The application of gene therapy in ocular diseases is gradually expanding from mono-gene inherited diseases to multigene, multifactorial, common and chronic diseases. This emerging therapeutic approach is still in the early exploratory stage of treating diseases, and the expected benefits and risks remain highly uncertain. In the delivery process of gene therapy drugs, viral vector is currently one of the most mature and widely used vectors. The occurrence of vector-associated immunity will affect the short-term and long-term effects of gene therapy, and even cause permanent and serious damage to visual function. Therefore, gene therapy vector-associated immunity is the focus and challenge for the safety and long-term efficacy of gene therapy. During the perioperative and follow-up of gene therapy, attention should be paid to the monitoring of vector-associated immune inflammation, and appropriate measures should be taken to deal with the corresponding immune response, so as to achieve the best visual benefits for patients.
Objective To investigate the effects of ulinastatin on Treg/Th17 and immune status in patients with severe sepsis.Methods A total of 80 patients with severe sepsis, who were hospitalized in ICU during October 2011 to July 2012, were randomly divided into a routine group and a ulinastatin group. The patients in the ulinastatin group were intravenously administered 30mg ulinastatin three times per day for 5 days in addition to routine bundle treatment. The expression of Treg, Th17 and HLA-DR were detected on the first day in ICU and 5 days after treatment. 20 healthy individuals served as controls. Results Compared with the control group, the severe sepsis group had overexpression of Treg and Th17 ( P lt;0. 01) , higher ratio of Treg/Th17( P lt;0. 01) , and decreased HLA-DR expression of CD14 monocyte ( P lt; 0. 01) . In the severe sepsis patients, ulinastatin injection reduced the abnormal expression of Treg and Th17 ( P lt; 0. 01) , decreased the ratio of Treg/Th17( P lt; 0. 01) , and improved the expression of HLA-DR ( P lt; 0. 01) more effectively compared with the routine treatment. Ulinastatin also lowered 28-day mortality of the patients with sepsis, but the difference between the ulinastatin group and the routine group was not significant. Conclusions In severe sepsis patients, there were abnormal overexpression of Treg and Th17, imbalance of Treg/Th17, and underexpression of HLA-DR which imply an immune suppression. Ulinastatin can decrease the expression of Treg and Th17, inverses the ratio of Treg/Th17, and improve the expression of HLA-DR, so as to improve the prognosis of severe sepsis patients.
Objectvie To explore the role of DNAJC5B in immunotherapy for esophageal cancer. MethodsThis study utilized the ESCC dataset from the TCGA database, and selected genes associated with DNAJC5B expression through Pearson correlation analysis, followed by Gene Ontology (GO) functional enrichment analysis and KEGG pathway analysis. Additionally, single-cell RNA sequencing data was used to analyze DNAJC5B expression in different T cell subgroups. The prognostic value of DNAJC5B was evaluated using Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, and Cox proportional hazards model analysis. ResultsDNAJC5B is highly expressed in advanced esophageal cancer patients, especially in males. GO and KEGG analyses revealed a significant correlation between DNAJC5B expression and immune-related processes, such as adaptive immune response and cell surface receptor signaling pathways. Single-cell analysis indicated that DNAJC5B expression is positively correlated with immune function and primarily accumulates in CD8+ T cells. Kaplan-Meier survival curves showed that the median survival time of patients with high DNAJC5B expression was 681 days, significantly lower than the 1361 days in patients with low expression. Independent prognostic analysis revealed hazard ratios of 3.577 and 4.114 for DNAJC5B, both with P-values less than 0.05. Conclusion DNAJC5B may play a significant immunomodulatory role in esophageal cancer, particularly in regulating CD8+ T cell function and tumor immune escape. These findings support the potential of DNAJC5B as a biomarker for treatment and prognosis evaluation in esophageal cancer
