1.Annual review of liver transplantation basic research of China in 2024
Desheng CHEN ; Linsen YE ; Wei LIU ; Yang YANG
Organ Transplantation 2025;16(3):338-349
Liver transplantation has currently become an important treatment for patients with end-stage liver disease or hepatocellular carcinoma (HCC), significantly improving patients’ prognosis. However, liver transplantation still facing many challenges, such as donor sources, liver preservation technology, transplant rejection, biliary complications and postoperative tumor recurrence after HCC liver transplantation, which urgently need to be solved and optimized. With the development of new technologies, liver transplantation in our country is facing new opportunities and challenges. Domestic research teams actively respond to the needs of the times and continuously promote innovation and breakthroughs in the basic research of liver transplantation. This article reviews the cutting-edge progress in the field of basic liver transplantation research in 2024 and evaluates the important research achievements obtained by Chinese research teams in this field. The systematic sorting out of these research advances not only helps to promote the integration of Chinese characteristic liver transplantation research into the international academic system and the docking of Chinese liver transplantation research with the global forefront, but also helps researchers and clinical surgeons to fully understand the current status of basic liver transplantation research in China, provides a clear direction for future basic research, and thus promotes the vigorous development of Chinese liver transplantation cause.
2.Inhibition of EMT in colorectal cancer by rosemarinic acid explored based on the Wnt/β-catenin pathway
Feng ZHOU ; Desheng SHA ; Yuanyuan LU ; Wei CHEN
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(5):726-733
Objective To investigate the role and action mechanism of rosemarinic acid(RA)on the malignant behavior of colorectal cancer(CRC)SW480 cells.Methods We collected tumor tissues from patients with primary untreated CRC who underwent surgery in People's Hospital of Rugao from January 2019 to December 2020,as well as colon tissues from normal individuals.The expression of β-catenin was detected by immunohistochemistry and Western blotting to analyze its relationship with the clinical stage,prognosis,and immune infiltration.CCK-8 was used to detect the effects of 10,15 and 20 μmol/L of RA on the proliferation of SW480 cells;flow cytometry detected apoptosis;Transwell and scratch assay detected changes in the invasion and migration ability of the cells,respectively.Western blotting detected the expressions of proteins related to apoptosis,epithelial-mesenchymal transition(EMT),and Wnt/β-catenin pathway.A mouse model of CRC transplant tumor was established,and the effect of RA on the growth of transplant tumor was investigated by gavage administration.The levels of inflammatory factors were detected by ELISA.Results The expression of β-catenin was low in normal colon tissues and significantly higher in CRC tissues.In the CRC patients with high expression of β-catenin,the number of patients with tumors larger than 5 cm was significantly higher than that in the low expression group,whereas the overall survival of the patients was significantly smaller than that in the low expression group(P<0.05).Cell proliferation was significantly inhibited and decreased in a concentration-dependent manner in the RA group at all concentrations(P<0.05).In animal experiments,the expression of apoptotic proteins Bax and Bad was significantly increased and the expression of anti-apoptotic protein Bcl-2 was significantly decreased in the RA-treated group compared with the control group(P<0.05).It was also found that the invasive and migratory ability of SW480 cells was significantly inhibited(P<0.05),the expression of E-cadherin protein was significantly increased,the expression of Snail,N-cadherin and Vimentin was significantly reduced(P<0.05),the expression of Axin and GSK-3β was increased,and the expression of β-catenin was reduced(P<0.05).Conclusion RA may inhibit the biological activity of SW480 by interfering with Wnt/β-catenin pathway-mediated EMT.
