1.Effect of transcutaneous phrenic nerve stimulation in preventing ventilator-induced diaphragmatic dysfunction in invasive mechanically ventilated patients.
Yuhua SHEN ; Hongyan ZHANG ; Lingyan WANG ; Xianbin SONG ; Xianjiang WANG ; Aili CAO
Chinese Critical Care Medicine 2025;37(4):343-347
OBJECTIVE:
To explore the preventive effect of transcutaneous phrenic nerve stimulation on ventilator-induced diaphragmatic dysfunction (VIDD) in patients requiring invasive mechanical ventilation.
METHODS:
A randomized controlled trial was conducted. The patients requiring invasive mechanical ventilation admitted to the intensive care unit (ICU) of Jiaxing First Hospital from November 2022 to December 2023 were enrolled. Participants were randomized into the control group and the observation group using a random number table. The control group was given ICU standardized nursing intervention, including turning over and slapping the back, raising the head of the bed, sputum aspiration on demand, aerosol inhalation, oral care, and monitoring of airbag pressure and gastric retention, the observation group was given additional transcutaneous phrenic nerve stimulation intervention on the basis of ICU standardized nursing intervention. The stimulation intensity was set to 10 U, the pulse frequency was set to 40 Hz, and the stimulation frequency was set to 12 times/min. Transcutaneous phrenic nerve stimulation was administered once a day for 30 minutes each time, for a total of 5 days. Diaphragm thickening fraction (DTF) and arterial blood gas parameters on days 1, 3, and 5 of intervention were compared between the two groups. After 5 days of intervention, other parameters including the incidence of VIDD, duration of mechanical ventilation, and length of ICU stay were compared.
RESULTS:
A total of 120 patients requiring invasive mechanical ventilation were enrolled, with 16 dropouts (dropout rate was 13.33%). Ultimately, 51 patients in the control group and 53 patients in the observation group were analyzed. Baseline characteristics, including gender, age, body mass index (BMI), acute physiology and chronic health evaluation II (APACHE II) score, albumin (Alb), hemoglobin (Hb), and disease type, showed no significant differences between the two groups. DTF in both groups gradually increased over duration of intervention [DTF on days 1, 3, and 5 in the control group was (20.83±2.33)%, (21.92±1.27)%, and (23.93±2.33)%, respectively, and that in the observation group was (20.89±1.96)%, (22.56±1.64)%, and (25.34±2.38)%, respectively], with more significant changes in DTF in the observation group, showing time effects (Ftime = 105.975, P < 0.001), intervention effects (Fintervention = 7.378, P = 0.008), and interaction effects (Finteraction = 3.322, P = 0.038). Arterial blood gas parameters did not differ significantly before intervention between the groups, but after 5 days of intervention, arterial partial pressure of oxygen (PaO2) in the observation group was significantly higher than that in the control group [mmHg (1 mmHg≈0.133 kPa): 100.72±15.75 vs. 93.62±15.54, P < 0.05], and arterial partial pressure of carbon dioxide (PaCO2) was significantly lower than that in the control group (mmHg: 36.53±3.10 vs. 37.69±2.02, P < 0.05). At 5 days of intervention, the incidence of VIDD in the observation group was significantly lower than that in the control group [15.09% (8/53) vs. 37.25% (19/51), P < 0.05], and both duration of mechanical ventilation and length of ICU stay were significantly shorter than those in the control group [duration of mechanical ventilation (days): 7.93±2.06 vs. 8.77±1.76, length of ICU stay (days): 9.64±2.35 vs. 11.01±2.01, both P < 0.05].
CONCLUSIONS
Transcutaneous phrenic nerve stimulation can improve diaphragmatic and respiratory function in patients receiving invasive mechanical ventilation, reduce the incidence of VIDD, and shorten the duration of mechanical ventilation and length of ICU stay.
Humans
;
Transcutaneous Electric Nerve Stimulation
;
Respiration, Artificial/adverse effects*
;
Diaphragm/physiopathology*
;
Phrenic Nerve
;
Intensive Care Units
;
Male
;
Female
;
Middle Aged
2.Advantages and limitations of transcutaneous electrical acupoint stimulation in the treatment of patients with severe gastrointestinal function injury in intensive care unit: a prospective randomized controlled trial.
