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.

Objective·To evaluate the feasibility and diagnostic performance of diffusion-relaxation correlation spectroscopic imaging(DR-CSI)in assessing the heterogeneity of benign and malignant head and neck tumors,as well as in identifying occult lymph node metastasis(OLNM).Methods·A prospective study was conducted from January to December 2024 at Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,enrolling patients with suspected head and neck tumors who were scheduled for surgery and had a confirmed pathological diagnosis.All patients underwent preoperative routine head and neck plain and contrast-enhanced magnetic resonance imaging(MRI)examinations,including DR-CSI sequence.Conventional imaging parameters,including maximal diameter(MD),depth of invasion(DOI)for tumors,and MD and short diameter(SD)for lymph nodes,were obtained.Post-processing was performed to obtain apparent diffusion coefficient(ADC),T2 value,and D-T2 spectra for all lesions.The compartment segmentation strategy was optimized based on the spectral peak distribution characteristics of different diseases,and the volume fraction(Vi)of each compartment was obtained.Independent sample t-tests,Mann-Whitney U tests,chi-square tests,or Fisher's exact tests were used to compare intergroup differences in clinical data and imaging metrics.Principal component analysis(PCA)and Adonis analysis were employed to evaluate the discriminative ability of imaging metrics among different subtypes of benign tumors.Receiver operating characteristic(ROC)analysis was used to evaluate the ability of univariate and multivariable models to characterize the malignancy of head and neck squamous cell carcinoma(HNSCC)and identify OLNM.Results·A total of 97 cases were collected,including 28 benign tumors and 69 HNSCCs.Fifteen pathologically confirmed OLNMs and 20 benign lymph nodes(BLNs)were also enrolled.Among the 28 benign tumors,there were 6 cases of pleomorphic adenoma stroma-rich(PA stroma-rich),9 cases of pleomorphic adenoma stroma-poor(PA stroma-poor),9 cases of Warthin's tumor(WT),and 4 cases of basal cell adenoma(BCA).Statistically significant differences were observed in certain imaging parameters(ADC,T2,and DR-CSI Vi)among benign tumor subtypes.PCA analysis demonstrated a strong discriminative ability of imaging parameters in distinguishing pathological subtypes of benign tumors(R2=0.64,P<0.001).Among the 69 HNSCCs,47 were classified as Grade 1(well/moderately well-differentiated)and 22 as Grade 2(moderately/poorly differentiated).Compared to Grade 1,Grade 2 showed lower ADC and higher T2 values,though differences were not statistically significant.As HNSCC malignancy increased,VA4 decreased and VB4 increased significantly.OLNM showed a significant increase in SD and VA4 compared to BLNs.The combination of SD and VA4 for preoperative OLNM identification achieved a diagnostic efficiency of 0.843.Conclusion·DR-CSI can analyze diffusion and relaxation characteristics at the sub-voxel level,offering valuable insights for characterizing benign head and neck tumor subtypes,assessing HNSCC malignancy,and identifying OLNMs.Compared to traditional parameters like ADC or T2,DR-CSI provides enhanced tissue microstructure analysis.

Objective To develop a novel type of transparent simulation manikin as a surgical training model to meet the surgical treatment demand on the medical train.Methods A transparent manikin was developed with the steps of basic data collection,motherboard design and manufacture and module production and assembly.Firstly,basic data collection was carried out with reference to standardized human anatomy and parameters.Secondly,some software such as UG NX7.5 was used to construct the motherboard of the manikin.Finally,module production and assembly were performed with the materials of acrylic,transparent rubber,silicone and hydrogel and the technology of silicone infusion.Results The transparent manikin developed had its anatomy structure close to that of the real body and high visuality for its internal and external components,which simulated a variety of war wounds and thus could be integrated with the surgical training scenarios on the medical train effectively.Conclusion The transparent manikin developed is characterized by high visuality,modularity and blood flow,and meets the demands for surgical training on the medical train.[Chinese Medical Equipment Journal,2025,46(6):111-115]

Pulmonary hypertension (PH) is a group of progressive diseases characterized by pulmonary vascular remodeling,and some patients already have right heart insufficiency at the time of diagnosis. Therefore,early diagnosis of PH is essential to improve patients' quality of life and prolong survival. Biomarkers are an important indicator for early diagnosis of the disease,and there are many traditional biomarkers for PH diagnosis,but the sensitivity and specificity are low. With the progress of research,some new biomarkers have been shown to predict disease progression in early PH and play an important role in the early diagnosis of PH. This study reviews the research progress of biomarkers of PH from the aspects of right heart insufficiency,endothelial dysfunction,pulmonary artery smooth muscle dysfunction,inflammation,and in situ thrombosis to provide exploration direction and reference value for early diagnosis of PH.

