Publications by authors named "Xiao-mei Shao"

68 Publications

Anxiolytic effect of GABAergic neurons in the anterior cingulate cortex in a rat model of chronic inflammatory pain.

Mol Brain 2021 09 10;14(1):139. Epub 2021 Sep 10.

Department of Neurobiology and Acupuncture Research, the Third School of Clinical Medicine, Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Hangzhou, 310053, China.

Chronic pain easily leads to concomitant mood disorders, and the excitability of anterior cingulate cortex (ACC) pyramidal neurons (PNs) is involved in chronic pain-related anxiety. However, the mechanism by which PNs regulate pain-related anxiety is still unknown. The GABAergic system plays an important role in modulating neuronal activity. In this paper, we aimed to study how the GABAergic system participates in regulating the excitability of ACC PNs, consequently affecting chronic inflammatory pain-related anxiety. A rat model of CFA-induced chronic inflammatory pain displayed anxiety-like behaviors, increased the excitability of ACC PNs, and reduced inhibitory presynaptic transmission; however, the number of GAD65/67 was not altered. Interestingly, intra-ACC injection of the GABAR agonist muscimol relieved anxiety-like behaviors but had no effect on chronic inflammatory pain. Intra-ACC injection of the GABAR antagonist picrotoxin induced anxiety-like behaviors but had no effect on pain in normal rats. Notably, chemogenetic activation of GABAergic neurons in the ACC alleviated chronic inflammatory pain and pain-induced anxiety-like behaviors, enhanced inhibitory presynaptic transmission, and reduced the excitability of ACC PNs. Chemogenetic inhibition of GABAergic neurons in the ACC led to pain-induced anxiety-like behaviors, reduced inhibitory presynaptic transmission, and enhanced the excitability of ACC PNs but had no effect on pain in normal rats. We demonstrate that the GABAergic system mediates a reduction in inhibitory presynaptic transmission in the ACC, which leads to enhanced excitability of pyramidal neurons in the ACC and is associated with chronic inflammatory pain-related anxiety.
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http://dx.doi.org/10.1186/s13041-021-00849-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431944PMC
September 2021

[Comparison of the effect between electroacupuncture and NSAIDs on pain memory based on cAMP/PKA/CREB pathway in anterior cingulate gyrus].

Zhongguo Zhen Jiu 2020 Apr;40(4):397-404

Third Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 310005, China; Zhejiang Key Laboratory of Acupuncture-Moxibustion and Neurology, Hangzhou 310053.

Objective: To observe the direct intervention effects of electroacupuncture (EA) and non-steroid anti-inflammatory drugs (NSAIDs) on pain memory, and to explore their effects on cAMP/PKA/cAMP pathway in anterior cingulate gyrus (ACC).

Methods: Fifty clean healthy male SD rats were randomly divided into a control group, a model group, an indomethacin group, an EA group and a sham EA group, 10 rats in each group. Except the control group, the pain memory model was established in the remaining four groups by twice injection of carrageenan at foot; 0.1 mL of 2%λ-carrageenan was subcutaneously injected at the left foot of rats; 14 days later, when the pain threshold of rats of each group returned to the basic level, the second injection was performed with the same procedure. The rats in the EA group were treated with EA at bilateral "Zusanli" (ST 36) for 30 min; the rats in the indomethacin group was treated with indomethacin intragastric administration with the dose of 3 mg/kg; the rats in the sham EA group was treated with EA without electricity at the point 0.3 mm forward "Zusanli" (ST 36) with the depth of 2 mm for 30 min; the rats in the control group was not given any invention. All the above interventions were performed 5 h, 1 d, 2 d and 3 d after the second injection of 2% λ-carrageenan. The left-side paw withdrawal thresholds (PWT) were observed before the first injection, 4 h, 3 d, 5 d after the first injection, before the second injection and 4 h, 1 d, 2 d, 3 d after the second injection. Three days after the second injection, the number of positive cells of cAMP, p-PKA, p-CREB and the number of positive cells of protein co-expression in the right ACC brain area were detected by immunofluorescence, and the relative protein expression of p-PKA and p-CREB were detected by Western blot.

Results: Compared with the control group, the PWTs in the model group decreased significantly 4 h, 3 d and 5 d after the first injection and 1 d, 2 d and 3 d after the second injection (<0.05); compared with the control group, the positive expression of cAMP, p-PKA and p-CREB in the right ACC brain area in the model group increased significantly (<0.05), and the number of positive cells of the co-expression of cAMP/p-PKA and p-PKA/p-CREB also increased significantly (<0.05). Compared with the model group, indomethacin group and sham EA group, the PWTs in the EA group were increased significantly 1 d, 2 d and 3 d after the second injection (<0.05); compared with the model group, indomethacin group and sham EA group, the positive expression of p-PKA and p-CREB in the right ACC brain area in the EA group decreased significantly (<0.05), and the number of positive cells of co-expression of cAMP/p-PKA and p-PKA/p-CREB was decreased significantly (<0.05). Compared with the model group and sham EA group, the positive expression of cAMP in the right ACC brain area was decreased in the EA group (<0.05).

Conclusion: EA have a direct intervention effect on pain memory, which have significant advantage over NSAIDs in the treatment of chronic pain. The advantage effect of EA on pain memory may be related to the inhibition of cAMP/PKA/CREB pathway in ACC area.
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http://dx.doi.org/10.13703/j.0255-2930.20190130-k0002DOI Listing
April 2020

[Effect of electroacupuncture on expression of GABA receptor mRNA in different brain regions in rats with chronic inflammatory pain].

Zhongguo Zhen Jiu 2020 Feb;40(2):173-8

Third College of Clinical Medicine, Zhejiang Chinese Medical University, Zhejiang Key Laboratory of Acupuncture Neurology, Hangzhou 310053, China.

Objective: To observe the expression of GABA receptor mRNA in different brain regions of the central nervous system in chronic inflammatory pain rats and the intervention effect of electroacupuncture (EA).

