OBJECTIVE: To explore the mechanism of action of asperosaponin VI (AVI) in the treatment of rheumatoid arthritis (RA) and validate it in ex vivo experiments using network pharmacology and molecular docking methods. METHODS: The predicted targets of AVI were obtained from PharmMaper, UniProt and SwissTarget Prediction platforms, the disease targets were collected from Online Mendelian Inheritance in Man, Therapeutic Target Database and GeneCards databases, the intersection targets of AVI and RA were obtained from Venny 2.1.0, and the protein-protein interaction (PPI) network was obtained from STRING database, which was analyzed by Cytoscape software and screened to obtain the core targets. Cytoscape software was used to analyze PPI network and screen the core targets. Based on the Database for Annotation, Visualization and Integrated Discovery database, Gene Ontology functional and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed, and Cytoscape software was used to construct the "Disease-Pathway-Target-Drug" network, which was finally verified by molecular docking and animal experiments. RESULTS: Network pharmacological studies showed that AVI was able to modulate 289 targets, with 102 targets for the potential treatment of RA, with the core pathway being the AKT/PI3K signaling pathway, and the core targets being the epidermal growth factor receptor (EGFR) and matrix metalloproteinase 9 (MMP9). Molecular docking results showed that AVI could produce strong binding with both of the 2 core targets. In vitro cellular experiments showed that AVI reduced nitric oxide, prostaglandin E₂, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1 β levels (P<0.05) and inhibited cyclooxygenase-2, nitric oxide synthase, EGFR, MMP9, phosphorylated phosphoinositide 3-kinase (p-PI3K), and phosphorylated serine-threonine kinase (p-AKT) proteins (P<0.05). The results of in vivo studies showed that AVI improved RA score and foot swelling thickness and decreased TNF-α, IL-6, p-PI3K and p-AKT levels in RA rats (P<0.05). CONCLUSION AVI exerts anti-inflammatory and anti-RA effects which might be related to the EGFR/MMP9/AKT/PI3K pathway.
Saponins/chemistry* ; ErbB Receptors/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Signal Transduction/drug effects* ; Molecular Docking Simulation ; Animals ; Arthritis, Rheumatoid/drug therapy* ; Proto-Oncogene Proteins c-akt/metabolism* ; Matrix Metalloproteinase 9/metabolism* ; Protein Interaction Maps/drug effects* ; Humans ; Network Pharmacology ; Male ; Rats

Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.

Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.