Objective:To investigate the therapeutic efficacy and safety of tislelizumab combined with platinum-based drugs in patients with advanced non-small cell lung cancer (NSCLC).Methods:A prospective randomized controlled study was conducted. Eighty-six patients with clinical stage Ⅳ NSCLC in Huaibei People's Hospital from June 2020 to June 2023 were selected as the study subjects, and the patients were divided into the control group and the observation group based on the randomized numerical table method, with 43 cases in each group. The control group was treated with platinum-based drugs, the observation group was treated with platinum-based drugs combined with tislelizumab, and all patients were treated for 4-6 cycles. The two groups were compared in terms of therapeutic efficacy, serum tumor markers [carcinoembryonic antigen (CEA), cytokeratin 19 soluble fragment (CYFRA21-1) and carbohydrate antigen 125 (CA125)] detected by chemiluminescence method, serum immune function indicators [CD3 +, CD4 +, CD8 + cell ratios and CD4 + cell number-to-CD8 + cell number ratio (CD4 +/CD8 +)] detected by flow cytometry, and quality of life [European Organization for Research and Treatment of Cancer (EORTC) quality of life measurement scale (QLQ-C30) scores in functional domain and symptom domain], and incidence of adverse reactions. Results:The differences in baseline data of age, gender, degree of tumor differentiation, pathological type, lesion location, programmed death receptor ligand 1 expression between the observation group and the control group were not statistically significant (all P > 0.05). After treatment, the objective remission rates in the observation and control groups were 34.9% (15/43) and 18.6% (8/43), respectively, and the difference was not statistically significant ( χ2 = 2.91, P = 0.088); the disease control rate in the observation group was 74.4% (32/43), which was higher than that in the control group [51.2% (22/43)], and the difference was statistically significant ( χ2 = 4.98, P = 0.026). The differences in the serum levels of CEA, CYFRA21-1 and CA125 between the observation group and the control group before treatment were not statistically significant (all P > 0.05); the serum levels of CEA, CYFRA21-1 and CA125 in the observation group were lower than those in the control group after treatment, and the differences were all statistically significant (all P < 0.01). The differences in the CD3 +, CD4 +, CD8 + cell ratios and CD4 +/CD8 + between the observation group and the control group before treatment were not statistically significant (all P > 0.05); the CD3 +, CD4 + cell ratios and CD4 +/CD8 + in the observation group were higher than those in the control group, the CD8 + cell ratio was lower than that in the control group after treatment, and the differences were all statistically significant (all P < 0.01). Before treatment, there were no statistically significant differences in the scores of EORTC QLQ-C30 functional domain and symptom domain between the observation group and the control group (both P > 0.05); after treatment, the functional domain score of the observation group was higher than that of the control group, the symptom domain score was lower than that of the control group, and the differences were statistically significant (both P < 0.01). The incidence rates of skin itching, rash and diarrhea in the observation group were 23.3% (10/43), 20.9% (9/43) and 48.8% (21/43), respectively, which were higher than those in the control group [4.7% (2/43), 2.3% (1/43) and 27.9% (12/43)], and the differences were statistically significant (all P < 0.05). Conclusions:Tislelizumab combined with platinum-based drugs in advanced NSCLC patients can enhance the short-term efficacy, reduce serum tumor marker levels, and improve the immune function and quality of life of the patients, but it will increase the occurrence of skin and digestive tract adverse reactions.

