1.Regulation of Immune Function by Exercise-induced Metabolic Remodeling
Hui-Guo WANG ; Gao-Yuan YANG ; Xian-Yan XIE ; Yu WANG ; Zi-Yan LI ; Lin ZHU
Progress in Biochemistry and Biophysics 2025;52(6):1574-1586
		                        		
		                        			
		                        			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. 
		                        		
		                        		
		                        		
		                        	
2.Syndrome-Based Treatment Strategy for Hypertension Using the Method of Raising Yang and Promoting Descent
Xiaotong LYU ; Linping ZHU ; Jingshun YAN ; Zejun DU ; Xueying WU ; Zongpei XU
Journal of Traditional Chinese Medicine 2025;66(13):1345-1349
		                        		
		                        			
		                        			Guided by the theories of yin-yang and collateral disease, this paper identifies the dysregulation of yang qi ascent and descent as the core pathomechanism of hypertension. Based on clinical experience, a treatment approach centered on the method of raising yang and promoting descent was proposed. Clinically, three major syndrome types were identified. Firstly, deficiency of zong qi (ancestral qi) with blood stasis, obstruction of phlegm-turbidity and blood stasis, and hyperactivity of liver yang. Corresponding empirical formulation, Yizong Huoxue Decoction (益宗活血汤) was applied to tonify zong qi, invigorate blood, and raise yang. Secondly, Lizong Huoxue Decoction (理宗活血汤) was used to resolve phlegm, promote yang qi circulation, and regulate qi and blood. Thirdly, Qinggan Tongluo Decoction (清肝通络饮) was used to clear the liver, dredge collaterals, and subdue hyperactive yang. For special types such as non-dipper hypertension, time-specific syndrome differentiation and treatment can be applied based on a thorough understanding of the underlying pathomechanism, aiming to provide new insights into clinical diagnosis and treatment of hypertension. 
		                        		
		                        		
		                        		
		                        	
3.Production of GTKO pigs and kidney xenotransplantation from pigs to rhesus macaques
Yan WANG ; Yue CHANG ; Chang YANG ; Taiyun WEI ; Xiaoying HUO ; Bowei CHEN ; Jiaoxiang WANG ; Heng ZHAO ; Jianxiong GUO ; Hongfang ZHAO ; Xiong ZHANG ; Feiyan ZHU ; Wenmin CHENG ; Hongye ZHAO ; Kaixiang XU ; Ameen Jamal MUHAMMAD ; Zhendi WANG ; Hongjiang WEI
Organ Transplantation 2025;16(4):526-537
		                        		
		                        			
		                        			Objective To explore the construction of α-1,3-galactosyltransferase (GGTA1) gene-knockout (GTKO) Diannan miniature pigs and the kidney xenotransplantation from pigs to rhesus macaques, and to assess the effectiveness of GTKO pigs. Methods The GTKO Diannan miniature pigs were constructed using the CRISPR/Cas9 gene-editing system and somatic cell cloning technology. The phenotype of GTKO pigs was verified through polymerase chain reaction, Sanger sequencing and immunofluorescence staining. Flow cytometry was used to detect antigen-antibody (IgM) binding and complement-dependent cytotoxicity. Kidney xenotransplantation was performed from GTKO pigs to rhesus macaques. The humoral immunity, cellular immunity, coagulation and physiological indicators of the recipient monkeys were monitored. The function and pathological changes of the transplanted kidneys were analyzed using ultrasonography, hematoxylin-eosin staining, immunohistochemical staining and immunofluorescence staining. Results Single-guide RNA (sgRNA) targeting exon 4 of the GGTA1 gene in Diannan miniature pigs was designed. The pGL3-GGTA1-sgRNA1-GFP vector was transfected into fetal fibroblasts of Diannan miniature pigs. After puromycin selection, two cell clones, C59# and C89#, were identified as GGTA1 gene-knockout clones. These clones were expanded to form cell lines, which were used as donor cells for somatic cell nuclear transfer. The reconstructed embryos were transferred into the oviducts of trihybrid surrogate sows, resulting in 13 fetal pigs. Among them, fetuses F04 and F11 exhibited biallelic mutations in the GGTA1 gene, and F04 had a normal karyotype. Using this GTKO fetal pig for recloning and transferring the reconstructed embryos into the oviducts of trihybrid surrogate sows, seven surviving piglets were obtained, all of which did not express α-Gal epitope. The binding of IgM from the serum of rhesus monkey 20# to GTKO pig PBMC was reduced, and the survival rate of GTKO pig PBMC in the complement-dependent cytotoxicity assay was higher than that of wild-type pig. GTKO pig kidneys were harvested and perfused until completely white. After the left kidney of the recipient monkey was removed, the pig kidney was heterotopically transplanted. Following vascular anastomosis and blood flow restoration, the pig kidney rapidly turned pink without hyperacute rejection (HAR). Urine appeared in the ureter 6 minutes later, indicating successful kidney transplantation. The right kidney of the recipient was then removed. Seven days after transplantation, the transplanted kidney had good blood flow, the recipient monkey's serum creatinine level was stable, and serum potassium and cystatin C levels were effectively controlled, although they increased 10 days after transplantation. Seven days after transplantation, the levels of white blood cells, lymphocytes, monocytes and eosinophils in the recipient monkey increased, while platelet count and fibrinogen levels decreased. The activated partial thromboplastin time, thrombin time and prothrombin time remained relatively stable but later showed an upward trend. The recipient monkey survived for 10 days. At autopsy, the transplanted kidney was found to be congested, swollen and necrotic, with a small amount of IgG deposition in the renal tissue, and a large amount of IgM, complement C3c and C4d deposition, as well as CD68+ macrophage infiltration. Conclusions The kidneys of GTKO Diannan miniature pigs may maintain normal renal function for a certain period in rhesus macaques and effectively overcome HAR, confirming the effectiveness of GTKO pigs for xenotransplantation.
		                        		
