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 investigate the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep. METHODS Network pharmacology was employed to identify the active components of L. ruthenicum and their associated disease targets， followed by enrichment analysis. A caffeine‑induced zebrafish model of sleep deprivation was established ， and the zebrafish were treated with L. ruthenicum Murr. extract （LRME） at concentrations of 0.1， 0.2 and 0.4 mg/mL， respectively； 24 h later， behavioral changes of zebrafish and pathological alterations in brain neurons were subsequently observed. The levels of inflammatory factors [interleukin-6 （IL-6）， IL-1β， IL-10， tumor necrosis factor-α （TNF-α）]， oxidative stress markers [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， catalase （CAT）]， and neurotransmitters [5- hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， glutamic acid （Glu）， dopamine （DA）， and norepinephrine （NE）] were measured. The protein expression levels of protein kinase B1 （AKT1）， phosphorylated AKT1 （p-AKT1）， epidermal growth factor receptor （EGFR）， B-cell lymphoma 2 （Bcl-2）， sarcoma proto-oncogene，non-receptor tyrosine kinase （SRC）， and heat shock protein 90α family class A member 1 （HSP90AA1） in the zebrafish were also determined. RESULTS A total of 12 active components and 176 intersecting disease targets were identified through network pharmacology analysis. Among these， apigenin， naringenin and others were recognized as core active compounds， while AKT1， EGFR and others served as key targets； EGFR tyrosine kinase inhibitor resistance signaling pathway was identified as the critical pathway. The sleep improvement rates in zebrafish of LRME low-， medium-， and high-dose groups were 54.60%， 69.03% and 77.97%， 开发。E-mail：hjp_yft@163.com respectively， while the inhibition ratios of locomotor distance were 0.57， 0.83 and 0.95， respectively. Compared with the model group， the number of resting counts， resting time and resting distance were significantly increased/extended in LRME medium- and high-dose groups （P＜0.05）. Neuronal damage in the brain was alleviated. Additionally， the levels of IL-6， IL-1β， TNF-α， MDA， Glu， DA and NE， as well as the protein expression levels of AKT1， p-AKT1， EGFR， SRC and HSP90AA1， were markedly reduced （P＜0.05）， while the levels of IL-10， SOD， GSH-Px， CAT， 5-HT and GABA， as well as Bcl-2 protein expression， were significantly elevated （P＜0.05）. CONCLUSIONS L. ruthenicum Murr. demonstrates sleep-improving effects， and its specific mechanism may be related to the regulation of inflammatory responses， oxidative stress， neurotransmitter balance， and the EGFR tyrosine kinase inhibitor resistance signaling pathway.

Objective:To investigate the differences in clinical outcomes of septic children with varying serum zinc levels,and to analyze the relationship between reduced serum zinc levels and organ dysfunction as well as 28-day mortality in septic children.Methods:This study conducted a retrospective analysis of clinical data from pediatric patients diagnosed with sepsis or septic shock in the Department of critical care medicine of the children's Hospital of Soochow University between January 2017 and December 2022.Clinical characteristics,organ dysfunction,and prognosis were compared between two groups:children with low serum zinc levels and those with normal zinc levels.Results:The serum zinc level of septic children within 24 hours of admission was 9.60(5.52,13.80)μmol/L,with 50.54%(94/186)of the children exhibiting low serum zinc levels(<10.07 μmol/L).Compared to the normal serum zinc group,the low serum zinc group had a significantly lower Pediatric Critical Illness Score(PCIS)[(78.71±9.35)vs.(85.12±8.51),P=0.005]and higher 28-day mortality(46.80%vs.14.13%,P<0.001).The low serum zinc group also had a higher proportion of invasive mechanical ventilation(64.89%vs.47.82%,P=0.019),renal replacement therapy(15.59%vs.3.26%,P=0.003),and use of vasoactive drugs(56.38%vs.30.43%,P<0.001).The rate of underlying conditions in the low serum zinc group was significantly higher than that in the normal serum zinc group(57.44%vs.36.95%,P=0.005).Additionally,the low serum zinc group had a higher incidence of disseminated intravascular coagulation(DIC),respiratory failure,acute kidney injury,shock,and multiple organ dysfunction syndrome(MODS)compared to the normal serum zinc group(P<0.05).Serum zinc levels had predictive value for 28-day mortality in septic children(AUC=0.813;95%CI:0.725～0.902;P<0.001).A serum zinc level of less than 6.950 μmol/L predicted the death of septic children with a sensitivity of 0.618 and a specificity of 0.902.Conclusion:Sepsis in children is commonly associated with low serum zinc levels,especially in those with underlying conditions such as hematologic and oncologic disorders.Sepsis patients hypozincemia with a higher incidence of DIC,respiratory failure,acute kidney injury,shock,and MODS.A serum zinc level below 6.95 μmol/L serves as a significant predictor of 28-day mortality in children with severe sepsis.