3.Quercetin increases the sensitivity of human colon cancer cells SW480 and SW620 to cisplatin
Feng ZHOU ; Desheng SHA ; Yuanyuan LU ; Wei CHEN
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(6):902-908
[Objective] To investigate the inhibitory effect of quercetin on cisplatin-resistant human colorectal cancer (CRC) cells SW480 and SW620 and its possible mechanism. [Methods] Cisplatin-resistant subtypes of SW480 and SW620 cells were first cultured and the effects of quercetin on cell proliferation and chemosensitivity were determined by MTT assay. Flow cytometry was used to detect apoptosis and protein blotting was used to detect the expressions of relevant proteins. [Results] MTT assay showed that quercetin at the concentrations of 80 μmol/L and 160 μmol/L significantly inhibited the proliferation of SW480 and SW620 cells. Flow cytometry results showed that the apoptosis rate was significantly higher in the cisplatin combined with quercetin group than in the other three groups. Protein blotting showed that cleaved-caspase-3 and caspase-9 expressions were significantly increased in the cisplatin combined with quercetin group. The chemotherapeutic drug sensitivity assay showed that the elevated IC
4.Establishment and performance evaluation of nanobody-based cat dander specific IgE antibody hypersensitivity assay
Yanyan SUN ; Desheng QI ; Furao SHEN ; Caiyue YANG ; Xiangmei SUN ; Guoning CHEN ; Jianwei WU
Chinese Journal of Immunology 2024;40(4):818-823
Objective:To prepare anti-human IgE nanobody by phage display technology,and to establish a method for hyper-sensitivity detection of cat dander specific IgE antibody.Methods:Allergen bio-information of cat was searched in WHO/IUIS Allergen Database.After synthesizing sequence,recombinant cat dander allergenic protein Fel d 1 was expressed and purified in prokaryotic ex-pression system.Human IgE was used to immunize Bactrian camel and RNA were extracted from lymphocyte to construct phage dis-play library.Library capacity,diversity and insertion rate were analyzed,anti-human IgE nanobody were obtained by screening and identification.A magnetic particle chemical method for cat dander specific IgE antibody detection was established using recombinant allergen-coupled magnetic particles and acridine ester-labeled nanobodies.Results:Capacity of phage display library was 1.88×108 cfu/ml,insertion rate was 93.6%,and purity of nanobody was>95%.Linear range of the method based on nanobody was 0.1~100 U/ml,who was consistent with ImmunoCAP detection system by clinical data.Conclusion:Nanobody-based cat dander specific IgE antibody hypersensitivity assay is successfully prepared,providing a technical basis for auxiliary diagnosis of cat allergic diseases.
5.Alternative Biological Material for Tissue Engineering of the Vagina: Porcine-Derived Acellular Vaginal Matrix
Yanpeng TIAN ; Yibin LIU ; Yanlai XIAO ; Zhongkang LI ; Mingle ZHANG ; Liang CHEN ; Zhen LI ; Wangchao ZHANG ; Zhiqiang ZHANG ; Desheng KONG ; Li MENG ; Yanfang DU ; Jingkun ZHANG ; Jingui GAO ; Xianghua HUANG
Tissue Engineering and Regenerative Medicine 2024;21(2):277-290
BACKGROUND:
Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a severe congenital disorder characterized by vaginal hypoplasia caused by dysplasia of the Müllerian duct. Patients with MRKH syndrome often require nonsurgical or surgical treatment to achieve satisfactory vaginal length and sexual outcomes. The extracellular matrix has been successfully used for vaginal reconstruction.
METHODS:
In this study, we developed a new biological material derived from porcine vagina (acellular vaginal matrix, AVM) to reconstruct the vagina in Bama miniature pigs. The histological characteristics and efficacy of acellularization of AVM were evaluated, and AVM was subsequently transplanted into Bama miniature pigs to reconstruct the vaginas.
RESULTS:
Macroscopic analysis showed that the neovaginas functioned well in all Bama miniature pigs with AVM implants. Histological analysis and electrophysiological evidence indicated that morphological and functional recovery was restored in normal vaginal tissues. Scanning electron microscopy showed that the neovaginas had mucosal folds characteristics of normal vagina. No significant differences were observed in the expression of CK14, HSP47, and a-actin between the neovaginas and normal vaginal tissues. However, the expression of estrogen receptor (ER) was significantly lower in the neovaginas than in normal vaginal tissues. In addition, AVM promoted the expression of b-catenin, c-Myc, and cyclin D1. These results suggest that AVM might promotes vaginal regeneration by activating the b-catenin/cMyc/cyclin D1 pathway.
CONCLUSION
This study reveals that porcine-derived AVM has potential application for vaginal regeneration.
6.Expert consensus on the detection of genome-wide copy number variations in abortive tissues and family reproductive consultation.
Xin CHEN ; Zhuo LI ; Desheng LIANG ; Lingqian WU
Chinese Journal of Medical Genetics 2023;40(2):129-134
Chromosomal aberrations including numerical abnormalities and segment duplications/deletions, as genome-wide copy number variations (CNVs), are a leading cause for spontaneous abortion. Analysis of abortive tissues for such CNVs can detect potential genomic variations in the couple and provide guidance for the choice of appropriate method to avoid further miscarriage or birth of child with chromosomal disorders. With evidence-based clinical data, an expert group jointly formed by the Genetic Disease Prevention and Control Group, Committee for Birth Defects Prevention and Control, Chinese Association of Preventive Medicine; the Clinical Genetics Group, the Society of Medical Genetics, Chinese Medical Association; the Professional Committee for Prenatal Diagnosis of Genetic Diseases, the Society of Medical Geneticists, Chinese Medical Doctor Association has discussed and formulated this consensus, with an aim to provide guidance for the application of genomic CNVs detection for the abortive tissue and genetic counseling for family reproduction.
