1.Plasma exchange and intravenous immunoglobulin prolonged the survival of a porcine kidney xenograft in a sensitized, brain-dead human recipient.
Shuaijun MA ; Ruochen QI ; Shichao HAN ; Zhengxuan LI ; Xiaoyan ZHANG ; Guohui WANG ; Kepu LIU ; Tong XU ; Yang ZHANG ; Donghui HAN ; Jingliang ZHANG ; Di WEI ; Xiaozheng FAN ; Dengke PAN ; Yanyan JIA ; Jing LI ; Zhe WANG ; Xuan ZHANG ; Zhaoxu YANG ; Kaishan TAO ; Xiaojian YANG ; Kefeng DOU ; Weijun QIN
Chinese Medical Journal 2025;138(18):2293-2307
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
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Immunosuppression Therapy/methods*
;
Plasma Exchange
;
Brain Death
;
Biopsy
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Male
;
Aged
2.Guideline-driven clinical decision support for colonoscopy patients using the hierarchical multi-label deep learning method.
Junling WU ; Jun CHEN ; Hanwen ZHANG ; Zhe LUAN ; Yiming ZHAO ; Mengxuan SUN ; Shufang WANG ; Congyong LI ; Zhizhuang ZHAO ; Wei ZHANG ; Yi CHEN ; Jiaqi ZHANG ; Yansheng LI ; Kejia LIU ; Jinghao NIU ; Gang SUN
Chinese Medical Journal 2025;138(20):2631-2639
BACKGROUND:
Over 20 million colonoscopies are performed in China annually. An automatic clinical decision support system (CDSS) with accurate semantic recognition of colonoscopy reports and guideline-based is helpful to relieve the increasing medical burden and standardize the healthcare. In this study, the CDSS was built under a hierarchical-label interpretable classification framework, trained by a state-of-the-art transformer-based model, and validated in a multi-center style.
METHODS:
We conducted stratified sampling on a previously established dataset containing 302,965 electronic colonoscopy reports with pathology, identified 2041 patients' records representative of overall features, and randomly divided into the training and testing sets (7:3). A total of five main labels and 22 sublabels were applied to annotate each record on a network platform, and the data were trained respectively by three pre-training models on Chinese corpus website, including bidirectional encoder representations from transformers (BERT)-base-Chinese (BC), the BERT-wwm-ext-Chinese (BWEC), and ernie-3.0-base-zh (E3BZ). The performance of trained models was subsequently compared with a randomly initialized model, and the preferred model was selected. Model fine-tuning was applied to further enhance the capacity. The system was validated in five other hospitals with 3177 consecutive colonoscopy cases.
RESULTS:
The E3BZ pre-trained model exhibited the best performance, with a 90.18% accuracy and a 69.14% Macro-F1 score overall. The model achieved 100% accuracy in identifying cancer cases and 99.16% for normal cases. In external validation, the model exhibited favorable consistency and good performance among five hospitals.
CONCLUSIONS
The novel CDSS possesses high-level semantic recognition of colonoscopy reports, provides appropriate recommendations, and holds the potential to be a powerful tool for physicians and patients. The hierarchical multi-label strategy and pre-training method should be amendable to manage more medical text in the future.
Humans
;
Colonoscopy/methods*
;
Deep Learning
;
Decision Support Systems, Clinical
;
Female
;
Male
3.Relationship of immune response with intestinal flora and metabolic reprogramming in patients with non-small cell lung cancer.
Rui GUO ; Zhe HE ; Fan LIU ; Hui-Zhen PENG ; Li-Wei XING
Acta Physiologica Sinica 2025;77(2):289-299
Numerous research conducted in recent years has revealed that gut microbial dysbiosis, such as modifications in composition and activity, might influence lung tissue homeostasis through specific pathways, thereby promoting susceptibility to lung diseases. The development and progression of lung cancer, as well as the effectiveness of immunotherapy are closely associated with gut flora and metabolites, which influence immunological and inflammatory responses. During abnormal proliferation, non-small cell lung cancer cells acquire more substances and energy by altering their own metabolic pathways. Glucose and amino acid metabolism reprogramming provide tumor cells with abundant ATP, carbon, and nitrogen sources, respectively, providing optimal conditions for tumor cell proliferation, invasion, and immune escape. This article reviews the relationship of immune response with gut flora and metabolic reprogramming in non-small cell lung cancer, and discusses the potential mechanisms by which gut flora and metabolic reprogramming affect the occurrence, development, and immunotherapy of non-small cell lung cancer, in order to provide new ideas for precision treatment of lung cancer patients.
