1.The Potential and Challenges of Temporal Interference Stimulation in Chronic Pain Management
Hao-Qing DUAN ; Yu-Qi GOU ; Ya-Wen LI ; Li HU ; Xue-Jing LÜ
Progress in Biochemistry and Biophysics 2026;53(2):369-387
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.
2.The Potential and Challenges of Temporal Interference Stimulation in Chronic Pain Management
Hao-Qing DUAN ; Yu-Qi GOU ; Ya-Wen LI ; Li HU ; Xue-Jing LÜ
Progress in Biochemistry and Biophysics 2026;53(2):369-387
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.
3.Clinical trial of thymopeptide enteric-coated capsules combined with human interferon α2b vaginal effervescent tablets in the treatment of patients with high-risk HPV infection-related cervical lesions
Xue BAI ; Shu-wei HAO ; Wei LÜ ; Ya-wen DING ; Nai-yi DU
The Chinese Journal of Clinical Pharmacology 2024;40(21):3082-3086
Objective To observe the therapeutic effect of thymopeptide enteric-coated capsules combined with human interferon α2b vaginal effervescent tablets in the treatment of patients with high-risk human papillomavirus(HPV)infection-related cervical lesions and the impact on T lymphocyte subsets.Methods The patients with high-risk HPV infection-related cervical lesions were divided into the treatment group and the control group according to the cohort method.The control group was given human interferon α2b vaginal effervescent tablets 5 × 105 U,once daily,for 2 months.On this basis,the treatment group was treated with thymopeptide enteric-coated capsules at a dose of 30 mg·time-1,three times a day,for 2 months.Therapeutic effects,cervical vaginal microecology indicators[pH values of vaginal secretions,Nugent scores and white blood cell count],T lymphocyte subsets,cytokines[interleukin-4(IL-4),IL-6,IL-10,tumor necrosis factor-α(TNF-α)and interferon-γ(IFN-γ)]were compared between the two groups,and the safety were evaluated.Results Seventy cases in the treatment group and 72 cases in the control group.After treatment,the total effective rate of the treatment group was 94.29%(66 cases/70 cases),which was higher than the control group's 80.56%(58 cases/72 cases),the differences were statistically significant(P<0.05).After treatment,pH values of vaginal secretions in treatment group and control group were 4.26±0.19 and 4.38±0.17;Nugent scores were(2.53±0.36)and(2.79±0.40)scores;Blood cell count were 5.12±1.14 and 6.03±1.21;CD3+were(69.32±8.10)%and(66.54±7.03)%;CD4+were(37.25±5.03)%and(34.67±4.82)%;CD4+/CD8+were 1.50±0.35 and 1.42±0.33;serum IL-4 levels were(7.49±1.64)and(9.20±2.18)pg·mL-1;serum IL-6 levels were(20.95±5.03)and(26.64±6.22)pg·mL-1;serum IL-10 levels were(11.72±2.46)and(13.43±2.97)pg·mL-1;serum TNF-α levels were(16.48±3.75)and(13.25±2.03)pg·mL-1;serum IFN-γ levels were(13.35±2.11)and(10.93±2.86)pg·mL-1;the differences were statistically significant(all P<0.05).Adverse drug reactions in the treatment group included nausea,fever,vaginal itching and pain;which in the control group included vaginal itching and pain.The total incidence rates of adverse reactions in the treatment group and the control group were 8.57%(6 cases/70 cases)and 5.56%(4 cases/72 cases),without statistically significant difference(P>0.05).Conclusion Thymopeptide enteric-coated capsules combined with human interferon α2b vaginal effervescent tablets can improve immune function,reduce inflammatory reactions,and improve cervical and vaginal micro-ecological environment in patients with high-risk HPV infection-related cervical lesions.