Methods: A total of 48 SPF male SD rats were randomly divided into a blank control group, a model control group, an EA group and a sham EA group, 12 rats in each group. The model of chronic inflammatory pain was established by injecting Freund's complete adjuvant into the foot. The EA group was treated with EA 28 days after the model establishment. The "Housanli" (ST 36) and "Kunlun" (BL 60) were selected and treated with dilatational wave, 2 Hz/100 Hz in frequency, 0.5-1.5 mA for 30 min; EA was given only once. In the sham EA group, the same acupoints were selected but the needles were only inserted into subcutaneous area; EA was connected for 30 min without electrical stimulation. The behavior changes of mechanical pain threshold and thermal pain threshold before model establishment, 1 day, 3 days, 7 days, 14 days, 21 days and 28 days after the model establishment as well as emotional behavior 29 days after the model establishment were observed; the relative expressions of GABA receptor mRNA in anterior cingulate cortex, amygdala and hypothalamus were observed.

Results: Compared with the blank control group, the change rates of mechanical pain threshold and thermal pain threshold in the model control group were decreased significantly 1 day, 3 days, 7 days, 14 days, 21 days, 28 days after model establishment (<0.01); 29 days after model establishment, the movement distance and staying time in the central area of open field test in the model control group were decreased significantly (<0.05). After EA intervention, compared with the model control group and the sham EA group, the change rates of mechanical pain threshold and thermal pain threshold, as well as the movement distance and the staying time of central area were significantly increased in the EA group (<0.01, <0.05). Twenty-nine days after model establishment, the expression of GABA receptor mRNA in anterior cingulate cortex and hypothalamus was not significantly different among all groups (>0.05). Compared with the blank control group, the expression of GABA receptor mRNA in the amygdala was decreased significantly in the model control group (<0.01); compared with the model control group and the sham EA group, the expression of GABA receptor mRNA in amygdala was increased after intervention in the EA group (<0.01).

Conclusion: Single treatment of EA could significantly increase the mechanical pain threshold and thermal pain threshold, improve abnormal emotional behavior in rats with chronic inflammatory pain, which may be related to the increasing of expression of GABA receptor mRNA in the amygdala.
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http://dx.doi.org/10.13703/j.0255-2930.20190129-k00054DOI Listing
February 2020

[Electroacupuncture combined with PNF on proprioception and motor function of lower limbs in stroke patients: a randomized controlled trial].

Zhongguo Zhen Jiu 2019 Oct;39(10):1034-40

Department of Rehabilitation, First People's Hospital of Huzhou, Huzhou 313000, Zhejiang Province, China.

Objective: To observe the clinical efficacy and correlation of electroacupuncture combined with proprioceptive neuromuscular facilitation (PNF) on proprioception and motor function of lower limbs in stroke patients.

Methods: A total of 96 stroke patients were randomized into an electroacupuncture (EA) group, a PNF group and a combination group, 32 cases in each one. In the EA group, acupuncture was applied at cephalic motor and sensory areas, Huantiao (GB 30), Yanglingquan (GB 34), Xuanzhong (GB 39), Zusanli (ST 36) and Sanyinjiao (SP 6) on affected side, and electroacupuncture was adopted at Yanglingquan (GB 34) and Xuanzhong (GB 39), continuous wave and 2 Hz in frequency for 20 min, once every day. In the PNF group, PNF was performed for 20 min, once a day. In the combination group, electroacupuncture was given before PNF, once a day. 4 weeks as one course and totally 3 courses were required, the effect was followed up after half a year. Before treatment, after 4, 8, 12 weeks of treatment and in follow-up, the average trace error (ATE) and Time, the scores of Fugl-Meyer scale (FMA) and modified Barthel index (MBI) were observed in the 3 groups. Correlation analysis between ATE, Time and FMA was performed.

Results: ① The total effective rate in the combination group was 90.3% (28/31), which was superior to 64.5% (20/31) in the EA group and 62.5% (20/32) in the PNF group (<0.05). ②After 4, 8, 12 weeks of treatment and in follow-up, the ATE and Time in the 3 groups were reduced compared with before treatment (<0.05, <0.01). After 8, 12 weeks of treatment and in follow-up, the ATE in the combination group were lower than the EA group and the PNF group (<0.05, <0.01). After 12 weeks of treatment and in follow-up, the Time in the combination group were lower than the EA group and the PNF group (<0.05, <0.01). ③After 4, 8, 12 weeks of treatment and in follow-up, the FMA scores in the EA group and the combination group were increased compared with before treatment (<0.01). After 8, 12 weeks of treatment and in follow-up, the FMA scores in the PNF group were increased compared with before treatment (<0.01). After 8, 12 weeks of treatment and in follow-up, the FMA scores in the combination group were higher than the EA group and the PNF group (<0.05, <0.01). ④After 4, 8, 12 weeks of treatment and in follow-up, the MBI scores in the 3 groups were increased compared with before treatment (<0.01). After 8, 12 weeks of treatment and in follow-up, the MBI scores in the combination group were higher than the EA group (<0.01). After 12 weeks of treatment and in follow-up, the MBI scores in the combination group were higher than the PNF group (<0.01). ⑤ The correlation coefficients of ATE, Time and FMA were from 0.4 to 0.75 (<0.05), suggesting a moderate intensity correlation.

Conclusion: Electroacupuncture, PNF and combination therapy can improve proprioception and motor function of lower limbs and activities of daily living, and combination therapy has a better effect. Proprioception and motor function have a strong correlation in the recovery of stroke patients.
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http://dx.doi.org/10.13703/j.0255-2930.2019.10.002DOI Listing
October 2019

[Feasibility of Joint Application of Techniques of Optogenetics and Neuroelectrophysiology to Research of Acupuncture Analgesia].

Zhen Ci Yan Jiu 2018 Aug;43(8):476-9

Neurobiological Lab for Studying Acupuncture-moxibustion, the Third Clinical Medical College of Zhejiang University of Traditional Chinese Medicine, Hangzhou 310053, China.

