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Online FirstList of IssuesDocument Types
- Abstract：ObjectiveTo investigate the effects of Liuwei Dihuang Wan on mammalian target of rapamycin （mTOR）-mediated synaptic plasticity in the prefrontal cortex-hippocampus circuit in the rat model of valproic acid （VPA）-induced autism spectrum disorder （ASD） and to explore its potential mechanism for reducing behavioral abnormalities in ASD rats.MethodsThirteen SD pregnant rats were randomized into the VPA group （10 rats） and the control group （3 rats）. On gestational day 13， the VPA group was intraperitoneally injected with VPA solution （600 mg·kg-1）， while the control group was injected with an equal volume of normal saline. Male pups of 21 days old from both groups underwent behavioral tests to screen the ASD model rats （32 rats）. These rats were then randomly assigned to the model （distilled water）， vitamin D （1 480 U·kg-1）， low-dose （0.75 g·kg-1） Liuwei Dihuang Wan， and high-dose （1.5 g·kg-1） Liuwei Dihuang Wan groups， and normal male pups were selected as the blank group （distilled water）， with 8 rats in each group. Each group was treated with the corresponding drug or an equal volume of distilled water via gavage daily. After drug administration， behavioral tests were conducted again， followed by anesthesia and tissue collection. Nissl staining was carried out to observe the morphological changes of neurons in the prefrontal cortex and hippocampus. Transmission electron microscopy was used to observe changes in hippocampal synaptic structure. Immunohistochemistry and Western blotting were employed to determine the expression of mTOR， phosphatidylinositol 3-kinase （PI3K）， and protein kinase B （Akt） in the prefrontal cortex， as well as synaptophysin-1 （SYP-1）， postsynaptic density 95 （PSD95）， and N-methyl-D-aspartate receptors （NMDARs） in the hippocampus.ResultsCompared with the control group， the model group exhibited severe growth retardation and developmental deformities， with abnormal behavioral performance and pathological damage to neurons and synapses in the prefrontal cortex and hippocampus. Compared with the model group， all treatment groups showed reduced behavioral abnormalities and pathological damage to neurons and synapses in the prefrontal cortex and hippocampus， with the most significant effects in the high-dose Liuwei Dihuang Wan group. Immunohistochemistry and Western blotting results showed that compared with the control group， the model group exhibited significantly increased protein levels and phosphorylation ratios of p-mTOR， p-Akt， and p-PI3K in the prefrontal cortex （P<0.05， P<0.01）， and decreased protein levels of SYP-1 and PSD95 and increased protein level of NMDARs in the hippocampus （P<0.01）. Compared with those in the model group， the protein levels of p-mTOR， p-Akt， and p-PI3K in the prefrontal cortex decreased in the vitamin D and high-dose Liuwei Dihuang Wan groups （P<0.05）， and the p-mTOR/mTOR， p-Akt/Akt， and p-PI3K/PI3K ratios in the prefrontal cortex declined in the vitamin D group （P<0.05）. The high-dose Liuwei Dihuang Wan group showed a reduction in p-PI3K/PI3K ratio （P<0.05）. The protein level of SYP-1 and PSD95 in the hippocampus increased in the vitamin D， low-dose Liuwei Dihuang Wan， and high-dose Liuwei Dihuang Wan groups （P<0.05， P<0.01）， while the protein level of NMDARs decreased in the vitamin D and high-dose Liuwei Dihuang Wan groups （P<0.01）.ConclusionLiuwei Dihuang Wan significantly reduces VPA-induced ASD-like behaviors and enhances the regeneration and repair of neurons in the prefrontal cortex and synaptic structures in the hippocampus by downregulating of PI3K/Akt/mTOR expression in the prefrontal cortex， upregulating SYP-1 and PSD95 expression in the hippocampus， and inhibiting NMDARs expression.Keywords：Liuwei Dihuang Wan;autism spectrum disorder;mammalian target of rapamycin （mTOR） signaling pathway;synaptic plasticity24|3|0
<HTML><H-PDF><L-PDF><XML>Updated：2026-09-29 Mechanism of Mitochondrial Dynamics in Chronic Heart Failure and Treatment from Perspective of Yin at Peace and Yang Being Compact AI Introduction
Abstract：Chronic heart failure is the terminal stage of various cardiovascular diseases， and its occurrence and progression are closely associated with impaired myocardial energy metabolism and mitochondrial dysfunction. Mitochondrial dynamics maintain cardiomyocyte energy homeostasis through fusion， fission， and quality control. Disruption of mitochondrial dynamics may lead to mitochondrial network fragmentation， insufficient adenosine triphosphate （ATP） production， enhanced oxidative stress， and activation of ferroptosis. The theory of Yin at peace and Yang being compact originates from the Chapter Discussion on Interrelationship between Life and Nature in the Plain Questions， and emphasizes that the dynamic balance between Yin and Yang is fundamental to normal life activities. According to this theory and mitochondrial dynamics， this paper explores the pathogenic connotations of Yang failing to remain compact and Yin failing to remain at peace in chronic heart failure. In traditional Chinese medicine （TCM）， chronic heart failure is characterized by deficiency in origin and excess in manifestation. Deficiency of heart Qi and Yang is the root， often accompanied by Yang deficiency or Yin deficiency， while blood stasis， phlegm turbidity， and water retention constitute the manifestations. When Yang fails to remain compact， cardiac propulsion becomes weakened and Qi transformation is impaired. When Yin fails to remain at peace， Yin pathogens are generated and Yin essence is consumed. At the microscopic level， imbalance of mitochondrial dynamics is manifested as insufficient mitochondrial fusion， excessive fission， reduced energy production， excessive ROS generation， expansion of the labile iron pool， and accumulation of lipid peroxidation products， which contribute to Yin-Yang imbalance in chronic heart failure. Furthermore， by integrating formula-pattern correspondence and the approach of inferring patterns from formula effects， this paper summarizes the possible molecular phenotypes corresponding to different syndrome elements and syndrome patterns. It further proposes keeping Yang compact and keeping Yin at peace as therapeutic principle for chronic heart failure， aiming to restore energy metabolism homeostasis by regulating mitochondrial dynamics with TCM and to provide new perspectives and ideas for the treatment of chronic heart failure.Keywords：chronic heart failure;Yin at peace and Yang being compact;mitochondrial dynamics;keeping Yang compact;keeping Yin at peace18|3|0<HTML><H-PDF><L-PDF><XML>Updated：2026-09-29Exploring Clinical Application and Mechanism of Huangqi Guizhi Wuwu Tang Based on Theory of Treating Different Diseases with Same Method AI Introduction
Abstract：Huangqi Guizhi Wuwu Tang was first documented in ZHANG Zhongjing's Synopsis of the Golden Chamber in the Eastern Han Dynasty as the principal formula for treating blood obstruction syndrome. It is composed of Astragali Radix， Cinnamomi Ramulus， Paeoniae Radix Alba， Zingiberis Rhizoma Recens， and Jujubae Fructus. This formula exhibits the effects of replenishing Qi， warming meridians， harmonizing blood， and relieving obstruction， being primarily indicated for blood obstruction syndrome characterized by diminished Yin and Yang functions with external manifestations of bodily numbness. Traditional Chinese Medicine （TCM） emphasizes strict adherence to pathogenesis while applying tailored therapies， employing consistent treatment approaches for conditions with diverse clinical presentations but shared pathogenesis， which embodies the principle of treating different diseases with the same method. In modern clinical practice， Huangqi Guizhi Wuwu Tang is widely applied in multisystem disorders presenting with symptoms such as cutaneous numbness， cold-induced pain and stiffness， and acidosis and weakness， including diabetic peripheral neuropathy， cervical radiculopathy， rheumatoid arthritis， coronary heart disease， pediatric spastic cerebral palsy， and recovery phases of