Electroacupuncture Promotes Liver Regeneration by Activating DMV Acetylcholinergic Neurons-Vagus-Macrophage Axis in 70% Partial Hepatectomy of Mice.

Lack of liver regenerative capacity is the primary cause of hepatic failure and even mortality in patients undergoing hepatectomy, with no effective intervention strategies currently available. Therefore, identifying efficacious interventions to enhance liver regeneration is pivotal for optimizing clinical outcomes. Recent studies have demonstrated that vagotomy exerts an inhibitory effect on liver regeneration following partial hepatectomy, thereby substantiating the pivotal role played by the vagus nerve in the process of liver regeneration. In recent years, electroacupuncture (EA) has emerged as a non-invasive technique for stimulating the vagus nerve. However, EA on hepatic regeneration remains uncertain. In this study, a 70% partial hepatectomy (PH) mouse model is utilized to investigate the effects of EA on acute liver regeneration and elucidate its underlying molecular mechanisms. It is observed that EA at ST36 acutely activated cholinergic neurons in the dorsal motor nucleus of the vagus nerve (DMV), resulting in increased release of acetylcholine from hepatic vagal nerve endings and subsequent activation of IL-6 signaling in liver macrophages. Ultimately, these events promoted hepatocyte proliferation and facilitated liver regeneration. These findings provide insights into the fundamental brain-liver axis mechanism through which EA promotes liver regeneration, offering a novel therapeutic approach for post-hepatectomy liver regeneration disorders.

Electroacupuncture treatment improves postoperative ileus by inhibiting the Th1 cell-mediated inflammatory response through the vagus nerve.

BACKGROUND: Electroacupuncture (EA) has been reported to improve intestinal motility in mice with postoperative ileus (POI). Previous studies, however, have yielded heterogeneous results regarding the effect of EA on POI. METHODS: Herein, a POI mouse model was constructed by intestinal manipulation. To evaluate the effect of EA treatment on colonic transit, the levels of inflammatory markers (macrophage inflammatory protein (MIP)-1α, interleukin (IL)-1ß, IL-6, monocyte chemotactic protein (MCP)-1 and intercellular adhesion molecule (ICAM)-1) were detected by enzyme-linked immunosorbent assay (ELISA); immune cell infiltration was detected by immunohistochemical staining of myeloperoxidase (MPO), ectodysplasin (ED)-1 and ED-2, and the percentage of CD4+ interferon (IFN)-γ+ Th1 cells and IFN-γ secretion levels were determined. Activated Th1 cells and pentoxifylline, a cell differentiation inhibitor, were used to assess the role of Th1 cells in EA treatment of POI. Neostigmine administration and unilateral vagotomy were performed to confirm whether the effects of EA treatment on Th1 cells were mediated by the vagus nerve (VN). RESULTS: The results revealed that EA treatment at ST36 improved POI, as indicated by a decreased level of inflammatory-related markers and immune cell infiltration and shortened colonic transit time. The activated Th1 cells abolished the effects of EA treatment on POI. The effects of EA treatment on POI were enhanced by stimulation of the VN along with a decreased level of Th1 cells, but these effects were abolished by vagotomy along with an increased percentage of Th1 cells; this result indicates that the VN mediates the role of Th1 cells in the effects of EA treatment of POI. CONCLUSION: Our findings showed that the effects of EA treatment of POI were mainly mediated by Th1 cells through the stimulation of the VN and inhibition of the inflammatory response.

Electroacupuncture Alleviates Pain by Suppressing P2Y12R-Dependent Microglial Activation in Monoarthritic Rats.

Electroacupuncture (EA) effectively improves arthritis-induced hyperalgesia and allodynia by repressing spinal microglial activation, which plays a crucial role in pain hypersensitivity following tissue inflammation. However, the mechanism by which EA suppresses spinal microglial activation in monoarthritis (MA) remains unclear. In the present study, a rat model of MA was established through unilateral ankle intra-articular injection of complete Freund's adjuvant (CFA). The relationship among P2Y12 receptor (P2Y12R) expression, spinal microglial activation, and EA analgesia was investigated using quantitative real-time PCR (qRT‒PCR), western blotting, immunofluorescence (IF), and behavioral testing. The results found that EA treatment at the ipsilateral "Huantiao" (GB30) and "Yanglingquan" (GB34) acupoints markedly attenuated pain and spinal microglia M1 polarization in MA rats. In particular, P2Y12R expression was significantly increased at the mRNA and protein levels in the spinal dorsal horn in MA rats, whereas EA treatment effectively repressed the MA-induced upregulation of P2Y12R. IF analysis further revealed that most P2Y12R was expressed in microglia in the spinal dorsal horn. Pharmacological inhibition of P2Y12R by its antagonist (AR-C69931MX) decreased MA-induced spinal microglial activation and subsequent proinflammatory cytokine production. Consequently, AR-C69931MX significantly intensified the anti-pain hypersensitive function of EA in MA rats. Taken together, these results demonstrate that EA alleviates MA-induced pain by suppressing P2Y12R-dependent microglial activation.

