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.

Researchers commonly use cyclization recombination enzyme/locus of X-over P1 (Cre/loxP) technology-based conditional gene knockouts of model mice to investigate the functional roles of genes of interest in Sertoli and Leydig cells within the testis. However, the shortcomings of these genetic tools include high costs, lengthy experimental periods, and limited accessibility for researchers. Therefore, exploring alternative gene silencing techniques is of great practical value. In this study, we employed adeno-associated virus (AAV) as a vector for gene silencing in Sertoli and Leydig cells. Our findings demonstrated that AAV serotypes 1, 8, and 9 exhibited high infection efficiency in both types of testis cells. Importantly, we discovered that all three AAV serotypes exhibited exquisite specificity in targeting Sertoli cells via tubular injection while demonstrating remarkable selectivity in targeting Leydig cells via interstitial injection. We achieved cell-specific knockouts of the steroidogenic acute regulatory ( Star ) and luteinizing hormone/human chorionic gonadotropin receptor (Lhcgr) genes in Leydig cells, but not in Sertoli cells, using AAV9-single guide RNA (sgRNA)-mediated gene editing in Rosa26-LSL-Cas9 mice. Knockdown of androgen receptor ( Ar ) gene expression in Sertoli cells of wild-type mice was achieved via tubular injection of AAV9-short hairpin RNA (shRNA)-mediated targeting. Our findings offer technical approaches for investigating gene function in Sertoli and Leydig cells through AAV9-mediated gene silencing.
Animals ; Male ; Leydig Cells/metabolism* ; Mice ; Dependovirus/genetics* ; Sertoli Cells/metabolism* ; Gene Silencing ; Genetic Vectors ; Testis/cytology*

OBJECTIVES: To explore the application of the colloidal gold method and chemiluminescence method in detecting gonadotropin (Gn) in morning urine for assessing pubertal development status in children. METHODS: A total of 132 children diagnosed with central precocious puberty (CPP), early and fast puberty (EFP), and premature thelarche (PT) at Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from November 2021 to December 2022 were included, along with 685 healthy children who underwent routine health examinations at the hospital's pediatric health care department during the same period. All 132 patients underwent a gonadotropin-releasing hormone (GnRH) stimulation test. Both patients and healthy children had their urinary Gn levels measured using the colloidal gold method and chemiluminescence method, including levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The correlation between serum Gn and urinary Gn detected by the two methods, as well as the correlation between Tanner stages of healthy children and urinary Gn, was analyzed. RESULTS: Urine Gn levels detected by both the colloidal gold method and chemiluminescence method showed a positive correlation with serum LH baseline values, LH peak values, baseline LH/FSH ratios, and peak LH/FSH ratios (P<0.05). In healthy children, urinary LH levels detected by the chemiluminescence method gradually increased from Tanner stage Ⅰ to Ⅳ (P<0.05), while urinary FSH levels were lower in Tanner stage I than in stages Ⅱ, Ⅲ, and IV (P<0.05). Urinary LH levels detected by the colloidal gold method were lower in Tanner stage I compared to stages Ⅱ, Ⅲ, and IV, with the highest levels observed in Tanner stage Ⅳ (P<0.05). Additionally, urinary FSH levels in Tanner stage Ⅲ were higher than in stages Ⅰ and Ⅱ (P<0.05). The area under the receiver operating characteristic curve for evaluating Tanner stages I and II in healthy children using urinary LH and FSH levels by the chemiluminescence method and urinary LH levels by the colloidal gold method were 0.730, 0.699, and 0.783, respectively. CONCLUSIONS The colloidal gold method and chemiluminescence method for detecting Gn in morning urine show good correlation with serum Gn levels. As a non-invasive and convenient detection method, the colloidal gold method can serve as a useful tool for screening the onset of pubertal development in children.
Humans ; Child ; Male ; Female ; Gold Colloid ; Luminescent Measurements/methods* ; Gonadotropins/urine* ; Puberty ; Luteinizing Hormone/urine* ; Child, Preschool ; Adolescent ; Follicle Stimulating Hormone/urine*

