ObjectiveBased on ultra-high performance liquid chromatography-quadrupole-electrostatic field orbital trap-linear ion-trap mass spectrometry（UPLC-Orbitrap Fusion Lumos Tribrid-MS）， the plasma concentration of ziyuglycoside Ⅰ was determined at different time points after oral administration， and its pharmacokinetic characteristics in normal rats and rats with acute kidney injury were compared. MethodsRats were randomly divided into normal group and model group， the model group received intraperitoneal cisplatin（10 mg·kg^-1） to establish the acute kidney injury model， the normal group was given the same volume of saline. After successful modeling， rats in the normal and model groups were randomly divided into the normal low， medium and high dose groups（2.5， 5， 7.5 mg·kg^-1） and the model low， medium and high dose groups（2.5， 5， 7.5 mg·kg^-1）， 6 rats in each group， and the plasma was collected at different time points after receiving the corresponding dose of ziyuglycoside Ⅰ. Then， the concentration of ziyuglycoside Ⅰ in rat plasma was determined by UPLC-Orbitrap Fusion Lumos Tribrid-MS， and the drug-time curve was poltted. The pharmacokinetic parameters were calculated by Kinetica 5.1 software， and the differences in pharmacokinetic parameters between different administration groups were compared by independent sample t-test with SPSS 22.0. ResultsThe pharmacokinetic results showed that after receiving the different doses of ziyuglycoside Ⅰ， its concentration increased first and then decreased， and all of them reached the maximum plasma concentration at about 0.5 h. The area under the curve（AUC_0-t） and mean retention time（MRT_0-t） of normal and model rats increased with the increased dose， and the clearance（CL） decreased with the increasing dose. Compared with the normal group， the AUC_0-t was significantly increased（P<0.01）， peak concentration（C_max） and CL decreased in model rats at different doses， indicating that the physiological state of the rats could affect the absorption and elimination of ziyuglycoside Ⅰ in vivo. ConclusionThe pharmacokinetic characteristics of ziyuglycoside Ⅰ are quite different in normal rats and acute kidney injury model rats， which may be due to the change of the body environment in the pathological state， then lead to changes in absorption and metabolic processes.

Traditional Chinese medicine (TCM) represents a paradigmatic approach to personalized medicine, developed through the systematic accumulation and refinement of clinical empirical data over more than 2000 years, and now encompasses large-scale electronic medical records (EMR) and experimental molecular data. Artificial intelligence (AI) has demonstrated its utility in medicine through the development of various expert systems (e.g., MYCIN) since the 1970s. With the emergence of deep learning and large language models (LLMs), AI's potential in medicine shows considerable promise. Consequently, the integration of AI and TCM from both clinical and scientific perspectives presents a fundamental and promising research direction. This survey provides an insightful overview of TCM AI research, summarizing related research tasks from three perspectives: systems-level biological mechanism elucidation, real-world clinical evidence inference, and personalized clinical decision support. The review highlights representative AI methodologies alongside their applications in both TCM scientific inquiry and clinical practice. To critically assess the current state of the field, this work identifies major challenges and opportunities that constrain the development of robust research capabilities-particularly in the mechanistic understanding of TCM syndromes and herbal formulations, novel drug discovery, and the delivery of high-quality, patient-centered clinical care. The findings underscore that future advancements in AI-driven TCM research will rely on the development of high-quality, large-scale data repositories; the construction of comprehensive and domain-specific knowledge graphs (KGs); deeper insights into the biological mechanisms underpinning clinical efficacy; rigorous causal inference frameworks; and intelligent, personalized decision support systems.
Medicine, Chinese Traditional/methods* ; Artificial Intelligence ; Humans ; Precision Medicine ; Decision Support Systems, Clinical

