1.Research progress and clinical challenges in immunosuppressive regimens for xenotransplantation
Yu ZHANG ; Kun WANG ; Xuyuan ZHU ; Yuxiang CHEN ; Tao LI ; Xiaojie MA ; Hongtao JIANG
Organ Transplantation 2026;17(1):28-35
As a pivotal strategy to alleviate the shortage of organ donors, xenotransplantation has achieved remarkable advances in both pre-clinical and clinical studies in recent years, driven by continuous optimization of gene modification techniques and immunosuppressive regimens. Nevertheless, clinical translation still confronts formidable challenges, including rejection and heightened infection risks, which severely compromise long-term graft survival. Consequently, the role of immunosuppressive regimens in xenotransplantation has become increasingly prominent. This article summarizes the mechanisms underlying xenogeneic immune rejection, the latest developments in immunosuppressive regimens, cutting-edge strategies for inducing immune tolerance and the major hurdles facing clinical xenotransplantation. It delves into potential optimization strategies and directions for future clinical research, aiming to offer theoretical insights and practical guidance for the safe and effective application of clinical xenotransplantation.
2.Traditional Chinese Medicine Treatment of Chronic Heart Failure Based on AMPK Signaling Pathway
Kun LIAN ; Lichong MENG ; Xueqin WANG ; Yubin ZHANG ; Lin LI ; Xuhui TANG ; Zhixi HU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):139-148
Chronic heart failure (CHF) is a group of complex clinical syndromes caused by abnormal changes in the structure and/or function of the heart due to various reasons, resulting in disorders of ventricular contraction and/or diastole. CHF is a condition where primary diseases such as coronary heart disease, hypertension and pulmonary heart disease recur frequently and persist for a long time, presenting blood stasis in meridians and collaterals, stagnation of water and dampness, and accumulation of Qi in collaterals. Its pathogenesis is complex and may involve myocardial energy metabolism disorders, oxidative stress responses, myocardial cell apoptosis, autophagy, inflammatory responses, etc. According to the theory of restraining hyperactivity to acquire harmony, we believe that under normal circumstances, the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway functions normally, maintaining human physiological activities and energy metabolism. Under pathological conditions, the AMPK signaling pathway is abnormal, causing energy metabolism disorders, inflammatory responses, and myocardial fibrosis. Traditional Chinese medicine (TCM) can regulate the AMPK signaling pathway through multiple mechanisms, targets, and effects, effectively curbing the occurrence and development of CHF. It has gradually become a research hotspot in the prevention and treatment of this disease. Guided by the theory of TCM, our research group, through literature review, summarized the relationship between the AMPK pathway and CHF and reviewed the research progress in the prevention and control of CHF with TCM active ingredients, TCM compound prescriptions, and Chinese patent medicines via regulating the AMPK pathway. The review aims to clarify the mechanism and targets of TCM in the treatment of CHF by regulating the AMPK pathway and guide the clinical treatment and drug development for CHF.
