This study aimed to investigate the mechanism of liquiritin (LQ) in the improvement of ventricular remodeling (VR) after acute myocardial infarction (AMI). Molecular docking was used to predict the binding affinity of liquiritin to thioredoxin-interacting protein (TXNIP). After 2 weeks of modeling, the rats were randomly divided into a model group, a low-dose liquiritin group (20 mg/kg LQ), and a high-dose liquiritin group (40 mg/kg LQ). Liquiritin was administered by gavage once a day, and the sham group and model group were given the same volume of 0.5% sodium carboxymethylcellulose (CMC-Na), with intervention of 4 consecutive weeks. Echocardiography was employed to detect the cardiac function, HE staining was used to observe cardiological changes, ELISA was used to detect the activity of serum creatine kinase-MB (CK-MB) activity, and the colorimetric method was adopted to detect serum malondialdehyde (MDA), total superoxide dismutase (T-SOD) and catalase (CAT) activities. RT-qPCR was used to detect the gene expressions of TXNIP, thioredoxin (TRX) and NACHT, LRR, and PYD domains-containing protein 3(NLRP3). Western blot was used to detect the protein expressions of TXNIP, TRX and NLRP3 in rat myocardial tissue. Molecular docking results showed that liquiritin had a good binding affinity to TNXIP target. After 20 and 40 mg/kg liquiritin intervention, the levels of ejection fraction (EF) and fractional shortening (FS) were significantly increased (P<0.01), and the levels of LVIDs, LVIDd, LVESV, and LVEDV were decreased (P<0.01). The myocardial structure was significantly improved, the cell arrangement tended to be regular, and the area of inflammatory cell infiltration and necrosis was reduced. Liquiritin significantly reduced the level of CK-MB (P<0.01), decreased the activity of MDA, and increased the activities of CAT and T-SOD (P<0.01). Liquiritin effectively inhibited the overexpression of TXNIP and NLRP3 genes and proteins, and enhanced the expression of TRX genes and proteins in the myocardial tissues of AMI rats. In conclusion, liquiritin has a regulatory effect on the TXNIP/TRX signaling pathway, inhibits the activation of the NLRP3 inflammasome, and thus improves ventricular remodeling after acute myocardial infarction.

Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

The digitization of traditional Chinese medicine (TCM) has generated vast amounts of data. However, these data are characterized by significant heterogeneity and complex semantic structures, posing substantial challenges for systematic integration and intelligent analysis, and limiting its potential for modern clinical and computational research. To address the challenges posed by the high heterogeneity and complex structure in TCM data, we designed and developed the TCM Data Hub platform, which is powered by the YiYuan large language models (LLMs). This platform aims to enhance intelligent data processing capabilities and unlock the potential for clinical application of TCM data through systematic integration and efficient utilization, thereby bridging the gap between traditional knowledge and modern computational research. This study first analyzed the heterogeneity and complexity of TCM information with respect to data types, structures, and semantics. A standardized data framework was constructed to enhance data integration and interoperability. Based on the TCM Intelligent Computing Platform of the China Academy of Chinese Medical Sciences, we trained the YiYuan LLMs to acquire domain-specific semantic understanding of TCM, thereby improving the platform’s comprehension of specialized terminology and knowledge systems. Leveraging the natural language processing capabilities of the LLMs, we developed a human-in-the-loop data processing system to enable efficient extraction, cleansing, and structured organization of TCM data. In addition, utilizing Vue and Java technologies, we developed multiple LLM-powered intelligent agents and systems, including a human-in-the-loop data processing system, as well as automated prescription mining and network pharmacology analysis agents. Task-specific agents tailored to TCM data processing were developed to enhance the model’s effectiveness in clinical knowledge discovery. System functionality and platform infrastructure were implemented using Java and Vue technologies.The TCM Data Hub platform has completed system construction and core functionality implementation. It supported integrated management and efficient access to 8 key types of TCM data: prescriptions, materia medica, ingredients, targets, diseases (Western medicine), diseases (TCM), syndromes, and therapeutic methods. The human-in-the-loop data processing system achieved an accuracy of 95.34% in structuring TCM data and supported annotation for data requiring manual labeling. The intelligent agent-driven big-data analytics module enabled 1-click, end-to-end workflows for TCM prescription mining, herb-syndrome association analysis, network pharmacology, and molecular biology research, completing a full data mining task in approximately 30 minutes. Users can interact with and manipulate data through a visual front-end interface. The system demonstrated stable performance, strong scalability, and a user-friendly experience. Empowered by the YiYuan LLMs, the TCM Data Hub platform significantly improves the accessibility, usability, and intelligence of TCM data. It effectively bridges traditional TCM knowledge with modern intelligent technologies, providing robust data support and intelligent tools for TCM research and clinical applications.

