To systematically review randomized controlled trials （RCTs） of traditional Chinese medicine （TCM） intervention in ulcerative colitis （UC）， and analyze the characteristics of these studies and their outcome indicators， thereby providing references for the design of future RCTs of TCM intervention in UC and offering evidence supporting the clinical application of TCM in UC. A computerized search was conducted in the China National Knowledge Infrastructure （CNKI）， Wanfang Data， VIP， SinoMed， PubMed， Cochrane Library， EMbase， and Web of Science databases for RCTs of TCM intervention in UC published from January 2021 to August 2024. The risk of bias was assessed， and outcome indicators were qualitatively analyzed. A total of 555 RCTs were included， with a sample size of 44 853 participants. The largest sample size was 218 cases， and the smallest was 28 cases， with most studies focusing on 60-100 participants. Of the 386 RCTs that explicitly reported TCM syndrome types， the top three were large intestine dampness-heat syndrome （31.05%）， spleen and kidney yang deficiency syndrome （12.47%）， and spleen deficiency with dampness syndrome （9.17%）. The interventions， ranked by frequency of use， included internal Chinese medicine compounds/preparations （64.5%）， Chinese medicine compounds/preparations with retained enema （18.2%）， internal Chinese medicine compounds/preparations + external TCM treatment （5.95%）， and external TCM treatment alone （4.86%）. The treatment duration was mainly 4-8 weeks （64.86%）， with 61 studies （10.99%） reporting follow-up time. A total of 157 outcome indicators were used， with a frequency of 3 460 occurrences， classified into six domains： TCM syndromes and symptoms （346 occurrences， 10%）， symptoms/signs （541 occurrences， 15.64%）， physical and chemical examinations （2 119 occurrences， 61.24%）， quality of life （107 occurrences， 3.09%）， long-term prognosis （61 occurrences， 1.76%）， and safety events （284 occurrences， 8.21%）. The analysis reveals several limitations in the outcome indicators of TCM intervention in UC， including the lack of a basis for sample size calculation， non-standardized TCM syndrome classification， absence of trial design and registration， inadequate blinding and allocation concealment， adherence issues with interventions， imbalanced selection of surrogate and endpoint indicators， inconsistency in the timing of outcome measurements， design issues that require standardization， and ethical and safety concerns. It is recommended that future studies actively construct a set of core indicators for UC that include standardized TCM syndrome classification， clear efficacy evaluation indicators， key endpoint indicators， and reasonable measurement time points. Long-term prognostic impacts， comprehensive assessments of patients' quality of life， and consideration of economic benefits should be emphasized， providing a basis for the clinical practice of TCM in the treatment of UC.

To systematically review randomized controlled trials （RCTs） of traditional Chinese medicine （TCM） intervention in ulcerative colitis （UC）， and analyze the characteristics of these studies and their outcome indicators， thereby providing references for the design of future RCTs of TCM intervention in UC and offering evidence supporting the clinical application of TCM in UC. A computerized search was conducted in the China National Knowledge Infrastructure （CNKI）， Wanfang Data， VIP， SinoMed， PubMed， Cochrane Library， EMbase， and Web of Science databases for RCTs of TCM intervention in UC published from January 2021 to August 2024. The risk of bias was assessed， and outcome indicators were qualitatively analyzed. A total of 555 RCTs were included， with a sample size of 44 853 participants. The largest sample size was 218 cases， and the smallest was 28 cases， with most studies focusing on 60-100 participants. Of the 386 RCTs that explicitly reported TCM syndrome types， the top three were large intestine dampness-heat syndrome （31.05%）， spleen and kidney yang deficiency syndrome （12.47%）， and spleen deficiency with dampness syndrome （9.17%）. The interventions， ranked by frequency of use， included internal Chinese medicine compounds/preparations （64.5%）， Chinese medicine compounds/preparations with retained enema （18.2%）， internal Chinese medicine compounds/preparations + external TCM treatment （5.95%）， and external TCM treatment alone （4.86%）. The treatment duration was mainly 4-8 weeks （64.86%）， with 61 studies （10.99%） reporting follow-up time. A total of 157 outcome indicators were used， with a frequency of 3 460 occurrences， classified into six domains： TCM syndromes and symptoms （346 occurrences， 10%）， symptoms/signs （541 occurrences， 15.64%）， physical and chemical examinations （2 119 occurrences， 61.24%）， quality of life （107 occurrences， 3.09%）， long-term prognosis （61 occurrences， 1.76%）， and safety events （284 occurrences， 8.21%）. The analysis reveals several limitations in the outcome indicators of TCM intervention in UC， including the lack of a basis for sample size calculation， non-standardized TCM syndrome classification， absence of trial design and registration， inadequate blinding and allocation concealment， adherence issues with interventions， imbalanced selection of surrogate and endpoint indicators， inconsistency in the timing of outcome measurements， design issues that require standardization， and ethical and safety concerns. It is recommended that future studies actively construct a set of core indicators for UC that include standardized TCM syndrome classification， clear efficacy evaluation indicators， key endpoint indicators， and reasonable measurement time points. Long-term prognostic impacts， comprehensive assessments of patients' quality of life， and consideration of economic benefits should be emphasized， providing a basis for the clinical practice of TCM in the treatment of UC.