3.Myocardial Metabolomics Reveals Mechanism of Shenfu Injection in Ameliorating Energy Metabolism Remodeling in Rat Model of Chronic Heart Failure
Xinyue NING ; Zhenyu ZHAO ; Mengna ZHANG ; Yang GUO ; Zhijia XIANG ; Kun LIAN ; Zhixi HU ; Lin LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):178-186
ObjectiveTo examine the influences of Shenfu injection on the endogenous metabolic byproducts in the myocardium of the rat model exhibiting chronic heart failure, thus deciphering the therapeutic mechanism of the Qi-reinforcing and Yang-warming method. MethodsSD rats were randomly allocated into a control group and a modeling group. Chronic heart failure with heart-Yang deficiency syndrome in rats was modeled by multi-point subcutaneous injection of isoproterenol, and the rats were fed for 14 days after modeling. The successfully modeled rats were randomized into model, Shenfu injection (6.0 mL·kg-1), and trimetazidine (10 mg·kg-1) groups and treated with corresponding agents for 15 days. The control group and the model group were injected with equal doses of normal saline, and the samples were collected after the intervention was completed. Cardiac color ultrasound was performed. Hematoxylin-eosin (HE) staining was used to observe histopathological morphology, and the serum level of N-terminal pro-brain natriuretic peptide (NT-proBNP) was assessed by enzyme-linked immunosorbent assay (ELISA). The mitochondrial morphological and structural changes of cardiomyocytes were observed by transmission electron microscopy, and the metabolic profiling was carried out by ultra high performance liquid chromatography-quantitative exactive-mass spectrometry (UHPLC-QE-MS). Differential metabolites were screened and identified by orthogonal partial least squares-discriminant analysis (OPLS-DA) and other methods, and then the MetaboAnalyst database was used for further screening. The relevant biological pathways were obtained through pathway enrichment analysis. The receiver operating characteristic (ROC) curve was established to evaluate the diagnostic value of each potential biomarker for myocardial injury and the evaluation value for drug efficacy. ResultsThe results of color ultrasound showed that Shenfu Injection improved the cardiac function indexes of model rats (P<0.05). The results of HE staining showed that Shenfu injection effectively alleviated the pathological phenomena such as myocardial tissue structure disorder and inflammatory cell infiltration in model rats. The results of ELISA showed that Shenfu injection effectively regulated the serum NT-proBNP level in the model rats. Transmission electron microscopy (TEM) showed that Shenfu injection effectively restored the mitochondrial morphological structure. The results of metabolomics showed that the metabolic phenotypes of myocardial samples presented markedly differences between groups. Nine differential metabolites could be significantly reversed in the Shenfu injection group, involving three metabolic pathways: pyruvate metabolism, histidine metabolism, and citric acid cycle (TCA cycle). The results of ROC analysis showed that the area under the curve (AUC) values of all metabolites were between 0.75 and 1.0, indicating that the differential metabolites had high diagnostic accuracy for myocardial injury, and the changes in their expression levels could be used as potential markers for efficacy evaluation. ConclusionShenfu injection significantly alleviated the damage of cardiac function, myocardium, and mitochondrial structure in the rat model of chronic heart failure with heart-Yang deficiency syndrome by ameliorating energy metabolism remodeling. Reinforcing Qi and warming Yang is a key method for treating chronic heart failure with heart-Yang deficiency syndrome.
4.Epidural fibrous scar formation in rabbits following autologous ligamentum flavum intervention
Debao ZHANG ; Peng WANG ; Kun LI ; Shaojie ZHANG ; Zhijun LI ; Shuwen LI ; Yimin WU
Chinese Journal of Tissue Engineering Research 2025;29(6):1168-1175
BACKGROUND:It has been proved clinically that adhesion of fibrous scar with the dura mater or nerve root after lumbar operation is an important factor for postoperative symptoms,such as postoperative pain and numbness. OBJECTIVE:To verify the inhibitory effect of autologous ligamentum flavum on the formation of epidural fibrous scar after lumbar surgery and explore the possible molecular biological mechanism. METHODS:Forty-eight Japanese white rabbits(6-8 months old)were randomly divided into three groups:a ligamentum flavum preservation group,a ligamentum flavum non-preservation group,and an autologous fat reposition group.A lumbar laminectomy model was established in all the three groups of rabbits,and rabbit epidural tissues were collected at 3 and 6 weeks after modeling.Hematoxylin-eosin staining was used to observe histological changes and the number and density of fibroblasts,VG staining was used to observe the percentage of collagen fiber area,and immunohistochemistry was used to observe the expression of transforming growth factor β1 and Smad3 proteins. RESULTS AND CONCLUSION:Hematoxylin-eosin staining results revealed that fibroblasts in the ligamentum flavum preservation group were few and loosely arranged,while the cells in the ligamentum flavum non-preservation and autologous fat reposition groups were more numerous and closely arranged.The number density of fibroblasts in the ligamentum flavum preservation group was lower than that in the ligamentum flavum non-preservation and autologous fat reposition groups at 3 and 6 weeks after surgery(P<0.05);however,there was no significant difference between the latter two groups.VG staining results showed that the collagen fibers in the ligamentum flavum preservation group were sparse and distributed unevenly,while a lot of red collagen fibers were gathered in the ligamentum flavum non-preservation and autologous fat reposition groups.The area percentage of collagen fibers in the ligamentum flavum preservation group was lower than that in the ligamentum flavum non-preservation and autologous fat reposition groups at 3 and 6 weeks after surgery(P<0.05),but there was no significant difference between the latter two groups.The results of immunohistochemistry showed that the degree of positive staining of retained histone the ligamentum flavum preservation group was significantly lower than that of the other two groups.The absorbance value of transforming growth factor β1 and Smad3 in the ligamentum flavum preservation group was significantly lower than that in the other two groups at 3 and 6 weeks after surgery(P<0.05),but there was no significant difference between the latter two groups.To conclude,there are different degrees of epidural fibrous scar formation after lumbar surgery.If the ligamentum flavum is preserved,it can help to reduce the number of epidural fibroblasts as well as the formation of collagen fibers,thus reducing the adhesion of the fibrous scar tissue to the dural sac and nerve root.The mechanism is not only a purely mechanical blockade,but also to reduce the formation of epidural fibrous scar by interfering with the transforming growth factor β1/Smad3 signaling pathway.
