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Biomedical subjects

Tao Jiang

Publications and source records attributed to Tao Jiang.

At least 19 recordsLinked to original sources

Protocol for haplotype-resolved structural variant detection via long-read sequencing using cuteHap.

Long-read sequencing technologies have revolutionized human genome exploration at an unparalleled resolution, particularly facilitating the analysis of structural variation (SV) at haplotype resolution. Here, we present a protocol for using cuteHap, a robust framework for haplotype-aware SV detection through phased alignment reads generated by diverse long-read sequencing platforms. We describe procedures for single-nucleotide variant (SNV) calling, read phasing, SV calling, and genotyping. We also establish a benchmarking pipeline to evaluate the detected SV callsets. For complete details on the use and execution of this protocol, please refer to Cao et al.1.

Bioinformatics↗

Large-scale whole-genome sequencing reveals the landscape and health implications of de novo mutations.

De novo mutations (DNMs) are an important source of congenital diseases. With delayed parenthood and assisted reproductive technology (ART) use increasing, it is essential to elucidate how these reproductive factors influence DNMs and whether resulting mutations influence offspring health. Here we performed whole-genome sequencing of 24,030 individuals from 7,851 parent-offspring families, identifying 390,924 de novo single-nucleotide variants (dnSNVs). Paternal and maternal aging exhibited distinct mutational patterns, with maternal DNM accumulation accelerating at advanced ages. Increased paternal dnSNVs partially accounted for the association between advanced parental age and shorter gestational duration. Moreover, ART showed age-independent, procedure-specific effects: intracytoplasmic sperm injection (ICSI) and ovarian stimulation were associated with increased paternal and maternal dnSNVs, respectively, and ICSI-associated paternal dnSNVs also partially accounted for the association between ICSI and shorter gestational duration. In vitro embryo manipulation was associated with increased early post-zygotic mosaic mutations, particularly C > A substitutions linked to delayed neurocognitive development at 1 year. Collectively, these findings advance understanding of the determinants and consequences of de novo mutagenesis.

Journal Article↗

Structural insights into histone mimicry by the small hepatitis delta antigen.

Hepatitis delta virus (HDV) is a satellite RNA virus that requires hepatitis B virus (HBV) for propagation but replicates its genome independently in the nucleus. The small form of the hepatitis delta antigen (S-HDAg) is essential for replication and is regulated by post-translational modifications. Acetylation at lysine 72 (K72ac) enables S-HDAg to interact with the bromodomain (BRD) of the host chromatin remodeler bromodomain adjacent to zinc finger domain protein 2B (BAZ2B) to promote viral replication. However, the structural basis for this interaction has remained elusive. Here, we provide structural and biophysical insights into this interaction through quantitative binding assays and X-ray crystallography. Isothermal titration calorimetry revealed that BRDs of BAZ2B and its close homolog BAZ2A bind to the viral peptide weakly, with BAZ2A-BRD exhibiting a modestly higher affinity. The crystal structure of BAZ2A-BRD in complex with the S-HDAg-K72ac peptide demonstrates an inverted binding orientation relative to canonical histone ligands, rationalizing the weak interaction. Mutagenesis studies confirmed the critical binding interface both in vitro and in cells. These findings elucidate the molecular mechanism by which HDV co-opts host BAZ2 bromodomains via a unique, weak-affinity interaction, providing a structural framework for understanding viral replication.

Hepatitis delta Antigens↗

The causal relationship between multiple cardiovascular diseases and glioblastoma: A Mendelian randomization study.

Observational studies suggest an association between glioblastoma (GBM) and cardiovascular diseases (CVDs), but a causal relationship remains unestablished. This study aimed to investigate the causal link between multiple CVDs and GBM risk. The inverse variance weighted method indicated that all 18 CVDs had significant causal associations with GBM (P&#x2005;<&#x2005;.05). Genetically predicted CVDs were uniformly associated with a lower risk of GBM (odds ratio&#x2005;<&#x2005;1), identifying them as potential protective factors. Sensitivity analyses confirmed the absence of significant heterogeneity or horizontal pleiotropy, and the MR-Steiger test validated the correct causal direction. This Mendelian randomization (MR) study provides evidence that a range of CVDs are causally associated with a decreased risk of developing GBM. These findings suggest shared biological pathways and offer new insights for understanding GBM etiology. We conducted a 2-sample MR analysis using publicly available genome-wide association study data. GBM was the outcome, and 18 cardiovascular-related traits (including coronary artery disease, myocardial infarction, and venous thromboembolism) were exposures. Instrumental variables were single-nucleotide polymorphisms significantly associated with exposures (P&#x2005;<&#x2005;5&#x2005;&#xd7;&#x2005;10-8). The primary analysis used the inverse variance weighted method, supplemented with MR-Egger, weighted median, and weighted mode methods. Sensitivity analyses, including Cochran Q test, MR-Egger intercept test, leave-one-out analysis, and MR-Steiger directionality test, were performed to ensure robustness.

