Exercise-induced metabolic remodeling is a fundamental adaptive process whereby the body reorganizes systemic and cellular metabolism to meet the dynamic energy demands posed by physical activity. Emerging evidence reveals that such remodeling not only enhances energy homeostasis but also profoundly influences immune function through complex molecular interactions involving glucose, lipid, and protein metabolism. This review presents an in-depth synthesis of recent advances, elucidating how exercise modulates immune regulation via metabolic reprogramming, highlighting key molecular mechanisms, immune-metabolic signaling axes, and the authors’ academic perspective on the integrated “exercise-metabolism-immunity” network. In the domain of glucose metabolism, regular exercise improves insulin sensitivity and reduces hyperglycemia, thereby attenuating glucose toxicity-induced immune dysfunction. It suppresses the formation of advanced glycation end-products (AGEs) and interrupts the AGEs-RAGE-inflammation positive feedback loop in innate and adaptive immune cells. Importantly, exercise-induced lactate, traditionally viewed as a metabolic byproduct, is now recognized as an active immunomodulatory molecule. At high concentrations, lactate can suppress immune function through pH-mediated effects and GPR81 receptor activation. At physiological levels, it supports regulatory T cell survival, promotes macrophage M2 polarization, and modulates gene expression via histone lactylation. Additionally, key metabolic regulators such as AMPK and mTOR coordinate immune cell energy balance and phenotype; exercise activates the AMPK-mTOR axis to favor anti-inflammatory immune cell profiles. Simultaneously, hypoxia-inducible factor-1α (HIF-1α) is transiently activated during exercise, driving glycolytic reprogramming in T cells and macrophages, and shaping the immune landscape. In lipid metabolism, exercise alleviates adipose tissue inflammation by reducing fat mass and reshaping the immune microenvironment. It promotes the polarization of adipose tissue macrophages from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype. Moreover, exercise alters the secretion profile of adipokines—raising adiponectin levels while reducing leptin and resistin—thereby influencing systemic immune balance. At the circulatory level, exercise improves lipid profiles by lowering pro-inflammatory free fatty acids (particularly saturated fatty acids) and triglycerides, while enhancing high-density lipoprotein (HDL) function, which has immunoregulatory properties such as endotoxin neutralization and macrophage cholesterol efflux. Regarding protein metabolism, exercise triggers the expression of heat shock proteins (HSPs) that act as intracellular chaperones and extracellular immune signals. Exercise also promotes the secretion of myokines (e.g., IL-6, IL-15, irisin, FGF21) from skeletal muscle, which modulate immune responses, facilitate T cell and macrophage function, and support immunological memory. Furthermore, exercise reshapes amino acid metabolism, particularly of glutamine, arginine, and branched-chain amino acids (BCAAs), thereby influencing immune cell proliferation, biosynthesis, and signaling. Leucine-mTORC1 signaling plays a key role in T cell fate, while arginine metabolism governs macrophage polarization and T cell activation. In summary, this review underscores the complex, bidirectional relationship between exercise and immune function, orchestrated through metabolic remodeling. Future research should focus on causative links among specific metabolites, signaling pathways, and immune phenotypes, as well as explore the epigenetic consequences of exercise-induced metabolic shifts. This integrated perspective advances understanding of exercise as a non-pharmacological intervention for immune regulation and offers theoretical foundations for individualized exercise prescriptions in health and disease contexts.

