Fibrosis, the pathological scarring of vital organs, is a severe and often irreversible condition that leads to progressive organ dysfunction. It is particularly pronounced in organs like the liver, kidneys, lungs, and heart. Despite its clinical significance, the full understanding of its etiology and complex pathogenesis remains incomplete, posing substantial challenges to diagnosing, treating, and preventing the progression of fibrosis. Among the various molecular players involved, platelet-derived growth factor-C (PDGF-C) has emerged as a crucial factor in fibrotic diseases, contributing to the pathological transformation of tissues in several key organs. PDGF-C is a member of the PDGFs family of growth factors and is synthesized and secreted by various cell types, including fibroblasts, smooth muscle cells, and endothelial cells. It acts through both autocrine and paracrine mechanisms, exerting its biological effects by binding to and activating the PDGF receptors (PDGFRs), specifically PDGFRα and PDGFRβ. This binding triggers multiple intracellular signaling pathways, such as JAK/STAT, PI3K/AKT and Ras-MAPK pathways. which are integral to the regulation of cell proliferation, survival, migration, and fibrosis. Notably, PDGF-C has been shown to promote the proliferation and migration of fibroblasts, key effector cells in the fibrotic process, thus accelerating the accumulation of extracellular matrix components and the formation of fibrotic tissue. Numerous studies have documented an upregulation of PDGF-C expression in various fibrotic diseases, suggesting its significant role in the initiation and progression of fibrosis. For instance, in liver fibrosis, PDGF-C stimulates hepatic stellate cell activation, contributing to the excessive deposition of collagen and other extracellular matrix proteins. Similarly, in pulmonary fibrosis, PDGF-C enhances the migration of fibroblasts into the damaged areas of lungs, thereby worsening the pathological process. Such findings highlight the pivotal role of PDGF-C in fibrotic diseases and underscore its potential as a therapeutic target for these conditions. Given its central role in the pathogenesis of fibrosis, PDGF-C has become an attractive target for therapeutic intervention. Several studies have focused on developing inhibitors that block the PDGF-C/PDGFR signaling pathway. These inhibitors aim to reduce fibroblast activation, prevent the excessive accumulation of extracellular matrix components, and halt the progression of fibrosis. Preclinical studies have demonstrated the efficacy of such inhibitors in animal models of liver, kidney, and lung fibrosis, with promising results in reducing fibrotic lesions and improving organ function. Furthermore, several clinical inhibitors, such as Olaratumab and Seralutinib, are ongoing to assess the safety and efficacy of these inhibitors in human patients, offering hope for novel therapeutic options in the treatment of fibrotic diseases. In conclusion, PDGF-C plays a critical role in the development and progression of fibrosis in vital organs. Its ability to regulate fibroblast activity and influence key signaling pathways makes it a promising target for therapeutic strategies aiming at combating fibrosis. Ongoing research into the regulation of PDGF-C expression and the development of PDGF-C/PDGFR inhibitors holds the potential to offer new insights and approaches for the diagnosis, treatment, and prevention of fibrotic diseases. Ultimately, these efforts may lead to the development of more effective and targeted therapies that can mitigate the impact of fibrosis and improve patient outcomes.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

BACKGROUND:The self-renewal and multi-directional differentiation of pluripotent stem cells possess the potential to revolutionize people's understanding of biology,medicine,development,and disease.Stem cells play an important role in the early stage of embryonic development,and the study of them could be beneficial to understanding of the basic principles of biological development and tissue or organ formation,exploring the potential mechanisms of various diseases,studying the repair and regeneration of damaged tissues or organs,and promoting drug discovery and personalized treatment. OBJECTIVE:To review the research progress of pluripotent stem cells,summarize and categorize the fundamental types of pluripotent stem cells,and elucidate the lineage situations of various types of pluripotent stem cells in common mammals. METHODS:PubMed,Web of Science,CNKI,and WanFang databases were searched systematically,with the keywords"pluripotent stem cells;embryonic stem cells;induced pluripotent stem cells;expanded potential stem cells;livestock pluripotent stem cells"in English and Chinese.The 99 articles related to mammalian pluripotent stem cells were systematically screened according to inclusion and exclusion criteria,and then reviewed. RESULTS AND CONCLUSION:(1)According to classical theory in mouse embryonic stem cell research,the pluripotent state of stem cells is divided into two forms:na?ve and primed.Na?ve state corresponds to the inner cell mass of pre-implantation embryos before attachment to the uterine wall,while primed state corresponds to the epiblast after implantation.These two states exhibit significant differences in epigenetic features,transcriptional activity,external signal dependency,and metabolic phenotype.It is later discovered that there is an intermediate state between na?ve and primed called formative pluripotency.Therefore,the pluripotency of pluripotent stem cells is a continuous developmental process rather than a unique cell state.(2)In addition to obtaining pluripotent stem cells from the inner cell mass,there are various methods and lineages for acquiring pluripotent stem cells,including embryonic germ cells established using primitive germ cells from mouse embryos,induced pluripotent stem cells created by the dedifferentiation of adult mouse and human fibroblasts with four factors—Oct3/4,Sox2,c-Myc,and Klf4;embryonic stem cell-like cell lines cultured from somatic cell nuclear transfer,parthenogenesis,neonatal or adult testicular or ovarian tissue,very small embryonic-like stem cells derived from various adult tissues and expanded pluripotent stem cells derived from pre-implantation stages.These pluripotent stem cells all share the common characteristics of continuous self-renewal,expressing core pluripotency factors and possessing the ability to differentiate into the three primary germ layers.(3)Currently,pluripotent stem cells are being used for disease modeling to study the mechanisms of various diseases and develop new drugs.Simultaneously,scientists are attempting to use pluripotent stem cells to cultivate various tissues and organs,offering new possibilities for regenerative medicine and transplantation.However,the clinical application of pluripotent stem cells faces safety challenges,including issues of cell mutations and immune rejection.Continual improvement in the methods of generating pluripotent stem cells will make them safer and more efficient for clinical applications.(4)Based on the methods of obtaining and lineage establishment of pluripotent stem cells in mice and humans,various types of pluripotent stem cells have been established in livestock,including embryonic stem cells,induced pluripotent stem cells,germ lineages of pluripotent stem cells,and expanded potential stem cells.Research on livestock pluripotent stem cells opens up new avenues for animal reproduction,breeding,genetic engineering,disease modeling,drug screening,and the conservation of endangered wildlife.

