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 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.
ObjectiveIn order to provide a data base for fund project applicants and funding priorities, we would summarize the basic situation and key points of basic research in liver transplantation by analyzing the projects funded by the Natural Science Foundation of China (NSFC) in the field of liver transplantation.MethodsThrough the big data knowledge management and service platform of NSFC, internet-based science information system, and shared service network of NSFC, we searched the funding project information in the liver transplantation relevant field from 2010 to 2019, then analyzed the effectiveness of the Young Scientists Fund of NSFC in promoting young researchers and the research focus and development direction of funding projects.ResultsIn the latest 10 years, NSFC persistently and stably funded the basic research in the field of liver transplantation, with the total number of funding projects was 387, and the funding budget was 198.215 million yuan. The main types of funding projects were the General Program and the Youth Science Fund. There were 210 General Program project (54.3%) with an amount of 113.14 million yuan (57.1%), 127 Young Scientists Fund (32.8%) with an amount of 27.9 million yuan (14.1%), and 22 Fund for Less Developed Regions (5.7%) with an amount of 9.03 million yuan (4.6%). Sun Yat-sen University and Zhejiang University were far ahead of other supporting institutions in both the total number of projects undertaken and the amount of funds granted. The youth/surface ratio reached as high as 72.2% (13/18). The conversion rate of Young Scientists Fund to higher-level projects reached about 50%, which was significantly higher than the overall level of 24.7% (21/85) in the field of liver transplantation. The funding projects were mainly distributed in application code H0318 (liver regeneration, liver protection, liver failure, and artificial liver, 58, 15.0%), H0321 (organ transplantation of digestive system, 169, 43.7%), and H1006 (organ transplantation and transplantation immunity, 50, 12.9%). The main research fields were transplantation immunity and liver injury and liver protection. At the same time, projects such as graft function and complications of liver transplantation were also funded. There were few studies on the immune status of long-term survival in patients after liver transplantation and the mechanism on prevention of immunosuppressant-related diseases.ConclusionsThe NSFC has a great leading effect on the discipline development and talent cultivation of liver transplantation. However, there are still some problems in the discipline layout, such as the lack of attention to the mechanism of long-term graft function and chronic immune rejection.
Wireless power transfer (WPT) is a new power transmission way, which can be widely used in electric vehicles and other fields. Its electromagnetic environment must be analyzed to ensure safe application. A low-power wireless power transfer system experimental platform was built, with 25 W receiving power and 47 kHz resonant frequency, which was used to carry out animal experiments. Treatment mice were exposed to environment of wireless power transfer system for 5 h a day and 6 days as one cycle. At the end of every cycle, learning memory behavior of mice were detected in T-shaped maze. The exposure experiment lasted for 12 weeks. Finally, immune parameters, sex hormones and part of organ physiological structure were detected. The results are as follows: as exposure time increased, memory behavior of mice did not change obviously with no statistical difference in sex hormone either (P > 0.05), the concentration of immune factors including tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6) and interleukin-1 beta (IL-1β) significantly increased (P < 0.05), and the structure of some organs showed some changes. The experimental results show that the environment of the wireless power transfer system has no effect on the memory behavior of mice, and has some effect on physiological properties of mice.
The pathogenesis of Vogt-Koyanagi Harada disease (VKH) has not yet been fully defined. Current studies mainly suggest that VKH is actually an autoimmune disease, especially related to the immune response mediated by various signal transduction pathways involved in the function of T cells. In recent years, the influence of the balance imbalance of various T cell subsets in cellular immunity on the pathogenesis of VKH has been a hot research direction. Currently, T helper cell 17/T regulatory cells, balance is the focus of clinical research, meanwhile, new discoveries and potential clinical treatment schemes have been made for related cellular pathways, particularly the Janus kinase/signal transducers and activators of transcription pathway and NF-kappa B pathway. The exploration of B cells in the pathogenesis of VKH has also achieved initial results through the successful application of various targeted drugs. In the future, further screening and localization of genes or proteins that are abnormally regulated or expressed in VKH, for which early comprehensive and in-depth exploration will be helpful, thus improve the efficacy of clinical treatment programs and develop new therapeutic targets.
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.
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.
ObjectiveTo investigate the characteristics and prognostic value of cellular immune function in severe patients with coronavirus disease 2019 (COVID-19).MethodsA cohort study was conducted to collect the clinical data of 119 severe patients admitted to the Renmin Hospital of Wuhan University (Eastern District) including 60 males (50.4%) and 59 females (49.6%), with an average age of 60.9±14.2 years. The primary endpoint of follow-up was death in the hospital, and the disease outcome classification was the secondary endpoint of follow-up within 30 days after admission. We analyzed the correlation between cellular immune function and COVID-19 prognosis.Results A total of 22 patients died during this process, and 47 patients were severe/critical during the follow-up period. The counts of CD3+, CD4+, CD8+, and CD19+ in the primary endpoint events were significantly different between the survival group and the death group (all P<0.05). The counts of CD3+, CD4+, CD8+, CD19+ in the secondary endpoint events were significantly different between the normal group and the severe/critical group (all P<0.05). The results of the receiver operating characteristic (ROC) curve showed that the area under the cellular immune function curve of dead patients and severe/critical patients had good predictive value (all P<0.05).ConclusionCell immune function has good clinical and prognostic value for COVID-19.