Synthesis and characterization of microencapsulated paraffin with melamine-urea-formaldehyde shell modified with lignin.

The study aims to fabricate MUF/paraffin microcapsules with lignin nanoparticles (LNPs)/ melamine-urea-formaldehyde (MUF) resin as hybrid shell material with different LNPs addition were synthesized in oil-in-water emulsion stabilized synergistically by styrene/maleic anhydride (SMA) and LNPs. The morphological characterization of LNPs was observed by transmission electron microscopy (TEM). The particle size of LNPs, the mean particle size and ξ potentials of SMA/LNPs mixture at pH =4.5 were investigated by zeta potential measurement. Field emission scanning electron microscopy (FE-SEM), Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), thermogravimetric analyzer (TGA), and differential scanning calorimetry (DSC) were characterized the morphologies, crystallography, chemical component, thermal stability and phase change properties of MUF/paraffin microcapsules with different LNPs addition. The results showed that MUF/paraffin microcapsules were spherical. The LNPs did not influence the chemical structure or crystal type of MUF/paraffin microcapsules. When the LNPs addition was 0.15 g, the melting enthalpy and crystallization enthalpy is respectively 130.03 and 121.92 J/g and the encapsulation efficiency of MicroC-15 is 61.04 %.

Randomized Controlled Trial Investigating the Impact of High-Flow Nasal Cannula Oxygen Therapy on Patients Undergoing Robotic-Assisted Laparoscopic Rectal Cancer Surgery, with a Post-Extubation Atelectasis as a Complication.

Background: Utilizing high-flow nasal cannula (HFNC) oxygen therapy may prevent the collapse of alveoli and improve overall alveolar ventilation. In this study, we aimed to investigate the impact of HFNC on postoperative atelectasis in individuals undergoing robotic-assisted laparoscopic surgery. Methods: Patients undergoing robotic-assisted laparoscopic surgery for rectal cancer were randomly assigned to the control or HFNC groups. After the surgical procedure was complete and the trachea was extubated, both groups underwent an initial lung ultrasound (LUS) scan. In the post-anesthesia care unit (PACU), the control group received conventional nasal cannula oxygen therapy, while the HFNC group received high-flow nasal cannula oxygen therapy. A second LUS scan was conducted before the patient was transferred to the ward. The primary outcome measured was the total LUS score at the time of PACU discharge. Results: In the HFNC group (n = 39), the LUS score and the incidence of atelectasis at PACU discharge were significantly lower compared to the control group (n = 39) [(5 vs 10, P < 0.001), (48.72% vs 82.05%, P = 0.002)]. None of the patients in the HFNC group experienced hypoxemia in the PACU, whereas six patients in the control group did (P = 0.03). Additionally, the minimum SpO2 value in the PACU was notably higher in the HFNC group compared to the control group [99 vs 97, P < 0.001]. Conclusion: Based on the results, HFNC improves the extent of postoperative atelectasis and decreases the occurrence of atelectasis in individuals undergoing robotic-assisted laparoscopic surgery for rectal cancer.

Bilirubin potentiates etomidate-induced sedation by enhancing GABA-induced currents after bile duct ligation.

