Effects of perioperative electroacupuncture on postoperative gastrointestinal recovery after thoracoscopic lung surgery.

OBJECTIVE: To study whether perioperative electroacupuncture (EA) can improve postoperative gastrointestinal recovery in patients receiving thoracoscopic lung surgery. METHODS: This study was a single-center, prospective, randomized open-label trial. 180 patients who underwent video-assisted thoracoscopic segmentectomy or lobectomy were randomized to EA group (three sessions, 24 h prior to surgery, postoperative 4 h and 24 h) or usual care group (UC group). The primary outcomes were time to first flatus and defecation. Secondary outcomes included incidence and degree of abdominal distention, postoperative nausea and vomiting (PONV) and pain scores within 72 h after surgery, postoperative morphine use, time to ambulation, and length of hospital stay. RESULTS: Time to first flatus (15.4 ± 3.2 h vs. 17.0 ± 3.7 h, P = 0.004) and time to first defecation (75.9 ± 7.9 vs. 79.7 ± 8.1 h, P = 0.002) in the EA group were significantly shorter than the UC group. The incidences of abdominal distension and PONV postoperative 24 h were significantly reduced in the EA group (P < 0.05). There was no difference in postoperative pain intensity, morphine use, time to ambulation, and length of hospital stay between the two groups (P>0.05). CONCLUSION: Electroacupuncture is a simple intervention for accelerating postoperative gastrointestinal recovery and may be considered as an adjunct strategy in enhanced recovery protocols in thoracoscopic lung surgery.

Effects of Preoperative Electroacupuncture on Remifentanil-Induced Post-Infusion Hyperalgesia in Patients Undergoing Thyroidectomy: A Double-Blind Randomized Controlled Trial.

Objective: Electroacupuncture (EA) delivered one day before surgery could reduce postoperative pain. Remifentanil-induced post-infusion hyperalgesia (RPH) was occurred after exposure to high-dose remifentanil. This study aimed to investigate the effects of preoperative EA on RPH in patients undergoing thyroidectomy. Methods: A total of 80 patients who were scheduled to undergo elective thyroidectomy were randomly assigned to two groups: an EA group and a sham EA (SEA) group. EA was delivered at the Zusanli (ST36) and Neiguan (PC6) acupoints 24 h before the surgery. To ensure uniformity across all patients, remifentanil was administered at the same set rate (0.3 µg/kg/min) to all patients. Mechanical pain thresholds were recorded by an electronic von Frey device around the skin incision and on the arm before surgery as well as at 30 min and 6, 24, and 48 h after surgery. Results: At 30 min and 6 h after surgery, the EA group showed considerably greater mechanical pain thresholds surrounding the surgical site compared with the SEA group. At 30 min and 6 h after surgery, the patients in the SEA group showed a greater incidence of postoperative hyperalgesia surrounding the surgical site than those in the EA group. At 24 and 48 h after surgery, no significant differences were found between the two groups, although the pain intensity of the EA group was less than that of the SEA group. There were also no substantial differences between the two groups in the frequency of postoperative adverse reactions and rescue analgesia needed. Conclusion: EA administered 24 h before surgery could alleviate RPH in patients undergoing thyroidectomy.

Electroacupuncture relieves postoperative cognitive dysfunction in elderly rats via regulating amp-activated protein kinase autophagy signaling.

Postoperative cognitive dysfunction (POCD) is a common complication after surgery in elderly patients. Electroacupuncture (EA) has been reported to relieve POCD in animal models, but the mechanism remains fully elucidated. The objective of this work was to clarify whether EA could alleviate POCD via regulating autophagy. In this study, aged rats were assigned into 4 groups: control, surgery (rats underwent exploratory laparotomy to induce POCD), EA + S (rats received EA pre-stimulation before surgery), and EA + S + Chloroquine (CQ) (rats were intraperitoneally injected with CQ before EA stimulation and then underwent surgery). The cognitive function of rats was assessed by Morris Water Maze (MWM) test after surgery, and autophagy in hippocampal tissues of rats was evaluated by western blotting and transmission electron microscope. Results indicated that the MWM test revealed that rats showed reduced platform crossing and increased total swimming distance after surgery. However, this impaired spatial memory was improved by EA and EA plus CQ pre-treatment. Besides, the surgery caused an increased expression in LC3II, Beclin-1, AMP-activated protein kinase (AMPK), and p-AMPK in hippocampal tissues of rats, while EA and EA plus CQ pre-treatment also reversed this effect. In addition, the surgery-induced increased amount of autophagic vesicles in hippocampal tissues of rats was reduced by EA and EA plus CQ pre-treatment. In conclusion, EA pre-stimulation could effectively attenuate cognitive impairment in aged rats with POCD via inhibiting AMPK signaling-mediated autophagy.

