Chronic pain is a complex condition shaped by long-standing alterations in both physiological and psychological processes. Rather than representing a simple continuation of acute nociceptive signaling, chronic pain is increasingly understood as the outcome of progressive dysregulation within distributed neural systems that govern sensation, affect, motivation, and cognitive control. Neuroimaging and electrophysiological studies indicate that this state is accompanied by extensive plastic changes in deep brain structures and large-scale networks. Beyond well-described central sensitization processes, chronic pain is characterized by disrupted oscillatory rhythms and altered connectivity within large-scale brain networks, including thalamo-cortical circuits and prefrontal-limbic-reward networks. These findings support a conceptual shift from viewing chronic pain as a focal, lesion-driven phenomenon toward recognizing it as a disorder of distributed network pathology. Pharmacological treatments remain central to clinical practice, yet their long-term efficacy is often limited and frequently accompanied by substantial side effects. The ongoing concerns about opioid-related risks and the inadequate therapeutic response in a subset of patients highlight the need for safe, non-pharmacological approaches that can address not only pain but also comorbid disturbances in mood, sleep, and social functioning. Neuromodulation provides a promising path toward mechanism-based and non-pharmacological management of chronic pain by employing physical or chemical stimulation to alter the excitability and synchrony of specific neural populations within central, peripheral, and autonomic systems. While invasive deep brain stimulation demonstrates that targeting deep brain structures can be effective, its clinical application is restricted by surgical risks and cost, highlighting the importance of non-invasive techniques capable of reaching deep targets. Current non-invasive approaches, such as transcranial electric stimulation, are constrained by limited penetration depth and insufficient spatial precision. These limitations hinder reliable engagement of deep regions implicated in pain, including the thalamus and nucleus accumbens, and tend to produce broad, non-specific modulation of cross-network oscillatory activity. Temporal interference (TI) stimulation has emerged as a means of overcoming these obstacles. By delivering interacting high-frequency currents that generate a low-frequency envelope within the head, TI enables focal stimulation of deep targets while minimizing superficial current delivery. Recent multiscale modeling and animal studies indicate that TI exploits the nonlinear rectification properties of neuronal membranes in response to high-frequency carriers, as well as their phase-locked responses to low-frequency envelopes, to generate “peak-focused” electric fields in deep regions under relatively low superficial current loads. Moreover, TI appears to exhibit potential advantages in terms of cell-type selectivity and rhythm-specific engagement, including differential responses across neuronal subtypes and distinct coupling to θ-, β-, and γ-band oscillations. These features suggest a promising avenue for correcting abnormal rhythms and network dynamics that contribute to chronic pain. This review summarizes current knowledge of the neural mechanisms underlying chronic pain and recent advances in TI research. It examines functional disturbances across key pain-related regions and networks, outlines the principles and technical characteristics of TI, and discusses potential deep-brain targets and stimulation strategies relevant to chronic pain. Evidence to date indicates that TI, with its non-invasiveness, tolerability, and capacity for precise deep brain modulation, holds great promise for the management of treatment-resistant chronic pain and may evolve into a new generation of precise and efficient non-pharmacological analgesic strategies.

