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.

Objective To investigate the disease spectrum and pathogenic genes of inherited metabolic disorder(IMD)among neonates in Gansu Province of China.Methods A retrospective analysis was conducted on the tandem mass spectrometry data of 286 682 neonates who received IMD screening in Gansu Provincial Maternal and Child Health Hospital from January 2018 to December 2021.A genetic analysis was conducted on the neonates with positive results in tandem mass spectrometry during primary screening and reexamination.Results A total of 23 types of IMD caused by 28 pathogenic genes were found in the 286 682 neonates,and the overall prevalence rate of IMD was 0.63‰(1/1 593),among which phenylketonuria showed the highest prevalence rate of 0.32‰(1/3 083),followed by methylmalonic acidemia(0.11‰,1/8 959)and tetrahydrobiopterin deficiency(0.06‰,1/15 927).In this study,166 variants were identified in the 28 pathogenic genes,with 13 novel variants found in 9 genes.According to American College of Medical Genetics and Genomics guidelines,5 novel variants were classified as pathogenic variants,7 were classified as likely pathogenic variants,and 1 was classified as the variant of uncertain significance.Conclusions This study enriches the database of pathogenic gene variants for IMD and provides basic data for establishing an accurate screening and diagnosis system for IMD in this region.

Objective To investigate the effect of ginkgo biloba flavonoids on children with lymphatic malformation(LM)driven by phosphatidylinoinosiol 3-kinase(PIK3CA)mutation and its mechanism.Methods The experiment was divided into human dermal lymphatic endothelial cell(HD-LEC)group(no treatment),lymphatic malformation lymphatic endothelial cell(LM-LEC)group(no treatment),ginkgo biflavone group(7.5 μmol·L-1 ginkgo biloba treated LM-LEC cells)and vascular endothelial growth factor-C(VEGF-C)inhibitor group(Sozinibercept group,treated LM-LEC cells with 1 μmol·L-1 VEGF-C inhibitor).The number of lumen and tube branches were observed in each group.Quantitative real-time polymerase chain reaction(qRT-qPCR)was used to detect the relative expression level of VEGF-C.The relative protein expression levels of vascular endothelial growth factor receptor 3(VEGFR3),neurofibrin-2(NRP2),protein kinase B(Akt)and extracellular regulatory protein kinase(ERK)were detected by Western blot.The positive expressions of VEGFR3 and NRP2 were detected by immunofluorescence assay.Results The relative expression levels of VEGF-C mRNA in LM-LEC group and HD-LEC group were 5.42±1.09 and 1.00±0.08;the relative expression levels of VEGFR3 protein were 2.79±0.54 and 1.00±0.10;the relative expression levels of NRP2 protein were 2.58±0.47 and 1.00±0.07;the phosphorylation levels of Akt S473 were 5.62±0.84 and 1.00±0.01;the phosphorylation levels of ERK were 2.37±0.62 and 1.00±0.05,respectively.The positive expressions of VEGFR3 in ginkgo diflavone group,Sozinibercept group and LM-LEC group were 0.35±0.08,0.29±0.08 and 1.00±0.16;the positive expressions of NRP2 were 0.33±0.07,0.31±0.05 and 1.00±0.09,respectively.The above indexes in LM-LEC group were significantly different from those in HD-LEC group,and the above indexes in ginkgo biloba flavonoids group and Sozinibercept group were significantly different from those in LM-LEC group(all P＜0.05).Conclusion Ginkgo biflavone may inhibit the expression of VEGF-C by blocking the VEGF-C/VEGFR-3 signaling pathway,and thus inhibit the lymphatic malformation caused by PIK3CA H1047R mutation.

The objective of this study was to investigate the protective effect and potential mechanism of action of hemin on bleomycin-induced pulmonary fibrosis in mice. Male C57BL/6 mice were randomly divided into control, bleomycin and bleomycin + hemin groups. Mice in the bleomycin and bleomycin + hemin groups were injected intratracheally with bleomycin to establish the pulmonary fibrosis model.The bleomycin + hemin group mice were injected intraperitoneally with hemin starting 7 days before modeling until the end of Day 21 after modeling. Pathological changes in lung tissue were assessed by HE and Masson staining. Malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) levels were determined in lung tissue. Immunohistochemistry was performed to assess the expression of α-SMA and collagen I. The serum levels of IL-6 and TNF-α were measured via ELISA.Western blotting was used to determine the expression of TGF-β1, SIRT1, PGC-1α and HO-1 and the phosphorylation levels of p38, ERK1/2, JNK, AMPK and NF-κB p65 in lung tissue. Hemin significantly reduced lung indices, increased terminal body weight. It also significantly increased SOD and CAT activities; decreased MDA, IL-6 and TNF-α levels; reduced the levels of α-SMA and collagen I-positive cells; upregulated SIRT1, PGC-1α and HO-1 expression; promoted AMPK phosphorylation; and downregulated TGF-β1 expression and p38, ERK1/2, JNK and NF-κB p65 phosphorylation. Hemin might attenuate oxidative damage and inflammatory responses and reduces extracellular matrix deposition by regulating the expression and phosphorylation of proteins associated with the TGF-β1/MAPK and AMPK/SIRT1/PGC-1α/HO-1/ NF-κB pathways, thereby alleviating bleomycin-induced pulmonary fibrosis.