Electroacupuncture attenuates spared nerve injury-induced neuropathic pain possibly by promoting the progression of AMPK/mTOR-mediated autophagy in spinal microglia.

Background: Neuropathic pain (NP) is a syndrome that arises from central or peripheral nerve injury, which manifests primarily as hyperalgesia, spontaneous pain, and allodynia. The recent trend has exhibited a shift towards the development of therapies for managing NP. Activation of autophagy is involved in the function of the glial cells, which may be implicated further to attenuate pain. Methods: In this study, the analgesic effects of electroacupuncture (EA) were evaluated among NP rats developed using spared nerve injury (SNI). Acupuncture treatment or EA was carried out after 7 days of SNI at two acupoints, i.e., the Zusanli (ST36) and Huantiao (GB30). Results: The application of EA was found to attenuate mechanical hyperalgesia. The marker protein for microglial cells (CD11b) alone, without either the astrocyte marker or neuronal marker, was co-expressed with the autophagy indicator p62, as illustrated with immunofluorescence staining. Western blotting demonstrated that the expression levels of p62, Beclin-1, and LC3-II/LC3-I were elevated in the spinal cords of rats in the SNI group compared to the control levels. EA treatment resulted in reduced expression of p62, while the expressions of Beclin-1 and LC3-II/LC3-I were increased. The electron microscopy results indicated that EA could induce autophagy progression in the microglia of the spinal dorsal horn in SNI rats. Furthermore, we explored the causal relationship between EA-induced inhibition of NP and increased autophagic levels in microglia using the AMPK inhibitor compound C, and found that the mechanism of EA-induced analgesia may contribute to the promotion of AMPK/mTOR-mediated autophagy in spinal microglia. Conclusions: Our work showed that the analgesic impact of EA is partly related to AMPK/mTOR pathway activation and autophagy induction in microglial cells, providing a potential therapeutic target for NP.

Electroacupuncture Before Gastrectomy Accelerates Recovery from Gastrointestinal Dysfunction: A Feasibility Study.

Objective: This study investigated the feasibility and effectiveness of preoperative electroacupuncture (EA), given within 30 minutes before surgery, on postoperative gastrointestinal dysfunction (PGD) in patients undergoing open gastrectomy. Materials and Methods: Patients (N = 60) undergoing open gastrectomy were allocated randomly to a usual care (UC) group (n = 30) or an EA group (n = 30). Patients in the EA group were given bilateral EA on ST-36 (Zusanli), ST-37 (Shangjuxv), and ST-39 (Xiajuxv) within 30 minutes before the surgery. The UC group had no acupuncture treatment. Primary outcomes were feasibility of recruitment, retention, acceptability, and patients' global satisfaction. Secondary outcomes included time to first flatus, defecation, liquid diet, incidence and severity of abdominal distension (AD), and incidence of postoperative nausea (PON) and postoperative vomiting (POV). EA-related adverse events were recorded. Results: Of the 61 recruited patients, 1 declined to participate and 60 were randomized into the 2 study groups. All participants completed the interventions. On the acceptability questionnaire, participants' acceptance of EA was statistically improved after the treatment (P < 0.001). Global satisfaction was higher in the EA group (P < 0.001) at 8 (range: 7-8) versus the UC group at 6 (range: 5-7), and the proportion of patients with at least good satisfaction (numerical scale of more than 7 of 10) reached 80% in the EA group. Compared to the UC group, the EA group had a shorter time to first flatus (EA: 57.67 ± 23.09 hours versus 71.27 ± 17.78 hours; P = 0.013). There were no significant differences in time to first defecation (P = 0.081) and liquid diet (P = 0.068), AD (P = 0.436), PON (P = 0.667), or POV (P = 1.000). EA-related adverse events were similar in the 2 groups (P = 1.000). Conclusions: EA is feasible, acceptable to patients, and associated with higher postoperative satisfaction in patients undergoing open gastrectomy. A large multicentered trial is needed to test the effectiveness of EA on PGD.

