OBJECTIVE To study the improvement effect and mechanism of Tripterygium wilfordii multiglucoside （TWM） on nephrotic syndrome in rats. METHODS The nephrotic syndrome model was established by intravenous injection of adriamycin via the tail vein. The modeling rats were randomly divided into the model group （distilled water）， prednisone group （10 mg/kg）， and TWM high- and low-dose groups （10 and 5 mg/kg， respectively）. Additionally， blank group （distilled water） without model induction was established. Each group consisted of 9 rats. Rats in each group were administered the corresponding drugs or distilled water by gavage， once a day， for 6 consecutive weeks. The histopathological morphology of kidney tissues in rats was observed； the levels of 24-hour urinary protein （24 h-UTP） and serum biochemical indicators [albumin （ALB）， blood urea nitrogen （BUN）， serum creatinine （SCr）， cholesterol （CHOL）， and triglyceride （TG）] in rats were determined； the levels of oxidative stress indicators [superoxide dismutase （SOD）， malondialdehyde （MDA）] in kidney tissue of rats were determined； expressions of hypoxia-inducible factor-1α （HIF-1α）/microRNA-155-5p （miR-155-5p）/nuclear factor erythriod 2- related factor 2 （Nrf2） signaling pathway-related mRNA and protein in the renal tissues of rats were detected. RESULTS Compared with the blank group， the rats in the model group exhibited disordered renal tissue structure， with a small amount of glomerular necrosis and edema of the renal tubular epithelial cells. 24 h-UTP， serum levels of SCr， BUN， CHOL and TG， MDA content， mRNA and protein expressions of HIF-1α and Keap1 as well as the expression of miR-155-5p in renal tissues were increased significantly （ P ＜0.05）. Serum level of ALB， SOD level in renal tissue as well as mRNA and protein expressions of Nrf2 were decreased significantly （ P ＜0.05）. Compared with the model group， TWM high-dose and low-dose groups exhibited significant improvements in renal injury， with notable reversals in the levels of the above quantitative indicators （ P ＜0.05）. CONCLUSIONS TWM can alleviate oxidative stress-induced damage and thereby improve nephrotic syndrome in rats by regulating the HIF-1α/miR-155-5p/Nrf2 signaling pathway.

Organ transplantation is an effective alternative treatment for patients with end-stage organ failure. However, the shortage of donor organs has limited the widespread application of clinical transplantation. In recent years, breakthroughs in CRISPR-Cas9 gene editing technology have overcome the barrier of hyperacute rejection in xenotransplantation, offering a potential solution to the organ shortage crisis. Rejection remains a critical factor affecting graft survival. Antigen-presenting cells play a vital role in the initiation and progression of rejection and immune regulation in xenotransplantation. Therefore, in-depth investigation into the role of antigen-presenting cells in xenotransplantation is of great significance. This article summarizes the roles and therapeutic strategies of professional antigen-presenting cells, including macrophages, dendritic cells and B cells in xenotransplantation, aiming to provide insights for future research on immune regulation mechanisms in this field.