In this study, high-throughput promoter screening was employed to optimize the heterologous expression of Mesorhizobium loti carbonic anhydrase (MlCA) in order to reduce the costs associated with carbon capture and storage (CCS). To simplify the complexity of traditional vectors, a fusion protein expression system was constructed using superfolder green fluorescent protein (sfGFP) and MlCA. The synthetic promoter library in Escherichia coli was utilized for efficient one-step screening. Based on fluorescence intensity on agar plates, a total of 143 monoclonal colonies were identified, forming a library with varying expression levels. The top four recombinants with the highest fluorescence intensity were selected, among which MlCA driven by the promoter 342042/+ exhibited the highest enzymatic activity, with a specific activity of the 34.6 Wilbur-Anderson units (WAU)/mg. Optimization experiments revealed that MlCA exhibited the best performance when cultured for 4 days under pH 7.0 and 40 ℃ conditions. The Michaelis constant (K_m·hdy) and maximum reaction rate (V_max·hdy) for CO₂ hydration were determined to be 62.46 mmol/L and 0.164 mmol/(s·L), respectively. For esterase hydrolysis, MlCA showed the K_m and V_max of 639.8 mmol/L and 0.035 mmol/(s·L), respectively. MlCA accelerated the CO₂ hydration process, promoting CO₂ mineralized into CaCO₃ within 9 min at low pH and room temperature conditions. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) analyses confirmed that the precipitated product was calcite. This study provides a low-cost and environmentally friendly alternative for future CCS applications.
Carbonic Anhydrases/biosynthesis* ; Promoter Regions, Genetic/genetics* ; Escherichia coli/metabolism* ; Carbon Sequestration ; Carbon Dioxide/metabolism* ; Green Fluorescent Proteins/metabolism*

Alzheimer's disease(AD) is a common neurodegenerative disease with increasing incidence rate. Up to now,there is no ideal treatment for AD. It has become a public health problem worldwide. Traditional Chinese medicine (TCM) believes that kidney deficiency is the key symptomatic element of deterioration and temporal progression symptoms,accompanied by the AD process. The treatment of tonifying kidneys,supplementing essence and replenishing marrow is the fundamental method for AD in TCM. Clinical studies have shown that kidney-tonifying formula can significantly improve the cognitive function and daily ability of patients with mild and moderate AD and have no obvious adverse reactions. Its mechanism of action may be related to the protection of nerves,reduction of β-amyloid (Aβ) level in the brain,inhibition of inflammatory factors activation and anti-oxidative stress. Besides reviewing the clinical and pharmacological research progress of kidney-tonifying formula for AD,this article also discusses the advantages and shortcomings of kidney-tonifying formula in the prevention and treatment of AD based on TCM theory and modern medical research. The aim of this study is to provide references of kidney nourishing therapy in TCM for the prevention and treatment of neurodegenerative diseases.

Liquid chromatography-electrospray ionization tandem mass spectrometry(LC-ESI-MS)is a widely utilized technique for in vivo pharmaceutical analysis.Ionization interference within electrospray ion source,occurring between drugs and metabolites,can lead to signal variations,potentially compromising quantitative accuracy.Currently,method validation often overlooks this type of signal interference,which may result in systematic errors in quantitative results without matrix-matched calibration.In this study,we conducted an investigation using ten different groups of drugs and their corresponding me-tabolites across three LC-ESI-MS systems to assess the prevalence of signal interference.Such in-terferences can potentially cause or enhance nonlinearity in the calibration curves of drugs and metabolites,thereby altering the relationship between analyte response and concentration for quanti-fication.Finally,we established an evaluation scheme through a step-by-step dilution assay and employed three resolution methods:chromatographic separation,dilution,and stable labeled isotope internal standards correction.The above strategies were integrated into the method establishment process to improve quantitative accuracy.