Objective To investigate the clinical characteristics of asthma patients with deficiency of various viscera through the analysis of mitochondrial dysfunction and related influencing factors,and to explore the DDAH1/L-Arg/ADMA pathway as well as the trend of changes in the mitochondrial function and oxygen metabolism of the asthma patients through the analysis.Methods A total of 122 patients with acute exacerbation of bronchial asthma who met the inclusion criteria were selected,and their clinical data were collected.The patients were divided into 3 groups based on the criteria of visceral deficiency syndrome differentiation,namely lung qi deficiency group(47 cases),lung-spleen qi deficiency group(39 cases),and lung-spleen-kidney deficiency group(36 cases).Meanwhile,the normal control group including 44 cases was set up.For the asthma patients with visceral deficiency,an observation was conducted in the lung function indicators of forced expiratory volume in the first second(FEV1),the ratio of FEV1 to forced vital capacity(FEV1/FVC)and peak expiratory flow(PEF)as well as the severity of the disease.Moreover,venous blood was sampled from the patients for the detection of L-arginine(L-Arg)and asymmetric dimethylarginine(ADMA)levels with high-performance liquid chromatography coupled with mass spectrometry(HPLC-MS/MS),and for the detection of arginine metabolism related indicators of protein arginine methyltransferase 1(PRMT1)and dimethylarginine dimethylammonium hydrolysate 1(DDAH1)as well as the oxidative damage parameters of reactive oxygen species(ROS),thiobarbituric acid reactive substance(TBARS),8-iso-prostaglandins(8-iso),lipid peroxide(LPO),and malondialdehyde(MDA)with enzyme-linked immunosorbent assay(ELISA).The platelet mitochondria were extracted from asthma patients and normal controls,and then the mitochondrial membrane potential(MMP),adenosine triphosphate(ATP),and activities of cytochrome C oxidase(COX)in the platelet were determined by JC-1 flow cytometric assay in order to assess the mitochondrial function.The changes in the mitochondrial function and their influence on the mitochondrial function of asthma patients with deficiency of various viscera were analyzed and then compared with those of the normal control group.Results(1)There were statistically significant differences in the age and lung function(FEV1,FEV1/FVC,PEF)among asthma patients with deficiency of various viscera(P＜0.01):the age of the lung-spleen-kidney deficiency group was significantly older than that of the lung qi deficiency group and the lung-spleen qi deficiency group(P＜0.05),and the lung function(FEV1,FEV1/FVC,PEF)showed a significant downward trend with the aggravation of viscera deficiency(P＜0.05).(2)There was a statistically significant difference in the illness grading of patients with deficiency of various viscera(P＜0.01).In the lung qi deficiency group,the illness status was predominated by intermittent state of asthma(grade 1),accounting for 65.96%,and then followed by mild asthma(grade 2),accounting for 25.53%.In the lung-spleen qi deficiency group,the illness status was predominated by moderate asthma(grade 3),accounting for 41.03%,and then followed by intermittent state of asthma(grade 1),accounting for 30.77%.In the lung-spleen-kidney deficiency group,the illness status was predominated by severe asthma(grade 4),accounting for 52.78%,and then followed by moderate asthma(grade 3),accounting for 33.33%.It is indicated that with the aggravation of viscera deficiency,the severity of asthma tended to be aggravated.(3)There were significant differences in plasma 8-iso,ROS,LPO and MDA levels between asthma patients with deficiency of various viscera and normal control group(P＜0.05).The plasma 8-iso and LPO levels of the asthma patients with deficiency of various viscera and the plasma MDA and ROS levels of asthma patients with lung-spleen qi deficiency and lung-spleen-kidney deficiency were significantly higher than those in normal control group(P＜0.05),and the plasma ROS level of asthma patients with lung-spleen qi deficiency and lung-spleen-kidney deficiency was significantly higher than that in asthma patients with lung qi deficiency(P＜0.05).The plasma TBARS level of asthma patients with deficiency of various viscera tended to be higher than that of normal control group,but the difference was not statistically significant(P＞0.05).It is indicated that reactive oxygen species and peroxide lipids accumulated in the body of asthma patients with deficiency of various viscera,and their levels increased with the aggravation of visceral deficiency.(4)The levels of MMP,ATP and COX in asthma patients with deficiency of various viscera were significantly lower than those in normal control group(P＜0.05),and the activity of COX decreased with the aggravation of visceral deficiency.(5)The levels of plasma L-Arg,L-Arg/ADMA and DDAH1 in asthma patients with deficiency of various viscera were significantly lower than those in normal control group(P＜0.05),and their levels decreased gradually with the aggravation of visceral deficiency.There was no significant difference in the plasma ADMA and PRMT1 levels between asthma patients with deficiency of various viscera and normal control group(P＞0.05).Conclusion It is indicated that the visceral deficiency in asthma patients is consistent with the progression of illness status,oxygen metabolism and its influencing factors,and the degree of oxidative damage.It is suggested that the progression of illness status can be judged by visceral deficiency in traditional Chinese medicine according to the parameters of body metabolism.

The establishment of a traceability system for the entire industry chain of Chinese medicinal materials can enhance regional brand building,raise the quality awareness of medicinal material producers,standardize the production processes of Chinese medicinal materials,and ensure the production of high-quality medicinal materials.Sichuan Province has successfully implemented a provincial-level Traditional Chinese Medicine(TCM)tracing system that is interconnected across provinces,cities,and counties.This system enables the complete tracking of the entire supply chain,starting from seed and seedling cultivation,through planting and breeding,harvesting and processing,and finally to the production and distribution of decoction pieces in trade and medical institutions.This research provides a comprehensive overview of the progress made in establishing the Chinese herbal medicine traceability system in Sichuan Province.It analyzes the existing challenges faced by participating enterprises,such as the hierarchy of involvement,information integrity,and the overall impact of the system.Moreover,the paper presents valuable insights and suggestions for the further development of the Chinese herbal medicine traceability system in Sichuan Province.These recommendations focus on enhancing the traceability scope,improving service capabilities,promoting data sharing,and establishing standardized norms and guidelines.

Seven novel linear polyketides,talaketides A-G(1-7),were isolated from the rice media cultures of the mangrove sed-iment-derived fungus Talaromyces sp.SCSIO 41027.Among these,talaketides A-E(1-5)represented unprecedented unsaturated lin-ear polyketides with an epoxy ring structure.The structures,including absolute configurations of these compounds,were elucidated through detailed analyses of nuclear magnetic resonance(NMR)and high-resolution mass spectrometry(HR-MS)data,as well as elec-tronic custom distributors(ECD)calculations.In the cytotoxicity screening against prostate cancer cell lines,talaketide E(5)demon-strated a dose-dependent inhibitory effect on prostate cancer PC-3 cell lines,with an IC50 value of 14.44 μmol·L-1.Moreover,com-pound 5 significantly inhibited the cloning formation of PC-3 cell lines and arrested the cell cycle in S-phase,ultimately inducing ap-optosis.These findings indicate that compound 5 may serve as a promising lead compound for the development of a potential treat-ment for prostate cancer.