		                        		
		                        		
		                        	
4.Research advances in the association of vitamin D with benign paroxysmal positional vertigo and residual dizziness
Xien ZHU ; Shuangmei YAN ; Ping GU
Journal of Apoplexy and Nervous Diseases 2025;42(6):568-572
		                        		
		                        			
		                        			Benign paroxysmal positional vertigo(BPPV)is a common peripheral vestibular disorder,and at present,otolith shedding and displacement is highly recognized as the main pathological mechanism of BPPV. An increasing amount of evidence has shown that otolith particle shedding is closely associated with vitamin D,and 25-(OH)D is expected to become a potential biomarker for BPPV and an important target for the treatment of BPPV and residual symptoms after successful repositioning. This article reviews the pathophysiological mechanism of vitamin D in BPPV and residual dizziness and summarizes the association of vitamin D with BPPV and residual symptoms based on the treatment methods for vitamin D regulation.
		                        		
		                        		
		                        		
		                        			Vitamin D
		                        			
		                        		
		                        	
5.Relationship between metabolic score for insulin resistance and overactive bladder in the US population based on NHANES data from 2005 to 2018
Guoliang XU ; Feiyang GAO ; Xihao WANG ; Jiangtao ZHU ; Wei LIN ; Pengyue LIU ; Yongjun YAN
Journal of Modern Urology 2025;30(5):416-423
		                        		
		                        			
		                        			Objective: To assess the association between the metabolic score for insulin resistance index (METS-IR) and overactive bladder (OAB) in the US population,so as to explore the potential of METS-IR as a predictive tool for OAB risk and to provide insights for early screening and intervention strategies. Methods: Based on the data from the National Health and Nutrition Examination Survey (NHANES) 2005-2018,a cross-sectional design was employed,and multivariate logistic regression models were used to analyze the association between METS-IR and OAB. METS-IR was analyzed both as a continuous variable and categorized into quartiles. To further validate the association between METS-IR and OAB across diverse populations,subgroup analyses were conducted in participants stratified by clinical characteristics. Smooth curve fitting was employed to test the linearity of the METS-IR-OAB relationship. Results: Elevated METS-IR was associated with an increased risk of OAB (P<0.001),and this positive correlation remained stable when METS-IR was categorized into quartiles (P<0.001). Subgroup analyses revealed that the association between METS-IR and OAB was more pronounced in females,participants younger than 55 years,and non-diabetic individuals (P<0.05). Furthermore,smooth curve fitting confirmed a linear positive correlation between METS-IR and OAB,with this linear relationship observed in both diabetic and non-diabetic groups. Conclusion: This study,based on the NHANES 2005-2018 database,found a linear positive correlation between METS-IR and OAB.
		                        		
		                        		
		                        		
		                        	
6.Multidimensional optimization strategies and practical effects of prescription pre-review system
Guangming GAO ; Tianjiao LIU ; Na XU ; Jing LIANG ; Xiangju SUN ; Zhanguo ZHU ; Hong YAN
China Pharmacy 2025;36(14):1797-1801
		                        		