Causality↗

Awake Craniotomy for Eloquent Region Glioblastoma Classified by Tumor Location-A Retrospective and Prospective Cohort Study.

INTRODUCTION: The efficacy of awake craniotomy (AC) with intraoperative mapping for glioblastoma (GBM) in eloquent regions remains debated. This study aims to evaluate functional and survival outcomes of GBM patients undergoing AC stratified by tumor locations. METHODS: A combined retrospective (2015-2023, n&#x2009;=&#x2009;114: 43&#x2009;AC vs. 71 standard craniotomy) and prospective cohort (2023-2025, n&#x2009;=&#x2009;28: 13&#x2009;AC vs. 15 standard craniotomy) of GBM patients with motor/language-eloquent tumors was analyzed. Tumors were classified into motor subtypes (I: precentral gyrus; II: premotor/supplementary motor; III: internal capsule posterior limb; IV: other) and language subtypes (I: Broca's/precentral; II: postcentral/supramarginal gyrus; III: Wernicke's; IV: insular; V: other). Outcomes included extent of resection (EOR), postoperative motor/language recovery, overall survival (OS), and progression-free survival (PFS). RESULTS: The retrospective cohort demonstrated that AC has advantages in functional preservation across various motor/language subtypes. However, AC was associated with significantly deteriorated survival outcomes specifically in precentral gyrus GBMs. A prospective cohort study, enrolling only precentral gyrus GBMs for validation, yielded results consistent with the retrospective findings: worsened OS and PFS (OS: HR&#x2009;=&#x2009;3.223, p&#x2009;=&#x2009;0.0450; PFS: HR&#x2009;=&#x2009;2.374, p&#x2009;=&#x2009;0.0476); reduced EOR (AC:&#xa0;74.3%&#x2009;&#xb1;&#x2009;5.3%; standard craniotomy: 86.9%&#x2009;&#xb1;&#x2009;12.3%, p&#x2009;=&#x2009;0.0470); and better motor recovery. CONCLUSIONS: Functional preservation and survival outcomes of AC in GBM exhibited subtype-specific correlations with tumor locations. AC with intraoperative mapping effectively preserves neurological function in GBM patients. However, for tumors involving the precentral gyrus, the AC approach carries greater risks than benefits and should be considered with caution. TRIAL REGISTRATION: Strategic Intervention on Preserving Motor Function During Awake Craniotomy: NCT05143788. Strategic Intervention on Preserving Language Function During Awake Craniotomy: NCT05143775.

Adult↗

NR3C1 Modulates Wnt Signalling to Influence the Invasiveness and Immune Features of Nonfunctioning Invasive Pituitary Adenomas.

Pituitary adenomas (PAs) are common intracranial tumours, and invasiveness in nonfunctioning invasive pituitary adenomas (NIPAs) predicts poor prognosis. The molecular mechanisms driving this phenotype remain unclear. This study explored the role of nuclear receptor subfamily 3 group C member 1 (NR3C1) in NIPA invasiveness and its regulation of Wnt signalling. mRNA expression profiles of 32 PA samples were generated by RNA-seq, and proteomic data from 19 samples were obtained by mass spectrometry. Immune-related differentially expressed genes (DEGs) were retrieved from GeneCards. Weighted gene coexpression network analysis identified modules and hub genes linked to invasiveness, while machine learning methods (support vector machine, LASSO, random forest) prioritised key genes. Gene set enrichment analysis (GSEA) assessed pathways associated with candidate gene expression. NR3C1 expression and function were validated by immunohistochemistry, Western blotting and invasion assays. Integration of transcriptomic, proteomic and immune-related datasets yielded 11 overlapping genes, with NR3C1 emerging as the top candidate. NR3C1 was significantly upregulated in NIPAs and demonstrated good discriminatory power by ROC analysis. GSEA associated high NR3C1 expression with Wnt pathway activation. Functional experiments confirmed that NR3C1 overexpression enhances the invasive capacity of PA cells. NR3C1 promotes the invasive phenotype of NIPAs by activating Wnt signalling. These findings suggest NR3C1 as a potential biomarker and therapeutic target for invasive pituitary adenomas.

