OBJECTIVES: To investigate the therapeutic effect of Ziwuliuzhu acupuncture in a rat model of insomnia and its regulatory effect on the glutamic acid (Glu)/γ-aminobutyric acid (GABA)-glutamine (Gln) metabolic loop. METHODS: Forty male SD rats were randomly assigned to control group, model group, Najia group and Nazi group (n=10). In the latter 3 groups, rat models of insomnia were established by intraperitoneal injections of p-chlorophenylalanine and verified using a sodium pentobarbital-induced sleep test. After modeling, the rats in Najia and Nazi groups received acupuncture for 7 days at specifically chosen sets of acupoints based on the Ziwuliuzhu rationale in traditional Chinese medicine. Pathological changes in the hypothalamic tissue of the rats were examined with HE staining, and the levels of Glu and GABA in the hypothalamus were determined with high-performance liquid chromatography (HPLC)-mass spectrometry (MS)/MS. Immunohistochemistry was used to detect the expressions of GABAA receptors (GABAARs) in the hypothalamus, and the expression levels of glutamate decarboxylase (GAD65/67) and glutamine synthetase (GS) were determined with Western blotting. RESULTS: Compared with the model group, the rats in Najia and Nazi groups exhibited decreased Glu levels and GABAA receptor expression and increased GABA levels with a decreased Glu/GABA ratio in the hypothalamus. Ziwuliuzhu acupuncture significantly increased the protein expressions of GAD65 and GAD67 and lowered the expression of GS in the hypothalamus in the rat models of insomnia. CONCLUSIONS Ziwuliuzhu acupuncture produces sedative and hypnotic effects in rat models of insomnia possibly by regulating Glu and GABA-Gln metabolism to restore the excitatory/inhibitory balance between Glu and GABA.
Animals ; Rats, Sprague-Dawley ; Male ; Rats ; gamma-Aminobutyric Acid/metabolism* ; Sleep Initiation and Maintenance Disorders/therapy* ; Glutamine/metabolism* ; Glutamic Acid/metabolism* ; Acupuncture Therapy ; Hypothalamus/metabolism* ; Receptors, GABA-A/metabolism* ; Acupuncture Points

OBJECTIVES: To investigate the therapeutic effect of electroacupuncture (EA) at Zusanli (ST36) acupoint on hyperlipidemia in mice and explore the underlying mechanisms. METHODS: Thirty C57BL/6J mice were equally randomized into normal diet group, high-fat diet (HFD) group, and EA group. The changes in blood lipids and serum malondialdehyde (MDA) content of the mice were evaluated, and histopathological changes and lipid accumulation in the liver were observed using Oil red O staining (ORO). The expressions of NLRP3, TLR4, and IL-1β proteins in the colon tissues were detected with Western blotting, and gut microbiota changes were analyzed using 16S rDNA sequencing. RESULTS: In mice with HFD feeding, 16 weeks of EA treatment significantly lowered body weight and serum TC, TG, LDL-C and MDA levels, obviously reduced lipid accumulation in the liver, and ameliorated HFD-induced elevations of protein expressions of NLRP3, TLR4, and IL-1β. 16S rRNA sequencing revealed that EA significantly altered gut microbiota composition, and increased the diversity and relative abundance of beneficial bacterial groups such as Muribaculaceae and Lachnospiraceae NK4A136_group. CONCLUSIONS Electroacupuncture at ST36 alleviates blood lipid disorders in hyperlipidemic mice possibly by improving intestinal microbiota structure, promoting degradation of high-caloric carbohydrates, cholesterol lipid metabolism and intestinal mucosa repair, and reducing toxin leakage, lipid peroxides, and liver fat deposition.
Animals ; Electroacupuncture ; Gastrointestinal Microbiome ; Hyperlipidemias/blood* ; Mice, Inbred C57BL ; Mice ; Diet, High-Fat ; Toll-Like Receptor 4/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein ; Acupuncture Points ; Male ; Lipids/blood* ; Interleukin-1beta/metabolism* ; Liver/metabolism*