ObjectiveTo investigate the effects of Yueju Wan on the 5-hydroxytryptamine （5-HT） signaling pathway in rats with functional dyspepsia （FD） and to explore its therapeutic mechanism in the treatment of FD. MethodsSixty Sprague-Dawley （SD） rats were randomly divided into a normal group， model group， mosapride group （1.575 mg·kg^-1）， and Yueju Wan low-， medium-， and high-dose groups （0.735， 1.47， and 2.94 g·kg^-1， respectively）. The FD rat model was established using GUO's tail-clamping stimulation combined with irregular feeding. After 14 days of modeling， rats were administered the corresponding drugs by gavage for 28 days. After treatment， gastric emptying rate and small intestinal propulsion rate were measured. Serum levels of 5-HT， tryptophan hydroxylase （TPH）， and substance P （SP） were detected by enzyme-linked immunosorbent assay （ELISA）， and acetylcholine （ACh） levels were determined by chemical methods. Histopathological changes in the gastric antrum were observed using hematoxylin-eosin （HE） staining. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to assess the mRNA and protein expression levels of 5-hydroxytryptamine 4 receptor （5-HT4R）， SP， and acetylcholinesterase （AChE） in colon tissue， as well as 5-hydroxytryptamine 3 receptor （5-HT3R）， SP， and AChE in hypothalamic tissue. Immunohistochemistry （IHC） was used to examine the expression of 5-HT and 5-HT4R in the colon and 5-HT and 5-HT3R in the hypothalamus. ResultsCompared with the normal group， the gastric emptying rate and small intestinal propulsion rate in the model group were significantly decreased （P<0.01）. Serum levels of 5-HT， SP， ACh， and TPH were significantly reduced （P<0.01）. Histopathological examination revealed irregular arrangement of glands in the gastric antrum， slight mucosal atrophy， and mild inflammatory cell infiltration. The mRNA and protein expression levels of 5-HT4R， SP， and AChE in colon tissue， as well as 5-HT3R， SP， and AChE in hypothalamic tissue， were significantly decreased （P<0.01）， and 5-HT protein expression in both the colon and hypothalamus was also significantly reduced （P<0.01）. Compared with the model group， all Yueju Wan groups showed significantly increased gastric emptying rate and small intestinal propulsion rate （P<0.01）. The glands in the gastric antrum were more regularly arranged， with no inflammatory cell infiltration observed. Serum levels of 5-HT， SP， ACh， and TPH were significantly increased （P<0.01）. The mRNA and protein expression levels of 5-HT4R， SP， and AChE in colon tissue and 5-HT3R， SP， and AChE in hypothalamic tissue were significantly upregulated （P<0.05， P<0.01）， and 5-HT protein expression in both the colon and hypothalamus was significantly increased （P<0.01）. ConclusionYueju Wan has preventive and therapeutic effects on FD， and its mechanism may be related to regulation of the 5-HT signaling pathway， promotion of brain-gut peptide secretion， and enhancement of gastric motility.

Based on LI Gao's theory of "heavy obstruction" and "blockage of the nine orifices"， this paper proposes the pathological concept of "heavy obstruction and orifice blockage". It is suggested that the core pathogenesis of functional constipation （FC） lies in simultaneous sinking of spleen and lung， together with accumulation and obstruction of dampness and turbidity， resulting in impaired movement of intestinal qi. Within this framework， spleen deficiency with sinking of dampness is considered as the primary pathological mechanism of outlet obstructive constipation （OOC）， while sinking of lung qi is regarded as the key mechanism underlying slow transit constipation （STC）. When both pathological mechanisms coexist， mixed constipation （MC） develops. Guided by this theory， FC is classified into three patterns for syndrome-based treatment. OOC is treated by promoting bowel movement， descending turbid pathogens， and opening the orifices to restore function， with self-formulated Shengxian Tongqiao Decoction （升陷通窍汤）. STC is treated by diffusing lung qi， regulating spleen function， raising sinking qi， and promoting transportation， with self-formulated Xuanfei Yunpi Decoction （宣肺运脾汤）. MC is treated by regulating lung and spleen function， simultaneously raising clear qi and descending turbidity， with self-formulated Xuanyun Tongqiao Decoction （宣运通窍汤）. In clinical practice， modifications should be made according to accompanying syndromes and individual conditions.

Based on LI Gao's theory of "heavy obstruction" and "blockage of the nine orifices"， this paper proposes the pathological concept of "heavy obstruction and orifice blockage". It is suggested that the core pathogenesis of functional constipation （FC） lies in simultaneous sinking of spleen and lung， together with accumulation and obstruction of dampness and turbidity， resulting in impaired movement of intestinal qi. Within this framework， spleen deficiency with sinking of dampness is considered as the primary pathological mechanism of outlet obstructive constipation （OOC）， while sinking of lung qi is regarded as the key mechanism underlying slow transit constipation （STC）. When both pathological mechanisms coexist， mixed constipation （MC） develops. Guided by this theory， FC is classified into three patterns for syndrome-based treatment. OOC is treated by promoting bowel movement， descending turbid pathogens， and opening the orifices to restore function， with self-formulated Shengxian Tongqiao Decoction （升陷通窍汤）. STC is treated by diffusing lung qi， regulating spleen function， raising sinking qi， and promoting transportation， with self-formulated Xuanfei Yunpi Decoction （宣肺运脾汤）. MC is treated by regulating lung and spleen function， simultaneously raising clear qi and descending turbidity， with self-formulated Xuanyun Tongqiao Decoction （宣运通窍汤）. In clinical practice， modifications should be made according to accompanying syndromes and individual conditions.

