Effect of electroacupuncture of "Jiaji" (EX-B2) on NOD-like receptor protein 3 mediated pyroptosis in spinal cord tissue of rats with acute spinal cord injury. / å¤¹è„Šç”µé’ˆå¯¹æ€¥æ€§è„Šé«“æŸä¼¤å¤§é¼ è„Šé«“ç»„ç»‡NODæ ·å—ä½“çƒ­è›‹ç™½ç»“æž„åŸŸç›¸å ³è›‹ç™½3介导的细胞焦亡的影响.

OBJECTIVES: To observe the effect of electroacupuncture (EA) stimulation of "Jiaji"(EX-B2) on motor function, histomorphology, and expression of NOD-like receptor protein 3 (NLRP3) and N-terminal domain of gasdermin D (GSDMD-N) in the spinal cord tissue of rats with spinal cord injury (SCI), so as to explore its mechanism underlying improvement of SCI. METHODS: Forty eight female SD rats were randomly divided into sham surgery (sham), SCI model (model), EA, and NLRP3 agonist (monosodium urate, MSU) combined with Jiaji EA (MSU+EA) groups, with 12 rats in each group which were further divided into 3 d and 7 d subgroups, with 6 rats at each time point. Two EA groups received EA stimulation of EX-B2 with a frequency of 100 Hz, electrical current of 1-2 mA for 30 min, once a day for 3 or 7 days. After 5 min, 6 h, and 24 h of modeling, rats of the MSU+EA group received intraperitoneal injection of MSU (200 µg/kg, 200 µg/mL) . The motor function was evaluated using Basso-Beattie-Bresnahan (BBB) scale, the morphological structure of rat spinal cord tissue was observed by H.E. staining. The expression of pyroptosis related factors NLRP3, cleaved Caspase-1 and GSDMD-N of the spinal cord was observed by using immunohistochemistry and Western blot separately, the expression and localization of Iba-1 and GSDMD-N in the spinal cord tissue were observed using immunofluorescence double staining method. RESULTS: Compared with the sham group, the BBB scores after modeling and on day 3 and 7 were decreased (P<0.05), while the average OD values (immunoactivity) and expression levels of NLRP3, cleaved Caspase-1 and GSDMD-N proteins, and the immunofluorescence intensity of Iba-1/GSDMD-N (co-expression) of the spinal cord tissues on day 3 and 7 were significantly increased in the model group (P<0.05). In comparison with the model group, the BBB scores on day 3 and 7 were obviously increased (P<0.05), while the immunoactivity and expression levels of NLRP3, cleaved Caspase-1 and GSDMD proteins, and the immunofluorescence intensity of Iba-1/GSDMD-N on day 3 and 7 significantly down-regulated in the EA group (P<0.05) but not in the MSU+EA group (P>0.05), suggesting an elimination of the effects of EA after administration of NLRP3 agonist (MSU). H.E. staining showed obvious bleeding area in the spinal cord tissue, loose tissue and inflammatory cell infiltration on day 3 after modeling, and basic absorption of the bleeding, loose tissue, obvious vacuolar changes of the white matter area, loss and contraction of neurons with infiltration of a large number of inflammatory cells, which was milder in the EA group but not in the MSU+EA group. CONCLUSIONS: EA of EX-B2 can improve the motor function of SCI rats, which may be related to its functions in inhibiting pyroptosis of microglia mediated by NLRP3/Caspase-1 signaling pathway.

Acupuncture activates IRE1/XBP1 endoplasmic reticulum stress pathway in Parkinson's disease model rats.