Various acupuncture clinical trials have been conducted on migraine; however, the conclusions remain controversial especially when acupuncture was compared with sham acupuncture. Sham acupuncture is sometimes performed at the same acupuncture points used for verum acupuncture despite the evidence on acupuncture point specificity. Four databases were searched for sham acupuncture or waiting list-controlled acupuncture trials for migraine on December 25, 2023. Sham acupuncture was classified according to the needling points: sham acupuncture therapy at verum points (SATV) or at sham points (SATS). Network meta-analysis was performed based on the frequentist framework for headache pain intensity and response rate. A total of 18 studies involving 1936 participants were analyzed. Headache pain intensity and response rate were significantly improved in verum acupuncture compared with SATS. However, there was no significant difference between SATV and verum acupuncture. When comparing SATS and SATV, there was no significant difference in headache pain intensity and response rate; however, the results were in favor of SATV. The effect of the risk of bias on the certainty of evidence between verum and sham acupunctures was judged to be generally low. SATV should not be misused as a placebo control to evaluate the efficacy of acupuncture.
Humans ; Migraine Disorders/therapy* ; Acupuncture Therapy/methods* ; Acupuncture Points ; Treatment Outcome ; Randomized Controlled Trials as Topic

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

OBJECTIVE: The analgesic effect of acupuncture has been widely accepted. Nevertheless, the mechanism behind its analgesic effect remains elusive, thus impeding the progress of research geared toward enhancing the analgesic effect of acupuncture. This paper investigated the role of acupuncture needle surface textures on acupuncture's analgesic effect by creating four experimental acupuncture needles with different patterns of surface augmentation. METHODS: Four types of acupuncture needles with different surface textures (the lined needle, circle needle, sandpaper needle, and threaded needle) were designed. Additionally, the force/torque measurement system used a robot arm and mechanical sensor to measure the force on the needle during insertion and manipulation. To perform acupuncture analgesia experiments, four experimental acupuncture needles and a normal needle were inserted into the Zusanli (ST36) acupoint of rats with inflammatory pain. By comparing the force and torque and the analgesic efficacy of the different acupuncture needles, these experiments tested the role of acupuncture needle body texture on acupuncture analgesia. RESULTS: The analgesic effects of different acupuncture needle body textures varied. Specifically, the force required to penetrate the skin with the lined needle was not greater than that for the normal needle; however, the needle with inscribed circles and the sandpaper-roughened needle both required greater force for insertion. Additionally, the torque of the lined needle reached 2 × 10^-4 N·m under twisting manipulation, which was four times greater the torque of a normal needle (5 × 10^-5 N·m). Furthermore, the lined needle improved pain threshold and mast cell degranulation rate compared to the normal needle. CONCLUSION Optimizing the texture of acupuncture needles can enhance acupuncture analgesia. The texture of our experimental acupuncture needles had a significant impact on the force needed to penetrate the skin and the torque needed to manipulate the needle; it was also linked to variable analgesic effects. This study provides a theoretical basis for enhancing the analgesic efficacy of acupuncture through the modification of needles and promoting the development of acupuncture therapy. Please cite this article as: Sun MZ, Wang X, Li YC, Liu YH, Yu Y, Ren LJ, Gu W, Yao W. Effects of acupuncture needle modification on acupuncture analgesia. J Integr Med. 2025; 23(1): 66-78.
Needles ; Acupuncture Analgesia/methods* ; Animals ; Rats ; Male ; Acupuncture Points ; Rats, Sprague-Dawley