ObjectiveTo develop and validate a nomogram based on the albumin-bilirubin （ALBI） score for predicting the risk of severe perioperative complications in patients undergoing hepatectomy for hepatolithiasis. MethodsA retrospective analysis was conducted on the clinical data of 163 hepatolithiasis patients who underwent hepatectomy. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for severe perioperative complications. A nomogram prediction model was constructed and its performance was evaluated. ResultsAmong the 163 patients， 66 and 97 were classified into the low-grade and high-grade ALBI groups， respectively. Significant intergroup differences were observed in gender， total bilirubin， albumin levels， and the incidence of severe complications （P0.05）. Severe complications occurred in 40 patients. Independent risk factors included age 60 years （OR=5.49， P0.001）， high-grade ALBI （OR=8.30， P0.001）， history of biliary surgery （OR=2.60， P=0.035）， hepatectomy （segmentectomy）≥3 （OR=2.75， P=0.028）， and open surgical approach （OR=4.00， P=0.009）. A nomogram for predicting severe perioperative complications was successfully established. Internal validation showed that the model had an area under the ROC curve （AUC） of 0.865， which outperformed traditional single predictors. The calibration curve closely aligned with the ideal curve， with a mean absolute error （MAE） of 0.027. Decision curve analysis （DCA） demonstrated a net clinical benefit when the threshold probability exceeded 10%， superior to that of traditional predictors. ConclusionThe ALBI score-based nomogram is successfully developed and validated to predict the risk of severe perioperative complications in hepatolithiasis patients undergoing hepatectomy. The model demonstrated favorable predictive performance and high clinical utility， serving as an effective tool for both preoperative risk assessment and postoperative risk stratification.

Objective: To address the lack of fine-grained clinical recognition for specific Yang deficiency syndrome subtypes and the limitations of conventional object detection models in extracting irregular, low-contrast tongue phenotypes. This study aims to develop an objective subtype recognition framework based on an improved You Only Look Once nano (YOLO11n) architecture, using a standardized visual phenotype matrix to translate macroscopic traditional Chinese medicine (TCM) descriptions into quantifiable clinical targets. Methods: This cross-sectional diagnostic study consecutively enrolled adult inpatients admitted to the Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Wannan Medical University (Yijishan Hospital), between September 1, 2024 and June 1, 2025, who were suspected of having Yang deficiency constitution based on initial TCM consultation. Clinical tongue image data were collected for analysis. Based on an Expert Visual Phenotype Annotation Matrix, a five-category recognition system was established, including the following TCM syndrome subtypes: spleen-dampness exuberance syndrome, mild kidney Yang deficiency syndrome, upper heat and lower cold syndrome, simultaneous Yin-Yang deficiency syndrome, and Yin deficiency and fluid depletion syndrome (negative control). The proposed Yang deficiency YOLO (YD-YOLO) model, built upon the YOLO11n baseline, integrates the Cross Stage Partial with kernel size 2 (C3k2)-GhostBottleneck-Dynamic Convolution (GBDC) module into the backbone to adaptively extract low-contrast features, and embeds the multipath aggregation coordinate attention (MACA) mechanism into the neck to suppress background interference through multi-scale spatial coordination. Gradient-weighted class activation mapping (Grad-CAM) was used to visualize feature attribution and evaluate the biological plausibility of the model’s focus. Model performance was evaluated through ablation and comparative experiments using mean average precision (mAP), precision, recall, F1 score, inference speed (frames per second, FPS), overall accuracy, Cohen’s kappa, and the area under the receiver operating characteristic (ROC) curve (AUC). Results: Based on the final inclusion of 1 186 clinical cases, the YD-YOLO model had an overall accuracy of 91.5%, a Cohen’s kappa of 0.912, and an mAP@50 of 0.731 [higher than the YOLO11n baseline (0.681)], with AUC ranging from 0.91 to 0.97 across all TCM syndrome subtypes. Among the TCM syndrome subtypes, the mild kidney Yang deficiency syndrome had the highest mAP@50 (0.900), and the inference speed reached 89.00 FPS. Grad-CAM analysis showed that the model localized activation to key TCM pathological features, such as marginal tooth marks and focal root coatings, while suppressing non-diagnostic oral background noise. Conclusion The YD-YOLO model demonstrates the feasibility of deep learning for the fine-grained classification of TCM Yang deficiency subtypes. By integrating visual phenotype quantification with model interpretability, the proposed framework provides an objective basis for syndrome differentiation, supporting the development of standardized digital diagnostic systems and the provision of clinical decision support in TCM practice.