4.Efficacy and safety of intravascular lithotripsy in interventional treatment of calcified lesions in patients with acute and chronic coronary syndromes
Hai-quan LI ; Gai-gai MA ; Xiao-jun LIU ; Dan SU ; Ya-rui LÜ ; Xin-hong WANG ; Zhen-hua HAN ; Jie DENG
Chinese Journal of Interventional Cardiology 2024;32(12):676-682
Objective To evaluate the efficacy and safety of intravascular lithotripsy(IVL)in the treatment of coronary artery calcification in patients with acute coronary syndrome(ACS)and chronic coronary syndrome(CCS).Methods In a retrospective study,patients with coronary artery calcified lesions who underwent IVL treatment at the Department of Cardiology,Second Affiliated Hospital of Xi'an Jiaotong University between February 2023 and June 2024 were enrolled.Among them,22 patients in ACS group and 25 patients in CCS group.The differences in baseline data,complication,clinical success rate and major cardiovascular adverse events(MACE)in patients followed one month after the procedure were compared between the two groups.Results In the ACS group,21 stent implantations were successful(95.5%success rate),while in the CCS group,25 cases were successful(100.0%success rate),showing no statistically significant difference between the two groups(P=0.468).There was one case of intraoperative IVL balloon rupture in the ACS group(1/22;4.5%),while in the CCS group,three cases were observed(3/25;12.0%).Additionally,one case in the ACS group(1/22;4.5%)with slow blood flow after IVL calcification modification.No instances of IVL-related vessel dissection or target vessel rupture occurred between the two groups,and there was no statistically significant difference in intraoperative complications(all P>0.05).There was no significant difference in the MACE(9.1%vs.4.0%,P=0.593)between the two groups for follow up of one month.Conclusions The technique of IVL is a safe and effective treatment option for patients with ACS or CCS who have coronary artery calcification lesions.
5.Pharmacokinetics study of single and multiple doses of azvudine in healthy young and elderly subjects
Yu ZHANG ; Xiao-Jian LIU ; Hao-Shuang JU ; Bin-Yuan HE ; Yuan-Hao WAN ; Li-Wei CHAI ; Le-Yang REN ; Min LÜ ; Ya-Qiang JIA ; Wei ZHANG ; Ping XU
The Chinese Journal of Clinical Pharmacology 2024;40(9):1316-1320
Objective To evaluate the pharmacokinetic characteristics and safety of single and multiple oral azvudine tablets in healthy young and elderly Chinese subjects.Methods This was a open-label and parallel-group study.The trial consisted of two groups:healthy young subjects group and healthy elderly subjects group,with 12 subjects in each group.Enrolled subjects were first given a single dose,fasting oral azvudine tablet 5 mg,after a 3-day cleansing period entered the multiple dose phase,fasting oral azvudine tablet 5 mg·d-1 for 7 days.Results After a single dose of azvudine 5 mg,Cmax and AUC0-∞ were(4.76±2.12)ng·mL-1,(6.53±2.20)ng·mL-1·h,and Tmax,t1/2 were 0.75,1.87 h in young subjects;Cmax and AUC0-∞ were(6.40±3.25)ng·mL-1,(9.50±3.70)ng·mL-1·h,and Tmax,t1/2 were 0.63,2.66 h in elderly subjects.After a multiple dose of azvudine 5 mg·d-1 for 7 d,Cmax and AUC0-∞ were(3.26±1.61)ng·mL-1,(5.38±2.19)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.88,2.13 h in young subjects;Cmax,ss and AUC0-∞,ss were(3.97±2.09)ng·mL-1,(6.71±3.26)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.75,2.56 h in elderly subjects.Elderly/young geometric mean ratios and 90%CIs were 128.37%(88.23%-186.76%),139.93%(105.42%-185.72%),140.03%(106.33%-184.41%)for azvudine Cmax,AUC0-t,AUC0-∞ after a single dose,and were 118.66%(80.83%-174.20%),118.41%(83.60%-167.69%),118.95%(84.78%-166.89%)for azvudine Cmax,AUC0-t,AUC0_∞ after a multiple dose of azvudine 5 mg·d-1 for 7 d.Conclusion After single and multiple oral administration of azvudine tablets,systemic exposure to azvudine was higher in healthy elderly subjects compared with healthy young subjects.After taking azvudine tablets,the types,severity and incidence of adverse events and adverse drug reactions in healthy elderly people were not significantly different from those in healthy young subjects.Azvudine was found to be safe and well tolerated in healthy elderly subjects.
