1.Allogeneic lung transplantation in miniature pigs and postoperative monitoring
Yaobo ZHAO ; Ullah SALMAN ; Kaiyan BAO ; Hua KUI ; Taiyun WEI ; Hongfang ZHAO ; Xiaoting TAO ; Xinzhong NING ; Yong LIU ; Guimei ZHANG ; He XIAO ; Jiaoxiang WANG ; Chang YANG ; Feiyan ZHU ; Kaixiang XU ; Kun QIAO ; Hongjiang WEI
Organ Transplantation 2026;17(1):95-105
Objective To explore the feasibility and reference value of allogeneic lung transplantation and postoperative monitoring in miniature pigs for lung transplantation research. Methods Two miniature pigs (R1 and R2) underwent left lung allogeneic transplantation. Complement-dependent cytotoxicity tests and blood cross-matching were performed before surgery. The main operative times and partial pressure of arterial oxygen (PaO2) after opening the pulmonary artery were recorded during surgery. Postoperatively, routine blood tests, biochemical blood indicators and inflammatory factors were detected, and pathological examinations of multiple organs were conducted. Results The complement-dependent cytotoxicity test showed that the survival rate of lymphocytes between donors and recipients was 42.5%-47.3%, and no agglutination reaction occurred in the cross-matching. The first warm ischemia times of D1 and D2 were 17 min and 10 min, respectively, and the cold ischemia times were 246 min and 216 min, respectively. Ultimately, R1 and R2 survived for 1.5 h and 104 h, respectively. Postoperatively, in R1, albumin (ALB) and globulin (GLB) decreased, and alanine aminotransferase increased; in R2, ALB, GLB and aspartate aminotransferase all increased. Urea nitrogen and serum creatinine increased in both recipients. Pathological results showed that in R1, the transplanted lung had partial consolidation with inflammatory cell infiltration, and multiple organs were congested and damaged. In R2, the transplanted lung had severe necrosis with fibrosis, and multiple organs had mild to moderate damage. The expression levels of interleukin-1β and interleukin-6 increased in the transplanted lungs. Conclusions The allogeneic lung transplantation model in miniature pigs may systematically evaluate immunological compatibility, intraoperative function and postoperative organ damage. The data obtained may provide technical references for subsequent lung transplantation research.
2.Progress in preclinical studies of xenogeneic lung transplantation and single-center technical experience
Xiaoting TAO ; Xinzhong NING ; Yong LIU ; Guimei ZHANG ; He XIAO ; Shiyu LIN ; Zizi ZHOU ; Taiyun WEI ; Chunxiao HU ; Hongjiang WEI ; Kun QIAO
Organ Transplantation 2025;16(6):874-880
Lung transplantation is the ultimate therapeutic option for end-stage pulmonary diseases such as interstitial pneumonia, chronic obstructive pulmonary disease and pneumoconiosis. Currently, the shortage of allogeneic lung donors significantly limits the opportunity for end-stage lung disease patients to receive lung transplantation. In recent years, with the rapid development of biomedical engineering technologies, especially the major breakthroughs in genetic modification and cloning, xenogeneic lung transplantation has shown important potential for clinical translation. Among them, genetically modified pigs have become the most promising xenogeneic lung source due to the close similarity of organ size and physiological characteristics to humans, and the ability to perform targeted gene knockouts (such as α-Gal antigen knockout) to reduce the occurrence of hyperacute rejection. This article focuses on the research progress of porcine xenogeneic lung transplantation, systematically reviews the latest achievements and challenges in animal experiments and human trials, and introduces the technical experience accumulated by Shenzhen Third People's Hospital in the porcine-to-monkey xenogeneic lung transplantation model, in the hope of providing practical references for future research in this field.
3.Cuproptosis-related lncRNA JPX regulates malignant cell behavior and epithelial-immune interaction in head and neck squamous cell carcinoma via miR-193b-3p/PLAU axis.