cerebral infarction， demonstrating proven efficacy. Modern pharmacological studies confirm its anti-inflammatory， antioxidant-stress， hemorheological-improving， immunomodulatory， and neuroprotective effects by regulating multiple signaling pathways such as nuclear factor （NF）-κB/NOD-like receptor family pyrin domain-containing protein 3 （NLRP3） and nuclear factor erythroid 2-related factor 2 （Nrf2）-antioxidant response element （ARE）， thereby addressing common pathological processes including inflammation， hypercoagulability， oxidative stress， immune dysregulation， and neural injury， highlighting the integrated regulatory advantages of TCM formulas with multi-target， multi-level， multi-component， and multi-pathway mechanisms. According to the theory of treating different diseases with the same method and focusing on three core syndromes of blood obstruction， this article systematically reviews and elucidates the clinical extensions and shared mechanisms of this formula， aiming to provide evidence-based insights for the modern adaptation and precise application of this classical formula in orthopedic and related disciplines for chronic musculoskeletal disorders.Keywords：treating different diseases with the same method;Huangqi Guizhi Wuwu Tang;blood obstruction syndrome;clinical application;mechanism36|3|0<HTML><H-PDF><L-PDF><XML>Updated：2026-09-29Lianpo Yin Ameliorates Bile Reflux Gastritis in Rats by Regulating TLR4/NF-κB Signaling Pathway AI Introduction
Abstract：ObjectiveTo investigate the ameliorative effect of Lianpo Yin on gastric mucosal injury in the rat model of bile reflux gastritis （BRG） and decipher the underlying mechanism based on the Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） signaling pathway.MethodsThirty-six SPF-grade male Sprague-Dawley （SD） rats were randomized into blank， model， hydrotalcite （positive control drug， 0.20 g·kg-1）， NF-κB inhibitor （BAY11-7082， 5.00 mg·kg-1）， low-dose Lianpo Yin （LPY-L， 9.77 g·kg-1）， and high-dose Lianpo Yin （LPY-H， 19.54 g·kg-1） groups （n=6）. Except that the blank group was administrated with distilled water by gavage， the rats in the other groups were induced for the modeling of BRG by gavage with reflux fluid for 35 consecutive days. From the 2nd week of modeling， each treatment group was administrated with the corresponding drugs by gavage 6 h after the end of daily reflux fluid gavage. The BAY11-7082 group received intraperitoneal injection. Meanwhile， the blank group and model group received an equal volume of distilled water by gavage. All interventions were performed for 28 consecutive days. During the experiment period， the general status of rats was observed and body mass changes were recorded， and the stomach index was calculated after the last administration. The histopathological changes of the gastric mucosa were observed under the light microscope after hematoxylin-eosin （HE） staining. The serum levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） were quantified by enzyme-linked immunosorbent assay （ELISA）. The protein levels of TLR4， NF-κB p65， phosphorylated NF-κB p65 （p-NF-κB p65） and IL-6 in the gastric mucosal tissue were determined by Western blot. The nuclear translocation of NF-κB p65 was observed by immunofluorescence （IF） staining.ResultsCompared with the blank group， the model group showed mental depression， retarded body weight gain （P<0.05， P<0.01）， an increased stomach index （P<0.01）， severely damaged gastric mucosal structure with massive inflammatory cell infiltration and intestinal metaplasia （P<0.01）， elevated serum levels of TNF-α and IL-6 （P<0.01）， up-regulated protein levels of TLR4， p-NF-κB p65/NF-κB p65， and IL-6 in the gastric tissue （P<0.01）， and evident nuclear translocation of NF-κB p65 （P<0.01）. Compared with the model group， all drug intervention groups showed improved general status of rats. The body mass of rats in the hydrotalcite group， LPY-L， and LPY-H groups increased （P<0.05）， while the average body mass of rats in the BAY11-7082 group was slightly higher than that in the model group at each time point. All drug intervention groups showed decreased stomach index （P<0.05， P<0.01）， alleviated pathological damage of gastric mucosa with reduced inflammatory cell infiltration （P<0.05， P<0.01）， and declined serum levels of TNF-α and IL-6 （P<0.01）. Hydrotalcite and LPY-L reduced the levels of TLR4 and IL-6 （P<0.05） but had no significant effect on p-NF-κB p65. LPY-H down-regulated the protein levels of TLR4， p-NF-κB p65/NF-κB p65， and IL-6 and inhibited the nuclear translocation of NF-κB p65 （P<0.01）， with its effect equivalent to that of BAY11-7082 and superior to that of hydrotalcite and LPY-L.ConclusionLianpo Yin can effectively ameliorate gastric mucosal inflammatory injury in BRG rats by inhibiting the activation of the TLR4/NF-κB signaling pathway， reducing the release of downstream pro-inflammatory cytokines， and suppressing the nuclear translocation of NF-κB p65.Keywords：Lianpo Yin;bile reflux gastritis;Toll-like receptor 4/nuclear factor-κB （TLR4/NF-κB） signaling pathway;inflammatory response;gastric mucosal injury14|4|0<HTML><H-PDF><L-PDF><XML>Updated：2026-09-29Mechanism of Wendan Tang Against Atherosclerosis by Regulating Ferroptosis Based on JAK2/STAT3 Signaling Pathway AI Introduction
Abstract：ObjectiveTo investigate the mechanism through which Wendan Tang ameliorates atherosclerosis （AS） in mice by regulating ferroptosis via the Janus kinase 2（JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway.MethodsTwelve 8-week-old male C57BL/6J mice of SPF grade were selected as the blank control group and fed a standard diet. Additionally， sixty age-matched male apolipoprotein E knockout （ApoE-/-） mice of the same strain and SPF grade were selected and assigned through a random number table into the following groups （n=12 per group）： a model group， a low-dose （3.9 g·kg-1·d-1） Wendan Tang group， a medium-dose （7.8 g·kg-1·d-1） Wendan Tang group， a high-dose （15.6 g·kg-1·d-1） Wendan Tang group， and an atorvastatin calcium （0.01 g·kg-1·d-1） group. All ApoE-/- mice were fed a high-fat diet for the modeling of AS. Starting from week 9， the blank and model groups were administrated with an equal volume of normal saline by gavage， and the remaining groups with corresponding agents by gavage. After 8 weeks of intervention， samples were collected for analysis. Oil Red O staining and Masson staining were used to observe lipid deposition in the aorta， and hematoxylin-eosin （HE） staining was employed to examine AS plaque formation. The serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were measured by an automatic biochemical analyzer. The serum levels of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， superoxide dismutase （SOD）， malondialdehyde （MDA）， and reduced glutathione （GSH） were determined by enzyme-linked immunosorbent assay （ELISA）. The level of Fe2+ in the aortic tissue was measured by ELISA. Western blotting was performed to determine the protein levels of JAK2， phosphorylated JAK2 （p-JAK2）， STAT3， phosphorylated STAT3 （p-STAT3）， solute carrier family 7 member 11 （SLC7A11）， and glutathione peroxidase 4 （GPX4） in the aortic tissue. Real-time PCR was utilized to measure the mRNA levels of JAK2， STAT3， SLC7A11， and GPX4 in the aortic tissue.ResultsCompared with the blank control group， the model group exhibited increased aortic plaque number and area， enhanced lipid deposition， elevated serum levels of TC， TG， LDL-C， TNF-α， IL-6， and MDA （P<0.05 or P<0.01）， declined serum levels of HDL-C， SOD， and GSH， and downregulated protein levels of SLC7A11 and GPX4 in the aortic tissue （P<0.05 or P<0.01）. The aortic tissue of the model group exhibited an elevated Fe2+ level and upregulated protein levels of p-JAK2 and p-STAT3 and mRNA levels of JAK2 and STAT3 （P<0.05， P<0.01）. Compared with the model group， low-， medium-， and high-dose Wendan Tang， as well as atorvastatin calcium， significantly attenuated these pathological alterations. Specifically， the treatments decreased aortic plaque burden and lipid deposition and lowered serum TC， TG， LDL-C， TNF-α， and MDA levels （P<0.05 or