Humans
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Gastrointestinal Microbiome/immunology*
;
Carcinoma, Non-Small-Cell Lung/therapy*
;
Lung Neoplasms/therapy*
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Immunotherapy
;
Metabolic Reprogramming
4.Visual analysis of dynamics and hotspots of biomechanics research on diabetic foot based on WoSCC.
Zhe WANG ; Wei-Dong LIU ; Jun LU ; Hong-Mou ZHAO ; Xue-Fei CAO ; Yun-Long ZHANG ; Xin CHANG ; Liang LIU
China Journal of Orthopaedics and Traumatology 2025;38(9):902-909
OBJECTIVE:
To explore the current research status and hotspots in the field of biomechanics of diabetic foot by bibliometric analysis methods.
METHODS:
Literatures related to biomechanics of diabetic foot published in the Web of Scienc Core Collection (WoSCC) from 1981 to 2024 were searched. CiteSpace software and R language bibliometrics plugin were used to conduct a visual analysis of annual publication volume of the literature, including publication volume of each country and region, the publication situation of authors and institutions, the citation situation of individual literature, and the co-occurrence network of keywords.
RESULTS:
Totally 996 literatures were included, and the number of published papers increased steadily. The United States (261 papers) and China (89 papers) were the top two countries in terms of the number of published papers. The mediating centrality of the United States was 0.94, and that of China was 0.01. Scholars such as Cavanagh and institutions like the Cleveland Clinic were at the core of research in this field. High-frequency keywords include plantar pressure (plantar pressure), diabetic foot (diabetic foot), ulceration (ulcer), etc. The research focuses on plantar pressure, ulcer formation and prevention, etc.
CONCLUSION
Biomechanical research on diabetic foot mainly focuses on the pressure distribution on the sole of the foot, callus formation, mechanical analysis of soft tissues on the sole of the foot, and the study of plantar decompression caused by Achilles tendon elongation. The research trend has gradually shifted from focusing on joint range of motion to gait and the design of braces and assistive devices, and has begun to pay attention to muscle strength, gait imbalance and proprioception abnormalities.
Humans
;
Diabetic Foot/physiopathology*
;
Biomechanical Phenomena
;
Bibliometrics
5.Psychological stress-activated NR3C1/NUPR1 axis promotes ovarian tumor metastasis.
Bin LIU ; Wen-Zhe DENG ; Wen-Hua HU ; Rong-Xi LU ; Qing-Yu ZHANG ; Chen-Feng GAO ; Xiao-Jie HUANG ; Wei-Guo LIAO ; Jin GAO ; Yang LIU ; Hiroshi KURIHARA ; Yi-Fang LI ; Xu-Hui ZHANG ; Yan-Ping WU ; Lei LIANG ; Rong-Rong HE
Acta Pharmaceutica Sinica B 2025;15(6):3149-3162
Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.
6.Spatiotemporal Mapping of the Oxytocin Receptor at Single-Cell Resolution in the Postnatally Developing Mouse Brain.
Hao LI ; Ying LI ; Ting WANG ; Shen LI ; Heli LIU ; Shuyi NING ; Wei SHEN ; Zhe ZHAO ; Haitao WU
Neuroscience Bulletin 2025;41(2):224-242
The oxytocin receptor (OXTR) has garnered increasing attention for its role in regulating both mature behaviors and brain development. It has been established that OXTR mediates a range of effects that are region-specific or period-specific. However, the current studies of OXTR expression patterns in mice only provide limited help due to limitations in resolution. Therefore, our objective was to generate a comprehensive, high-resolution spatiotemporal expression map of Oxtr mRNA across the entire developing mouse brain. We applied RNAscope in situ hybridization to investigate the spatiotemporal expression pattern of Oxtr in the brains of male mice at six distinct postnatal developmental stages (P7, P14, P21, P28, P42, P56). We provide detailed descriptions of Oxtr expression patterns in key brain regions, including the cortex, basal forebrain, hippocampus, and amygdaloid complex, with a focus on the precise localization of Oxtr+ cells and the variance of expression between different neurons. Furthermore, we identified some neuronal populations with high Oxtr expression levels that have been little studied, including glutamatergic neurons in the ventral dentate gyrus, Vgat+Oxtr+ cells in the basal forebrain, and GABAergic neurons in layers 4/5 of the cortex. Our study provides a novel perspective for understanding the distribution of Oxtr and encourages further investigations into its functions.
