1.The interventional treatment for shunt stenosis or occlusion after mesocaval shunts in portal hypertension
Qi ZHAO ; Zhiwei WANG ; Jiaxiang WANG ; Zhen LI ; Sheng GUAN ; Xiuxian MA ; Kun DU
Chinese Journal of General Surgery 2013;(4):266-269
Objective To evaluate interventional therapy in the treatment of interposition graft stenosis or occlusion after mesocaval shunts.Methods The clinical data of 19 cases of artificial vessel stenosis or occlusion after mesocaval shunts for portal hypertension at our department from march 2009 to march 2012 were retrospectively analyzed.Results In the 19 cases with artificial vessels stenosis or occlusion developed after mesocaval interposition shunts for portal hypertension,there were 5 cases in which acute thrombosis occurred within a week after the surgery.Catheter directed thrombolysis was successfully conducted.In 6 cases in which shunt stenosis developing 1 to 8 years after surgery were managed by balloon dilatation or stent angioplasty successfully.The shunt graft occlusion occurred in 8 cases after 1 to 4 years of surgery was successfully managed and the shunt was reopened by balloon dilatation or stent angioplasty in 6 cases,and in 2 the procedure was failed for the guide wire can't go through the anastomotic site of artificial vessel-superior mesenteric vein.In 11 cases embolization of the esophagogastric varices was successfully carried out for postoperative standard anticoagulation.During a period of 3 months to 3 years follow-up,stenosis recurred 1 year after balloon dilatation in one case,and stenosis was managed by angioplasty successfully.Conclusions Interventional radiological techniques by percutaneous puncture through femoral vein-inferior vena cava-artificial vessel-portal vein (including catheter directed thrombolysis,balloon dilatation,stent placement,etc) are less traumatic,highly successful in the treatment of shunt stenosis or occlusion after mesocaval shunts in portal hypertension.
2.Research progress of bioartificial liver
Songlin YU ; Baosan HAN ; Rui ZHANG ; Zhiyong DU ; Xubo WU ; Jiaxiang WANG ; Fang HUANG ; Chenghong PENG
Chinese Journal of Tissue Engineering Research 2009;13(53):10513-10516
OBJECTIVE: To analyze the research literatures related to bioartificial liver, and to make a conclusion concerning the development of bio-artificial liver.DATA SOURCES: Using bioartificial liver, liver cell, hepatocyte culture and bioreactor as search terms, searching Ovid, Springer Link database, and China National Knowledge Infrastructure, Vip Information database and Wanfang Date (1990.09-2008.09). Literatures search was limited to English and Chinese languages.DATA SELECTION: Researches regarding liver cells of bioartificial liver, reactors and auxiliary equipment was included, and the studies about immune and animal infection studies of bioartificial liver were excluded.MAIN OUTCOME MEASURES: ①The source, quantity and culturing of bio-artificial liver hepatocytes. ②Bioreactor type, nature and type of films. ③Composition of oxygen and temperature control devices of bioartificial liver.RESULTS: Totally 3898 documents seized initially in the searching by computer, according to inclusion and exclusion criteria, 29 were analyzed. Bioartificial liver was a hybrid device in which can culture hepatocytes in vitro, when the patient's blood flows through the device, material exchange with the cultured hepatocytes through semi-permeable membrane or direct contacting can take place, which can perform the same roles of detoxification, synthesis, biological transformation and other functions as real liver cells, so as to achieve the purpose of support and treatment. Bioartificial liver can also be involved in metabolism of the three major nutritive substances, as well as secretion of hepatocyte growth promo ting substances. So it is an effective alternative to the real liver as the function of detoxification and synthesis, and can fills the essential gap between the transplantation and acute liver failure.CONCLUSION: Although the bioartificial liver research has made significant progress, it still faces the problems such as limited liver cells sources, long-term maintenance of liver cell activity and function, and further optimization of the reactor design.
