Chronic heart failure （CHF） is an end-stage cardiac syndrome driven by multiple factors. Its pathological process involves interactions of multiple pathways such as energy metabolism dysfunction， neuroendocrine dysregulation， and myocardial fibrosis. Although current clinical medicine can alleviate symptoms through single-target approaches， significant limitations in reversing cardiac remodeling and disease progression remain. Puerarin， a major bioactive isoflavone constituent derived from Pueraria lobata， exhibits multidimensional pharmacological effects， such as vasodilatory effects， regulation of neuroendocrine balance， enhancement of metabolic homeostasis， and suppression of myocardial apoptosis. This review systematically integrated puerarin's multi-target regulatory network， elucidating its mechanisms such as improving energy metabolism by AMP-activated protein kinase/mechanistic target of rapamycin （AMPK/mTOR） pathway， inhibiting fibrosis mediated by transforming growth factor-β （TGF-β）/Smad signals， and attenuating oxidative-inflammatory cascades by regulating nuclear factor erythroid 2 （E₂）-related factor 2/nuclear transcription factor-κB（Nrf2/NF-κB） axis. Clinical research data was used to validate its efficacy in improving the left ventricular ejection function and reducing the therapeutic potential of cardiovascular events' risks. The study proposed that puerarin's "systemic regulation" characteristic breaks through the limitations of traditional single-target drugs and prospected its clinical translation pathway based on metabolomics and nano-delivery technology， offering an integrative perspective from molecular mechanisms to precise therapy for the research on modernization of traditional Chinese medicine.

Chronic heart failure （CHF） is an end-stage cardiac syndrome driven by multiple factors. Its pathological process involves interactions of multiple pathways such as energy metabolism dysfunction， neuroendocrine dysregulation， and myocardial fibrosis. Although current clinical medicine can alleviate symptoms through single-target approaches， significant limitations in reversing cardiac remodeling and disease progression remain. Puerarin， a major bioactive isoflavone constituent derived from Pueraria lobata， exhibits multidimensional pharmacological effects， such as vasodilatory effects， regulation of neuroendocrine balance， enhancement of metabolic homeostasis， and suppression of myocardial apoptosis. This review systematically integrated puerarin's multi-target regulatory network， elucidating its mechanisms such as improving energy metabolism by AMP-activated protein kinase/mechanistic target of rapamycin （AMPK/mTOR） pathway， inhibiting fibrosis mediated by transforming growth factor-β （TGF-β）/Smad signals， and attenuating oxidative-inflammatory cascades by regulating nuclear factor erythroid 2 （E₂）-related factor 2/nuclear transcription factor-κB（Nrf2/NF-κB） axis. Clinical research data was used to validate its efficacy in improving the left ventricular ejection function and reducing the therapeutic potential of cardiovascular events' risks. The study proposed that puerarin's "systemic regulation" characteristic breaks through the limitations of traditional single-target drugs and prospected its clinical translation pathway based on metabolomics and nano-delivery technology， offering an integrative perspective from molecular mechanisms to precise therapy for the research on modernization of traditional Chinese medicine.