OBJECTIVES: Our previous clinical trial showed that etomidate requirements to reach an appropriate level of anesthesia in patients with obstructive jaundice were reduced, which means that these patients are more sensitive to etomidate. However, the mechanism is still not completely clear. The present study was aimed to investigate the mechanism by which bilirubin facilitates etomidate induced sedation. METHODS: A bile duct ligation (BDL) rat model was used to simulate obstructive jaundice. Anesthesia sensitivity to etomidate was determined by the time to loss of righting reflex (LORR). Intrathecal injection of bilirubin was used to test the effects of bilirubin on etomidate induced sedation. The modulating effects of bilirubin on GABA responses were studied using the whole-cell patch clamp technique. RESULTS: The time to LORR induced by etomidate was significantly decreased in the BDL groups (p < 0.05), and unconjugated bilirubin in serum and cerebrospinal fluid (CSF) were markedly increased (p < 0.05). The time to LORR induced by etomidate was decreased after intrathecal injection of bilirubin (p < 0.05). A bilirubin concentration of 1.0 µM increased the GABA-induced currents of rat cortical pyramidal neurons (p < 0.05). Furthermore, 1.0 µM bilirubin enhanced GABA-induced currents modulated by etomidate (p < 0.05). CONCLUSIONS: Our results demonstrated that pathologic bilirubin in CSF could enhance etomidate induced sedation. The mechanism may be that bilirubin increase the GABA-induced currents of rat pyramidal neurons.

Threshold effects and inflection points of flavonoid intake in dietary anti-inflammatory effects: Evidence from the NHANES.

Flavonoids have been shown to be beneficial in a variety of inflammatory and metabolic diseases because of their anti-inflammatory and antioxidant properties. However, previous epidemiological studies have only demonstrated a negative correlation between flavonoid intake on inflammatory markers, and the optimal intake of dietary flavonoids and subclasses in terms of dietary anti-inflammatory efficacy remains undetermined. This study was based on 3 cycles (2007-2010, 2017-2018) of the National Health and Nutrition Examination Survey and the corresponding expanded flavonoid database. Weighted multiple linear regression was used to assess linear relationships between flavonoid intake and Dietary inflammation index (DII). Smoothed curve fit and a generalized additive model were used to investigate the nonlinear relationships and threshold effects, the 2-tailed linear regression model was used to find potential inflection points. A total of 12,724 adults were included in the study. After adjusting for potential confounders, flavonoid intake was significantly associated with DII, with the strongest negative association effect for flavonols (-0.40 [-0.45, -0.35]). In subgroup analyses stratified by sex, race, age, body mass index, education levels, and diabetes, flavonol intake maintained a significant negative linear correlation with DII. In addition, we found significant nonlinear relationships (L-shaped relationships) and threshold effects between total flavonoids, flavan-3-ols, and flavanols and DII, with inflection points of 437.65 mg/days, 157.79 mg/days, and 46.36 mg/days, respectively. Our results suggest a threshold for the dietary anti-inflammatory capacity of flavonoid intake in U.S. adults.

Safety of prone emergence from general endotracheal anesthesia in patients undergoing ERCP: a randomized controlled trial.

BACKGROUND: Conventional supine emergence and prone extubation from general endotracheal anesthesia (GEA) are associated with extubation-related adverse events (ERAEs). Given the minimally invasive nature of endoscopic retrograde cholangiopancreatography (ERCP) as well as the improved ventilation/perfusion matching and easier airway opening in the prone position, we aimed to assess the safety of prone emergence and extubation in patients undergoing ERCP under GEA. METHODS: Totally, 242 eligible patients were recruited and randomized into the supine extubation group (n = 121; supine group) and the prone extubation group (n = 121; prone group). The primary endpoint was the incidence of ERAEs during emergence, including hemodynamic fluctuations, coughing, stridor, and hypoxemia requiring airway maneuvers. The secondary endpoints included the incidence of monitoring disconnections, extubation time, recovery time, room exit time, and post-procedure sore throat. RESULTS: The incidence of ERAEs was significantly lower in the prone group compared with the supine group (8.3% vs 34.7%, OR = 0.17, 95% CI 0.18-0.56; P < 0.001). Moreover, the prone group demonstrated no monitoring disconnections, shorter extubation time and room exit time, faster recovery, and, lower frequency and milder sore throat after the procedure. CONCLUSIONS: For patients undergoing ERCP under GEA, compared with supine, prone emergence, and extubation had remarkably lower rates of EAREs and better recovery, and can maintain continuous monitoring and improve efficiency.

Efficacy and safety of electrical acupoint stimulation for postoperative nausea and vomiting: A systematic review and meta-analysis.