Objective:To investigate the efficacy and safety of fluoroscopically-guided percutaneous gastrostomy (FGPG) for establishing enteral nutrition access in the treatment of esophageal fistula after radiotherapy for cervical esophageal cancer (CEC).Methods:A retrospective analysis was conducted on the clinical data of 54 patients who underwent FGPG due to esophageal fistula after radiotherapy for CEC at our department from November 2009 to August 2019. All patients received endoscopy before radiotherapy, and CEC was pathologically confirmed. Enteral nutrition support was offered through a gastrostomy tube postoperatively. The success rate of FGPG, complications, and healing of perforation were recorded and analyzed.Results:FGPG was successfully performed in all 54 patients (100%). During the 12-month follow-up, 50 patients (92.6) survived while four (7.4%) died. Among 36 patients with esophagomediastinal fistula, 32 (88.9%) healed in a median of 12 weeks; of 18 patients with esophagotracheal fistula, 8 (44.4%) healed in a median of 18 weeks. Thus, patients with esophagomediastinal fistula had a significantly higher healing rate ( P<0.01) and shorter healing time ( P=0.017). Gastrostomy tube-related complications were minimal, and no serious complication was noted. Conclusions:FGPG is effective for the treatment of esophageal fistula after CEC radiotherapy and may be an alternative treatment for esophageal fistula.

Objective To analyze the risk factors for increased drainage volume after open transforaminal lumbar interbody fusion(TLIF),and to establish a predictive model and then validate it.Methods The clinical data of 680 patients who underwent open TLIF at the General Hospital of Northern Theater Command from January 2016 to December 2019 were collected and the patients were randomly divided into the training group(n=476)and the validation group(n=204).Taking the predictive factors screened out by LASSO regression analysis as independent variables,a multivariate Logistic regression predictive model was constructed.The model was internally validated through the receiver operating characteristic(ROC)curve,Hosmer-Lemeshow goodness-of-fit test,and calibration curve,and its clinical utility was assessed via decision curve analysis(DCA).Results LASSO regression analysis screened out four predictive variables:age,number of surgical segments,operative duration,and intraoperative blood loss.The multivariate Logistic regression predictive model demonstrated that age≥60 years,number of surgical segments≥4,operative duration≥2 hours,and intraoperative blood loss≥200 mL were independent influencing factors for the increased postoperative drainage volume in patients undergoing TLIF(P<0.05).ROC curve analysis revealed an area under the curve(AUC)of 0.816(95%CI:0.798 to 0.867)in the training group and 0.783(95%CI:0.685 to 0.823)in the validation group,indicating that the predictive model had good discriminatory ability.Additionally,the Hosmer-Lemeshow goodness-of-fit test and calibration curve indicated that the predictive model had a good degree of fit,and the predicted probability was basically consistent with the actual probability,demonstrating a good calibration.The DCA results confirmed that this predictive model could be applied in clinical practice.Conclusion The risk factors for increased drainage volume after open TLIF include age,number of surgical segments,operative duration,and intraoperative blood loss.The predictive model established based on these factors demonstrates good performance,and it can be applied in clinical guidance for the selection of drainage tube removal time after TLIF.