Objective To investigate the relevance and changes of mucosal immunity in asthma rats’lung, nose and intestine. Methods Twenty Wistar rats were randomly divided into a normal group and an asthma group. Asthma rat model was established by sensitization and challenge with ovalbumin. CD4 + ,CD8 + , eotaxin protein and its mRNA in rats’lung tissues, rhinal and intestinal mucosa were measured by immunohistochemical methods and situ hybridization. The content of sIgA in bronchoalveolar lavage fluid ( BALF) , nasopharyngeal washings and intestinal mucus supernatant were detected by enzyme-linked immunosorbent assay. Results Compared with the normal group, the levels of CD4 + , CD8 + in rats’lung tissues, rhinal and intestinal mucosa, the expression of eotaxin protein and mRNA in rats’lung tissues, the content of sIgA in nasopharyngeal washing, and the expression of eotaxin protein in intestinal mucosa were significantly higher in the asthma group( P lt; 0. 05) . There were no significant differences of other indices between the two groups. In the normal group, the eotaxin protein expression had a negative correlationbetween lung tissue and rhinal mucosa( r = - 0. 572, P = 0. 008) , and a positive correlation between intestinal and rhinal mucosa( r=0. 638, P =0. 002) . The eotaxin mRNA expression had a positive correlation between lung tissue and rhinal mucosa( r= 0. 502, P = 0. 024) , and a positive correlation between intestinaland rhinal mucosa( r=0. 594, P =0. 006) . In the asthma group, such a correlation was not found except the eotaxin protein expression which had a negative correlation between lung tissue and intestinal mucosa( r =- 0. 448, P = 0. 048) . Conclusions Mucosal immunity in lung, nose and intestine remains a dynamic balance. The balance of mucosal immunity is destroyed in asthma.
Objective To review the methods of overcoming immunological rejection in xenotransplantation.Methods The strategies of overcoming immunological rejection in xenotransplantation were analyzed and summaried on the basis of an extensive review of the latest l iterature concerned. Results The research development of immunological rejection mechanism and molecular biological technique provided new approaches for overcoming immunological rejection in xenotransplantation. Conclusion It is only a matter of time for xenotransplantation to be appl ied cl inically.
ObjectiveTo learn further the local immunity changes of rectal cancer after neoadjuvant therapy and improve the cognition of this project. MethodsSixty cases of paraffin-embedded sections of the excised specimen from the two groups of middle and low rectal cancer patients, with (therapy group) or without (control group) neoadjuvant therapy, were studied respectively. Tumor infiltrating lymphocytes (TIL) in the two groups were counted under microscope, and also, dendritic cells (DC) were counted and morphology and distribution of the DCs were recorded through immunohistochemistry stain with monoclonal antibody, S-100. ResultsTILs and DCs in the two groups mainly assembled in the pericancerous tissues. The positive rate of TIL in therapy group was 75.00% (45/60) and 90.00% (54/60) in control group (χ2=10.58, P=0.014). S-100 positive DCs were (36.85±11.17)/HPF versus (26.50±7.68)/HPF in the therapy group and control group, respectively (P=0.001). ConclusionNeoadjuvant therapy for rectal cancer can influence the local tumor immunity enviroment by reducing TILs and increasing DCs.
ObjectiveTo investigate the change of cellmediated immunity in gut mucosa after major hepatectomy and to study its relationship with the bacteria translocation.MethodsFortyeight Spraguedawley adult male rats were randomly allocated into two groups, the sham operation group and the operation group. Besides without the hepatectomy, the sham operation group has the same course with the operation group. Seventy percent hepatectomy rats are divided as postoperative 6 h group (n=6)，12 h group (n=6)，24 h group (n=6) and 72 h group (n=6). Sixhour, 12hour, 24hour and 72hour after operation specimens were taken from jejunoileum respectively. Immunohistochemical staining was performed on frozen sections and image pattern analysis was used. We also investigate the change of liver function. ResultsTwentyfour hours and 72 hours after 70% hepatectomy, there was a significant reduction in the number of CD3+，CD4+and CD8+ T lymphocytes in the mucosal lamina propria of the operation group compared with the sham operation group （Plt;0.05）. There was significant difference between these two groups in liver function change （Plt;0.05）.ConclusionThere is an altered pattern of intestinal mucosal T lymphocytes after major hepatectomy, then the local cellmediated immunity was depressed, which may be the cause of translocation of enteric bacteria.