3.Protective role of expression of human complement regulatory protein hCD55 in islet xenotransplantation
Xin LI ; Dengke PAN ; Jia ZHOU ; Jie YAN ; Jun CHEN ; Jiaxiang DU ; Manlin GONG
Organ Transplantation 2022;13(4):475-
Objective To validate whether the expression of human cluster of differentiation 55 (hCD55) protein in porcine islet cells could inhibit the activation of complement components in human serum. Methods Four adult pigs with WT (wild type), GTKO [α-1, 3-galactosyltransferase (GGTA1) knockout], GTKO/hCD55 and hCD55 genotypes were selected. Islet cells were isolated from WT, GTKO and GTKO/hCD55 pigs, and the purity and insulin secretion function were detected. The expression of hCD55 at the DNA, RNA and protein levels was analyzed by agarose gel electrophoresis, reverse transcription polymerase chain reaction (RT-PCR) and flow cytometry, respectively. Complement-dependent cytotoxicity assay and complement deposition assay were performed under the incubation conditions with fresh human serum. Results The purity of isolated porcine islet cells from three genotype pigs was > 75%, and the glycemic index was > 1. The expression of hCD55 messenger RNA(mRNA) and protein in GTKO/hCD55 porcine islet cells decreased the deposition of human complement component C3c and membrane-attacking complex C5b-9, and reduced the cytotoxicity. Conclusions The expression of hCD55 protein in porcine islet cells could inhibit the activation of human complement and reduce complement-mediated killing effect, indicating that hCD55 protein could exert complement protection effect on porcine islet cells. These findings provide theoretical basis for the application of hCD55 in islet xenotransplantation.
4.Factors related to household rodent abundance in rodent-borne disease foci in western Yunnan
Xiufang WANG ; Jiaxiang YIN ; Guangcan YANG ; Zhengxiang LIU ; Chunhong DU ; Liyuan SHI ; Liqiong SU
Chinese Journal of Epidemiology 2015;36(2):139-143
Objective To analyze the factors related to the household abundance of rodents in rodent-borne disease foci in the western part of Yunnan province.Methods From July 2011 to October 2012,800 households (20 households in 1 village) were randomly selected in 40 natural villages of 10 counties in western Yunnan where rodent borne disease was endemic to conduct a study on relationship between rodent abundance and environmental factors.Five cages were placed in each household for 3 consecutive nights to capture rodents.The rodent species were identified based on their morphological characteristics.The data on potential factors related to rodent abundance were collected through questionnaires and field observation.A dataset was established by using EpiData software and the analysis was performed with hurdle regression model under R software.Results A total of 421 rodents were captured in 800 households,belonging to 9 species,6 genera,2 families,2 orders.Rattus tanezumi was the predominant species (66.03%).The final hurdle regression model showed that the probability of capturing rodents in the households where family member had high education level and the garbage was placed outside declined by 50%-68% ; The probability of capturing rodents in the households of Dai and Yi ethnic groups increased by 2.16-2.87 times; The probability of capturing rodents in the households where rodents were observed or vegetables grown near houses increased by 1.54-1.59 times; In the households where many rodents were believed to exist,the probability of capturing rodents and the number of rodents captured increased by 1.59 and 1.84 times respectively.The number of rodents captured in the houses with cement or tile floor increased by 3.62 times.Conclusion The household abundance of rodents in the area in western Yunnan,where the rodent-borne disease survey was conducted,seemed to be closely related to the social economy status,human intervention and ecological environment.To control the abundance of rodents effectively,it is necessary to take these factors into consideration.
5.Preliminary report of perioperative monitoring of six-gene-edited pig-to-cynomolgus monkey kidney xenotransplantation
Shujun YANG ; Hao WEI ; Yong XU ; Heng'en WANG ; Xiangyu SONG ; Zhibo JIA ; Jiang PENG ; Mengyi CUI ; Boyao YANG ; Leijia CHEN ; Aitao GUO ; Xiaoli ZHANG ; Dengke PAN ; Jiaxiang DU ; Panfeng SHANG ; Shengkun SUN
Organ Transplantation 2023;14(4):521-
Objective To investigate the establishment of a six-gene-edited pig-to-non-human primate kidney xenotransplantation model. Methods The kidney of humanized genetically-edited pig (GTKO/β4GalNT2KO/CMAHKO/hCD55/hCD46/hTBM) was transplanted into a cynomolgus monkey. The survival of the recipient and kidney condition after blood perfusion were observed. The parenchymal echo, blood flow changes, and size of the kidney were monitored on a regular basis. Routine blood test, kidney function test and electrolyte assessment were carried out. Dynamic changes of urine, feces and body mass were monitored. At the end of life, the transplant kidney, heart, liver, spleen, lung, and cecum were collected for pathological examination. Results The recipient died at postoperative 7 d. After blood flow was restored, the kidney was properly perfused, the organ was soft and