Objective:To explore the correlation between thyroid hormone levels and the 90-day prognosis in patients with severe pulmonary tuberculosis, with a particular focus on the impact of age.Methods:This retrospective cohort study included 156 patients(43 females, 113 males; ages ranging from 21 to 93 years)diagnosed with severe pulmonary tuberculosis between January 2022 and December 2023.Patients were categorized into deceased( n=46)and survived( n=110)groups based on their 90-day survival status.Further subcategorization into elderly and non-elderly subgroups was conducted.Thyroid hormone levels and other relevant laboratory markers were measured and analyzed. Results:Total triiodothyronine(TT3) [(0.92±0.36)nmol/L] and free triiodothyronine(FT3) [(2.19±0.87)pmol/L] in deceased group were lower than in survival group [TT3(1.09±0.38)nmol/L], FT3 [(2.79±0.99)pmol/L], both P<0.05.T3 levels positively correlated with 90-day survival (TT3: r=-0.202, P=0.011; FT3: r=-0.276, P<0.001).In elderly patients, this correlation was weakened (TT3: r=-0.071, P=0.526; FT3: r=-0.206, P=0.059), but remained significant in non-elderly patients (TT3: r=-0.360, P=0.002; FT3: r=-0.345, P=0.003).FT3 was a better prognostic indicator than TT3. Conclusions:Low serum T3 levels are indicative of a poor prognosis in severe pulmonary tuberculosis; however, their predictive value diminishes in elderly patients.

Spine fracture and dislocation are common traumatic spinal conditions that often require surgical intervention due to compromised spinal stability. Surgical approaches include anterior, posterior, and combined anterior-posterior spinal procedures. According to the specific surgical requirements, patients may be placed in the prone position or repositioned between prone and supine positions during surgery. Intraoperative repositioning has become an essential step in patient positioning. However, during repositioning, patients with spinal fracture and dislocation are at increased risk for complications such as hemodynamic instability, nerve injury, and pressure injuries to the skin and soft tissue. Notably, due to the instability of the spinal cord, even minor manipulations can further exacerbate the damage, potentially leading to severe outcomes like paraplegia. Although the current clinical guidelines provide instructive recommendations for standard position, there remains no specific protocols for intraoperative repositioning in patients with spine fracture and dislocation. With a concern for the lack of clinical studies on positioning techniques, risk prevention, and operational norms for special patients, no applicable guidelines or standards are available. A consensus was required to provide clinical reference, meet the requirements of surgical treatment, and minimize the safety risks of patients caused by improper placement of positions. Professional Committee of Operating Room Nursing of Shaanxi Nursing Association organized experts in nursing management and operating room nursing from major hospitals across China to formulate Expert consensus on intraoperative repositioning for patients with spinal fracture and dislocation ( version 2025). The consensus provides 11 recommendations covering pre-repositioning preparation, intraoperative maneuvers, and post-repositioning observation, aiming to provide references for clinical standardization of the intraoperative repositioning process and protection of patients′ safety.