Pregnancy
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Child
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Female
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Humans
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DNA Copy Number Variations
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Consensus
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Chromosome Aberrations
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Chromosome Disorders/genetics*
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Abortion, Spontaneous/genetics*
7.Clinical efficacy of hip arthroscopy in the treatment of acetabular labral injury with cysts
Hongzhou LI ; Tao ZHANG ; Desheng CHEN ; Yu GOU ; Qian ZHAO ; Jiangang CAO
Chinese Journal of Orthopaedics 2023;43(23):1580-1586
Objective:To investigate the clinical efficacy of hip arthroscopy in the treatment of acetabular labral injury combined with cysts.Methods:A total of 14 patients (5 males and 9 females) aged 35.46±12.62 years (range, 26-57 years) with acetabular labral injury complicated with cyst who underwent hip arthroscopy in Department of Sports Injury and Arthroscopy, Tianjin Hospital from January 2017 to April 2022 were retrospectively analyzed. There were 8 cases of left hip and 6 cases of right hip with an average body mass index of 24.35±3.14 kg/m 2 (range, 20.2-28.4 kg/m 2). The duration of symptoms was 6.25±4.39 months (range, 3-11 months). All patients underwent hip arthroscopic cyst cleaning and glenoid labral suturing. The femoral neck α angle, lateral center rim angle, visual analogue score (VAS), Harris hip score (HHS), and international hip outcome tool scores (iHOT-12) were compared before and after operation. Results:All patients successfully completed the operation and were followed up for 10.23±2.45 months (range, 1.5-18 months). The difference between the patients' hip VAS before and after operation was statistically significant ( F=108.47, P<0.001). The VAS score at 18 months after operation was 1.34±0.83, which was significantly lower than that before operation 7.85±1.12 and at 6 weeks after operation 5.03±1.60 ( P<0.05). The difference between the patients' hip HHS scores before and after operation was statistically significant ( F=96.89, P<0.001). The HHS score at 18 months after operation was 85.58±4.65, which was significantly higher than that before operation 54.36±2.31 and 6 weeks after operation 61.12±1.20 ( P<0.05). The differences of iHOT-12 scores before and after operation were statistically significant ( F=117.92, P<0.001). The iHOT-12 score of 18 months after operation was 78.36±2.28 points, which was higher than that before operation 31.39±5.21 points and 6 weeks after operation 47.88±2.20 points, and the difference was statistically significant ( P<0.05). The difference of α angle of femoral neck before and after operation was statistically significant ( F=101.56, P<0.001). The α angle of femoral neck at 12 months after operation was 45.32°±3.16°, which was significantly lower than that before operation 50.86°±8.41° ( P<0.05). The difference of lateral center rim angle before and after operation was statistically significant ( F=100.38, P<0.001). The lateral center rim angle was 28.23°±5.32° at 12 months after operation, which was smaller than that before operation 32.16°±5.13°, and the difference was statistically significant ( P<0.05). Conclusion:Hip arthroscopy in the treatment of acetabular labral injury with cysts can relieve hip pain and improve hip function.
8.Primary construction and application of National bank for HIV-1 standard strains
Li REN ; Lin HE ; Meiling ZHU ; Yan WANG ; Desheng KONG ; Chen WANG ; Yi FENG ; Yiming SHAO ; Hui XING ; Chuntao MA ; Liying MA
Chinese Journal of Experimental and Clinical Virology 2023;37(3):280-285
Objective:To construct standard strains representing the main epidemic clades of HIV-1 in China, amplify the virus strains, and establish a seed lot.Methods:Six isolates of HIV-1 virus were identified and analyzed in genotype and phenotype, according to " interpretation for the social organization of the Standard strains of pathogenic microorganism- technical specifications for establishment of HIV strains". The isolates were amplified and cultivated to generate the secondary generation primary seed lot and the third generation working seed lot as frozen storage in liquid nitrogen. Results:Six HIV-1 standard strains were obtained, of which 3 strains are CRF_ 07BC (NRPC2.4.9003, NRPC2.4.9005, NRPC2.4.9006), 1 strain is CRF_ 01AE (NRPC2.4.9001), 1 strain is CRF_ 08BC (NRPC2.4.9002), and 1 strain is URF (NRPC2.4.9004). Phenotypic detection showed that all six strains are CCR5 tropics and Non syncytia inducing virus. TCID 50 were all greater than 1 × 10 5/ml, and concentrations of p24 antigen were all higher than 2 ng/ml. A primary seed lot with no less than 20 vials per strain and a working seed lot with no less than 50 vials per strain were constructed. The standard virus strains were used in evaluating antiviral drugs PEG2kC34, PEG5kC34, LP-19, and neutralizing antibody LSEVh LS-F. Conclusions:Six standard strains of HIV-1 virus covering the three main epidemic subtypes of HIV-1 in China have been obtained, and a storage of HIV-1 standard strain was constructed. It meets the need of the preservation of HIV-1 standard strains in China and provides support for drug and vaccine evaluation.