Electroacupuncture alleviates neuropathic pain caused by spared nerve injury by promoting AMPK/mTOR-mediated autophagy in dorsal root ganglion macrophage.

Background: Dorsal root ganglia (DRG) plays an important role in mediating the peripheral sensation transduction through the primary afferent neurons in pain research. Neuropathic pain (NP) is a syndrome of hyperalgesia, spontaneous pain and allodynia caused by central or peripheral nerve injury. Recent trends of study are turning towards the development of therapies for the management of NP. Activation of autophagy in glial cells in the spinal cord has been reported to be associated with attenuation of NP, but the autophagic process in DRG is rarely studied. Methods: The analgesic effect of electroacupuncture (EA) was evaluated in NP-induced rats developed using spared nerve injury (SNI). Acupuncture or EA was performed after 7 days of SNI at Zusanli (ST36) and Huantiao (GB30) acupoints. Then, the activation status of autophagy process in DRGs of rats treated with SNI and EA were investigated, and the possible mechanism of the analgesic effect of EA were explored. Results: Application of EA has been found to reduce mechanical hyperalgesia. Autophagy indicator p62 was colocalized with the marker proteins for macrophages (CD11b), but not with NeuN (marker protein for neurons) or GFAP (marker protein for satellite glial cells), as shown by immunofluorescence. Western blots results indicate that the expression levels of p62, Beclin-1 and LC3-II in the L4-L6 DRG of rats in the SNI group were increased, compared with that in the control group. EA treatment resulted in decreased expression of p62 and increased expression of Beclin-1 and LC3-II/LC3-I. Furthermore, we explored the causal relationship between EA-induced suppression of NP and increased levels of autophagy in DRG using electron microscopy and the AMPK (AMP-activated protein kinase) inhibitor compound C. Conclusions: SNI achieved a significant upregulation of autophagy levels in DRG macrophages. Furthermore, EA attenuated NP, which may contribute to the promotion of AMPK/mTOR (mammalian target of rapamycin)-mediated autophagy in DRG macrophages. Therefore, this strategy provides a new target for therapeutic intervention of NP.

Electroacupuncture Pretreatment Alleviates Cerebral Ischemia-Reperfusion Injury by Regulating Mitophagy via mTOR-ULK1/FUNDC1 Axis in Rats.

OBJECTIVE: Electroacupuncture (EA) pretreatment has been shown to alleviate cerebral ischemia-reperfusion (I/R) injury; however, the underlying mechanism remains unclear. To investigate the involvement of mTOR signaling in the protective role of EA in I/R-induced brain damage and mitochondrial injury. METHODS: Sprague-Dawley male rats were pretreated with vehicle, EA (at Baihui and Shuigou acupoints), or rapamycin + EA for 30 min daily for 5 consecutive days, followed by the middle cerebral artery occlusion to induce I/R injury. The neurological functions of the rats were assessed using the Longa neurological deficit scores. The rats were sacrificed immediately after neurological function assessment. The brains were obtained for the measurements of cerebral infarct area. The mitochondrial structural alterations were observed under transmission electron microscopy. The mitochondrial membrane potential changes were detected by JC-1 staining. The alterations in autophagy-related protein expression were examined using Western blot analysis. RESULTS: Compared with untreated I/R rats, EA-pretreated rats exhibited significantly decreased neurological deficit scores and cerebral infarct volumes. EA pretreatment also reversed I/R-induced mitochondrial structural abnormalities and loss of mitochondrial membrane potential. Furthermore, EA pretreatment downregulated the protein expression of LC3-II, p-ULK1, and FUNDC1 while upregulating the protein expression of p-mTORC1 and LC3-I. Rapamycin effectively blocked the above-mentioned effects of EA. CONCLUSION: EA pretreatment at Baihui and Shuigou alleviates cerebral I/R injury and mitochondrial impairment in rats through activating the mTORC1 signaling. The suppression of autophagy-related p-ULK1/FUNDC1 pathway is involved in the neuroprotective effects of EA.

