with chemotherapy—in patients with CRC.This article reviews biological and preclinical data for checkpoint inhibitors and discusses various immunotherapy trials in CRC,as well as current efforts in CRC immunotherapy.