Mouyuan SUN ; Ning ZHAN ; Zhan YANG ; Xiaoting ZHANG ; Jingyu ZHANG ; Lianjie PENG ; Yaxian LUO ; Lining LIN ; Yiting LOU ; Dongqi YOU ; Tao QIU ; Zhichao LIU ; Qianting WANG ; Yu LIU ; Ping SUN ; Mengfei YU ; Huiming WANG
International Journal of Oral Science 2024;16(1):63-63
The development, progression, and curative efficacy of head and neck squamous cell carcinoma (HNSCC) are influenced by complex interactions between epithelial and immune cells. Nevertheless, the specific changes in the nature of these interactions and their underlying molecular mechanisms in HNSCC are not yet fully understood. Cuproptosis, a form of programmed cell death that is dependent on copper, has been implicated in cancer pathogenesis. However, the understanding of cuproptosis in the context of HNSCC remains limited. In this study, we have discovered that cuproptosis-related long non-coding RNAs (CRLs) known as JPX play a role in promoting the expression of the oncogene urokinase-type plasminogen activator (PLAU) by competitively binding to miR-193b-3p in HNSCC. The increased activity of the JPX/miR-193b-3p/PLAU axis in malignant epithelial cells leads to enhanced cell proliferation, migration, and invasion in HNSCC. Moreover, the overexpression of PLAU in tumor epithelial cells facilitates its interaction with the receptor PLAUR, predominantly expressed on macrophages, thereby influencing the abnormal epithelial-immune interactome in HNSCC. Notably, the JPX inhibitor Axitinib and the PLAU inhibitor Palbociclib may not only exert their effects on the JPX/miR-193b-3p/PLAU axis that impacts the malignant tumor behaviors and the epithelial-immune cell interactions but also exhibit synergistic effects in terms of suppressing tumor cell growth and arresting cell cycle by targeting epidermal growth factor receptor (EGFR) and cyclin-dependent kinase (CDK4/6) for the treatment of HNSCC.
Humans
;
MicroRNAs/metabolism*
;
RNA, Long Noncoding/metabolism*
;
Head and Neck Neoplasms/metabolism*
;
Cell Proliferation
;
Squamous Cell Carcinoma of Head and Neck/genetics*
;
Urokinase-Type Plasminogen Activator/genetics*
;
Cell Movement
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Cell Line, Tumor
;
Gene Expression Regulation, Neoplastic
;
Carcinoma, Squamous Cell/genetics*
;
Neoplasm Invasiveness
4.Effects of neuroticism on memory in patients with first-episode depression and the mediating role of depression
Ning SUN ; Xiaoting HE ; Qiaorong DU ; Xinrong LI ; Suping LI ; Kerang ZHANG
Chinese Journal of Behavioral Medicine and Brain Science 2016;25(11):977-980
Objective To explore the relationship between neuroticism and memory in patients with first-episode depression and the mediating effect of depression in this relationship.Methods Hamilton de pression rating scale (HAMD),Eysenck personality questionnaire (EPQ),repeatable battery for the assess ment of neuropsychological status (RBANS) were used to evaluate 278 patients with first-episode depression.Results (1) Neuroticism was negatively correlated with immediate memory(r=-0.26,P<0.01),delayed memory (r=-0.30,P<0.01),and positively correlated with depressive symptom (r =0.30,P< 0.01).Depres-sive symptom was negatively correlated with immediate memory (r=-0.55,P<0.01),delayed memory (r=-0.44,P<0.01).(2) The effect of neuroticism on immediate memory and delayed memory was partially mediated by depressive symptom (β=-0.521,-0.388,P<0.01).The ratio of mediating effect to total effect in immediate memory was 0.597,and the ratio of mediating effect to total effect in delayed memory was 0.383.Conclusion Memory can be affected by neuroticism through the indirect effect of depression.
5.Influencing factors of anxiety symptoms in patients with depression
Xiaoting HE ; Ning SUN ; Qiaorong DU ; Chunxia YANG ; Zhifen LIU ; Yanfang WANG ; Suping LI ; Kerang ZHANG
Chinese Journal of Nervous and Mental Diseases 2016;42(4):206-210
Objective To investigate the status of depression with anxiety symptoms, and analyze the influencing factors of anxiety symptoms from demographic data and social psychological factors. Methods Hamilton depression rat?ing scale (HAMD), Hamilton anxiety rating scale (HAMA), Eysenck personality questionnaire (EPQ), life event scale (LES), trait coping style questionnaire (TCSQ) and social support scale (SSS) were used to evaluate 729 patients with de?pression. According to HAMA scores, patients were divided into non anxiety symptoms group (HAMA<7) and anxiety symptoms group (HAMA>14). Social psychological factors were compared between two groups, and the influencing fac?tors of anxiety symptoms were analyzed. Results The incidence of anxiety symptoms in depression was 58.85% (429/729), and 119 cases (16.32%) were certainly without anxiety symptoms. Compared with the group without anxiety symp?toms, the anxiety symptoms group had higher scores on neuroticism, psychoticism, negative life events and negative cop?ing style (P<0.001), but lower scores on introversion and extroversion (P=0.010). Degree of depression (OR=9.255, 95%CI:4.726~18.127), neuroticism (OR=1.595, 95%CI:1.197~2.125), negative life events (OR=1.009, 95%CI:1.001~1.017) and negative coping style (OR=1.046, 95%CI:1.013~1.080) were the risk factors of anxiety symptoms (P<0.05). Conclu?sion The incidence of anxiety symptoms in patients with depression is high. Patients with higher degree of depression and typical neurotic personality experiencing more negative life events and those with tendency to adopt negative coping style are more susceptible to anxiety symptoms.