OBJECTIVE To establish the UPLC fingerprint and the method for multi-component content determination in Jingangteng capsules， and to evaluate its quality by combining chemical pattern recognition analysis. METHODS An UPLC method was established. Separation was performed on a Zorbax SB-C 18 Rapid Resolution HD column， with acetonitrile-0.1% formic acid as the mobile phase for gradient elution.Using the Similarity Evaluation System for Chromatographic Fingerprints of Traditional Chinese Medicines （2012 edition）， UPLC fi ngerprints were established for 10 batches of Jingangteng capsules， and similarity was evaluated. SPSS 22.0 and SIMCA 14.1 software were used to perform hierarchial-cluster analysis and orthogonal partial least squares discriminant analysis （OPLS-DA）， respectively. The same UPLC method was employed to determine the contents of chlorogenic acid， 3，5-dihydroxy-2-methylbenzoic acid-3- O -glucoside （M1）， caffeic acid， astilbin， oxyresveratrol， quercitrin and resveratrol in the 10 batches of samples. RESULTS A total of 17 common peaks were identified in UPLC fingerprints of the 10 batches of samples， of which 7 were identified as chlorogenic acid， M1， caffeic acid， astilbin， oxyresveratrol， quercitrin， and resveratrol. The similarities of 10 batches of samples ranged from 0.820 to 0.985. The results of hierarchial-cluster analysis showed that 10 batches of samples were grouped into four categories： S1-S4 formed one group， S5 and S6 formed another， S7， S8 and S10 formed a third， and S9 formed a fourth， consistent with the OPLS-DA results； the variable importance projection values for peaks 7， 10， 2， 16 （resveratrol）， 13 （oxyresveratrol）， 11， 6 （caffeic acid）， 5 （M1） and 15 （quercitrin） were ＞1. Quantitative analysis results showed that the contents of chlorogenic acid， M1， caffeic acid， astilbin， oxyresveratrol， quercitrin， and resveratrol were 1.650 8-4.213 7， 0.636 2-2.161 7， 0.031 0-0.086 5， 0.239 1-1.069 3， 0.211 9-1.104 0， 0.488 8-2.399 2， and 0.164 0-0.699 8 mg/g， respectively. CONCLUSIONS UPLC fingerprint and content determination methods established in this study are simple to operate， accurate， reliable and reproducible； when combined with chemical pattern recognition analysis， they can be used to evaluate the quality of Jingangteng capsules. Nine components， such as resveratrol， oxyresveratrol， caffeic acid， M1 and quercitrin， may serve as markers of quality variation.