		                        			
		                        			OBJECTIVE To optimize the prescription pre-review system in our hospital and evaluate its application effects. METHODS Aiming at the problems of imperfect rule base and high false positive rate in the early operation of the system, optimization measures were taken, including improving the content of the rule base, adjusting the interception level and prompt mode, refining the working model of prescription review pharmacists, and strengthening clinical communication. A retrospective cohort study was conducted, with prescription data from June to December 2023 (before optimization) as the control group and June to December 2024 (after optimization) as the observation group. Through inter group comparative analysis, the actual effect of optimizing the prescription pre-approval system was evaluated. RESULTS The prescription qualified rate increased from (82.51± 4.04)% before optimization to (90.98±1.55)% after optimization; the false positive rate decreased from (20.87±1.64)% before optimization to (7.41±2.04)% after optimization. The monthly range of prescription qualified rate narrowed from 10.24% to 4.11%, and the coefficient of variation decreased from 4.92% to 1.73%. The monthly range of false positive rate slightly increased from 4.40% to 5.34%, the coefficient of variation rose from 8.32% to 26.18%. CONCLUSIONS Through multi-dimensional optimizations of the prescription pre-review system in our hospital, its prescription review efficiency has been significantly enhanced, the quality of prescriptions has steadily improved, and the accuracy of reviews has notably improved.
		                        		
		                        		
		                        		
		                        	
7.Application and prospect of artificial intelligence and population pharmacokinetics in personalized medication after organ transplantation
Shuai HE ; Huiying ZONG ; An’an LI ; Penglin ZHOU ; Rui GAO ; Xichao WU ; Yanjiao ZHU ; Yan LI
China Pharmacy 2025;36(14):1813-1818
		                        		
		                        			
		                        			Artificial intelligence (AI) and population pharmacokinetics (PPK) technologies have demonstrated significant potential in the personalized medication of immunosuppressants after organ transplantation, enabling precise prediction of drug dosages. This article provides a comprehensive review of the application status of AI and PPK in the individualized administration of immunosuppressants after organ transplantation, focuses on monitoring blood drug concentration, predicting efficacy/adverse reactions, and establishing individualized dosing models for organ transplant recipients after immunosuppressant administration, and analyzes and compares the application characteristics of different methods in different organ transplant patients as well as the integration and future development of AI and PPK technologies. AI and PPK technologies can not only significantly reduce the dependence on human resources, but also greatly improve the level of individualized treatment of immunosuppressants after organ transplantation, and reduce the discomfort and burden caused by frequent blood concentration monitoring to patients.
		                        		
		                        		
		                        		
		                        	
8.Comparison of Therapeutic Effect of Different Preparation Processes of Baihe Dihuangtang on Depressed Mice Based on Q-Marker
Yan LIU ; Jiameng LIU ; Jiahui PENG ; Dan LI ; Shengjun MA ; Jingfan YANG ; Yu FU ; Guangwei ZHU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):159-167
		                        		
		                        			
		                        			ObjectiveBased on modern analytical techniques and a depressed mouse model established by chronic unpredictable mild stress(CUMS), to evaluate the quality marker(Q-Marker) and pharmacodynamic difference of Baihe Dihuangtang prepared by different processes. MethodsHigh performance liquid chromatography(HPLC) was used to establish the characteristic profiles of Baihe Dihuangtang, and determine the content of Q-Marker in the samples prepared by ancient and modern processes. Seventy C57BL/6J mice were randomly divided into the normal group, model group, fluoxetine group(3 mg·kg-1), low and high dose groups of ancient process(6.5, 26 g·kg-1), and low and high dose groups of modern process(6.5, 26 g·kg-1), with 10 mice in each group. Except for the normal group, CUMS was used to induce depression in mice from the other groups for 28 d. After successful modeling, administration groups were given the corresponding drugs by gavage every day, and the normal and model groups were given an equal volume of pure water by gavage for 21 consecutive days. Change in body mass of mice was recorded, tail suspension test and open field test were used to evaluate the depressive behavior of mice, and enzyme-linked immunosorbent assay(ELISA) was employed to determine the contents of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β and IL-6 in serum. ResultsCharacteristic profiles of Baihe Dihuangtang prepared by the two processes were established, the similarity between the two was 0.951, and 8 characteristic peaks were recognized with the reference peak of regaloside A. The results of quantitative analysis showed that the Q-Marker content was similar in Baihe Dihuangtang prepared by ancient and modern processes. The results of pharmacodynamics showed that, compared with the normal group, the model group showed increased immobility time in the tail suspension test, reduced total movement distance in the open field test, and elevated IL-1β, IL-6 and TNF-α levels in the serum(P<0.01). Compared with the model group, the behavioral indicators of mice in the Baihe Dihuangtang treatment group were significantly improved in terms of tail suspension time and open field exercise, and the levels of IL-1β, IL-6 and TNF-α in serum were significantly reduced(P<0.05, P<0.01). Baihe Dihuangtang prepared by the two processes both had antidepressant effects, and the difference between the two was not statistically significant in improving depressive symptoms. ConclusionQ-Marker of Baihe Dihuangtang prepared by modern and ancient methods are equivalent in content, and the pharmacological effects are consistent, indicating that dried Lilii Bulbus can replace fresh products in the preparation of Baihe Dihuangtang. This study provides a scientific basis for the development of new drugs of Baihe Dihuangtang and a reference for its rational application and clinical use. 
		                        		