Since the invention of optogenetic technology, it has greatly promoted the development of neuroscience. Currently, optogenetic approaches have been mostly used to map neural circuits and new neuropharmacology but are rarely seen in the research field of acupuncture analgesia. The mechanism of neural circuits contributing to acupuncture analgesia, an important research hotspot in recent years, has not been fully determined. The optogenetic techniques can be used to modulate and control specific cells, provides highly precise spatial and temporal resolution, is repeatable, and may functionally dissect neuronal networks in vivo. The neuronal activities and their information transmission, processing and storage in intercluster neural networks in different brain regions, and the correlation between behavioral changes and electrical activities of neurons in vivo studies are mainly captured by the implanted microelectropode array, etc. If these two (or more) approaches are combined together, it is definitely and highly helpful to reveal the driving dynamics of neural circuits, plasticity and temporal-spatial activity mode of neurons, as well as behavioral reactions of animals with chronic pain during acupuncture analgesia and may open a new prospect for the application of acupuncture analgesia study.
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http://dx.doi.org/10.13702/j.1000-0607.170777DOI Listing
August 2018

Suppressing PKC-dependent membrane P2X3 receptor upregulation in dorsal root ganglia mediated electroacupuncture analgesia in rat painful diabetic neuropathy.

Purinergic Signal 2018 12 7;14(4):359-369. Epub 2018 Aug 7.

Department of Neurobiology and Acupuncture Research, the Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053, China.

Painful diabetic neuropathy (PDN) is a common and troublesome diabetes complication. Protein kinase C (PKC)-mediated dorsal root ganglia (DRG) P2X3 receptor upregulation is one important mechanism underlying PDN. Accumulating evidence demonstrated that electroacupuncture (EA) at low frequency could effectively attenuate neuropathic pain. Our previous study showed that 2-Hz EA could relieve pain well in PDN. The study aimed to investigate whether 2-Hz EA relieves pain in PDN through suppressing PKC-mediated DRG P2X3 receptor upregulation. A 7-week feeding of high-fat and high-sugar diet plus a single injection of streptozotocin (STZ) in a dose of 35 mg/kg after a 5-week feeding of the diet successfully induced type 2 PDN in rats as revealed by the elevated body weight, fasting blood glucose, fasting insulin and insulin resistance, and the reduced paw withdrawal threshold (PWT), as well as the destructive ultrastructural change of sciatic nerve. DRG plasma membrane P2X3 receptor level and DRG PKC expression were elevated. Two-hertz EA failed to improve peripheral neuropathy; however, it reduced PWT, DRG plasma membrane P2X3 receptor level, and DRG PKC expression in PDN rats. Intraperitoneal administration of P2X3 receptor agonist αβ-meATP or PKC activator phorbol 12-myristate 13-acetate (PMA) blocked 2-Hz EA analgesia. Furthermore, PMA administration increased DRG plasma membrane P2X3 receptor level in PDN rats subject to 2-Hz EA treatment. These findings together indicated that the analgesic effect of EA in PDN is mediated by suppressing PKC-dependent membrane P2X3 upregulation in DRG. EA at low frequency is a valuable approach for PDN control.
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http://dx.doi.org/10.1007/s11302-018-9617-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6298917PMC
December 2018

[Correlation Between Referred Pain Region and Sensitized Acupoints in Patients with Stable Angina Pectoris and Distribution of Sensitized Spots in Rats with Myocardial Ischemia].

Zhen Ci Yan Jiu 2018 May;43(5):277-84

Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing 100700.

Objective: To observe the correlation between the referred pain regions of stable angina pectoris (SAP) and the acupoints in coronary heart disease (CHD) patients and to investigate the rule of regional sensitized point distribution in rats.

Methods: A total of 1 046 CHD patients with SAP from 8 hospitals in China were recruited in the present study. The tenderness was palpated along the left and right chest, back, shoulder, upper limb, etc. by a specially-assigned researcher in each hospital. Among them, 77 patients accepted pain threshold (PT) measurement by using a hand-held esthesiometer. In animal experiments, 14 SD rats were subjected to occlusion of the left anterior descending branch of the left coronary artery for 4 h for establishing myocardial ischemia (MI) model, and other 4 normal rats were used as the sham-operation control group. Four hours after MI, all the rats accepted tail venous injection of 5% Evans blue (50 mg/kg) for examining the distribution of the blue dye exudation spots at the body surface where the mechanical PT was also detected by a von Frey.

Results: In 1 046 CHD patients, 987 (94.36%) were found to have at least one tenderness spot. The tenderness spots were found at the left chest (87.47%), right chest (13.67%), left arm (ulnar side, 41.30%), right upper limb (4.68%), left shoulder back (30.21%), right shoulder back (7.07%), etc., accompanied with rash or pigmentation, subcutaneous induration, cord-like tissue contracture, skin sag, etc. The mechanical PT level was significantly lower at the tenderness spots of the left upper limb than at non-tender points of the right upper limb in CHD patients (<0.001). Tenderness and cutaneous abnormal changes in angor pectoris patients distributed mostly on the left chest, back, shoulder and upper limb, and some also on the right. Tender points scattered on, near or outside acupoints. A similar distribution of the blue exudation spots and lower mechanical PT spots were found in MI rats, but not in sham-MI rats.

Conclusion: In the case of MI, a regular "referred sensitization" response frequently occurs in the dermatomere area innervated by the corresponding segments (T 1-T 5) in both CHD patients and MI rats, which may be closely associated with the formation of acupoints in ancient China.
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http://dx.doi.org/10.13702/j.1000-0607.180123DOI Listing
May 2018

[New Trains of Thoughts About Acupuncture Analgesia-Acupuncture Analgesia Feb Involve Multi-dimensional Regulation of Pain].

Zhen Ci Yan Jiu 2017 Feb;42(1):85-9

Zhejiang University of Traditional Chinese Medicine, Hangzhou 310053, China.

With the development of pain study, researchers gradually recognized that pain is composed of three main dimensions, namely "sensory-discriminative" "affective-motivational" and "cognitive-evaluative" which influence each other and are also independent from each other. Pain study has shifted away from focusing on the single mode of nociception to the multi-dimensional mode of sensory-affection-cognition. It is held early in traditional Chinese medicine that "when there is a stoppage, there is a pain" and a worsening disease Feb induce depression, which has already shown a multi-dimensional recognition about pain. Acupuncture therapy has been considered to be an effective adjuvant approach for relieving pain. In the present paper, the authors introduced applicability of acupuncture analgesia by modulating the abovementioned multi-dimensions of pain from the following 4 aspects:1) multi-dimensions of pain and related brain regions; 2) recognitions of traditional Chinese medicine about pain; 3) development of researches on acupuncture analgesia, including a) balancing activities of endogenous analgesic and algogenic substances, and triggering intracellular mitogen-activated protein kinase (MAPK) signaling to reduce algesia, b) improving psychological symptoms of patients with depression, anxiety, insomnia, etc., c) modulating functional activities of some common brain regions (as hippocampus, anterior cingutate, frontal lobe of cerebral cortex, etc.) sharing both pain information and learning-memory processing. Hence, the authors hold that if the clinical study and application and experimental researches conducted on the underlying mechanisms of acupuncture analgesia extend towards the multi-dimensions of pain, a series of new concepts or thoughts will be brought out, thereby possibly opening a bright applicable prospect for acupuncture analgesia.
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February 2017

Alleviating Mechanical Allodynia and Modulating Cellular Immunity Contribute to Electroacupuncture's Dual Effect on Bone Cancer Pain.