ObjectiveTo investigate the role of interleukin （IL）-17A in acute inhalational pneumonia induced by the highly drug-resistant and hypervirulent Staphylococcus aureus strain USA300-R in mice. MethodsAn acute inhalational pneumonia model was established in mice using an aerosolized pulmonary delivery technique. RNA sequencing （RNA-seq） and enzyme-linked immunosorbent assay （ELISA） were employed to examine the expression dynamics of Il17a mRNA and IL-17A protein， respectively， in the lungs of infected mice. Il17a knockout （Il17a^-/-） mice were generated using CRISPR/Cas9 gene editing technology. The survival rate， body weight， bacterial load in lung tissue， and histopathological changes were compared between Il17a^-/- and wild-type （WT） mice following inhalational infection with USA300-R. Results12 hours after USA300-R infection， compared to pre-infection， the expression level of Il17a mRNA in lung tissue and the level of IL-17A protein in bronchoalveolar lavage fluid （BALF） increased by approximately 50-fold （P<0.01） and 6-fold （P<0.001）， respectively. Compared to WT mice， Il17a^-/- mice exhibited approximately 10-fold higher bacterial loads in lung tissue at both 12 and 24 hours post-infection （P<0.001， P<0.05）. However， they showed significantly attenuated lung histopathological injury， reduced alveolar wall thickening， markedly decreased neutrophil infiltration， and an approximately 50% improvement in survival rate （P<0.05）. ConclusionIn acute Staphylococcus aureus USA300-R inhalational pneumonia， IL-17A contributes to bacterial clearance by recruiting neutrophils； however， excessive neutrophil infiltration exacerbates pulmonary inflammation and injury， reduces survival rates， and represents a potential therapeutic target.

ObjectiveTo explore the effects and mechanism of the modified Danggui Yinzi on "itch-anxiety" model rats of chronic urticaria （CU）. MethodsThe 36 SPF-grade 6-8-week-old female SD rats were randomly divided into a blank control group，a model group，a positive control group，a low-dose modified Danggui Yinzi group，a medium-dose modified Danggui Yinzi group，and a high-dose modified Danggui Yinzi group. A "itch-anxiety" model was established by intraperitoneal injection of a suspension of sodium chloride and aluminum hydroxide and ovalbumin，combined with chronic unpredictable emotional stress stimulation. After successful modeling，rats in each group were administered drugs by gavage. The positive control group was given intragastric administration of the drug solutions of cetirizine and fluoxetine （2.08 mg·kg^-1·d^-1 fluoxetine， 2 mg·kg^-1·d^-1 cetirizine）， the low-，medium-，and high-dose modified Danggui Yinzi groups were administered traditional Chinese medicine at 1.44，2.88， 5.76 g·kg^-1， respectively，while the blank control group and model group were given an equal volume of normal saline. All interventions lasted for 15 days. Behavioral changes were evaluated by the elevated plus-maze test （detecting the percentage of entries into the open arms （OE%），the percentage of time spent in the open arms （OT%），and the total number of entries into the open and closed arms （TNE）），the open-field test （detecting total activity，average movement speed，and latency to enter the central area），and scratching behavior observation. Pathological changes of skin tissues were observed by hematoxylin-eosin （HE） staining and toluidine blue staining，while those of amygdala tissues were observed by HE staining，Nissl staining，and immunofluorescence detection of ionized calcium-binding adapter molecule-1 （Iba-1）. The content of immunoglobulin E （IgE），interleukin-33 （IL-33），histamine in serum and glutamate in the amygdala was detected by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the protein expression of striatal-enriched protein tyrosine phosphatase （STEP），N-methyl-D-aspartate receptor subunit 2B （NR2B）， calmodulin-dependent protein kinase Ⅱ （CaMKⅡ），phosphorylated CaMKⅡ （p-CaMKⅡ），mitogen-activated protein kinase （MAPK），phosphorylated MAPK （p-MAPK），nuclear factor kappa-light-chain-enhancer of activated B cells （NF-κB），phosphorylated NF-κB （p-NF-κB），and postsynaptic density protein-95 （PSD-95） in the amygdala. ResultsCompared with the blank control group，the model group rats showed obvious anxiety-like behaviors （decreased OE%，OT%，and TNE，reduced total activity，slower average movement speed，and prolonged latency to enter the central area），increased scratching times，obvious skin inflammation and mast cell degranulation，severe amygdala tissue damage，increased glutamate content in the amygdala，and elevated levels of IgE and IL-33 in serum. The expression of STEP，NF-κB，p-NF-κB，NR2B，MAPK，p-MAPK，CaMKⅡ，and p-CaMKⅡ proteins in the amygdala increased，while the expression of PSD-95 protein decreased （P<0.05）. Compared with the model group，the modified Danggui Yinzi group of each dose had increased OE%，OT%，TNE，total activity，and average movement speed，shortened latency to enter the central area， reduced scratching times，alleviated skin inflammation and mast cell degranulation，relieved amygdala tissue damage，decreased glutamate content in the amygdala，and reduced levels of IgE and IL-33 in serum. Moreover，compared with the model group，the low -，medium-，and high-dose modified Danggui Yinzi groups showed decreased expression levels of STEP，NF-κB，p-NF-κB，NR2B，MAPK，p-MAPK，CaMKⅡ，and p-CaMKⅡ proteins in the amygdala，and increased expression of PSD-95 protein. There was a significant dose-effect relationship，with the high-dose group showing the most significant regulatory effect （P<0.05）. ConclusionThe modified Danggui Yinzi has a therapeutic effect on "itch-anxiety" model rats of CU. Its mechanism may be related to regulating glutamate metabolism in the amygdala，modulating the STEP/NR2B/CaMKⅡ/MAPK/NF-κB pathway，and regulating the expression of PSD-95.