Objective:The aim of this study is to explore the influencing factors of fertility preservation decision-making in tes-ticular cancer patient and provide a basis for clinical decision.Methods:A descriptive qualitative study was conducted using purpos-ive sampling in 18 testicular cancer patients.Semi-structured interviews were performed,and data were analyzed through content analy-sis.Results:A total of 3 themes and 10 subthemes were extracted including individual factors(fertility circumstance,concerns a-bout sperm cryopreservation efficacy/quality,the preferred choice between treatment and fertility preservation,confidence in future fer-tility),medical factors(physicians' recommendations on fertility preservation,fertility-related information,urgency of treatment),and socio-environmental factors(traditional beliefs of fertility,family/partner support,accessibility/cost of cryopreservation).Conclusion:This study highlights many influencing factors of fertility preservation decision-making in testicular cancer patients,em-phasizing the need for clinicians to enhance awareness of fertility preservation,provide timely and targeted information,and advocate for policy interventions to reduce financial barriers.Strengthening healthcare support and systemic safeguards may optimize patients' de-cision-making outcomes.

Yanchi Tan sheep,a specialty of Ningxia,China,is famous for its excellent meat quality,but the detailed mechanisms of its muscle development and meat quality formation are still unclear.In or-der to preliminarily investigate the unique molecular mechanisms in the muscle development of the sheep,the present study was carried out to collect the longest dorsal muscle(LDM)samples from 6-month-old and 12-month-old female Tan sheep,and we screened the genes and long non-coding RNA(lncRNAs)that may play important roles in regulating the muscle development and meat quality formation through transcriptome sequencing(RNA-seq).The results showed that a total of 504 mRNAs and 1,483 lncRNAs were detected between the two groups of LDMs,with significant differences(P＜0.05).And we also pre-dicted 103 potential lncRNA-mRNA cis-regulatory relationship pairs with significant differences(P＜0.05).Skeletal muscle development-related genes such as MSTN,CDKN1A,FHL1 and skeletal muscle metabolism-related genes such as LPL and SCD were subsequently screened based on the functional anal-ysis of differentially expressed mRNA.Based on the functional analysis of differentially expressed lncRNA target genes,13 lncRNAs potentially related to muscle development(LNC.17926.1,LNC.981.1,LNC.16284.1,etc.)and 8 lncRNAs potentially related to skeletal muscle metabolism(LNC.15496.1,LNC.18149.1,etc.)were identified.5 lncRNAs and 4 mRNAs expressed in both groups were randomly selected for qPCR validation experiments,and their results were consistent with RNA-seq,which corrob-orated with the reliability of the sequencing results.This study lays a solid foundation for future investiga-tions of muscle development,meat quality formation mechanism and molecular breeding in Tan sheep,and provides a scientific basis for improving the meat production performance of other domestic sheep breeds.

This study employed 16S r RNA gene high-throughput sequencing and metabolomics to explore the mechanism of Angelicae Dahuricae Radix polysaccharides(RP) in the treatment of ulcerative colitis(UC). A mouse model of UC was induced with 2. 5% dextran sulfate sodium. The therapeutic effects of RP on UC in mice were evaluated based on changes in body weight, disease activity index( DAI), and colon length, as well as pathological changes. RT-qPCR was performed to assess the m RNA levels of interleukin(IL)-6, IL-1β, tumor necrosis factor(TNF)-α, myeloperoxidase(MPO), mucin 2(Muc2), Occludin, Claudin2, and ZO-1 in the mouse colon tissue. ELISA was employed to measure the expression of IL-1β and TNF-α in the colon tissue. The intestinal permeability of mice was evaluated by the fluorescent dye permeability assay. Immunohistochemistry was employed to detect the expression of Muc2 and occludin in the colon tissue. Changes in gut microbiota and metabolites were analyzed by 16S r RNA sequencing and ultra-high-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry( UPLC-Q-Exactive Plus Orbitrap MS), respectively. The results indicated that low-dose RP alleviated general symptoms, reduced colonic inflammation and intestinal permeability, and promoted Muc2 secretion and tight junction protein expression in UC mice. In addition, low-dose RP increased gut microbiota diversity in UC mice and decreased the relative abundance of harmful bacteria such as Ochrobactrum and Streptococcus. Twenty-seven differential metabolites were identified in feces, and low-dose RP restored the levels of disturbed metabolites. Notably, arginine and proline metabolism were the most significantly altered amino acid metabolic pathways following lowdose RP intervention. In conclusion, RP can ameliorate general symptoms, inhibit colonic inflammation, and maintain intestinal mucosal barrier integrity in UC mice by modulating gut microbiota composition and arginine and proline metabolism.
Animals ; Gastrointestinal Microbiome/drug effects* ; Colitis, Ulcerative/genetics* ; Mice ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Polysaccharides/administration & dosage* ; Angelica/chemistry* ; Humans ; Colon/metabolism* ; Disease Models, Animal ; Mucin-2/metabolism* ; Tumor Necrosis Factor-alpha/metabolism*

