Human umbilical cord mesenchymal stem cell （hUC-MSC） as a cell-based therapeutic strategy have demonstrated significant application potential in the field of intervention for neurodegenerative disease （NDD） due to their advantages such as self-renewal， multi-directional differentiation， and low immunogenicity. hUC-MSC effectively intervenes in the pathological features and neurological functions of various disease models such as Alzheimer disease， Parkinson’s disease， amyotrophic lateral sclerosis， and multiple sclerosis primarily through multiple mechanisms such as homing and differentiation， mediating paracrine actions and releasing exosomes， as well as immune regulation and anti-inflammation. Some clinical studies have also preliminarily verified their safety and effectiveness. Currently， its research still faces challenges such as immune rejection reactions requiring further observation， long-term safety needing evaluation， mechanisms of action not being fully elucidated， and slow progress in clinical trials. Future research needs to establish pharmaceutical standards for hUC-MSC， deepen their pharmacological mechanisms and clinical trials， ultimately providing new and effective drug treatment options for patients with NDD.

OBJECTIVE To draw upon the United States’ experience in charging for drug dispensing services and provide reference for designing China’s fee scheme for such services. METHODS Relevant literature and official websites were reviewed to systematically summarize the evolution of dispensing fees in the U.S.， charging methods and standards across different health insurance plans， and factors influencing fee determination. The key characteristics of the U.S. fee system were summarized. Recommendations for improving China’s related practices were then proposed. RESULTS & CONCLUSIONS The U.S. dispensing fee system has undergone four stages of conceptual emergence， model exploration， system establishment， and professional development， forming a prescription-based charging model independent of drug prices. Under a unified federal framework， health insurance programs set a differentiated dispensing fee system based on actual costs and factors such as drug category， pharmacy type， prescription volume， and policy objectives， reflecting pharmacists’ professional value and ensuring sustainable service provision. Although China has recognized dispensing fees at the national level， implementation still faces barriers including insufficient value recognition and pressure on medical insurance payment. Drawing on U.S. experience and considering China’s national context， it is recommended to strengthen empirical research on the value assessment of dispensing services to support medical insurance decision-making； standardize the methodology for dispensing cost measurement and clarify the basis for fee setting by incorporating pharmacists’ professional and technical value as well as public interests； explore differentiated charging models at the provincial level with prescriptions as the basic unit， with emphasis on professional expertise and dispensing risks， and continuously strengthen pharmacists’ professional capacity to facilitate the scientific formulation and effective implementation of dispensing service fee policies.

Background and aims:Hepatocellular carcinoma(HCC)is a leading cause of cancer-related mortality worldwide,and its etiology involves a complex interplay of genetic and environmental factors.Despite ad-vancements in our understanding of HCC biology and the development of novel therapeutic strategies,the molecular mechanisms underlying its onset,progression,and resistance to therapy remain largely vague.This study aimed to investigate the role of mechanosensitive ion channel-related genes(MICRGs)in HCC,focusing on their potential as prognostic biomarkers and their involvement in immune modulation and drug resistance.Methods:A comprehensive analysis was conducted using The Cancer Genome Atlas database to identify MICRGs that are upregulated in HCC.Gene expression profiling,bioinformatics tools,and functional experiments were employed to elucidate the role of these channels.In addition,protein-protein interaction(PPI)network analyses and enrichment analyses were performed to explore the biological significance of these genes.An immune cell infiltration analysis was also conducted to understand MICRG-related immune landscape.Single-cell RNA sequencing(scRNA-seq)data were utilized to identify MICRGs in different cell types within the HCC tissue.Deep-learning neural network analysis across patient cohorts was conducted to identify genes associated with sorafenib resistance.Knockdown ex-periments,cell viability assays,and apoptosis assays on HCC cell lines were performed to examine the role of Piezo-type mechanosensitive ion channel component 1(PIEZO1)in sorafenib resistance.Results:The analysis identified a subset of MICRGs,including PIEZO1,that were significantly upregulated in HCC and associated with poor prognosis.The PPI network analysis revealed complex interactions among these genes.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses proposed the involvement of these genes in calcium signaling pathways.Immune cell infiltration analysis demonstrated distinct associations between MICRGs and various immune subpopulations,highlighting their potential roles in immune modulation.scRNA-seq data indicated the upregulation of MICRGs in various cell types in HCC tissues,particularly in endothelial cells and tumor-associated macrophages.Deep-learning neural network analysis across different patient cohorts identified PIEZO1 as a crucial regulator of sorafenib resistance in HCC,which was further validated by functional assays on HCC cell lines.Conclusions:This study provides evidence that MICRGs,particularly PIEZO1,take on crucial roles in HCC progression and drug resistance.The upregulation of PIEZO1 in HCC cells is associated with poor prog-nosis and resistance to sorafenib.These findings indicate that PIEZO1 could serve as a potential thera-peutic target for overcoming drug resistance and a prognostic biomarker in HCC.Future studies should focus on validating these findings in larger patient cohorts and exploring the functional implications of targeting PIEZO1 in preclinical models.