BACKGROUND: Postoperative nausea and vomiting are typical postsurgical complications. Drug therapy is only partially effective. The goal of our meta-analysis is to systematically evaluate the efficacy and safety of electrical acupoint stimulation for postoperative nausea and vomiting and to score the quality of evidence supporting this concept. METHODS: PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched from inception to March 19, 2020. RESULTS: Twenty-six studies (2064 patients) were included. Compared with control treatment, electrical acupoint stimulation reduced the incidence of postoperative nausea and vomiting (RR 0.49, 95% CI 0.41 to 0.57, P < 0.001), postoperative nausea (RR 0.55, 95% CI 0.47 to 0.64, P < 0.001) and postoperative vomiting (RR 0.56, 95% CI 0.45 to 0.70, P < 0.001). Electrical acupoint stimulation also reduced the number of patients requiring antiemetic rescue (RR 0.60, 95% CI 0.43 to 0.85, P = 0.004). No differences in adverse events were observed. Subgroup analysis showed that both electroacupuncture (RR 0.58, 95% CI 0.46 to 0.74, P < 0.001) and transcutaneous electrical acupoint stimulation (RR 0.44, 95% CI 0.34 to 0.58, P < 0.001) had significant effects. Electrical acupoint stimulation was effective whether administered preoperatively (RR 0.40, 95% CI 0.27 to 0.60, P < 0.001), postoperatively (RR 0.59, 95% CI 0.46 to 0.76, P < 0.001), or perioperatively (RR 0.50, 95% CI 0.37 to 0.67, P < 0.001). The quality of evidence was moderate to low. CONCLUSIONS: Electrical acupoint stimulation probably reduce the incidence of postoperative nausea and vomiting, postoperative nausea, postoperative vomiting, and reduce the number of patients requiring antiemetic rescue, with few adverse events.

Development of the Emoji Faces Pain Scale and Its Validation on Mobile Devices in Adult Surgery Patients: Longitudinal Observational Study.

BACKGROUND: Measuring pain on digital devices using classic unidimensional pain scales such as the visual analog scale (VAS), numerical rating scale (NRS), and faces pain scale (FPS) has been proven to be reliable and valid. Emoji are pictographs designed in colorful form following the Unicode standard. It could be more beneficial to use emoji as faces of FPS on digital devices because emoji can easily fit on most devices and emoji are open-source so no approval would be needed before use. With a concise and user-friendly design, the emoji faces pain scale (Emoji-FPS) might be more generalizable to a wider population and more preferred by digital device users. OBJECTIVE: This study was designed to develop an Emoji-FPS as well as to evaluate its reliability, validity, and preference on mobile devices in adult patients who underwent surgery. METHODS: A modified Delphi technique with 2 rounds of web-based surveys was applied to obtain panelists' consensus on the sequence of emoji that can best represent 6 levels of pain. The initial candidate sequences of emoji for the Delphi process were constructed referring to 2 well-validated FPSs (Wong-Baker FACES pain rating scale [Wong-Baker FACES] and faces pain scale-revised [FPS-R]). Then, a prospective cohort of patients scheduled to receive perianal surgery was recruited and asked to complete a web-based questionnaire on a mobile device at 5 time points (before surgery [T1], wake up after surgery [T2], 4 hours after surgery [T3], the second day after surgery [T4], and 15 minutes after T4 [T5]). The 4 well-validated pain scales (NRS, VAS, Wong-Baker FACES, and FPS-R) were used as reference scales. RESULTS: After 2 rounds of surveys on 40 Delphi panelists, an Emoji-FPS was finally determined to represent 6 pain levels (0, 2, 4, 6, 8, and 10) from "no hurt" to "hurts worst." For validation, 300 patients were recruited and 299 were analyzed, the mean age of whom was 38.5 (SD 10.5) years, and 106 (35.5%) were women. For concurrent validity, the Emoji-FPS was highly correlated with 4 reference scales with Spearman correlation coefficient ρ ranging from 0.91 to 0.95. Excellent agreements were observed between 4 versions of Emoji-FPS (iOS, Android, Microsoft, and OpenMoji), with weighted κ coefficients ranging from 0.96 to 0.97. For discriminant validity, patients' mean preoperative Emoji-FPS score (T1) was significantly higher than their postoperative Emoji-FPS score (T4) with a difference of 1.4 (95% CI 1.3-1.6; P<.001). For test-retest reliability, Emoji-FPS scores measured at T4 and T5 were highly correlated with a ρ of 0.91. The Emoji-FPS was mostly preferred, followed by the Wong-Baker FACES, FPS-R, NRS, and VAS. CONCLUSIONS: The Emoji-FPS is reliable and valid compared with traditional pain scales in adult surgery patients.