Objective: To investigate the association of special family structure and physical activity with psychological sub health among secondary vocational school students, so as to provide reference to inform mental health promotion in the population. Methods: From September to December 2024, a convenience sample was drawn from 16 schools including 5 141 secondary vocational school students across 8 provinces (municipalities) in China (Fujian, Chongqing, Guangdong, Guangxi, Hubei, Jiangxi, Shanghai, Zhejiang). A self developed questionnaire, Multidimensional Sub health Questionnaire of Adolescents and International Physical Activity Questionnaire Short Form were used to investigate and evaluate basic information, family structure, psychological sub health status and physical activity. Descriptive statistics and Logistic regression analysis were performed to explore relationships of special family structures and physical activity with psychological sub health in secondary vocational school students. Results: The detection rate of psychological sub health among secondary vocational school students was 11.0%. The reporting rates for secondary vocational school students who lost their father or lost their mother, whose parents divorced, whose parents remarried, and those from special family structures were 2.8%, 0.8%, 11.8%, 3.9%, and 14.7%, respectively. Moreover, the detection rates of psychological sub health and its sub dimensions significantly differed among secondary vocational school students grouped by family type (divorced parental families, remarried parental families and special family structures)( χ 2=5.90-22.67, all P <0.05). Binary Logistic regression indicated that maternal bereavement was associated with a higher risk of conduct problems [ AOR ( 95% CI )= 2.90(1.15-7.33)], and parental divorce was associated with a higher risk of psychological sub health ( AOR= 2.71 , 95%CI =1.04- 7.06 ) among secondary vocational school students (both P <0.05). Interaction analysis showed that both students with a special family structure and insufficient physical activity [ AOR (95% CI )=1.99(1.44-2.75)] and those with a non-special family structure and insufficient physical activity [ AOR (95% CI )=1.81(1.48-2.22)] were associated with increased risks of psychological sub health among secondary vocational school students (both P <0.01). Conclusion Special family structure and physical activity are associated with psychological sub health among secondary vocational school students; early identification and assessment based interventions for those with a special family structure should be strengthened, while school based physical activity should be implemented to increase physical activity levels,thereby reducing the risk of psychological sub health.

Hyperlipidemia is a common metabolic disorder driven by dysregulated lipid metabolism， whose pathological progression involves multifaceted interactions across various signaling pathways， including disrupted cholesterol homeostasis， insulin resistance， chronic inflammation， and oxidative stress. Although existing clinical medications such as statins can effectively reduce low-density lipoprotein cholesterol through single-target inhibition， significant limitations remain in comprehensively improving reverse cholesterol transport， metabolic inflammation， and coordinated regulation of glucose and lipid metabolism. Curcumin， the primary polyphenolic active compound derived from the traditional medicinal herb turmeric， exhibits multi-dimensional pharmacological effects including modulation of lipid metabolism， improvement of insulin sensitivity， suppression of inflammatory responses， and enhancement of antioxidant defense. This review systematically integrates the multi-target regulatory network of curcumin， elucidating its key mechanisms： Balancing the low density lipoprotein receptor/proprotein convertase subtilisin/kexin type 9 （LDLR/PCSK9） signaling pathway to promote reverse cholesterol transport， activating peroxisome proliferator-activated receptor α/γ （PPARα/γ） signaling pathways to coordinate glucolipid metabolic homeostasis， remodeling the gut microbiota-bile acid axis， inhibiting nuclear factor kappa-B （NF-κB）-mediated inflammatory responses， and activating the nuclear factor erythroid 2-related factor 2/antioxidant response element （Nrf2/ARE） antioxidant signaling pathway. Furthermore， supported by clinical research data， the review validates curcumin's therapeutic potential in reducing total cholesterol （TC） and triglyceride （TG） levels， increasing high-density lipoprotein cholesterol （HDL-C）， as well as improving vascular endothelial function and insulin sensitivity. The study highlights the multi-target regulatory properties of curcumin and discusses future clinical applications based on nano-delivery systems and personalized treatment strategies， providing a theoretical basis and novel insights for the prevention and treatment of hyperlipidemia and related metabolic disorders.