Lele XU ; Yanjun CHEN ; Jian LU ; Yaou CHEN
Chinese Critical Care Medicine 2025;37(5):458-464
OBJECTIVE:
To evaluate the advantages and limitations of transcutaneous electrical acupoint stimulation (TEAS) in the treatment of patients with severe gastrointestinal function injury in intensive care unit (ICU) by analyzing dynamic changes of intestinal fatty acid binding protein (I-FABP), D-lactic acid and citrulline.
METHODS:
A prospective single-center randomized controlled trial was conducted. Patients with severe gastrointestinal function injury admitted to the ICU from February 2021 to January 2024 were enrolled [age > 18 years old, acute gastrointestinal injury (AGI) grade 2 to 3, stable hemodynamics]. Patients with different AGI grades were randomly assigned in a 1:1 ratio to the TEAS group and the control group using simple randomization. Both groups received conventional treatment and enteral nutrition (EN). In addition, the TEAS group underwent TEAS at the Neiguan and Zusanli points for 30 minutes per session, twice daily for 7 days. Baseline data, including age, gender, underlying diseases, and primary diagnoses, were recorded. Three intestinal biomarkers, such as I-FABP, D-lactic acid, and citrulline were measured before and after 7 days of treatment. EN tolerance indicators and 28 days survival status were documented. The differences in various indicators were compared between the two groups, subgroup analyses were conducted based on AGI grading, and interaction between AGI grade and TEAS were analyzed. The 28-day Kaplan-Meier survival curves were generated for both groups.
RESULTS:
Finally, 133 patients were included, with 68 in the TEAS group and 65 in the control group. Baseline characteristics were comparable between the two groups. A comparison of the dynamic changes in intestinal biomarkers revealed that the I-FABP level in both groups decreased after treatment compared to pre-treatment, with a more pronounced reduction in the TEAS group. The least square mean difference (LS Mean difference) for the corrected I-FABP level between the two groups during the observation period was -0.23 μg/L [95% confidence interval (95%CI) was -0.45 to -0.01], which was statistically significant (P = 0.041). Additionally, a significant interaction with AGI was observed (P = 0.004). Post-treatment, D-lactic acid level decreased in both groups compared to pre-treatment, with a more significant reduction in the TEAS group. The LS Mean difference for the corrected D-lactic acid level was -0.08 mmol/L (95%CI was -0.11 to -0.05), which was statistically significant (P < 0.001), and the interaction with AGI was also significant (P = 0.005). There was no significant change in citrulline levels between the two groups before and after treatment. The LS Mean difference for the corrected citrulline level was -0.17 μmol/L (95%CI was -1.87 to 1.53), which was not statistically significant (P = 0.845), and no significant interaction with AGI was observed (P = 0.913). Comparison of EN tolerance parameters between the two groups revealed that the TEAS group had a longer total EN time (hours: 72±31 vs. 60±28) and higher total EN calories (kJ: 11 469.23±7 237.34 vs. 6 638.76±5 098.37), as well as a higher 70% target caloric attainment rate (52.9% vs. 32.3%) compared to the control group (all P < 0.05). The incidence of abdominal distension after EN was lower in the TEAS group than that in the control group (23.5% vs. 43.1%, P < 0.05), while the incidence of diarrhea after EN was higher in the TEAS group (22.1% vs. 7.7%, P < 0.05). There were no significantly differences in AGI grade reduction rate, post-EN vomiting/gastric retention rate, incidence of feeding interruption, and 28-day survival rate between the two groups. Furthermore, there were no significantly interaction between these observation measures and AGI. Kaplan-Meier survival analysis showed that there was no significantly difference in 28-day cumulative survival rate between the TEAS group and the control group [Log-Rank test: P = 0.501, hazard ratio (HR) = 0.81, 95%CI was 0.43-1.51), and there was no significantly interaction with AGI (P = 0.702).
CONCLUSIONS
The advantage of TEAS in the treatment of ICU patients with severe gastrointestinal function injury lies in its ability to reverse intestinal cell necrosis and promote the reconstruction of intestinal barrier function. Additionally, gastrointestinal tolerance is significantly improved, and both the duration and total calories of EN are increased. However, the limitation of TEAS therapy is that it does not promote the recovery of intestinal cell absorption and synthesis function in the target patients. Moreover, it may lead to nutrient solution overload due to improved gastrointestinal tolerance. Furthermore, TEAS does not appear to improve 28-day cumulative survival rate in the target patients.