Prescription optimization is a crucial aspect in the study of traditional Chinese medicine （TCM） compounds. In recent years， the introduction of mathematical methods， data mining techniques， and artificial neural networks has provided new tools for elucidating the compatibility rules of TCM compounds. The study of TCM compounds involves numerous variables， including the proportions of different herbs， the specific extraction parts of each ingredient， and the interactions among multiple components. These factors together create a complex nonlinear dose-effect relationship. In this context， it is essential to identify methods that suit the characteristics of TCM compounds and can leverage their advantages for effective application in new drug development. This paper provided a comprehensive review of the cutting-edge optimization experimental design methods applied in recent studies of TCM compound compatibilities. The key technical issues， such as the optimization of source material selection， dosage optimization of compatible herbs， and multi-objective optimization indicators， were discussed. Furthermore， the evaluation methods for component effects were summarized during the optimization process， so as to provide scientific and practical foundations for innovative research in TCM and the development of new drugs based on TCM compounds.

ObjectiveTo explore the mechanism of herbal cake-separated moxibustion using the classical formula Xiaoyaosan in alleviating neuroimmune inflammatory responses in chronic fatigue syndrome （CFS） rats， based on the regulation of the toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear transcription factor-κB （NF-κB） signaling pathway. MethodsFifty SPF-grade SD rats aged 6-8 weeks were randomly divided into five groups： Normal group， model group， sham herbal cake moxibustion group， Chinese medicine intragastric administration group， and herbal cake-separated moxibustion group， with 10 rats in each group. Except for the normal group， all other groups underwent a 21-day modeling process， followed by behavioral testing. The herbal cake-separated moxibustion and sham herbal cake moxibustion groups received interventions at the Shenque （CV8）， Guanyuan （CV4）， Zusanli （ST36）， and Qimen （LR14） acupoints. The Chinese medicine intragastric administration group was treated with a Xiaoyaosan suspension via gavage. Behavioral tests were conducted after 10 days of continuous intervention. Serum levels of interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α）， as well as hippocampal levels of IL-1β， IL-6， TNF-α， and NF-κB， were detected by enzyme-linked immunosorbent assay （ELISA）. Morphological changes in the hippocampus were observed using hematoxylin-eosin （HE） staining. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA expression levels of TLR4， MyD88， and NF-κB in the hippocampus. Western blot analysis was performed to detect the relative expression levels of TLR4， MyD88， NF-κB， and p65 proteins in the hippocampus. ResultsCompared with the normal group， the model group showed a significant decrease in upright times during the open field test （P<0.01）， as well as significant reductions in total movement distance， resting time， and center region duration （P<0.01）. In the tail suspension test， immobility time increased （P<0.01）， and struggle times decreased （P<0.01）. Serum and hippocampal levels of IL-1β， IL-6， and TNF-α， as well as hippocampal NF-κB levels and TLR4， MyD88， and NF-κB mRNA expression， were significantly elevated （P<0.01）. After treatment， compared with the model group， the total movement distance and upright times in the open field test were significantly increased in all treatment groups （P<0.01）， while resting time and center region duration were notably prolonged （P<0.05， P<0.01）. Immobility time in the tail suspension test was significantly shortened （P<0.01）， and struggle times significantly increased （P<0.05）. Serum and hippocampal levels of IL-1β， IL-6， TNF-α， hippocampal NF-κB levels， and TLR4 and NF-κB mRNA expression were significantly reduced （P<0.05， P<0.01）. Compared with the sham herbal cake moxibustion group， the herbal cake-separated moxibustion group showed a significant extension in center region duration during the open field test （P<0.05） and a significant increase in upright times （P<0.01）. In the tail suspension test， immobility time was reduced （P<0.01）， and struggle times increased （P<0.01）. Serum TNF-α levels in the Chinese medicine intragastric administration group were significantly reduced （P<0.01）， while serum IL-6 levels， as well as hippocampal levels of IL-1β， TNF-α， NF-κB， and TLR4， MyD88， and NF-κB mRNA expression， were significantly decreased in both the Chinese medicine intragastric administration group and the herbal cake-separated moxibustion group （P<0.05， P<0.01）. Compared with the Chinese medicine intragastric administration group， the herbal cake-separated moxibustion group exhibited significantly increased upright times in the open field test （P<0.01）. In the tail suspension test， immobility time was reduced （P<0.01）， and struggle times increased （P<0.01）. Serum IL-1β， hippocampal TNF-α levels， and TLR4， MyD88， and NF-κB mRNA expression were significantly decreased （P<0.05， P<0.01）. ConclusionHerbal cake-separated moxibustion effectively improves fatigue and memory function in CFS rats， regulates neuroimmune inflammatory responses， and its mechanism may be related to the modulation of the TLR4/MyD88/NF-κB signaling pathway.

