Effect of dual-acupoint and single-acupoint electric stimulation on postoperative outcomes in elderly patients subjected to gastrointestinal surgery: study protocol for a randomized controlled trial.

BACKGROUND: Transcutaneous electric acupoint stimulation (TEAS) has shown benefits when used peri-operatively. However, the role of numbers of areas with acupoint stimulation is still unclear. Therefore, we report the protocol of a randomized controlled trial of using TEAS in elderly patients subjected to gastrointestinal surgery, and comparing dual-acupoint and single-acupoint stimulation. METHODS/DESIGN: A multicenter, randomized, controlled, three-arm design, large-scale trial is currently undergoing in four hospitals in China. Three hundred and forty-five participants are randomly assigned to three groups in a 1:1:1 ratio, receiving dual-acupoint TEAS, single-acupoint TEAS, and no stimulation, respectively. The primary outcome is incidence of pulmonary complications at 30 days after surgery. The secondary outcomes include the incidence of pulmonary complications at 3 days after surgery; the all-cause mortality within 30 days and 1 year after surgery; admission to the intensive care unit (ICU) and length of ICU stay within 30 days after surgery; the length of postoperative hospital stay; and medical costs during hospitalization after surgery. DISCUSSION: The result of this trial (which will be available in September 2019) will confirm whether TEAS before and during anesthesia could alleviate the postoperative pulmonary complications after gastrointestinal surgery in elderly patients, and whether dual-acupoint stimulation is more effective than single-acupoint stimulation. TRIALS REGISTRATIONS: ClinicalTrials.gov, ID: NCT03230045 . Registered on 10 July 2017.

Electroacupuncture Potentiates Cannabinoid Receptor-Mediated Descending Inhibitory Control in a Mouse Model of Knee Osteoarthritis.

Knee osteoarthritis (KOA) is a highly prevalent, chronic joint disorder, which can lead to chronic pain. Although electroacupuncture (EA) is effective in relieving chronic pain in the clinic, the involved mechanisms remain unclear. Reduced diffuse noxius inhibitory controls (DNIC) function is associated with chronic pain and may be related to the action of endocannabinoids. In the present study, we determined whether EA may potentiate cannabinoid receptor-mediated descending inhibitory control and inhibit chronic pain in a mouse model of KOA. We found that the optimized parameters of EA inhibiting chronic pain were the low frequency and high intensity (2 Hz + 1 mA). EA reversed the reduced expression of CB1 receptors and the 2-arachidonoylglycerol (2-AG) level in the midbrain in chronic pain. Microinjection of the CB1 receptor antagonist AM251 into the ventrolateral periaqueductal gray (vlPAG) can reversed the EA effect on pain hypersensitivity and DNIC function. In addition, CB1 receptors on GABAergic but not glutamatergic neurons are involved in the EA effect on DNIC function and descending inhibitory control of 5-HT in the medulla, thus inhibiting chronic pain. Our data suggest that endocannabinoid (2-AG)-CB1R-GABA-5-HT may be a novel signaling pathway involved in the effect of EA improving DNIC function and inhibiting chronic pain.

[Involvement of cerebral neuroglobin in electroacupuncture preconditioning-induced protection effect in cerebral ischemia-reperfusion rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) preconditioning on cerebral ischemia and the role of cerebral neuroglobin (NgB) in EA-induced brain protection in focal cerebral ischemia and reperfusion injury (CI/RI) rats. METHODS: Male SD rats were randomly assigned to sham control, CI/RI 6 h, CI/RI 24 h and CI/RI 72 h groups (n = 6) for observing changes of NgB at different time-points. Additional SD rats were randomly assigned to sham, model, and EA preconditioning (EA-PC) groups (n = 16) for observing changes of cerebral NgB positive cell counts in the ischemic penumbra region 24 h after reperfusion. EA pre-conditioning was applied to "Baihui" (GV 20) for 30 min, once daily for 5 days before CI/RI. CI/RI model was established by occlusion of the right middle cerebral artery and reperfusion for 6 h, 24 h and 72 h respectively. The neurological behavior scores (NBS) of all the rats were evaluated according to Garcia's methods. The cerebral infarct volume was determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining. The number of cerebral NgB positive cells was detected by immunofluorescent staining. RESULTS: No infarct loci were found in the sham group. The cerebral infarction volume percentage was significantly higher in the model group than in the EA-PC group (P < 0.01), while the NBS was significantly lower in the model group than in the EA-PC group (P < 0.01). The number of cerebral NgB positive cells in the ischemic penumbra was up-regulated 6 h after CI/RI injury, peaked at 24 h and continued at 72 h. Compared with the sham group, the number of cerebral NgB positive cells of the model group was increased significantly, whereas that of the EA-PC group up-regulated further obviously in comparison with the model group (P < 0.01). CONCLUSION: EA pretreatment has a significant neuroprotective effect on cerebral ischemia-reperfusion, which is closely related to its effect in up-regulating NgB protein expression.