ObjectiveTo investigate the influencing factors for traditional Chinese medicine （TCM） syndromes of primary liver cancer， and to provide a theoretical basis for the TCM syndrome differentiation and standardized treatment of liver cancer. MethodsTCM syndrome differentiation was performed for 415 patients who were admitted to Shanxi Institute of Traditional Chinese Medicine and were diagnosed with primary liver cancer based on pathological or clinical examinations from January 2019 to December 2023. The chi-square test was used for comparison of categorical data between groups， and the unordered polytomous logistic regression model was used to investigate the influencing factors for TCM syndromes of liver cancer. ResultsThe common initial symptoms of the 415 patients with primary liver cancer included pain in the liver area （31.81%）， abdominal distension （25.30%）， abdominal pain （15.18%）， and weakness （13.98%）， and the main clinical symptoms included poor appetite （70.84%）， fatigue （69.16%）， pain in the liver area （67.47%）， poor sleep （59.04%）， abdominal distension （53.01%）， and constipation （52.53%）. There were significant differences in TCM syndromes between patients with different sexes， courses of the disease， clinical stages， Child-Pugh classes， presence or absence of intrahepatic and extrahepatic metastasis， and presence or absence of transcatheter arterial chemoembolization （TACE） and radiofrequency ablation （all P<0.05）. The logistic regression analysis showed that male sex was a risk factor for damp-heat accumulation （odds ratio ［OR］=2.036， P=0.048） and the syndrome of spleen-kidney Yang deficiency （OR=5.240， P<0.001）； a course of disease of<1 year was a risk factor for damp-heat accumulation （OR=2.837， P=0.004） and syndrome of Qi stagnation and blood stasis （OR=2.317， P=0.021）， but it was a protective factor against syndrome of spleen-kidney Yang deficiency （OR=0.385， P=0.005）； Child-Pugh class A/B was a protective factor against liver-kidney Yin deficiency （OR=0.079， P<0.001）； intrahepatic metastasis was a risk factor for liver-kidney Yin deficiency （OR=5.117， P=0.003） and syndrome of spleen-kidney Yang deficiency （OR=3.303， P=0.010）； TACE was a protective factor against liver-kidney Yin deficiency （OR=0.171， P<0.001） and syndrome of spleen-kidney Yang deficiency （OR=0.138， P<0.001）； radiofrequency ablation was a risk factor for damp-heat accumulation （OR=4.408， P<0.001） and liver-kidney Yin deficiency （OR=32.036， P<0.001）. ConclusionSex， course of disease， Child-Pugh class， intrahepatic metastasis， TACE， and radiofrequency ablation are the main influencing factors for TCM syndromes of liver cancer.