Effects of Gentiopicroside on activation of NLRP3 inflammasome in acute gouty arthritis mice induced by MSU.

Acute gouty arthritis is a self-limiting inflammatory disease resulting from the deposition of monosodium urate (MSU) crystals. It has been shown that Gentiopicroside (GPS) possesses anti-inflammatory and analgesic functions. The aim of this study was to parse out whether GPS has an effect on acute gouty arthritis. We established an acute gouty arthritis model by the injection of MSU into the paw, and found that GPS relieves MSU-induced mechanical, thermal hyperalgesia, and paw swelling. Furthermore, GPS down-regulated the release of pro-inflammatory cytokines in paw tissues, including IL-1ß, IL-6, IL-18, and TNF-α. The results of H&E staining and MPO activity measurement showed that GPS inhibits neutrophil infiltration. And the over-expressions of NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and Caspase-1 induced by MSU were inhibited by treatment with GPS. These results revealed that GPS can treat acute gouty arthritis based on anti-inflammatory and analgesic properties in vivo, which might be ascribed to the inhibition on NLRP3 inflammasome. Furthermore, we performed in vitro study to confirm the results of in vivo study. Consistently, the results proved that GPS could inhibit the activation of NLRP3 inflammasome in RAW264.7 macrophages stimulated by LPS-MSU. In conclusion, this study provides an experimental basis for the application of GPS and expands the potential value of GPS in the therapy of acute gouty arthritis.

[Transcutaneous electrical acupoint stimulation promotes general anesthesia recovery in patients undergoing gastrointestinal surgery].

OBJECTIVE: To observe the effect of transcutaneous electrical acupoint stimulation (TEAS) on the recovery of patients undergoing gastrointestinal surgery under general anesthesia. METHODS: Sixty patients (ASA Ⅱ-Ⅲ) selected for scheduled gastrointestinal surgery were randomly divided into control group and TEAS group (n=30 cases per group). Patients in the two groups received general anesthesia, and those of the TEAS group also received TEAS for 30 min (8-12 mA) immediately after surgery. The changes of systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) before anesthesia, before acupoint stimulation, before extubation, immediately after extubation, 10 and 30 min after extubation were recorded. The recovery time of spontaneous breathing, extubation time, VAS scores and Bruggman comfort scale (BCS) scores at the time of discharging from postanesthesia care unit (PACU) were recorded. RESULTS: Compared with the control group, the recovery time of spontaneous breathing and extubation time were significantly shorter （P<0.05）, the VAS score was significantly lower (P<0.05), and the BCS score significantly increased in the TEAS group (P<0.05). There were no significant differences between two groups in the levels of SBP, DBP and HR at each time point (P>0.05). CONCLUSION: TEAS can accelerate the gastrointestinal surgery patients' recovery from general anesthesia, enhance the postoperative analgesic effect, improve patients' discomfort, has less adverse reactions, and is thus conducive to promote the postoperative rehabilitation.

[Application of transcutaneous electrical acupoint stimulation in perioperative period].

Transcutaneous electrical acupoint stimulation (TEAS) has the characteristics of simple operation, non-invasive, and high patient acceptability, and is widely used in clinical practice. This article summarized the effects of TEAS on analgesia, gastrointestinal tract regulation, circulation regulation, postoperative cognitive function improvement, immune function regulation, anti-inflammatory and anti-stress during the perioperative period. At the same time, this article analyzed the problems of the application of TEAS in the perioperative period, and aimed to promote its clinical application.

Electroacupuncture Pretreatment against Cerebral Ischemia/Reperfusion Injury through Mitophagy.

