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: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective To explore the physical function indicators of elderly women with fall experiences,so as to provide more data reference for fall prevention,risk assessment,and solving of aging-related health problems in elderly women.Methods The fall history of 167 elderly women in communities in Tianjin was investigated by a questionnaire.The participants were assigned into a fall group(more than 2 falls in the last 1 year)and a non-fall group according to the number of falls.Body composition was tested by an Inbody 770 Body Composition Analyzer,and the calcaneus bone mineral density was measured by a UBD2002A Ultrasound Bone Densitometer.The muscle strength and proprioception of knee and ankle joints of lower limbs were measured by a PRIMUS BTE Isokinetic Tester.The muscle strength of lower limbs was evaluated by the number of 30-second sitting-rising.The visual sensitivity was examined by two-contrast near point reading cards(with a small number of strokes).The dynamic and static balance abilities were determined by a Korebalance Tester,and the static balance ability was tested by one-leg standing with eyes closed.The dynamic and static balance was assessed based on the Berg balance scale,and walking gait characteristics were studied by a BTS three-dimensional motion capture system.Results The skeletal muscle content(P<0.001),strength of non-dominant knee flexor muscle(P=0.002),number of 30-second sitting-rising(P=0.006),and average walking speed(P=0.013)in the fall group were lower than those in the non-fall group.The visual acuity at 10% grayscale(P=0.001),active knee joint position sense(P<0.001),strength of non-dominant ankle flexor muscle(P<0.001),and one-leg standing time with eyes closed(P<0.001)in the fall group were lower than those in the non-fall group.The fall group outperformed the non-fall group in right-left balance rate(P=0.031)and forward-backward balance rate(P=0.028)during static and dynamic balance tests.Conclusion The ankle angle,proprioception,muscle strength,and skeletal muscle content of lower limbs,visual sensitivity,dynamic and static balance abilities,and walking ability of elderly women with fall experiences were lower than those without fall experiences.
Humans ; Accidental Falls ; Aged ; Female ; Postural Balance ; Muscle Strength ; Body Composition ; Bone Density ; Surveys and Questionnaires ; Gait

Objective To investigate the incidence of placental abruption in the third trimester of pregnancy in Hebei Province,identify its associated risk factors,and develop a corresponding nomogram prediction model.Methods Data from pregnant women at 22 monitored hospitals in Hebei Province,collected between 2013 and 2023,were analyzed to assess the incidence,trends,and associated risk factors of placental abruption.A prediction model was developed and visualized using R programming to generate the receiver operating characteristic(ROC)curve.The model's predictive performance was evaluated using the area under the curve(AUC)and calibration curve parameters.Results A total of 480 690 pregnant women were included in this study over the specified period.The incidence of placental abruption was 0.29%(1 395 out of 480 690),with an average annual percentage change of 2.73%,indicating a stable trend(P=0.34).Multivariate logistic regression analysis revealed that pregnancy-related anemia,preeclampsia,placenta previa,vaginal bleeding before 28 weeks'gestation,and between 28 and 31+6 weeks'gestation were significant risk factors for placental abruption(all P<0.05).In contrast,regular prenatal examinations(7～11 visits)and multiple pregnancies were identified as protective factors against placental abruption(both P<0.05).The area under the curve(AUC)for the nomogram model constructed based on independent risk factors for placental abruption was 0.79,and the calibration curve demonstrated that the predicted values closely aligned with the observed values.Conclusions Prenatal examinations should be prioritized,especially for women with preeclampsia,placenta previa,or a history of vaginal bleeding before 28 weeks of gesta-tion.Management of pregnancies between 28 and 31+6 weeks is also crucial to reduce the incidence of placental abruption and mitigate adverse maternal and neonatal outcomes.The nomogram model constructed based on these factors exhibits excellent predictive performance,providing a solid theoretical foundation for the prevention and clinical management of placental abruption.