Alzheimer’s disease (AD), a progressive neurodegenerative disorder and the leading cause of dementia in the elderly, is characterized by severe cognitive decline, loss of daily living abilities, and neuropsychiatric symptoms. This condition imposes a substantial burden on patients, families, and society. Despite extensive research efforts, the complex pathogenesis of AD, particularly the early mechanisms underlying cognitive dysfunction, remains incompletely understood, posing significant challenges for timely diagnosis and effective therapeutic intervention. Among the various cellular components implicated in AD, GABAergic interneurons have emerged as critical players in the pathological cascade, playing a pivotal role in maintaining neural network integrity and function in key brain regions affected by the disease. GABAergic interneurons represent a heterogeneous population of inhibitory neurons essential for sustaining neural network homeostasis. They achieve this by precisely modulating rhythmic oscillatory activity (e.g., theta and gamma oscillations), which are crucial for cognitive processes such as learning and memory. These interneurons synthesize and release the inhibitory neurotransmitter GABA, exerting potent control over excitatory pyramidal neurons through intricate local circuits. Their primary mechanism involves synaptic inhibition, thereby modulating the excitability and synchrony of neural populations. Emerging evidence highlights the significant involvement of GABAergic interneuron dysfunction in AD pathogenesis. Contrary to earlier assumptions of their resistance to the disease, specific subtypes exhibit vulnerability or altered function early in the disease process. Critically, this impairment is not merely a consequence but appears to be a key driver of network hyperexcitability, a hallmark feature of AD models and potentially a core mechanism underlying cognitive deficits. For instance, parvalbumin-positive (PV⁺) interneurons display biphasic alterations in activity. Both suppressing early hyperactivity or enhancing late activity can rescue cognitive deficits, underscoring their causal role. Somatostatin-positive (SST⁺) neurons are highly sensitive to amyloid β-protein (Aβ) dysfunction. Their functional impairment drives AD progression via a dual pathway: compensatory hyperexcitability promotes Aβ generation, while released SST-14 forms toxic oligomers with Aβ, collectively accelerating neuronal loss and amyloid deposition, forming a vicious cycle. Vasoactive intestinal peptide-positive (VIP⁺) neurons, although potentially spared in number early in the disease, exhibit altered firing properties (e.g., broader spikes, lower frequency), contributing to network dysfunction (e.g., in CA1). Furthermore, VIP release induced by 40 Hz sensory stimulation (GENUS) enhances glymphatic clearance of Aβ, demonstrating a direct link between VIP neuron function and modulation of amyloid pathology. Given their central role in network stability and their demonstrable dysfunction in AD, GABAergic interneurons represent promising therapeutic targets. Current research primarily explores three approaches: increasing interneuron numbers (e.g., improving cortical PV⁺ interneuron counts and behavior in APP/PS1 mice with the antidepressant citalopram; transplanting stem cells differentiated into functional GABAergic neurons to enhance cognition), enhancing neuronal activity (e.g., using low-dose levetiracetam or targeted activation of specific molecules to boost PV⁺ interneuron excitability, restoring neural network γ‑oscillations and memory; non-invasive neuromodulation techniques like 40 Hz repetitive transcranial magnetic stimulation (rTMS), GENUS, and minimally invasive electroacupuncture to improve inhibitory regulation, promote memory, and reduce Aβ), and direct GABA system intervention (clinical and animal studies reveal reduced GABA levels in AD-affected brain regions; early GABA supplementation improves cognition in APP/PS1 mice, suggesting a therapeutic time window). Collectively, these findings establish GABAergic interneuron intervention as a foundational rationale and distinct pathway for AD therapy. In conclusion, GABAergic interneurons, particularly the PV⁺, SST⁺, and VIP⁺ subtypes, play critical and subtype-specific roles in the initiation and progression of AD pathology. Their dysfunction significantly contributes to network hyperexcitability, oscillatory deficits, and cognitive decline. Understanding the heterogeneity in their vulnerability and response mechanisms provides crucial insights into AD pathogenesis. Targeting these interneurons through pharmacological, neuromodulatory, or cellular approaches offers promising avenues for developing novel, potentially disease-modifying therapies.