Pain Trajectory after Short-Stay Anorectal Surgery: A Prospective Observational Study.

The evolution of pain after anorectal surgery has not been well characterized. The main objective of this study is to evaluate patterns in acute postoperative pain in patients undergoing short-stay anorectal surgery. A total of 217 patients were included in the study, which used group-based trajectory modeling to estimate postoperative pain and then examined the relationships between sociodemographic or surgical factors and pain trajectories. Three distinct postoperative pain trajectories were determined: hemorrhoidectomy (OR, 0.15), higher anxiety (OR, 3.26), and a higher preoperative pain behavior score (OR, 3.15). In multivariate analysis, they were associated with an increased likelihood of being on the high pain trajectory. The pain trajectory group was related to postoperative analgesic use (p < 0.001), with the high-low group needing more nonsteroidal analgesics. The study showed that there were three obvious pain trajectories after anorectal surgery, including an unreported low-moderate-low type. More than 60% of patients maintained moderate to severe pain within 7 days after the operation. These postoperative pain trajectories were predominantly defined by surgery factors and patient factors.

Superficial Circumflex Iliac Artery Perforator Flap with Bilobed Design for the Donor Defect after Wrap-Around Flap Transfer Reconstruction.

OBJECTIVE: The repair of great toe donor site defect after wrap-around flap transfer is still controversial. The bilobed superficial circumflex iliac artery perforator (SCIP) flap can improve the aesthetics of the great toe while maintaining its function. Thus, this study aimed to report our experience in the reconstruction of big toe donor site defects with the bilobed SCIP flap and describe the clinical outcomes. METHODS: This study was a retrospective trial. From May 2017 to May 2020, 13 patients with the great toe donor site defect after wrap-around flap transfer were included in this study. The average age of the patients was 44 years (range, 23-60 years). All patients received free bilobed SCIP flaps to reconstruct the donor site defect of the great toe. Relevant clinical features were recorded preoperatively. The thickness and design of the SCIP flap and the harvesting layer of the flap were measured during the operation. The survival rate of flaps and skin grafts and the incidence of infection were recorded after operation. At follow-up, donor site complications and postoperative outcomes were evaluated. RESULTS: In all cases, the SCIP flap covering the donor site of the great toe survived. All patients were followed up for 24-40 months (mean, 30.5 months). The average thickness of the SCIP flap was 0.38cm. All SCIP flaps were harvested from the superficial fascial layer except for three obese patients. The thin SCIP flap had a bilobed design with no further defatting procedures. Postoperatively, the great toe-nail flap donor site regained its original appearance without bloating or flap necrosis. There was a hidden linear scar in the groin donor site, which did not affect hip joint movement. All patients were satisfied with the aesthetics of the surgical site. CONCLUSION: The SCIP flap with bilobed design for repairing the donor defect of the great toe after wrap-around flap transfer is a kind of surgical method with excellent contour, meeting the requirements of function and aesthetics.

Activation of P2X4 receptors in midbrain cerebrospinal fluid-contacting nucleus leads to mechanical hyperalgesia in chronic constriction injury rats.

Neuropathic pain is a refractory pain state, and its mechanism is still not clear. Previous studies have shown that the purine receptor P2X4R expressed on hyperactive microglia in the spinal cord is essential for the occurrence and development of neuropathic pain. The cerebrospinal fluid-contacting nucleus (CSF-contacting nucleus) in the midbrain has been found to play an important role in the descending inhibition system of modulation. However, there have been no studies on P2X4R in the CSF-contacting nucleus involved in neuropathic pain. To investigate whether P2X4R is expressed in the CSF-contacting nucleus and whether its expression in the CSF-contacting nucleus is involved in the regulation of neuropathic pain, we used a model of chronic sciatic nerve ligation injury (CCI) to simulate neuropathic pain conditions. Immunohistochemistry experiments were conducted to identify the expression of P2X4R in the CSF-contacting nuclei in CCI rats, and western blot analysis showed a significant increase in P2X4R levels 7 days after modeling. Then, we packaged a P2rx4 gene-targeting shRNA in scAAV9 to knock down the P2X4R level in the CSF-contacting nucleus, and we found that CCI-induced mechanical hyperalgesia was reversed. In conclusion, P2X4R expressed in the CSF-contacting nucleus is involved in the process of neuropathic pain, and downregulating P2X4R protein in the CSF-contacting nucleus can reverse the occurrence and development of hyperalgesia, which could represent a potent therapeutic strategy for neuropathic pain.