6.Correlation between subchondral bone mass and cartilage degeneration
Guorong SHE ; Zhengang ZHA ; Fei WANG ; Ning LIU ; Xiaoting PAN ; Jian GONG ; Yanping YANG
Chinese Journal of Tissue Engineering Research 2015;19(20):3134-3140
BACKGROUND:Correlation between subchondral bone and articular cartilage in the process of osteoarthritis has not been fuly elucidated. Degeneration of cartilage is the focus of attention, and the subchondral bone also plays an important role in the process of osteoarthritis. OBJECTIVE: To observe the differences between experimental osteoarthritis models in rabbit knees established by two kinds of surgical methods and two kinds of proteases inducing methods, and to explore the correlation between subchondral bone mass and degeneration of cartilage. METHODS:Thirty-two New Zealand rabbits were randomly and averagely divided into four groups: Hulth group (group A), anterior cruciate ligament transaction group (group B), colagenase type II group (group C) and papain group (group D). The right knees of rabbits were established as osteoarthritis models, and the left knees served as controls. Bone mineral density of the knee joint was evaluated by dual-energy X-ray absorptiometry scanning at 0, 4 and 8 weeks after modeling. The rabbits were sacrificed at 8 weeks after MRI scanning, bilateral knee joints were harvested for general and histological observation. Quantitative analysis was done according to Mankin scores. RESULTS AND CONCLUSION: Bone mineral density of the right knees decreased at 0, 4 and 8 weeks after modeling, and the rank was as folows: group A > group B > group C > group D. MRI scanning showed that the articular cartilage thickness of the medial and lateral femoral condyle on the right knees became thinner compared with the left side, and the rank was as folows: group A < group B < group C < group D. Observation by specimens and pathological slices showed that the articular cartilage degeneration of the surgery groups worsened, group A was the most serious one, and group 1D was the lightest. Both surgery and proteases inducing methods can successfuly establish osteoarthritis models in rabbit knees. Surgery inducing models resemble the advanced or intermediate stage of osteoarthritis, while the proteases inducing models resemble the early stage of osteoarthritis. Degeneration of the articular cartilage and changes of subchondral bone are related in progressive development.
7.The Distribution of the Lipid Droplets within Hensen Cells in the Guinea -pig Cochlea
Fengbo YANG ; Daxiong DING ; Ping LV ; Xiaoting CHENG ; Hongmiao REN ; Guowei HUANG ; Xiaodong WANG ; Chen LIU ; Yue ZHANG ; Tao CONG ; Shiming YANG ; Suoqiang ZHAI ; Ning YU
Journal of Audiology and Speech Pathology 2015;(5):500-504
Objective To study the distribution and properly of the transparent globules within Hensen cells (HC) of guinea -pig Corti organ .Methods The cochlear epithelial cells were isolated from 10 guinea pigs .The cells of cochlea were marked by Bodipy493/503 ,sudan III ,oil red O ,and osmium tetroxide .Results The transpar‐ent globules within the HCs of the guinea -pigs were green staining by Bodipy493/503 ,jacinth staining by Sudan III ,ruby red by oil red O .And they were black globules stripe as post -fixed in 1% osmium tetroxide .Conclusion The results indicate that the transparent globules within guinea -pigs HCs'lipid droplets by four methods .
8.Chondrocyte supernatant induces chondrogenesis and pellet cultivation of rat synovial mesenchymal stem cells
Bo SHAO ; Zhongcheng GONG ; Hui LIU ; Bin LING ; Remu KE ; Xiaopeng YIN ; Lulu HU ; Bing WANG ; Xiaoting NING ; Zhaoquan LIN
Chinese Journal of Tissue Engineering Research 2014;(1):100-105
BACKGROUND:Synovial mesenchymal stem cells have the ability of multilineage differentiation in vitro, which are expected to be seed cells for the treatment of cartilage defects in cartilage tissue engineering. Appropriate growth factors are critical for the chondrocyte differentiation of synovial mesenchymal stem cells.
OBJECTIVE:To study the role of secreted factors by chondrocytes to induce chondrogenesis of synovial mesenchymal stem cells.
METHODS:The synovial mesenchymal stem cells and chondrocytes were harvested from rat knee joints and cultured through the digestion method. The supernatant was col ected from chondrocytes, and centrifuged, filtered and cryopreserved. The third passage synovial mesenchymal stem cells centrifuged as pel ets were cultured in the chondrocyte supernatant for 21 days. And the cells morphology was examined and the type II col agen and aggrecan were detected through immunohistochemistry and RT-PCR.