ObjectiveTo investigate the effects of Dihuang Yinzi on the cognitive function in the mouse model of learning and memory impairments induced by scopolamine （SCOP） and explore the treatment mechanism. MethodsA mouse model of learning and memory impairment was induced by intraperitoneal injection of SCOP. Sixty male C57BL/6J mice were randomized into six groups： control （0.9% NaCl， n=10）， model （SCOP 1 mg·kg^-1·d^-1， n=10）， low-， medium-， and high-dose Dihuang Yinzi （SCOP 1 mg·kg^-1·d^-1 + Dihuang Yinzi 5.5， 11.0， and 22.0 g·kg^-1·d^-1， n=10）， and donepezil （SCOP 1 mg·kg^-1·d^-1 + donepezil 0.84 mg·kg^-1·d^-1， n=10）. Mice were administrated with corresponding drugs for 6 weeks. Modeling started in the 4th week， and mice in other groups except the control group were injected with SCOP intraperitoneally 40 min after daily gavage. Behavioral testing began in the 5th week， 30 min after modeling each day. The Morris water maze and novel object recognition tests were carried out to evaluate the spatial learning and memory function of mice. Nissl staining was employed to observe the survival of neurons and Nissl bodies in the hippocampal CA1 region. Western blot was employed to determine the protein levels of silent information regulator 2 （SIRT2）， α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid （AMPA） receptor 1 （GluA1）， protein kinase A （PKA）， cAMP response element-binding protein （CREB）， phosphorylated-CREB （p-CREB）， postsynaptic density protein 95 （PSD95）， growth-associated protein-43 （GAP-43）， and synaptophysin （SYN） in the hippocampus. Immunofluorescence was used to detect the expression of doublecortin （DCX） in the hippocampal dentate gyrus （DG） region. ResultsCompared with the control group， the model group showed impaired learning and memory （P<0.01）， obvious neuronal damage in the hippocampal CA1 region， a reduction in neuron survival （P<0.01）， a decrease in DCX expression in the hippocampal DG region （P<0.01）， down-regulated proteins levels of GluA1， PKA， p-CREB/CREB， PSD95， SYN， and GAP-43 in the hippocampal tissue （P<0.05， P<0.01）， and an up-regulated protein level of SIRT2 （P<0.01）. Compared with the model group， the medium- and high-dose Dihuang Yinzi groups and the donepezil group showed improvements in learning and memory （P<0.05， P<0.01）， while the low-， medium-， and high-dose Dihuang Yinzi groups and the donepezil group had increased neuron survival （P<0.05， P<0.01）. The medium-dose Dihuang Yinzi group and the donepezil group showed increased DCX expression （P<0.05， P<0.01）. The medium- and high-dose Dihuang Yinzi groups and the donepezil group showed up-regulation in the protein levels of GluA1， PKA， p-CREB/CREB， PSD95， SYN， and GAP-43 （P<0.05， P<0.01） and down-regulation in the protein level of SIRT2 （P<0.01）. ConclusionDihuang Yinzi can improve the cognitive function in the mouse model of learning and memory impairments induced by SCOP by inhibiting the upregulation of SIRT2， activating the PKA/CREB signaling pathway， improving synaptic plasticity， and reducing hippocampal neuronal damage.