ObjectiveTo investigate the influencing factors for traditional Chinese medicine （TCM） syndromes in pancreatic cancer by analyzing 608 cases， and to provide a theoretical reference for TCM syndrome differentiation and standardized treatment of pancreatic cancer. MethodsA total of 608 patients with a pathological or clinical diagnosis of pancreatic cancer who were admitted to Shanxi Institute of Traditional Chinese Medicine， The Affiliated Hospital of Shanxi University of Chinese Medicine， and Shanxi Provincial Hospital of Integrated Traditional Chinese and Western Medicine from January 2019 to December 2023 were enrolled， and TCM syndrome differentiation was performed. The chi-square test was used for comparison of categorical data between groups. The clinical data with statistical significance between groups were included in the regression analysis， and the unordered polytomous logistic regression model was used to investigate the influencing factors for the TCM syndrome of pancreatic cancer. ResultsFor the 608 patients with pancreatic cancer， common initial symptoms included abdominal pain （32.40%）， abdominal distension （23.85%）， fatigue （16.12%）， and emaciation （10.03%）， and the main clinical symptoms included poor appetite （75.97%）， abdominal pain （67.27%）， fatigue （61.84%）， abdominal distension （57.40%）， and emaciation （53.62%）. There were significant differences between the patients with different TCM syndromes of pancreatic cancer in sex （χ²=62.823， P<0.001）， disease duration （χ²=14.868， P=0.011）， clinical stage （χ²=21.006， P<0.001）， lymph node metastasis （χ²=2.205， P=0.032）， surgery （χ²=38.008， P<0.001）， chemotherapy （χ²=21.384， P<0.001）， radiotherapy （χ²=17.510， P=0.004）， and immunotherapy （χ²=18.573， P=0.002）. The logistic regression analysis showed that male sex was a protective factor against Qi and blood deficiency syndrome （odds ratio ［OR］=0.081， 95% confidence interval ［CI］： 0.031‍ ‍—‍ ‍0.213， P<0.001）， Qi stagnation and blood stasis syndrome （OR=0.100， 95%CI： 0.041‍ ‍—‍ ‍0.247， P<0.001）， and syndrome of Yin deficiency with internal heat （OR=0.158， 95%CI： 0.057‍ ‍—‍ ‍0.444， P<0.001）， while it was a risk factor for the syndrome of damp-heat accumulation （OR=2.378， 95%CI： 1.074‍ ‍—‍ ‍5.266， P=0.033）； the course of the disease of<1 year was a protective factor against Qi and blood deficiency syndrome （OR=0.167， 95%CI： 0.073‍ ‍—‍ ‍0.383， P<0.001）， syndrome of spleen-kidney Yang deficiency （OR=0.183， 95%CI： 0.089‍ ‍—‍ ‍0.378， P<0.001）， and syndrome of Yin deficiency and internal heat （OR=0.164， 95%CI： 0.070‍ ‍—‍ ‍0.385， P<0.001）； clinical stage Ⅰ/Ⅱ/Ⅲ was a risk factor for damp-heat accumulation （OR=2.793， 95%CI： 1.259‍ ‍—‍ ‍6.196， P=0.012） and Qi stagnation and blood stasis syndrome （OR=7.863， 95%CI： 2.808‍ ‍—‍ ‍22.020， P<0.001）； lymph node metastasis was a risk factor for Qi and blood deficiency syndrome （OR=4.005， 95%CI： 1.477‍ ‍—‍ ‍10.861， P=0.006）； surgical treatment was a risk factor for Qi and blood deficiency syndrome （OR=4.151， 95%CI： 1.916‍ ‍—‍ ‍8.995， P<0.001）， syndrome of spleen-kidney yang deficiency （OR=5.352， 95%CI： 2.436‍ ‍—‍ ‍11.759， P<0.001）， Qi stagnation and blood stasis syndrome （OR=2.334， 95%CI： 1.071‍ ‍—‍ ‍5.088， P=0.033）， and syndrome of Yin deficiency and internal heat （OR=4.167， 95%CI： 1.789‍ ‍—‍ ‍9.707， P<0.001）； chemotherapy was a protective factor against damp-heat accumulation （OR=0.188， 95%CI： 0.082‍ ‍—‍ ‍0.428， P<0.001）； radiotherapy was a risk factor for damp-heat accumulation （OR=2.571， 95%CI： 1.151‍ ‍—‍ ‍5.746， P=0.021） and syndrome of Yin deficiency with internal heat （OR=8.384， 95%CI： 3.348‍ ‍—‍ ‍20.997， P<0.001）； immunotherapy was a risk factor for Qi and blood deficiency syndrome （OR=2.114， 95%CI： 1.021‍ ‍—‍ ‍4.379， P=0.044）. ConclusionSex， course of the disease， clinical stage， presence or absence of lymph node metastasis， surgery， chemotherapy， radiotherapy， and immunotherapy are the main influencing factors for the TCM syndrome of pancreatic cancer.