the color was normal. At the end of the recipient's life, a slight amount of purulent secretion was attached to the ventral side of the kidney, with evident congestion and swelling, showing the appearance of "red kidney". Postoperatively, the echo of renal parenchyma was increased, blood flow was decreased, the cortex was gradually thickened, and a slight amount of effusion surrounded the kidney and abdominal cavity over time. In the recipient, the amount of peripheral red blood cells, hemoglobin, albumin, and platelets was progressively decreased, and serum creatinine level was increased to 308 μmol/L at postoperative 7 d, whereas the K+ concentration did not significantly change. Light yellow urine was discharged immediately after surgery, diet and drinking water were resumed within postoperative 3 h, and light yellow and normal-shape stool was discharged. The reddish urine was gradually restored to normal color within postoperative 1 d, which were consistent with the results of the routine urine test. A large amount of brown bloody stool was discharged twice in the morning of 2 d after surgery. Omeprazole was given for acid suppression, and the stool returned to normal at postoperative 4 d. The β2-microglobulin level was increased to 0.75 mg/L at postoperative 7 d. The body mass was increased by 1.7 kg. Autopsy pathological examination showed interstitial edema and bleeding of the transplant kidney, a large amount of infiltration of lymphocytes and macrophages, infiltration of lymphocytes in the arteriole wall and arterial cavity, accompanied by arteritis changes, lymphocyte infiltration in the cecal stroma and congestion in the spleen tissues. No significant abnormal changes were observed in other organs. Conclusions The humanized genetically-edited pig-to-non-human primate kidney xenotransplantation model is successfully established, and postoperative survival of the recipient is 1 week.
6.The discussion on the Genetically Modified Pigs for the treatment of acute liver failure
Guoli HUAI ; Jiaxiang DU ; Dengke PAN
Journal of Clinical Hepatology 2022;38(10):2214-2218
Liver transplants are in huge demand in China, but facing the problem of extreme shortage of donor organs. Xenogeneic (pig) liver transplantation may be a potential way to alleviate the shortage of donors. The liver is a detoxifying organ with synthetic functions, and when genetically modified pigs are used as donors, it faces the dual problem of overcoming immune rejection and resolving physiological function mismatches. Therefore, suppressing the innate immune response can better alleviate the immune rejection of xenotransplantation. In addition, the use of chimeras of humanized cell livers may resolve the problem of physiological function mismatch. Moreover, with the development of gene editing technology, it has become possible to obtain multiple gene edited pigs and chimeras. Therefore, exploring and researching from these two aspects will hopefully solve the current problems of liver xenotransplantation and promote the further development of the field of liver xenotransplantation.
7.In vitro study of immunocompatibility of humanized genetically modified pig erythrocytes with human serum
Leijia CHEN ; Mengyi CUI ; Xiangyu SONG ; Kai WANG ; Zhibo JIA ; Liupu YANG ; Yanghui DONG ; Haochen ZUO ; Jiaxiang DU ; Dengke PAN ; Wenjing XU ; Hongbo REN ; Yaqun ZHAO ; Jiang PENG
Organ Transplantation 2024;15(3):415-421
Objective To investigate the differences and the immunocompatibility of wild-type (WT), four-gene modified (TKO/hCD55) and six-gene modified (TKO/hCD55/hCD46/hTBM) pig erythrocytes with human serum. Methods The blood samples were collected from 20 volunteers with different blood groups. WT, TKO/hCD55, TKO/hCD55/hCD46/hTBM pig erythrocytes, ABO-compatible (ABO-C) and ABO-incompatible (ABO-I) human erythrocytes were exposed to human serum of different blood groups, respectively. The blood agglutination and antigen-antibody binding levels (IgG, IgM) and complement-dependent cytotoxicity were detected. The immunocompatibility of two types of genetically modified pig erythrocytes with human serum was evaluated. Results No significant blood agglutination was observed in the ABO-C group. The blood agglutination levels in the WT and ABO-I groups were higher than those in the TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups (all P<0.001). The level of erythrocyte lysis in the WT group was higher than those in the ABO-C, TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups. The level of erythrocyte lysis in the ABO-I group was higher than those in the TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups (both P<0.01). The pig erythrocyte binding level with IgM and IgG in the TKO/hCD55 group was lower than those in the WT and ABO-I groups. The pig erythrocyte binding level with IgG and IgM in the TKO/hCD55/hCD46/hTBM group was lower than that in the WT group and pig erythrocyte binding level with IgG was lower than that in the ABO-I group (all P<0.05). Conclusions The immunocompatibility of genetically modified pig erythrocytes is better than that of wild-type pigs and close to that of ABO-C pigs. Humanized pig erythrocytes may be considered as a blood source when blood sources are extremely scarce.