1.Application of xenotransplantation in clinical practice
Shengkun SUN ; Shujun YANG ; Hao WEI ; Haihong YANG ; Jing LU ; Jiang PENG
Organ Transplantation 2024;15(2):200-206
Organ transplantation is the optimal treatment for end-stage organ failure. Nevertheless, organ shortage is a global problem, which limits further development of organ transplantation. Recent research shows that genetically modified pig may become a realistic alternative source of clinical organ transplantation donor. Xenotransplantation may serve as one of the effective measures to resolve the problem of organ shortage. Since 2021, 2 cases of living xenotransplantation and 6 cases of xenotransplantation in brain death recipients have been performed worldwide, and phase Ⅰ clinical trial of xenotransplantation has been launched, and the results have exceeded expectations. Therefore, in this article, recent clinical trial results of xenotransplantation in living and brain death recipients were retrospectively analyzed, and scientific, technical and ethical issues related to clinical research of xenotransplantation were illustrated, hoping to provide reference for clinical research of xenotransplantation in China and promote the development of xenotransplantation in clinical practice.
2.Research report of living donor kidney harvesting in Bama miniature pigs with six gene modified
Yong XU ; Xiangyu SONG ; Heng’en WANG ; Shujun YANG ; Zhibo JIA ; Hao WEI ; Shengfeng CHEN ; Mengyi CUI ; Yanling REN ; Jiang PENG ; Shengkun SUN
Organ Transplantation 2024;15(2):229-235
Objective To summarize the experience and practical value of living donor kidney harvesting in Bama miniature pigs with six gene modified. Methods The left kidney of Bama miniature pigs with six gene modified was obtained by living donor kidney harvesting technique. First, the ureter was occluded, and then the inferior vena cava and abdominal aorta were freed. During the harvesting process, the ureter, renal vein and renal artery were exposed and freed in sequence. The vascular forceps were used at the abdominal aorta and inferior vena cava, and the renal artery and vein were immediately perfused with 4℃ renal preservation solution, and stored in ice normal saline for subsequent transplantation. Simultaneously, the donor abdominal aorta and inferior vena cava gap were sutured. The operation time, blood loss, warm and cold ischemia time, postoperative complications and the survival of donors and recipients were recorded. Results The left kidney of the genetically modified pig was successfully harvested. Intraoperative bleeding was 5 mL, warm ischemia time was 45 s, and cold ischemia time was 2.5 h. Neither donor nor recipient pig received blood transfusion, and urinary function of the kidney transplanted into the recipient was recovered. The donor survived for more than 8 months after the left kidney was resected. Conclusions Living donor kidney harvesting is safe and reliable in genetically modified pigs. Branch blood vessels could be processed during kidney harvesting, which shortens the process of kidney repair and the time of cold ischemia. Living donor kidney harvesting contributes to subsequent survival of donors and other scientific researches.
3.Construction and validation of a prediction model for public acceptance of kidney xenotransplantation in China
Shujun YANG ; Hao WEI ; Jiang PENG ; Mengyi CUI ; Panfeng SHANG ; Shengkun SUN
Organ Transplantation 2024;15(1):102-111
Objective To explore the public attitude towards kidney xenotransplantation in China by constructing and validating the prediction model based on xenotransplantation questionnaire. Methods A convenient sampling survey was conducted among the public in China with the platform of Wenjuanxing to analyze public acceptance of kidney xenotransplantation and influencing factors. Using random distribution method, all included questionnaires (n=2 280) were divided into the training and validation sets according to a ratio of 7:3. A prediction model was constructed and validated. Results A total of 2 280 questionnaires were included. The public acceptance rate of xenotransplantation was 71.3%. Multivariate analysis showed that gender, marital status, resident area, medical insurance coverage, religious belief, vegetarianism, awareness of kidney xenotransplantation and whether on the waiting list for kidney transplantation were the independent influencing factors for public acceptance of kidney xenotransplantation (all P<0.05). The area under the curve (AUC) of receiver operating characteristic (ROC) of the prediction model in the training set was 0.773, and 0.785 in the validation set. The calibration curves in the training and validation sets indicated that the prediction models yielded good prediction value. Decision curve analysis (DCA) suggested that the prediction efficiency of the model was high. Conclusions In China, public acceptance of kidney xenotransplantation is relatively high, whereas it remains to be significantly enhanced. The prediction model based on questionnaire survey has favorable prediction efficiency, which provides reference for subsequent research.