Humans↗

SHICEDO: single-cell Hi-C data enhancement with reduced over-smoothing.

MOTIVATION: Single-cell Hi-C (scHi-C) technologies have significantly advanced our understanding of the 3D genome organization. However, scHi-C data are often sparse and noisy, leading to substantial computational challenges in downstream analyses. RESULTS: In this study, we introduce SHICEDO, a novel deep-learning model specifically designed to enhance scHi-C contact matrices by imputing missing or sparsely captured chromatin contacts through a generative adversarial framework. SHICEDO leverages the unique structural characteristics of scHi-C matrices to derive customized features that enable effective data enhancement. Additionally, the model incorporates a channel-wise attention mechanism to mitigate the over-smoothing issue commonly associated with scHi-C enhancement methods. Through simulations and real-data applications, we demonstrate that SHICEDO outperforms the state-of-the-art methods, achieving superior quantitative and qualitative results. Moreover, SHICEDO enhances key structural features in scHi-C data, thus enabling more precise delineation of chromatin structures such as A/B compartments, TAD-like domains, and chromatin loops. AVAILABILITY AND IMPLEMENTATION: SHICEDO is publicly available at https://github.com/wmalab/SHICEDO.

Single-Cell Analysis↗

eccDNABase: A Comprehensive and High-Quality Database for Extrachromosomal Circular DNA.

Extrachromosomal circular DNA (eccDNA) refers to small, circular DNA molecules that originate from chromosomal sequences and are prevalent across nearly all eukaryotic organisms. In humans, eccDNAs are widely distributed in normal tissues, cancerous tissues, and body fluids, where they play important roles in tumorigenesis and are often associated with poor clinical outcomes. Given their biological and clinical significance, a well-integrated and high-quality database is essential for advancing eccDNA-related research. To address this need, we developed eccDNABase, a comprehensive and curated resource for browsing, searching, and analyzing eccDNAs across multiple species. The database systematically catalogs eccDNA-disease associations from diverse tissues and organisms. Currently, eccDNABase contains 1,875,452 eccDNA-disease associations, encompassing 8,398 ecDNA entries across nine species, 63 diseases, and healthy individuals. Each entry provides detailed information, including eccDNA ID, type, chromosomal localization, species, tissue or cell line source, disease name and Disease Ontology ID, overlap length and percentage with genes, oncogene overlap, detection method, and links to literature and source databases. Given its extensive and curated datasets, eccDNABase serves as a valuable resource for both basic and translational research, offering deeper insights into the role of eccDNA in health and disease. The database is publicly accessible at http://cgga.org.cn/eccDNABase/.

Humans↗

N-formylation of lysine in histone proteins as a secondary modification arising from oxidative DNA damage.

The posttranslational modification of histone and other chromatin proteins has a well recognized but poorly defined role in the physiology of gene expression. With implications for interfering with these epigenetic mechanisms, we now report the existence of a relatively abundant secondary modification of chromatin proteins, the N(6)-formylation of lysine that appears to be uniquely associated with histone and other nuclear proteins. Using both radiolabeling and sensitive bioanalytical methods, we demonstrate that the formyl moiety of 3'-formylphosphate residues arising from 5'-oxidation of deoxyribose in DNA, caused by the enediyne neocarzinostatin, for example, acylate the N(6)-amino groups of lysine side chains. A liquid chromatography (LC)-tandem mass spectrometry (MS) method was developed to quantify the resulting N(6)-formyl-lysine residues, which were observed to be present in unperturbed cells and all sources of histone proteins to the extent of 0.04-0.1% of all lysines in acid-soluble chromatin proteins including histones. Cells treated with neocarzinostatin showed a clear dose-response relationship for the formation of N(6)-formyl-lysine, with this nucleosome linker-selective DNA-cleaving agent causing selective N(6)-formylation of the linker histone H1. The N(6)-formyl-lysine residue appears to represent an endogenous histone secondary modification, one that bears chemical similarity to lysine N(6)-acetylation recognized as an important determinant of gene expression in mammalian cells. The N(6)-formyl modification of lysine may interfere with the signaling functions of lysine acetylation and methylation and thus contribute to the pathophysiology of oxidative and nitrosative stress.