5.Development and application of a three-dimensional digital visualization system for children's neck acupoints
Xiaojing AO ; Kun LI ; Yuhang LIU ; Xiaoxuan YANG ; Xing WANG ; Zhijun LI ; Xiaoyan REN ; Shaojie ZHANG
Chinese Journal of Tissue Engineering Research 2025;29(9):1834-1840
BACKGROUND:Currently,there have been studies on three-dimensional digitalization and visualization systems for adult acupoints,but there are not many reports on the visualization of pediatric acupoints based on real pediatric digital sectional anatomical datasets. OBJECTIVE:To design and develop a digital three-dimensional visualization system for children's neck acupoints,to provide a basis for acupuncture and moxibustion,meridian and acupoint science teaching,clinical practice,acupuncture manipulation practice,and acupuncture safety research,and to provide a basis for the development of children's acupoint simulation system. METHODS:Based on a real cross-sectional anatomical dataset of pre-school boys,a three-dimensional digital virtual anatomical model of the neck region of children and internal multi-organ three-dimensional reconstruction were completed using PhotoShop 2021 and Digihuman Reconstruction System software.A database of 11 acupoints was compiled,including Fengfu and Fengchi,using the Unity database language.A three-dimensional model of children's neck anatomy,acupoint database,and writing acupuncture operation codes were integrated in Unity3D software.A three-dimensional digital visualization system for children's neck acupoints was successfully created,which integrated simulation acupoint positioning,three-dimensional acupoint anatomy,acupuncture training,clinical teaching,and acupuncture safety research. RESULTS AND CONCLUSION:(1)This study was based on real child specimens.Manual layer by layer segmentation of cross-sectional images was used to ensure the accuracy of the three-dimensional model to the greatest extent possible.The 3D software Digihuman Reconstruction System was utilized to extract and save independent segmentation data.PhotoShop 2021 software was collaborated with to complete dozens of three-dimensional reconstruction anatomical models of the outer skin of the neck and its internal bone structure,cervical spinal cord,blood vessels and nerves,muscles,and ligaments in children.The basic morphology and overall contour integrity verification of each independent structure were completed in MeshLab software.The 3-material research 13.0 software was applied for final fine tuning and anatomical position confirmation,successfully simulating and restoring the true anatomical morphology of the neck of preschool children.(2)Based on and referring to the national standards of the People's Republic of China,a database of commonly used acupoints in children's neck region was collected and organized,including their names,meridians,positioning,local anatomy,needle insertion levels,acupuncture methods,acupuncture accidents and prevention,acupoint indications,and two-dimensional anatomical sectional images.(3)Unity3D software was employed to integrate the three-dimensional model of children's neck,acupuncture simulation operation,and acupoint database,and a three-dimensional digital children's neck acupoint acupuncture visualization system was successfully constructed.The system displayed information on children's neck acupoints,two-dimensional and three-dimensional anatomical structures,and achieved two-dimensional and three-dimensional acupuncture simulation functions and acupuncture safety research functions for children's neck acupoints.Based on the ultra-thin sectional anatomical dataset of real child specimens,the first three-dimensional digital and visualization system for acupoints in the neck region of children had been constructed.Compared with previous acupoint acupuncture systems,it is more in line with the anatomical and morphological development characteristics of Asian children and has high application value in the fields of acupuncture safety research,clinical teaching,and acupuncture simulation training.