AIM To investigate the effects of rice wine type and wine processing method on chemical constituents and anti-coagulation effect of Angelicae sinensis Radix.METHODS Wine-washed products and wine-stir-fried products were prepared by different types and ages of rice wine,respectively,after which HPLC was adopted in the content determination of tryptophan,chlorogenic acid,vanillic acid,phthalic acid,ferulic acid,senkyunolide I,senkyunolide H,coniferyl ferulate and ligustilide,and PT,APTT,TT were detected in rabbit plasma.RESULTS Phenolic acids and volatile constituents demonstrated lower contents in the wine-stir-fried products than those in the raw product(P＜0.05),while those in the wine-washed products displayed no obvious changes(except for senkyunolide I)(P＞0.05).The contents of volatile constituents in the wine-washed products were higher than those in the wine-stir-fried products(P＜0.05).After being processed with dry rice wine,various constituents exhibited increased contents as compared with those after being processed with sweet rice wine(P＜0.05).Compared with the raw product,prolonged PT,APTT and TT were observable in the processed products prepared by 3-year semi-dry rice wine(P＜0.05).CONCLUSION The optimal rice wine type is determined to be 3-year semi-dry.Wine-washed Angelicae sinensis Radix shows high contents of ferulic acid and volatile constituents,whose activating blood and resolving stasis effect may be stronger.

Objective To investigate the impacts of epidural anesthesia with ropivacaine combined with dezocine on lower limb motor nerve block and maternal and infant outcomes in primipara undergoing painless delivery.Methods A total of 159 primiparas who delivered in Nanjing Jiangbei Hospital were selected as the research objects,and divided into the blank group(53 cases),the ropivacaine group(53 cases)and the combined group(53 cases)by the random number table method.Parturients in the blank group were given natural delivery mode,parturients in the ropivacaine group were given ropivacaine epidural anesthesia,and parturients in the combined group were given dezocine anesthesia on the basis of ropivacaine.Analgesic effect at different time points,time of the first,second and third stage of labor,pressing times of analgesic pump,lower limbs motor nerve block,maternal and infant outcomes,and adverse reactions of parturients were compared among the three groups.Results At 10 minutes after analgesia,60 minutes after analgesia,when the cervix was fully dilated and when the fetus was delivered,the VAS scores of the parturients in the ropivacaine group and the combined group were lower than those in the blank group(P<0.05),and the VAS scores of the parturients in the combined group were significantly lower than those in the ropivacaine group(P<0.05).There was no significant difference in the time of the first,second or third stage of labor of parturients among the three groups(P>0.05);The pressing times of analgesic pump of parturients in the combined group was significantly less than that in the ropivacaine group(P<0.05).There was no statistically significant difference in terms of low limb motor nerve block after painless labor of parturients among the three groups(P>0.05).There were no statistically significant differences in the perineal incision rate or the Apgar scores of newborns at 1 minute and 5 minutes after birth among the three groups(P>0.05).The usage rate of forceps and the rate of conversion to cesarean section in the combined group were significantly lower than those in the ropivacaine group and the blank group(P<0.05).There was no statistically significant difference in the incidence of total adverse reactions among the blank group,the ropivacaine group and the combined group(P>0.05).Conclusion The combination of ropivacaine and dezocine for epidural anesthesia has a better analgesic effect on primiparas with painless delivery,has a smaller impact on lower limb motor nerve block in parturients,and can achieve better maternal and infant outcomes.

BACKGROUND: The association of systemic inflammatory response index (SIRI) with prognosis of coronary artery disease (CAD) patients has never been investigated in a large sample with long-term follow-up. This study aimed to explore the association of SIRI with all-cause and cause-specific mortality in a nationally representative sample of CAD patients from United States. METHODS: A total of 3386 participants with CAD from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were included in this study. Cox proportional hazards model, restricted cubic spline (RCS), and receiver operating characteristic curve (ROC) were performed to investigate the association of SIRI with all-cause and cause-specific mortality. Piece-wise linear regression and sensitivity analyses were also performed. RESULTS: During a median follow-up of 7.7 years, 1454 all-cause mortality occurred. After adjusting for confounding factors, higher lnSIRI was significantly associated with higher risk of all-cause (HR = 1.16, 95% CI: 1.09-1.23) and CVD mortality (HR = 1.17, 95% CI: 1.05-1.30) but not cancer mortality (HR = 1.17, 95% CI: 0.99-1.38). The associations of SIRI with all-cause and CVD mortality were detected as J-shaped with threshold values of 1.05935 and 1.122946 for SIRI, respectively. ROC curves showed that lnSIRI had robust predictive effect both in short and long terms. CONCLUSIONS SIRI was independently associated with all-cause and CVD mortality, and the dose-response relationship was J-shaped. SIRI might serve as a valid predictor for all-cause and CVD mortality both in the short and long terms.