Animals
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Receptors, Oxytocin/metabolism*
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Male
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Brain/growth & development*
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Mice
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Mice, Inbred C57BL
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Neurons/metabolism*
;
Single-Cell Analysis
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Gene Expression Regulation, Developmental
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RNA, Messenger/metabolism*
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Animals, Newborn
7.Quantitative research on tongue diagnosis in traditional Chinese medicine for obstructive coronary artery disease: a computational analysis based on multimodal feature fusion
Yanyun ZHANG ; Dongsheng WEI ; Yue ZHANG ; Yanshu LIU ; Zhe ZHANG
Digital Chinese Medicine 2025;8(4):443-454
Objective:
To investigate morphological differences between obstructive and non-obstructive coronary artery disease (CAD) patients using computer-aided image analysis, and identify color and texture features for traditional Chinese medicine (TCM) syndrome differentiation.
Methods:
This prospective study enrolled patients undergoing coronary computed tomography angiography (CTA) at the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine between May 1, 2024 and August 7, 2025. Based on CTA results, patients were categorized into obstructive CAD and non-obstructive CAD groups. Standardized tongue images were acquired using a dedicated mobile application (Traditional Chinese Medicine Tongue Image-Assisted Diagnosis System) and analyzed for the overall tongue surface and three macroscopic features (tooth marks, fissures, and red dots) from which high-dimensional color and texture parameters were extracted. Multi-scale texture features were derived using spatial-domain Laplacian pyramid and frequency-domain wavelet transform methods. Dimensionality reduction and feature selection were performed using principal component analysis (PCA) and random forest with 5-fold cross-validation. Feature stability was assessed using Hodges-Lehmann estimator and Cliff’s δ. A multi-view XGBoost model was developed to differentiate the two groups and evaluated on a temporally independent validation set using accuracy and the area under the receiver operating characteristic curve (AUC). SHapley Additive exPlanations (SHAP) analysis was applied to interpret model decisions.
Results:
This study analyzed 373 CAD patients, including 167 with obstructive CAD and 206 with non-obstructive CAD according to CTA results. The whole cohort was divided into training set (n = 316, obstructive : non-obstructive = 142 : 174 ) and validation set (n = 57, obstructive : non-obstructive = 25 : 32), with balanced baseline characteristics (P > 0.05). Macroscopic tongue analysis revealed that patients with obstructive CAD had fewer tooth marks [odds ratio (OR) = 0.43, P < 0.05] and red dots (OR = 0.46, P < 0.05). High-dimensional color analysis identified pronounced intergroup differences, most notably a reduction in hue values in the hue-saturation-intensity (HSI) color space among obstructive CAD patients (Cliff’s δ = – 0.31, P = 2.72 × 10–6; Hodges-Lehmann estimator: – 0.31). PCA results suggested that tongue surface features explained the highest proportion of variance (48.2%). Random forest screening identified 77 stable features across all tongue regions, with wavelet-transformed texture features demonstrating the highest importance. The multi-view XGBoost fusion model achieved an accuracy of 75% and an AUC of 0.779 in the independent validation set. SHAP analysis identified the wavelet-based feature—left-handed lower-level gray-level size zone matrix zone variance (LHL_glszm_ZoneVariance) as the top predictor, accounting for 40.6% of the model's decision variance, and indicated that 85.3% of the predictive power came from wavelet-based texture features.
Conclusion
This study has provided objective evidence for the TCM concept that “the tongue reflects the heart” by identifying distinct morphological and colorimetric tongue patterns in patients with obstructive CAD through artificial intelligence (AI)-driven image analysis, and the promising performance of the computational model suggests its potential as a non-invasive adjunctive tool for CAD assessment.
8.Clinical trial of Morinda officinalis oligosaccharides in the continuation treatment of adults with mild and moderate depression
Shu-Zhe ZHOU ; Zu-Cheng HAN ; Xiu-Zhen WANG ; Yan-Qing CHEN ; Ya-Ling HU ; Xue-Qin YU ; Bin-Hong WANG ; Guo-Zhen FAN ; Hong SANG ; Ying HAI ; Zhi-Jie JIA ; Zhan-Min WANG ; Yan WEI ; Jian-Guo ZHU ; Xue-Qin SONG ; Zhi-Dong LIU ; Li KUANG ; Hong-Ming WANG ; Feng TIAN ; Yu-Xin LI ; Ling ZHANG ; Hai LIN ; Bin WU ; Chao-Ying WANG ; Chang LIU ; Jia-Fan SUN ; Shao-Xiao YAN ; Jun LIU ; Shou-Fu XIE ; Mao-Sheng FANG ; Wei-Feng MI ; Hong-Yan ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(6):815-819
Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P<0.05).After continuation treatment,the remission rate was 54.59%(202 cases/370 cases),and the recurrence rate was 6.49%(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35%(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.
