By exploring theories related to yin-yang， body and spirit， and the relationship between nature and human beings， this study proposed the holistic functional perspective in Traditional Chinese Medicine （TCM） rehabi-litation. This perspective emphasizes the influence of various internal and external factors on the body's function and health status， with the integration of form and spirit as its core concept. It integrates the principles of correspondence between nature and human beings， as well as the unity of individuals and society， positioning holistic function as the key focus in TCM rehabilitation practice. It guides the prevention， assessment， and rehabilitation treatment of functional disorders， ultimately achieving the goal of comprehensive recovery of health. Additionally， the study reviewed the current application status of the holistic functional perspective in clinical TCM rehabilitation， clarified its integration throughout the entire TCM rehabilitation process， with the goal of providing a theoretical and practical foundation for further research and application in TCM rehabilitation.

OBJECTIVES: To investigate the effect of amentoflavone (AF) for alleviating lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and inhibiting NLRP3/ASC/Caspase-1 axis-mediated pyroptosis. METHODS: Female BALB/c mice were randomly divided into control group, LPS group, and AF treatment groups at low, moderate and high doses (n=12). ALI models were established by tracheal LPS instillation, and in AF treatment groups, AF was administered by gavage 30 min before LPS instillation. Six hours after LPS instillation, the mice were euthanized for examining lung tissue histopathological changes, protein levels in BALF, and MPO levels in the lung tissue. In the in vitro experiment, RAW264.7 cells were pretreated with AF, AC (a pyroptosis inhibitor), or their combination for 2 h before stimulation with LPS and ATP. The changes in cell proliferation and viability were detected using CCK-8 assay, and IL-1β, IL-6, IL-18, and TNF-α levels were determined with ELISA. Immunohistochemistry, immunofluorescence assay, and immunoblotting were used to detect the protein levels of NLRP3, ASC, cleaved caspase-1, and GSDMD N in rat lung tissues and the treated cells. RESULTS: In mice with LPS exposure, AF treatment significantly improved lung pathologies and edema, reduced protein levels in BALF and pulmonary MPO level, inhibited the high expression of NLRP3/ASC/Aspase-1 axis, reduced the expression of GSDMD N, and lowered the release of IL-1β, IL-6, IL-18, and TNF‑α. In RAW264.7 cells with LPS and ATP stimulation, AF pretreatment effectively reduced cell death, inhibited activation of the NLRP3/ASC/Aspase-1 axis, and reduced GSDMD N expression and the inflammatory factors. The pyroptosis inhibitor showed a similar effect to AF, and their combination produced more pronounced effects in RAW264.7 cells. CONCLUSIONS Amentoflavone can alleviate ALI in mice possibly by inhibiting NLRP3/ASC/Caspase-1 axis-mediated cell pyroptosis.
Animals ; Pyroptosis/drug effects* ; Acute Lung Injury/pathology* ; Mice ; Mice, Inbred BALB C ; Female ; Lipopolysaccharides ; Biflavonoids/pharmacology* ; RAW 264.7 Cells ; NLR Family, Pyrin Domain-Containing 3 Protein ; Caspase 1/metabolism* ; Lung

Reprogramming of energy metabolism is one of the basic characteristics of cancer and has been proved to be an important cancer treatment strategy. Isocitrate dehydrogenases (IDHs) are a class of key proteins in energy metabolism, including IDH1, IDH2, and IDH3, which are involved in the oxidative decarboxylation of isocitrate to yield α-ketoglutarate (α-KG). Mutants of IDH1 or IDH2 can produce d-2-hydroxyglutarate (D-2HG) with α-KG as the substrate, and then mediate the occurrence and development of cancer. At present, no IDH3 mutation has been reported. The results of pan-cancer research showed that IDH1 has a higher mutation frequency and involves more cancer types than IDH2, implying IDH1 as a promising anti-cancer target. Therefore, in this review, we summarized the regulatory mechanisms of IDH1 on cancer from four aspects: metabolic reprogramming, epigenetics, immune microenvironment, and phenotypic changes, which will provide guidance for the understanding of IDH1 and exploring leading-edge targeted treatment strategies. In addition, we also reviewed available IDH1 inhibitors so far. The detailed clinical trial results and diverse structures of preclinical candidates illustrated here will provide a deep insight into the research for the treatment of IDH1-related cancers.

Brain glucose metabolism disorder is one of the pathophysiological features of Alzheimer's disease (AD), in which aerobic glycolysis (Warburg effect) metabolic pathway abnormality is one of the causes of early cognitive impairment in AD, and improving brain energy metabolism has become an important strategy to prevent AD. AMP-activated protein kinase (AMPK) is a central hub regulating glucose metabolism, the most sensitive molecular compound for sensing fluctuations of energy levels in the body. Activation of AMPK can affect the Warburg effect and its key rate-limiting enzyme activity, regulate brain glucose metabolism involved in the pathogenesis of AD, to achieve the purpose of delaying AD progression and improving cognitive function in early clinical stage. In this review, we will discuss the pathogenesis of AD and targeting of AMPK from the perspective of Warburg effect in glucose metabolism.