Humans
;
Prospective Studies
;
Intensive Care Units
;
Acupuncture Points
;
Fatty Acid-Binding Proteins/metabolism*
;
Transcutaneous Electric Nerve Stimulation
;
Male
;
Female
;
Citrulline/metabolism*
;
Lactic Acid/metabolism*
;
Gastrointestinal Diseases/therapy*
;
Middle Aged
;
Enteral Nutrition
;
Adult
3.A simulation study of nerve fiber activation in the lumbar segment under kilohertz-frequency transcutaneously spinal cord stimulation.
Qi XU ; Xinru LI ; Zhixin LU ; Yongchao WU
Journal of Biomedical Engineering 2025;42(2):300-307
Clinical trials have demonstrated that kilohertz-frequency transcutaneous spinal cord stimulation (TSCS) can be used to facilitate the recovery of sensory-motor function for patients with spinal cord injury, whereas the neural mechanism of TSCS is still undetermined so that the choice of stimulation parameters is largely dependent on the clinical experience. In this paper, a finite element model of transcutaneous spinal cord stimulation was used to calculate the electric field distribution of human spinal cord segments T 12 to L 2, whereas the activation thresholds of spinal fibers were determined by using a double-cable neuron model. Then the variation of activation thresholds was obtained by varying the carrier waveform, the interphase delay, the modulating frequency, and the modulating pulse width. Compared with the sinusoidal carrier, the usage of square carrier could significantly reduce the activation threshold of dorsal root (DR) fibers. Moreover, the variation of activation thresholds was no more than 1 V due to the varied modulating frequency and decreases with the increased modulating pulse width. For a square carrier at 10 kHz modulated by rectangular pulse with the frequency of 50 Hz and the pulse width of 1 ms, the lowest activation thresholds of DR fibers and dorsal column fibers were 27.6 V and 55.8 V, respectively. An interphase delay of 5 μs was able to reduce the activation thresholds of the DR fibers to 20.1 V. The simulation results can lay a theoretical foundation on the selection of TSCS parameters in clinical trials.
Humans
;
Spinal Cord Stimulation/methods*
;
Nerve Fibers/physiology*
;
Finite Element Analysis
;
Spinal Cord/physiology*
;
Computer Simulation
;
Spinal Cord Injuries/physiopathology*
;
Lumbosacral Region
;
Lumbar Vertebrae
;
Transcutaneous Electric Nerve Stimulation/methods*
;
Models, Neurological
4.Electroacupuncture reduced airway inflammation by activating somatosensory-sympathetic pathways in allergic asthmatic rats.
Hongli MA ; Xiaowen LIU ; Huamei CAI ; Yun YAN ; Weixia LI ; Jing ZHAO
Chinese Medical Journal 2025;138(6):702-712
BACKGROUND:
Electroacupuncture (EA) treatment is efficacious in patients with respiratory disorders, although the mechanisms of its action in lung-function protection are poorly understood. This study aimed to explore the neuroanatomical mechanisms of EA stimulation at the BL13 acupoint (Feishu, EA-BL13) improvement in asthma.
METHODS:
Allergic asthma was induced by intranasal 2.0% ovalbumin (OVA) instillation combined with intraperitoneal injection of the 10.0% OVA. The levels of interleukin (IL)-4 and IL-5 were detected by enzyme-linked immunosorbent assay. Hematoxylin and eosin and periodic acid-schiff stain were used to evaluate inflammatory cell infiltration and mucus secretion. Cellular oncogene fos induction in neurons after EA stimulation was detected by immunofluorescent staining. The messenger RNA expression levels of adrenergic receptors were quantified with real-time polymerase chain reaction.
RESULTS:
EA improved airway inflammation and mucus secretion mainly by activating somatosensory-sympathetic pathways ( P <0.001). Briefly, the intermediolateral (IML) nuclei of the spinal cord received signals from somatic EA stimulation and then delivered the information via the sympathetic trunk to the lung. Excited sympathetic nerve endings in lung tissue released large amounts of catecholamines that specifically activated the β2 adrenergic receptor (β2AR) on T cells ( P <0.01) and further decreased the levels of IL-4 and IL-5 ( P <0.001) through the cyclic adenosine monophosphate/protein kinase A signaling pathway.
CONCLUSION
This study provided a new explanation and clinical basis for the use of EA-BL13 as a treatment for allergic asthma in both the attack and remission stages and other respiratory disorders related to airway inflammation.