Cerebral ischemia/reperfusion (I/R) injury can induce the mitophagy of neurons in the ischemic brain. Electroacupuncture (EA) pretreatment has a protective effect on cerebral ischemia/reperfusion injury. However, its internal mechanism still needs to be further studied. The present study's purpose is to investigate whether mitophagy is involved in neuroprotection elicited by EA pretreatment in a rat model of cerebral ischemia/reperfusion injury. The rats were pretreated with vehicle, EA at the Baihui (GV20) and Shuigou (GV26) acupoints 30 min daily, for 5 days consecutively prior to the focal cerebral ischemia injury induced by the middle cerebral artery occlusion (MCAO) model. Compared to the sham group, the neurological scores, infarction volume, number of autophagosomes, FUNDC1, p62, and the ratio of LC3-II/I were significantly increased but mitochondrial membrane potential and autophagy-related protein p-mTORC1 significantly decreased in the I/R group. However, EA pretreatment significantly reversed these trends. Overall, the results of this study demonstrated that EA pretreatment protected the cerebral ischemia/reperfusion injury which maybe correlated with mitophagy.

Study on metastasis inhibition of Kejinyan decoction on lung cancer by affecting tumor microenvironment.

BACKGROUND: Kejinyan decoction, as an experienced formula of Zhou Zhongying (the Master of Traditional Chinese Medicine) has been widely used in clinic for lung cancer treatment in China, while the anti-lung cancer mechanism of it is still remained to be elucidated. Herein, our basic study found that the survival of lung cancer xenograft mice was significantly prolonged after intragastrically administered high dose of Kejinyan decoction (3.8 g per kg BW) for 15 days. More importantly, we found that Kejinyan decoction inhibited the metastasis of lung cancer cells in vivo. Thus in this study, we aim to elucidate the anti-metastasis effects of Kejinyan decoction. METHODS: RNA-Seq was used to find out the gene regulation of Kejinyan decoction on the mice, flow cytometry assay was used to detect the immunocytes in the spleen, ELISA assay was used to detect the inflammatory factors in the serum and spleen, and immunofluorescence assay was used to detect the level of immune cells and the expression of glycol-metabolism related enzymes in situ. Also, we established a lung cancer orthotopic xenograft tumor model to assess the influence of Kejinyan decoction on the metastatic ability of lung cancer cells in vivo. RESULTS: GO analysis of gene sequencing of tumor tissue samples showed that Kejinyan decoction regulated immune response. Further flow cytometry analysis of splenic lymphocyte showed that Kejinyan decoction upregulated M1 macrophages and downregulated M2 macrophages, while the total level of macrophages changed little, which was verified by detection of CD68, F4/80, CD206, and CD86 in tumor tissue section. Moreover, detection of inflammatory cytokines showed that Kejinyan decoction downregulated TNF-α, IFN-γ, IL-6, as well as IL-4, IL-13 in tumor microenvironment. Further studies also showed that Kejinyan decoction had little effect on tumor hypoxia, but downregulated glycolysis in tumor tissues. More importantly, we found that Kejinyan decoction inhibited the metastasis of lung cancer cells in vivo. CONCLUSION: Our findings conclude that Kejinyan decoction inhibited lung cancer cell metastasis through affecting macrophage polarization and energy reprogramming.

Effect of Electroacupuncture on Postoperative Gastrointestinal Recovery in Patients Undergoing Thoracoscopic Surgery: A Feasibility Study.

BACKGROUND The aim of this study was to study the feasibility and acceptability of electroacupuncture (EA) for preventing postoperative gastrointestinal complications in patients undergoing thoracoscopic segmentectomy/lobectomy. MATERIAL AND METHODS Sixty patients who underwent video-assisted thoracoscopic (VATS) segmentectomy/lobectomy received either EA treatments plus usual care (EA group) or usual care alone (UC group). Patients in the EA group were given 30 minutes of bilateral electroacupuncture on 3 acupoints [Neiguan (PC6), Zusanli (ST36), and Shangjuxu (ST37)] at 3 time points (24 hours before surgery, and 4 hours and 24 hours after surgery). The primary outcomes were recruitment, retention, acceptability of the EA intervention, incidence and severity of abdominal distension (AD), and time to first flatus and defecation. Secondary outcomes included postoperative nausea and vomiting (PONV), pain intensity, and duration of hospital stay. RESULTS We recruited 60 participants and 59 were randomized into 2 groups for this study: 30 in the EA group and 29 in the UC group. In total, 57 participants completed the study. With the exception of one participant in the EA group, all participants completed all three sessions of EA. The one exclusion was a case where a paravertebral block was not used during the surgery. Qualitative findings from the acceptability questionnaire indicated that participants viewed the EA treatment as acceptable. After EA treatment, there was a small but statistically significant improvement in participants' acceptance of EA for alleviating postoperative gastrointestinal discomfort (P=0.001). The EA group showed improved outcomes compared to the UC group in terms of time to first flatus (20.8±4.6 versus 24.1±6.2 hours, P=0.026) and defecation (53.9±6.0 versus 57.5±7.2 hours, P=0.046). No significant differences appeared regarding AD, rescue medication, or duration of hospitalization. PONV and pain intensity were similar in both groups at the recorded time periods. CONCLUSIONS EA is feasible and acceptable to patients undergoing VATS surgery. Our preliminary findings of EA promoting postoperative recovery of gastrointestinal function warrants large randomized controlled trials.