Acupuncture has demonstrated its efficacy as a treatment for Parkinson's disease (PD). Thus, the objective of this study was to investigate the potential mechanisms underlying acupuncture's effects on PD treatment. Our approach involved several steps. Firstly, we assessed the behavioral changes in PD rats, the modulation of dopamine (DA) and 5-hydroxytryptamine (5-HT) levels in the striatum, as well as the alteration in α-synuclein (α-syn) levels in the midbrain, aiming to evaluate the efficacy of acupuncture in PD treatment. Secondly, we selected endoplasmic reticulum (ER) stress inhibitors and activators to assess the impact of ER stress on PD rats. Lastly, we utilized an IRE1 inhibitor to observe the influence of acupuncture on the IRE1/XBP1 pathway in PD rats. The findings of this study revealed that acupuncture improved the autonomous motor function, balance ability, coordination, and sensory motor integration function in the PD model rats. Additionally, it increased the levels of DA and 5-HT in the striatum while decreasing the levels of α-syn in the midbrain. Acupuncture also activated the expression of ER stress in the midbrain and upregulated the expression of IRE1/XBP1 in the striatum of PD model rats. Based on these results, we concluded that acupuncture may enhance the behavior of PD rats by activating the IRE1/XBP1 ER stress pathway, associated with the reduction of midbrain α-syn expression and the increase in striatal DA and 5-HT levels in unilateral 6-OHDA lesioned rats.

The rapid antidepressant effect of acupuncture on two animal models of depression by inhibiting M1-Ach receptors regulates synaptic plasticity in the prefrontal cortex.

BACKGROUND: It is unclear whether acupuncture has a rapid antidepressant effect and what is the main mechanism. METHODS: In this study, forced swimming stress test (FST) in mice were divided into five groups: control group, acupuncture group, scopolamine group, arecoline group, and acupuncture + arecoline group. Chronic unpredictable mild stress (CUMS) model rats were divided into six groups: naïve (non-CUMS) group, CUMS group, acupuncture group, scopolamine group, arecoline group, and acupuncture + arecoline group. Twenty-four hours after the end of treatment, FST was conducted in mice and rats. The expression of M1-AchR, AMPA receptors (GluR1 and GluR2), BDNF, mTOR, p-mTOR, synapsin I, and PSD95 in the prefrontal cortex was determined by western blot. The spine density of neurons in the prefrontal cortex was detected by golgi staining. RESULTS: The results showed that acupuncture reduced the immobility time of FST in two depression models. Acupuncture inhibited the expression of M1-AchR and promoted the expression of GluR1, GluR2, BDNF, p-mTOR, synapsin I, PSD95, and increased the density of neuron dendritic spine in the prefrontal cortex. CONCLUSIONS: The rapid antidepressant effect of acupuncture may be activating the "glutamate tide" - AMPA receptor activation - BDNF release - mTORC1 pathway activation through inhibiting the expression of M1-AchR in the prefrontal cortex, thereby increasing the expression of synaptic proteins and regulating synaptic plasticity.

Sweet Gradient matters: Designing consistent and efficient estimator for Zero-shot Architecture Search.

Zero-shot Neural Architecture Search has garnered attention due to its training-free nature and rapid search speed. However, existing zero-shot estimators commonly suffer from low consistency, which hampers their practicality. In this work, we theoretically analyze that network generalization and convergence are highly correlated with Sweet Gradient of Parameter, i.e., the number of parameters whose gradient absolute values are within a certain interval. Empirical results indicate that Sweet Gradient of Parameter brings a higher consistency than the overall number of parameters. Additionally, we demonstrate a positive correlation between the network depth and the proportion of parameters with sweet gradients in each layer. Based on the analysis, we propose a training-free method to find the Sweet Gradient interval and obtain an estimator, named Sweetimator. Furthermore, Sweet Gradient can be an effective and general approach to promote the consistency of zero-shot estimators. Experiments show that Sweetimator and Sweet-enhanced estimators have significant consistency improvement in multiple benchmarks. Our method achieves state-of-the-art performance with 256x speedup in NAS-Bench-201 and maintains high competitiveness in DARTS, MobileNet, and Transformer search spaces. The source code is available at https://github.com/xingxing-123/SweetGradient.

[Research progress of acupuncture-moxibustion in treatment of spinal cord injury through mediating inflammatory reaction].