ObjectiveTo investigate the potential mechanism of Yiqi Yangyin Huoxue Formula （益气养阴活血方， YYHF） in the treatment of membranous nephropathy （MN） based on the NOX4-mediated stromal cell-derived factor-1α（SDF-1α）/CXC chemokine receptor 4 （CXCR4） signaling pathway. MethodsA total of 42 male SD rats were randomly divided into blank group （n=6） and modeling group （n=36）. The modeling rats were given a single injection of sheep antirat Fx1A （6 ml/kg） serum into the tail vein to establish MN model. Thirty-six rats with successful modeling were further divided into model group （normal saline， 10 ml/kg）， benazepril group （10 mg·kg^-1·d^-1）， the medium-dose YYHF group （11.0 g·kg^-1·d^-1） and high-dose YYHF group （22.0 g·kg^-1·d^-1）， with 9 rats in each group. All groups received daily intragastric administration for 6 consecutive weeks. During the experimental period， the general condition of rats in each group was observed. After gavage administration finished， a fully automated biochemical analyzer was used to measure the 24-hour urine total protein （24 h-UTP） and serum biochemical parameters， including albumin （ALB）， aspartate aminotransferase （AST）， blood urea nitrogen （BUN）， serum creatinine （SCr）， total cholesterol （TC）， and triglyceride （TG）. Hematoxylin-eosin （HE） staining and periodic acid-silver metheramine （PASM） staining were used to observe the histopathological changes of renal tissues in each group of rats. The levels of superoxide dismutase （SOD） and malondialdehyde （MDA） in renal tissues were detected by ELISA. The protein expression levels of NOX4， SDF-1α， CXCR4， Nrf2， nuclear factor kappa B subunit p65 （NF-κB p65） and podocyte slit diaphragm protein nephrin in rat renal tissues were detected by Western Blotting. The mRNA expressions of NOX4， SDF-1α， CXCR4， Nrf2， NF-κB p65 and Nephrin in renal tissues were detected by real-time fluorescence quantitative polymerase chain reaction （RT-PCR）. ResultsCompared to the blank group， rats in the model group exhibited typical features of MN， including lethargy， reduced activity， dull and coarse fur， marked edema， and massive proteinuria. Compared to the model group， these abnormal conditions were improved to varying degrees in all treatment groups. The high-dose YYHF group showed a level of improvement comparable to that of the benazepril group， with overall recovery superior to that of the medium-dose YYHF group. Compared to the blank group， the model group showed increased levels of 24 h-UTP， BUN， SCr， TC and TG， decreased level of ALB， increased levels of MDA and protein and mRNA expressions of NOX4， SDF-1α， CXCR4 and NF-κB p65 in renal tissue， along with decreased levels of SOD and protein and mRNA expressions of Nrf2， Nephrin （P＜0.01）， accompanied by severe renal pathological damage. Compared to the model group， the benazepril and the medium- and high-dose YYHF groups showed significant improvements in the above indicators （P＜0.01）， along with alleviation of renal pathological injury. The 24 h-UTP level in the high-dose YYHF group was lower than that in the medium-dose group （P＜0.01）， while no statistically significant difference was observed among the other treatment groups （P＞0.01）. ConclusionYYHF may alleviate oxidative stress and inflammatory responses by down-regulating the expression of NOX4 and inhibiting the SDF-1α/CXCR4-Nrf2 signaling pathway， thereby improving podocyte damage and protecting renal function.