BACKGROUND:3D-printed bone tissue engineering scaffolds have obvious advantages in the research and clinical treatment of bone defect repair.As one of the important raw materials for 3D printed bone scaffolds,poly-L-lactic acid has a great potential for application in performing bone defect repair,but clinical patients with different bone defect causative factors have different requirements for the comprehensive performance of poly-L-lactic acid bone scaffolds.OBJECTIVE:To summarize and review the development of 3D printing technology and poly-L-lactic acid scaffolds and the design strategies chosen for scaffolds for bone repair in the setting of bone diseases such as osteomyelitis,bone tumor,osteonecrosis,and osteoporosis.METHODS:Literature from CNKI,WanFang,PubMed,Science Direct,and Web of Science databases were searched and screened from 1994 to 2024.Search terms were"3D printing,polylactic acid,bone tissue engineering scaffold,osteomyelitis,bone tumor,osteonecrosis,osteoporosis,bone defect"in Chinese and English.The screened 62 articles were systematically summarized and analyzed.RESULTS AND CONCLUSION:(1)Poly-L-lactic acid is considered to be an ideal raw material for artificial bone scaffold design due to its non-toxicity,processability,biocompatibility,and ability to self-degrade in the human environment.The application of 3D printing technology has enabled poly-L-lactic acid bone scaffolds to meet the multilayered and porous structural design requirements of biomimetic artificial bone repair materials,and to optimize the mechanical properties for better bone repair.(2)According to different bone disease microenvironments,timely adjustment of the functional design of poly-L-lactic acid scaffolds is important for the comprehensive osteogenic efficacy of the scaffolds.The article discusses the application of poly-L-lactic acid scaffolds in bone disease environments such as osteomyelitis,bone tumor,osteonecrosis,and osteoporosis,and highlights the importance of rationally grasping the timing of bone disease treatment and bone tissue regeneration for bone defects caused by different bone diseases.(3)Although poly-L-lactic acid scaffolds show potential in bone repair,there are still some problems,such as the need to further optimize the structural design of the scaffolds to fit new bone regeneration,enhance the bioactivity of the scaffolds,and take into account other functions(e.g.,antimicrobial,anti-tumor,and anti-osteoporosis)in order to adapt to the needs of bone tissue repair in different pathological environments.