Stroke at the acute stage is a major cause of disability in adults, and is associated with dysfunction of brain networks. However, the mechanisms underlying changes in brain connectivity in stroke are far from fully elucidated. In the present study, we investigated brain metabolism and metabolic connectivity in a rat ischemic stroke model of middle cerebral artery occlusion (MCAO) at the acute stage using F-fluorodeoxyglucose positron emission tomography. Voxel-wise analysis showed decreased metabolism mainly in the ipsilesional hemisphere, and increased metabolism mainly in the contralesional cerebellum. We used further metabolic connectivity analysis to explore the brain metabolic network in MCAO. Compared to sham controls, rats with MCAO showed most significantly reduced nodal and local efficiency in the ipsilesional striatum. In addition, the MCAO group showed decreased metabolic central connection of the ipsilesional striatum with the ipsilesional cerebellum, ipsilesional hippocampus, and bilateral hypothalamus. Taken together, the present study demonstrated abnormal metabolic connectivity in rats at the acute stage of ischemic stroke, which might provide insight into clinical research.
Acute Disease ; Animals ; Brain ; diagnostic imaging ; metabolism ; Brain Mapping ; Disease Models, Animal ; Fluorodeoxyglucose F18 ; Glucose ; metabolism ; Infarction, Middle Cerebral Artery ; diagnostic imaging ; metabolism ; Male ; Neural Pathways ; diagnostic imaging ; metabolism ; Positron-Emission Tomography ; Radiopharmaceuticals ; Random Allocation ; Rats, Sprague-Dawley

Objective To investigate the relationship between learning and memory deficit and demyelination of the corpus callosum in twelve-month old APP/PS1 transgenic mice. Methods Twelve twelve-month old APP/PS1 transgenic mice were as AD group, and age-matched wild type (WT) littermates were as WT group. Learning and memory ability was tested with Morris water maze, and the mor-phology of nerve fiber of corpus callosum was detected with Luxol Fast Blue staining. Immunohistochemistry was used to detect myelin ba-sic protein (MBP) in the corpus callosum. Thioflavine S staining was used to detect amyloid plaque in the corpus callosum. Results Com-pared with WT group, the latency increased (Z>2.873, P<0.01) and the times crossing the location of the platform decreased (t=-7.339, P<0.001) in AD group. The nerve fibers were sparse and disorganized, with a lot of vacuoles in the corpus callosum of AD group. The positive expression of MBP in the corpus callosum was significantly decreased (t=-4.481, P<0.001) in AD group compared with WT group. There were amyloid plaques in the corpus callosum of AD group. Conclusion Twelve-month old APP/PS1 transgenic mice exhibit learning and memory deficit, which may be attributed to the deposition of the amyloid plaque mediated demyelinated injury of the corpus callosum.

With the development of aging population, the morbidity of Alzheimer's disease (AD) is increasing. Electroacupuncture on several acupoints, especially Baihui (GV20), may improve the cognitive function, brain morphology, and reduceβ-amyloid deposition and tau protein phosphorylation, in AD models.

There are two phenotypes of microglia, M1 and M2. Microglia in M2 polarization may associate with the phagorytosis of be-ta-amyloid and inhibition of Tau hyperphosphorylation, as well as in other pathology. Electroacupuncture can impact the phenotypes of mi-croglia, which may play a role in the treatment for Alzheimer's disease.

Diffusion tensor imaging (DTI) can detect the integrity of white matter in vivo, through which various white matter damages of the brains have been found in patients with Alzheimer's disease (AD), even mild cognitive impairment. These damages of white matter may relate to the impairment of cognitive function, otherwise, damages in various area may result in various clinical features. DTI may fur-ther be used in the study of AD development and therapeutic evaluation.

Objective To explore the effect of electroacupuncture at Quchi (LI11) and Zusanli (ST36) acupoints on motor behaviors, the axonal integrity and nerve bundle of motor cortex and striatum in rat model of ischemic stroke induced by middle cerebral artery occlusion (MCAO) using diffusion tensor imaging (DTI). Methods Thirty-six adult male Sprague-Dawley rats were randomly assigned to sham opera-tion group (sham group), ischemia control group (model group) and electroacupuncture treatment group (EA group) with twelve rats in each group. The later two groups were occluded their middle cerebral arteries for two hours. Twenty-four hours after modeling, EA group re-ceived electroacupuncture at Quchi (LI11) and Zusanli (ST36) acupoints on the paralyzed limb, once a day, for 14 days. They were assessed with modified Neurological Severity Scores (mNSS) and Rota-rod test, and scanned with small animal magnetic resonance imaging system for T2-weighted image (T2WI) and DTI, the infarct size, related fractional anisotropy (rFA) and related number of tracks of motor cortex and striatum were recorded. Results Compared with the sham group, the score of mNSS increased in the model group and EA group after model-ing, and was lower in EA group than in the model group seven days and 14 days after intervention (P<0.05). Rota-rod test showed that the retention time was significantly longer in EA group than in the model group (P<0.05). T2WI showed that the infarct size was smaller in EA group than in the model group (P<0.05). DTI showed that rFA in motor cortex and striatum was higher in EA group than in the model group (P<0.05), as well as the related number of tracks (P<0.05) in motor cortex. Conclusion Electroacupuncture at Quchi and Zusanli acupoints could improve the motor function in rats with ischemic stroke, which may be related to the recovery of nerve bundle of motor cortex and stri-atum in ischemic side.