ObjectiveTo investigate the protective effect of liver-targeted fibroblast growth factor 21 （FGF21） overexpression against CCl₄-induced acute liver injury （ALI） and its association with silent information regulator 1/glutathione peroxidase 4 （SIRT1/GPX4） expression and ferroptosis-related markers. MethodsFemale ICR mice （8 weeks old） were randomly divided into Control， CCl₄， adeno-associated virus （AAV）-FGF21， and AAV-FGF21 + CCl₄ groups. Liver-targeted FGF21 overexpression was achieved via tail vein injection of AAV8-FGF21 virus with green fluorescent protein （GFP） labeling. ALI was induced by intraperitoneal injection of CCl₄ （0.3 mL/kg）， with sample collection at 12 hours. Body weight and liver weight were recorded to calculate the liver weight/body weight. Alanine aminotransferase （ALT） and aspartate aminotransferase （AST） levels were measured using a biochemical analyzer. FGF21 expression in liver tissues was detected by immunofluorescence. Hepatic histopathology was evaluated by HE staining. RT-qPCR was performed to assess mRNA expression of ferroptosis and iron metabolism-related genes （ACSL4， PTGS2， HJV， FPN， GPX4）， FGF21， and SIRT1. Protein expression of FGF21， SIRT1， and GPX4 were determined by Western blot. Iron content， malondialdehyde （MDA）， glutathione （GSH）， and superoxide dismutase （SOD） activity in liver homogenate were quantified using assay kits. ResultsCompared with the Control group， the FGF21 mRNA and protein expression elevated in CCl₄ group； serum ALT/AST levels and liver weight/body weigh increased. The HE staining results showed that the liver cell membranes were ruptured. The mRNA levels of ACSL4 and PTGS2， the iron content and MDA levels all increased （P<0.01）. The mRNA levels of SIRT1， GPX4， HJV， and FPN， the GSH level and SOD activity all decreased （P<0.05）， and the protein levels of SIRT1 and GPX4 both decreased （P<0.05）. Compared with the CCl₄ group， the serum levels of ALT and AST in the AAV-FGF21 + CCl4 group were decreased （P<0.01）， and the liver/body ratio of mice decreased （P<0.01）. The results of HE staining showed that the degree of liver injury was alleviated. The mRNA levels of ACSL4 and PTGS2， iron content and MDA level all decreased （P<0.01）， while the mRNA levels of SIRT1， GPX4， HJV， FPN， GSH level and SOD activity all increased （P<0.05）. The protein levels of SIRT1 and GPX4 both increased （P<0.05）. ConclusionFGF21 overexpression is associated with enhanced SIRT1/GPX4 expression and suppression of ferroptosis features， thereby contributing to the alleviation of CCl₄-induced ALI.

BACKGROUND:Osteosarcoma has a complex pathogenesis and a poor prognosis.While advancements in medical technology have led to some improvements in the 5-year survival rate,substantial progress in its treatment has not yet been achieved. OBJECTIVE:To screen key molecular markers in osteosarcoma,analyze their relationship with osteosarcoma treatment drugs,and explore the potential disease mechanisms of osteosarcoma at the molecular level. METHODS:GSE99671 and GSE284259(miRNA)datasets were obtained from the Gene Expression Omnibus database.Differential gene expression analysis and Weighted Gene Co-expression Network Analysis(WGCNA)on GSE99671 were performed.Functional enrichment analysis was conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes separately for the differentially expressed genes and the module genes with the highest positive correlation to the disease.The intersection of these module genes and differentially expressed genes was taken as key genes.A Protein-Protein Interaction network was constructed,and correlation analysis on the key genes was performed using CytoScape software,and hub genes were identified.Hub genes were externally validated using the GSE28425 dataset and text validation was conducted.The drug sensitivity of hub genes was analyzed using the CellMiner database,with a threshold of absolute value of correlation coefficient|R|>0.3 and P<0.05. RESULTS AND CONCLUSION:(1)Differential gene expression analysis identified 529 differentially expressed genes,comprising 177 upregulated and 352 downregulated genes.WGCNA analysis yielded a total of 592 genes with the highest correlation to osteosarcoma.(2)Gene Ontology enrichment results indicated that the development of osteosarcoma may be associated with extracellular matrix,bone cell differentiation and development,human immune regulation,and collagen synthesis and degradation.Kyoto Encyclopedia of Genes and Genomes enrichment results showed the involvement of pathways such as PI3K-Akt signaling pathway,focal adhesion signaling pathway,and immune response in the onset of osteosarcoma.(3)The intersection analysis revealed a total of 59 key genes.Through Protein-Protein Interaction network analysis,8 hub genes were selected,which were LUM,PLOD1,PLOD2,MMP14,COL11A1,THBS2,LEPRE1,and TGFB1,all of which were upregulated.(4)External validation revealed significantly downregulated miRNAs that regulate the hub genes,with hsa-miR-144-3p and hsa-miR-150-5p showing the most significant downregulation.Text validation results demonstrated that the expression of hub genes was consistent with previous research.(5)Drug sensitivity analysis indicated a negative correlation between the activity of methotrexate,6-mercaptopurine,and pazopanib with the mRNA expression of PLOD1,PLOD2,and MMP14.Moreover,zoledronic acid and lapatinib showed a positive correlation with the mRNA expression of PLOD1,LUM,MMP14,PLOD2,and TGFB1.This suggests that zoledronic acid and lapatinib may be potential therapeutic drugs for osteosarcoma,but further validation is required through additional basic experiments and clinical studies.