6.Textual Research on Historical Evolution and Key Information of Classical Famous Formula of Da Qinjiaotang
Na LI ; Jianying BAI ; Fuping LI ; Xiufen ZHANG ; Di LU ; Yishuo BAI ; Cuixiang WANG ; Kun SU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):201-211
Da Qinjiaotang is the 54th formula of the 100 formulas in the Catalogue of Ancient Classical Formulas (the first batch) ,and it originated from the Collection of Writings on the Mechanism of Disease, Suitability of Qi, and Safeguarding of Life Discussed in Plain Questions. Da Qinjiaotang is composed of Gentiana macrophylla, Glycyrrhizae Radix et Rhizoma, Ligusticum chuanxiong, Angelica sinensis, Paeonia lactiflora, Asari Radix et Rhizoma, Notopterygium incisum, Saposhnikoviae Radix, Scutellariae Radix, Gypsum, Angelica dahurica, Atractylodis Macrocephalae Rhizoma, Rehmanniae Radix, Rehmanniae Radix Praeparata, Poria, and Angelicae Pubescentis Radix. It is a classical formula for treating strokes. Da Qinjiaotang is widely used in modern clinical practices for treating ischemic stroke, peripheral facial paralysis, cervical spondylosis, rheumatic arthritis, neurodermatitis, and other multisystem diseases. Therefore, following the Principles of Textual Research on the Key Information of Ancient Classical Famous Formulas, the authors collected the ancient Chinese medical literature of Da Qinjiaotang by the method of bibliometrics and screened out 177 valid data, involving 100 ancient books of traditional Chinese medicine. Based on the historical evolution, composition, dosage, method of preparation, and preparation of the original medicinal materials of Da Qinjiaotang, a systematic study was carried out. It was found that among the 175 records of the main diseases and syndromes, stroke (144) was the most, accounting for 82.29% of the total diseases and syndromes. Later generations mostly followed the practice of LIU Wansu in using Da Qinjiaotang to treat stroke caused by "weak blood and inability to nourish tendon", featuring "hands and feet cannot move, stiff tongue hinders speaking", as well as other symptoms, such as slant of the mouth, hemiplegia, numbness of the limbs, paroxysmal pain, and acerbic syncope. The treatment scope was expanded, covering tendon dryness, clonic convulsion, spasm syndrome, and arthralgia syndrome. At the same time, it was found that there was a controversy between "internal wind" and "external wind" in the treatment of stroke by Da Qinjiaotang. LIU Wansu thought that stroke was caused by internal factors, created the theory of "hot stroke", and used Da Qinjiaotang to treat "internal wind". Many doctors in later generations focused on treating the "external wind" of "internal deficiency and evil". There were 76 valid data on the composition of drugs, 59 of which had doses for each drug. It was suggested to use the modern conversion dosage of the original formula, with 41.30 g per dose. The drug should be boiled in 600 mL water until 300 mL, decocted once, and taken in a warm state after removing the dregs anytime. Through the analysis and study of the ancient books about Da Qinjiaotang, the paper clarified its historical evolution and confirmed its key information, so as to provide the ancient literature evidence for the research and development of the classical famous formula Daqinjiaotan and its better clinical application.