P<0.01）. Concurrently， these interventions raised serum HDL-C， SOD， and GSH levels， upregulated the protein levels of SLC7A11 and GPX4 in the aortic tissue （P<0.05 or P<0.01）， reduced the Fe2+ level， and downregulated the protein levels of p-JAK2 and p-STAT3 and the mRNA levels of JAK2 and STAT3 in the aortic tissue （P<0.05， P<0.01）.ConclusionWendan Tang ameliorates aortic lesions， dyslipidemia， and oxidative stress， decreased the phosphorylation levels of JAK2/STAT3， and increased the expression of SLC7A11 and GPX4 in the mouse model of AS. The results suggest that the anti-AS effect of Wendan Tang may be associated with the modulation of the JAK2/STAT3 signaling pathway and inhibition of ferroptosis.Keywords：Wendan Tang;atherosclerosis;ferroptosis;Janus kinase 2/signal transducer and activator of transcription 3（JAK2/STAT3） signaling pathway20|5|0<HTML><H-PDF><L-PDF><XML>Updated：2026-09-29- Abstract：ObjectiveTo investigate the mechanism by which Shengjiang Pingchuan Zhike pills （SPZW） alleviate airway injury in the rat model of cough variant asthma （CVA） via regulating autophagy through activating the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR）/Unc-51-like autophagy activating kinase 1 （ULK1） signaling pathway based on transcriptomics， thus providing experimental evidence for the clinical application of SPZW.MethodsForty SPF-grade SD rats were enrolled in the present study and randomly via the random number table method assigned into four groups： a blank group， a model group， a SPZW （2 160 mg·kg-1·d-1） group， and a positive drug （montelukast sodium， MTL， 0.9 mg·kg-1·d-1）， with 10 rats in each group. After one week of adaptive feeding， the rat model of cough variant asthma （CVA） was established by two-week sensitization with ovalbumin （OVA） and aluminium hydroxide， followed by capsaicin atomization challenge. Rats in the blank group received an equal volume of normal saline during modeling. Upon successful modeling， rats in the SPZW group and positive drug group were administrated with SPZW suspension and MTL solution， respectively， while those in the blank and model groups received the same dose of normal saline by gavage. The whole intervention lasted for 21 consecutive days. After the intervention， general behaviors of rats in each group were observed. Pulmonary function indicators were subsequently detected. Hematoxylin-eosin （HE） staining was performed to visualize the pathological morphology of the lung tissue， and periodic acid-Schiff （PAS） staining was adopted to evaluate airway mucus secretion. Transcriptomic sequencing was conducted to screen differentially expressed genes in the lung tissue across groups. The levels of inflammatory cytokines including interleukin （IL）-4， IL-5， immunoglobulin E （IgE）， and interferon-γ （IFN-γ） in the bronchoalveolar lavage fluid （BALF） were quantified by enzyme-linked immunosorbent assay （ELISA）. Immunofluorescence staining was used for detecting the co-localization of autophagy-related protein Beclin-1 and phosphorylated mammalian target of rapamycin （p-mTOR）. Transmission electron microscopy was employed to count autophagosomes and observe mitochondrial morphological changes in the lung tissue. Western blot assay was utilized to measure the expression levels of AMPK/mTOR/ULK1 axis-related proteins， including AMPK， phosphorylated adenosine monophosphate-activated protein kinase （p-AMPK）， mTOR， phosphorylated mammalian target of rapamycin （p-mTOR）， ULK1， and phosphorylated Unc-51-like autophagy activating kinase 1 （p-ULK1） as well as the autophagy biomarkers Beclin-1 and selective autophagy adaptor protein p62 in lung specimens.ResultsCompared with the blank group， the model group exhibited markedly elevated cough frequency accompanied by wheezing and stridor， dull fur， poor mental activity， diminished motor activity， accelerated respiratory rate， and weakened sensory response and mobility to external stimuli， accompanied by a declining tendency of body mass. Meanwhile， the model group exhibited decreased dynamic lung compliance， increased airway resistance （P<0.01）， severe pathological damage and excessive mucus secretion in the lung tissue （P<0.01）， and elevated levels of IL-4， IL-5， and IgE and declined level of IFN-γ in the BALF （P<0.01）. Ultrastructural observation revealed damaged mitochondrial morphology and a sharp reduction in the number of autophagosomes in the lung tissue. In addition， the expression of p-AMPK， p-ULK1， and Beclin-1 was downregulated， whereas p-mTOR and p62 were highly expressed （P<0.05， P<0.01） in the model group. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses demonstrated significant enrichment of AMPK， mTOR， and autophagy-related pathways. Compared with the model group， both the positive drug group and SPZW group obtained visible improvements in general behavioral manifestations and obvious recovery of pulmonary function indicators （P<0.05）， alleviated pulmonary pathological lesions and suppressed excessive airway mucus secretion （P<0.05）， recovered levels of inflammatory cytokines in the BALF （P<0.05）， restored mitochondrial morphology， increased autophagosomes， upregulated expression levels of p-AMPK， p-ULK1， and Beclin-1， and downregulated expression levels of p-mTOR and p62 （P<0.05）.ConclusionSPZW can effectively ameliorate airway inflammation and improve the pulmonary function in the rat model of CVA by activating the AMPK/mTOR/ULK1 signaling pathway， enhancing autophagy in the lung tissue， and inhibiting excessive airway mucus secretion and immune inflammatory imbalance.Keywords：Shengjiang Pingchuan Zhike pills;cough variant asthma;autophagy;adenosine monophosphate-activated protein kinase/mammalian target of rapamycin/Unc-51-like autophagy activating kinase 1 （AMPK/mTOR/ULK1） signaling pathway;transcriptomics;autophagosome23|3|0<HTML><H-PDF><L-PDF><XML>Updated：2026-09-29
Traditional Chinese Medicine Manages Lung Cancer Based on Epigenetic Regulation： A Review AI Introduction
Abstract：Lung cancer is the malignant tumor with the highest morbidity and mortality worldwide. The number of cases and deaths in China also remains at a high level， posing a severe threat to human health. In recent years， although early diagnostic and therapeutic strategies for lung cancer have been continuously optimized， with clinical interventions mainly consisting of surgery， radiotherapy， chemotherapy， targeted therapy， and immunotherapy， the patient prognosis remains unsatisfactory. The core reason is that the mechanisms underlying lung cancer development and progression have not yet been fully elucidated. Therefore， delving into the molecular mechanisms and key regulatory nodes is of great significance for improving diagnostic and therapeutic outcomes. In recent years， traditional Chinese medicine （TCM） and its active components have demonstrated unique advantages and potential in the prevention and treatment of lung cancer through epigenetic regulation. Studies have confirmed that single herbs， compound formulas， and active components of TCM can exert anti-tumor effects by modulating epigenetic pathways such as DNA methylation， histone modification， and non-coding RNAs. These effects include inhibiting tumor cell proliferation， inducing apoptosis， reducing invasive and metastatic capacity， regulating the cell cycle， and modulating the tumor microenvironment， thereby blocking the initiation and progression of lung cancer. Furthermore， TCM shows significant advantages in enhancing the anti-tumor efficacy of chemotherapeutic agents and alleviating treatment-related adverse effects. However， the current research on TCM-based epigenetic regulation of lung cancer remains at a preliminary exploratory stage. Common limitations include the complexity of targets， a predominant focus on crude herbal extracts or single epigenetic modifications， and a lack of systematic elucidation of the synergistic effects among multiple epigenetic modifications and the regulatory networks involving multicellular interactions. This article reviews the epigenetic mechanisms involved in the development and progression of lung cancer and summarizes the basic and clinical research progress in TCM interventions， aiming to offer insights for further elucidating lung cancer pathogenesis and exploring TCM-based therapeutic strategies.Keywords：epigenetics;lung cancer;traditional Chinese medicine;DNA methylation;histone modification;non-coding RNA25|3|0<HTML><H-PDF><L-PDF><XML>Updated：2026-09-29Therapeutic Mechanisms of Active Components and Compound Formulas of Astragali Radix for Ischemic Stroke： A Review AI Introduction