4.Research progress on T lymphocyte subsets in immunosuppression of sepsis in children
Xue LIU ; Zhiyuan WANG ; Peng SHEN ; Shujun LI
Chinese Pediatric Emergency Medicine 2024;31(1):57-61
Although a great deal of research has been done on sepsis in children,its pathogenesis remains controversial and unresolved,one of which is immune dysfunction.Immunosuppression is the core part of immune dysfunction,and it is related to the disease progression,treatment options,and prognosis changes in patients with sepsis.Since T lymphocytes play a crucial role in immune function,they have been regarded as an important indicator for judging changes in immune function in clinical practice.This review explained the mechanism of immunosuppression caused by some T lymphocyte subsets and its clinical application value in the evaluation,prognosis and immune intervention of sepsis.
5.Bibliometrics-based visualization analysis of xenotransplantation(2014-2023)
Shujun YANG ; Hao WEI ; Jiang PENG ; Panfeng SHANG ; Shengkun SUN
Organ Transplantation 2024;15(5):816-823
Objective To analyze the research progress and development trend of xenotransplantation in China.Methods Literatures related to xenotransplantation in Chinese and English were searched from CNKI and Web of Science Core Collection databases from January 1,2014 to December 31,2023.Visualization analysis of the research progress,hot topics and research frontiers in this field was performed by CiteSpace software and R language from the aspects of number of publications,keywords,distribution of journal origin,core author cooperation network,main research institutions,and citation of key literatures,etc.Results Chinese scholars published 684 articles in Chinese and 624 articles in English,ranking 2nd worldwide.The top 3 Chinese journals regarding the number of publications were Organ Transplantation,Practical Journal of Organ Transplantation(Electronic Version)and Acta Laboratorium Animalis Scientia Sinica.The top 3 English journals were Xenotransplantation,Frontiers in Immunology and Scientific Reports.The top 5 authors regarding the number of publications in Chinese were Pan Dengke,Cai Zhiming,Mou Lisha,Li Xiao and Dou Kefeng.The top 5 authors regarding the number of publications in English were Mou Lisha,Cai Zhiming,Dai Yifan,Wang Yi and Pan Dengke.High-frequency Chinese keywords included xenotransplantation,immune rejection,transplantation,xenogenic,animal model,xenogeneic bone,liver transplantation,gene editing,kidney transplantation,burn and bone transplantation.High-frequency English keywords were expression,xenotransplantation,cells,transplantation and survival.Conclusions In recent years,certain research achievement and global influence have been obtained in the field of xenotransplantation in China,involving a variety of disciplines and a wide range of research contents.However,cooperation among different institutions is still lacking.In the future,cross-regional and interdisciplinary communication and cooperation should be prompted.Resource sharing and integration should be strengthened to maintain rapid and steady advancement in this field.
6.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.