Electroacupuncture/methods*
;
Animals
;
Asthma/immunology*
;
Rats
;
Rats, Sprague-Dawley
;
Male
;
Inflammation/therapy*
;
Interleukin-4/metabolism*
;
Interleukin-5/metabolism*
5.A spinal neural circuit for electroacupuncture that regulates gastric functional disorders.
Meng-Ting ZHANG ; Yi-Feng LIANG ; Qian DAI ; He-Ren GAO ; Hao WANG ; Li CHEN ; Shun HUANG ; Xi-Yang WANG ; Guo-Ming SHEN
Journal of Integrative Medicine 2025;23(1):56-65
OBJECTIVE:
Acupuncture therapies are known for their effectiveness in treating a variety of gastric diseases, although the mechanisms underlying these effects are not fully understood. This study tested the effectiveness of electroacupuncture (EA) at acupoints Zhongwan (RN12) and Weishu (BL21) for managing gastric motility disorder (GMD) and investigated the underlying mechanisms involved.
METHODS:
A GMD model was used to evaluate the impact of EA on various aspects of gastric function including the amplitude of gastric motility, electrogastrogram, food intake, and the rate of gastric emptying. Immunofluorescence techniques were used to explore the activation of spinal neurons by EA, specifically examining the presence of cholera toxin B subunit (CTB)-positive neurons and fibers emanating from acupoints RN12 and BL21. The stimulation of γ-aminobutyric acid (GABA)-ergic neurons in the spinal dorsal horn, the inhibition of sympathetic preganglionic neurons in the spinal lateral horn, and their collective effects on the activity of sympathetic nerves were examined.
RESULTS:
EA at RN12 and BL21 significantly improved gastric motility compromised by GMD. Notably, EA activated spinal neurons, with CTB-positive neurons and fibers from RN12 and BL21 being detectable in both the dorsal root ganglia and the spinal dorsal horn. Further analysis revealed that EA at these acupoints not only stimulated GABAergic neurons in the spinal dorsal horn but also suppressed sympathetic preganglionic neurons in the spinal lateral horn, effectively reducing excessive activity of sympathetic nerves triggered by GMD.
CONCLUSION
EA treatment at RN12 and BL21 effectively enhances gastric motility in a GMD model. The therapeutic efficacy of this approach is attributed to the activation of spinal neurons and the modulation of the spinal GABAergic-sympathetic pathway, providing a neurobiological foundation for the role of acupuncture in treating gastric disorders. Please cite this article as: Zhang MT, Liang YF, Dai Q, Gao HR, Wang H, Chen L, Huang S, Wang XY, Shen GM. A spinal neural circuit for electroacupuncture that regulates gastric functional disorders. J Integr Med. 2025; 23(1): 56-65.
Electroacupuncture
;
Animals
;
Male
;
Acupuncture Points
;
Stomach Diseases/physiopathology*
;
Rats, Sprague-Dawley
;
Gastrointestinal Motility
;
Rats
;
Gastric Emptying
;
Neurons
;
Spinal Cord
;
Stomach/physiopathology*
6.Brain functional changes following electroacupuncture in a mouse model of comorbid pain and depression: A resting-state functional magnetic resonance imaging study.
Xuan YIN ; Xiao-Ling ZENG ; Jing-Jing LIN ; Wen-Qing XU ; Kai-Yu CUI ; Xiu-Tian GUO ; Wei LI ; Shi-Fen XU
Journal of Integrative Medicine 2025;23(2):159-168
OBJECTIVE:
Comorbid pain and depression are common but remain difficult to treat. Electroacupuncture (EA) can effectively improve symptoms of depression and relieve pain, but its neural mechanism remains unclear. Therefore, we used resting-state functional magnetic resonance imaging (rs-fMRI) to detect cerebral changes after initiating a mouse pain model via constriction of the infraorbital nerve (CION) and then treating these animals with EA.
METHODS:
Forty male C57BL/6J mice were divided into 4 groups: control, CION model, EA, and sham acupuncture (without needle insertion). EA was performed on the acupoints Baihui (GV20) and Zusanli (ST36) for 20 min, once a day for 10 consecutive days. The mechanical withdrawal threshold was tested 3 days after the surgery and every 3 days after the intervention. The depressive behavior was evaluated with the tail suspension test, open-field test, elevated plus maze (EPM), sucrose preference test, and marble burying test. The rs-fMRI was used to detect the cerebral changes of the functional connectivity (FC) in the mice following EA treatment.