7.Textual Research on Historical Evolution and Key Information of Classical Famous Formula of Da Qinjiaotang
Na LI ; Jianying BAI ; Fuping LI ; Xiufen ZHANG ; Di LU ; Yishuo BAI ; Cuixiang WANG ; Kun SU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):201-211
Da Qinjiaotang is the 54th formula of the 100 formulas in the Catalogue of Ancient Classical Formulas (the first batch) ,and it originated from the Collection of Writings on the Mechanism of Disease, Suitability of Qi, and Safeguarding of Life Discussed in Plain Questions. Da Qinjiaotang is composed of Gentiana macrophylla, Glycyrrhizae Radix et Rhizoma, Ligusticum chuanxiong, Angelica sinensis, Paeonia lactiflora, Asari Radix et Rhizoma, Notopterygium incisum, Saposhnikoviae Radix, Scutellariae Radix, Gypsum, Angelica dahurica, Atractylodis Macrocephalae Rhizoma, Rehmanniae Radix, Rehmanniae Radix Praeparata, Poria, and Angelicae Pubescentis Radix. It is a classical formula for treating strokes. Da Qinjiaotang is widely used in modern clinical practices for treating ischemic stroke, peripheral facial paralysis, cervical spondylosis, rheumatic arthritis, neurodermatitis, and other multisystem diseases. Therefore, following the Principles of Textual Research on the Key Information of Ancient Classical Famous Formulas, the authors collected the ancient Chinese medical literature of Da Qinjiaotang by the method of bibliometrics and screened out 177 valid data, involving 100 ancient books of traditional Chinese medicine. Based on the historical evolution, composition, dosage, method of preparation, and preparation of the original medicinal materials of Da Qinjiaotang, a systematic study was carried out. It was found that among the 175 records of the main diseases and syndromes, stroke (144) was the most, accounting for 82.29% of the total diseases and syndromes. Later generations mostly followed the practice of LIU Wansu in using Da Qinjiaotang to treat stroke caused by "weak blood and inability to nourish tendon", featuring "hands and feet cannot move, stiff tongue hinders speaking", as well as other symptoms, such as slant of the mouth, hemiplegia, numbness of the limbs, paroxysmal pain, and acerbic syncope. The treatment scope was expanded, covering tendon dryness, clonic convulsion, spasm syndrome, and arthralgia syndrome. At the same time, it was found that there was a controversy between "internal wind" and "external wind" in the treatment of stroke by Da Qinjiaotang. LIU Wansu thought that stroke was caused by internal factors, created the theory of "hot stroke", and used Da Qinjiaotang to treat "internal wind". Many doctors in later generations focused on treating the "external wind" of "internal deficiency and evil". There were 76 valid data on the composition of drugs, 59 of which had doses for each drug. It was suggested to use the modern conversion dosage of the original formula, with 41.30 g per dose. The drug should be boiled in 600 mL water until 300 mL, decocted once, and taken in a warm state after removing the dregs anytime. Through the analysis and study of the ancient books about Da Qinjiaotang, the paper clarified its historical evolution and confirmed its key information, so as to provide the ancient literature evidence for the research and development of the classical famous formula Daqinjiaotan and its better clinical application.
8.Clinical practice guidelines for intraoperative cell salvage in patients with malignant tumors
Changtai ZHU ; Ling LI ; Zhiqiang LI ; Xinjian WAN ; Shiyao CHEN ; Jian PAN ; Yi ZHANG ; Xiang REN ; Kun HAN ; Feng ZOU ; Aiqing WEN ; Ruiming RONG ; Rong XIA ; Baohua QIAN ; Xin MA
Chinese Journal of Blood Transfusion 2025;38(2):149-167
Intraoperative cell salvage (IOCS) has been widely applied as an important blood conservation measure in surgical operations. However, there is currently a lack of clinical practice guidelines for the implementation of IOCS in patients with malignant tumors. This report aims to provide clinicians with recommendations on the use of IOCS in patients with malignant tumors based on the review and assessment of the existed evidence. Data were derived from databases such as PubMed, Embase, the Cochrane Library and Wanfang. The guideline development team formulated recommendations based on the quality of evidence, balance of benefits and harms, patient preferences, and health economic assessments. This study constructed seven major clinical questions. The main conclusions of this guideline are as follows: 1) Compared with no perioperative allogeneic blood transfusion (NPABT), perioperative allogeneic blood transfusion (PABT) leads to a more unfavorable prognosis in cancer patients (Recommended); 2) Compared with the transfusion of allogeneic blood or no transfusion, IOCS does not lead to a more unfavorable prognosis in cancer patients (Recommended); 3) The implementation of IOCS in cancer patients is economically feasible (Recommended); 4) Leukocyte depletion filters (LDF) should be used when implementing IOCS in cancer patients (Strongly Recommended); 5) Irradiation treatment of autologous blood to be reinfused can be used when implementing IOCS in cancer patients (Recommended); 6) A careful assessment of the condition of cancer patients (meeting indications and excluding contraindications) should be conducted before implementing IOCS (Strongly Recommended); 7) Informed consent from cancer patients should be obtained when implementing IOCS, with a thorough pre-assessment of the patient's condition and the likelihood of blood loss, adherence to standardized internally audited management procedures, meeting corresponding conditions, and obtaining corresponding qualifications (Recommended). In brief, current evidence indicates that IOCS can be implemented for some malignant tumor patients who need allogeneic blood transfusion after physician full evaluation, and LDF or irradiation should be used during the implementation process.