Effect of electroacupuncture on the repair of stress ulcer injury in neurocritical patients: A randomized clinical trial.

Background: Stress ulcer (SU) is one of the main causes of prolonged hospital stay, poor prognosis, and increased mortality in critically ill patients. This study aimed to investigate the effect of electroacupuncture (EA) on SU in patients with severe neurological diseases and explore its possible mechanisms. Methods: Taking patients with SU in adult neurocritical care as the research object, they were randomly divided into the EA group and the control group. Through the perioperative EA intervention, the following indicators were documented: main observation indicator (the effective rate of SU treatment), secondary observation indicators (gastric juice pH, gastric juice occult blood test, and stool occult blood test), related mechanisms [repair factors trefoil factor family 2 (TFF2), vascular endothelial growth factor (VEGF), and heat shock protein 70 (HSP70)], complications during hospitalization, and intensive care unit (ICU) stay time. Results: Compared with the control treatment, EA increased the effective rate of SU treatment (85.4% for the EA group, 57.5% for the control group, risk difference: 27.9% (95% CI: 8.3%-45.1%); P < 0.01). EA increased the success rate of gastric juice pH treatment on days 1, 2, and 3 (P < 0.01 for day 1, P < 0.05 for days 2 and 3). EA lowered the positive rate of gastric occult blood test on days 1 and 3 (all P-values < 0.05) and the positive rate of fecal occult blood test on day 3 (P < 0.05). EA also reduced the ICU stay time (P < 0.01) and total hospitalization time (P < 0.05). Compared with day 0, all serum repair factors (VEGF, HSP70, and TFF2) of both groups significantly increased on days 1, 3, and 5 (all P-values < 0.01). Compared with the control group, VEGF in the EA group was increased on days 3 and 5 (all P-values < 0.01); HSP70 was increased on days 1, 3, and 5 (P < 0.05 for day 1, P < 0.01 for days 3 and 5); and TFF2 was increased on days 1, 3, and 5 (all P-values < 0.01). Conclusion: Electroacupuncture promoted the repair of SU damage in severe neurological disease, and its effect was related to enhancing the expression of gastric mucosal repair factors. Clinical trial registration: [https://www.chictr.org.cn/showprojen.aspx?proj=127012], identifier [ChiCTR2100046701].

The Relationship Between Ferroptosis and Diseases.

Ferroptosis is an iron-dependent mode of cell death. It can occur through two major pathways, exogenous (or transporter-dependent) and endogenous (or enzyme-regulated) pathways are activated by biological or chemical inducers, and glutathione peroxidase activity is inhibited, which causes intracellular iron accumulation and lipid Peroxidation. Ferroptosis is closely related to the pathological process of many diseases. How to intervene in the occurrence and development of related diseases by regulating ferroptosis has become a hot research topic. At present, studies have shown that ferroptosis is found in common diseases such as tumors, inflammatory diseases, bacterial infections, pulmonary fibrosis, hepatitis, inflammatory bowel disease, neurodegenerative diseases, kidney injury, ischemia-reperfusion injury and skeletal muscle injury. This article reviews the characteristics and mechanism of ferroptosis, and summarizes how ferroptosis participates in the pathophysiological process in various systemic diseases of the body, which may provide new references for the treatment of clinical diseases in the future.

[Electroacupuncture improves long-term survival of myocardial infarction mice by promoting myocardial angiogenesis and inhibiting ventricular remodeling].