RESULTS:
Compared with the CION group, the mechanical withdrawal threshold increased in the EA group at the end of the intervention (P < 0.05); the immobility time in tail suspension test decreased (P < 0.05); and the times of the open arm entry and the open arm time in the EPM increased (both P < 0.001). There was no difference in the sucrose preference or marble burying tests (both P > 0.05). The fMRI results showed that EA treatment downregulated the amplitude of low-frequency fluctuations and regional homogeneity values, while these indicators were elevated in brain regions including the amygdala, hippocampus and cerebral cortex in the CION model for comorbid pain and depression. Selecting the amygdala as the seed region, we found that the FC was higher in the CION group than in the control group. Meanwhile, EA treatment was able to decrease the FC between the amygdala and other brain regions including the caudate putamen, thalamus, and parts of the cerebral cortex.
CONCLUSION
EA can downregulate the abnormal activation of neurons in the amygdala and improve its FC with other brain regions, thus exerting analgesic and antidepressant effects. Please cite this article as: Yin X, Zeng XL, Lin JJ, Xu WQ, Cui KY, Guo XT, Li W, Xu SF. Brain functional changes following electroacupuncture in a mouse model of comorbid pain and depression: a resting-state functional magnetic resonance imaging study. J Integr Med. 2025; 23(2): 159-168.
Animals
;
Electroacupuncture
;
Male
;
Magnetic Resonance Imaging
;
Depression/diagnostic imaging*
;
Mice, Inbred C57BL
;
Brain/diagnostic imaging*
;
Disease Models, Animal
;
Mice
;
Pain/diagnostic imaging*
;
Acupuncture Points
7.Does acupuncture at motor-related acupoints affect corticospinal excitability? A systematic review and meta-analysis.
Renming LIU ; Aung Aung Kywe MOE ; Weiting LIU ; Maryam ZOGHI ; Shapour JABERZADEH
Journal of Integrative Medicine 2025;23(2):113-125
BACKGROUND:
Acupuncture is widely used in modulating brain excitability and motor function, as a form of complementary and alternative medicine. However, there is no existing meta-analysis evaluating the effectiveness and safety of acupuncture on corticospinal excitability (CSE), and the credibility of the evidence has yet to be quantified.
OBJECTIVE:
This study was designed to assess the efficacy and safety of electroacupuncture (EA) and manual acupuncture (MA) in enhancing brain excitability, specifically focusing on CSE as measured by transcranial magnetic stimulation (TMS).
SEARCH STRATEGY:
This study followed a systematic approach, searching 9 databases up to August 2024 and examining grey literature, in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
INCLUSION CRITERIA:
Studies were included if they compared the clinical efficacy of EA or MA with sham acupuncture, no treatment or usual training.
DATA EXTRACTION AND ANALYSIS:
Three investigators independently conducted literature screening, data extraction, and risk of bias assessment. The primary outcome focused on motor-evoked potentials as measured by TMS, with treatment effects quantified using mean differences or standardized mean differences between pre- and post-treatment. Subgroup analyses were conducted using mixed-effects models, while random-effects or fixed-effects models were used to estimate average treatment differences across studies.
RESULTS:
Based on 34 studies involving 1031 adults, acupuncture techniques significantly enhanced CSE. EA had a greater impact than MA, with effect sizes of 0.53 mV vs 0.43 mV (95% confidence interval [CI]: [0.30, 0.76], P < 0.00001 vs 95% CI: [0.28, 0.59], P < 0.00001). The 5 most frequently used acupoints were LI4 (Hegu, 32 times), ST36 (Zusanli, 10 times), LI11 (Quchi, 7 times), TE5 (Waiguan, 6 times), and GB34 (Yanglingquan, 5 times).
CONCLUSION
This systematic review indicates that both EA and MA could effectively and safely enhance CSE, bringing the corticospinal pathway closer to the threshold for firing, which may ultimately improve motor function. LI4, ST36, LI11, TE5 and GB34 are the most commonly used acupoints. Please cite this article as: Liu R, Moe AAK, Liu W, Zoghi M, Jaberzadeh S. Does acupuncture at motor-related acupoints affect corticospinal excitability? A systematic review and meta-analysis. J Integr Med. 2025; 23(2): 113-125.