Integr Cancer Ther 2018 06 4;17(2):401-410. Epub 2017 Sep 4.

1 The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.

Hypothesis: Electroacupuncture (EA) has been used as an alternative analgesic therapy for hundreds of years, yet its analgesic potency and therapeutic advantage against bone cancer pain (BCP) in comparison with morphine remains unclear. This study aimed to investigate the effects of EA on mechanical allodynia and cellular immunity of BCP rats, and to further explore the potential mechanism.

Methods: The BCP model was established by implanting Walker 256 mammary gland carcinoma cells into the left tibia of adult female Sprague-Dawley rats. EA (dilatational wave, 2/100 Hz, 0.5 mA-1mA-1.5 mA for 10 minutes each intensity) was applied bilaterally to Zusanli (ST 36) and Kunlun (BL 60) for 30 minutes. Both EA stimulation and morphine (10 mg/kg, intraperitoneally) was given once every other day. Naloxone (0.3 mg/kg, intraperitoneally) was injected at 30 minutes prior to EA. Mechanical allodynia were demonstrated by paw withdrawal thresholds (PWTs) which measured by dynamic plantar aesthesiometer. T cell proliferation, percentage of CD3, CD4 and CD8 T lymphocytes in spleen as well as expression of interleukin-2 (IL-2) in plasma were detected by WST-8, flow cytometry, and enzyme-linked immunosorbent assay technique, respectively.

Results: An intratibial inoculation of Walker 256 mammary gland carcinoma cells significantly decreased PWTs to mechanical stimuli. EA stimulation alleviated mechanical allodynia in BCP rats, and the analgesic potency of EA was weaker than that of morphine. In contrast to morphine, EA stimulation of BCP rats increased splenic concanavalin A (Con A)-induced T cell proliferation and plasma IL-2 content, as well as increased the percentages of splenic CDCD and CDCD T cell subsets. Moreover, both the analgesic effect and the partial immunomodulation of EA were suppressed by an intraperitoneal injection of naloxone.

Conclusion: EA could significantly alleviate BCP-induced mechanical allodynia. Although the analgesic effect of EA was weaker than that of morphine, EA had an immunomodulation effect on cellular immunity. Both analgesic and immunomodulatory effect of EA might share the same mechanism via the opioid-mediated pathway, which needs further investigation.
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http://dx.doi.org/10.1177/1534735417728335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6041932PMC
June 2018

5-HT in the dorsal raphe nucleus is involved in the effects of 100-Hz electro-acupuncture on the pain-depression dyad in rats.

Exp Ther Med 2017 Jul 19;14(1):107-114. Epub 2017 May 19.

Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China.

The pain-depression dyad is becoming widespread in the clinic and is attracting increasing attention. A previous study by our group found that 100-Hz electro-acupuncture (EA), but not 2-, 50- and 2/100-Hz EA, was effective against the reserpine-induced pain-depression dyad. This finding is in contrast to the fact that low-frequency EA is commonly used to treat supraspinal-originating diseases. The present study aimed to investigate the mechanism underlying the effects of 100-Hz EA on the pain-depression dyad. Repeated reserpine injection was found to induce allodynia and depressive behaviors in rats. It decreased 5-hydroxytryptamine (5-HT) levels and immunoreactive expressions in the dorsal raphe nucleus (DRN). 100-Hz EA alleviated the pain-depression dyad and upregulated 5-HT in the DRN of reserpine-injected rats. Intracerebroventricular injection of para-chlorophenylalanine, an inhibitor of 5-HT resynthesis, suppressed the upregulation of 5-HT in the DRN by 100-Hz EA and partially counteracted the analgesic and anti-depressive effects of 100-Hz EA. The present study was the first to demonstrate that 5-HT in the DRN is involved in mediating the analgesic and anti-depressive effects of 100-Hz EA on the pain-depression dyad. This finding provided a scientific basis for high-frequency EA as a potential treatment for the pain-depression dyad.
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http://dx.doi.org/10.3892/etm.2017.4479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5488474PMC
July 2017

Effect of Electroacupuncture on the NTS is modulated primarily by acupuncture point selection and stimulation frequency in normal rats.

BMC Complement Altern Med 2017 Mar 31;17(1):182. Epub 2017 Mar 31.

Department of Neurobiology & Acupuncture Research, the Third Clinical College, Zhejiang Chinese Medical University, 548 Binwen Road, Binjiang District, Hangzhou, Zhejiang Province, 310053, China.

Background: The effect of electroacupuncture (EA) is affected by both the acupuncture point selection and the frequency of stimulation. However, little is known regarding acupuncture point and simulation frequency selection. Neuronal activation of the nucleus of the solitary tract (NTS) is one of the important targets of EA for modulating gastrointestinal function. This study investigated the effects of various combinations of EA frequencies and acupuncture points on NTS neurons.

Methods: Rats were randomly divided into normal, 2 Hz EA, 100 Hz EA and the alternate 2/100 Hz EA groups. Then rats in each group were randomly divided into the following two subgroups according to the acupuncture point: ST 36 group and ST 25 group. All the rats underwent electrode implantation surgery. Rats in all EA groups received one treatment with EA (a constant square wave at, 2 Hz,100 Hz or 2/100 Hz frequencies with intensities ranging from 1 to 2 mA), and NTS neuronal activation was recorded before and after EA treatment. Finally, to confirm the effect of EA on the NTS, minimal acupuncture was administered and its effect on NTS was detected.