BACKGROUND:The quadriceps strength of patients with osteoporosis and sarcopenia is significantly reduced,which can further reduce the function of the knee joint,affect the function of the lower limbs and even lead to a decrease in whole-body coordination.It is speculated that a reasonable quadriceps training program and personalized guidance are beneficial to the recovery of knee joint function in patients with osteoporosis and sarcopenia.OBJECTIVE:To observe the effect of short-term moderate-intensity resistance rehabilitation training on the mass and function of the quadriceps and knee joint function in patients with osteoporosis and sarcopenia.METHODS:Using the integrated physical examination and rehabilitation model,375 patients with osteoporosis and sarcopenia were screened at the Health Management Center of Shanghai Public Health Clinical Center.They underwent 12 weeks of combined/comprehensive exercise rehabilitation based on resistance exercise,including quadriceps resistance isotonic and isometric contraction training twice a week(3-5 sets each time,10-15 minutes per set)and aerobic exercise/balance exercise two or three times a week(30 minutes each time).Assessments and data collection were performed before rehabilitation training,12 weeks after rehabilitation training,and at follow-up 12 weeks after stopping rehabilitation training,mainly including knee joint range of motion and proprioception,quadriceps muscle strength,and cross-sectional area(magnetic resonance imaging results),pain,knee joint function(Hospital for Special Surgery score)and walking function("up-and-go"time and 6 m pace test results)as well as the patient's psychological status assessment.RESULTS AND CONCLUSION:All 375 patients completed 12 weeks of rehabilitation training and 12 weeks of follow-up without any adverse events.(1)Compared with before training,the patients' gait speed and knee range of motion increased significantly after 12 weeks of rehabilitation training(P＜0.01),the time of"stand-to-walk"decreased(P＜0.01),and the proprioception of the knee joint and the strength of the quadriceps femoris were significantly improved(P＜0.01);and at the follow-up visit 12 weeks after stopping training,the above indicators and functions of the patients were well maintained(P＞0.05).(2)Magnetic resonance imaging results showed that the effective cross-sectional area of the quadriceps femoris did not improve significantly after 12 weeks of rehabilitation training(P＞0.05);but the Hospital for Special Surgery score of knee joint function increased significantly(P＜0.01),and the visual analog pain scale score decreased significantly(P＜0.01),suggesting that this may be related to the improvement of quadriceps femoris quality by resistance rehabilitation training.(3)The results of the Hospital Anxiety and Depression Scale score showed that the anxiety and depression scores of the patients continued to decrease,both at 12 weeks of rehabilitation training and at 12 weeks after stopping training(P＜0.01).It is suggested that resistance rehabilitation training of the quadriceps can help patients with osteoporosis and sarcopenia to restore quadriceps muscle strength,increase range of motion,improve proprioception and joint stability,thereby enhancing knee joint function,reducing pain,improving depression and anxiety,and to a certain extent promoting the coordinated recovery of the musculoskeletal system.

This paper introduces a real-world cohort research model for community-acquired pneumonia （CAP） based on the Jiangsu Traditional Chinese Medicine （TCM） Dominant Diseases Diagnosis and Treatment Data Platform. Firstly， data cleaning is performed by standardizing diagnosis， symptoms， treatment and imaging， intelligently extracting unstructured information， and cleaning and constructing a standardized database. Secondly， for cohort establishment， CAP patients across the province are screened in accordance with CAP diagnostic criteria to build a high-quality disease-specific cohort. Lastly， in terms of protocol design， the characteristics of TCM research and the CAP disease profile are considered to determine appropriate inclusion and exclusion criteria， estimate sample size， define interventions， outcomes and economic evaluations， providing a reference for real-world TCM research on CAP.

This paper introduces a real-world cohort research model for community-acquired pneumonia （CAP） based on the Jiangsu Traditional Chinese Medicine （TCM） Dominant Diseases Diagnosis and Treatment Data Platform. Firstly， data cleaning is performed by standardizing diagnosis， symptoms， treatment and imaging， intelligently extracting unstructured information， and cleaning and constructing a standardized database. Secondly， for cohort establishment， CAP patients across the province are screened in accordance with CAP diagnostic criteria to build a high-quality disease-specific cohort. Lastly， in terms of protocol design， the characteristics of TCM research and the CAP disease profile are considered to determine appropriate inclusion and exclusion criteria， estimate sample size， define interventions， outcomes and economic evaluations， providing a reference for real-world TCM research on CAP.