Humans
;
Evoked Potentials, Motor/physiology*
;
Acupuncture Points
;
Acupuncture Therapy/methods*
;
Transcranial Magnetic Stimulation
;
Electroacupuncture
;
Pyramidal Tracts/physiology*
8.Early improvement to electroacupuncture at week 3 predicts ultimate response in patients with chronic severe functional constipation.
Zhi-Yi XIONG ; Shi-Yan YAN ; Si-Xing LIU ; Zhi-Shun LIU
Journal of Integrative Medicine 2025;23(3):274-281
OBJECTIVE:
To investigate whether the presence or absence of improvement in chronic severe functional constipation (CSFC) at the early stage of treatment with electroacupuncture predicts subsequent response or non-response, and to determine the optimal treatment duration for assessing subsequent responses to electroacupuncture.
METHODS:
This is a post hoc analysis using data pooled from two large-scale randomized controlled trials. Patients with CSFC were recruited, and those in the electroacupuncture groups were included in the present study. Early improvement was defined as a weekly increase of ≥1 complete spontaneous bowel movement (CSBM) compared to baseline. Three treatment response criteria were evaluated: ≥ 3 CSBMs per week, overall CSBM response, and sustained CSBM response. Predictive statistics, including sensitivity, specificity, positive predictive value, and negative predictive value, were calculated at weeks 1-4. Receiver operating characteristic curves and accuracy rates were used to determine the optimal timepoint for differentiation between responders and non-responders.
RESULTS:
Cases from a total of 813 participants who received electroacupuncture were analyzed. The proportion of improvers was 40.34% by week 1, increasing to 52.52% by week 4. After 8 weeks of treatment, the response rates were 30.14%, 25.83% and 25.58% according to the three aforementioned criteria, respectively. Early improvement was a strong predictor of treatment response, with week 3 demonstrating the highest predictive accuracy.
CONCLUSION
Early improvement with electroacupuncture, especially at week 3, can predict subsequent outcomes. Our findings suggest that acupuncturists may identify non-responders who might require adjustments to therapeutic strategies early in treatment. Please cite this article as: Xiong ZY, Yan SY, Liu SX, Liu ZS. Early improvement to electroacupuncture at week 3 predicts ultimate response in patients with chronic severe functional constipation. J Integr Med. 2025; 23(3): 274-281.
Humans
;
Constipation/physiopathology*
;
Electroacupuncture
;
Male
;
Female
;
Middle Aged
;
Chronic Disease
;
Adult
;
Treatment Outcome
;
Aged
9.Electroacupuncture alleviates behaviors associated with posttraumatic stress disorder by modulating lipocalin-2-mediated neuroinflammation and neuronal activity in the prefrontal cortex.
Yu-Die YANG ; Wen ZHONG ; Ming CHEN ; Qing-Chen TANG ; Yan LI ; Lu-Lu YAO ; Mei-Qi ZHOU ; Neng-Gui XU ; Shuai CUI
Journal of Integrative Medicine 2025;23(5):537-547
OBJECTIVE:
To elucidate the specific mechanisms by which electroacupuncture (EA) alleviates anxiety and fear behaviors associated with posttraumatic stress disorder (PTSD), focusing on the role of lipocalin-2 (Lcn2).
METHODS:
The PTSD mouse model was subjected to single prolonged stress and shock (SPS&S), and the animals received 15 min sessions of EA at Shenmen acupoint (HT7). Behavioral tests were used to investigate the effects of EA at HT7 on anxiety and fear. Western blotting and enzyme-linked immunosorbent assay were used to quantify Lcn2 and inflammatory cytokine levels in the prefrontal cortex (PFC). Additionally, the activity of PFC neurons was evaluated by immunofluorescence and in vivo electrophysiology.
RESULTS:
Mice subjected to SPS&S presented increased anxiety- and fear-like behaviors. Lcn2 expression in the PFC was significantly upregulated following SPS&S, leading to increased expression of the proinflammatory cytokines tumor necrosis factor-α and interleukin-6 and suppression of PFC neuronal activity. However, EA at HT7 inhibited Lcn2 release, reducing neuroinflammation and hypoexcitability in the PFC. Lcn2 overexpression mitigated the effects of EA at HT7, resulting in anxiety- and fear-like behaviors.