Tujia ethnic group medicine Xuetong is derived from Kadsura heteroclita, the stem of which has the medicinal value for anti-rheumatoid arthritis, liver protection, anti-tumor, anti-oxidation effects, and has been widely used in Hunan and Guangdong in China. The selection of reliable and stable reference genes is the basis for subsequent molecular research on K. heteroclita. In this study, GAPDH, TUA, Actin, UBQ, EF-1α, 18S-rRNA, CYP, UBC, TUB, H2A, and RPL were selected as candidate reference genes in Kadsura heteroclita. The gene expression levels of the 11 candidate reference genes of K. heteroclita in its 6 different parts(stem-inside of the cambium, stem-outside of the cambium, fruit, flower, root, and leaf) and under different intervention conditions [drought stress, salt stress, and methyl jasmonate(MeJA) treatment] were detected by quantitative real-time polymerase chain reaction(qRT-PCR). The expression stability of the 11 candidate reference genes was comprehensively analyzed and evaluated by geNorm, NormFinder, ΔCT algorithm, and RefFinder software. The results showed that the expression of UBC and RPL was relatively stable in 6 different parts, and UBC and GAPDH genes were relatively stable under different intervention conditions. To verify the reliability of reference genes for K. heteroclita, this study further examined the relative expression levels of KhFPS, KhIDI, KhCAS, KhSQE, KhSQS, KhSQS-2, KhHMGS, KhHMGR, KhMVD, KhMVK, KhDXR, KhDXS, KhPMVK, and KhGGPS in different parts and under different intervention conditions, which might relate to the synthesis of the main component(Xuetongsu) of K. heteroclita. The results showed that with UBC and RPL or UBC and GAPDH as the reference genes, the expression trends of these 14 genes were basically consistent in different parts or under different intervention conditions for K. heteroclita. In conclusion, UBC can be used as a reference gene of K. heteroclita for its different parts and different intervention conditions, which lays a foundation for further research on the biosynthetic pathway of main components in K. heteroclita.
Real-Time Polymerase Chain Reaction/methods* ; Reference Standards ; Gene Expression Regulation, Plant ; Gene Expression Profiling ; Plant Proteins/metabolism* ; Drugs, Chinese Herbal

Objective To analyze the research literature on fire needling therapy published on China National Knowledge Infrastructure(CNKI),Wanfang Data Knowledge Service Platform(Wanfang),and China Science and Technology Journal Database(VIP)in the last 20 years,and to explore the current status and the hotspots of the research,thus to summarize and analyze the spectrum of the dominant diseases and technological transformations of fire needling therapy.Methods CiteSpace and VOSviewer were applied to analyze the keywords,authors and institutions,to draw the scientific knowledge map,and to summarize the disease spectrum.Results A total of 4 226 literature were included,from 2000 to 2023,the number of publications on fire needling therapy research showed an increasing trend,with each of the four periods showing its own characteristics of the times.The"filiform fire needling"and"pricking of fire needling"were widely used as acupuncture tools and acupuncture techniques in the studies,the emergence of high-frequency disease keywords such as"shingles""vitiligo"and"acne"indicates that research on the treatment of skin diseases with fire needling has attracted much attention.The disease spectrum of fire needling therapy was enlarged,involving a total of 356 diseases distributed in 20 disease systems.Conclusion Skin diseases and arthralgia became the dominant diseases of fire needling therapy,the rise of research hot words such as"acne vulgaris""vitiligo""stroke""chronic eczema""filiform fire needling"and"Lingnan fire needling"indicates that fire needling therapy is developing towards research standardization,theoretical diversification and disease diversification.