ObjectiveStudies have shown that nuciferine has anti-cerebral ischemia effect， but the specific mechanism of action has not been elaborated. Based on the transcriptome results， the pharmacological mechanism of nuciferine against cerebral ischemia was analyzed from multiple dimensions including tissue， cell， pathological process， biological process and signaling pathway. MethodsThirty SD rats were randomly divided into the sham group， model group and nuciferine group（40 mg·kg^-1） according to weight. Except for the sham group， the model of middle cerebral artery occlusion（MCAO） was established by thread embolization method after 30 min of administration in the other two groups. Twenty-four hours after surgery， transcriptome sequencing was used to detect the gene expression profiles in the cortex penumbra of rat cerebral tissue， and gene ontology（GO） and kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis were performed for differentially expressed genes. The mechanismof nuciferine against cerebral ischemia was analyzed from 5 dimensions of tissue， cell， pathological process， biological process and signaling pathway by the transcriptome-based multi-scale network pharmacology platform（TMNP）. ResultsTranscriptome sequencing and gene quantitative analysis showed that 667 genes were significantly reversed by nuciferine. Further enrichment analysis of KEGG and GO suggested that the pathways of nuciferine involved regulating stress response， ion transport， cell proliferation and differentiation， and synaptic function. TMNP research found that at the tissue level， nuciferine could significantly improve the cerebral tissue injury caused by ischemia. At the cellular and pathological levels， nuciferine could play an anti-cerebral ischemia role by improving the state of various nerve cells， mobilizing immune cells， regulating inflammation. And at the level of biological processes and signaling pathways， nuciferine mainly acted on the processes such as vascular remodeling， inflammation-related signaling pathways， and synaptic signaling. ConclusionCombined with the results of transcriptome sequencing， gene quantitative analysis and TMNP， the mechanism of nuciferine against cerebral ischemia may be related to processes such as intervening in stress response and inflammation， affecting vascular remodeling and regulating synaptic function. These results can provide a basis and reference for further study of the pharmacological mechanism of nuciferine against cerebral ischemia.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

ObjectiveTo explore the molecular mechanism of aerobic exercise to improve hippocampal neuronal degeneration by regulating tryptophan metabolic pathway. Methods60 SPF-grade C57BL/6J male mice were divided into a young group (2 months old, n=30) and a senile group (12 months old, n=30), and each group was further divided into a control group (C/A group, n=15) and an exercise group (CE/AE group, n=15). An aerobic exercise program was used for 8 weeks. Learning memory ability was assessed by Y-maze, and anxiety-depression-like behavior was detected by absent field experiment. Hippocampal Trp levels were measured by GC-MS. Nissl staining was used to observe the number and morphology of hippocampal neurons, and electron microscopy was used to detect synaptic ultrastructure. ELISA was used to detect the levels of hippocampal Trp,5-HT, Kyn, KATs, KYNA, KMO, and QUIN; Western blot was used to analyze the activities of TPH2, IDO1, and TDO enzymes. ResultsGroup A mice showed significant decrease in learning and memory ability (P<0.05) and increase in anxiety and depressive behaviors (P<0.05); all of AE group showed significant improvement (P<0.05). Hippocampal Trp levels decreased in group A (P<0.05) and increased in AE group (P<0.05). Nidus vesicles were reduced and synaptic structures were degraded in group A (P<0.05), and both were significantly improved in group AE (P<0.05). The levels of Trp, 5-HT, KATs, and KYNA were decreased (P<0.05) and the levels of Kyn, KMO, and QUIN were increased (P<0.05) in group A. The activity of TPH2 was decreased (P<0.05), and the activities of IDO1 and TDO were increased (P<0.05). The AE group showed the opposite trend. ConclusionThe aging process significantly reduces the learning memory ability and increases the anxiety-depression-like behavior of mice, and leads to the reduction of the number of nidus vesicles and degenerative changes of synaptic structure in the hippocampus, whereas aerobic exercise not only effectively enhances the spatial learning memory ability and alleviates the anxiety-depression-like behavior of aging mice, but also improves the morphology and structure of neurons in hippocampal area, which may be achieved by the mechanism of regulating the tryptophan metabolic pathway.