Inflammatory reaction after spinal cord injury (SCI) is the main obstacle to the recovery of neural function. In the occurrence and development of SCI, the complex regulatory mechanisms are involved in inflammatory reaction, including the activation of inflammatory cells (e.g.macrophages and microglia), and the release of cytokines (e.g. tumor necrosis factor, interleukin and chemokines). Acupuncture-moxibustion is significantly effective in clinical treatment of SCI, and its mechanism is related to adjusting the function of inflammatory cells after SCI, modulating the expression of cytokines and the activation of NLRP3 inflammatory bodies, as well as the expression of high mobility group protein B1 and calcitonin gene related peptide. This article summarizes the research progress of mechanism of inflammatory reaction after SCI and the effects of acupuncture-moxibustion intervention in recent years so that the new ideas can be provided to clarify the pathogenesis of SCI and the effect of acupuncture-moxibustion intervention.

Acupuncture inhibits autophagy and repairs synapses by activating the mTOR pathway in Parkinson's disease depression model rats.

Acupuncture is a good treatment for depression in Parkinson's disease (DPD), so the possible mechanism of acupuncture in the treatment of DPD was explored in this study. Firstly, observing the behavioral changes of the DPD rat model, the regulation of monoamine neurotransmitters dopamine (DA) and 5-hydroxytryptamine (5-HT) in the midbrain, the change of α-synuclein (α-syn) in the striatum, the efficacy of acupuncture in the treatment of DPD was discussed. Secondly, autophagy inhibitors and activators were selected to judge the effect of acupuncture on autophagy in the DPD rat model. Finally, an mTOR inhibitor was used to observe the effect of acupuncture on the mTOR pathway in the DPD rat model. The results showed that acupuncture could improve the motor and depressive symptoms of DPD model rats, increase the content of DA and 5-HT, and decrease the content of ɑ-syn in the striatum. Acupuncture inhibited the expression of autophagy in the striatum of DPD model rats. At the same time, acupuncture upregulates p-mTOR expression, inhibits autophagy, and promotes synaptic protein expression. Therefore, we concluded that acupuncture might improve the behavior of DPD model rats by activating the mTOR pathway, inhibiting autophagy from removing α-syn and repairing synapses.

[Professor LI Xiao-ning's experience for post-stroke dysphagia treated with penetrating-needling and swallowing technique of acupuncture].

Professor LI Xiaoning's experience for post-stroke dysphagia treated with penetrating-needling and swallowing technique of acupuncture is summarized in this paper. The key pathogenesis of this disease is dysfunction of zangfu organs, impairment of the house of mental activity and dysfunction of meridian sinew. Innovatively, the anatomic structure related to swallowing is divided into three zones. Based on the distributions of heart, kidney and stomach meridians on the neck, three lines are determined. Hence, the theory of "three-zone and three-line" as well as the penetrating-needling and swallowing technique of acupuncture are put forward. In this paper, the theoretic evidences of penetrating-needling and swallowing technique of acupuncture, point selection and manipulation in treatment of post-stroke dysphagia are introduced.