Abstract：Ischemic stroke （IS） is characterized by a high incidence， a high disability rate， and a high mortality rate. Its pathological mechanism is complex， involving oxidative stress， neuroinflammation， glutamate excitotoxicity， blood-brain barrier （BBB） disruption， abnormal autophagy and apoptosis， energy metabolism disorder， ferroptosis， and cuproptosis. Long-term use of conventional clinical drugs is associated with certain adverse reactions. As a classic Chinese herbal medicine for replenishing Qi， Astragali Radix is widely used in the prevention and treatment of IS. Modern research has confirmed that it contains various active components， including total astragalosides， total polysaccharides， and total flavonoids， which exert cerebroprotective effects by regulating signaling pathways such as nuclear factor erythroid 2-related factor 2/heme oxygenase-1 （Nrf2/HO-1）， nuclear factor-κB （NF-κB）， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， adenosine monophosphate-activated protein kinase/mammalian target of rapamycin （AMPK/mTOR）. These effects include anti-oxidation， anti-inflammation， inhibition of excitotoxicity， protection of BBB， regulation of autophagy and apoptosis， suppression of ferroptosis， and improvement of energy metabolism. This article systematically reviews the core pathological links of IS， summarizes the cerebroprotective effects of the main active components， classic herb pairs， and representative compound formulas of Astragali Radix， and analyzes their synergistic intervention patterns against the above pathological mechanisms. Furthermore， this paper discusses the current research limitations in clinical translation， material basis， and emerging cell death modalities， along with future perspectives， aiming to provide a theoretical reference for the clinical application of Astragali Radix and its combinations in treating IS and for the development of new drugs.Keywords：Astragali Radix;active components;compound formulas;ischemic stroke;mechanism of action34|2|0<HTML><H-PDF><L-PDF><XML>Updated：2026-09-29Chinese Medicine in Treatment of Colorectal Cancer by Regulating Hedgehog Signaling Pathway： A Review AI Introduction
Abstract：Colorectal cancer （CRC）， as a highly prevalent malignant tumor worldwide， continues to rank among the leading malignancies in both incidence and mortality. At present， the clinical treatment of CRC mainly relies on surgery， radiotherapy， chemotherapy， and drug therapy. However， due to individual differences among patients and the emergence of drug resistance in cancer cells， the postoperative recurrence rate remains high， significantly affecting patient prognosis. In recent years， traditional Chinese medicine （TCM） has attracted extensive attention in the field of tumor prevention and treatment because of its therapeutic advantages of multi-component， multi-target， multi-pathway， and holistic regulation. Aberrant activation of the Hedgehog signaling pathway is closely associated with the occurrence of various cancers. Studies have shown that the Hedgehog signaling pathway plays a key regulatory role in the occurrence and development of CRC. This pathway regulates the expression of downstream target genes through glioma-associated oncogene homolog （GLI） transcription factors and participates in biological processes such as tumor cell proliferation， apoptosis， invasion， and metastasis. It exerts anti- CRC effects through mechanisms including inducing apoptosis of CRC cells， inhibiting cancer cell proliferation， reversing drug resistance， and suppressing epithelial-mesenchymal transition （EMT）， thereby influencing the progression of CRC. This article systematically reviews the latest research progress in China and abroad and comprehensively discusses the molecular regulatory mechanisms of the Hedgehog signaling pathway in CRC. It particularly focuses on the specific mechanisms by which active components of Chinese medicine， such as alkaloids and terpenoids， and Chinese medicine compound formulas， such as Baitouwengtang and Zhizhenfang， exert anti-CRC effects by interfering with the Hedgehog-GLI signaling axis. By integrating and analyzing the molecular relationship between the Hedgehog signaling pathway and the pathological progression of CRC， and combining the TCM theories of “holistic concept” and “syndrome differentiation and treatment”， this article explores new TCM therapeutic strategies based on the Hedgehog signaling pathway， with the aim of providing innovative theoretical foundations and practical guidance for the prevention and treatment of CRC with TCM.Keywords：colorectal cancer;Hedgehog signaling pathway;active ingredients of Chinese medicine;Chinese herbal compound prescription;research progress32|4|0<HTML><H-PDF><L-PDF><XML>Updated：2026-09-29Current Status of Prediction Models of Traditional Chinese Medicine for Emerging Acute Infectious Diseases AI Introduction
Abstract：ObjectiveTo analyze the current status of traditional Chinese medicine （TCM） prediction model research for emerging acute infectious diseases， in order to provide reference for subsequent model construction and optimization.MethodsEight databases， including PubMed， Cochrane Library， and Embase， were systematically searched to comprehensively collect Chinese and English literature on TCM prediction models for emerging acute infectious diseases. The search period ranged from database inception to July 5， 2024. Reporting quality compliance was evaluated using the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis—Traditional Chinese Medicine （TRIPOD-TCM） guideline. Risk of bias and applicability were assessed using the Prediction Model Risk of Bias Assessment Tool （PROBAST）.ResultsA total of 21 studies were included， comprising 11 early warning model studies， 5 diagnostic model studies， 3 prognostic model studies， and 2 prescription prediction model studies， involving 84 models in total. The diseases involved were mainly viral infectious diseases such as coronavirus disease 2019 （COVID-19） and hepatitis B. The most frequently applied TCM theory was the "five movements and six climates" theory. The most commonly used modeling method was neural network-based approaches. The most frequently reported predictive factors were meteorological variables， including daily mean temperature， wind speed， precipitation， relative humidity， and vapor pressure. In terms of reporting quality， the included studies showed poor item-level compliance， with only 13 sub-items achieving compliance rates above 50%. Overall compliance ranged from 27% to 59% across studies. Although the included studies showed relatively good applicability， all were assessed as having a high risk of bias. The main sources of bias included inappropriate handling of missing data， absence of calibration methods， and unreasonable validation strategies， indicating deficiencies across multiple stages of model development.ConclusionCurrent research on TCM prediction models for emerging acute infectious diseases exhibits distinctive modeling characteristics. These models are based on traditional TCM theories such as the "five movements and six climates"， incorporate TCM-specific features as predictive variables， and use TCM syndromes as outcomes. However， they generally suffer from low reporting compliance and a high risk of bias. Future studies should systematically design model development and validation processes， adhere to TRIPOD-TCM reporting standards， and apply PROBAST or develop dedicated bias risk assessment tools for TCM prediction models to improve methodological quality and promote their translation into clinical practice.Keywords：emerging acute infectious