【Abstract】ObjectiveTo investigate the effect of RNA editing enzyme ADAR1 on the function of lymphocyte immune by transferring mouse lymphocytes with plasmid of sense siRNA and by suppressing the expression of ADAR1. MethodsThe cell strains of human hepatic cellular carcinoma （HCC） were frozen and thawed repeatedly to prepare for tumor soluble antigen. The isolated mouse lymphocytes, which were transferred with antisense siRNA plasmid of ADAR1 and were sensitized with soluble tumor antigen were used as the study group; those which were not transferred but were sensitized were used as the control group. The 3HTdR adulteration experiment was used to test the sensitivity of lymphocytes. The effect of ADAR1 on lymphocyte immunity was detected by lymphocytotoxicity tests. ResultsThe observation of the isolated lymphocytes implied that the growth cycle of lymphocyte was 10-14 days. The 3HTdR adulteration experiment showed the result was optimal. The number of HCCs decreased significantly for both of the groups compared with those in the blank holes, but the amplitude was much larger in the control group. The expression of ADAR1 in lymphocytes of the study group was significantly lower than that of the control group, which demonstrated that the RNA plasmid of ADAR1 suppressed the expression of ADAR1 in sensitized lymphocytes and the suppressing rate of the control group (87.47±4.62)% was significantly higher than that of study group （53.19±3.95）%. The function of lymphocytes killing targetcells in the study group was significantly inferior to that of control group (P＜0.05). ConclusionRNA editing enzyme ADAR1 may play an important role in mouse cellullar immunologic response and it is possible to attenuate the cellimmune response by depressing the expression of ADAR1.
Objective To explore the operative safety of HIV-infected patients with colorectal cancer in different degrees of immunodeficiency. Methods A total of 56 patients, including 26 cases of HIV positive (HIV-positive group) and 28 cases of HIV negative (HIV-negative group), who underwent radical operation for colorectal cancer between January 2012 and December 2015, were enrolled in our study. We divided HIV-positive patients into three groups according to CD4+ T cells count in peripheral venous blood before 1 day (D0) of the surgery (HIV-positive Ⅰgroup with CD4+ T cells count >500/μL, HIV-positive Ⅱgroup with CD 4+ T cells count among 200–500/μL, and HIV-positive Ⅲ group with CD4+ T cells count <200/μL). Non-infective patients were enrolled in HIV-negative group. Leukocyte count, neutrophil percentage, lymphocyte percentage, CD 4+ T cells subsets count, and CD8+ T cells subsets count of the 4 groups in different time points were tested. In addition, we compared postoperative complications, carcinoembryonic antigen (CEA), and postoperative survival rate between the HIV-positive group and the HIV-negative group. Results In 56 cases, there were 26 cases of HIV-positive patients (including 10 cases of HIV-positive Ⅰ group, 8 cases of HIV-positive Ⅱ group and 10 cases of HIV-positive Ⅲ group). Variance results about repeated measurement data showed that, variation of leukocyte count, neutrophil percentage, lymphocyte percentage, and CD8+ T cells count among 4 groups after surgery had no statistical significance (P>0.05), in addition there was no significant on time effect and interactive effect of time and group (P>0.05). CD4+ T cells count in the 4 groups showed a trend from decline to rising with time going, and the time effect had statistical significance (P<0.05). The speed and amplitude of decline and recovery of CD4+ T cells count were different among groups, and the group effect had statistical significance (P<0.05). CEA showed a trend of decline after surgery in both HIV-positive group and HIV-negative group, and the time effect had statistical significance (P<0.05), but the group effect and interactive effect of time and group had no statistical significance (P>0.05). No statistically significant differences in amount of blood loss, duration of surgery, postoperative stay, nor complication rate (including incision infection, pulmonary infection, and opportunistic infections after surgery) were found between the HIV-positive group and the HIV-negative group (P>0.05). The overall survival situation of the HIV-positive group and the HIV-negative group had no statistical significance (P>0.05). Conclusions Radical operation for HIV-infected patients with colorectal cancer has an impact of " first inhibition and recovery” on cellular immunity over a period of time. Incidence of postoperative complications and survival rates are similar in HIV-positive patients and HIV-negative patients. In a word, it’s safe to have radical operation for colorectal cancer in HIV-positive patients under the proper perioperative treatment.