【Abstract】 Objective To review the research progress of possible mechanism of indoleamine 2, 3-dioxygenase(IDO) in immunological regulation and function of transplantation immunity. Methods The advances in the IDO location, immunological regulatory mechanism and function of transplantation immunity were introduced based on the recent related l iterature. Results IDO played an immunoregulatory role by locally depleting tryptophan in tissue microenvironment which resulted in immunosuppression of allogeneic T-cell prol iferation. IDO cDNA was del ivered to chromosome in interesting cells by gene transfection and stimulated to express, which was associated with a prolongation in allograft survival in vivo . Conc lu sion IDO offers a new way in transplantation immunity, and this provid novel method for elevating allograft survival rate.
ObjectiveTo analyze the association between nutritional and immune-related laboratory indices and pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer patients and focused on constructing a combination of laboratory indices to serve as a clinical predictor of pCR after NAC in breast cancer. MethodsRetrospectively collected the pre-NAC laboratory indices [albumin (ALB), total cholesterol, triglyceride, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol, apolipoprotein A- Ⅰ, apolipoprotein B, white blood cell, neutrophil, lymphocyte, monocyte (MON), and platelet ] and clinicopathologic data of 310 patients with invasive breast cancer who had received NAC in the Department of Breast Surgery, Affiliated Hospital of Southwest Medical University, from September 1, 2020 to October 31, 2022. Logistic regression analysis was conducted to determine the correlation between laboratory indices and post-NAC pCR. The combinations of laboratory indices were constructed by simple mathematical operation. The area under the receiver operating characteristic curve (AUC) was used to evaluate the efficacy of different combinations of laboratory indices in predicting pCR and to determine the optimal combination of liboratory indices. Multivariate logistic regression analysis was used to analysis the relevance between clinicopathologic features and post-NAC pCR in breast cancer patients and to determine the independent predictor of post-NAC pCR. ResultsAmong the 310 patients, 49.4% (153/310) of them achieved pCR after NAC. Logistic regression analysis revealed that ALB (Z=5.203, P<0.001) and HDL-C (Z=2.129, P=0.033) were positively correlated with post-NAC pCR, while MON (Z=–4.883, P<0.001) was negatively correlated with post-NAC pCR. The AUC analysis of 6 different combinations of laboratory indices showed that the ALB/MON combination (the optimal combination of liboratory indices) had the highest predictive performance (median AUC=0.708) and was determined to be the neoadjuvant therapy predictive index (NTPI). Multivariate logistic regression analysis showed that estrogen receptor (Z=–3.273, P=0.001), human epidermal growth factor 2 (Z=7.041, P<0.001), Ki-67 (Z=2.457, P=0.014), and NTPI (Z=4.661, P<0.001) were the independent predictors for post-NAC pCR. ConclusionNTPI could serve as a predictive index for post-NAC pCR in patients with breast cancer.
ObjectiveTo analyze the difference of expression of B7 superfamily member 1 (B7S1) in gastric cancer and adjacent cancer tissues, and to explore the relationship between B7S1 expression and the clinicopathological characteristics and the prognosis of gastric cancer patients.MethodsReverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry were performed to investigate the expression of B7S1 in 78 cases of gastric cancer tissues and adjacent tissues. The correlation of B7S1 expressions with the clinicopathological characteristics and prognosis of the patients was analyzed.ResultsThe results showed that cancer tissues relative expression of B7S1 mRNA was higher than that of adjacent tissues, and the difference was statistically significant (P<0.05). The results showed that positive rate of B7S1 protein expression in gastric cancer tissues was significantly higher than that of adjacent tissues, 74.36% and 11.54%, the difference was statistically significant (P=0.001). Chi-square analysis showed that the expression of B7S1 protein was associated with tumor diameter (P=0.006), pathological-stage (P=0.002), T-stage (P=0.011), and lymph node metastasis (P=0.001). There were no relationship with gender, age, tumor site, and M-stage (P>0.05). B7S1 protein expression was correlated with the overall survival rate for gastric cancer patients. Both univariate and Cox multivariate survival analysis suggested that B7S1 positive expression was a risk factor for poor prognosis in patients with gastric cancer.ConclusionsThe relative expression level of B7S1 mRNA and the positive rate of protein expression in gastric cancer tissues are higher than those in adjacent tissues. The positive expression of B7S1 is correlated with the poor clinicopathological characteristics and prognosis. We speculate that B7S1 may be involved in the malignant progression of gastric cancer.