Effects of electroacupuncture of different intensities on energy metabolism of mitochondria of brain cells in rats with cerebral ischemia-reperfusion injury.

OBJECTIVE: To observe the effects of electroacupuncture (EA) of different intensities on lactate dehydrogernase (LDH), succinate dehydrogenase (SDH) and ATPase in brain tissue of rats with cerebral ischemia-reperfusion injury (CI/R). METHODS: Forty male SD rats were uniformly randomized into sham operation group (group A), CI/R group (group B), CI/R+5 mA EA (group C), CI/R+3 mA EA (group D) and CI/R+1 mA EA (group E) groups with eight rats in each group. Transient general brain ischemia was induced by four-vessel occlusion and reperfusion. The rats in group C, group D and group E were punctured and stimulated at Baihui (GV20), Mingmen (GV4) and Zusanli (ST36) with the same intermittent and rarefaction-dense wave (30 to 50 Hz) and different electric current intensities: 5 mA, 3 mA and 1 mA for 20 min after CI/R. Then the activities of Na(+)-K(+)-ATPase, SDH and LDH in mitochondria of brain tissue were measured by spectrophotometry. The ischemic cerebral cortex tissue was taken for observing the ultrastructure changes of impaired nerve cells. RESULTS: Compared with group A, the activities of LDH, SDH and Na(+)-K(+)-ATPase were lowerer in the group B (P<0.05 or P<0.01). However, the activities of LDH, SDH and Na(+)-K(+)-ATPase were higher in the group D than those in the group B (P<0.05 orP<0.01). In group A, the anatomical structure of the cerebral cortex cells was basically normal; in group B, the neuronal cellular structures were severely damaged, the neuronal mitochondria got swelling, the mitochondrial cristae were broken, the medullated nerve fifibers were not integrated. In group C, group D and group E, the ultrastructure of impaired neuron were improved. Group D was the best among three groups above. CONCLUSION: EA of 3 mA intensity could strengthen aerobic metabolism by elevating the activities of SDH and LDH, meanwhile maintaining the ionic equilibrium in the exterior and interior brain cell and relieving the cellular edema by reinforcing the activities of Na(+)-K(+)-ATPase.

Preparing two-dimensional microporous carbon from Pistachio nutshell with high areal capacitance as supercapacitor materials.

Two-dimensional (2D) porous carbon AC-SPN-3 possessing of amazing high micropore volume ratio of 83% and large surface area of about 1069 m(2) g(-1) is high-yield obtained by pyrolysis of natural waste Pistachio nutshells with KOH activation. The AC-SPN-3 has a curved 2D lamellar morphology with the thickness of each slice about 200 nm. The porous carbon is consists of highly interconnected uniform pores with the median pore diameter of about 0.76 nm, which could potentially improve the performance by maximizing the electrode surface area accessible to the typical electrolyte ions (such as TEA(+), diameter = ~0.68 nm). Electrochemical analyses show that AC-SPN-3 has significantly large areal capacitance of 29.3/20.1 µF cm(-2) and high energy density of 10/39 Wh kg(-1) at power of 52/286 kW kg(-1) in 6 M KOH aqueous electrolyte and 1 M TEABF4 in EC-DEC (1:1) organic electrolyte system, respectively.