In recent years, the incidence of dry eye disease(DED)is increasing, positioning it as one of the most prevalent diseases affecting the ocular surface. Inflammatory response is the pathological basis of DED, involving various inflammatory mediators and inflammatory signaling pathways. Consequently, anti-inflammatory treatment emerges as a fundamental strategy for preventing and managing DED. This review summarizes the classic inflammatory factors involved in the development and progression of DED, including interleukins, tumor necrosis factor, matrix metalloproteinases, chemokines, and cell adhesion molecules. It also discusses the relevant inflammatory signaling pathways: the MAPKs pathway, NF-κB pathway, Wnt pathway and TLR pathway. Additionally, this review addresses the mechanisms of action and alterations in relevant biomarkers associated with current first-line recommended anti-inflammatory therapies, including corticosteroids, immunosuppressants, nonsteroidal anti-inflammatory drugs, and traditional Chinese medicine approaches to inflammation management. This comprehensive overview aims to enhance understanding of the inflammatory mechanisms underlying DED while exploring future therapeutic prospects.

In recent years, the incidence of dry eye disease(DED)is increasing, positioning it as one of the most prevalent diseases affecting the ocular surface. Inflammatory response is the pathological basis of DED, involving various inflammatory mediators and inflammatory signaling pathways. Consequently, anti-inflammatory treatment emerges as a fundamental strategy for preventing and managing DED. This review summarizes the classic inflammatory factors involved in the development and progression of DED, including interleukins, tumor necrosis factor, matrix metalloproteinases, chemokines, and cell adhesion molecules. It also discusses the relevant inflammatory signaling pathways: the MAPKs pathway, NF-κB pathway, Wnt pathway and TLR pathway. Additionally, this review addresses the mechanisms of action and alterations in relevant biomarkers associated with current first-line recommended anti-inflammatory therapies, including corticosteroids, immunosuppressants, nonsteroidal anti-inflammatory drugs, and traditional Chinese medicine approaches to inflammation management. This comprehensive overview aims to enhance understanding of the inflammatory mechanisms underlying DED while exploring future therapeutic prospects.