Objective To analyze the acupoint selection rules of acupuncture for the treatment of tic disorders in children based on data mining techniques.Methods A computerized search was conducted for the clinical research literature on acupuncture treatment of tic disorders in children included in the CNKI,Wanfang,VIP,SinoMed,and PubMed databases from January 1992 to December 2022.A database was established by Excel 2019 to count the commonly used treatment methods and analyze the high-frequency application methods acupuncture(high-frequency acupoints,channel entry of acupoints,acupoint association rules,and acupoint clustering),auricular point seed-pressing(high-frequency auricular points,and acupoint association rules),and the high frequency division of cluster needling of scalp point.Results A total of 190 valid literature articles were included,involving 270 acupuncture prescriptions;among them,184 acupoints were counted in the acupuncture method,with a total application frequency of 1 906 times,and the high-frequency application of the acupoints in descending order were Baihui(DU20),Taichong(LR3),Fengchi(GB20),Hegu(LI4),Sanyinjiao(SP6),Neiguan(PC6),Shenmen(HT7),Zusanli(ST36),Yintang(EX-HN3),Sishencong(EX-HN1);and the high-frequency meridians were governor vessol,foot taiyang stomach meridian,foot taiyang stomach meridian,foot shaoyang gallbladder meridian,hand taiyang large intestine meridian,foot taiyang bladder meridian,foot jueyin gallbladder meridian;three sets of strong association rules and five clusters of acupoints were analyzed by SPSS modeler 18.0 and IBM SPSS Statistics 26.0 software.There were 29 acupoints of auricular point seed-pressing,application total frequency was 206 times,high-frequency application of auricular points in descending order of Shenmen(HT7),liver,heart,subcortex,kidney;four groups of acupoint strong association rules were obtained through the analysis of SPSS modeler 18.0 software.A total of 14 zones were involved in the application of cephalic acupoint plexus zoning,of which the high-frequency zones were parietal anterior temporal diagonal,parietal parietal 1,and chorea tremor control zone.Conclusion Acupuncture treatment of tic disorders in children,according to its pathogenesis(liver hyperactivity,kidney depletion,spleen deficiency,phlegm disturbance,etc.)and tic site,select acupoints compatibility,and mostly choose yang meridian acupoints,which is related to the nature and treatment characteristics of wind pathogen.Children's tic disorders are closely related to emotional disorders,therefore acupuncture and auricular acupoints all emphasize the method of soothing the liver and clearing the heart,and regulating the emotional state.Cluster needling of scalp point mostly used parietal temporal anterior oblique line,parietal 1 line,and dance tremor control area for the treatment of tic disorders.For children,auricular point seed-pressing and cluster needling of scalp point has the minimun of pain,the effect of treatment is long,and it is not easy to have dangerous situations such as bent needle,broken needle and so on.

Objective:To evaluate the effect of individualized positive end-expiratory pressure (PEEP) titration based on open-lung strategy on the intraoperative thoracic fluid content (TFC) in elderly patients undergoing transurethral ultrasound-guided laser-induced prostatectomy (TULIP).Methods:Eighty-six American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, patients, aged 65-80 yr, with body mass index of 18-28 kg/m 2, scheduled for elective TULIP, were divided into 2 groups ( n=43 each) by the random number table method: fixed PEEP group (group C) and individualized PEEP titration group (group P). PEEP was set at 4 cmH 2O after routine mechanical ventilation in group C. Patients underwent pulmonary recruitment maneuvers combined with individualized PEEP titration during surgery in group P. TFC was measured using a non-invasive cardiac output monitor at 5 min after tracheal intubation (T 0), 30 min after PEEP titration and ventilation (T 1), 5 min before surgery (T 2), and 5 min before leaving the recovery room (T 3). Cardiac output, oxygenation index and stroke volume index were recorded from T 0-T 2, arterial blood gas analysis was simultaneously performed to record peak airway pressure and dynamic lung compliance, and oxygenation index was calculated. The duration of postanesthesia care unit stay, pulmonary complications within 7 days after surgery, and length of hospital stay were also recorded. Results:Eighty-three patients were finally included, with 42 in group C and 41 in group P. Compared with group C, TFC was significantly decreased at T 1-T 3, cardiac index, cardiac output and stroke volume index were decreased at T 1, dynamic lung compliance, PaO 2 and oxygenation index were increased at T 1 and T 2, PaCO 2 was decreased, the incidence of postoperative pulmonary complications was reduced, and the duration of postanesthesia care unit stay and postoperative length of hospital stay were shortened in group P ( P<0.05). Conclusions:Individualized PEEP titration based on open-lung strategy can effectively decrease TFC and improve intraoperative oxygenation and prognosis in elderly patients undergoing TULIP.