Chronic pain is a complex condition shaped by long-standing alterations in both physiological and psychological processes. Rather than representing a simple continuation of acute nociceptive signaling, chronic pain is increasingly understood as the outcome of progressive dysregulation within distributed neural systems that govern sensation, affect, motivation, and cognitive control. Neuroimaging and electrophysiological studies indicate that this state is accompanied by extensive plastic changes in deep brain structures and large-scale networks. Beyond well-described central sensitization processes, chronic pain is characterized by disrupted oscillatory rhythms and altered connectivity within large-scale brain networks, including thalamo-cortical circuits and prefrontal-limbic-reward networks. These findings support a conceptual shift from viewing chronic pain as a focal, lesion-driven phenomenon toward recognizing it as a disorder of distributed network pathology. Pharmacological treatments remain central to clinical practice, yet their long-term efficacy is often limited and frequently accompanied by substantial side effects. The ongoing concerns about opioid-related risks and the inadequate therapeutic response in a subset of patients highlight the need for safe, non-pharmacological approaches that can address not only pain but also comorbid disturbances in mood, sleep, and social functioning. Neuromodulation provides a promising path toward mechanism-based and non-pharmacological management of chronic pain by employing physical or chemical stimulation to alter the excitability and synchrony of specific neural populations within central, peripheral, and autonomic systems. While invasive deep brain stimulation demonstrates that targeting deep brain structures can be effective, its clinical application is restricted by surgical risks and cost, highlighting the importance of non-invasive techniques capable of reaching deep targets. Current non-invasive approaches, such as transcranial electric stimulation, are constrained by limited penetration depth and insufficient spatial precision. These limitations hinder reliable engagement of deep regions implicated in pain, including the thalamus and nucleus accumbens, and tend to produce broad, non-specific modulation of cross-network oscillatory activity. Temporal interference (TI) stimulation has emerged as a means of overcoming these obstacles. By delivering interacting high-frequency currents that generate a low-frequency envelope within the head, TI enables focal stimulation of deep targets while minimizing superficial current delivery. Recent multiscale modeling and animal studies indicate that TI exploits the nonlinear rectification properties of neuronal membranes in response to high-frequency carriers, as well as their phase-locked responses to low-frequency envelopes, to generate “peak-focused” electric fields in deep regions under relatively low superficial current loads. Moreover, TI appears to exhibit potential advantages in terms of cell-type selectivity and rhythm-specific engagement, including differential responses across neuronal subtypes and distinct coupling to θ-, β-, and γ-band oscillations. These features suggest a promising avenue for correcting abnormal rhythms and network dynamics that contribute to chronic pain. This review summarizes current knowledge of the neural mechanisms underlying chronic pain and recent advances in TI research. It examines functional disturbances across key pain-related regions and networks, outlines the principles and technical characteristics of TI, and discusses potential deep-brain targets and stimulation strategies relevant to chronic pain. Evidence to date indicates that TI, with its non-invasiveness, tolerability, and capacity for precise deep brain modulation, holds great promise for the management of treatment-resistant chronic pain and may evolve into a new generation of precise and efficient non-pharmacological analgesic strategies.

ObjectiveThe present study aimed to investigate alterations in white matter microstructure and spontaneous neural activity in male college smokers, and to further explore their associations with nicotine dependence. Given that adolescence and early adulthood represent critical periods for brain maturation, particularly for white matter development, understanding the neural correlates of smoking behavior during this stage is of substantial importance for both neuroscience and public health. MethodsA total of 115 male undergraduate students were initially recruited for this study. After quality control and exclusion procedures, 52 male college smokers and 42 demographically matched healthy non-smokers were included in the final analysis. All participants underwent multimodal magnetic resonance imaging (MRI), including diffusion tensor imaging (DTI) and resting-state functional MRI (rs-fMRI). White matter fiber tracts were reconstructed using the automated fiber quantification (AFQ) method, which enables precise identification and quantification of major fiber bundles. Eighteen major white matter tracts were segmented for each participant. Along the core trajectory of each tract, 100 equidistant nodes were sampled. Fractional anisotropy (FA) was calculated at each node to assess white matter microstructural integrity, while amplitude of low-frequency fluctuation (ALFF) was computed to evaluate spontaneous neural activity within white matter tracts. Between-group differences in FA and ALFF were assessed using two-sample t-tests, with appropriate corrections applied for multiple comparisons. Furthermore, Pearson correlation analyses were conducted to examine the relationships between imaging-derived metrics (FA and ALFF values in regions showing significant group differences) and nicotine dependence severity, as measured by the Fagerström test for nicotine dependence (FTND). ResultsCompared with healthy non-smokers, male college smokers exhibited significantly increased FA values in several white matter tracts, including the left thalamic radiation, right corticospinal tract, forceps major of the corpus callosum, left uncinate fasciculus, and right arcuate fasciculus. These findings suggest altered microstructural organization or increased directional coherence within these pathways. In addition, smokers demonstrated significantly elevated ALFF values in the forceps major, right uncinate fasciculus, and left arcuate fasciculus, indicating enhanced spontaneous neural activity in these white matter regions. Correlation analyses revealed that FA values in the left thalamic radiation and right corticospinal tract were negatively correlated with FTND scores, suggesting that higher levels of nicotine dependence were associated with reduced microstructural integrity or altered fiber organization in these regions. In contrast, ALFF values in the forceps major and right uncinate fasciculus were positively correlated with FTND scores, indicating that greater nicotine dependence was associated with increased spontaneous neural activity in specific white matter pathways. ConclusionThe present study provides evidence that male college smokers exhibit distinct alterations in both white matter microstructure and functional activity. These abnormalities are not uniformly distributed but rather localized to specific fiber tracts implicated in sensorimotor processing, interhemispheric communication, and higher-order cognitive and emotional regulation. Importantly, the observed associations between imaging metrics and nicotine dependence severity suggest that these structural and functional alterations may reflect neurobiological mechanisms underlying addiction. The combination of AFQ-based tract profiling and multimodal MRI offers a sensitive approach for detecting subtle changes along white matter pathways, highlighting its potential utility in identifying neuroimaging biomarkers of nicotine dependence. Overall, these findings indicate that smoking during early adulthood may disrupt ongoing white matter maturation, potentially leading to long-term consequences for brain function. This study provides novel insights into the neural basis of nicotine dependence and underscores the importance of early intervention and prevention strategies targeting young smokers.

Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

This paper summarizes professor LIN Yi's clinical experience in treating brain metastases of triple-negative breast cancer （TNBC）. It is believed that the pathogenesis of this disease is fundamentally based on spleen and lung qi deficiency， with the binding of phlegm， stasis， and toxins acting as the critical link for disease progression， and qi stagnation serving as a major factor in its protracted course. The core therapeutic principle of "consolidating the root and cultivating the origin， resolving phlegm and dredging collaterals" is proposed. Clinically， the disease is staged into active， stable， and convalescent phases. During the active phase， characterized by spleen and lung qi deficiency alongside hyperactivity of phlegm-toxin pathogens， the treatment focuses on supplementing qi， fortifying the spleen， resolving phlegm， and dredging collaterals， utilizing the Yiqi Jiangtan Tongluo Formula （益气降痰通络方）. During the stable phase， marked by spleen deficiency， weak qi， and residual phlegm， stasis， and toxins lingering in the collaterals， the treatment aims to fortify spleen， cultivate the origin， expel pathogens， and dredge collaterals， using modified Baihua Qiling Formula （白花芪苓方）. During the convalescent phase， characterized by depletion of healthy qi， dysfunction of zang-fu （脏腑） organs， and deep-seated residual phlegm， stasis， and toxins within the brain collaterals， the treatment focuses on regulating qi movement， protecting body fluids， and applying constitution-based treatments， mostly using mild and nourishing medicinals.

This paper summarizes professor LIN Yi's clinical experience in treating brain metastases of triple-negative breast cancer （TNBC）. It is believed that the pathogenesis of this disease is fundamentally based on spleen and lung qi deficiency， with the binding of phlegm， stasis， and toxins acting as the critical link for disease progression， and qi stagnation serving as a major factor in its protracted course. The core therapeutic principle of "consolidating the root and cultivating the origin， resolving phlegm and dredging collaterals" is proposed. Clinically， the disease is staged into active， stable， and convalescent phases. During the active phase， characterized by spleen and lung qi deficiency alongside hyperactivity of phlegm-toxin pathogens， the treatment focuses on supplementing qi， fortifying the spleen， resolving phlegm， and dredging collaterals， utilizing the Yiqi Jiangtan Tongluo Formula （益气降痰通络方）. During the stable phase， marked by spleen deficiency， weak qi， and residual phlegm， stasis， and toxins lingering in the collaterals， the treatment aims to fortify spleen， cultivate the origin， expel pathogens， and dredge collaterals， using modified Baihua Qiling Formula （白花芪苓方）. During the convalescent phase， characterized by depletion of healthy qi， dysfunction of zang-fu （脏腑） organs， and deep-seated residual phlegm， stasis， and toxins within the brain collaterals， the treatment focuses on regulating qi movement， protecting body fluids， and applying constitution-based treatments， mostly using mild and nourishing medicinals.