Pharmacokinetic, tissue distribution and excretion of ginsenoside-Rd in rodents.

Ginsenoside-Rd (GS-Rd) is one of the major active components of Panax ginseng, and was shown to have the protective effects against several insults. However, we still lack some basic knowledge of GS-Rd, including its pharmacokinetic, tissue distribution and excretion in vivo in experimental animal, such as mice and rats. In this study, HPLC and radioactive tracer assays were performed to determine pharmacokinetic, tissue distribution and excretion of GS-Rd in rodents. After intravascular administration with 20, 50 or 150 mg/kg GS-Rd, the dynamic changes of GS-Rd concentrations in plasma were consistent with a two-compartment model while the concentration of ³H-labeled GS-Rd was rapidly reached the peak in plasma, and distributed to various tissues, among which the highest concentration was observed in the lung.

Effect of electroacupuncture preconditioning on serum S100beta and NSE in patients undergoing craniocerebral tumor resection.

OBJECTIVE: To investigate the effect of electroacupuncture preconditioning on the serum level of S100 calcium-binding protein beta (S100beta) and neuron-specific enolase (NSE) in patients undergoing craniocerebral tumor operation. METHODS: A total of 32 patients, who would go through craniocerebral tumor resection under general anesthesia, were randomly assigned to two groups, 16 in each group. Patients in the electroacupuncture (EA) group received electroacupuncture on Fengfu acupoint (Du16) and Fengchi acupoint (GB20) for 30 min, 2 h before operation. The stimulus is 1-4 mA with a density wave frequency of 2/15 Hz. Patients in the control group received no pretreatment. Anesthesia was maintained with remifentanil at the dose of 4-8 mg/kg per hour, pumped intravenous drip of vecuronium at 1.0-2.0 microg/kg each hour, and discontinuous intravenous dripped with vecuronium bromide at 0.5-1 mg. The serum levels of S100beta and NSE were measured with ELISA before operation, before skin incision, after tumor removal, at the end of operation, and at 24 h after operation. RESULTS: The serum level of S100beta and NSE did not change before skin incision. The serum level of NSE increased significantly and the level of S100beta increased insignificantly after the tumor resection. The serum levels of S100beta and NSE in the EA group and the control group were 1.16+/-0.28 microg/L vs 1.47+/- 0.33 microg/L, 24.7+/-13.3 microg/L vs 31.4+/-14.1 microg/L at the end of the operation, respectively. Twenty-four h after operation, the correspondence indices were 1.18+/-0.31 microg/L vs 1.55+/-0.26 microg/L, and 25.5+/-12.4 microg/L vs 32.4+/- 11.7 microg/L. The two indices at these two time points were significantly increased than those before operation, respectively (P<0.05). At the end of the operation and 24 h post-operation, the serum levels of S100beta and NSE in the EA group were significantly lower than those in the control group (P<0.05). CONCLUSION: Electroacupuncture Fengchi and Fengfu for 30 min before craniocerbral tumor operation could decrease the serum level of S100beta and NSE, thus may have potential protective effect on brain damage, which needs to be further studied.

Repeated electroacupuncture preconditioning attenuates matrix metalloproteinase-9 expression and activity after focal cerebral ischemia in rats.

OBJECTIVE: This study investigates the effects of electroacupuncture (EA) preconditioning on blood-brain barrier (BBB) integrity and matrix metalloproteinase-9 (MMP-9) expression in subsequent ischemic hemisphere. METHODS: Focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in rats. Animals were randomly divided into four groups: normal, sham-operated, MCAO and EA groups. In EA group, rats received electroacupuncture stimuli at the Baihui acupoint (GV 20) 30 minutes/day for 5 days. Twenty-four hours after last treatment, the MCAO was performed. The brain water content and BBB permeability were measured 24 hours after MCAO. MMP-9 expression and activity were measured at 6, 12 and 24 hours after MCAO. RESULTS: The results showed that the brain water content of ischemic hemisphere was lower in EA group (81.45 +/- 1.09%) compared with MCAO group (83.98 +/- 1.30%; p<0.05). Similarly, the Evans blue content in EA group (4.90 +/- 1.77 microg/g) was lower compared with MCAO group (9.41 +/- 2.87 microg/g; p<0.05). The protein expression and enzyme activity of MMP-9 increased and reached maximum at 24 hours after reperfusion. However, the protein expression was lower in EA group at 12 and 24 hours after reperfusion (p<0.01, versus MCAO group), and enzyme activity was lower in EA group only at 24 hours (p<0.01, versus MCAO group). DISCUSSION: EA preconditioning could attenuate brain edema and BBB disruption caused by subsequent cerebral ischemia. EA preconditioning could decrease MMP-9 expression and activity, which may be an important mechanism of cerebral ischemic tolerance.