		                        		
		                        		
		                        	
9.Comparison of Therapeutic Effect of Different Preparation Processes of Baihe Dihuangtang on Depressed Mice Based on Q-Marker
Yan LIU ; Jiameng LIU ; Jiahui PENG ; Dan LI ; Shengjun MA ; Jingfan YANG ; Yu FU ; Guangwei ZHU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):159-167
		                        		
		                        			
		                        			ObjectiveBased on modern analytical techniques and a depressed mouse model established by chronic unpredictable mild stress(CUMS), to evaluate the quality marker(Q-Marker) and pharmacodynamic difference of Baihe Dihuangtang prepared by different processes. MethodsHigh performance liquid chromatography(HPLC) was used to establish the characteristic profiles of Baihe Dihuangtang, and determine the content of Q-Marker in the samples prepared by ancient and modern processes. Seventy C57BL/6J mice were randomly divided into the normal group, model group, fluoxetine group(3 mg·kg-1), low and high dose groups of ancient process(6.5, 26 g·kg-1), and low and high dose groups of modern process(6.5, 26 g·kg-1), with 10 mice in each group. Except for the normal group, CUMS was used to induce depression in mice from the other groups for 28 d. After successful modeling, administration groups were given the corresponding drugs by gavage every day, and the normal and model groups were given an equal volume of pure water by gavage for 21 consecutive days. Change in body mass of mice was recorded, tail suspension test and open field test were used to evaluate the depressive behavior of mice, and enzyme-linked immunosorbent assay(ELISA) was employed to determine the contents of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β and IL-6 in serum. ResultsCharacteristic profiles of Baihe Dihuangtang prepared by the two processes were established, the similarity between the two was 0.951, and 8 characteristic peaks were recognized with the reference peak of regaloside A. The results of quantitative analysis showed that the Q-Marker content was similar in Baihe Dihuangtang prepared by ancient and modern processes. The results of pharmacodynamics showed that, compared with the normal group, the model group showed increased immobility time in the tail suspension test, reduced total movement distance in the open field test, and elevated IL-1β, IL-6 and TNF-α levels in the serum(P<0.01). Compared with the model group, the behavioral indicators of mice in the Baihe Dihuangtang treatment group were significantly improved in terms of tail suspension time and open field exercise, and the levels of IL-1β, IL-6 and TNF-α in serum were significantly reduced(P<0.05, P<0.01). Baihe Dihuangtang prepared by the two processes both had antidepressant effects, and the difference between the two was not statistically significant in improving depressive symptoms. ConclusionQ-Marker of Baihe Dihuangtang prepared by modern and ancient methods are equivalent in content, and the pharmacological effects are consistent, indicating that dried Lilii Bulbus can replace fresh products in the preparation of Baihe Dihuangtang. This study provides a scientific basis for the development of new drugs of Baihe Dihuangtang and a reference for its rational application and clinical use. 
		                        		
		                        		
		                        		
		                        	
10.SHI Zaixiang's Clinical Experience in Using Chaihu Guizhi Ganjiang Decoction (柴胡桂枝干姜汤) to Treat High Fever in Sepsis
Tingting ZHU ; Yingying LIU ; Hailan CUI ; Zhiying REN ; Mingjing SHAO ; Yan BIAN ; Liyan WANG ; Zhenjie CHEN ; Yuan LIU ;
Journal of Traditional Chinese Medicine 2025;66(16):1645-1648
		                        		
		                        			
		                        			This paper summarizes Professor SHI Zaixiang's clinical experience in treating high fever caused by sepsis using Chaihu Guizhi Ganjiang Decoction (柴胡桂枝干姜汤). He holds that the key pathogenesis of sepsis involves constrained heat in the shaoyang and internal accumulation of water and fluids. The clinical manifestations such as high fever, chills, and alternating sensations of cold and heat are attributed to pathogenic heat constrained in the shaoyang. Meanwhile, soft tissue edema and serous cavity effusions are due to shaoyang dysfunction and internal water retention. In clinical practice, treating sepsis-related high fever requires addressing both the shaoyang-constrained heat and the associated edema and effusions. The therapeutic approach focuses on harmonizing the shaoyang and resolving internal fluids, using Chaihu Guizhi Ganjiang Decoction as the base formula with flexible modifications. Professor SHI emphasizes that this formula shows a rapid antipyretic effect, particularly in cases where multiple anti-infective treatments have failed. 
		                        		
		                        		
		                        		
		                        	
            
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