BACKGROUND: The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation. METHODS: We conducted a kidney xenotransplantation in a brain-dead human recipient using a porcine kidney with five gene edits (5GE) on March 25, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22 days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation. RESULTS: The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24 h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient. CONCLUSIONS 5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.
Transplantation, Heterologous/methods* ; Kidney Transplantation/methods* ; Heterografts/pathology* ; Immunoglobulins, Intravenous/administration & dosage* ; Graft Survival/immunology* ; Humans ; Animals ; Sus scrofa ; Graft Rejection/prevention & control* ; Kidney/pathology* ; Gene Editing ; Species Specificity ; Immunosuppression Therapy/methods* ; Plasma Exchange ; Brain Death ; Biopsy ; Male ; Aged

Neoadjuvant therapy has become the standard treatment for locally advanced resectable esophageal cancer, significantly improving long-term survival compared to surgery alone. Neoadjuvant therapy has evolved to include various strategies, such as concurrent chemoradiotherapy, chemotherapy, immunotherapy, or targeted combination therapy. This enriches clinical treatment options and provides a more personalized and scientific treatment approach for patients. This article aims to comprehensively summarize current academic research hot topics, review the rationale and evaluation measures of neoadjuvant therapy, discuss challenges in restaging methods after neoadjuvant therapy, and identify the advantages and disadvantages of various neoadjuvant therapeutic strategies.

Rheumatoid arthritis(RA)is a common autoimmune disease with synovitis as core pathological manifestation,with strong injury and high disability rate,which can not be cured completely at present.Recent studies have shown that tumor necro-sis factor receptor-related factor 6(TRAF6),as a ubiquitin ligase E3,plays a key role in autoimmune diseases and inflammatory diseases through a variety of pathways.This article reviews structure,function,ubiquitin regulation of TRAF6 and research progress of pathogenesis of RA.

OBJECTIVE To analyze the differences in chemical composition of mussels from Shengsi,Zhoushan in different har-vest months,and to compare the differences in the composition of mussels from different origins,so as to provide ideas for the compre-hensive utilization of its resources.METHODS Ultra-high performance liquid chromatography-triple quadrupole mass spectrometry(UHPLC-QqQ-MS)and spectrophotometry were used to analyze and evaluate the contents of nucleosides,amino acids,water-soluble proteins,total sugars and polysaccharides in mussels from Shengsi,Zhoushan in 12 months of the year and from 5 different origins;principal component analysis(PCA),partial least squares discriminant method(PLS-DA)and TOPSIS method were used to compre-hensively evaluate mussels.RESULTS A total of 16 amino acids and 11 nucleosides were detected in mussels.The average content of total amino acids in Shengsi mussels throughout the year was 4 851.74 μg·g-1,the average content of total nucleosides was 921.40 μg·g-1,and the average contents of water-soluble protein,polysaccharides,and total sugars were 51.32 mg·g-1,74.39 μg·g-1,and 417.22 mg·g-1,respectively.The nucleosides of Shengsi mussels were the highest in March and April,the ami-no acids and water-soluble proteins were the highest in April and May,and the polysaccharides and total sugars were the highest in Oc-tober and November.The PCA and PLS-DA results of the chemical components of different resources showed that there were great differences in Shengsi mussel samples harvested in different seasons.The entropy weight TOPSIS analysis showed that the comprehen-sive scores of Shengsi mussels in March and April(S7 and S8)were better than those in other areas,and the comprehensive score of Shengsi mussels in April(S8)was the highest,which was determined to be the best harvesting month.CONCLUSION The comparison results of multi-type resource chemistry show that there are great differences in the chemical compo-sition of Shengsi mussels in different harvesting seasons;the quality of Shengsi mussels is better than that of other areas;April is the best harvesting season,providing a reference for the quality evaluation and comprehensive development and utilization of mussels.

