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.

Geniposidic acid(GA), a natural iridoid, exists in the roots, stems, leaves, flowers, bark, fruits, and seeds of medicinal plants of Rubiaceae, Eucommiaceae, and Plantaginaceae. Modern pharmacological studies have revealed that GA has multiple pharmacological activities, including organ-protective, anti-inflammatory, antioxidative, anti-osteoporosis, anti-neurodegenerative, and anti-cardiovascular effects. GA can enhance cell/organism defenses by upregulating key anti-inflammatory and antioxidant cytokines, while downregulating key node proteins in pro-inflammatory signaling pathways such as AhR and TLR4/MyD88, thereby exerting pharmacological effects such as organ protection. Pharmacokinetic investigations have suggested that after oral administration, GA can be distributed in multiple organs(kidney, liver, heart, spleen, lung, etc.). In addition, the pharmacokinetic behavior of GA could be significantly altered under disease conditions, as demonstrated by a marked increase in systematic exposure. This article comprehensively summarizes the reported pharmacological activities and mechanisms and systematically analyzes the pharmacokinetic characteristics and key parameters of GA, with the aim of providing a theoretical basis and scientific reference for the precise clinical application of GA-related Chinese patent medicines, as well as for the investigation and development of innovative drugs based on GA.
Humans ; Drugs, Chinese Herbal/chemistry* ; Animals ; Iridoid Glucosides/chemistry* ; Plants, Medicinal/chemistry* ; Anti-Inflammatory Agents/pharmacology*

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

Aim To investigate the protective effect of Vaccarin(Va)on epithelial-mesenchymal transition(EMT)in renal fibrosis model mice through regulating STAT3,and the underlying mechanism.Methods Left ureter ligation was used to establish a mouse model of unilateral ureteral obstruction(UUO);human kid-ney tubular epithelial(HK2)cells were induced to differentiate by transforming growth factor-β(TGF-β)in vitro.HE and Masson staining were used to observe the morphological changes of renal tissue;kits were used to detect the levels of BUN,Cr,IL-1β and IL-7 in mouse serum;CCK-8 was used to detect the effect of Va on the viability of HK2 cells;RT-PCR was used to detect the levels of inflammatory factors in HK2 cells;Western blot was used to detect the expression of STAT3,p-STAT3,E-cadherin,and α-SMA proteins in renal tissue and HK2 cells;to further investigate the regulation of Va on STAT3,JAK/STAT3 pathway acti-vator RO8191 was used to treat TGF-β-induced HK2 cells,and functional loss was detected.Results Va improved the pathological damage in UUO mice,inhibi-ted the levels of BUN,Cr and inflammatory factors;Va inhibited the phosphorylation of STAT3,upregulated E-cadherin,and downregulated α-SMA protein expres-sion;RO8191 counteracted the inhibitory effect of Va on the phosphorylation of STAT3.Conclusions Va inhibits the phosphorylation of STAT3 and the release of inflammatory factors,improves EMT,thus exerting an anti-renal fibrosis effect.

Aim To investigate the protective effect of Vaccarin(Va)on epithelial-mesenchymal transition(EMT)in renal fibrosis model mice through regulating STAT3,and the underlying mechanism.Methods Left ureter ligation was used to establish a mouse model of unilateral ureteral obstruction(UUO);human kid-ney tubular epithelial(HK2)cells were induced to differentiate by transforming growth factor-β(TGF-β)in vitro.HE and Masson staining were used to observe the morphological changes of renal tissue;kits were used to detect the levels of BUN,Cr,IL-1β and IL-7 in mouse serum;CCK-8 was used to detect the effect of Va on the viability of HK2 cells;RT-PCR was used to detect the levels of inflammatory factors in HK2 cells;Western blot was used to detect the expression of STAT3,p-STAT3,E-cadherin,and α-SMA proteins in renal tissue and HK2 cells;to further investigate the regulation of Va on STAT3,JAK/STAT3 pathway acti-vator RO8191 was used to treat TGF-β-induced HK2 cells,and functional loss was detected.Results Va improved the pathological damage in UUO mice,inhibi-ted the levels of BUN,Cr and inflammatory factors;Va inhibited the phosphorylation of STAT3,upregulated E-cadherin,and downregulated α-SMA protein expres-sion;RO8191 counteracted the inhibitory effect of Va on the phosphorylation of STAT3.Conclusions Va inhibits the phosphorylation of STAT3 and the release of inflammatory factors,improves EMT,thus exerting an anti-renal fibrosis effect.