Objective The high post-surgery recurrence rate of endometriosis(EMs)has emerged as a challenge in the long-term manaagement of the condition.This study is aimed at investigating the mechanisms of Neiyiting(NYT)decoction in preventing postoperative recurrence of EMs.Methods An animal model of EMs postoperative recurrence and a model of endometrial stromal cells(hEM15A)cocultured with macrophages(RAW 264.7 cell line)were established for both in vivo and in vitro experiments.An autotransplantation method was used to establish a rat model of EMs.The rats were divided into 4 groups(6 rats per group)and received the corresponding treatments:a Model group receiving distilled water,a Gestrinone group receiving gestrinone at 0.325 mg/kg,a low-dose NYT(NYT-L)group receiving NYT decoction at 5.04 g/(kg-d),and a high-dose NYT(NYT-H)group receiving NYT decoction at 10.08 g/(kg-d).The treatment was administered for 3 weeks via intragastric gavage.In addition,6 SD rats were randomly selected for the control group(Control group),and were given distilled water for 3 weeks via intragastric gavage.The sizes and pathological changes of recurrent lesions in EMs rats were observed.Immunohistochemistry and qRT-PCR were performed to assess the expression of M1 macrophage marker CD86 protein and mRNA in vivo.Additionally,immunohistochemistry and qRT-PCR were used to assess the expression of indicator proteins related to the triggering receptor expressed on myeloid cells 1(TREM1)/Toll-like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)signaling pathway and mRNA.The proliferation of hEM15A cells in the coculture experiment was observed.Flow cytometry was performed to determine the polarization of RAW264.7 macrophages,and qRT-PCR was used to determine the expression levels of inducible nitric oxide synthase(iNOS)and interleukin 1β(IL-1β)mRNA.Western blot was performed to determine the expression of signaling pathway-related indicator proteins in vitro.ELISA was performed to determine the levels of inflammatory factors in vitro.Results Compared with the Model group,the volume of recurrent lesions in the NYT-H group was reduced(P＜0.01).Findings from the macrophage M1 polarization assessment showed that the expression levels of CD86 protein and mRNA in the recurrent lesions of the Model group were higher than those in the control group(P＜0.01).The expression levels of CD86 protein and mRNA in the recurrent lesions of the NYT-H group were lower than those of the Model group(P＜0.01).In addition,the RAW 264.7 cell experiment further verified that NYT decoction could reduce the number of CD86-positive macrophages induced by plasmids overexpressing TREM1 and reduce the expression of IL-1β and iNOS mRNA(P＜0.01).The results of the hEM15A cell proliferation assay showed that NYT decoction down-regulated KI-67 protein expression in hEM15A cells induced by macrophage M1 polarization(P＜0.01).The results of TREM1/TLR4/NF-κB signaling pathway showed that the protein and mRNA expression levels of TREM1,TLR4,and NF-κB in the recurrent lesions of the Model group were higher than those of the control group(P＜0.01).Compared with those in the Model group,the protein and mRNA expression levels of TREM1,TLR4,and NF-κB in the recurrent lesions of the NYT-H group were lower(P＜0.01).In addition,the coculture experiment of RAW264.7 and hEM15A cells further confirmed that NYT decoction reduced the expression of TREM1,TLR4,and P-P65 proteins(P＜0.01).Conclusion NYT decoction can inhibit macrophage M1 polarization through the TREM1/TLR4/NF-κB signaling pathway,improve the inflammation level,and inhibit the formation of ectopic endometrial lesions,thereby preventing postoperative recurrence of EMs.

Objective To explore the neuroprotective effects and mechanisms of the sesquiterpene lactone compound ACT001 on rotenone(ROT)-induced Parkinson's disease(PD)model mouse.Methods SPF C57BL/6 mice were randomly divided into 6 groups,including control group,solvent control group,ROT model group,ACT001 5 mg/kg group(ROT+ACT001-5),ACT001 20 mg/kg group(ROT+ACT001-20),and levodopa(L-dopa)positive control group(ROT+L-dopa),with 9 mice in each group.The control group received an equivalent amount of intraperitoneal injection of saline,the solvent control group received an equivalent amount of rotenone solvent without rotenone,the remaining groups of mice were used to establish a PD mouse model by intraperitoneal injection of rotenone.Mice in different ACT001 dosage groups received intraperitoneal injections of high and low doses of ACT001,while the positive control group received levodopa intraperitoneally for 15 consecutive days.Behavioral changes in mice were assessed using open field,rotarod,pole-climbing,and balance beam tests.Immunofluorescence(IF)assay to detect the expression of tyrosine hydroxylase(TH)neurons,content of TH-positive fibers in the striatum and to detect the activation status of nigrostriatal microglia in the mouse midbrain;Real-time PCR was employed to measure the levels of interleukin(IL)-6,IL-1β,and tumor necrosis factor-α(TNF-α)in the substantia nigra of the mouse brain.Western blotting was used to measure the protein levels of TH,nuclear factor-κB(NF-κB)p65,NF-κB inhibitor α(IκBα),and phosphorylated IκBα(p-IκBα)in the substantia nigra of the mouse brain.Results Compared to the control group and the solvent control group,the rotenone-induced PD model group exhibited motor impairments in behavioral tests,a decrease in the number of TH positive neurons in the substantia nigra(P＜0.0001),decreased levels of TH-positive fibers in the striatum,activation of midbrain substantia microglia,and elevated levels of IL-6,IL-1β,TNF-α,p-IκBα,and NF-κB p65 expression.ACT001 significantly improved the behavioral impairments and substantia nigra damage in PD mice,increased the number of TH-positive neurons in the substantia nigra,increased levels of TH-positive fibers in the striatum,inhibition of microglial cell activation in the midbrain substantia nigra,and elevated the protein expression levels of IκBα while reducing the levels of IL-6,IL-1β,TNF-α,p-IκBα,and NF-κB p65 in the substantia nigra(P＜0.05).At a dose of 5 mg/kg,ACT001 significantly improved behavioral impairments in rotenone-induced PD mice,reduced the loss of dopaminergic neurons,and its mechanism may be related to the inhibition of the NF-κB signaling pathway and the suppression of inflammation.In summary,the intervention of ACT001 in the rotenone-induced PD mouse model inhibited the inflammatory response in the midbrain,increased the number of TH-positive neurons,and augmented the population of dopaminergic neurons in the substantia nigra,exerting a protective effect on neurons.Conclusion ACT001 significantly improves behavioral deficits in ROT-induced PD mice,ameliorates of dopaminergic neuron loss from the midbrain substantia nigra and striatum,inhibits the activation of nigrostriatal microglia in the midbrain,and suppresses inflammatory responses by inhibiting the activation of the NF-κB signaling pathway.