Objective To investigate the setup error in patients with spinal bone metastasis who underwent radiotherapy under the guidance of kilovoltage cone-beam CT (KV-CBCT). Methods A total of 118 patients with spinal metastasis who underwent radiotherapy, including 17 cases of cervical spine, 62 cases of thoracic spine, and 39 cases of lumbar spine, were collected. KV-CBCT scans were performed using the linear accelerators from Elekta and Varian’s EDGE system. CBCT images were registered with reference CT images in the bone window mode. A total of 973 data were collected, and 3D linear errors were recorded. Results The patients with spinal bone metastasis were grouped by site, height, weight, and BMI. The P value of the patients grouped only by site was P<0.05, which was statistically significant. Conclusion When grouped by site in the 3D direction, the positioning effect of cervical spine is better than that of thoracic and lumbar spine. The positioning effect of the thoracic spine is better in the head and foot direction but worse in the left and right direction compared with that of the lumbar spine. Instead of extending or narrowing the margin according to the BMI of patients with spinal metastasis, the margin must be changed according to the site of spinal bone metastasis.

Objective: To retrospectively analyze the prevalence of hepatitis C virus (HCV) infection among voluntary blood donors in Qinghai Province over a ten-year period and to provide evidence for refining blood safety screening strategies. Methods: Blood samples from 362 066 blood donors in Qinghai collected between January 2015 and April 2024 were simultaneously screened using enzyme-linked immunosorbent assay (ELISA) and nucleic acid testing (NAT). Follow-up was conducted for donors with reactive HCV RNA screening results, and alanine transaminase (ALT) was detected by rate method. Results: The HCV positive rate among blood donors in Qinghai was 0.22%. Gender, marital status, number of blood donations, and educational level were associated with HCV infection. Significant differences in HCV positive rates were observed among donors across regions and ethnic groups. The HCV positive rate among donors in Golog Tibetan Autonomous Prefecture (with an average altitude of 4 330 m) was significantly higher than that in Xining (0.52% vs 0.21%, P<0.001). Positivity rates were also significantly higher in Salar (0.84%), Hui (0.81%), Zang (0.60%), and Tu (0.45%) ethnic groups compared to the Han ethnic group (0.17%) (P<0.001). The abnormal rate of ALT in HCV-positive donors was higher than in non-HCV donors (6.13% vs 1.55%) (P<0.001). Conclusion: The relatively high HCV positivity rate among blood donors in Qinghai highlights the need for further investigation into viral sources, risk factors, and transmission routes. Optimized screening strategies are essential to ensure blood safety.

Cognitive impairment is a major public health challenge facing global aging societies， and currently lacks effective treatment measures. Herb pair， characterized by their rigorous compatibility and synergistic effects， demonstrate unique advantages in clinical practice. Acorus tatarinowii-Polygala tenuifolia is a classic herbal pair for treating cognitive impairment， widely utilized in various traditional Chinese medicine formulations， such as Kaixin san， Shenghui tang， and Yuanzhi san. This article summarizes the pharmacological mechanisms of A. tatarinowii， P. tenuifolia and their compatible compound prescriptions in ameliorating cognitive impairment. It is found that they can exert effects in ameliorating cognitive impairment through mechanisms such as reducing amyloid β-protein deposition and inhibiting excessive phosphorylation of Tau protein， suppressing inflammatory responses， alleviating oxidative stress， protecting neurons and regulating neurotransmitters， modulating the structure and function of the blood- brain barrier， and regulating autophagy. Subsequently， in-depth analysis can be conducted on the active ingredients of A. tatarinowii- P. tenuifolia herb pair that ameliorate cognitive impairment， along with the addition of relevant clinical trials for verification. This will provide theoretical foundations and research approaches for the treatment of cognitive impairment using traditional Chinese medicine.