Acetylation↗

HGF protects rat mesangial cells from high-glucose-mediated oxidative stress.

BACKGROUND: Oxidative stress has been considered to be a common pathogenetic factor of diabetic nephropathy. Recent observations suggested that hepatocyte growth factor (HGF) was an antioxidant growth factor; thus, its renoprotective effects in diabetic nephropathy might be related to antioxidant mechanism. The aim of the present study was to evaluate whether HGF could prevent rat mesangial cells (RMC) from high-glucose-mediated oxidative stress and explore its relevant mechanism. METHODS: RMC were cultured in 5.6 mM (NG) or 30 mM (HG) glucose in the absence or presence of HGF (20 ng/ml) and c-met inhibitor SU11274 (5 microM) for 24 h. RESULTS: c-met expression in HG was markedly increased. Enhanced oxidative stress was observed in HG as evidenced by elevated reactive oxygen species and malondialdehyde levels and decreased glutathione level, which was markedly attenuated by HGF. HGF also inhibited HG-induced p22(phox) and aldose reductase upregulation and prevented HG-reduced glutamate-cysteine ligase catalytic subunit (GCLC) expression through inhibiting USF binding to negative regulatory region of GCLC promoter. Reduced glucose-6-phosphate dehydrogenase activity and expression in RMC by HG was rescued by HGF. CONCLUSION: HGF could function as an antioxidant factor and protect against HG-mediated oxidative stress by enhancing ROS scavenging and suppressing ROS production.

Animals↗

Structure of the ligand-binding domain (LBD) of human androgen receptor in complex with a selective modulator LGD2226.

The androgen receptor (AR) is a ligand-inducible steroid hormone receptor that mediates androgen action, determining male sexual phenotypes and promoting spermatogenesis. As the androgens play a dominant role in male sexual development and function, steroidal androgen agonists have been used clinically for some years. However, there is a risk of potential side effects and most steroidal androgens cannot be dosed orally, which limits the use of these substances. 1,2-Dihydro-6-N,N-bis(2,2,2-trifluoroethyl)amino-4-trifluoromethyl-2-quinolinone (LGD2226) is a synthetic nonsteroidal ligand and a novel selective AR modulator. The crystal structure of the complex of LGD2226 with the androgen receptor ligand-binding domain (AR LBD) at 2.1 A was solved and compared with the structure of the AR LBD-R1881 complex. It is hoped that this will aid in further explaining the selectivity of LGD2226 observed in in vitro and in vivo assays and in developing more selective and effective therapeutic agents.

Binding Sites↗

Structural and functional analysis of natrin, a venom protein that targets various ion channels.

Cysteine-rich secretory proteins (CRISPs) are secreted single-chain proteins found in different sources. Natrin is a member of the CRISP family purified from the snake venom of Naja naja atra, which has been reported as a BKca channel blocker. In our study, crystals of natrin were obtained in two different crystal forms and the structure of one of them was solved at a resolution of 1.68A. Our electrophysiological experiments indicated that natrin can block the ion channel currents of the voltage-gated potassium channel Kv1.3. Docking analyses of the interaction between natrin and Kv1.3 revealed a novel interaction pattern different from the two previously reported K(+) channel inhibition models termed "functional dyad" and "basic ring". These findings offered new insights into the function of natrin and how the specific interactions between CRISPs and different ion channels can be achieved.

Amino Acid Sequence↗

Inhibition of STAT3 activity with AG490 decreases the invasion of human pancreatic cancer cells in vitro.

Signal transducer and activator of transcription 3 (STAT3) is a central cytoplasmic transcription factor. Abnormal activation of STAT3 plays a critical role in oncogenesis and has been found frequently in a wide variety of human tumors including pancreatic cancer. In this study, we elucidated the significance of the STAT3 signaling pathway on metastatic potentials of pancreatic cancer. We found that phosphorylated STAT3 (p-STAT3) protein levels were significantly higher in highly metastatic SW1990 cells compared to the poorly metastatic CaPan-2 cells, which expressed weak levels of this protein. Furthermore, a Janus kinase (JAK) specific inhibitor, AG490, significantly inhibited the expression of p-STAT3, and subsequently reduced invasion and adhesion potential of SW1990 cells compared to the cells treated with vehicle only. Finally, inhibition of the STAT3 signaling pathway by AG490 also led to a decrease in matrix metalloproteinase-2 and vascular endothelial growth factor expression at the protein and mRNA levels. These results demonstrate that activation of the STAT3 signaling pathway plays an important role in the progression of pancreatic cancer and that inhibition of this pathway may be useful for an anti-invasive therapeutic option in pancreatic cancer.