9.Development and evaluation of the children′s postoperative health-related quality of life scale for thyroid cancer
Wei PANG ; Shengcai WANG ; Xiaodan LI ; Yuwei LIU ; Zhe LI ; Yuanhu LIU ; Yanzhen LI ; Xuexi ZHANG ; Qiaoyin LIU ; Nian SUN ; Zhiyong LIU ; Xin NI
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2024;59(11):1183-1192
Objective:To develop the children′s postoperative health-related quality of life scale for thyroid cancer and to test its reliability and validity.Methods:The first draft of the scale was developed through literature search, focus group meetings, and a pre-survey, and 116 children (76 for testing and 40 for external validation) with thyroid cancer attending Beijing Children′s Hospital of Capital Medical University were selected to answer the scale, to screen and categorize the questions and to form the final scale with multiple dimensions.Results:The children′s postoperative health-related quality of life scale for thyroid cancer contained 5 dimensions and 29 questions. Exploratory factor analysis showed that the cumulative variance explained by the 5 factors was 64.343%. Confirmatory factor analysis showed correlations between the questions and dimensions of this scale, fair convergent validity for the scale, and good discriminant validity. The validity of the validity scale showed that there was a existing correlation between the questions and the validity scale of this scale. The item-dimension correlation coefficients showed that the questions in each dimension were well differentiated. The total Cronbach′s α coefficient of the scale was 0.930, the folded half reliability was 0.843, and retest reliabilities at 2 weeks, 1 month, and 3 months after the initial test were respectively 0.936, 0.922, and 0.910.Conclusion:The developed children′s postoperative health-related quality of life scale for thyroid cancer has good reliability and validity and can be used to assess the health-related quality of life of children after thyroid cancer surgery.
10.Research on the differential diagnosis of phlegm and blood stasis pattern and qi deficiency and blood stasis pattern in stable angina pectoris based on coronary artery CT angiography radiomics
Dongsheng WEI ; Jiajie QI ; Xiaosheng LIU ; Luzhen LI ; Han LI ; Yuting LIU ; Chengkang DENG ; Xu DAI ; Baoying ZHAO ; Zhe ZHANG
Journal of Beijing University of Traditional Chinese Medicine 2024;47(4):545-554
Objective To establish a differential model of phlegm and blood stasis pattern and qi deficiency and blood stasis pattern in stable angina pectoris using radiomics.Methods A total of 91 patients with stable angina pectoris who underwent coronary artery CT angiography in Affiliated Hospital of Liaoning University of Traditional Chinese Medicine from January 2021 to January 2022 were collected,including 47 cases of phlegm and blood stasis pattern and 44 cases of qi deficiency and blood stasis pattern.The patients were divided into train set(64 cases)and test set(27 cases)according to the ratio of 7∶3 by stratified random sampling method.3D-slicer software was used to extract the radiomics features of pericoronary adipose tissue(PCAT)images.Principal component analysis was used to visualize the distribution of radiomics features of pattern of phlegm and blood stasis and pattern of qi deficiency and blood stasis.The least absolute shrinkage and selection operator regression analysis and support vector machine decreasing feature elimination were used for feature selection.The multinomial logistics regression was used for model construction.The receiver operating characteristic(ROC)curve was used to verify the model in the train set and the test set to evaluate the effectiveness of the radiomics features in differentiating phlegm and blood stasis pattern and qi deficiency and blood stasis pattern.Finally,Spearman coefficient was used to analyze the correlation between the differential features and clinical physicochemical data.Results A total of 837 radiomics features were extracted from PCAT images by 3D-slicer software.In the principal component analysis,PC1 and PC2 explained 77.9%and 8.1%of the total variance,respectively,and there was a relatively obvious separation trend between the two pattern groups.After feature screening,7 radiomics features were used to construct the differential model of phlegm and blood stasis pattern and qi deficiency and blood stasis pattern.The area under the ROC curve(AUC)of the differential model was 0.844 in the train set and 0.834 in the test set.Spearman correlation analysis showed that the differential features were significantly correlated with cTnI,neutrophil,triglyceride,total cholesterol,and leukocyte.Conclusion The CT radiomics model based on PCAT has a high discrimination efficiency for stable angina pectoris with phlegm and blood stasis pattern and qi deficiency and blood stasis pattern.

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