Objective To study the protective effect of exogenous matrix metalloproteinases9(MMP-9) inhibitor Doxycycline against lung injury during cardiopulmonary bypass(CPB) in dogs. Methods Twenty healthy mongrel puppies(weighed 10 -12 kg) were divided into control group (n=10) and experimental group(n=10) with random number table. In control group, no measure was taken to protect lung before and after CPB. In experimental group, the feeding food was mixed with Doxycycline (30 mg/kg, body weight) daily for three days before operation. Enzymelinked immunosorbent assay(ELISA) was used to measure the plasma concentration of MMP-9. Hemodynamic and respiratory parameters in two groups were monitored. The preoperative and postoperative alveolararterial oxygen partial pressure difference (A-aDO2) and respiratory index(RI) were calculated. The myeloperoxidase（MPO）activity of bronchoalveolar lavage fluid（BALF）was determined by colorimetry. The total protein of BALF was measured by Coomassie Brilliant Blue G-250. After CPB, light microscope and electronic microscope were used to observe the morphological changes of lung tissue. The dry to wet weight index(W/D) was calculated. Results In both groups, the plasma concentrations of MMP-9 increased significantly as the time of CPB prolonged. The plasma MMP-9 at 150 min and 270 min after CPB in experimental group decreased significantly than those in control group (9.45±5.29 [CM(159mm]ng/ml vs. 18.66±5.90 ng/ml,t=3.664, P=0.005;16.63±2.90 ng/ml -vs.26.17±5.96 ng/ml, t=5.216, P=0.001). MPO activity, total protein of BALF, W/D, postoperative A-aDO2 and RI in experimental group decreased significantly than those in control group. There were significant differences between two groups（t=5.622,P=0.000; t=5.081, P=0.001; t=2.266, P=0.050; t=4.927, P=0.001; t=6.679,P=0.000）. The lung histopathology and electronic microscope showed that the lung injury reduced significantly. Conclusion Doxycycline plays a role in lung protection by inhibiting the secretion of MMP9, reducing the degradation of cell basement membrane, pulmonary neutrophil infiltration and pulmonary edema. Key words: Cardiopulmonary bypass; Acute lung injury; Matrix metalloproteinase; Doxycycline; Lung protection
Objective To study the effect of knockdown of signal transducer and activator of transcription 3 (STAT3) expression by short hairpin RNA (shRNA) on proliferation, apoptosis and invasion of human gastric cancer cell line MKN-45 in vitro . Methods Specific shRNA plasmids to STAT3 were constructed, and then transfected into MKN-45 cells by lipofectamine methods. Cells were divided into three groups: control group, psiRNA-H1 transfected group as negative group and psiRNA-H1/STAT3 transfected group. Semi-quantitative RT-PCR and Western blotting were used to detect the expression of STAT3 mRNA and protein, respectively. Proliferation and apoptosis of the transfected cells were observed by methyl thiazolyl tetrazolium (MTT) method and flow cytometry (FCM), respectively. The invasion of the transfected MKN-45 cells was measured by Boyden chamber. Results Compared with the negative control cells, semi-quantitative RT-PCR and Western blotting showed that the expressions of STAT3 mRNA and protein were down-regulated in the psiRNA-H1/STAT3 transfected group ( P ＜ 0.05) . The subcloned recombinant plasmid expressing shRNA effectively inhibited MKN-45 cell growth and proliferation while empty plasmid had no such specific effect. Cell apoptosis rate increased significantly in psiRNA-H1/STAT3 transfected group （ P ＜ 0.01）, and the invasion of MKN-45 cells was efficiently inhabited in psiRNA-H1/STAT3 transfected group as compared with control group and psiRNA-H1 transfected group( P ＜ 0.01).Conclusion Recombinant plasmid psiRNA-H1/STAT3 shRNA significantly inhibits the proliferation and invasion of MKN-45 cells and promotes their apoptosis.
Objective To investigate the relationship between the level of serum-insulin like growth factor-1( IGF-1) and the nut ritional status of cancerous cachexia. Methods Colon cancer CT-26 cells were implanted subcutaneously to 30 liver2specified IGF-1 gene deleted (L ID) C57BL/ 6 mice to establish cancerous cachexia model and theother 30 C57BL/ 6 mice were included as cont rol group. The serum levels of IGF-1 , cytokine TNF-αand IL-6 , bloodglucose , albumin and t riglyceride were detected respectively on day 14 , 18 and 22 af ter the plantation of tumor. Thebody weight of mice , tumor weight and the weight af ter tumor removed in two group s were measured respectively.Results Af ter the plantation , the levels of IGF-1 in L ID group at different times were all significantly lower thanthose in cont rol group ( Plt; 0. 05) . The serum levels of TNF-α, IL-6 , blood glucose and t riglyceride were ascendinggradually over time ( Plt; 0. 05) , but weight s af ter tumor removed and the level of albumin were descending in twogroup s ( Plt; 0. 05) . Compared with the cont rol group , the serum levels of IL-6 , TNF-α, blood glucose and t riglyceride in L ID tumor-bearing mice were all significantly higher at different time point s ( P lt; 0. 05) . On day 18 and 22 ,the weight s af ter tumor removed and the amount of ingestion in L ID group were significantly lower than those in thecont rol group ( Plt; 0. 05) . Conclusion Compared with the low level of IGF-1 in cancerous cachexia , normal level ofserum IGF-1 may represent lower degree of cancerous cachexia2related cytokines and better nut ritional state , whichmay provide a novel idea of the therapy of cancerous cachexia.