Objective:To explore the relationship between mindfulness, optimism, and subjective well-being in post-lung transplantation patients, so as to provide a basis for nursing staff to improve patients' subjective well-being.Methods:This study was a cross-sectional survey. Convenience sampling was used to select 205 post-lung transplantation patients admitted to the First Affiliated Hospital of Guangzhou Medical University from October 2022 to November 2023 for the study. General Information Questionnaire, World Health Organization-Five Well-Being Scale, Mindful Attention Awareness Scale (MAAS) and Life Orientation Test-R (LOT-R) were used to investigate the study participants. Pearson correlation was used to analyze the correlation between subjective well-being and mindfulness and optimism in patients after lung transplantation. AMOS 24.0 software was used to construct a mediating model to analyze the path relationship between mindfulness, optimism and subjective well-being.Results:A total of 205 questionnaires were distributed and 202 valid questionnaires were recovered, with an effective recovery rate of 98.54% (202/205). In 202 patients after lung transplantation, the WHO-5 Well-Being Scale total score, MAAS total score, and LOT-R score were (16.31±4.73), (56.75±9.44), and (18.49±3.85), respectively. Lung transplantation patients' subjective well-being was positively correlated with mindfulness and optimism ( r=0.570, 0.600, both P<0.01). Optimism partially mediated the relationship between mindfulness and subjective well-being, with an effect value of 0.290 and an effect proportion of 52.35% (0.290/0.554) . Conclusions:Mindfulness and optimism are both positively correlated with subjective well-being in post-lung transplantation patients, and mindfulness could also influence subjective well-being through the mediating effect of optimism. Healthcare professionals should fully explore and cultivate positive psychological resources, such as mindfulness, in lung transplant patients, by increasing optimism as the target of intervention, which in turn improves patients' subjective well-being.

Aim To investigate the role of corylin in angiotensin Ⅱ(Ang Ⅱ)-induced cardiomyocyte hy-pertrophy and its underlying mechanisms.Methods An Ang Ⅱ-induced cardiomyocyte hypertrophy model was established and treated with corylin.Real-time PCR was employed to assess hypertrophic gene mRNA expression,and immunofluorescence was used to meas-ure cardiomyocyte surface area.Western blot and en-zyme activity assay kits were used to evaluate SIRT1 expression and activity.Results Corylin markedly mitigated Ang Ⅱ-induced hypertrophic gene expression and cardiomyocyte surface area enlargement.Moreo-ver,it prevented the Ang Ⅱ-mediated decline in SIRT1 protein levels and deacetylase activity.Further investi-gation indicated that corylin inhibited Ang Ⅱ-driven NF-κB transcriptional activity and the expression of its downstream target genes,such as TNF-α,IL-6,and IL-1β.Notably,SIRT1 silencing abolished the protective effects of corylin against cardiomyocyte hypertrophy,as well as its regulation of the SIRT1/NF-κB signaling pathway.Conclusion Corylin suppresses cardiomyo-cyte hypertrophy by modulating the SIRT1-dependent NF-κB signaling pathway.

Objective To investigate the practical effects of pediatric rapid sequence intubation(RSI)nursing coordination training based on the LSPPDM(learn,see,practice,prove,do,maintain)framework in order to provide evidence for optimizing pediatric RSI nursing training programs.Methods Nurses from the intensive care unit(ICU)of Children's Hospital,Fudan University during Feb 2023 and Jan 2024 were divided into the experimental group(n=35)and the control group(n=35)by block randomization.The experimental group received LSPPDM framework-based training,while the control group underwent conventional training with theoretical lectures and procedural demonstrations.Outcomes included training satisfaction,theoretical knowledge and procedural skill assessment scores,team collaboration compliance and RSI procedure time were compared between the two groups.Results The experimental group demonstrated significantly higher training satisfaction(123.80±2.04 vs.117.26±9.82,P<0.05),superior post-training theoretical knowledge and procedural skills(P<0.05),enhanced team collaboration compliance(P<0.05),and shorter RSI completion time(P<0.05)compared with the control group.Conclusion Pediatric RSI nursing coordination training based on the LSPPDM framework can effectively increase training satisfaction,promote theoretical and procedural skills and reduce completion time in nurses.

Objective:A gas chromatographic method was established for the determination of alcohol and phenolic bacteriostatic agents(chlorobutanol,phenol,benzyl alcohol,phenethyl alcohol,phenoxyethanol,4-chloro-o-cresol and thymol)in eye drops for related quality control.Methods:A capillary column with(5%phenyl)methylsilox-ane as the fixing solution.The initial temperature was 60℃and keep for 10 min.The temperature was rised to 150℃at a rate of 20℃·min-1 and keep for 3 min,Next,the temperature was rised to 230℃at a rate of 50℃·min-1 and keep for 2 min.The detector temperature was 250℃,the inlet temperature was 200℃,and the detector was FID.Direct injection of 1 μL was used for injection.Results:The were a good linear relationship between peak area and concentration in the concentration range of 0.05-1.0 mg·mL-1(chlorobutanol),0.05-1.0 mg·mL-1(phenol),0.1-2.0 mg·mL-1(benzyl alcohol),0.05-1.0 mg·mL-1(phenethyl alco-hol),0.05-1.0 mg·mL-1(phenoxyethanol),0.03-0.6 mg·mL-1(4-chloro-o-cresol)and 0.01-0.20 mg·mL-1(thymol)(r values were 0.999 7,0.999 6,0.999 5,0.999 5,0.999 5,0.999 5,0.999 5 and 0.999 5 respectively).The average recoveries of seven component were 103.4%,95.2%,98.4%,97.2%,97.9%,100.5%and 93.5%respectively.All meet the requirements of methodological research.According to the method,79 batches of samples were tested for alcohol and phenolic bacteriostatic agents.Chlorobutanol was detected in 8 batches of samples,and no other bacteriostatic agents were detected.Conclusion:This method meets the require-ments for specificity and sensitivity,and is suitable for the confirmation and determination of alcohol and phenolic antibacterial agents in eye drops.It can be used for related quality control.