Objective:To investigate the value of a deep learning radiomics (DLR) nomogram model based on intra-tumoral and peri-tumoral MRI features for differentiating IgG4-related ophthalmic disease (IgG4-ROD) from orbital mucosa-associated lymphoid tissue (MALT) lymphoma.Methods:This was a case-control study. The clinical and imaging data of 233 patients pathologically confirmed with either IgG4-ROD or orbital MALT lymphoma were retrospective collected between January 2020 and December 2024 from the Second Hospital of Jilin University (Center 1) and Beijing Tongren Hospital, Capital Medical University (Center 2). Patients from Center 1 ( n=158) were used as the training cohort, while those from Center 2 ( n=75) served as the validation cohort. Among the cases, 102 were IgG4-ROD (70 in training, 32 in validation) and 131 were orbital MALT lymphoma (88 in training, 43 in validation). Univariate and multivariate logistic regression analyses were used to identify independent clinical imaging predictors and build a clinical imaging model. Based on T 1WI, T 2WI, and diffusion weighted images, intra-tumoral regions were manually delineated, a 2 mm peri-tumoral margin was automatically generated, and both regions were combined as a single region of interest for radiomics feature extraction. Deep learning features were extracted using a ResNet-50 backbone, and after feature selection and dimensionality reduction, a DLR model was constructed. The clinical imaging features and DLR features were integrated to build a combined nomogram model. Model performance in differentiating IgG4-ROD from orbital MALT lymphoma was assessed using receiver operating characteristic curves, calibration curves, and decision curve analysis. The area under the curve (AUC) were compared using the DeLong test. Results:Bilateral orbital involvement ( OR=1.983, 95% CI 1.166-2.843, P=0.046) and extraocular muscle involvement ( OR=1.246, 95% CI 1.079-1.764, P=0.015) were identified as independent predictors for distinguishing IgG4-ROD from orbital MALT lymphoma and were used to construct the clinical model. Fourteen features (9 radiomics and 5 deep learning features) were selected for the DLR model, and a nomogram was developed. In the training set, the AUCs for the clinical model, DLR model, and nomogram were 0.762 (95% CI 0.712-0.812), 0.865 (95% CI 0.822-0.908), and 0.943 (95% CI 0.909-0.953), respectively. In the validation set, the AUCs were 0.733 (95% CI 0.675-0.791), 0.823 (95% CI 0.762-0.884), and 0.924 (95% CI 0.902-0.958), respectively. The nomogram showed significantly higher AUCs than those of the clinical and DLR models alone (training set: Z=3.92, 2.87, P0.001, P=0.004; validation set: Z=3.25, 2.46, P=0.001, 0.014). Calibration curves indicated good agreement between predicted and actual IgG4-ROD incidence, and decision curve analysis demonstrated the highest net benefit for the nomogram. Conclusion:A nomogram that incorporates both intra-tumoral and peri-tumoral DLR features and clinical imaging characteristics demonstrates excellent performance in distinguishing IgG4-ROD from orbital MALT lymphoma.

OBJECTIVE To analyze the differences in chemical composition of mussels from Shengsi,Zhoushan in different har-vest months,and to compare the differences in the composition of mussels from different origins,so as to provide ideas for the compre-hensive utilization of its resources.METHODS Ultra-high performance liquid chromatography-triple quadrupole mass spectrometry(UHPLC-QqQ-MS)and spectrophotometry were used to analyze and evaluate the contents of nucleosides,amino acids,water-soluble proteins,total sugars and polysaccharides in mussels from Shengsi,Zhoushan in 12 months of the year and from 5 different origins;principal component analysis(PCA),partial least squares discriminant method(PLS-DA)and TOPSIS method were used to compre-hensively evaluate mussels.RESULTS A total of 16 amino acids and 11 nucleosides were detected in mussels.The average content of total amino acids in Shengsi mussels throughout the year was 4 851.74 μg·g-1,the average content of total nucleosides was 921.40 μg·g-1,and the average contents of water-soluble protein,polysaccharides,and total sugars were 51.32 mg·g-1,74.39 μg·g-1,and 417.22 mg·g-1,respectively.The nucleosides of Shengsi mussels were the highest in March and April,the ami-no acids and water-soluble proteins were the highest in April and May,and the polysaccharides and total sugars were the highest in Oc-tober and November.The PCA and PLS-DA results of the chemical components of different resources showed that there were great differences in Shengsi mussel samples harvested in different seasons.The entropy weight TOPSIS analysis showed that the comprehen-sive scores of Shengsi mussels in March and April(S7 and S8)were better than those in other areas,and the comprehensive score of Shengsi mussels in April(S8)was the highest,which was determined to be the best harvesting month.CONCLUSION The comparison results of multi-type resource chemistry show that there are great differences in the chemical compo-sition of Shengsi mussels in different harvesting seasons;the quality of Shengsi mussels is better than that of other areas;April is the best harvesting season,providing a reference for the quality evaluation and comprehensive development and utilization of mussels.