Renal fibrosis is the common pathological endpoint of many forms of chronic kidney disease (CKD), yet the mechanisms determining effective repair versus persistent fibrotic remodeling remain incompletely understood. Peritubular capillaries (PTCs) are not merely passive targets of fibrotic injury, but form a dynamic vascular microenvironment linking regional perfusion, oxygen delivery, tubular metabolism, endothelial barrier integrity, pericyte support, immune-cell trafficking, and extracellular matrix (ECM) remodeling. We propose that PTC abnormalities should not be interpreted simply as reduced capillary density, but as a multidimensional disturbance of microvascular structure and function. Structural vascular preservation does not necessarily indicate effective microcirculation: anatomically detectable capillaries may still exhibit impaired perfusion, barrier dysfunction, abnormal endothelial-pericyte interactions, disturbed oxygen metabolism, or reduced network connectivity. Conversely, increased angiogenesis does not necessarily signify successful vascular repair if vessels remain immature, poorly perfused, or inadequately integrated into the existing network. To organize these abnormalities, we conceptualize PTC remodeling into four predominant but nonexclusive states: endothelial barrier disruption with inflammatory adhesion; endothelial-pericyte uncoupling with no-reflow; dysregulated angiogenesis with network simplification; and capillary rarefaction with fibrotic matrix locking. These states are not sequential stages of CKD. They may coexist within the same kidney, overlap within the same anatomical region, and vary with disease etiology, injury phase, vascular compartment, and treatment exposure. We further propose six dimensions for evaluating PTC status—structural presence, functional perfusion, barrier integrity, pericyte coupling, oxygen metabolism, and network connectivity—so that vascular quantity, function, and reparative capacity are assessed separately rather than inferred from a single endothelial marker or capillary-density measurement. Mechanistically, these states converge on a bidirectional microvascular-fibrotic feedback loop. Barrier disruption facilitates leukocyte recruitment and alters vascular paracrine signaling. Endothelial-pericyte uncoupling compromises capillary stability, whereas abnormal pericyte contraction may increase local vascular resistance and contribute to no-reflow before overt capillary loss. Dysregulated angiogenesis may generate vessels that fail to mature or connect to an effective perfusion network. Progressive capillary rarefaction compromises oxygen delivery, while sustained tubular transport demand and mitochondrial dysfunction may aggravate regional oxygen supply-demand mismatch. Injured tubules, immune cells, endothelial cells, pericytes, and fibroblasts communicate through soluble mediators, extracellular vesicles, direct cell contact, and cell-matrix signaling. Importantly, fibrosis is not merely a downstream consequence of microvascular injury. Altered ECM may increase diffusion distance, modify mechanotransduction, impair endothelial survival and migration, and restrict capillary reopening and regeneration. We use the term matrix locking to describe this sustained constraint on vascular repair, while emphasizing that current evidence does not establish irreversible disease in humans. This framework also has therapeutic implications. PTC-directed treatment should not be reduced to increasing vessel number or uniformly promoting angiogenesis. Instead, intervention should be matched to the dominant and potentially reversible abnormality: preserving endothelial barrier function; restoring endothelial-pericyte stability and reducing pathological microvascular resistance; normalizing angiogenesis so that vascular growth is accompanied by maturation, barrier competence, network integration, and effective perfusion; and, in advanced rarefaction, relieving matrix-related constraints while supporting vascular regeneration. The context- and time-dependent effects of signaling through VEGF, Tie2, PDGF-B/PDGFRβ, eNOS/NO, and related pathways indicate that the same molecular signal may exert different effects depending on disease context and timing. Therapeutic efficacy should therefore be evaluated by restoration of effective microcirculation and tissue function rather than by isolated molecular changes or capillary counts alone. Despite increasing mechanistic evidence, the translational basis for this framework remains limited. Most causal and interventional data derive from animal or cell models, whereas human evidence is largely limited to pathological observations, patient-sample associations, and prognostic studies. Currently available circulating and urinary candidate biomarkers generally lack sufficient specificity for PTC injury or state assignment, and no standardized quantitative thresholds have been externally validated. The four-state model should therefore be regarded as a hypothesis-generating analytical framework rather than a clinicopathological classification system. Future studies should integrate spatially resolved tissue phenotyping, blood and urine biomarkers, and dynamic microcirculatory assessment in longitudinal cohorts. They should test reproducibility, assess prognostic value beyond conventional pathology, estimated glomerular filtration rate, and proteinuria, and determine whether changes in PTC status precede or mediate therapeutic benefit. Linking reproducible microvascular phenotypes to defined mechanisms, treatment response, and long-term renal outcomes will be essential to determine whether state-directed assessment and restoration of the PTC microenvironment can ultimately inform patient stratification and therapeutic decision-making.