Results: ST 36 stimulated with 2 Hz EA significantly increased the population of excited NTS neurons and spike frequency. However, ST 36 stimulated with 100 Hz or 2/100 Hz EA produced only a transient effect on the activity of NTS neurons and did not induce any effect on the spike frequency. Furthermore, the excitatory effect of 100 Hz or 2/100 Hz EA on NTS neurons in the ST 36 group was lower than 2 Hz EA at the same point. When applied to ST 25, 2 Hz EA had no significant excitatory effect on NTS neurons or spike frequency. However, 100 Hz EA or 2/100 Hz EA at ST 25 decreased both NTS neuronal excitability and spike frequency. By comparing the effects of different EA combinations, it was shown 2 Hz EA applied to ST 36 had the strongest excitatory effect on NTS neurons, while 100 Hz EA applied to ST 25 had the greatest inhibitory effect. Minimal acupuncture stimulation produced no effect on NTS neurons.

Conclusion: EA's effects on NTS were mainly affected by the acupuncture point selection, but the frequency of EA also played a role. Different combinations of acupuncture points and frequency selection may lead to different EA effects on NTS neuronal excitability.
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http://dx.doi.org/10.1186/s12906-017-1690-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5374564PMC
March 2017

Inhibition of the cAMP/PKA/CREB Pathway Contributes to the Analgesic Effects of Electroacupuncture in the Anterior Cingulate Cortex in a Rat Pain Memory Model.

Neural Plast 2016 20;2016:5320641. Epub 2016 Dec 20.

Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.

Pain memory is considered as endopathic factor underlying stubborn chronic pain. Our previous study demonstrated that electroacupuncture (EA) can alleviate retrieval of pain memory. This study was designed to observe the different effects between EA and indomethacin (a kind of nonsteroid anti-inflammatory drugs, NSAIDs) in a rat pain memory model. To explore the critical role of protein kinase A (PKA) in pain memory, a PKA inhibitor was microinjected into anterior cingulate cortex (ACC) in model rats. We further investigated the roles of the cyclic adenosine monophosphate (cAMP), PKA, cAMP response element-binding protein (CREB), and cAMP/PKA/CREB pathway in pain memory to explore the potential molecular mechanism. The results showed that EA alleviates the retrieval of pain memory while indomethacin failed. Intra-ACC microinjection of a PKA inhibitor blocked the occurrence of pain memory. EA reduced the activation of cAMP, PKA, and CREB and the coexpression levels of cAMP/PKA and PKA/CREB in the ACC of pain memory model rats, but indomethacin failed. The present findings identified a critical role of PKA in ACC in retrieval of pain memory. We propose that the proper mechanism of EA on pain memory is possibly due to the partial inhibition of cAMP/PKA/CREB signaling pathway by EA.
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http://dx.doi.org/10.1155/2016/5320641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5206448PMC
August 2017

Electroacupuncture treatment partly promotes the recovery time of postoperative ileus by activating the vagus nerve but not regulating local inflammation.

Sci Rep 2017 01 4;7:39801. Epub 2017 Jan 4.

Department of Neurobiology &Acupuncture Research, the Third Clinical College, Zhejiang Chinese Medical University, Hangzhou, China.

Postoperative ileus (POI) after abdominal surgery significantly lowers the life quality of patients and increase hospital costs. However, few treatment strategies have successfully shortened the duration of POI. Electroacupuncture (EA) is a modern way of administering acupuncture and widely used in various gastrointestinal (GI) diseases in the world. Here, we studied the effect of EA on POI and its underlying mechanisms. Intestinal manipulation resulted in significant delays of GI transit, colonic transit and gastric emptying. Surgery also up-regulated c-fos in nucleus of the solitary tract (NTS) and induced inflammation response in the small intestine. Further, operation and inhale anesthesia inhibited NTS neuron excitation duration for the whole observation time. EA administered at ST36 indeed shortened the recovery time of GI and colonic transit, and significantly increased the gastric emptying. EA also significantly activated the NTS neurons after operation. However, there was no anti-inflammation effect of EA during the whole experiment. Finally, atropine blocked the regulatory effect of EA on GI function, when it was injected after surgery, but not before surgery. Thus, the regulatory effect of EA on POI was mainly mediated by exciting NTS neurons to improve the GI tract transit function but not by activating cholinergic anti-inflammatory pathway.
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http://dx.doi.org/10.1038/srep39801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5209726PMC
January 2017

[Suggestions for standardized management of nomenclature and classification of neonatal diseases].

Zhongguo Dang Dai Er Ke Za Zhi 2016 Nov;18(11):1059-1064

Sichuan Academy of Medical Sciences/Sichuan Provincial People's Hospital, Chengdu 610072, China.

Nomenclature and classification of diseases are not only related to clinical diagnosis and treatment, but also involved in the fields such as management and exchange of medical information, medical expense payments, and medical insurance payment. In order to standardize clinical physicians' diagnostic and treatment activities, medical records, and the first page of medical records, this article elaborates on the basic principles and methods for nomenclature and classification of diseases with reference to international nomenclature of diseases and international classification of diseases. Meanwhile, in view of the problems in clinical practice, this article proposes the classification of neonatal diseases, the basic procedure and writing rules in the diagnosis of neonatal diseases, and death diagnosis principles.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7389846PMC
November 2016

Effect of systemic injection of heterogenous and homogenous opioids on peripheral cellular immune response in rats with bone cancer pain: A comparative study.

Exp Ther Med 2016 Oct 1;12(4):2568-2576. Epub 2016 Sep 1.

Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China.