This study was aimed at understanding the genomic characteristics of the Vibrio cholerae O1 group isolated from humans in Fujian Province,to provide essential data for the molecular epidemiological study of cholera.From 2008 to 2022,16 strains of the V.cholerae O1 group from patients and carriers were collected,and antibiotic sensitivity was determined accord-ing to the minimum inhibitory concentration(MIC).The whole genome sequences obtained through second generation sequen-cing were analyzed in open source software,including snippy,Roary,and Prokka,as well as online analysis websites,inclu-ding NCBI and BacWGSTdb,for core-genome multilocus sequence typing(cgMLST),core-genome single nucleotide polymor-phism analysis(cgSNP),virulence gene analysis,drug resistance gene prediction,and pan-genomic diversity analysis.The whole genome sequences of V.cholerae were divided into five sequence types(STs),among which the newly discovered ST182 and ST1480 were the evolutionary branches of the current dominant clonal group ST75 in China,and were highly related to two strains isolated from Taiwan in 2010 and 2013,respectively.Both toxigenic strains and non-toxigenic strains carried a variety of virulence factors and showed gene variation to varying degrees.Thirteen drug resistance genes in seven categories were predicted,among which the distribution of colistin and tetracycline resistance genes was consistent with the drug resistance phenotype.Pan-ge-nomic analysis indicated that V.cholerae had an open pan-genome,and Roary cluster analysis showed higher resolution than cgMLST.In summary,V.cholerae O1 group isolates from humans in Fujian Province have polymorphisms in genome structure and function,and the newly discovered ST1480 clone group has epidemic potential.Therefore,the monitoring of such strains must be strengthened.

Cancer stem cells,a small population of cells with self-renewal and multidirectional differenti-ation potential in tumor tissues,can initiate primary tumors and mediate treatment resistance,tumor re-currence,and metastasis,but the mechanism of how they affect colorectal cancer at the cellular level is unknown.Therefore,in this study,we explored the effect of cancer stem cells and their exosomes on the malignant phenotype of colorectal cancer.First,CD 166+CD44+cancer stem cells(CSCs)were isolated from colorectal cancer tumor tissues,and then cancer stem cell-derived exosomes(CSCexo)and colorec-tal cancer SW480 cell-derived exosomes(Sexo)were extracted by ultracentrifugation.Then,exosomes were subjected to NTA particle size analysis,electron microscopic observation and identification by West-ern blotting.Subsequently,the successfully isolated CSC and CSCexo were co-cultured with colorectal cancer SW480 cells.The apoptosis rate of SW480 cells after co-culture was found to decrease from 20％to about 13％by CCK-8,apoptosis assay(P＜0.01)and the invasive ability was significantly increased(P＜0.001)after co-culture with CSC or CSCexo.In addition,in vivo animal experiments revealed that the tumor growth rate of the S-exo treatment group was slower than that of the CSCexo treatment group,and that CSCexo inhibited the drug efficacy of 5-FU against colorectal cancer tumors.PET/CT imaging,immunohistochemical analysis,and Western blotting experiments showed that CSCexo enhanced the up-take of the glucose analog 18F-FDG and the expression of the glycolytic enzymes HK2,PFKFB2,PKM2,and LDHA in colorectal cancer.In addition,interfering with the expression of glycolytic enzymes with siRNAs blocked the drug resistance induced by CSCexo.In summary,this study demonstrates that color-ectal cancer stem cells deliver exosomes that affect tumor glucose metabolism pathways and promote chemotherapy resistance and invasive ability,revealing the mechanism of formation and dynamic changes in the malignant tumor microenvironment.