AIM To investigate the tumor-suppressive mechanism of Guiqi Yiyuan Extract combined with cisplatin in Lewis lung cancer mice.METHODS Ten intact C57BL/6J mice were assigned to the blank group.Sixty additional mice were developed into Lewis lung cancer models bearing transplanted tumor and subsequently allocated into the model group,the cisplatin group(5 mg/kg),the high-dose Guiqi Yiyuan Extract group(6.6 g/kg),and the low-dose,medium-dose and high-dose Guiqi Yiyuan Extract combined with cisplatin group(1.6,3.3,6.6 g/kg+5 mg/kg),with 10 mice in each group.Mice in the blank and model groups received saline via daily gavage,while treatment groups were administered Guiqi Yiyuan Extract orally(once daily),and cisplatin injection intraperitoneally(once every other day).After 14 days of drug administration,mice were euthanized for endpoint analysis.The following assessments were conducted:general health status and body weight changes monitored throughout the study period;tumor excision and weighing for inhibition rate calculation;histopathological examination of tumors via hematoxylin-eosin(HE)staining;serum quantification of IL-1 β,IL-18 and HMGB1 by ELISA;ultrastructural analysis of tumor cell death using transmission electron microscopy(TEM);spatial localization of TXNIP and GSDMD-N in tumor sections via immunofluorescence(IF);and Western blot detection of TXNIP,NLRP3,Caspase-1,cleaved Caspase-1,GSDMD,GSDMD-N protein expressions in tumor tissues.RESULTS Compared to the model group,the cisplatin group and all combination therapy groups exhibited significant reduction in tumor weight(P＜0.05)and increased tumor suppression rate;enhanced tumor tissue necrosis with characteristic pyroptotic morphology;elevated serum levels of IL-1β,IL-18 and HMGB1(P＜0.05);and upregulated expressions of pyroptosis-associated proteins TXNIP,NLRP3,Caspase-1,cleaved Caspase-1,GSDMD and GSDMD-N(P＜0.05).The high dose combination group demonstrated optimal therapeutic efficacy(P＜0.05).CONCLUSION Guiqi Yiyuan Extract enhances cisplatin sensitivity,demonstrating synergistic anti-tumor effects in Lewis lung carcinoma-bearing mice.This combinatorial therapeutic effect likely involves modulation of the TXNIP/NLRP3/Caspase-1/GSDMD pathway.

AIM To study the chemical constituents from Euphorbia humifusa Willd.and their in vitro anti-hepatoma activity.METHODS Silica gel,D101 macroporous adsorption resin and semi-preparative RP-HPLC were used for isolated and purified,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The anti-hepatocellular carcinoma activity was determined by MTT mothod.RESULTS Eighteen compounds were isolated and identified as 22-O-angeloyl-R1-barrigenol(1),dimethyl 3,3'-[oxybis(4,1-phenylene)](2E,2'E)-diacrylate(2),N-(3-methoxy-1,3-dioxopropyl)-D-tryptophan methyl ester(3),N-acetyltryptophan methyl ester(4),N-(methoxycarbonyl)-tryptophan methyl ester(5),(3β,5α,17β)-4,4,8,14-tetramethyl-18-norandrostane-3,17-diol(6),3β,18,19β-trihydroxylupane(7),pregnenolone(8),3-hydroxy-5,6-epoxy-7-megastigmen-9-one(9),dehydrovomifoliol(10),loliolide(11),2,2'-oxybis(1,4-di-tert-butylbenzene)(12),dibutyl phthalate(13),4-methoxycinnamic acid(14),3,4-dimethoxycinnamic acid(15),methyl 4-hydroxybenzoate(16),kaempferol(17),quercetin(18).The IC50 values of compounds 1,7 and 8 on HepG2 cells were(17.27±0.92),(19.11±2.14)and(7.53±1.09)μmol/L,respectively.CONCLUSION Compounds 1-16 are first isolated from this plant.Compounds 1,7 and 8 have anti-hepatoma activity.

A centrifugation-free,single-reaction colorimetric method for detection of glucose,utilizing a dual nanozyme cascade system based on gold nanoparticles(AuNPs)and iron-doped carbon dots(FeCDs),was developed in this work.The AuNPs exhibited glucose oxidase-like activity to catalyze glucose oxidation for generation of H2O2,while the FeCDs demonstrated peroxidase-like activity to subsequently catalyze the H2O2-mediated oxidation of 3,3',5,5'-tetramethylbenzidine(TMB).To prevent interference from the blue signal generated by self-aggregation of AuNPs in subsequent quantitative detection,the reaction system was terminated with HCl,converting oxTMB into a stable yellow product.Based on changes in the absorbance at 450 nm of this yellow solution,a quantitative relationship was established between glucose concentration and absorbance at 450 nm(A450).Experimental results demonstrated that this sensor achieved a linear detection range of 44 μmol/L to 11.11 mmol/L(R2=0.993)with a detection limit of 30.68 μmol/L and spiked recoveries of 97.9%-104.7%.By integrating smartphone-based color recognition capabilities,a rapid visual detection platform was established for quantification of glucose through RGB analysis.The validation experimental results using commercial glucose injection samples further confirmed the practical application potential of this methodology.