The regulation of spermatogonial proliferation and apoptosis is of great significance for maintaining spermatogenesis. The single-cell RNA sequencing (scRNA-seq) analysis of the testis was performed to identify genes upregulated in spermatogonia. Using scRNA-seq analysis, we identified the spermatogonia upregulated gene origin recognition complex subunit 6 (Orc6), which is involved in DNA replication and cell cycle regulation; its protein expression in the human and mouse testis was detected by western blot and immunofluorescence. To explore the potential function of Orc6 in spermatogonia, the C18-4 cell line was transfected with control or Orc6 siRNA. Subsequently, 5-ethynyl-2-deoxyuridine (EdU) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays, flow cytometry, and western blot were used to evaluate its effects on proliferation and apoptosis. It was revealed that ORC6 could promote proliferation and inhibit apoptosis of C18-4 cells. Bulk RNA sequencing and bioinformatics analysis indicated that Orc6 was involved in the activation of wingless/integrated (Wnt)/ β-catenin signaling. Western blot revealed that the expression of β-catenin protein and its phosphorylation (Ser675) were significantly decreased when silencing the expression of ORC6. Our findings indicated that Orc6 was upregulated in spermatogonia, whereby it regulated proliferation and apoptosis by activating Wnt/β-catenin signaling.

Aim To study the inhibitory effect of attenuated salmonella SGN1, overexpressing methioninase, on nasopharyngeal carcinoma (NPC) and the underlying mechanism. Methods The cell proliferation, cell cycle, cell apoptosis, clony formation and migration a-bility of 5-8F, HNE-2, CNE-2 cells were measured u-sing flow cytometry assay, clone formation assay, and wound assay after the methionine restriction treatment. 5-8F, HNE-2, CNE-2 cells were infected with SGN1 at the multiplicity of infection (MOI) of 1: 100 for 5 hours, followed with the measurement of cell growth. A xenograft model was constructed by subcutaneous injection of 5-8F cells in mice to observe the inhibitory effect of SGN1 on nasopharyngeal carcinoma. Results Compared with the control group, methionine restriction significantly inhibited the proliferation, migration ability, and clone formation of nasopharyngeal carcinoma cells and blocked the G

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Objectives: To analyze the long-term survival of patients with localized renal cell carcinoma after partical nephrectomy. Methods: The clinicopathological records and survival follow-up data of 2 046 patients with localized renal cell carcinoma, who were treated with partial nephrectomy from August 2001 to February 2021 in the Department of Urology, Sun Yat-sen University Cancer Center, were retrospectively analyzed. There were 1 402 males and 644 females, aged (M(IQR)) 51 (19) years (range: 6 to 86 years). The primary end point of this study was cancer-specific survival. Survival curves were estimated using the Kaplan-Meier method, and the difference test was performed by Log-rank test. Univariate and multivariate Cox analysis were fitted to determine factors associated with cancer-specific survival. Results: The follow-up time was 49.2 (48.0) months (range: 1 to 229 months), with 1 974 patients surviving and 72 dying. The median cancer-specific survival time has not yet been reached. The 5- and 10-year cancer specific survival rates were 97.0% and 91.2%, respectively. The 10-year cancer-specific survival rates for stage pT1a (n=1 447), pT1b (n=523) and pT2 (n=58) were 95.3%, 81.8%, and 81.7%, respectively. The 10-year cancer-specific survival rates of patients with nuclear grade 1 (n=226), 2 (n=1 244) and 3 to 4 (n=278) were 96.6%, 89.4%, and 85.5%, respectively. There were no significant differences in 5-year cancer-specific survival rates among patients underwent open, laparoscopic, or robotic surgery (96.7% vs. 97.1% vs. 97.5%, P=0.600). Multivariate analysis showed that age≥50 years (HR=3.93, 95%CI: 1.82 to 8.47, P<0.01), T stage (T1b vs. T1a: HR=3.31, 95%CI: 1.83 to 5.99, P<0.01; T2+T3 vs. T1a: HR=2.88, 95%CI: 1.00 to 8.28, P=0.049) and nuclear grade (G3 to 4 vs. G1: HR=2.81, 95%CI: 1.01 to 7.82, P=0.048) were independent prognostic factors of localized renal cell carcinoma after partial nephrectomy. Conclusions: The long-term cancer-specific survival rates of patients with localized renal cancer after partial nephrectomy are satisfactory. The type of operation (open, laparoscopic, or robotic) has no significant effect on survival. However, patients with older age, higher nuclear grade, and higher T stage have a lower cancer-specific survival rate. Grasping surgical indications, attaching importance to preoperative evaluation, perioperative management, and postoperative follow-up, could benefit achieving satisfactory long-term survival.