Musculoskeletal trauma services in China.

China is a developing country with a population over 1.3 billion with the second largest group of people in poverty next to India. There are about 159 million motor vehicles, with 163,887,372 drivers. From 2001 to 2004 over 100,000 people died each year in traffic accidents. With law enforcement and public education, traffic accidents have decreased, and the death rate is now less than 100,000 each year.

Shenfu injection attenuates neurotoxicity of bupivacaine in cultured mouse spinal cord neurons.

BACKGROUND: Our previous in vivo study in the rat demonstrates that Shenfu injection, a clinically used extract preparation from Chinese herbs, attenuates neural and cardiac toxicity induced by intravenous infusion of bupivacaine, a local anesthetic. This study was designed to investigate whether bupivacaine could induce a toxic effect in primary cultured mouse spinal cord neuron and if so, whether the Shenfu injection had a similar neuroprotective effect in the cell model. METHODS: The spinal cords from 11- to 14-day-old fetal mice were minced and incubated. Cytarabine was added into the medium to inhibit the proliferation of non-neuronal cells. The immunocytochemical staining of beta-tubulin was used to determine the identity of cultured cells. The cultured neurons were randomly assigned into three sets treated with various doses of bupivacaine, Shenfu and bupivacaine + Shenfu, for 48 hours respectively. Cell viability in each group was analyzed by methyl thiazoleterazolium (MTT) assay. RESULTS: The viability of the cultured neurons treated with bupivacaine at concentrations of 0.01%, 0.02%, 0.04% and 0.08% was decreased in a dose-dependent manner. Although the Shenfu injection at concentrations ranging from 1/50 to 1/12.5 (V/V) had no significant influence on the viability of cultured neurons (P < 0.05 vs control), the injection significantly increased the cellular viability of cultured neurons pretreated with 0.03% bupivacaine (P < 0.05). CONCLUSION: Although Shenfu injection itself has no effect on spinal neurons, it was able to reduce the bupivacaine-induced neurotoxicity in vitro.

Involvement of delta-and mu-opioid receptors in the delayed cerebral ischemic tolerance induced by repeated electroacupuncture preconditioning in rats.

BACKGROUND: Preconditioning with repeated electroacupuncture (EA) could mimic ischemic preconditioning to induce cerebral ischemic tolerance in rats. The present study was designed to investigate whether mu (micro)-, delta (delta)- or kappa (kappa)-opioid receptors are involved in the neuroprotection induced by repeated EA preconditioning. METHODS: The rats were pretreated with naltrindole (NTI), nor-binaltorphimine (nor-BNI) or D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), which is a highly selective delta-, kappa- or micro-opioid receptor antagonist respectively, before each EA preconditioning (30 minutes per day, 5 days). Twenty-four hours after the last EA treatment, the middle cerebral artery occlusion (MCAO) was induced for 120 minutes. The brain infarct volume was determined with 2, 3, 5-triphenyltetrazolium chloride staining at 24 hours after MCAO and compared with that in rats which only received EA preconditioning. In another experiment, the met-enkephalin-like immunoreactivity in rat brain was investigated by immunohistochemistry in both EA preconditioning and control rats. RESULTS: The EA preconditioning reduced brain infarct volume compared with the control rats (P = 0.000). Administration of both NTI and CTOP attenuated the brain infarct volume reduction induced by EA preconditioning, presenting with larger infarct volume than that in the EA preconditioning rats (P < 0.001). But nor-BNI administration did not block the infarct volume reduction induced by EA preconditioning, presenting with smaller infarct volume than the control group rats (P = 0.000). The number of met-enkephalin-like immunoreactivity positive neurons in the EA preconditioning rats was more than that of the control rats (P = 0.000). CONCLUSION: Repeated EA preconditioning stimulates the release of enkephalins, which may bind delta- and micro-opioid receptors to induce the tolerance against focal cerebral ischemia.