Objective:To investigate the value of a deep learning radiomics (DLR) nomogram model based on intra-tumoral and peri-tumoral MRI features for differentiating IgG4-related ophthalmic disease (IgG4-ROD) from orbital mucosa-associated lymphoid tissue (MALT) lymphoma.Methods:This was a case-control study. The clinical and imaging data of 233 patients pathologically confirmed with either IgG4-ROD or orbital MALT lymphoma were retrospective collected between January 2020 and December 2024 from the Second Hospital of Jilin University (Center 1) and Beijing Tongren Hospital, Capital Medical University (Center 2). Patients from Center 1 ( n=158) were used as the training cohort, while those from Center 2 ( n=75) served as the validation cohort. Among the cases, 102 were IgG4-ROD (70 in training, 32 in validation) and 131 were orbital MALT lymphoma (88 in training, 43 in validation). Univariate and multivariate logistic regression analyses were used to identify independent clinical imaging predictors and build a clinical imaging model. Based on T 1WI, T 2WI, and diffusion weighted images, intra-tumoral regions were manually delineated, a 2 mm peri-tumoral margin was automatically generated, and both regions were combined as a single region of interest for radiomics feature extraction. Deep learning features were extracted using a ResNet-50 backbone, and after feature selection and dimensionality reduction, a DLR model was constructed. The clinical imaging features and DLR features were integrated to build a combined nomogram model. Model performance in differentiating IgG4-ROD from orbital MALT lymphoma was assessed using receiver operating characteristic curves, calibration curves, and decision curve analysis. The area under the curve (AUC) were compared using the DeLong test. Results:Bilateral orbital involvement ( OR=1.983, 95% CI 1.166-2.843, P=0.046) and extraocular muscle involvement ( OR=1.246, 95% CI 1.079-1.764, P=0.015) were identified as independent predictors for distinguishing IgG4-ROD from orbital MALT lymphoma and were used to construct the clinical model. Fourteen features (9 radiomics and 5 deep learning features) were selected for the DLR model, and a nomogram was developed. In the training set, the AUCs for the clinical model, DLR model, and nomogram were 0.762 (95% CI 0.712-0.812), 0.865 (95% CI 0.822-0.908), and 0.943 (95% CI 0.909-0.953), respectively. In the validation set, the AUCs were 0.733 (95% CI 0.675-0.791), 0.823 (95% CI 0.762-0.884), and 0.924 (95% CI 0.902-0.958), respectively. The nomogram showed significantly higher AUCs than those of the clinical and DLR models alone (training set: Z=3.92, 2.87, P0.001, P=0.004; validation set: Z=3.25, 2.46, P=0.001, 0.014). Calibration curves indicated good agreement between predicted and actual IgG4-ROD incidence, and decision curve analysis demonstrated the highest net benefit for the nomogram. Conclusion:A nomogram that incorporates both intra-tumoral and peri-tumoral DLR features and clinical imaging characteristics demonstrates excellent performance in distinguishing IgG4-ROD from orbital MALT lymphoma.

Rheumatoid arthritis(RA)is a common autoimmune disease with synovitis as core pathological manifestation,with strong injury and high disability rate,which can not be cured completely at present.Recent studies have shown that tumor necro-sis factor receptor-related factor 6(TRAF6),as a ubiquitin ligase E3,plays a key role in autoimmune diseases and inflammatory diseases through a variety of pathways.This article reviews structure,function,ubiquitin regulation of TRAF6 and research progress of pathogenesis of RA.