Objective To investigate the expression and prognostic value of spindle and kinetochore-associated complex subunit 2(SKA2)in cervical cancer tissues,as well as its impact on the proliferation,migration and invasion of cervical cancer cells.Methods The expression of SKA2 in cervical cancer tissues was analyzed by bioinformatics database and immunohistochemical SP method,and the relationship between SKA2 expression level and clinicopathological features of cervical cancer patients and its prognostic value was analyzed.The mRNA expression of SKA2 in human normal cervical cells(HcerEpic)and cervical cancer cells(HeLa,SiHa,CaSki,C-33A)was detected by RT-qPCR.Cervical cancer cells SiHa with higher SKA2 expression level was selected for further study.SiHa cell model with down-regulated SKA2 expression was constructed,and its knockdown effect was verified.Cell proliferation capacity was detected by CCK-8 method,cell migration capacity was detected by cell scratch wound healing assay,and cell migration and invasion capacity was detected by Transwell assay.Results Compared with normal cervical tissues and cells,the expression levels of SKA2 mRNA and protein were higher in cervical cancer tissues and cells,and the differences were statistically significant(P<0.05).High SKA2 expression was associated with FIGO staging in patients with cervical cancer.Furthermore,SKA2 knockdown could inhibit the proliferation,migration and invasion of SiHa cells in cervical cancer(P<0.05).Conclusion SKA2 is up-regulated in cervical cancer tissues and cells,and can promote the proliferation,migration and invasion of cervical cancer cells.The expression level of SKA2 is associated with the progression of cervical cancer,and the prognosis of cervical cancer patients with high SKA2 expression is worse.

Objective To investigate the protective effect of placental mesenchymal stem cells(P-MSCs)on pancreatic trauma(PT)in rats.Methods Sixty healthy adult male SD rats were randomly divided into control group,pancreatic trauma group(inject 1 ml of PBS solution locally in the pancreatic injury area and around the trauma area),and P-MSCs group[inject 1 ml of P-MSCs(1×106/ml)locally in the pancreatic injury area and around the trauma area],with 20 rats in each group.The pancreatic trauma rat model was established using a traumatic pressure of 400 kPa.Five rats were sacrificed at 1,3,5,and 7 d after modeling in each group,and serum and pancreatic tissue were collected.HE staining was used to observe the pathological changes of pancreatic tissue and pathological scores were performed.The ELISA method was used to measure the concentrations of serum amylase(AMS),lipase(LPS),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-10,and transforming growth factor-β1(TGF-β1),as well as the activities of myeloperoxidase(MPO)and superoxide dismutase(SOD)in pancreatic tissue.The TUNEL method was used to observe the level of apoptosis in pancreatic tissue was observed by the TUNEL method.Results Compared with control group,pancreatic trauma group and P-MSCs group showed significant differences after pancreatic trauma,including the generation of peritoneal fluid increased(P<0.05),the ratio of pancreas to body weight and the total score of pancreatic tissue pathological damage increased(P<0.05),and serum levels of AMS,LPS,TNF-α,IL-6,and MPO activity increased early and showed a decreasing trend over time(P<0.05),while anti-inflammatory factors IL-10 and SOD activity showed an increasing trend over time(P<0.01),level of TGF-β1 in the early decline showed an upward trend over time(P<0.01),and the apoptosis index(AI)significantly increased(P<0.001).Compared with pancreatic trauma group,P-MSCs group showed an improvement in the overall morphology of pancreatic tissue,the generation of peritoneal fluid decreased(P<0.001),the pancreas to body weight ratio and the total score of pancreatic tissue pathological damage decreased(P<0.05),and serum levels of AMS,LPS,IL-6,TNF-α and MPO activity returned to normal levels faster(P<0.05);and the rate of anti-inflammatory factors IL-10,TGF-β1 and SOD activity elevation increased(P<0.05),the AI increased(P<0.001).Conclusion P-MSCs can achieve therapeutic effects on pancreatic trauma in rats by promoting pancreatic tissue repair,reducing local and systemic inflammation,improving tissue oxidative stress,and enhancing pancreatic acinar cell apoptosis.

Lipids,including fats(triglycerides)and lipoids(phospholipids and sterols),not only serve as an energy source for the body but also play a pivotal role throughout the reproductive process,particularly in the establishment and maintenance of early pregnancy.This encompasses the regulate of early embryonic development and uterine tolerance,and the facilitation of embryo implantation.Given the diversity of lipids,this review focuses on extensively studied lipid mediators such as polyunsaturated fatty acids,endocannabinoids,prostaglandins,lysophosphatidic acid,sphingolipids and steroid hormones.It systematically elaborates on the regulatory effects of fatty acid,phospholipid,and cholesterol metabolism on the formation of endometrial receptivity and embryo implantation,as well as the potential underlying mechanisms.The review aims to provide new insights and feasible intervention approaches for predicting and improving the outcomes of natural pregnancy and/or assisted reproductive technology.