7.Facial artery perforator flap in repairing lower eyelid cicatricial ectropion
Xue WEI ; Peng HU ; Jian ZHOU ; Zairong WEI ; Guijia HE ; Shujun LI ; Wei CHEN ; Kaiyu NIE
Chinese Journal of Plastic Surgery 2021;37(4):399-404
Objective:To investigate the clinical effect of the facial artery perforator flap in repairing the lower eyelid cicatricial ectropion.Methods:The clinical data of patients with lower eyelid cicatricial ectropion admitted to the Department of Burn and Plastic Surgery, Affiliated Hospital of Zunyi Medical University from January 2016 to December 2019 were retrospectively analyzed. After the lower eyelid scar was removed and contracture was released, the facial artery perforator flap was designed to repair the skin defect, and the donor site was sutured directly. The appearance and complications of the recipient and donor sites were followed up after the operation, and the operation effect was evaluated as good, general and poor.Results:A total of 22 patients with lower eyelid cicatricial ectropion were enrolled, including 15 males and 7 females, with an average age of 35.2 years (range, 27-68 years). The area of skin defect after scar release was 3.0 cm×1.5 cm-4.0 cm×2.0 cm, and the area of skin flap was 3.1 cm×1.6 cm-4.1 cm×2.1 cm. All flaps survived with good blood supply and healed well. All patients were followed up for 6-48 months, and there was no recurrence of lower eyelid ectropion, blepharon separation, local pigmentation and other phenomena. All patients showed good anatomical structure and functional improvement, and the postoperative effect evaluation of all cases was good.Conclusions:The facial artery perforator flap has the advantages of the stable perforator, good blood supply, flexible rotation, close position with the lower eyelid, and similar color, texture, and thickness. Good result can be obtained in repairing lower eyelid cicatricial ectropion by using a facial artery perforator flap.
8.Facial artery perforator flap in repairing lower eyelid cicatricial ectropion
Xue WEI ; Peng HU ; Jian ZHOU ; Zairong WEI ; Guijia HE ; Shujun LI ; Wei CHEN ; Kaiyu NIE
Chinese Journal of Plastic Surgery 2021;37(4):399-404
Objective:To investigate the clinical effect of the facial artery perforator flap in repairing the lower eyelid cicatricial ectropion.Methods:The clinical data of patients with lower eyelid cicatricial ectropion admitted to the Department of Burn and Plastic Surgery, Affiliated Hospital of Zunyi Medical University from January 2016 to December 2019 were retrospectively analyzed. After the lower eyelid scar was removed and contracture was released, the facial artery perforator flap was designed to repair the skin defect, and the donor site was sutured directly. The appearance and complications of the recipient and donor sites were followed up after the operation, and the operation effect was evaluated as good, general and poor.Results:A total of 22 patients with lower eyelid cicatricial ectropion were enrolled, including 15 males and 7 females, with an average age of 35.2 years (range, 27-68 years). The area of skin defect after scar release was 3.0 cm×1.5 cm-4.0 cm×2.0 cm, and the area of skin flap was 3.1 cm×1.6 cm-4.1 cm×2.1 cm. All flaps survived with good blood supply and healed well. All patients were followed up for 6-48 months, and there was no recurrence of lower eyelid ectropion, blepharon separation, local pigmentation and other phenomena. All patients showed good anatomical structure and functional improvement, and the postoperative effect evaluation of all cases was good.Conclusions:The facial artery perforator flap has the advantages of the stable perforator, good blood supply, flexible rotation, close position with the lower eyelid, and similar color, texture, and thickness. Good result can be obtained in repairing lower eyelid cicatricial ectropion by using a facial artery perforator flap.
9.Characteristics of exosomes secreted by -infected mouse dendritic DC2.4 cells.
Dongliang LI ; Shujun YANG ; Hongjuan PENG
Journal of Southern Medical University 2020;40(5):727-732
OBJECTIVE:
To investigate the changes in the exosomes secreted by mouse dendritic cell line DC2.4 after infection with and to analyze the possible regulatory mechanisms underlying such changes.
METHODS:
The exosomes were extracted by ultracentrifugation from DC2.4 cells at 28 h after infection with . The morphology of the exosomes was examined with transmission electron microscopy, and the exosome size and density were determined using a nanoparticle tracker. High-throughput sequencing was carried out to identify the differentially expressed small RNAs in the exosomes derived from the infected cells.