CONCLUSION
EA at HT7 can ameliorate PTSD-associated anxiety and fear, and its mechanism of action appears to involve the inhibition of Lcn2-mediated neural activity and inflammation in the PFC. Please cite this article as: Yang YD, Zhong W, Chen M, Tang QC, Li Y, Yao LL, et al. Electroacupuncture alleviates behaviors associated with posttraumatic stress disorder by modulating lipocalin-2-mediated neuroinflammation and neuronal activity in the prefrontal cortex. J Integr Med. 2025; 23(5):537-547.
Electroacupuncture
;
Stress Disorders, Post-Traumatic/metabolism*
;
Animals
;
Lipocalin-2/metabolism*
;
Prefrontal Cortex/physiopathology*
;
Male
;
Mice
;
Neurons/physiology*
;
Disease Models, Animal
;
Fear
;
Behavior, Animal
;
Mice, Inbred C57BL
;
Neuroinflammatory Diseases/metabolism*
;
Anxiety/therapy*
;
Acupuncture Points
10.Electroacupuncture at ST36 improves gastrointestinal motility disorders by promoting enteric nervous system regeneration through GDNF/Ret signaling in diabetic mice.
Jin-Lu GUO ; Shi LIU ; Sheng-Jie DING ; Xin YANG ; Fan DU
Journal of Integrative Medicine 2025;23(5):548-559
OBJECTIVE:
Diabetes-induced gastrointestinal (GI) motility disorders are increasingly prevalent. Damage to the enteric nervous system (ENS), composed primarily of enteric neurons and glial cells, is an essential mechanism involved in these disorders. Although electroacupuncture (EA) has shown the potential to mitigate enteric neuronal loss, its mechanism is not fully understood. Additionally, the effects of EA on enteric glial cells have not been investigated. Enteric neural precursor cells (ENPCs) contribute to the structural and functional integrity of the ENS, yet whether EA enhances their differentiation into enteric neurons and glial cells remains unexplored. This study investigates whether EA promotes ENS repair through enhancing ENPC-derived neurogenesis and gliogenesis and elucidates the potential molecular mechanisms involved.
METHODS:
Transgenic mice were used to trace Nestin+/nerve growth factor receptor (Ngfr)+ ENPCs labeled with green fluorescent protein (GFP) in vivo. Mice were randomly divided into four groups: control, diabetes mellitus (DM), DM + sham EA, and DM + EA. The effects of EA on diabetic mice were evaluated by GI motility, ENS structure, and ENPC differentiation. Glial cell line-derived neurotrophic factor (GDNF)/Ret signaling was detected to clarify the underlying molecular mechanisms.
RESULTS:
EA alleviated diabetes-induced GI motility disorders, as indicated by reduced whole gut transit time, shortened colonic bead expulsion time, and enhanced smooth muscle contractility. Furthermore, EA attenuated diabetes-induced losses of enteric neurons and glial cells, thereby restoring ENS integrity. Notably, EA reversed the diabetes-induced decrease in ENPCs and significantly increased the absolute number and the proportion of ENPC-derived enteric neurons. However, immunofluorescence analyses revealed no colocalization between EA-induced glial fibrillary acidic protein+ glial cells and GFP-labeled ENPCs. Mechanistically, GDNF/Ret signaling was elevated in intestinal tissues and upregulated in ENPCs in EA-treated diabetic mice.
CONCLUSION
EA facilitates ENS repair by promoting Nestin+/Ngfr+ ENPC differentiation into enteric neurons via upregulation of GDNF/Ret signaling, and driving enteric gliogenesis from non-Nestin+/Ngfr+ ENPCs. These findings highlight EA's role in ameliorating diabetes-induced GI dysmotility through ENPC-derived ENS restoration. Please cite this article as: Guo JL, Liu S, Ding SJ, Yang X, Du F. Electroacupuncture at ST36 improves gastrointestinal motility disorders by promoting enteric nervous system regeneration through GDNF/Ret signaling in diabetic mice. J Integr Med. 2025; 23(5):548-559.
Animals
;
Electroacupuncture
;
Enteric Nervous System/physiology*
;
Gastrointestinal Motility/physiology*
;
Glial Cell Line-Derived Neurotrophic Factor/metabolism*
;
Diabetes Mellitus, Experimental/therapy*
;
Signal Transduction
;
Mice
;
Gastrointestinal Diseases/physiopathology*
;
Proto-Oncogene Proteins c-ret/metabolism*
;
Mice, Transgenic
;
Male
;
Nerve Regeneration
;
Neural Stem Cells
;
Mice, Inbred C57BL
;
Acupuncture Points

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