OBJECTIVES: To explore the mechanism by which astragaloside IV (AS-IV) alleviates D-galactose (D-GAL)-induced senescence in human umbilical vein endothelial cells (HUVECs). METHODS: Cultured HUVECs were treated with D-GAL (40 g/L), AS-IV (200 μmol/L), D-GAL+AS-IV, or D-GAL+AS-IV+MTK458 (a mitochondrial autophagy agonist, 25 μmol/L) for 48 h, and the changes in cell proliferation, migration, and angiogenesis capacity were evaluated. Cell apoptosis, reactive oxygen species (ROS) levels, mitochondrial membrane potential, and expressions of autophagy-related proteins (LC3-II/LC3-I) and PINK1/Parkin pathway proteins in the treated cells were detected. RESULTS: AS-IV treatment significantly reduced the inhibitory effect of D-GAL on HUVEC viability, effectively alleviated D-GAL-induced impairment of tube-forming ability, and promoted angiogenesis and migration ability of the cells. AS-IV also significantly reduced the rate of D-GAL-induced HUVECs positive for senescence-associated β-galactosidase (SA-β-Gal) staining and inhibited the expression of senescence-related genes P21 and P53. AS-IV restored mitochondrial membrane potential and reduced intracellular ROS levels in D-GAL-induced HUVECs, and inhibited the fusion of autophagosomes and lysosomes to prevent the completion of autophagic flux. In HUVECs treated with both D-GAL and AS-IV, the application MTK458 significantly increased the number of yellow spots and enhanced the expressions of P21, P53, PINK1, Parkin, LC3, and Beclin proteins. CONCLUSIONS AS-IV alleviates D-GAL-induced endothelial cell senescence by inhibiting the PINK1/Parkin pathway to regulate mitochondrial autophagy.
Humans ; Human Umbilical Vein Endothelial Cells/drug effects* ; Cellular Senescence/drug effects* ; Autophagy/drug effects* ; Saponins/pharmacology* ; Ubiquitin-Protein Ligases/metabolism* ; Mitochondria/drug effects* ; Triterpenes/pharmacology* ; Protein Kinases/metabolism* ; Galactose/pharmacology* ; Reactive Oxygen Species/metabolism* ; Signal Transduction/drug effects* ; Cells, Cultured ; Apoptosis/drug effects* ; Membrane Potential, Mitochondrial ; Cell Proliferation/drug effects*

ObjectiveTo explore the potential mechanism by which Huangqi Baijiang Yiren decoction （HBY） repairs the intestinal mucosal injury in the rat model of ulcerative colitis （UC） via the miR-21/suppressor of cytokine signaling 1 （SOCS1）/Janus kinase 1 （JAK1）/signal transducer and activator of transcription 6 （STAT6） signaling pathway. MethodsSixty SPF-grade male SD rats were randomly assigned into six groups： blank， model， low-dose （3.68 g·kg^-1） HBY， medium-dose （7.35 g·kg^-1） HBY， high-dose （14.5 g·kg^-1） HBY， and mesalazine （0.035 g·kg^-1）， with 10 rats in each group. The rat model of UC was established in other groups except the blank group by 3% dextran sulfate sodium solution. The rats were administrated with corresponding drugs once a day for 7 consecutive days since the 3th day after modeling. The histopathological changes of the colon were observed by hematoxylin-eosin staining， and the Robarts histopathology index （RHI） was scored. Enzyme-linked immunosorbent assay was employed to measure the levels of pro-inflammatory cytokines ［interleukin （IL）-6， IL-18， IL-1β， and tumor necrosis factor-α （TNF-α）］ in the serum. Real-time PCR was employed to determine the mRNA levels of miR-21， SOCS1， JAK1， and STAT6 in the colon tissue. Western blot was employed to determine the protein levels of SOCS1， JAK1， phosphorylated （p）-JAK1， STAT6， p-STAT6， Occludin， and Claudin-1 in the colon tissue. ResultsCompared with the blank group， the model group showed an increase in disease activity index （DAI） （P<0.01）， shortening of colon length （P<0.01）， severe histopathological damage in the colon tissue， and an increase in RHI， rises in serum levels of IL-6， IL-1β， IL-18， and TNF-α （P<0.01）， up-regulation in mRNA levels of miR-21， JAK1， and STAT6 and protein levels of p-JAK1 and p-STAT6 （P<0.01）， and down-regulation in mRNA and protein levels of SOCS1 and protein levels of Occludin and Claudin-1 （P<0.01）. The treatment with HBY reduced the DAI （P<0.01）， alleviated colon shortening and histopathological damage in the colon tissue， decreased the RHI （P<0.01）， lowered the serum levels of IL-6， IL-1β， IL-18， and TNF-α （P<0.01）， down-regulated the mRNA levels of miR-21， JAK1， and STAT6 （P<0.05， P<0.01）， up-regulated the mRNA level of SOCS1 （P<0.05）， up-regulated the protein levels of SOCS1， Occludin， and Claudin-1 （P<0.05， P<0.01）， and down-regulated the protein levels of p-JAK1 and p-STAT6 （P<0.05， P<0.01）. ConclusionHBY may modulate the miR-21/SOCS1/JAK1/STAT6 signaling pathway to suppress inflammatory responses and restore the intestinal mucosal barrier in UC rats.