BACKGROUND:Halo gravity traction is a pre-operative traction method recognized by many scholars,but most of them rely on clinical observation and lack finite element analysis. OBJECTIVE:To explore the best traction force of Halo gravity traction on Lenke 3 scoliosis by finite element method and to provide a theoretical basis for clinics from a biomechanical point of view. METHODS:The CT images scanned by patients with scoliosis were processed by reverse modeling,and a finite element model was established.The validity of the model was verified by taking normal segments(T1-T4 vertebral bodies).Five groups of different stress conditions were set on the lumbar-thoracic scoliosis model to simulate the correction of patients under different traction forces.In all five groups,the lower surface of L5 was completely restrained,and different traction forces were applied to the upper surface of T1 along the positive direction of the Z axis(the opposite direction of gravity),which were 50,100,150,200,and 250 N,respectively.The displacement of the scoliosis spine,Cobb angle change of the main bending,elongation of the spine,and Von Mises stress were compared under different traction forces. RESULTS AND CONCLUSION:(1)When the Halo gravity traction force was 150 N to 200 N,the reduction of the Cobb angle of the main bending was 69.4%to 88.9%of the maximum reduction;the elongation of the Z axis was 69.4%to 85.9%,and the stress was 63.6%to 82.9%of the maximum stress.(2)When the traction force was greater than 200 N,the reduction of the Cobb angle and the elongation of the Z axis did not change obviously,but the stress value increased sharply.At this time,the distance from the centroids of T6,T7,and T8 to the vertical line of L5 was the most obvious.(3)When the Halo gravity traction force was 150 N to 200 N,the correction effect on this type of patient was the best—the reduction of Cobb angle and the elongation of the Z axis were better without the sharp increase in stress.(4)It has certain theoretical support for clinical correction and can ensure the safety of patients when scoliosis is corrected to a large extent.

Objective To observe the effects of electroacupuncture on intestinal flora and serum inflammatory factors in rabbit model with rheumatoid arthritis(RA);To explore the mechanism of its therapeutic effect on RA.Methods RA model rabbits were established by ovalbumin induction combined with Freund's complete adjuvant,and the rabbits after successful modeling were randomly divided into model group,probiotic group and electroacupuncture group,with 6 rabbits in each group.Another 6 rabbits were set as the normal group.The electroacupuncture group received electroacupuncture at the bilateral"Zusanli"and"Dubi"for 30 minutes,the probiotic group was given probiotic capsules solution(14.5 mg/kg)by gavage,once a day,for two consecutive weeks.The knee joint circumference and pain threshold of rabbits were measured,histopathological morphological changes of colonic tissue and synovial tissue ws observed by HE staining,16S rDNA sequencing was used to analyze structural changes of intestinal flora,the contents of TNF-α,IL-1β and IL-6 in serum were detected by ELISA.Results Compared with the normal group,the circumference of knee joint of rabbits in the model group increased significantly,the pain threshold was significantly decreased(P<0.01);the colonic mucosal damage was serious,the goblet cells were missing,a large number of inflammatory cells were infiltrate;the joint capsule synovial surface was rough,the synovial cell layer was hyperplasia and thickening,the synovial tissue inflammatory cell infiltration was obvious;the number and evenness of gut microbiota species decreased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes decreased(P<0.05,P<0.01),the relative abundance of Desulfobacteria increased(P<0.01),while the relative abundance of Campylobacter,Lawsonella,and Pseudomonas increased(P<0.01),while the relative abundance of Heshanomonas and Herbaspirillum decreased(P<0.01);the contents of serum TNF-α,IL-1β and IL-6 increased(P<0.01).Compared with the model group,the knee joint circumference of the probiotic group and the electroacupuncture group decreased,the pain threshold increased(P<0.01,P<0.05);the degree of intestinal mucosal damage was reduced,the goblet cells were basically arranged neatly,the inflammatory cell infiltration was reduced;synovial cells proliferation and thickening decreased,with a small amount of inflammatory cell infiltration;the number and evenness of gut microbiota species increased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes increased(P<0.05,P<0.01),the relative abundance of Desulfobacteria decreased(P<0.01),while the relative abundance of Campylobacter,Lawsonella and Pseudomonas decreased(P<0.01),the relative abundance of Heshanomonas and Herbaspirillum increased(P<0.05,P<0.01);the contents of serum TNF-α,IL-1β and IL-6 significantly decreased(P<0.01).Conclusion Electroacupuncture can significantly improve the symptoms of RA rabbits and reduce the inflammatory reaction in synovial tissue of joint,and the mechanism may be related to the regulation of intestinal flora structure.