Hepatocellular carcinoma （HCC）， as the sixth most common malignant tumor worldwide， poses a serious threat to human health due to its insidious onset and high mortality rate. This article reviews the molecular mechanisms and intervention strategies of gut microbiota （GM） homeostasis in the development and progression of HCC， in order to provide new ideas for the intervention and treatment of HCC. Studies have shown that GM dysbiosis， intestinal leakage， microbial-associated molecular pattern， bacterial translocation， and metabolic products play key roles in the progression of HCC. GM imbalance may lead to immune escape， thereby promoting tumor cell proliferation and metastasis. This article elaborates on the association between GM and HCC， deeply analyzes the mechanism of action of GM in the development and progression of HCC， investigates the role of bile acid-related metabolites， short-chain fatty acid-related metabolites， and other metabolites in HCC， and explores the strategies for targeting GM in the treatment of HCC， including probiotics， prebiotics， antibiotics， Toll-like receptor 4 antagonists， and fecal microbiota transplantation. This article emphasizes that maintaining the integrity of the intestinal barrier and GM homeostasis is of great significance in the prevention and treatment of HCC， which provides a direction for developing new diagnosis and treatment strategies.

Objective To establish radioresistant human non-small cell lung cancer NCI-H460R model cells and evaluate the sensitivity of these radioresistant cells to a ferroptosis inducer. Methods Radioresistant cell lines, designated as NCI-H460 R20Gy and NCI-H460 R116Gy, were generated by subjecting parental NCI-H460 cells to fractionated irradiation with varying cumulative doses. Both parental cells and the established radioresistant cell lines were each randomly divided into four groups and exposed to irradiation at 0, 2, 4, and 6 Gy, respectively. Successful establishment of the radioresistant cell lines was confirmed by colony formation assay. Subsequently, cells were treated with increasing concentrations of the ferroptosis inducer RSL-3 to assess differential sensitivity between parental and radioresistant cells to ferroptosis. Results In comparison to the parental NCI-H460 cells (D_0WT=1.2), both NCI-H460 R116Gy and NCI-H460 R20Gy cells exhibited radioresistance, with NCI-H460 R116Gy demonstrating a stronger radioresistance (D_0R116Gy=1.5) than NCI-H460 R20Gy (D_0R20Gy=1.4). Furthermore, NCI-H460 R116Gy cells exhibited increased sensitivity to RSL-3 relative to the parental cells (P < 0.001), while NCI-H460 R20Gy cells did not display a significant difference in sensitivity to RSL-3. Conclusion Human non-small cell lung cancer cells with radioresistance induced by a high cumulative irradiation dose exhibit increased sensitivity to the glutathione peroxidase 4-specific ferroptosis inducer RSL-3. This finding provides an experimental basis for optimizing combined treatment regimens involving radiotherapy and RSL-3 for non-small cell lung cancer patients with radiotherapy resistance.

Objective To carry out a proficiency testing of content determination of geniposide in Gardeniae fructus,evaluate the content determination ability of index components in traditional Chinese medicine in the laboratory of inspection and detection in drug-related fields,and improve the quality control ability of content determination of related laboratories.Methods The laboratory's capability-verification activities were conducted based on the CNAS-RL02 Rules for Proficiency Testing and ISO/IEC 17043 Conformity Assessment-General Requirements for Proficiency Testing.After preparing the sample,the results of homogeneity and stability tests were analyzed according to CNAS-GL003 Guidance on Evaluating the Homogeneity and Stability of Samples Used for Proficiency Testing.After the test results were qualified,they were used as proficiency testing samples and randomly distributed to participants.The results were collected,and the robust statistical method and the Z scores were used to analyze the results of these laboratories'reports.Results 403 laboratories in this proficiency testing program reported the results,of which 367 results were acceptable,accounting for 91.07％,17(4.22％)laboratories obtained suspicious results,and 19 laboratories gave unsatisfactory results,with the dissatisfaction rate of 4.71％.Conclusion The majority of the 403 participant laboratories have the ability to determine the content of geniposide in Gardeniae fructus by HPLC and the laboratory testing ability and quality management level of the drug monitoring system are high.This proficiency testing provides a basis for understanding the technical reserve capacity and management level of China's pharmaceutical inspection and testing laboratories,and provides technical support for future government supervision.