[Electroacupuncture Improves Limb Locomotor Function Possibly by Suppressing Rho-ROCK â ¡ Pathway Related Factors in Anterior Horns of Spinal Cord in Rats with Acute Spinal Cord Injury].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Jiaji" (EX-B 2) on limb locomotor function and expression of Ras homolog gene family member A (RhoA), Rho-associated kinase Ⅱ (ROCK Ⅱ) and myosin light chain (MLC) proteins in the anterior horn of spinal cord in acute spinal cord injury (ASCI) rats, so as to explore its mechanisms under-lying improvement of SCI-induced limb locomotor dysfunction. METHODS: Forty-eight female Wistar rats were randomly divided into sham operation (sham), ASCI model (model), EA EX-B 2 (EA) and ROCK inhibitor (Fasudil) groups which were further divided into 14 d and 28 d subgroups (n=6 in each). The ASCI model was made by using weight drop striking method. Three hours after modeling, EA (100 Hz, 0.4, 0.6 mA) was applied to EX-B 2 (T 9, T 11) for 30 min, once daily for 14 d and 28 d, respectively. The ROCK inhibitor (hydrochloride Fasudil, 10 mg/kg) was administrated by intraperitoneal injection immediately after modeling, once a day, continuously for 14 d or 28 d. The expression of RhoA, ROCK Ⅱ and MLC proteins in the spinal cord anterior horn tissue (T 10) was detected by immunohistochemistry. The rats' hindlimb locomotor function was assessed according to Basso, Beattie and Bresnahan (BBB) locomotor rating scale (21-points). RESULTS: After ASCI, the BBB scores were significantly lower in the model group than in the sham group on day 14 and 28 (P<0.05), and obviously higher in the EA and inhibitor groups than in the model group (P<0.05), suggesting an improvement of the hindlimb locomotor function after EA intervention or suppression of ROCK. Immunohistochemical results indicated that the numbers of RhoA, ROCK Ⅱ and MLC immune-reaction positive cells in the anterior horn of spinal cord were significantly more in the model group than in the sham group (P<0.05), and remarkably decreased in both EA and inhibitor groups on day 14 and 28 relevant to the model group (P<0.05). The therapeutic effects of EA were markedly weaker than those of inhibitor Fasudil in up-regulating BBB score and down-regulating the number of RhoA, ROCK Ⅱ and MLC positive cells (P<0.05). CONCLUSION: EA of EX-B 2 can improve the hindlimb locomotor function in ASCI rats, which may be associated with its effect in down-regulating the expression of RhoA, ROCK Ⅱ and MLC proteins (i.e., inhibiting the RhoA/ROCK signaling pathway) in the anterior horn of spinal cord.

[Effect of Electroacupuncture Intervention at Different Time-points on Locomotor Function and Apoptosis in Rats with Acute Spinal Cord Injury].

OBJECTIVE: To observe the effect of electroacupuncture (EA) intervention at different treatment time-points on locomotor function and neuronal apoptosis in rats with acute spinal cord injury (ASCI), so as to explore its mechanism under-lying improvement of ASCI. METHODS: Seventy-two female Wistar rats were randomly divided into sham operation, ASCI model and EA groups which were further divided into 4 time-points:1, 3, 7 and 14 d (n=6 at each). The ASCI model was established by weight-drop striking the exposed spinal cord (T10) using a NYU impactor device. EA (0.4-0.6 mA, 100 Hz) was applied to bilateral "Jiaji" (EX-B 2) for 30 min, once a day for 1, 3, 7 and 14 days, respectively in the EA group. The Basso-Beattie-Bresnahan (BBB) grading score was used to assess the animals' locomotor function, and H.E. staining was used to display the pathological changes of spinal cord injury at different time points. The TUNEL staining was used to detect the nerve cell apoptosis of spinal cord tissue. RESULTS: After ASCI, the BBB scores were significantly decreased and the numbers of the apoptotic nerve cells considerably increased on day 1, 3, 7 and 14 in the model group compared with the sham operation group (P<0.05). In addition, H.E. staining showed severe damage of the spinal cord tissue, infiltration of inflammatory cells, increase of dead nerve neurons and glia cells in the number from day 3 to 7, and additional increase of vacuoles on day 14. Following EA intervention, the decrease of BBB scores and the increase of apoptotic nerve cell numbers were markedly suppressed on day 3, 7 and 14 (P<0.05). The TUNEL staining showed a decrease of the apoptotic nerve cells from day 3 on and an improvement of the injured tissue structure from day 7 to 14 in the EA group. CONCLUSIONS: EA stimulation of EX-B 2 can significantly improve locomotor function, and lighten the spinal cord injury in ASCI rats, presenting a time-dependant tendency, which may be associated with its effect in reducing neuronal apoptosis in the spinal cord.