9.Restoration of FMRP expression in adult V1 neurons rescues visual deficits in a mouse model of fragile X syndrome.
Chaojuan YANG ; Yonglu TIAN ; Feng SU ; Yangzhen WANG ; Mengna LIU ; Hongyi WANG ; Yaxuan CUI ; Peijiang YUAN ; Xiangning LI ; Anan LI ; Hui GONG ; Qingming LUO ; Desheng ZHU ; Peng CAO ; Yunbo LIU ; Xunli WANG ; Min-Hua LUO ; Fuqiang XU ; Wei XIONG ; Liecheng WANG ; Xiang-Yao LI ; Chen ZHANG
Protein & Cell 2022;13(3):203-219
Many people affected by fragile X syndrome (FXS) and autism spectrum disorders have sensory processing deficits, such as hypersensitivity to auditory, tactile, and visual stimuli. Like FXS in humans, loss of Fmr1 in rodents also cause sensory, behavioral, and cognitive deficits. However, the neural mechanisms underlying sensory impairment, especially vision impairment, remain unclear. It remains elusive whether the visual processing deficits originate from corrupted inputs, impaired perception in the primary sensory cortex, or altered integration in the higher cortex, and there is no effective treatment. In this study, we used a genetic knockout mouse model (Fmr1KO), in vivo imaging, and behavioral measurements to show that the loss of Fmr1 impaired signal processing in the primary visual cortex (V1). Specifically, Fmr1KO mice showed enhanced responses to low-intensity stimuli but normal responses to high-intensity stimuli. This abnormality was accompanied by enhancements in local network connectivity in V1 microcircuits and increased dendritic complexity of V1 neurons. These effects were ameliorated by the acute application of GABAA receptor activators, which enhanced the activity of inhibitory neurons, or by reintroducing Fmr1 gene expression in knockout V1 neurons in both juvenile and young-adult mice. Overall, V1 plays an important role in the visual abnormalities of Fmr1KO mice and it could be possible to rescue the sensory disturbances in developed FXS and autism patients.
Animals
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Disease Models, Animal
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Fragile X Mental Retardation Protein/metabolism*
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Fragile X Syndrome/metabolism*
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Humans
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Mice
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Mice, Knockout
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Neurons/metabolism*
10.Genome-wide analysis identify novel germline genetic variations in ADCY1 influencing platinum-based chemotherapy response in non-small cell lung cancer.
Chenxue MAO ; Juan CHEN ; Ting ZOU ; Yuankang ZHOU ; Junyan LIU ; Xi LI ; Xiangping LI ; Min LI ; Pinhua PAN ; Wei ZHUO ; Yang GAO ; Shuo HU ; Desheng XIAO ; Lin WU ; Zhan WANG ; Heng XU ; Wen YANG ; Yingjie XU ; Haihua XIAO ; Kazuhiko HANADA ; Wei ZHANG ; Honghao ZHOU ; Jiye YIN ; Zhaoqian LIU
Acta Pharmaceutica Sinica B 2022;12(3):1514-1522
To explore the pharmacogenomic markers that affect the platinum-based chemotherapy response in non-small-cell lung carcinoma (NSCLC), we performed a two-cohort of genome-wide association studies (GWAS), including 34 for WES-based and 433 for microarray-based analyses, as well as two independent validation cohorts. After integrating the results of two studies, the genetic variations related to the platinum-based chemotherapy response were further determined by fine-mapping in 838 samples, and their potential functional impact were investigated by eQTL analysis and in vitro cell experiments. We found that a total of 68 variations were significant at P < 1 × 10-3 in cohort 1 discovery stage, of which 3 SNPs were verified in 262 independent samples. A total of 541 SNPs were significant at P < 1 × 10-4 in cohort 2 discovery stage, of which 8 SNPs were verified in 347 independent samples. Comparing the validated SNPs in two GWAS, ADCY1 gene was verified in both independent studies. The results of fine-mapping showed that the G allele carriers of ADCY1 rs2280496 and C allele carriers of rs189178649 were more likely to be resistant to platinum-based chemotherapy. In conclusion, our study found that rs2280496 and rs189178649 in ADCY1 gene were associated the sensitivity of platinum-based chemotherapy in NSCLC patients.

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