The specific binding of T cell receptors (TCRs) to antigenic peptides plays a key role in the regulation and mediation of the immune process and provides an essential basis for the development of tumour vaccines. In recent years, studies have mainly focused on TCR prediction of major histocompatibility complex (MHC) class I antigens, but TCR prediction of MHC class II antigens has not been sufficiently investigated and there is still much room for improvement. In this study, the combination of MHC class II antigen peptide and TCR prediction was investigated using the ProtT5 grand model to explore its feature extraction capability. In addition, the model was fine-tuned to retain the underlying features of the model, and a feed-forward neural network structure was constructed for fusion to achieve the prediction model. The experimental results showed that the method proposed in this study performed better than the traditional methods, with a prediction accuracy of 0.96 and an AUC of 0.93, which verifies the effectiveness of the model proposed in this paper.
Objective To investigate the application and advancement of hepatocyte t ransplantation ( HCT) .Methods Literatures about the advancement of HCT were reviewed and analyzed. Results There have been manynovel technologies and advancement s in the application of HCT. For example , gene modified cell can be used as seedcell , subcutaneous t ransplantation can be taken when combined with giant molecule material and the encap sulationpreconditioning technique can also carried before operation to improve the rate of survival. Conclusion With moreand deeper understanding of hepatocyte t ransplantation and the development of advanced techniques such as the application of giant molecule , HCT will be extensively used in the clinical t reatment of acute and chronic hepatic diseases.
This paper introduces the application and funding of evidence-based research projects on traditional Chinese medicine (TCM) of the National Natural Science Foundation of China (NSFC) in 2019 in terms of clinical research and methodology research, summarizes the primary problems existing in evidence-based research on TCM, discusses the quality of evidence-based research on TCM in clinical research, highlights the characteristics of TCM and reveals the evidence-based methodology on TCM.
OBJECTIVE To study the relationship between the changes of mRNA expression in wound tissues of diabetic ulcers and tissue repair. METHODS The mRNA expression of TGF-beta 1 and IL-6 in eight bioptic samples of diabetic ulcers were detected by RT-PCR and pathologic methods, and the surrounding normal skins from the same patients were measured as control group. RESULTS The mRNA expression levels of TGF-beta 1 were markedly decreased in the diabetic ulcers compared with control group, while the mRNA expression levels of IL-6 were increased at the same reaction conditions. CONCLUSION The different changes of mRNA expression level of TGF-beta 1 and IL-6 in wound tissue result in low production and decreased activity of TGF-beta 1 and IL-6, which lower the reparative ability of wound tissue.
The study of tissue engineering heart valves is one of the focus about cardiovascular surgery and is developing. Especially acellular tissue engineering heart valves have many advantages in low immunogenicity,non cytotoxicity,recellularation,excellent bionics,durability etc.Therefore, the study of acellular tissue engineering heart valves is becoming the important direction of future development about valves studies. Some development about it is reviewed.
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.
Objective To explore application of preoperative examination in the colorectal cancer patients. Methods The preoperative examination data of patients diagnosed definitely as colorectal cancer at West China Hospital of Sichuan University from November 2006 to June 2007 was retrospectively study, and the application situation and relationship among all preoperative examination in the colorectal cancer patients were analyzed. Results According to the inclusion criteria, 438 colorectal cancer patients were included which involved 260 males and 178 females. Preoperative examinations included two to sixteen items, with an average of 10.61 items. According to correlation analysis, positive correlation existed among lung function and blood type ( r =0.161, P =0.001), tumor marker ( r =0.118, P =0.014), chest X-ray ( r =0.113, P =0.018), routine electrocardiogram ( r =0.198, P =0.000) , while lung function and immune and stress reaction exhibit a negative correlation ( r =-0.106, P = 0.027) with preoperative examinations. At the same time, immune and stress reaction had positive correlation to CT examinations of abdomen ( r =0.151, P =0.001) as well as endorectal ultrasound ( r =0.330, P =0.000). Using univariate analysis, the influence of tumor location ( P =0.012) and operative method ( P =0.004) on the number of examination items was significant. Conclusion Preoperative examination of colorectal tumor surgery mainly includes routine examination, neoplasm-related examination and important organs function detection. And three levels of preoperative menu can be set up in early stage. Establishment of normalization preoperative combined examination may be helpful to consummate preoperative evaluation and improve medical quality.