6. Effects of tricholoma matsutake polysaccharides on 1-methy-4-pehnyl-pyridine ion-induced PC12 cell damage
Hai-Yan LÜ ; Xi-Ya SHEN ; Fu-Sheng ZHAO ; Mei ZHU
Acta Anatomica Sinica 2024;55(1):49-54
Objective To investigate the protective mechanism of tricholoma matsutake polysaccharides(TMP) against 1-methy-4-pehnyl-pyridine ion (MPP
7.Construction and Evaluation of Intimate Partner Homicide Prediction Model
Wei-Ping LÜ ; Xin-Biao LIAO ; Li-Ju REN ; Xiao-Ping KONG ; Yan-Chang CHEN ; Ya-Fei CHANG ; Bin LUO
Journal of Forensic Medicine 2024;40(6):582-588
Objective To analyze the independent influencing factors of intimate partner homicide(IPH)cases,construct an IPH prediction model,and provide a basis for criminal profiling.Methods A total of 476 convicted homicide cases in Guangdong Province from January 1,2014,to December 31,2020,were collected as modeling dataset.They were divided into the IPH group(n=180)and the non-intimate partner homicide(N-IPH)group(n=296)based on whether the offender and victim were intimate partners.Logistic regression was used to build the model,the model was evaluated through the receiver operating characteristic(ROC)curve analysis and a nomogram was drawn.Inter-nal validation was conducted using ten-fold cross-validation method.A total of 126 court judgments from outside Guangdong Province from January 1,2011,to December 31,2020,were randomly col-lected for external validation.Results Through multi-factor Logistic regression analysis,7 variables were ultimately selected for inclusion in the model.The Hosmer-Lemeshow goodness of fit test result of the model was χ2=13.158,P=0.068.The ROC area under the curve(AUC)of the model was 0.939(95%CI:0.919-0.959),the cut-off value was 0.292,the sensitivity was 0.900,and the specificity was 0.865.The calibration curve was close to the ideal curve.The ten-fold cross-validation showed the accuracy of 0.863 and a Kappa value of 0.708.The external validation results showed an AUC of 0.922(95%CI:0.872-0.971),a cut-off value of 0.292,a sensitivity of 0.890,and a specificity of 0.886.The calibration curve tended to the ideal curve.Conclusion The IPH prediction model based on forensic field indicators has good predictive ability,reliable accuracy and stability,and can provide a scientific method for criminal profiling.
8.Simultaneous content determination of twelve constituents in Tufuling Qiwei Powder by HPLC-MS/MS
Yu-xia HU ; Jun LI ; Yue-wu WANG ; Xiao-li LÜ ; Meng-di ZHANG ; Nan LI ; Tu-ya BAI ; Fu-hou CHANG
Chinese Traditional Patent Medicine 2024;46(12):3906-3910
AIM To establish an HPLC-MS/MS method for the simultaneous content determination of berberine,coptisine,gallic acid,corilagin,geniposide,toosendanin,rutinum,chlorogenic acid,luteolin,asiatica,emodin and astilbin in Tufuling Qiwei Powder.METHODS The analysis was performed on a 35℃ thermostatic Shim-pack GIST-HP C18 column (2.1 mm × 100 mm,3 μm),with the mobile phase comprising of methanol-water (containing 0.1% formic acid) flowing at 0.25 mL/min in a gradient elution manner,and electron spray ionization source was adopted in negative and positive ion detection with multiple reaction monitoring mode.RESULTS Twelve constituents showed good linear relationships within their own ranges (r≥0.9990),whose average recoveries were 94.83%-104.42% with the RSDs of 1.30%-4.88%.CONCLUSION This simple,rapid and accurate method can be used for the quality control of Tufuling Qiwei Powder.