Objective To investigate the effects of Gli2 on the proliferation,growth,migration,and invasion of oral cancer cells(Tca8113)at the cellular level,and to clarify the molecular mechanism of how Gli2 regulation affects the migration and invasion of oral cancer cells.Methods Small interfering(si)RNA was used to inhibit Gli2 expression in Tca8113 cells.The effects of Gli2 on the proliferation,growth,migration,and invasion of Tca8113 cells were examined by CCK-8,platb cloning,and transwell chamber assay.Further qRT-PCR and Western blot assays were used to explore the mechanism of how Gli2 regulation effects the malignant proliferation and metastasis of Tca8113 cells.Results The mRNA and protein expression of Gli2 in oral cancer cells(Tca8113)increased.Interference of Gli2 expression inhibited the proliferation,growth,migration,and invasion of Tca8113 cells.Further experiments showed that interfering with Gli2 expression inhibited the mRNA and protein expression of key factors in the Hedgehog(Hh)pathway.In addition,interference of Gli2 expression significantly affected the mRNA and protein expression of key factors in epithelial mesenchymal transformation(EMT)pathways.Conclusions Gli2 is abnormally activated during oral cancer,and interference of Gli2 expression significantly inhibits the proliferation,growth,migration,and invasion of oral cancer cells.Gli2 influences the migration and invasion of oral cancer cells by regulating the Hh and EMT pathways.This study has provided a new way to elucidate the pathogenesis of oral cancer and new perspectives on the clinical treatment of oral cancer.

Objective:To summarize the clinicopathologic characteristics of undifferentiated embryonal sarcoma of the liver.Methods:The clinical data of 16 patients with undifferentiated embryonal sarcoma of the liver admitted to Shandong Provincial Hospital and Yantai Yuhuangding Hospital from Jan 2000 to Jan 2023 was retrospectively analyzed.Results:The diagnosis of undifferentiated embryonal sarcoma in all the 16 patients was established by postoperative pathology. The clinical manifestations of the patients were mainly asymptomatic abdominal mass, abdominal pain and discomfort. The laboratory examination was mostly nonspecific, the image exam showed mostly solid cystic mass. 14 cases underwent radical surgical resection.The minimum survival time was 7 months, maximum survival time was 121 months with median survival time of 35.9 months.Conclusions:Undifferentiated embryonal sarcoma of the liver is an extremely rare malignant tumor of the liver. The disease lacks specific clinical manifestations. CT examination can assist in the diagnosis of the disease. Diagnosis of undifferentiated embryonal sarcoma of the liver depends on pathological examination. The prognosis of patients is poor, surgical resection of the tumor is an effective treatment.

Diabetes mellitus(DM)is a disease syndrome characterized by chronic hyperglycaemia.A long-term high-glucose environment leads to reactive oxygen species(ROS)production and nuclear DNA damage.Human umbilical cord mesenchymal stem cell(HUcMSC)infusion induces significant antidiabetic effects in type 2 diabetes mellitus(T2DM)rats.Insulin-like growth factor 1(IGF1)receptor(IGF1R)is important in promoting glucose metabolism in diabetes;however,the mechanism by which HUcMSC can treat diabetes through IGF1R and DNA damage repair remains unclear.In this study,a DM rat model was induced with high-fat diet feeding and streptozotocin(STZ)administration and rats were infused four times with HUcMSC.Blood glucose,interleukin-6(IL-6),IL-10,glomerular basement membrane,and renal function were examined.Proteins that interacted with IGF1R were determined through coimmunoprecipitation assays.The expression of IGF1R,phosphorylated checkpoint kinase 2(p-CHK2),and phosphorylated protein 53(p-p53)was examined using immunohistochemistry(IHC)and western blot analysis.Enzyme-linked immunosorbent assay(ELISA)was used to determine the serum levels of 8-hydroxydeoxyguanosine(8-OHdG).Flow cytometry experiments were used to detect the surface markers of HUcMSC.The identification of the morphology and phenotype of HUcMSC was performed by way of oil red"O"staining and Alizarin red staining.DM rats exhibited abnormal blood glucose and IL-6/10 levels and renal function changes in the glomerular basement membrane,increased the expression of IGF1 and IGF1R.IGF1R interacted with CHK2,and the expression of p-CHK2 was significantly decreased in IGF1R-knockdown cells.When cisplatin was used to induce DNA damage,the expression of p-CHK2 was higher than that in the IGF1R-knockdown group without cisplatin treatment.HUcMSC infusion ameliorated abnormalities and preserved kidney structure and function in DM rats.The expression of IGF1,IGF1R,p-CHK2,and p-p53,and the level of 8-OHdG in the DM group increased significantly compared with those in the control group,and decreased after HUcMSC treatment.Our results suggested that IGF1R could interact with CHK2 and mediate DNA damage.HUcMSC infusion protected against kidney injury in DM rats.The underlying mechanisms may include HUcMSC-mediated enhancement of diabetes treatment via the IGF1R-CHK2-p53 signalling pathway.

Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable success in the treatment of hematological malignancies. Based on the immunomodulatory capability of CAR-T cells, efforts have turned toward exploring their potential in treating autoimmune diseases. Bibliometric analysis of 210 records from 128 academic journals published by 372 institutions in 40 countries/regions indicates a growing number of publications on CAR-T therapy for autoimmune diseases, covering a range of subtypes such as systemic lupus erythematosus, multiple sclerosis, among others. CAR-T therapy holds promise in mitigating several shortcomings, including the indiscriminate suppression of the immune system by traditional immunosuppressants, and non-sustaining therapeutic levels of monoclonal antibodies due to inherent pharmacokinetic constraints. By persisting and proliferating in vivo, CAR-T cells can offer a tailored and precise therapeutics. This paper reviewed preclinical experiments and clinical trials involving CAR-T and CAR-related therapies in various autoimmune diseases, incorporating innovations well-studied in the field of hematological tumors, aiming to explore a safe and effective therapeutic option for relapsed/refractory autoimmune diseases.

Objective To investigate the effects of circ_UBE2C on the proliferation and glycolysis of lung cancer cells and its mechanism of action.Methods The expression of circ_UBE2C,miR-107,and hexokinase 2(HK2)in lung cancer tissues and normal lung tissues were analyzed based on the The Cancer Genome Atlas(TCGA)database.Kaplan-Meier survival curve was plotted to analyze the correlation between circ_UBE2C/miR-107/HK2 expression and survival of the lung cancer patients.qRT-PCR was used to detect the expression of circ_UBE2C and miR-107,and Western blotting was employed to measure the expression of HK2 and PCNA in human normal lung epithelial cells(BEAS-2B)and human lung cancer cell lines(A549,NCI-H460,and NCI-H1299).Then A549 and NCI-H1299 cells were divided into the blank group(NC),circ_UBE2C knockdown group(si-circ),HK2 knockdown group(si-HK2),simultaneous knockdown of miR-107+HK2 group(miR-inhibitor+si-HK2),and simultaneous knockdown of circ_UBE2C+miR-107 group(si-circ+miR-inhibitor).CCK-8 assay and colony formation assay were employed to measure the proliferation of above cell groups.The glucose uptake,lactate generation,and ATP production in the cells were measured by glucose uptake colorimetric assay kit,lactic acid detection kit,and ATP content determination kit,respectively.Seahorse XF glycolytic stress test and Seahorse XF cellular mitochondrial stress test were respectively performed to detect the extracellular acidification ratio(ECAR)and cellular oxygen consumption ratio(OCR).The targeting relationship between the circ_UBE2C and miR-107,and miR-107 and HK2 was validated by dual-luciferase reporter gene assay.Results Compared with normal lung tissues,the expression of circ_UBE2C and HK2 was up-regulated,while that of miR-107 was down-regulated in lung cancer tissues(P＜0.05).The expression of circ_UBE2C and HK2 was elevated,and that of miR-107 was reduced in A549 and NCI-H1299 cells when compared with BEAS-2B cells(P＜0.05).Survival analysis showed that the patients with high expression of circ_UBE2C and HK2 or low expression of miR-107 had shorter survival(P＜0.05).Compared with the NC group,both si-circ and si-HK2 resulted in significantly reduced proliferation,glucose uptake,lactate generation,ATP production,and ECAR and OCR values in A549 and NCI-H1299 cells(P＜0.05).Dual luciferase reporter gene assay confirmed that circ_UBE2C could directly bind to and negatively regulate miR-107 expression.HK2 was then identified as a downstream target of miR-107.Compared with the si-HK2 group,the proliferative ability and glycolysis level of A549 and NCI-H1299 cells were significantly increased in the miR-inhibitor+si-HK2 group and the si-circ+miR-inhibitor group.Conclusion Knockdown of circ_UBE2C significantly suppresses the proliferation and glycolysis of lung cancer cells via targeting up-regulation of miR-107 and then exerting inhibitory effect on HK2 expression.