RESULTS:
infection resulted in a significantly increased density of exosomes secreted by DC2.4 cells. Small RNA sequencing revealed that infection caused an increase in the number of miRNAs and piRNAs in the exosomes. The significantly up-regulated piRNAs after the infection included piR-mmu-159, piR-mmu-1526, piR-mmu-9082, piR-mmu-17405, and piR-mmu-25576.
CONCLUSIONS
infection causes accumulation and enrichment of exosomes secreted by DC2.4 cells with increased miRNAs and piRNAs in the exosomes.
Animals
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Cell Line
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Dendritic Cells
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Exosomes
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Mice
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MicroRNAs
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RNA, Small Interfering
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Toxoplasma
10.Diagnostic value of diffusion tensor imaging in spinal neurotype brucellosis spondylitis
Peng WU ; Yujiao ZHANG ; Hongbing GUO ; Shujun CUI
Chinese Journal of Endemiology 2019;38(3):193-198
Objective To investigate the diagnostic effect of diffusion tensor imaging (DTI) on spinal neurotype brucellosis spondylitis (BS).The characteristics of apparent diffusion coefficient (ADC) value and fractional anisotropy (FA) value of spinal neurotype BS in different disease stages were quantitatively analyzed to evaluate the different forms of spinal neurofibrillary tract injury.Methods A prospective design was used to collect data of BS patients with spinal neurological symptoms from June 2015 to July 2017 in the First Affiliated Hospital of Hebei North University as the brucellosis group (n =39),including 23 males and 16 females,aged (20.8 ± 15.3) years old.Healthy subjects were selected as the control group (n =30),including 20 males and 10 females,aged (25.2 ± 4.0) years old.The brucellosis group was divided into acute stage (< 3 months),subacute stage (3-6 months) and chronic stage (> 6 months),with 12,10 and 17 cases,respectively.Routine spinal scans and DTI scans were performed using a 3.0T superconducting magnetic resonance imaging (MRI) scanner,DTI used Fiber Trak package to measure ADC value and FA value and perform quantitative analysis [receiver operating characteristic (ROC) curve],and reconstructed the changed form of the spinal neurotype BS nerve fiber bundle.Results A total of 39 patients' data were collected in the brucellosis group.Among them,5 patients showed segmental thickening of spinal nerves on conventional MRI,high signal on T2 weighted imaging (T2WI) and short time inversion recovery (STIR),and color code changes on DTI scan FA imaging.Routine MRI of 34 patients showed spinal cord compression,spinal cord morphological changes or cauda equina nerve aggregation and displacement,while DTI scan FA imaging showed spinal cord or cauda equina nerve morphological changes,but no color code changes.The ADC values of patients in the acute and subacute stages were higher than that of the control group [(1.41 ± 0.05),(1.31 ± 0.05),(1.23 ± 0.05) × 10-3 mm2/s,P < 0.05],and the FA values were lower than that of the control group (0.40 ± 0.04,0.68 ± 0.08,0.76 ± 0.05,P < 0.05).There were no statistically significant differences in ADC and FA values between patients with chronic spinal neurotype BS [(1.25 ± 0.04) × 10-3 mm2/s,0.72 ± 0.04] and the control group (P > 0.05).ROC curve analysis showed that the area under curve (AUC),specificity,sensitivity and accuracy of ADC were 0.912,0.942,0.930 and 0.924,respectively.The AUC,specificity,sensitivity and accuracy of FA were 0.901,0.937,0.928 and 0.943,respectively.The change forms of spinal neurotype BS were:① color code change;② loss/fracture;③ displacement and pressure;④ rarity.Conclusion DTI plays a diagnostic role in spinal neurotype BS,and can quantitatively analyze the characteristics of changes in ADC value and FA value in different periods,and can clearly display the forms of changes in spinal neurofiber,providing a reliable basis for the diagnosis of spinal neurotype BS.

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