Collagen is a major structural protein in the matrix of animal cells and the most widely distributed and abundant functional protein in mammals. Collagen’s good biocompatibility, biodegradability and biological activity make it a very valuable biomaterial. According to the source of collagen, it can be broadly categorized into two types: one is animal collagen; the other is recombinant collagen. Animal collagen is mainly extracted and purified from animal connective tissues by chemical methods, such as acid, alkali and enzyme methods, etc. Recombinant collagen refers to collagen produced by gene splicing technology, where the amino acid sequence is first designed and improved according to one’s own needs, and the gene sequence of improved recombinant collagen is highly consistent with that of human beings, and then the designed gene sequence is cloned into the appropriate vector, and then transferred to the appropriate expression vector. The designed gene sequence is cloned into a suitable vector, and then transferred to a suitable expression system for full expression, and finally the target protein is obtained by extraction and purification technology. Recombinant collagen has excellent histocompatibility and water solubility, can be directly absorbed by the human body and participate in the construction of collagen, remodeling of the extracellular matrix, cell growth, wound healing and site filling, etc., which has demonstrated significant effects, and has become the focus of the development of modern biomedical materials. This paper firstly elaborates the structure, type, and tissue distribution of human collagen, as well as the associated genetic diseases of different types of collagen, then introduces the specific process of producing animal source collagen and recombinant collagen, explains the advantages of recombinant collagen production method, and then introduces the various systems of expressing recombinant collagen, as well as their advantages and disadvantages, and finally briefly introduces the application of animal collagen, focusing on the use of animal collagen in the development of biopharmaceutical materials. In terms of application, it focuses on the use of animal disease models exploring the application effects of recombinant collagen in wound hemostasis, wound repair, corneal therapy, female pelvic floor dysfunction (FPFD), vaginal atrophy (VA) and vaginal dryness, thin endometritis (TE), chronic endometritis (CE), bone tissue regeneration in vivo, cardiovascular diseases, breast cancer (BC) and anti-aging. The mechanism of action of recombinant collagen in the treatment of FPFD and CE was introduced, and the clinical application and curative effect of recombinant collagen in skin burn, skin wound, dermatitis, acne and menopausal urogenital syndrome (GSM) were summarized. From the exploratory studies and clinical applications, it is evident that recombinant collagen has demonstrated surprising effects in the treatment of all types of diseases, such as reducing inflammation, promoting cell proliferation, migration and adhesion, increasing collagen deposition, and remodeling the extracellular matrix. At the end of the review, the challenges faced by recombinant collagen are summarized: to develop new recombinant collagen types and dosage forms, to explore the mechanism of action of recombinant collagen, and to provide an outlook for the future development and application of recombinant collagen.

In this study, RAW264.7 cells were employed to investigate the effects of honey-processed Astragalus on their energy metabolism and polarization, and explore the scientific connotation of the enhanced efficacy of honey-processed Astragalus on invigorating spleen-stomach and replenishing Qi. The medicated sera were prepared by intragastric administration of rats with water extracts of crude and honey-processed Astragalus, and the composition changes of medicated sera of crude and honey-processed Astragalus were analyzed by using LC-MS technology. The cell survival rates were detected and the concentrations of medicated sera were screened through CCK-8 assay. The differences of cell phagocytic rates, ATP energy metabolism, and NO secretion between crude and honey-processed Astragalus were evaluated by using neutral red phagocytosis assay, ATP detection kit, and NO detection kit. The effects of crude and honey-processed Astragalus on TNF-α secretion of RAW264.7 cells were detected by employing ELISA kit. The effects of crude and honey-processed Astragalus on polarization of RAW264.7 cells were evaluated by utilizing flow cytometry. The differential metabolites related to glycolysis in cell lysates and culture media were screened by using LC-MS technology. The experiment was approved by the experimental animal ethics committee from Shanxi University of Chinese Medicine (No. AWE202407352). The results showed that the contents of betaine, amino acids, and ononin in the prepared medicated sera of rats treated by intragastric administration with water extracts of honey-processed Astragalus increased compared to those in crude one. The results of CCK-8 experiment showed that there were no cytotoxic effects on RAW264.7 cells in the medicated sera of crude and honey-processd Astragalus at different concentration. The phagocytic index and ATP yield both increased to varying degrees after administration of the medicated sera to cells. The secretion of NO in normal and inflammatory cells increased and decreased respectively, and the effect of honey-processed Astragalus was better than that of crude one. The results of ELISA kit showed that the medicated sera of both crude and honey-processed Astragalus could promote the secretion of TNF-α in a concentration-dependent manner, and the promoting effect of honey-processed Astragalus was stronger than that of crude one. The results of flow cytometry showed that the medicated sera of both crude and honey-processed Astragalus could promote M1-type polarization and inhibit M2-type polarization of RAW264.7 cells, and the effect of honey-processed Astragalus was better than that of crude one. Compared to crude Astragalus, the metabolites related to glycolysis in the cell lysates and culture media of the medicated sera of honey-processed Astragalus were generally on the rise, indicating that the effect on promoting glycolysis of honey-processed Astragalus was better than that of crude one. In summary, honey-processed Astragalus can promote the polarization and energy metabolism of RAW264.7 cells, and participate in positive immune regulation, which is correlated with its enhanced effect of invigorating spleen-stomach and replenishing Qi.

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.