Blotting, Western↗

Prevalence of the initiator over the TATA box in human and yeast genes and identification of DNA motifs enriched in human TATA-less core promoters.

The core promoter of eukaryotic genes is the minimal DNA region that recruits the basal transcription machinery to direct efficient and accurate transcription initiation. The fraction of human and yeast genes that contain specific core promoter elements such as the TATA box and the initiator (INR) remains unclear and core promoter motifs specific for TATA-less genes remain to be identified. Here, we present genome-scale computational analyses indicating that approximately 76% of human core promoters lack TATA-like elements, have a high GC content, and are enriched in Sp1-binding sites. We further identify two motifs - M3 (SCGGAAGY) and M22 (TGCGCANK) - that occur preferentially in human TATA-less core promoters. About 24% of human genes have a TATA-like element and their promoters are generally AT-rich; however, only approximately 10% of these TATA-containing promoters have the canonical TATA box (TATAWAWR). In contrast, approximately 46% of human core promoters contain the consensus INR (YYANWYY) and approximately 30% are INR-containing TATA-less genes. Significantly, approximately 46% of human promoters lack both TATA-like and consensus INR elements. Surprisingly, mammalian-type INR sequences are present - and tend to cluster - in the transcription start site (TSS) region of approximately 40% of yeast core promoters and the frequency of specific core promoter types appears to be conserved in yeast and human genomes. Gene Ontology analyses reveal that TATA-less genes in humans, as in yeast, are frequently involved in basic "housekeeping" processes, while TATA-containing genes are more often highly regulated, such as by biotic or stress stimuli. These results reveal unexpected similarities in the occurrence of specific core promoter types and in their associated biological processes in yeast and humans and point to novel vertebrate-specific DNA motifs that might play a selective role in TATA-independent transcription.

Base Composition↗

[Function magnetic resonance imaging and diffusion tensor tractography in patients with brain gliomas involving motor areas: clinical application and outcome].

OBJECTIVE: To explore the role of preoperative blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) and diffusion tensor tractography (DTT) to identify the relationship between motor cortical area, pyramidal tracts with brain gliomas in neurosurgical treatment of intraoperative electrical stimulation for gliomas involving motor areas at 3T. METHODS: Twenty-eight patients with brain gliomas involving motor areas were included. They underwent MRI examination, which included conventional T1WI, T2WI, BOLD-fMRI of bilateral hands movement paradigm and diffusion tensor imaging (DTI). The data of BOLD-fMRI and DTI were transferred to the workstation (Leonardo syngo 2003A, Siemens) and analyzed. Activation mapping of hands movement, fractional Anisotropy (FA) Color and three dimensional pyramidal tracts were produced. The relationship between motor cortical area, pyramidal tracts and brain gliomas was demonstrated, which was used to optimize the pre-surgical planning. With guidance of the result of BOLD-fMRI and DTT, all patients received microsurgery under anaesthesia retaining consciousness using intraoperative motor functional brain mapping with the method of direct electrical stimulations. The brain lesions were removed as far as possible in the case of eloquent areas and sub-cortical important white matters preservation. The preoperative and postoperative KPS of all patients were operated to evaluate the state of patients. RESULTS: BOLD-fMRI, DTI were performed successfully in 28 patients. The relationship between the primary motor cortex, premotor area, supplementary motor area, pyramidal tracts and brain gliomas localized by preoperative fMRI and DTI. Under anaesthesia retaining consciousness, the primary motor area was monitored by the method of direct electrical stimulations with the guidance of preoperative BOLD-fMRI. There was good correlation between preoperative fMRI and intraoperative cortical stimulation. Furthermore, the preoperative mappings and DTT could make up for the un-monitored motor areas and pyramidal tracts during operative cortical stimulation. Comparing the preoperative KPS, the postoperative KPS was advanced. CONCLUSIONS: BOLD-fMRI and DTT could non-invasively localize the relationship between brain motor cortex, pyramidal tracts and brain gliomas in vivo to optimize the surgical planning, guide the microsurgery under anaesthesia retaining consciousness using intraoperative motor functional brain mapping with the method of direct electrical stimulations and remove brain tumors as far as possible in the case of eloquent areas and sub-cortical important white matters preservation.