Objective To analyze the expression of ILT4 and CD147 in lung adenocarcinoma and their relationships with tumor immunoinfiltration and prognosis of patients.Methods The specimens of cancer tissues and adjacent tissues of 134 patients with lung adenocarcinoma who underwent surgical treatment at our hospital from January to December 2024 were collected,and a retrospective analysis was conducted on the clinical data of the patients.The protein and mRNA expression of ILT4 and CD147 in different tissues were detected by immunohistochemistry and qRT-PCR,respectively.The correlations of the expression of ILT4 and CD147 with the clinicopatho-logical characteristics of lung adenocarcinoma were analyzed.The expression of ILT4 and CD147 in pan-cancer tissues were retrieved based on the GEPIA2 database,and their relationships with the prognosis of lung adenocarcinoma were analyzed.The correlations of the expression of ILT4 and CD147 with the infiltration of 6 kinds of immune cells in lung adenocarcinoma samples were analyzed based on TIMER database.Results The protein positive rates and mRNA expression levels of ILT4 and CD147 in lung adenocarcinoma tissues were significantly higher than those in adjacent tissues(P<0.05).The analysis of GEPIA database showed that ILT4 and CD147 upregulated in various tumors,and the expression levels of ILT4 and CD147 in lung adenocarcinoma tissues were both higher than those in unpaired adjacent tissues.The expression of ILT4 protein was closely related to the TNM stage and lymph node metastasis of lung adenocarcinoma(P<0.05);the expression of CD147 protein was correlated with TNM stage,lymph node metastasis and degree of differentiation(P<0.05).The analysis of GEPIA database showed that the patients with high expression of ILT4 and CD147 had lower overall survival rates than those with low expression(Log-rank P=0.000 58,0.002 6).The analysis of the TIMER database showed that the expression of ILT4 was negatively correlated with the infiltration of macrophages,neutrophils and dendritic cells(P<0.05);the expression of CD147 was negatively correlated with the infiltration of B cells,CD4+T cells and dendritic cells(P<0.05).Conclusion ILT4 and CD147 are highly expressed in lung adenocarcinoma tissues,which are related to clinicopathological features,prognosis and immunoinfiltration of patients.They may be the potential markers for prognosis evaluation and immunotherapeutic targets of patients with lung adenocarcinoma.

Objective:To investigate the efficacy and safety of fluoroscopically-guided percutaneous gastrostomy (FGPG) for establishing enteral nutrition access in the treatment of esophageal fistula after radiotherapy for cervical esophageal cancer (CEC).Methods:A retrospective analysis was conducted on the clinical data of 54 patients who underwent FGPG due to esophageal fistula after radiotherapy for CEC at our department from November 2009 to August 2019. All patients received endoscopy before radiotherapy, and CEC was pathologically confirmed. Enteral nutrition support was offered through a gastrostomy tube postoperatively. The success rate of FGPG, complications, and healing of perforation were recorded and analyzed.Results:FGPG was successfully performed in all 54 patients (100%). During the 12-month follow-up, 50 patients (92.6) survived while four (7.4%) died. Among 36 patients with esophagomediastinal fistula, 32 (88.9%) healed in a median of 12 weeks; of 18 patients with esophagotracheal fistula, 8 (44.4%) healed in a median of 18 weeks. Thus, patients with esophagomediastinal fistula had a significantly higher healing rate ( P<0.01) and shorter healing time ( P=0.017). Gastrostomy tube-related complications were minimal, and no serious complication was noted. Conclusions:FGPG is effective for the treatment of esophageal fistula after CEC radiotherapy and may be an alternative treatment for esophageal fistula.