Lipophosphatidic acid(LTA)was used to stimulate Mac-T cells,and the expression lev-els and phosphorylation levels of key proteins of nuclear factor-κB(NF-κB)and mitogen-activated protein kinase(MAPK)signaling pathway and the expression levels of upstream key action factors TLR4 and MyD88 proteins were detected by Western blot,and EDU assay was used to detect cell proliferation levels and flow cytometry was used to detect apoptosis.The results showed that acti-vation of GPR120 significantly decreased the phosphorylation levels of LTA-induced NF-κB(P65 and IκBα)(P＜0.01)and MAPK(JNK,ERK,p38)(P＜0.01)in Mac-T cells;inhibition of GPR120 was able to upregulate LTA-induced NF-κB(p65 and IκBα)in Mac-T cells(P＜0.01)and MAPK(JNK,ERK,p38)phosphorylation levels(P＜0.01);and activation of GPR120 significantly allevia-ted LTA-induced upregulation of TLR4 and MyD88(P＜0.01);inhibition of GPR120 significantly exacerbated LTA-induced upregulation of TLR4 and MyD88(P＜0.05);LTA stimulation led to a trend of diminished Mac-T cell proliferation and significantly increased apoptosis,whereas activa-tion of the GPR120 gene significantly increased cell activity(P＜0.01),promoted cell proliferation and significantly reduced apoptosis(P＜0.05)thereby alleviating the damage to Mac-T cells by LTA;LTA stimulation led to a highly significant increase in apoptosis(P＜0.01).In contrast,acti-vation of the GPR120 gene significantly reversed the increase in the apoptosis rate of Mac-T cells induced by LTA(P＜0.01),while inhibition of the GPR120 gene enhanced the apoptosis-promo-ting effect of LTA(P＜0.05),indicating that activation of the GPR120 gene attenuated the in-crease of apoptosis rate caused by LTA-induced inflammatory Mac-T cells.The results suggest that GPR120 can regulate inflammation by mediating TLR4 and MyD88 expression to inhibit NF-κB/MAPK inflammatory pathway activation and can promote cell proliferation.

This study performed to determine whether OX40L overexpressed by recombinant rabies virus(LBNSE-OX40L)can enhance the innate immune response through activation of dendritic cells and thus activate early antibody production.Bone marrow dendritic cells(BMDCs)were extracted from the femur of Balb/c mice and cultured for 6 days,and the cultured BMDCs were infected with the parental virus LBNSE and the recombinant virus LBNSE-OX40L with the multiplicity of infections(MOI)=1.The effect of each virus on the maturation of BMDCs was analyzed by flow cytometry;ELISA was used to detect the expression of innate immunity-related cytokines such as interferon-α(IFN-α)and interleukin-12p40(IL-12p40)in the supernatants of the infected BMDCs.For in vivo study,Balb/c female mice were injected intramuscularly with 106 FFU of parental virus LBNSE and recombinant virus LBNSE-OX40L in both hind limbs,and the inguinal lymph nodes of mice were collected on day 6 after immunization,and the proportion of mature DCs was detected by flow cytometry.The serum was collected on day 6 after immunization,and the content of virus-neutralizing antibody(VNA)was detected by antiviral neutralizing antibody titration.Mouse serum was collected on day 6 after immunization,and virus neutralizing antibody content was measured by titration of antiviral neutralizing antibody,while IgG antibody in mouse serum was detected by ELISA.IgM antibody subclasses were detected by ELISA on days 2,4,and 6 after immunization.Compared with the parental virus LBNSE,the recombinant virus LBNSE-OX40L was able to activate more BMDCs in vitro and produce significantly higher levels of IFN-α and IL-12p40.Furthermore,the recombinant virus LBNSE-OX40L stimulated the maturation and differentiation of the DCs in vivo,which led to the rapid production of high levels of VNA and RABV-specific IgG and IgM antibodies.Taken together,LBNSE-OX40L activates dendritic cells to promote the body's innate immune response,and in turn enhances early antibody production,thus can be an early effective rabies vaccine candidate.

Chronic prostatitis is a process of kidney deficiency and blood stasis mixed with various pathological factors involving the essence chamber,which is manifested as kidney deficiency and blood stasis.Based on the concept of the"brain-heart-kidney-es-sence chamber"axis of medication,Xiongji Formula is applied to the treatment of chronic prostatitis,due to its"simultaneous holistic and local action"and effects of tonifying the kidney yang and assisting the systemic yang,acting on the brain,heart and kidney as a whole,and meanwhile activating blood circulation,eliminating blood stasis and restoring the function of the essence chamber.This pa-per discusses the etiology and pathogenesis of chronic prostatitis with kidney deficiency and blood stasis in Chinese medicine,expounds the significance of"brain-heart-kidney-essence chamber"axis of medication,and explores the specific value and clinical application of Xiongji Formula.

Humans ; Factor XIII/genetics* ; Factor XIII Deficiency/genetics* ; Mutation ; Pedigree