G protein-coupled receptors(GPCRs)are the largest family of membrane proteins in eukaryotes,with nearly 800 genes coding for these proteins.They are involved in many physiological processes,such as light perception,taste and smell,neurotransmitter,metabolism,endocrine and exocrine,cell growth and migration.Importantly,GPCRs and their ligands are the targets of approximately one third of all mar-keted drugs.GPCRs are traditionally known for their role in transmitting signals from the extracellular environment to the cell's interior via the plasma membrane.However,emerging evidence suggests that GPCRs are also localized on mitochondria,where they play critical roles in modulating mitochondrial functions.These mitochondrial GPCRs(mGPCRs)can influence processes such as mitochondrial respi-ration,apoptosis,and reactive oxygen species(ROS)production.By interacting with mitochondrial signaling pathways,mGPCRs contribute to the regulation of energy metabolism and cell survival.Their presence on mitochondria adds a new layer of complexity to the understanding of cellular signaling,highlighting the organelle's role as not just an energy powerhouse but also a crucial hub for signal transduction.This expanding understanding of mGPCR function on mitochondria opens new avenues for research,particularly in the context of diseases where mitochondrial dysfunction plays a key role.Ab-normalities in the phase conductance pathway of GPCRs located on mitochondria are closely associated with the development of systemic diseases such as cardiovascular disease,diabetes,obesity and Alz-heimer's disease.In this review,we examined the various types of GPCRs identified on mitochondrial membranes and analyzed the complex relationships between mGPCRs and the pathogenesis of various diseases.We aim to provide a clearer understanding of the emerging significance of mGPCRs in health and disease,and to underscore their potential as therapeutic targets in the treatment of these conditions.

Age-related macular degeneration(AMD)is a disease that affects the vision of elderly individuals worldwide.Although current therapeutics have shown effectiveness against AMD,some patients may remain unresponsive and continue to experience disease progression.Therefore,in-depth knowledge of the mechanism underlying AMD pathogenesis is urgently required to identify potential drug targets for AMD treatment.Recently,studies have suggested that dysfunction of mitochondria can lead to the ag-gregation of reactive oxygen species(ROS)and activation of the cyclic GMP-AMP synthase(cGAS)/stimulator of interferon genes(STING)innate immunity pathways,ultimately resulting in sterile inflammation and cell death in various cells,such as cardiomyocytes and macrophages.Therefore,combining strategies targeting mitochondrial dysfunction and inflammatory mediators may hold great potential in facilitating AMD management.Notably,emerging evidence indicates that natural products targeting mitochondrial quality control(MQC)and the cGAS/STING innate immunity pathways exhibit promise in treating AMD.Here,we summarize phytochemicals that could directly or indirectly influence the MQC and the cGAS/STING innate immunity pathways,as well as their interconnected mediators,which have the potential to mitigate oxidative stress and suppress excessive inflammatory responses,thereby hoping to offer new insights into therapeutic interventions for AMD treatment.