Objective To explore the mechanism which drives nimbolide(NIM)in treating acute pneumonia caused by Staphylococcus aureus(S.auteus).Methods A mouse model of acute pneumonia caused by S.auteus was constructed through endotracheal intubation.After NIM treatment,the survival rate was observed,the amount of bacteria in the lung was tested by plate culture,and the expression of inflammatory cytokines in the lung tissues was detected with ELISA.After primary cultured peritoneal macrophages(PM)were infected with S.auteus,the effect of NIM on the expression of inflammatory cytokines and activation of inflammatory pathway were studied with ELISA and Western blotting,respectively.The effect of RNF114 knockdown by lentiviral shRNA infection on inflammation responses in PM was explored with ELISA and Western blotting.Results Acute infection of S.auteus in the lung could cause acute death in the mice,while NIM treatment significantly improved the survival rate and down-regulated the levels of inflammatory cytokines in the lung.However,it had no effect on the lung colonization of S.auteus in the short term.The results of in vitro experiments indicated that NIM may regulate RNF114 function to down-regulate the phosphorylation level of ERK,inhibit the activation of MAPK pathway,and thus suppress the expression of inflammatory cytokines.Conclusion NIM may inhibit the activation of MAPK pathway by regulating the function of RNF114,and thus suppress the expression of inflammatory cytokines in the lung,and finally inhibit the death of mice with acute pulmonary hyperinflammation caused by S.auteus.

On the basis of the laboratory detection results of influenza viruses in Jiangsu Province from 2022 to 2023,this study was aimed at conducting a analysis of the genetic characteristics and resistance of the H3N2 influenza virus,and evalua-ting the effectiveness of vaccines and drugs.The full genome of 29 H3N2 isolates submitted by provincewide influenza surveil-lance network laboratories was amplified and sequenced.Phylogenetic trees of the HA and NA genes were constructed.The mutation characteristics of antigenic sites,glycosylation sites,and resistance sites were analyzed,and the influenza virus neura-minidase was detected with a fluorescence luminescence method.The homology of the 29 H3N2 isolates in Jiangsu Province was relatively high.The isolates belonged to the same evolutionary branch as domestic reference strains and the 2021-2022 vaccine strains,but were in different evolutionary branches from foreign reference strains and the 2022-2023 vaccine strains.Compared with the 2021-2022 vaccine strain A/Cambodia/e0826360/2020,the H3N2 influenza viruses isolated in Jiangsu Province during 2022-2023 had four amino acid substitutions in the HA protein and two amino acid substitutions in the NA protein.No changes in glycosylation sites,receptor-binding sites,and conserved amino acid residue regions were observed.IC50 analysis indicated that the 29 H3N2 isolates were not resistant to the antiviral drugs oseltamivir and zanamivir.The pre-dominant influenza viruses detected in Jiangsu Province during 2022-2023 were type A H3N2 influenza viruses.Monitoring of variations in HA and NA gene sites and influenza virus resistance aids in rapid understanding gene mutations,and can inform the selection of effective vaccine strains,and contribute to the prevention and control of influenza virus outbreaks.

Objective:To analyze the distribution characteristics of prognostic factors affecting recurrence in peripheral T-cell lymphoma(PTCL)patients with different levels of histone deacetylase(HDAC)based on latent class analysis.Methods:112 PTCL patients who were treated in our hospital from September 2012 to September 2019 were selected and divided into recurrence group and non-recurrence group.The clinical data of the two groups of patients were compared.Multivariate logistic regression was used to analyze the risk factors for recurrence.Latent class analysis was used to compare the distribution characteristics of prognostic factors affecting recurrence between the high-risk group and the low-risk group.Results:There were 87 patients(77.68％)in recurrence group and 25 patients(22.32％)in non-recurrence group.The result of multivariate logistic regression showed that ECOG score ≥2,Ann Arbor stage Ⅲ-Ⅳ,IPI score＞2,bone marrow involvement,elevated serum β2-microglobulin(β2-MG),short-term efficacy not reaching complete remission(CR)or partial remission(PR),and the high expression of HDAC were all independent risk factors for recurrence in patients with PTCL(P＜0.05).The recurrence rate of patients with high HDAC levels was significantly higher than that of patiens with low HDAC levels(P＜0.05).The results of cluster analysis showed that the risk of recurrence was obviously clustered,and the patients could be divided into high recurrence risk group(HDAC＞5 points)and low recurrence risk group(HDAC≤5 points).The results of latent class analysis showed that patients with multiple risk factors account for a higher proportion in the high recurrence risk group,compared with the low recurrence risk group(P＜0.05).Conclusion:There are differences in recurrence rates among PTCL patients with different HDAC levels and in distribution characteristics of risk factors between high recurrence risk and low recurrence risk groups.