This study aims to reveal the effect and mechanism of Gentianella turkestanorum total extract(GTI) in ameliorating non-alcoholic steatohepatitis(NASH). UPLC-Q-TOF-MS was employed to identify the chemical components in GTI. SwissTarget-Prediction, GeneCards, OMIM, and TTD were utilized to screen the targets of GTI components and NASH. The common targets shared by GTI components and NASH were filtered through the STRING database and Cytoscape 3.9.0 to identify core targets, followed by GO and KEGG enrichment analysis. AutoDock was used for molecular docking of key components with core targets. A mouse model of NASH was established with a methionine-choline-deficient high-fat diet. A 4-week drug intervention was conducted, during which mouse weight was monitored, and the liver-to-brain ratio was measured at the end. Hematoxylin-eosin staining, Sirius red staining, and oil red O staining were employed to observe the pathological changes in the liver tissue. The levels of various biomarkers, including aspartate aminotransferase(AST), alanine aminotransferase(ALT), hydroxyproline(HYP), total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), malondialdehyde(MDA), superoxide dismutase(SOD), and glutathione(GSH), in the serum and liver tissue were determined. RT-qPCR was conducted to measure the mRNA levels of interleukin 1β(IL-1β), interleukin 6(IL-6), tumor necrosis factor α(TNF-α), collagen type I α1 chain(COL1A1), and α-smooth muscle actin(α-SMA). Western blotting was conducted to determine the protein levels of IL-1β, IL-6, TNF-α, and potential drug targets identified through network pharmacology. UPLC-Q-TOF/MS identified 581 chemical components of GTI, and 534 targets of GTI and 1 157 targets of NASH were screened out. The topological analysis of the common targets shared by GTI and NASH identified core targets such as IL-1β, IL-6, protein kinase B(AKT), TNF, and peroxisome proliferator activated receptor gamma(PPARG). GO and KEGG analyses indicated that the ameliorating effect of GTI on NASH was related to inflammatory responses and the phosphoinositide 3-kinase(PI3K)/AKT pathway. The staining results demonstrated that GTI ameliorated hepatocyte vacuolation, swelling, ballooning, and lipid accumulation in NASH mice. Compared with the model group, high doses of GTI reduced the AST, ALT, HYP, TC, and TG levels(P<0.01) while increasing the HDL-C, SOD, and GSH levels(P<0.01). RT-qPCR results showed that GTI down-regulated the mRNA levels of IL-1β, IL-6, TNF-α, COL1A1, and α-SMA(P<0.01). Western blot results indicated that GTI down-regulated the protein levels of IL-1β, IL-6, TNF-α, phosphorylated PI3K(p-PI3K), phosphorylated AKT(p-AKT), phosphorylated inhibitor of nuclear factor kappa B alpha(p-IκBα), and nuclear factor kappa B(NF-κB)(P<0.01). In summary, GTI ameliorates inflammation, dyslipidemia, and oxidative stress associated with NASH by regulating the PI3K/AKT/NF-κB signaling pathway.
Animals ; Non-alcoholic Fatty Liver Disease/genetics* ; Mice ; Network Pharmacology ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Chromatography, High Pressure Liquid ; Liver/metabolism* ; Mice, Inbred C57BL ; Humans ; Mass Spectrometry ; Tumor Necrosis Factor-alpha/metabolism* ; Disease Models, Animal ; Molecular Docking Simulation