Exogenous and endogenous opioids have been shown to modulate the immune system. Morphine-induced immunosuppression has been investigated extensively. However, the immune-regulating function of endogenous opioid peptides is unclear. The present study aimed to evaluate the difference in effects on cellular immune function between recombinant rat β-endorphin (β-EP; 50 µg/kg) and plant source morphine (10 mg/kg) via intraperitoneal injection treatment in a rat model of bone cancer pain. Walker 256 cells were injected into a tibial cavity injection to establish the bone cancer pain model. The paw withdrawal thresholds and body weights were measured prior to surgery, at 6 days after surgery, and following 1, 3,6 and 8 treatments. The spleen cells were harvested for detection of T cell proliferation, natural killer (NK) cell cytotoxicity, and the relative quantities of T cell subtypes (CD3, CD4 and CD8 cells). Plasma levels of interleukin-2 (IL-2) were also determined. It was found that single or multiple treatments with β-EP (a homogenous opioid peptide) and morphine (a heterogenous opioid) had good analgesic effects on bone cancer pain, while the analgesia provided by morphine was stronger than that of β-EP. Treatment with β-EP 3, 6 and 8 times increased the body weight gain in the rat model of bone cancer pain, while morphine treatment had on effect on it. With regard to immunomodulatory functions, β-EP treatment increased T cell proliferation and NK cell cytotoxicity, and increased the relative quantities of T cell subtypes, but no effect on T cell secretion. However, morphine treatment decreased T cell proliferation and the levels of T cell subtypes. These data indicate that opioids from different sources have different effects on cellular immune function . A small dose of homogenous opioid peptide exhibited positive effects (analgesia and immune enhancement) on cancer pain. These results provide experimental evidence supporting the exploitation of human opioids for the treatment of cancer pain.
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http://dx.doi.org/10.3892/etm.2016.3647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5038897PMC
October 2016

[Effect of Transcutaneous Electrical Acupoint Stimulation on Post-surgical Gastrointestinal Function, Autonomic Nerve Activities and Plasma Brain-gut Peptide Levels in Patients Undergoing Gastrointestinal Surgery].

Zhen Ci Yan Jiu 2016 Jun;41(3):240-6

The 3rdClinical Medical College of Zhejiang University of Traditional Chinese Medicine, Hangzhou 310053.

Objective: To observe the effect of transcutaneous electrical acupoint stimulation (TEAS) on ileus-postope-rative gastrointestinal functions and plasma ghrelin, motilin, and gastrin contents, and heart rate variability (HRV) in patients undergoing gastrointestinal surgery, so as to explore the interaction of vagus-brain-gut peptide.

Methods: A total of 58 patients undergoing elective gastrointestinal surgery were randomly assigned to TEAS (=29) and sham-TEAS group (=29, patients had no subjective sensation to 1 mA TEAS, thus, being considered to be sham-TEAS). TEAS (2 Hz/100 Hz, 6-8 mA for LI 4-PC 6, 12-18 mA for ST 36-SP 6) was applied to bilateral Hegu (LI 4)-Neiguan (PC 6) from 30 min pre-operation to the end of the operation and to bilateral LI 4-PC 6 and Zusanli (ST 36)-Sanyinjiao (SP 6) for 30 minutes twice daily in 3 consecutive post-operative days. ECGs of 12 leads were recorded to analyze different parameters of HRV from 2 days before and 4 days after surgery. Plasma ghrelin, motilin and gastrin contents were assayed by radioimmunoassay, and the patients' first bowel sound, first independent walk, first flatus, first solid food-intake and first defecation were recorded to evaluate the recovery state of gastrointestinal motility.

Results: Postoperative gastrointestinal motility:compared with the sham-TEAS group, the first bowel sound and the first defecation after surgery appeared apparently earlier in the TEAS group (<0.05), but no significant differences were found between the two groups at the time of the first independent walk, first flatus and the first solid food-intake in patients undergoing gastrointestinal surgery. Plasma brain-gut peptides:the plasma ghrelin and motilin contents 4 days post-surgery were significant increased in the TEAS group than in the sham-TEAS group (<0.05). No significant difference was found between the two groups in plasma gastrin contents (>0.05). HRV domains:in comparison with pre-surgery, the levels of low frequency (LF) and high frequency (HF) of frequency domain (FD) and root mean square of successive differences (rMSSD) of the time domain (TD) of HRV 4 days after surgery were significantly decreased in the sham-TEAS group (<0.05), but no significant changes were found in both FD and TD domains of the TEAS group 4 days after surgery (>0.05). Compared with the sham-TEAS group, the HF and rMSSD levels were significantly increased in the TEAS group 4 days after the surgery (<0.05). No significant differences were found between the two groups in the levels of very low frequency, LF and LF/HF levels of FD, and standard deviation of NN (beat-to-beat) intervals, the standard deviation of the average NN intervals and the proportion of NN 50 (the number of pairs of successive NNs that differ by more than 50 ms) divided by total number of NNs of TD.

Conclusions: TEAS can promote gastrointestinal activities (i.e., reducing the time spending of first bowel sound and the first defecation) in gastrointestinal surgery patients, which may be related to its effects in up-regulating ghrelin and motilin contents and parasympathetic activity.
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June 2016

Strong Manual Acupuncture Stimulation of "Huantiao" (GB 30) Reduces Pain-Induced Anxiety and p-ERK in the Anterior Cingulate Cortex in a Rat Model of Neuropathic Pain.

Evid Based Complement Alternat Med 2015 3;2015:235491. Epub 2015 Dec 3.

Department of Neurobiology & Acupuncture Research, The Third Clinical College, Zhejiang Chinese Medical University, Hangzhou 310053, China.

Persistent neuropathic pain is associated with anxiety. The phosphorylation of extracellular signal-regulated kinase (p-ERK) in the anterior cingulate cortex (ACC) plays an important role in pain-induced anxiety. Acupuncture is widely used for pain and anxiety. However, little is known about which acupuncture technique is optimal on pain-induced anxiety and the relationship between acupuncture effect and p-ERK. The rat model was induced by L5 spinal nerve ligation (SNL). Male adult SD rats were randomly divided into control, SNL, strong manual acupuncture (sMA), mild manual acupuncture (mMA), and electroacupuncture (EA) group. Bilateral "Huantiao" (GB 30) were stimulated by sMA, mMA, and EA, respectively. The pain withdrawal thresholds (PWTs) and anxiety behavior were measured, and p-ERK protein expression and immunoreactivity cells in ACC were detected. PWTs increased significantly in both sMA and EA groups. Meanwhile, anxiety-like behavior was improved significantly in the sMA and mMA groups. Furthermore, the overexpression of p-ERK induced by SNL was downregulated by strong and mild manual acupuncture. Therefore, strong manual acupuncture on bilateral "Huantiao" (GB 30) could be a proper therapy relieving both pain and pain-induced anxiety. The effect of different acupuncture techniques on pain-induced anxiety may arise from the regulation of p-ERK in ACC.
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http://dx.doi.org/10.1155/2015/235491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681793PMC
January 2016

Electroacupuncture alleviates retrieval of pain memory and its effect on phosphorylation of cAMP response element-binding protein in anterior cingulate cortex in rats.