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*

BACKGROUND: China is seeing a growing demand for rehabilitation treatments for post-stroke upper limb spastic paresis (PSSP-UL). Although acupuncture is known to be effective for PSSP-UL, there is room to enhance its efficacy. OBJECTIVE: This study explored a semi-personalized acupuncture approach for PSSP-UL that used three-dimensional kinematic analysis (3DKA) results to select additional acupoints, and investigated the feasibility, efficacy and safety of this approach. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This single-blind, single-center, randomized, controlled trial involved 74 participants who experienced a first-ever ischemic or hemorrhagic stroke with spastic upper limb paresis. The participants were then randomly assigned to the intervention group or the control group in a 1:1 ratio. Both groups received conventional treatments and acupuncture treatment 5 days a week for 4 weeks. The main acupoints in both groups were the same, while participants in the intervention group received additional acupoints selected on the basis of 3DKA results. Follow-up assessments were conducted for 8 weeks after the treatment. MAIN OUTCOME MEASURES: The primary outcome was the Fugl-Meyer Assessment for Upper Extremity (FMA-UE) response rate (≥ 6-point change) at week 4. Secondary outcomes included changes in motor function (FMA-UE), Brunnstrom recovery stage (BRS), manual muscle test (MMT), spasticity (Modified Ashworth Scale, MAS), and activities of daily life (Modified Barthel Index, MBI) at week 4 and week 12. RESULTS: Sixty-four participants completed the trial and underwent analyses. Compared with control group, the intervention group exhibited a significantly higher FMA-UE response rate at week 4 (χ² = 5.479, P = 0.019) and greater improvements in FMA-UE at both week 4 and week 12 (both P < 0.001). The intervention group also showed bigger improvements from baseline in the MMT grades for shoulder adduction and elbow flexion at weeks 4 and 12 as well as thumb adduction at week 4 (P = 0.007, P = 0.049, P = 0.019, P = 0.008, P = 0.029, respectively). The intervention group showed a better change in the MBI at both week 4 and week 12 (P = 0.004 and P = 0.010, respectively). Although the intervention group had a higher BRS for the hand at week 12 (P = 0.041), no intergroup differences were observed at week 4 (all P > 0.05). The two groups showed no differences in MAS grades as well as in BRS for the arm at weeks 4 and 12 (all P > 0.05). CONCLUSION: Semi-personalized acupuncture prescription based on 3DKA results significantly improved motor function, muscle strength, and activities of daily living in patients with PSSP-UL. TRIAL REGISTRATION Chinese Clinical Trial Registry ChiCTR2200056216. Please cite this article as: Huang XY, Liao OP, Jiang SY, Tao JM, Li Y, Lu XY, Li YY, Wang C, Li J, Ma XP. Three-dimensional kinematic analysis can improve the efficacy of acupoint selection for post-stroke patients with upper limb spastic paresis: A randomized controlled trial. J Integr Med. 2025; 23(1): 15-24.
Humans ; Male ; Female ; Middle Aged ; Acupuncture Points ; Upper Extremity/physiopathology* ; Biomechanical Phenomena ; Single-Blind Method ; Aged ; Stroke/therapy* ; Acupuncture Therapy/methods* ; Stroke Rehabilitation/methods* ; Adult ; Muscle Spasticity/therapy* ; Paresis/physiopathology* ; Treatment Outcome

OBJECTIVE: The present study evaluated the effects of deep acupuncture at Weizhong acupoint (BL40) on bladder function and brain activity in a rat model of overactive bladder (OAB), and investigated the possible mechanisms around the acupuncture area that initiate the effects of acupuncture. METHODS: Adult female Sprague-Dawley rats were randomly divided into six groups, comprising a control group, model group, group treated with deep acupuncture at BL40, group treated with shallow acupuncture at BL40, group treated with acupuncture at non-acupoint next to BL40, and group treated with acupuncture at Xuanzhong (GB39). Urodynamic evaluation was used to observe the urination, and functional magnetic resonance imaging was used to observe the brain activation. The mechanism of acupuncture at BL40 in regulating bladder function was explored by toluidine blue staining and enzyme-linked immunosorbent assay, and the mechanism was verified by stabilizing mast cells (MCs) or blocking tibial nerve. RESULTS: Deep acupuncture at BL40 significantly increased the intercontraction interval in OAB rats and enhanced the mean amplitude of low frequency fluctuation of primary motor cortex (M1), periaquaductal gray matter (PAG), and pontine micturition center (PMC). It also increased the zero-lag functional connectivity between M1 and PAG and between PAG and PMC. Shallow acupuncture at BL40 and acupuncture at non-acupoint or GB39 had no effect on these indexes. Further studies suggested that deep acupuncture at BL40 increased the number and degranulation rate of MCs as well as the contents of 5-hydroxytryptamine, substance P, and histamine in the tissues around BL40. Blocking the tibial nerve by lidocaine injection or inhibiting MC degranulation by sodium cromoglycate injection obstructed the effects of acupuncture on restoring urinary function and modulating brain activation in OAB rats. CONCLUSION Deep acupuncture at BL40 may be more effective for inhibiting OAB by promoting degranulation of MCs around the acupoint and stimulating tibial nerve, thereby regulating the activation of the brain area that controls the lower urinary tract. Please cite this article as: Liu X, Zhang CY, Du XY, Li SS, Wang YQ, Zheng Y, Deng HZ, Fang XQ, Li JY, Wang ZQ, Xu SF, Mi YQ. Acupuncture at Weizhong (BL40) attenuates acetic acid-induced overactive bladder in rats by regulating brain neural activity through the modulation of mast cells and tibial nerves. J Integr Med. 2025; 23(1): 46-55.
Animals ; Urinary Bladder, Overactive/physiopathology* ; Mast Cells/physiology* ; Rats, Sprague-Dawley ; Female ; Acupuncture Therapy ; Acupuncture Points ; Rats ; Brain/physiopathology* ; Tibial Nerve/physiopathology* ; Acetic Acid ; Urinary Bladder/physiopathology*