BACKGROUND:Spine osteoarthritis is a chronic inflammatory disease of the spine,articular ligaments,and tendons,and is the main cause of chronic low back pain.Artificial tiger bone powder has anti-inflammatory and pain-relieving biological effects,so it is expected to provide a new strategy for targeted therapy of spinal osteoarthritis.OBJECTIVE:To investigate the mechanism of artificial tiger bone meal in regulating the expression level of interleukin-23/interleukin-17 immune axis in improving spine osteoarthritis in rats.METHODS:Sixty SD rats were randomly divided into blank control group,model group,artificial tiger bone meal low-,medium-and high-dose groups,with 12 rats in each group.Except for the blank control group,osteoarthritis models were established in the other groups by injecting 0.1 mL of iodoacetic acid into the joint cavity of the lumbar vertebral joint capsule of the rats.15 days after modeling,the artificial tiger bone meal low,medium and high dose groups were treated by intragastric administration of 120,240 and 480 mg/kg per day respectively.The blank control group and model group were given the same volume of normal saline by gavage.After 21 days of treatment,the expression levels of interleukin-17,interleukin-23,matrix metalloproteinase-3,and chemokine receptor-6 in rat spinal articular cartilage were measured by western blot assay.The expression levels of related inflammatory factors in rat serum were detected by ELISA.The degree of joint injury and degeneration in rats was observed by hematoxylin-eosin staining and safranin O-fast green staining.RESULTS AND CONCLUSION:(1)The results of western blot assay showed that the expression levels of interleukin 17,interleukin 23,matrix metalloproteinase 3,and chemokine receptor 6 in the articular cartilage of rats in the artificial tiger bone meal high-dose group were significantly lower than those in the model group(P＜0.05).(2)ELISA results showed that compared with the model group,the artificial tiger bone meal medium-and high-dose groups had a significant down-regulating effect on the levels of serum interleukin 17,tumor necrosis factor α,interleukin 1β,and matrix metalloproteinase 3(P＜0.05).(3)Hematoxylin-eosin staining and saffron O-solid green staining showed that the infiltration and proliferation of synovial inflammatory cells in each treatment group of artificial tiger bone meal were significantly improved compared with the model group,and the pathological inflammation Osteoarthritis Research Society International score and Mankin's score in the medium-and high-dose groups of artificial tiger bone meal were significantly reduced(P＜0.05).(4)It is suggested that artificial tiger bone meal could significantly improve the inflammation and degeneration of spinal facet joints caused by iodoacetic acid chemical stimulation.Among them,the effect of the high-dose group was more significant.The mechanism may be to inhibit the expression of interleukin-23/interleukin-17 immune axis-related inflammatory factors and improve the immune microenvironment of articular cartilage.

BACKGROUND:During the treatment of posterolateral tibial plateau fractures through the fibular head approach,the gap between the fibular head and the lateral plateau cannot accommodate the posterior placement of a plate for all patients.OBJECTIVE:To analyze,via finite element analysis,the differences in fixation strength resulting from varying the angles and quantities of horizontal arm variable angle screws in the plate during the treatment of posterolateral tibial plateau fractures through the fibular head approach.METHODS:A finite element model was established based on CT images of the knee to ankle joints of a 30-year-old healthy adult male volunteer.The models were divided into two categories:posteriorly placed group and non-posteriorly placed group based on whether the lateral locking compression plate was posteriorly placed.The posteriorly placed group was further subdivided into groups A-D based on the offset angle of the two variable angle screws(0°,5°,10°,and 15°).The non-posteriorly placed group was subdivided into groups E and F based on offset angles(0° and 15°).Finite element analysis was used to evaluate the von Mises stress distribution,maximum von Mises stress,and compressive displacement under loads of 250,500,and 750 N,exploring the mechanical differences between the groups.RESULTS AND CONCLUSION:(1)Finite element analysis results showed that under a 750 N load,the maximum compressive displacement trend of the internal fixation device was D＜B=C=F＜A＜E.The trend for maximum von Mises stress was B＜C＜A＜D＜F＜E.The trend for maximum compressive displacement on the bone was C=D＜B＜A＜F＜E,and for maximum von Mises stress,it was B＜C＜A＜F＜D＜E.The displacement and stress trends for the six models were similar under loads ranging from 250 N to 750 N.(2)These results suggest that for posterolateral tibial plateau fractures fixed through the fibular head approach,posterior placement of the plate should aim to accommodate two screws.If only one screw can be fixed during surgery,variable angle screws should be offset in the range of 0-15° to increase the probability of securing two screws.