9.Efficacy and safety of intravascular lithotripsy in interventional treatment of calcified lesions in patients with acute and chronic coronary syndromes
Hai-quan LI ; Gai-gai MA ; Xiao-jun LIU ; Dan SU ; Ya-rui LÜ ; Xin-hong WANG ; Zhen-hua HAN ; Jie DENG
Chinese Journal of Interventional Cardiology 2024;32(12):676-682
Objective To evaluate the efficacy and safety of intravascular lithotripsy(IVL)in the treatment of coronary artery calcification in patients with acute coronary syndrome(ACS)and chronic coronary syndrome(CCS).Methods In a retrospective study,patients with coronary artery calcified lesions who underwent IVL treatment at the Department of Cardiology,Second Affiliated Hospital of Xi'an Jiaotong University between February 2023 and June 2024 were enrolled.Among them,22 patients in ACS group and 25 patients in CCS group.The differences in baseline data,complication,clinical success rate and major cardiovascular adverse events(MACE)in patients followed one month after the procedure were compared between the two groups.Results In the ACS group,21 stent implantations were successful(95.5%success rate),while in the CCS group,25 cases were successful(100.0%success rate),showing no statistically significant difference between the two groups(P=0.468).There was one case of intraoperative IVL balloon rupture in the ACS group(1/22;4.5%),while in the CCS group,three cases were observed(3/25;12.0%).Additionally,one case in the ACS group(1/22;4.5%)with slow blood flow after IVL calcification modification.No instances of IVL-related vessel dissection or target vessel rupture occurred between the two groups,and there was no statistically significant difference in intraoperative complications(all P>0.05).There was no significant difference in the MACE(9.1%vs.4.0%,P=0.593)between the two groups for follow up of one month.Conclusions The technique of IVL is a safe and effective treatment option for patients with ACS or CCS who have coronary artery calcification lesions.
10.Clinical trial of thymopeptide enteric-coated capsules combined with human interferon α2b vaginal effervescent tablets in the treatment of patients with high-risk HPV infection-related cervical lesions
Xue BAI ; Shu-wei HAO ; Wei LÜ ; Ya-wen DING ; Nai-yi DU
The Chinese Journal of Clinical Pharmacology 2024;40(21):3082-3086
Objective To observe the therapeutic effect of thymopeptide enteric-coated capsules combined with human interferon α2b vaginal effervescent tablets in the treatment of patients with high-risk human papillomavirus(HPV)infection-related cervical lesions and the impact on T lymphocyte subsets.Methods The patients with high-risk HPV infection-related cervical lesions were divided into the treatment group and the control group according to the cohort method.The control group was given human interferon α2b vaginal effervescent tablets 5 × 105 U,once daily,for 2 months.On this basis,the treatment group was treated with thymopeptide enteric-coated capsules at a dose of 30 mg·time-1,three times a day,for 2 months.Therapeutic effects,cervical vaginal microecology indicators[pH values of vaginal secretions,Nugent scores and white blood cell count],T lymphocyte subsets,cytokines[interleukin-4(IL-4),IL-6,IL-10,tumor necrosis factor-α(TNF-α)and interferon-γ(IFN-γ)]were compared between the two groups,and the safety were evaluated.Results Seventy cases in the treatment group and 72 cases in the control group.After treatment,the total effective rate of the treatment group was 94.29%(66 cases/70 cases),which was higher than the control group's 80.56%(58 cases/72 cases),the differences were statistically significant(P<0.05).After treatment,pH values of vaginal secretions in treatment group and control group were 4.26±0.19 and 4.38±0.17;Nugent scores were(2.53±0.36)and(2.79±0.40)scores;Blood cell count were 5.12±1.14 and 6.03±1.21;CD3+were(69.32±8.10)%and(66.54±7.03)%;CD4+were(37.25±5.03)%and(34.67±4.82)%;CD4+/CD8+were 1.50±0.35 and 1.42±0.33;serum IL-4 levels were(7.49±1.64)and(9.20±2.18)pg·mL-1;serum IL-6 levels were(20.95±5.03)and(26.64±6.22)pg·mL-1;serum IL-10 levels were(11.72±2.46)and(13.43±2.97)pg·mL-1;serum TNF-α levels were(16.48±3.75)and(13.25±2.03)pg·mL-1;serum IFN-γ levels were(13.35±2.11)and(10.93±2.86)pg·mL-1;the differences were statistically significant(all P<0.05).Adverse drug reactions in the treatment group included nausea,fever,vaginal itching and pain;which in the control group included vaginal itching and pain.The total incidence rates of adverse reactions in the treatment group and the control group were 8.57%(6 cases/70 cases)and 5.56%(4 cases/72 cases),without statistically significant difference(P>0.05).Conclusion Thymopeptide enteric-coated capsules combined with human interferon α2b vaginal effervescent tablets can improve immune function,reduce inflammatory reactions,and improve cervical and vaginal micro-ecological environment in patients with high-risk HPV infection-related cervical lesions.

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