RESULTS AND CONCLUSION:The synovial mesenchymal stem cellpel ets cultured in the chondrocyte supernatant became cartilage-like tissue after 21 days. The type II col agen was detected positively in the matrix of synovial mesenchymal stem cellpel et immunohistochemical y. RT-PCR examination showed that the type II col agen and aggrecan expressed in the synovial mesenchymal stem cellpel et cultured in the chondrocyte supernatant. It suggested that synovial mesenchymal stem cellcould be induced to differentiate into chondrocytes depending on soluble factors secreted by chondrocytes.
9.Chondrogenesis of synovial mesenchymal stem cells co-cultured with chondrocytes on the three-dimensional scaffold
Xiaoting NING ; Bo SHAO ; Zhongcheng GONG ; Hui LIU ; Bin LING ; Abass KEREMU ; Zhaoquan LIN ; Meng YANG ; Xiaopeng YIN ; Lulu HU
Chinese Journal of Tissue Engineering Research 2014;(34):5434-5440
BACKGROUND:Articular chondrocytes with the ability of autocrine and paracrine can provide the growth factors and microenvironment for synovial mesenchymal stem cels differentiating into the chondrocyte. The
three-dimensional scaffold could provide space for cels adhesion, proliferation and differentiation.
OBJECTIVE: To study the ability of chondrogenesis by co-culturing synovial mesenchymal stem cels and chondrocytes under the three-dimensional condition.
METHODS:The synovial membrane and articular cartilage were harvested from rat knee joint. The synovial
mesenchymal stem cels and chondrocytes were obtained through the method of enzyme digestion. The passage 3 synovial mesenchymal stem cels and passage 2 chondrocytes were co-cultured in the chitosan/I colagen
composite scaffolds at the ratio of 1:2. Then, the cels/scaffold composite was harvested to be examined
morphologicaly, histologicaly and immunohistochemicaly after being cultured 21 days. The confocal laser was also employed to detect the cels distribution in the scaffold.
RESULTS AND CONCLUSION: After being cultured 72 hours, it could be observed from the cels/scaffold composite examined through the scanning electron microscope that the cels adhered on the surface of the
scaffold and extracelular matrix surrounding the cels was seen on the scaffold. After being cultured 21 days, it could be found through the confocal laser scanning that the cels were wel-distributed on the scaffold, and cels decreased gradualy. Type II colagen was positive in the extracelular matrix immunohistochamicaly. It
suggested from this study that the synovial mesenchymal stem cels could be co-cultured with chondrocytes in the chitosan/I colagen composite scaffolds and have the ability of chondrogenesis differentiation.
10.Chondrogenic differentiation of rat synovial-derived mesenchymal stem cells
Bo SHAO ; Zhongcheng GONG ; Hui LIU ; Bin LING ; Abass KEREMU ; Xiaopeng YIN ; Lulu HU ; Bing WANG ; Xiaoting NING ; Meng YANG ; Zhaoquan LIN
Chinese Journal of Tissue Engineering Research 2014;(15):2338-2344
BACKGROUND:Compared with other sources of mesenchymal stem cells, synovial-derived mesenchymal stem cells have significant characteristics of chondrogenesis and cloning. Therefore, synovial-derived mesenchymal stem cells are one of the most promising seed cells in cartilage tissue engineering.
OBJECTIVE:To isolate and culture synovial-derived mesenchymal stem cells of Sprague-Dawley rats, identify the multipotential differentiation and the potential ability of chondrogenic differentiation in three-dimensional culture condition.
METHODS:The synovium tissue was harvested from Sprague-Dawley rats. The synovial-derived mesenchymal stem cells were isolated with typeⅠcol agen enzyme digestion method and cultured in vitro. The passage 3 cells were detected with giemsa staining, the cellcycle, adipogenic and osteogenic differentiation were determined. The passage 3 cells were centrifuged as pel ets and cultured in the chondriogenic medium for 21 days. And the pel ets were examined by toluidine blue staining, typeⅡcol agen immunohistochemical staining and RT-PCR.
RESULTS AND CONCLUSION:The mesenchymal stem cells isolated from the synovium tissue of rats have the characteristics of mesenchymal stem cells, and exhibit fibroblast-like morphology after cultured in vitro. The multilineage differentiation potentials were also revealed. After the cellwere cultured in chondrogenic medium for 21 days, chondroid tissue was found, type II col agen and aggrecan could be detected positively by toluidine blue staining, typeⅡcol agen immunohistochemical staining, and expressed by RT-PCR examination. Therefore, synovial mesenchymal stem cells have a chondrogenic differentiation potential.

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