Gastric ulcer (GU) is a common digestive system disease. Acupuncture, as one of the external treatments of traditional Chinese medicine (TCM), has the characteristics of multi-target, multi-pathway and multi-level action in the treatment of GU. The relationship between meridian points and Zang-fu is an important part of the theory of TCM, which is crucial for the diagnosis and treatment of diseases. There is an external and internal link between acupoints and Zang-fu. The pathological reaction of Zang-fu can manifest as acupoint sensitization, while stimulation of acupoints can play a therapeutic role in the internal Zang-fu. Therefore, the acupoint has the functions of reflecting and treating diseases. This review explores the tender points on the body surface of patients with GU and the rules of acupoint selection. In addition, Zusanli (ST36), as one of the most used acupoints of the stomach meridian, was selected to show the mechanisms behind acupoint stimulation in the treatment of GU in greater detail, specifically in the well-studied model of the stress GU (SGU). Hence, the mechanisms of acupuncture at ST36 and points commonly used in combination with ST36 to treat SGU are discussed further. Treatment effects can be achieved through anti-inflammatory and antioxidant activities, gastric mucosal injury repair, and interaction with the brain-gut axis. In summary, this review provides evidence for a comprehensive understanding of the phenomena and mechanism of acupoint functions for GU. Please cite this article as: He M, Lim XY, Li J, Li L, Zhang T. Mechanisms of acupuncture at Zusanli (ST36) and its combinational acupoints for stress gastric ulcer based on the correlation between Zang-fu and acupoints. J Integr Med. 2025; 23(1): 1-11.
Acupuncture Points ; Humans ; Stomach Ulcer/therapy* ; Acupuncture Therapy/methods* ; Animals ; Meridians

BACKGROUND: There is a gap in understanding the effects of different acupoints and treatment methods (acupuncture and moxibustion) on microcirculatory changes in the lumbar region. OBJECTIVE: This study aimed to assess the thermal effects of acupuncture at Weizhong (BL40), with acupuncture at Chize (LU5) and moxibustion at both acupoints as control interventions. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: In this randomized controlled trial, 140 healthy participants were equally divided into four groups: acupuncture at BL40 (Acu-BL40), acupuncture at LU5 (Acu-LU5), moxibustion at BL40 (Mox-BL40) and moxibustion at LU5 (Mox-LU5). Participants underwent a 30-minute session of their assigned treatment. Infrared thermal imaging was used to collect temperature data on the areas of interest for analysis. MAIN OUTCOME MEASURES: The primary measure was the change in average temperature of the observed area after the intervention. The secondary measures included periodic temperature changes every 5 min and the temperature changes of the Governor Vessel and Bladder Meridian in the observed area after the intervention. RESULTS: Significant interactions were observed between treatments and acupoints affecting temperature (P < 0.001). The Acu-BL40 group showed a notably higher increase in mean temperature after 30 min compared to the Acu-LU5 and Mox-BL40 groups, with increases of 0.29 (95% confidence interval [CI] = 0.17 to 0.41) and 0.24 (95% CI = 0.08 to 0.41) °C, respectively. CONCLUSION: Acupuncture at BL40 acupoint can significantly increase the mean temperature in the observed area, highlighting the specific thermal effect of acupuncture compared to moxibustion in the lumbar area. This suggests a potential therapeutic benefit of acupuncture at BL40 for managing lumbar conditions. TRIAL REGISTRATION ClinicalTrials.gov (NCT05665426). Please cite this article as: Zheng SY, Wang XY, Lin LN, Liu S, Huang XX, Liu YY, Yu XS, Pan W, Fang JQ, Liang Y. Lumbar temperature change after acupuncture or moxibustion at Weizhong (BL40) or Chize (LU5) in healthy adults: A randomized controlled trial. J Integr Med. 2025; 23(2): 145-151.
Adult ; Female ; Humans ; Male ; Young Adult ; Acupuncture Points ; Acupuncture Therapy ; Body Temperature ; Healthy Volunteers ; Lumbosacral Region/physiology* ; Moxibustion ; Adolescent