ObjectiveTobacco-related diseases remain one of the leading preventable public health challenges worldwide and are among the primary causes of premature death. In recent years, accumulating evidence has supported the classification of nicotine addiction as a chronic brain disease, profoundly affecting both brain structure and function. Despite the urgency, effective diagnostic methods for smoking addiction remain lacking, posing significant challenges for early intervention and treatment. To address this issue and gain deeper insights into the neural mechanisms underlying nicotine dependence, this study proposes a novel graph neural network framework, termed TI-GNN. This model leverages functional magnetic resonance imaging (fMRI) data to identify complex and subtle abnormalities in brain connectivity patterns associated with smoking addiction. MethodsThe study utilizes fMRI data to construct functional connectivity matrices that represent interaction patterns among brain regions. These matrices are interpreted as graphs, where brain regions are nodes and the strength of functional connectivity between them serves as edges. The proposed TI-GNN model integrates a Transformer module to effectively capture global interactions across the entire brain network, enabling a comprehensive understanding of high-level connectivity patterns. Additionally, a spatial attention mechanism is employed to selectively focus on informative inter-regional connections while filtering out irrelevant or noisy features. This design enhances the model’s ability to learn meaningful neural representations crucial for classification tasks. A key innovation of TI-GNN lies in its built-in causal interpretation module, which aims to infer directional and potentially causal relationships among brain regions. This not only improves predictive performance but also enhances model interpretability—an essential attribute for clinical applications. The identification of causal links provides valuable insights into the neuropathological basis of addiction and contributes to the development of biologically plausible and trustworthy diagnostic tools. ResultsExperimental results demonstrate that the TI-GNN model achieves superior classification performance on the smoking addiction dataset, outperforming several state-of-the-art baseline models. Specifically, TI-GNN attains an accuracy of 0.91, an F1-score of 0.91, and a Matthews correlation coefficient (MCC) of 0.83, indicating strong robustness and reliability. Beyond performance metrics, TI-GNN identifies critical abnormal connectivity patterns in several brain regions implicated in addiction. Notably, it highlights dysregulations in the amygdala and the anterior cingulate cortex, consistent with prior clinical and neuroimaging findings. These regions are well known for their roles in emotional regulation, reward processing, and impulse control—functions that are frequently disrupted in nicotine dependence. ConclusionThe TI-GNN framework offers a powerful and interpretable tool for the objective diagnosis of smoking addiction. By integrating advanced graph learning techniques with causal inference capabilities, the model not only achieves high diagnostic accuracy but also elucidates the neurobiological underpinnings of addiction. The identification of specific abnormal brain networks and their causal interactions deepens our understanding of addiction pathophysiology and lays the groundwork for developing targeted intervention strategies and personalized treatment approaches in the future.

Objective To investigate the value of repeat renal biopsy in the treatment and prognosis of nephrotic syndrome(NS)and acute kidney injury(AKI)following immunosuppressive therapy in patients with lupus nephritis(LN). Methods A retrospective analysis was conducted for the clinicopathological data and follow-up records of LN patients undergoing repeat renal biopsy at Peking Union Medical College Hospital from January 1,2009 to December 31,2021. Results A total of 76 patients(55 females,72.4%)were included in this study,with the mean age at the first biopsy being(29.0±10.4)years,the median inter-biopsy interval of 4.0(2.0,7.0) years,and the median total follow-up duration of 7.5(5.0,13.8)years.Pathological transformation occurred in 46(60.5%)patients,and 2 patients had comorbid diabetic nephropathy.At repeat renal biopsy,50(65.8%) patients presented NS.These patients demonstrated lower estimated glomerular filtration rate(eGFR)(P<0.001),higher chronicity index(CI)(P=0.029),and higher complement C3(P<0.001)and C4(P<0.001)levels than those with NS at the first renal biopsy(n=50).Among the 28(36.8%) patients with AKI at repeat renal biopsy,8(28.6%)experienced acute exacerbation of chronic renal insufficiency.These patients exhibited higher serum creatinine level(P=0.002),C4 level(P=0.033),CI(P=0.042),and prevalence of thrombotic microangiopathy(P=0.046)than the patients showing AKI at the first renal biopsy(n=16),while the activity index(AI)showed no significant difference(P=0.051).Over 50% of NS and AKI patients underwent treatment modifications post-repeat renal biopsy,with clinical remission rates comparable to those after the first renal biopsy(both P>0.05).Elevated CI(≥5,P=0.001)and serum creatinine(≥140 μmol/L,P<0.001)at repeat renal biopsy were identified as independent risk factors for poor prognosis.The patients with AKI at repeat renal biopsy had higher incidence of endpoint events than the non-AKI patients(P=0.015).Neither AKI at the first renal biopsy nor NS at both biopsies had significant associations with prognosis. Conclusions Repeat renal biopsy reveals not only sustained high disease activity but also accelerates chronic progression in LN patients,which underscore its critical role in guiding the therapy for severe LN post-immunosuppression.AKI,CI≥5,and serum creatinine ≥140 μmol/L at repeat renal biopsy are strongly associated with poor prognosis.
Humans ; Lupus Nephritis/drug therapy* ; Female ; Retrospective Studies ; Adult ; Male ; Prognosis ; Biopsy ; Kidney/pathology* ; Acute Kidney Injury/pathology* ; Nephrotic Syndrome/pathology* ; Glomerular Filtration Rate ; Young Adult ; Immunosuppressive Agents/therapeutic use* ; Middle Aged