Adult↗

The comparative study of magnetic resonance angiography diagnosis and pathology of blunt vertebral artery injury.

STUDY DESIGN: Observational and comparative study of the vertebral artery injury detected by 2-dimensional (2-D) time-of-flight magnetic resonance angiography (MRA) for admitting patients. Construct a strike-induced flexion injury model of cervical spine with blunt vertebral artery injury in dogs. OBJECTIVES: To evaluate the value of MRA for diagnosing vertebral artery injury in cervical spinal trauma patients, and conduct a comparative study of MRA image and pathology of blunt vertebral artery injury in an animal experiment. SUMMARY OF BACKGROUND DATA: The 2-D time-of-flight MRA is the most important method for diagnosing vertebral artery injury. However, there is still controversy over MRA's accuracy in detecting vertebral artery injury of varying degrees. In addition, to our knowledge, no animal studies regarding this subject have been found in the literature so far. METHODS: In a clinical study, 319 patients with close cervical spinal trauma underwent 2-D time-of-flight MRA prospective examination. The 2-D time-of-flight MRA detected vertebral artery injury in 52 of the 319 subjects. Of the 52 patients, 51 had unilateral vertebral artery injuries, including 22 injuries on the left vertebral artery and 29 on the right vertebral artery. One case involved bilateral vertebral artery injury. In an animal experiment, the strike-induced flexion injury model of cervical spine was constructed based on an animal experiment with 26 adult dogs. A radiograph was taken immediately after injury, and 2-D time-of-flight MRA was taken in 24-36 hours. The vertebral artery sample was then harvested for pathologic examination. RESULTS: In the animal experiment, cervical facet dislocation occurred in 14 of the 26 dogs. Of the 26 dogs, 7 had unilateral vertebral artery injury as detected by MRA. There were 2 dogs that had incomplete blood flow imaging on one side of the vertebral artery, which MRA diagnosed as suspect positive. There were no vertebral artery injuries in the other 17 dogs. The vertebral artery sample of all 26 dogs underwent the pathologic study. Of the 7 dogs with positive MRA, 4 had disruption of the intima and media, and 3 had disruption of the intima. Of the 2 dogs with suspicious positive MRA diagnosis, 1 had no intima injury, while the other had intima disruption and late mural thrombus. There was no intima injury in the 17 dogs with negative MRA findings. CONCLUSIONS: The 2-D time-of-flight MRA is an effective diagnostic method for blunt vertebral artery injury. It may have difficulties differentiating spasm, small disruption of the intima from others under certain conditions.

Adolescent↗

Formation of microchimerism in rat small bowel transplantation by splenocyte infusion.

AIM: To investigate the effect of donor splenocyte infusion combined with cyclosporine A (CsA) on rejection of rat small bowel transplantation (SBT). METHODS: Male Sprague-Dawley (SD) rats and female Wistar rats weighing 230-270 g were used as donors and recipients respectively in the study. Heterotopic small bowel transplantation was performed. The rats were divided into three groups: group one receiving allotransplantation (SD rarr Wistar), group two receiving allotransplantation (SD rarr Wistar) + donor splenocyte infusion, group three receiving allotransplantation (SD rarr Wistar) + donor splenocyte infusion + CsA followed by CsA 10 mg/kg per day after transplantation, in which recipient Wistar rats were injected with 2 x 10(8) SD splenocytes 28 d before transplantation, and treated with CsA after transplantation. Finally, the specific DNA fragment of donor Y chromosome was detected in recipient peripheral blood and skin by PCR. The survival time after small bowel transplantation was observed. Gross and histopathological examinations were performed. RESULTS: The survival time after small bowel trans-plantation was 7.1 +/- 1.2 d in group 1, 18.4 +/- 3.6 d in group 2 and 31.5 +/- 3.1 d in group 3. The survival time was significant longer (P < 0.01) in group 3 than in groups 1 and 2. The gross and histopathological examination showed that the rejection degree in group 3 was lower than that in groups 1 and 2. CONCLUSION: Donor splenocyte infusion combined with CsA decreases remarkably the rejection and prolongs the survival time after rat small bowel transplantation.

Animals↗