diseases;traditional Chinese medicine;prediction model research;methodological quality;current analysis28|3|0<HTML><H-PDF><L-PDF><XML>Updated：2026-09-29- Abstract：ObjectiveTo examine the effects of Chaihu Longgu Muli Tang （CLMT）-containing serum on Neuro-2A cell damage when exposed to conditioned medium from lipopolysaccharide （LPS）-stimulated microglia （BV-2） and explore the underlying mechanism.MethodsBV-2 cells were activated by LPS at a concentration of 1 mg·L-1 to generate conditioned medium. Concurrently， a blank control group and groups treated with varying concentrations of CLMT （5%， 10%， and 15%）， dexamethasone （2.5 μmol·L-1）， stimulator of interferon genes （STING） agonist （MSA-2， 10 μmol·L-1）， and STING inhibitor （STING-IN-4， 4 μmol·L-1） were established. Neuro-2A cells were subsequently cultured in the conditioned medium from each treatment group. The viability of BV-2 cells following interventions was assessed by the Cell Counting Kit-8 （CCK-8） assay. The levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in the supernatant of Neuro-2A cells from each group were measured through enzyme linked immunosorbent assay （ELISA）. Additionally， the expression of tyrosine hydroxylase （TH） in Neuro-2A cells was evaluated through immunohistochemistry （IHC）， while the expression of phosphorylated alpha-synuclein （p-α-syn） was assessed by immunofluorescence （IF） assay. The expression levels of STING， interferon regulatory factor 3 （IRF3）， phosphorylated interferon regulatory factor 3 （p-IRF3）， nuclear transcription factor-kappa B p65 （NF-κB p65）， and phosphorylated nuclear transcription factor-kappa B p65 （p-NF-κB p65） in Neuro-2A cells were determined by Western blot.ResultsIn comparison to the control group， both the model group and the MSA-2 group exhibited reduced viability of Neuro-2A cells （P<0.01）， elevated concentrations of TNF-α， IL-1β， and IL-6 in the cell supernatant （P<0.01）， reduced expression of TH （P<0.01）， increased expression of p-α-syn （P<0.01）， and upregulated relative protein levels of STING， p-IRF3， and p-NF-κB p65 （P<0.01）. Compared with the model group， medium- and high-dose CLMT enhanced the viability of Neuro-2A cells （P<0.01）， lowered the levels of TNF-α， IL-1β， and IL-6 （P<0.01）， promoted TH expression， and suppressed p-α-syn expression （P<0.01）. In the dexamethasone group， the levels of IL-6， TNF-α， and IL-1β were reduced （P<0.05， P<0.01）. In the STING-IN-4 group， the levels of TNF-α and IL-1β were decreased （P<0.01）. The expression of TH was increased in both the dexamethasone group and the STING-IN-4 group （P<0.01）， while the expression of p-α-syn was reduced （P<0.01）. The relative protein levels of p-IRF3， STING， and p-NF-κB p65 were reduced in medium- and high-dose CLMT groups （P<0.05， P<0.01）. Similarly， the dexamethasone group exhibited decreases in the expression levels of STING， p-IRF3， and p-NF-κBp65 （P<0.01）. In the STING-IN-4 group， the expression levels of p-NF-κB p65， STING， and p-IRF3 were also diminished （P<0.05， P<0.01）. However， no statistically significant differences were observed in the expression of IRF3 or NF-κB p65 across the groups.ConclusionCLMT has the potential to suppress the activation of BV-2 microglial cells， consequently mitigating the inflammatory response induced by LPS and further preventing inflammation-mediated damage to Neuro-2A cells. The underlying mechanism is likely associated with the modulation of the STING/NF-κB signaling pathway， which results in reduced inflammation and confers neuroprotective effects.Keywords：Parkinson's disease;neuroinflammation;Chaihu Longgu Muli Tang （CLMT）;lipopolysaccharide （LPS）;neuroprotective effect21|2|0<HTML><H-PDF><L-PDF><XML>Updated：2026-09-29
Traditional Chinese Medicine Treats Coronary Heart Disease by Intervening in Cardiovascular Cell Apoptosis： A Review AI Introduction
Abstract：Coronary heart disease （CHD）， as a globally prevalent disease with high mortality， is closely associated with cardiovascular cell apoptosis in its pathogenesis. Although current therapies such as percutaneous coronary intervention （PCI） can alleviate local stenosis and significantly improve revascularization， challenges such as postoperative reperfusion injury and microcirculation dysfunction persist. Due to the limitations of single-target therapy in modern medicine， traditional Chinese medicine （TCM） has attracted increasing attention for its multi-component and multi-target interventions. Modern medical research indicates that cardiovascular cell apoptosis contributes to CHD progression through multiple pathways， including the mitochondrial pathway， death receptor pathway， and endoplasmic reticulum stress pathway. In TCM theory， CHD falls under the categories of chest obstruction， heart pain， and real heart pain. The Synopsis of the Golden Chamber （Jin Gui Yao Lue） proposes the pathogenesis theory of Yang deficiency and Yin excess， emphasizing the therapeutic principles of activating blood， regulating Qi movement， resolving stasis， and unblocking collaterals. TCM demonstrates unique advantages in ameliorating myocardial ischemia and combating atherosclerosis. However， existing studies are largely confined to clinical observations， lacking in-depth exploration of TCM mechanisms in inhibiting cardiovascular cell apoptosis. This article systematically reviews the regulatory mechanisms of cardiovascular cell apoptosis in CHD and TCM intervention strategies， aiming to provide a theoretical basis for elucidating the scientific rationale behind TCM's role in suppressing apoptosis and improving cardiac function， while offering insights for developing innovative treatment approaches combining TCM and modern medicine. Future studies should leverage modern molecular biological technologies to further uncover the scientific essence of TCM regulation of apoptotic pathways. Integrating TCM's holistic regulation and multi-target intervention strengths with modern medicine's targeted therapies can advance both fundamental research and clinical translation， ultimately providing superior strategies for the prevention and treatment of CHD.Keywords：coronary heart disease;endogenous apoptosis;exogenous apoptosis;endoplasmic reticulum stress （ERS） pathway;traditional Chinese medicine25|4|0<HTML><H-PDF><L-PDF><XML>Updated：2026-09-29- Abstract：Alzheimer's disease （AD） is a neurodegenerative disorder characterized by amyloid-β （Aβ） plaque deposition， neurofibrillary tangle （NFT） formation， and chronic neuroinflammation. Its global incidence and mortality continue to rise， yet effective curative therapies remain unavailable. In recent years， dysregulated cholesterol metabolism and immune-inflammatory responses have been increasingly recognized as key drivers of AD pathological progression. Both clinical and experimental studies have shown that patients with AD exhibit disrupted cholesterol homeostasis and aberrant T-cell function， with a significant correlation between these alterations， suggesting that cholesterol metabolic disturbances may participate in and amplify neuroinflammatory responses by modulating T-cell differentiation and activation states. This review systematically delineates the coupling relationship among cholesterol homeostasis imbalance， T-cell abnormalities， AD neuroinflammation， and related pathological injury. Specifically， we summarize the immunometabolic pathological links spanning the peripheral and central compartments， ranging from the effects of peripheral cholesterol metabolic disturbances on T-cell activation， differentiation， and blood–brain barrier permeability to the regulatory role of impaired brain cholesterol homeostasis in infiltrating T-cell inflammatory responses， glial activation， and neural microenvironment remodeling. We further highlight how abnormalities in cholesterol synthesis， transport， efflux， and oxidative product accumulation promote Th17/Treg imbalance， enhanced CD8⁺T-cell effector activity， increased inflammatory cytokine release， as well as Aβ deposition， blood-brain barrier disruption， glial activation， and neuronal injury. In addition， we review recent progress in natural herbal formulas and bioactive phytochemicals that alleviate T-cell abnormalities and neuroinflammation through restoration of cholesterol homeostasis. Taken together， current evidence suggests that cholesterol homeostasis imbalance is not only a fundamental metabolic abnormality in AD， but may also construct and amplify AD neuroinflammation and related pathological injury by reshaping T-cell immunophenotypes. Therefore， immunometabolic intervention strategies aimed at restoring cholesterol homeostasis may provide a new theoretical basis for mechanistic studies and multi-target prevention and treatment of AD.Keywords：Alzheimer's disease;cholesterol homeostasis imbalance;T-cell abnormalities;neuroinflammation;cholesterol synthesis;cholesterol efflux18|3|0<HTML><H-PDF><L-PDF><XML>Updated：2026-09-29