9.Current Situation, Problems and Countermeasures of Experimental Research on Traditional Chinese Medicine Regulating PI3K/Akt Signaling Pathway in Rats with Polycystic Ovary Syndrome
Pengxuan YAN ; Yiqing LIU ; Nanxing XIAN ; Linjing PENG ; Kun LI ; Jingchun ZHANG ; Yukun ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):259-266
Polycystic ovary syndrome(PCOS) and its resulting infertility is one of the common diseases of gynecology and reproductive endocrinology. The phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt) signaling pathway is relatively well-studied in the development of intervention in PCOS, and the experiments on PCOS in rats conducted by traditional Chinese medicine through this signaling pathway is also the main direction of mechanistic research. In this paper, 20 articles published in academic journals in the past 5 years were selected through the corresponding criteria, and the objective situation and existing problems of the selected research projects were analyzed from five aspects, namely, baseline data, modeling and treatment, grouping, evaluative indexes, and pharmacodynamic indexes. It is found that there were different degrees of problems in each research project, such as the observation indicators of modeling, criteria for judging the success of the model, the treatment period, the calculation of dosage of prescription/active ingredients and specific dosage were not clearly defined, which could easily lead the bias of the results or reduce the validity of experimental data. Based on this, the list of PCOS rat experimental research operations was formed, involving five categories of experimental rats, model construction, study implementation, outcome measures and analysis and report with a total of 21 operation lists, with a view to provide a reference for the subsequent PCOS experiments related to scientific research and helping to form high-quality results.
10.Diagnosis and treatment of 281 elderly patients with pulmonary ground-glass opacity: A retrospective study in a single center
Lei SU ; Yi ZHANG ; Yan GAO ; Bing WEI ; Tengteng WANG ; Yuanbo LI ; Kun QIAN ; Peilong ZHANG ; Leiming WANG ; Xiuqin WEI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(01):94-99
Objective To explore the diagnosis and treatment strategies for elderly patients with ground-glass opacity (GGO). Methods The imaging features and postoperative pathological findings of the elderly patients with pulmonary GGO receiving surgery in our hospital from 2017 to 2019 were retrospectively analyzed. The patients were divided into an elderly patient group and a non-elderly patient group based on their age. Results Finally 575 patients were included in the study. There were 281 elderly patients, including 83 males and 198 females, with an average age of (67.0±5.3) years. There were 294 non-elderly patients, including 88 males and 206 females, with an average age of (49.1±7.3) years. Compared with the non-elderly patients, elderly GGO patients showed the following distinct clinical features: long observation time for lesions (P=0.001), high proportion of rough edges of GGO (P<0.001), significant pleural signs (P<0.001) and bronchial signs (P<0.001), and high proportion of type Ⅱ-Ⅳ GGO (P<0.001), lobectomy type (P=0.013), and invasive lesions reported in postoperative pathology (P<0.001). There was no statistical difference in the average hospital stay between the two groups (P=0.106). Multivariate logistic regression analysis showed that GGO diameter and GGO type were the main factors affecting the operation. Observation time, GGO diameter, GGO type and pleural signs were the main influencing factors for postoperative pathological infiltrative lesions. The cut-off value of GGO diameter in predicting infiltrating lesions was 10.5 mm in the elderly patients group. Conclusion The size and type of GGO are important factors in predicting invasive lesions and selecting surgical methods. Elderly patients with radiographic manifestations of type Ⅱ-Ⅳ GGO lesions with a diameter greater than 10.5 mm should be closely followed up.

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