Behav Brain Funct 2015 Mar 4;11. Epub 2015 Mar 4.

Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.

Background: Recent evidence suggests that persistent pain and recurrent pain are due to the pain memory which is related to the phosphorylation of cAMP response element-binding protein (p-CREB) in anterior cingulate cortex (ACC). Eletroacupuncture (EA), as a complementary Chinese medical procedure, has a significant impact on the treatment of pain and is now considered as a mind-body therapy.

Methods: The rat model of pain memory was induced by two injections of carrageenan into the paws, which was administered separately by a 14-day interval, and treated with EA therapy. The paw withdrawal thresholds (PWTs) of animals were measured and p-CREB expressions in ACC were detected by using immunofluorescence (IF) and electrophoretic mobility shift assay (EMSA). Statistical comparisons among different groups were made by one-way, repeated-measures analysis of variance (ANOVA).

Results: The second injection of carrageenan caused the decrease of PWTs in the non-injected hind paw. EA stimulation applied prior to the second injection, increased the values of PWTs. In ACC, the numbers of p-CREB positive cells were significantly increased in pain memory model rats, which were significantly reduced by EA. EMSA results showed EA also down-regulated the combining capacity of p-CREB with its DNA. Furthermore, the co-expression of p-CREB with GFAP, OX-42, or NeuN in ACC was strengthened in the pain memory model rats. EA inhibited the co-expression of p-CREB with GFAP or OX-42, but not NeuN in ACC.

Conclusions: The present results suggest the retrieval of pain memory could be alleviated by the pre-treatment of EA, which is at least partially attributed to the down-regulated expression and combining capacity of p-CREB and the decreased expression of p-CREB in astrocytes and microglia cells.
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http://dx.doi.org/10.1186/s12993-015-0055-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4364627PMC
March 2015

Effects of Electroacupuncture with Dominant Frequency at SP 6 and ST 36 Based on Meridian Theory on Pain-Depression Dyad in Rats.

Evid Based Complement Alternat Med 2015 4;2015:732845. Epub 2015 Mar 4.

Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China.

Epidemic investigations reveal an intimate interrelationship between pain and depression. The effect of electroacupuncture (EA) on pain or depression has been demonstrated individually, but its effect on pain-depression dyad is unknown. Our study aimed to screen a dominant EA frequency on pain-depression dyad and determine the validity of acupoint selection based on meridian theory. The pain-depression dyad rat model was induced by reserpine and treated using EA with different frequencies at identical acupoints to extract a dominant frequency and then administrated dominant-frequency EA at different acupoints in the above models. Paw withdrawal latency (PWL), emotional behavior of elevated zero maze (EZM) test, and open field (OF) test were conducted. We found that 100 Hz EA at Zusanli (ST 36) and Sanyinjiao (SP 6) (classical acupoints for spleen-deficiency syndrome) were the most effective in improving PWL, travelling distance in the EZM, and maximum velocity in OF compared to EA with other frequencies; ST 36 and SP 6 were proved more effective than other acupoints beyond the meridian theory and nonacupoints under the same administration of EA. Therefore, we concluded that 100 Hz is the dominant frequency for treating the pain-depression dyad with EA, and acupoints on spleen and stomach meridians are preferable choices.
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http://dx.doi.org/10.1155/2015/732845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4364048PMC
March 2015

[Effect of mild and strong manual acupuncture stimulation of "Huantiao" (GB 30) on mechanical pain thresholds and extracellular signal-regulated kinase protein expression in spinal dorsal horns in rats with neuropathic mirror-image pain].

Zhen Ci Yan Jiu 2014 Apr;39(2):106-11

Objective: To observe the effect of different intensities of manual acupuncture (MA) stimulation on mechanical pain thresholds (PTs) and the expression of phosphorylated extracellular signal-regulated kinases (p-ERK) in lumbar spinal dorsal horn regions in rats with neuropathic mirror-image pain, so as to explore its mechanisms underlying analgesia.

Methods: Forty male SD rats were equally and randomly divided into control, spinal nerve ligation (SNL) model, mild MA-stimulation, and strong MA-stimulation groups. Neuropathological pain model was established by ligature of the spinal nerve (L 5). Three days after the SNL, bilateral "Huantiao" (GB 30) were stimulated by rotating the thin (0.22 mm x 13 mm) or thick (0.3 mm x 13 mm) filiform needles at a frequencies of 60 times/min or 180 times/min and at an angle of 180 degrees or 360 degrees for 2 min for rats in the mild and strong MA-stimulation groups, respectively, followed by remaining the needle in place for 30 min. The mechanical PTs were measured before and after SNL. The expression of p-ERK protein in bilateral dorsal horn regions of the lumbar spinal cord (L4- L 6) was detected by Western blot.

Results: In comparison with the control group, the mechanical PTs were significantly decreased beginning from the 3rd day on after SNL on the affected side and from the 7th day on after SNL on the healthy hindpaw (P < 0.05), simultaneously, p-ERK protein expression levels of dorsal horn regions on both sides of the spinal cord were considerably up-regulated on the 12th day (P < 0.05). Compared with the model group, the PTs of the affected hindpaw and the healthy hindpaw were significantly increased on the 7th and 12th day in the strong MA-stimulation group (P < 0.05, P < 0.01), whereas pERK expression levels in the bilateral spinal dorsal horn regions were obviously down-regulated in the strong MA-stimulation group (P < 0.05). No significant differences were found between the model and mild MA-stimulation groups in the PTs of bilateral hindpaws and p-ERK expression levels of the bilateral spinal dorsal horn regions (P > 0.05) except the PTs of the healthy hindpaw on 7th day (P < 0.05).

Conclusion: Strong MA-stimulation can alleviate neuropathic mirror-image pain in SNL rats, which is closely related to its effect in down-regulating the expression of p-ERK in the bilateral spinal dorsal horn regions.
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April 2014

[Primary dysmenorrhea treated with staging acupoint catgut embedment therapy: a randomized controlled trial].