OBJECTIVE: To investigate the mechanism of electroacupuncture (EA) in improving the long-term survival rate of mice after myocardial infarction by promoting angiogenesis and inhibiting ventricular remodeling. METHODS: A total of 102 male C57BL/6 mice were randomly divided into sham operation, model and EA groups (n=34 /group). The myocardial infarction model was established by permanent ligation of the anterior descending branch of the left coronary artery. Beginning from the 3rd day after ligation, EA (2 Hz/20 Hz) was applied to bilateral "Neiguan" (PC6) and "Ximen" (PC4) for 30 min, once a day for 28 days. The survival rate in 140 d was recorded and the left ventricular ejection fraction (EF) calculated by using echocardiography after the treatment. The left cardiac ventricular tissue was cut into sections to be stained with Masson's trichrome, wheat germ agglutinin (WGA) or α-smooth muscle actin (α-SMA) immunohistochemistry method, followed by measuring the collagen area in the marginal region of myocardial infarction and calculating the collagen volume fraction (for assessing the severity of myocardial fibrosis), measuring the sectional area of cardiomyocytes (for assessing the degree of myocardial hypertrophy), and ob-serving the newborn blood vessels and calculating the ratio of neovascularization area (for assessing the state of angiogenesis). The expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF)-1α protein in the boundary area of myocardial infarction were detected by Western blot. RESULTS: After modeling, the survival rate, EF, and the thickness of the left cardiac ventricle were significantly decreased (P<0.01), whereas the percentage of collagen deposition area, sectional area of cardiomyocyte, percentage of angiogenesis area, and the expression levels of VEGF and HIF-1α proteins were significantly increased (P<0.01) in the model group relevant to the sham operation group. Compared with the model group, the survival rate, EF, the thickness of the left cardiac ventricle, the percentage of angiogenesis area, and the expression levels of VEGF and HIF-1α proteins were significantly increased (P<0.05, P<0.01), while the percentage of collagen deposition area and the sectional area of the cardiomyocyte were considerably decreased in the EA group (P<0.01, P<0.05). CONCLUSION: EA of PC6 and PC4 can significantly improve the cardiac function and long-term survival rate in mice with myocardial infarction, which may be related to its functions in up-regulating the expression of HIF-1α and VEGF to promote angiogenesis and in inhibiting ventricular remodeling.

Electroacupuncture ameliorates postoperative cognitive dysfunction and associated neuroinflammation via NLRP3 signal inhibition in aged mice.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is associated with worsened prognosis especially in aged population. Clinical and animal studies suggested that electroacupuncture (EA) could improve POCD. However, the underlying mechanisms especially EA's regulatory role of inflammasomes remain unclear. METHODS: The model of POCD was established by partial hepatectomy surgery in 18-month mice with or without postoperative EA treatment to the Baihui acupoint (GV20) for 7 days. Cognitive functions were assessed by Morris water maze test, and proinflammatory cytokines IL-1ß and IL-6 and microglia activity were assayed by qPCR, ELISA, or immunohistochemistry. Tight junction proteins, NLRP3 inflammasome and downstream proteins, and NF-κB pathway proteins were evaluated by western blotting. RESULTS: EA markedly preserved cognitive dysfunctions in POCD mice, associated with the inhibition of neuroinflammation as evidenced by reduced microglial activation and decreased IL-1ß and IL-6 levels in brain tissue. EA also preserved hippocampal neurons and tight junction proteins ZO-1 and claudin 5. Mechanistically, the activation of NLRP3 inflammasome and NF-κB was inhibited by EA, while NLRP3 activation abolished EA's treatment effects on cognitive function. CONCLUSION: EA alleviates POCD-mediated cognitive dysfunction associated with ameliorated neuroinflammation. Mechanistically, EA's treatment effects are dependent on NLRP3 inhibition.

Electroacupuncture treatment ameliorated the long-term cognitive impairment via activating eNOS/NO pathway and related Aß downregulation in sepsis-survivor mice.

OBJECTIVE: Sepsis is a major challenge in intensive care unit worldwide and the septic survivors are left with long-term cognitive deficits. This work aims to explore the effects of electroacupuncture (EA) on long-term cognitive function and its underlying mechanism in sepsis-survivor mice. METHODS: Sepsis was induced by cecal ligation and puncture in C57BL/6 male mice. Seven days post-surgery, sepsis-survivor mice were treated with EA or nonacupoint EA for 17 days twice daily. Then, cognitive function was evaluated by Morris water maze task. The hippocampus tissue were collected from the mice at 30 days post-surgery. The level of nitric oxide and the expression of endothelial nitric oxide (eNOS), phospho-eNOS (p-eNOS), and amyloid ß-peptide (Aß) were measured. RESULTS: Compared with the sham-operated control, sepsis-survivors had significant cognitive deficits evidenced by the increased time of escape latency and reduced crossing number in Morris water maze task, as well as lower NO and p-eNOS level and higher Aß level. EA treatment at GV20 and ST36 acupoints but not at a nonacupoint improved the cognitive function, increased the NO and p-eNOS level, and decreased Aß generation; while eNOS inhibitor (l-NAME) undermined the efficacy of EA treatment. CONCLUSION: In conclusion, repeated EA treatment could ameliorate the long-term cognitive impairment via manipulating the expression of p-eNOS and related Aß in sepsis-survivor mice.