Investigating Therapeutic Effect and Mechanism of Zhengqi Prescription on Cancer-related Fatigue by UPLC-MS and Network Pharmacology AI Introduction
Abstract：ObjectiveTo characterize the systemically absorbed components of Zhengqi prescription （ZQP） and investigate its therapeutic effects and mechanisms against cancer-related fatigue （CRF） through an integrated approach of network pharmacology and animal experiments.MethodsThe systemically absorbed components of ZQP were identified by ultra-performance liquid chromatography coupled with quadrupole-Orbitrap mass spectrometry （UPLC-Q-Exactive Orbitrap MS）. Network pharmacology was employed to predict the potential targets and signaling pathways involved in the anti-CRF effects of ZQP. A mouse model of paclitaxel-induced CRF， mimicking breast cancer-related fatigue， was established. Mice were administered different doses of ZQP extract. The therapeutic efficacy was evaluated based on fatigue-related indicators， behavioral test results， and energy metabolism parameters. Western blot analysis was conducted to validate the regulation of core signaling pathways.ResultsA total of 48 systemically absorbed components were identified. Network pharmacology analysis revealed 124 intersecting targets （including Akt1） and implicated signaling pathways such as phosphatidylinositol 3-kinase/protein kinase （PI3K/Akt）. Pharmacodynamic studies with the established CRF model demonstrated that ZQP alleviated fatigue symptoms. Specifically， ZQP-treated mice exhibited increased exhaustive swimming time （P<0.05）， prolonged struggling time in the tail suspension test， and enhanced movement duration and distance in the open field test （P<0.05， P<0.01）. Furthermore， ZQP treatment decreased serum lactate and blood urea nitrogen levels （P<0.05， P<0.01）， increased liver and muscle glycogen content （P<0.05， P<0.01）， and upregulated the expression of phosphorylated （p）-Akt and p-PI3K in the gastrocnemius muscle （P<0.05， P<0.01）.ConclusionZQP exerts significant therapeutic effects on paclitaxel-induced breast cancer-related fatigue by regulating the PI3K/Akt signaling pathway. Furthermore， this study provides a preliminary foundation for subsequent quality control of the formula and further investigation into its mechanism against CRF.Keywords：Zhengqi prescription;cancer-related fatigue;ultra-performance liquid chromatography coupled with quadrupole-Orbitrap mass spectrometry （UPLC-Q-Exactive Orbitrap MS）;network pharmacology;phosphatidylinositol 3-kinase/protein kinase （PI3K/Akt） signaling pathway19|3|0<HTML><H-PDF><L-PDF><XML>Updated：2026-09-29- Abstract：ObjectiveTo investigate the effect and mechanism of Hei Xiaoyaosan in preventing and treating Alzheimer's disease （AD） by activating autophagy through regulating the adenosine monophosphate-activated protein kinase （AMPK）/UNC-51 like autophagy activating kinase 1 （ULK1） signaling pathway.MethodsNinety 8-week-old male SPF-grade SD rats were selected and randomized into two groups： a blank control group （n=10） and a modeling group （n=80）. From the modeling group， 10 rats were randomly assigned as a sham group （bilateral hippocampal injection of 1 μL normal saline）， while the remaining 70 rats were injected with 1 μL Aβ1-42 solution bilaterally into the hippocampus to replicate the AD model. The Morris water maze test was conducted to screen the successfully modeled rats， which were then randomly allocated to the model， donepezil hydrochloride， 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside （AICAR， an AMPK agonist）， and high-， medium-， and low-dose Hei Xiaoyaosan groups， with 10 rats per group. After 42 days of drug intervention， the Morris water maze and open field tests were conducted to assess learning and memory abilities and motor function. Pathological changes in the hippocampal tissue were observed by Nissl staining， and autophagy-related pathological damage was examined via transmission electron microscopy （TEM）. The expression of LC3 in the hippocampus was observed by immunofluorescence staining. The protein levels of AMPK， phosphorylate （p）-AMPK， ULK1， p-ULK1， p62， and autophagy related 7 （Atg7） were determined by Western blot， while the mRNA levels of AMPK and ULK1 were measured by Real-time polymerase chain reaction （Real-time PCR）.ResultsCompared with the blank control group， the model group showed increased escape latency （P<0.01） and decreased platform crossings （P<0.01） on day 6 in the water maze test， reduced total distance traveled and average speed in the open field test （P<0.01）， disarranged neurons with Nissl body loss and evident autophagic damage， weakened LC3 fluorescence signal （P<0.01）， downregulated protein levels of p-AMPK， p-ULK1， and Atg7 and mRNA levels of AMPK and ULK1 in the hippocampus （P<0.01）， and upregulated protein level of p62 （P<0.01）. Compared with the model group， the positive drug group， high-dose Hei Xiaoyaosan group， and AICAR group showed decreased escape latency （P<0.05， P<0.01） and increased platform crossings （P<0.01） on day 6， and increased total distance traveled and average speed in the open field test （P<0.05， P<0.01）. The positive drug group， high- and medium-dose Hei Xiaoyaosan groups， and the AICAR group showed alleviated cellular structural damage， regular neuronal arrangement， increased Nissl bodies， and orderly distribution of autophagosomes. Furthermore， the LC3 fluorescence intensity was enhanced in the positive drug group， high- and medium-dose Hei Xiaoyaosan groups， and the AICAR group （P<0.01）. The positive drug group， high-dose Hei Xiaoyaosan group， and the AICAR group exhibited upregulated protein and mRNA levels of p-AMPK and p-ULK1 （P<0.05， P<0.01）， upregulated protein level of Atg7 （P<0.05， P<0.01）， and downregulated protein level of p62 （P<0.05， P<0.01）.ConclusionHei Xiaoyaosan can improve learning and memory abilities and alleviate pathological status in the rat model of AD by regulating the AMPK/ULK1 signaling pathway， enhancing cellular autophagy， and repairing damaged nerve cells.Keywords：Alzheimer's disease;Hei Xiaoyaosan;autophagy;adenosine monophosphate-activated protein kinase （AMPK）/UNC-51 like autophagy activating kinase 1 （ULK1） signaling pathway21|3|0<HTML><H-PDF><L-PDF><XML>Updated：2026-09-29
Paeoniflorin Ameliorates Neuroinflammation and Cognitive Impairment in Rat Model of Alzheimer's Disease via JAK2/STAT3 Signaling Pathway AI Introduction