[Experimental study of evaluation on neuroprotective effect for tetramethylpyrazine against focal cerebral ischemic injury with diffusion-weighted magnetic resonance imaging].

OBJECTIVE: To evaluate the neuroprotective effect of tetramethylpyrazine (TMP) against focal cerebral ischemic injury in rats with diffusion-weighted magnetic resonance imaging (DWMRI). METHODS: Rat models of focal cerebral ischemic injury were established in 16 male SD rats. They were randomly divided into the TMP group and the control group, eight in each group, and pretreated with TMP and normal saline respectively before modeling. Change of infarcted cerebral focus was observed with DWMRI at 1, 2, 6, 12 and 24 hrs after infarction, and the infarction volume (IV) at 24 hrs after modeling was estimated by triphenyltetrazolium chloride (TTC) stain. RESULTS: The IV in all time points observed in the TMP group with DWMRI was significantly smaller than that in the control group (P<0.01). Compared with that at 1 hr after infarction, in the control group at 2, 6, 12 and 24 hrs after modeling, the IV enlarged by 13.3%, 29.7%, 50.3% and 57.3% respectively, while that in the TMP group 9.9%, 21.3%, 37.1% and 40.5% respectively. The cerebral IV estimated by TTC stain 24 hrs after modeling was larger than that estimated by DWMRI. CONCLUSION: TMP pretreatment before modeling was effective in protecting brain against cerebral ischemic damage in rats. DWMRI dynamic scanning observation has important significance in observing the cerebral ischemic developing process and evaluating the effectiveness of brain protective measures.

[Study on protective effect of shenfu injection on cardiac function of patients undergoing valve replacement].

OBJECTIVE: To investigate the protective effect of Shenfu injection (SFI) on cardiac function of patients undergoing valve replacement operation under cardio-pulmonary bypass. METHODS: One hundred and twenty patients undergoing valve replacement operation under cardio-pulmonary bypass were randomly divided into the SFI group and the control group, 60 in each group. Intravenous infusion of 1 ml/kg SFI was given to the SFI group, 30 min before anesthesia, and to the control group, equal volume of normal saline was given instead. The following indices were observed: (1) the hemodynamic changes occurred in the operational period; (2) the dosage of vaso-active drugs used during and after operation; (3) the post-operational recovery time of patients. RESULTS: The mean arterial pressure and heart rate in the SFI group during operation were higher, while the central venous pressure was lower than those in the control group (P < 0.05). The dosage of vaso-active drugs, such as dopamine, dobutamine, sodium nitroprusside and lidocaine, used during and after operation was lower, and the extubation time and the intensive care unit (ICU) staying time were shorter in the SFI group when compared with those in the control group (P < 0.05). CONCLUSION: SFI has certain protective effects on the cardiac function of patients undergoing valve replacement operation under cardio-pulmonary bypass.

[Effect of sodium ferulate on activation of extracellular signal regulated kinase after cerebral ischemia/reperfusion injury in rats].

OBJECTIVE: To study the activation of extracellular signal regulated kinase (ERK) after focal cerebral ischemia/reperfusion in rats and the effect of sodium ferulate (SF) on it. METHODS: Forty-five male adult SD rats were randomly divided into 3 groups, the sham-operated group, the control group and the SF group. The model of middle cerebral artery occlusion (MCAO) was established by thread ligation method, and in the ischemic phase, to rats in the sham-operated and the control group 4 ml of normal saline was intraperitoneally injected, and to rats in the SF group, 100 mg/kg of SF dissolved in 4 ml of normal saline was injected. The rats were decapitated at 2 hrs, 6 hrs, 12 hrs, 24 hrs and 72 hrs after reperfusion, 3 rats of every group at each time point, and rats brains were taken for immunohistochemistry and histopathological examination. RESULTS: Histopathological examination showed that the cerebral ischemic damage in the SF group was significantly milder than that in the control group at 2 hrs after reperfusion. The cerebral ischemia induced ERK activation reached the peak at 6 hrs and maintained to 72 hrs after reperfusion. As compared with the control group, the ERK activation in the SF group was significantly enhanced with increased positive immune reacted cells (P < 0.01). CONCLUSION: Cerebral ischemia/reperfusion could induce the activation of ERK in the ischemic brain cells, intervention of SF could enhance the activation and alleviate the ischemic injury in cerebral cortex.