Pretreatment with transcutaneous electrical acupoint stimulation to prevent postoperative ileus in patients undergoing laparoscopic colon surgery: study protocol for a randomised controlled trial.

INTRODUCTION: Postoperative ileus (POI), a common complication after surgery, severely affects postoperative recovery. It is unclear whether pretreatment with transcutaneous electrical acupoint stimulation (TEAS) can improve recovery from POI. This trial will evaluate the effects of pretreatment with TEAS on POI. METHODS AND ANALYSIS: This will be a prospective, randomised controlled trial. American Society of Anesthesiologists (ASA) physical status classification I-III level patients, aged 18-75 years and scheduled for laparoscopic colon surgery, will be included in the study. It is planned that 146 subjects will be randomised to the TEAS and sham TEAS (STEAS) groups. The groups will undergo two sessions of TEAS/STEAS daily for 3 days before surgery, with a final TEAS/STEAS treatment 30 min before anaesthesia. The primary endpoint of the study will be time to first defaecation. Secondary endpoints will include time to first flatus, time to tolerance of oral diet, GI-2 (composite outcome of time to first defaecation and time to tolerance of oral diet), time to independent walking, length of hospital stay, postoperative pain Visual Analogue Scale score on the first 3 days after surgery, analgesic requirements, complications and plasma concentrations of interferon-ß (IFN-ß), IFN-γ, interleukin-6 (IL-6) and IL-1ß. Multiple linear regression will be used to identify independent predictors of outcome measures. ETHICS AND DISSEMINATION: This study has been approved by the Chinese Registered Clinical Trial Ethics Review Committee (No. ChiECRCT-20170084). The results of the trial will be published in an international peer-reviewed journal. TRIAL REGISTRATION NUMBER: This study has been registered with the Chinese Clinical Trial Registry (No. ChiCTR-INR-17013184). TRIAL STATUS: The study was in the recruitment phase at the time of manuscript submission.

Electroacupuncture Pretreatment Alleviates LPS-Induced Acute Respiratory Distress Syndrome via Regulating the PPAR Gamma/NF-Kappa B Signaling Pathway.

Electroacupuncture (EA) is reported to possess anti-inflammatory properties and has beneficial effects on acute respiratory distress syndrome (ARDS). However, the underlying mechanisms of the effects of EA on ARDS remain unclear. This study aims to investigate the protective effect of EA on LPS-induced ARDS. In this study, Sprague-Dawley male rats were treated with EA at Hegu (LI4) for 45 minutes before LPS instillation (0.4 mg/kg, 100 ul). H&E staining, wet-to-dry weight (W/D) ratio, PaO2, and protein content in BALF were employed to determine the function of lung tissues. Inflammatory cytokines in serum and BALF were detected by enzyme-linked immunoassay assay (ELISA). The levels of oxidative stress markers were detected to determine the oxidative stress status. Cell apoptosis was observed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining and western blot. Here, we found that EA pretreatment effectively alleviated lung pathological damage. Moreover, EA suppressed the oxidative stress damage by upregulating glutathione and superoxide dismutase and downregulating malondialdehyde. EA pretreatment also regulated apoptosis-related proteins, such as Bax and Bcl-2. We found that peroxisome proliferators-activated receptors γ (PPARγ) play a critical role during ARDS, EA up-regulated the expression of PPARγ, which inhibited the activation of nuclear factor-kappa B (NF-κB) and decreased the inflammatory cytokines (interleukin-1ß, interleukin-6, and tumor necrosis factor-α). When rats were treated with GW9662, a selective PPARγ antagonist, these effects of EA were reversed. Our study demonstrated that EA pretreatment had a beneficial effect on LPS-induced ARDS in rats by anti-inflammatory, antioxidative, and antiapoptotic properties which was regulated via PPARγ/NF-κB signaling pathway.