Abstract：ObjectiveTo investigate the effects of paeoniflorin （PF） on neuroinflammation and cognitive impairment in the rat model of Alzheimer's disease （AD） and to clarify whether its mechanism is associated with regulation of the Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway.MethodsGlycosides related to AD-associated neuroinflammation were screened through bibliometric analysis， and the potential targets of PF were predicted through network pharmacology and molecular docking. A rat model of AD was established by intraperitoneal injection of D-galactose （100 mg·kg-1·d-1）. Rats were assigned into a control group， a model group， a PF （200 mg·kg-1） group， and a donepezil （0.5 mg·kg-1·d-1） group， and drugs were administered by gavage for 21 days. The learning and memory abilities were evaluated by the Morris water maze （MWM）. Hematoxylin-eosin （HE） staining and Nissl staining were performed to observe hippocampal neuronal morphology. The mRNA levels of inflammatory factors were determined by Real-time PCR， and the protein levels of molecules in the JAK2/STAT3 signaling pathway were determined by Western blot.ResultsCompared with the control group， the model group showed prolonged escape latency and decreased platform crossings and time spent in the target quadrant （P<0.05， P<0.01）， accompanied by increased expression of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α）， as well as elevated ratios of phosphorylated （p）-JAK2/JAK2 and p-STAT3/STAT3 （P<0.01）. Compared with the model group， the PF group and donepezil group exhibited shortened escape latency and increased platform crossings and time spent in the target quadrant （P<0.05， P<0.01）， decreased expression levels of IL-1β and TNF-α， upregulated mRNA levels of interleukin-4 （IL-4） and interleukin-10 （IL-10）， and reduced ratios of p-JAK2/JAK2 and p-STAT3/STAT3 （P<0.05， P<0.01）.ConclusionPaeoniflorin can alleviate cognitive impairment and neuroinflammation in the rat model of AD by inhibiting the JAK2/STAT3 signaling pathway.Keywords：paeoniflorin;Alzheimer's disease;neuroinflammation;Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway;cognitive impairment15|5|0<HTML><H-PDF><L-PDF><XML>Updated：2026-09-29Effect of Schisanlactone E on Neuroinflammation and Synaptic Damage in APP/PS1 Mice and Their Relationship with Th17/Treg Immune Balance AI Introduction
Abstract：ObjectiveTo investigate the effect of schisanlactone E in ameliorating neuroinflammation and synaptic injury in APP/PS1 mice and to elucidate whether its mechanism is related to the regulation of helper T cell 17 （Th17）/regulatory T cell （Treg） immune balance.MethodsAPP/PS1 transgenic mice were assigned into model， low- and high-dose （2 mg·kg-1·d-1 and 4 mg·kg-1·d-1， respectively） schisanlactone E， and donepezil （1 mg·kg-1·d-1） groups. C57BL/6J mice were used as the control group. Each group received the corresponding drug by gavage for 30 days. Learning and memory abilities were assessed by the Morris water maze and novel object recognition tests. The percentages of Th17 and Treg cells in the peripheral blood were analyzed by flow cytometry. The mRNA levels of retinoid-related orphan receptor γt （RORγt）， interleukin （IL）-17A， forkhead box protein 3 （FoxP3）， and IL-4 in the hippocampus were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The synaptic ultrastructure in the hippocampus was observed by transmission electron microscopy. The protein levels of synapsin Ⅰ and postsynaptic density protein 95 （PSD95） in the hippocampus were measured by Western blot. Aβ aggregation and microglial activation in the hippocampus were observed by immunofluorescence staining. The mRNA levels of tumor necrosis factor （TNF）-α， IL-6， and IL-1β in the hippocampus were determined by Real-time PCR.ResultsCompared with the control group， the model group showed prolonged escape latency （P<0.05）， decreased time spent in the target quadrant， platform crossings， novel object exploration time， and percentage of novel object contact frequency （P<0.05， P<0.01）， increased Aβ aggregation in the hippocampal tissue （P<0.01）， an increased proportion of Th17 cells （P<0.05）， a decreased proportion of Treg cells （P<0.05）， and an increased Th17/Treg ratio （P<0.01） in the peripheral blood. Furthermore， the hippocampal tissue in the model group exhibited upregulated mRNA levels of RORγt and IL-17A （P<0.05， P<0.01）， downregulated mRNA levels of FoxP3 and IL-4 （P<0.01）， decreased synapses （P<0.05）， decreased PSD density， synaptic interface curvature， and active zone length （P<0.05， P<0.01）， and increased synaptic cleft width （P<0.05）， downregulated protein levels of Synapsin Ⅰ and PSD95 （P<0.01）， increased microglial activation （P<0.01）， and upregulated mRNA levels of TNF-α， IL-6， and IL-1β （P<0.05）. Compared with the model group， the high-dose schisanlactone E group and the donepezil group exhibited shortened escape latency and increased time in the target quadrant and platform crossings （P<0.05， P<0.01）. The schisanlactone E groups and the donepezil group showed increased novel object exploration time （P<0.05， P<0.01） and percentage of novel object contact frequency （P<0.05， P<0.01）， and reduced hippocampal Aβ aggregation （P<0.05， P<0.01）. The schisanlactone E groups showed a decreased proportion of Th17 cells （P<0.05） and an increased proportion of Treg cells （P<0.05） in the peripheral blood， and all treatment groups showed a decreased Th17/Treg ratio （P<0.05， P<0.01）. The high-dose schisanlactone E group showed a downregulated mRNA level of RORγt in the hippocampal tissue （P<0.05）， and all treatment groups showed a downregulated mRNA level of IL-17A （P<0.05， P<0.01）， and upregulated mRNA levels of FoxP3 and IL-4 （P<0.05， P<0.01）. The schisanlactone E groups and the donepezil group showed increased synapses， active zone length， synaptic interface curvature， and PSD density， decreased synaptic cleft width （P<0.05， P<0.01）， and upregulated protein levels of synapsin Ⅰ and PSD95 （P<0.05， P<0.01）. The high-dose schisanlactone E group and the donepezil group showed decreased microglial activation in the hippocampus （P<0.01）. The schisanlactone E groups and the donepezil group showed downregulated mRNA levels of TNF-α， IL-6， and IL-1β in the hippocampal tissue （P<0.05， P<0.01）.ConclusionSchisanlactone E significantly improves the cognitive function in APP/PS1 mice by regulating the Th17/Treg immune balance， inhibiting neuroinflammation， and ameliorating synaptic injury.Keywords：schisanlactone E;Alzheimer's disease;synapses;helper T cell 17 （Th17）;regulatory T cell （Treg）;neuroinflammation14|3|0<HTML><H-PDF><L-PDF><XML>Updated：2026-09-29Aspirin Curcumin Ester Inhibits High Glucose/Aβ1-42-induced Microglial Inflammatory Response by Regulating Glucose Metabolism Reprogramming AI Introduction
Abstract：ObjectiveTo observe the effect of Aspirin-Curcumin ester （CA） on the activation and glucose metabolism reprogramming of mouse microglia （BV2） inflammation model induced by high glucose/β-amyloid （Aβ）1-42， and to explore the potential mechanism of CA reducing neuroinflammatory response in the brain.MethodsBV2 activation model was constructed by high glucose combined with Aβ1-42 oligomers. BV2 cells were treated with Aβ1-42 oligomers （10 μmol·L-1） in high glucose （50 mmol·L-1） environment and divided into normal group， high glucose group， Aβ group and high glucose + Aβ group. The morphology of each group was observed under bright field. Quantitative real-time PCR （Real-time PCR） was used to detect the mRNA expression of inflammatory factors including tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， interleukin-1β （IL-1β） and glycolysis-related glucose transporter type 1 （GLUT1）， hexokinase2 （HK2）， phospofructokinase-2/fructose-2，6-bisphosphatase 3 （PFKFB3）， pyruvate kinase M2 （PKM2）. The effect of CA on inflammatory response and glucose metabolism in BV2 cells induced by high glucose/Aβ1-42： BV2 cells were constructed as an inflammatory activation model by high glucose and Aβ1-42 oligomer intervention， and divided into normal group， model group （50 mmol·L-1 glucose+10 μmol·L-1 Aβ1-42）， CA group （10 μmol·L-1）， 2DG group （0.2 mmol·L-1） and DADA group （1 mmol·L-1）. Cell counting kit-8 （CCK-8） was used to detect cell survival rate ； observe the cell morphology of each group under bright field ； the expression of inflammatory factors TNF-α， IL-6， IL-1β and glycolysis key enzymes GLUT1， HK2， PFKFB3 and PKM2 mRNA in each group was detected by Real-time PCR. The protein expression levels of GLUT1， HK2， PFKFB3 and PKM2 were detected by Western blot. The changes of glycolysis rate in each group were detected by seahorse. LC-MS was used to detect the changes of glucose metabolism intermediates ； the morphology of mitochondria in cells was detected by electron microscopy.ResultsConstruction of the BV2 cell model： Compared with the control group， the Aβ group and the high glucose + Aβ group showed more amoeboid-shaped cells and cell aggregation. The high glucose + Aβ group exhibited increased mRNA levels of the inflammatory cytokines TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01）， as well as increased mRNA expression of the key glycolytic enzymes GLUT1， HK2， PFKFB3， and PKM2 （P<0.01）. The Aβ group also showed significantly increased mRNA expression levels of PKM2 and PFKFB3 （P<0.01）.Effect of CA on the inflammatory response and glucose metabolism in BV2 cells induced by high glucose/Aβ1-42： Compared with the control group， BV2 cells in the M group exhibited an amoeboid shape and formed aggregates. The mRNA expression of TNF-α， IL-1β， IL-6， iNOS， GLUT1， HK2， PFKFB3， and PKM2 was increased （P<0.01）， and the protein expression of GLUT1， HK2， and PFKFB3 was increased （P<0.05， P<0.01）. The basal glycolysis rate was elevated （P<0.01）， while the compensatory glycolysis rate was decreased （P<0.01）. Glycolytic intermediates were increased， whereas TCA cycle intermediates were decreased. Mitochondrial number was reduced （P<0.05）， cristae integrity was diminished （P<0.01）， the proportion of vacuolization was increased （P<0.01）， and mitochondrial morphology was abnormal. Compared with the model group， following intervention with CA， 2DG， and DADA， the number of BV2 cells with amoeboid morphology was reduced in the CA and 2DG groups， while most BV2 cells in the DADA group became elongated spindle-shaped. The mRNA expression of TNF-α， IL-1β， IL-6， GLUT1， HK2， PFKFB3， and PKM2 was decreased in all three treatment groups （P<0.05， P<0.01）. Protein expression of GLUT1， HK2， and PFKFB3 was also decreased （P<0.05， P<0.01）. The compensatory glycolysis rate and the basal glycolysis rate were reduced （P<0.05， P<0.01）. Glycolytic intermediates were decreased and TCA cycle intermediates were increased in the CA and 2DG groups. Mitochondrial morphology largely returned to normal in all three treatment groups， with an increase in mitochondrial number （P<0.05）， improved cristae integrity （P<0.05， P<0.01）， and a decreased proportion of vacuolization （P<0.05）.ConclusionAβ1-42 oligomers can activate BV2 cells and enhance glycolytic activity in high glucose environment. CA can reduce the expression of inflammatory factors and inhibit the activation of BV2 cells by regulating the reprogramming of glucose metabolism in BV2 cells.Keywords：microglia;glycolysis;aspirin curcumin ester;Alzheimer's disease;neuroinflammation24|3|0<HTML><H-PDF><L-PDF><XML>Updated：2026-09-29Outcome Indicators in Randomized Controlled Trials of Traditional Chinese Medicine Intervention in Chronic Kidney Disease AI Introduction
Abstract：ObjectiveTo systematically collate the randomized controlled trials （RCTs） on the intervention of traditional Chinese medicine （TCM） in chronic kidney disease （CKD） and analyze the characteristics of clinical trials and the current situation of outcome indicators， thus providing references for constructing a core outcome set （COS） for CKD.MethodsThe RCTs on the intervention of TCM in CKD were retrieved from CNKI， Wanfang Data， VIP， SinoMed， PubMed， Cochrane Library， EMbase， and Web of Science with the time interval from January 2022 to December 2024. The risk of bias was evaluated， and the outcome indicators were qualitatively analyzed.ResultsA total of 242 RCTs were included， which reported 238 outcome indicators， with the cumulative frequency of 2 724 times. These outcome indicators can be classified into seven domains： TCM syndromes and diseases （270 times， accounting for 9.90%）， symptoms and signs （218 times， 8.00%）， physical and chemical examinations （1 609 times， 59.07%）， quality of life （29 times， 1.06%）， long-term prognosis （6 times， 0.22%）， economic evaluation （0 times）， and safety events （535 times， 19.64%）. The results demonstrated that the RCTs of TCM intervention for CKD had several shortcomings such as the lack of a basis for sample size estimation， lack of standardization in TCM syndrome differentiation and classification， room for improvement in methodological quality， flaws in the design of the timing of efficacy measurement， absence of long-term prognosis evaluation， imbalance in the selection of surrogate and endpoint indicators， disconnection between overall evaluation and individualized assessment， lack of TCM characteristic indicators， and insufficient reporting of safety indicators.ConclusionAt present， the design of outcome indicators in the RCTs for TCM intervention in CKD is still not standardized. It is recommended that future research endeavors to enhance methodological quality， establish a standardized COS for TCM intervention in CKD， and thereby propel the high-quality development of TCM.Keywords：chronic kidney disease;traditional Chinese medicine;randomized controlled trials;outcome indicators;core set of indicators30|3|0<HTML><H-PDF><L-PDF><XML>Updated：2026-09-29Ditantang Ameliorates MAFLD in Rats Through UDPG-S1P-SREBP Axis-mediated Glycogen Synthesis AI Introduction
Abstract：ObjectiveTo investigate the effects of Ditantang on metabolic dysfunction-associated fatty liver disease （MAFLD） in rats by focusing on the regulation of glycogen synthesis mediated by the uridine diphosphate glucose （UDPG）-site-1-protease （S1P）-sterol regulatory element-binding protein （SREBP） axis.MethodsMAFLD was modeled in SD rats by feeding a high-fat diet for 12 weeks. Rats were randomized into a control group， a model group， low-， medium-， and high-dose （2.68， 5.36， and 10.72 g·kg-1·d-1， respectively） Ditantang groups， and a positive control （Yishanfu， 0.18 g·kg-1·d-1） group. Starting from week 9 of modeling， each treatment group received corresponding drug interventions via gavage. After the experiment， the serum levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were measured. The levels of TG， non-esterified fatty acids （NEFA）， glycogen， glucose-6-phosphate （G6P）， glucose-1-phosphate （G1P）， and UDPG in the liver tissue samples were measured by biochemical assay kits. Liver pathological morphology and lipid/glycogen deposition were observed via hematoxylin-eosin （HE） staining， oil red O staining， and Periodic acid-Schiff （PAS） staining. Immunofluorescence assay was conducted to detect the expression and localization of phosphoglucomutase-1 （Pgm1） and UDP-glucose pyrophosphorylase 2 （Ugp2） in the rat liver. Real-time PCR and Western blot were employed to quantify mRNA and protein levels， respectively， of key glycogen synthesis enzymes （Pgm1 and Ugp2）， key lipogenesis-related transcription factor SREBP and its target genes ［acetyl-CoA carboxylase （ACC）， fatty acid synthetase （FASN）， and stearoyl-CoA desaturase （SCD1）］， as well as S1P.ResultsCompared with the control group， the model group exhibited elevated levels of TC， TG， LDL-C in the serum and TG and NEFA in the liver， decreased serum HDL-C level （P<0.01）， reduced hepatic levels of G1P， G6P， UDPG， and glycogen （P<0.01）， appearance of fat vacuoles of varying sizes and abundant red lipid droplets， with prominent lipid deposition and reduced areas of deep glycogen staining in the liver tissue， upregulated mRNA and protein levels of SREBP1， S1P， ACC， FASN， and SCD1 （P<0.01）， and downregulated mRNA and protein levels of Pgm1 and Ugp2 （P<0.01）. Compared with the model group， all doses of Ditantang reduced the levels of TC and TG in the serum and TG and NEFA in the liver， while elevating the serum HDL-C level. Additionally， medium- and high-dose Ditantang reducted the LDL-C level （P<0.05）. Ditantang at all doses increased the hepatic levels of G1P， G6P， UDPG， and glycogen， alleviated hepatic steatosis and lipid deposition， enhanced glycogen storage， downregulated the mRNA and protein levels of SREBP1， S1P， ACC， FASN， and SCD1 （P<0.05）， while upregulating the expression of Pgm1 and Ugp2 （P<0.01）. Immunofluorescence analysis revealed decreased fluorescence intensity of S1P and enhanced fluorescence intensity of Ugp2 （P<0.01）.ConclusionDitantang can regulate glycogen synthesis through the UDPG-S1P-SREBP axis to prevent and treat MAFLD.Keywords：Ditantang;metabolic dysfunction-associated fatty liver disease;the uridine diphosphate glucose （UDPG）-site-1-protease （S1P）-sterol regulatory element-binding protein （SREBP） axis;glycogen synthesis;lipid metabolism24|3|0<HTML><H-PDF><L-PDF><XML>Updated：2026-09-29