Zhongguo Zhen Jiu 2014 Feb;34(2):115-9

Objective: To observe the short-term and long-term efficacies on primary dysmenorrhea treated with staging acupoint embedment therapy.

Methods: Seventy cases of primary dysmenorrhea were randomized into an embedment therapy group and a fenbid group, 35 cases in each one. In the embedment therapy group, the embedment therapy was applied twice during the menstrual cycle, one treatment 3 days before menstruation and one treatment during the 12th-14th days of menstruation, respectively. Guanyuan (CV 4), Zigong (EX-CA 1), Diji (SP 8) and Ciliao (BL 32) were the main acupoints in the treatment 3 days before menstruation. Shenshu (BL 23), Ganshu (BL 18) and Pishu (BL 20) were the main acupoints in the treatment during menstruation. In the fenbid group, fenbid was prescribed for oral administration, 0.3 g each time, twice a day, starting 3 days before menstruation till pain was relieved. The treatment of one menstrual cycle was one session. The continuous treatment of 3 menstrual cycles was required. The short-term and long-term efficacies were evaluated at the end of the 3rd cycle and in 3 months after the treatment terminal. The dysmenorrhea score was used to evaluate the efficacy. Visual analogue scale (VAS) and SF-36 were for the assessment of pain degree and life quality.

Results: (1) The total effective rate was 91.4% (32/35) in the embedment therapy group after the 3 menstrual cycles, which was better than 74.3% (26/35) in the fenbid group (P < 0.01). In the follow-up stage, the total effective rate was 91.4% (32/35) in the embedment therapy group, which was better than 40.0% (14/35) in the fenbid group (P < 0.01). (2) The differences were not significant in dysmenorrhea score and VAS score after the 1st and 2nd menstrual cycle treatments between the two groups (all P > 0.05). In the 3rd menstrual cycle and the follow-up stage, the dysmenorrhea score and VAS score were reduced obviously in the embedment therapy group as compared with those in the fenbid group (P < 0.05, P < 0.01). The rebound effect occurred in the follow-up stage in the fenbid group. (3) In the 3rd menstrual cycle and the follow-up stage, the improvement in the total score of life quality of the embedment therapy group was superior apparently to the fenbid group (P < 0.05, P < 0. 01).

Conclusion: The staging acupoint embedment therapy achieves the superior short-term and long-term efficacies as compared with the oral administration of fenbid in the treatment of primary dysmenorrhea. As the symptoms of dysmenorrhea and pain are relieved, the life quality is improved.
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February 2014

Changes in amplitude-integrated electroencephalograms in piglets during selective mild head cooling after hypoxia-ischemia.

Pediatr Neonatol 2014 Aug 17;55(4):282-90. Epub 2014 Jan 17.

Department of Neonatology, Children's Hospital of Fudan University, Shanghai 201102, China. Electronic address:

Background: Amplitude-integrated electroencephalogram (aEEG) is a simplified, alternative means of monitoring cerebral function and may be more useful clinically in some situations than conventional EEG. The aim of this study is to evaluate newborn piglets as an animal model to examine the effect of selective mild head cooling (HC) on aEEG after hypoxia-ischemia (HI).

Methods: Thirty-four piglets were randomly allocated to the following treatment groups: normothermic control group (NC, n = 7), selective HC control group (HC, n = 9), normothermic HI group (NHI, n = 9), and selective HC HI group (SHC-HI, n = 9). HI was induced by temporary occlusion of both carotid arteries and simultaneous reduction of the concentration of inspired oxygen to 6% for 30 minutes. Mild hypothermia (35°C) was induced after HI using a HC cap and was maintained for 24 hours. Changes in aEEG were monitored for 6 days after these treatments and the incidence of abnormalities analyzed. Physiological parameters were also measured during this period.

Results: In the two HI groups, animals exhibited severely abnormal aEEGs [continuous low voltage (CLV), burst-suppression, or flat tracing (FT)] 20 minutes after the beginning of HI. At 2 hours, the aEEG returned to normal in most of these animals. From 12 hours to 6 days, all animals in the NHI group exhibited severely abnormal aEEGs. Fewer animals in the SHC-HI group exhibited severe abnormal aEEGs during this time period, and four out of nine (44.4%) animals had continuous normal voltage (CNV) at 6 days.

Conclusions: Selective mild HC decreases the incidence of severe abnormal aEEGs at late times after HI in newborn piglets.
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http://dx.doi.org/10.1016/j.pedneo.2013.09.012DOI Listing
August 2014

[Controlled observation of the efficacy between floating acupuncture at Tianying point and warm-needling therapy for supraspinous ligament injury].

Zhongguo Zhen Jiu 2013 Apr;33(4):309-13

Third Clinical Medical College of Zhejiang University of CM, Hangzhou 301153, China.

Objective: To compare the efficacy difference in the treatment of supraspinous ligament injury between floating acupuncture at Tianying point and the conventional warm needling therapy.

Methods: Ninety patients were randomized into a floating acupuncture group and a warm needling group, 45 cases in each one. In the floating acupuncture group, the floating needling technique was adopted at Tianying point. In the warm needling group, the conventional warm needling therapy was applied at Tianying point as the chief point in the prescription. The treatment was given 3 times a week and 6 treatments made one session. The visual analogue scale (VAS) was adopted for pain comparison before and after treatment of the patients in two groups and the efficacy in two groups were assessed.

Results: The curative and remarkably effective rate was 81.8% (36/44) in the floating acupuncture group and the total effective rate was 95.5% (42/44), which were superior to 44.2% (19/43) and 79.1% (34/43) in the warm needling group separately (P < 0.01, P < 0.05). VAS score was lower as compared with that before treatment of the patients in two groups (both P < 0.01) and the score in the floating acupuncture group was lower than that in the warm needling group after treatment (P < 0.01). Thirty-six cases were cured and remarkably effective in the floating acupuncture group after treatment, in which 28 cases were cured and remarkably effective in 3 treatments, accounting for 77.8 (28/36), which was apparently higher than 26.3 (5/19) in the warm-needling group (P < 0.01).

Conclusion: The floating acupuncture at Tianying point achieves the quick and definite efficacy on supraspinous ligament injury and presents the apparent analgesic effect. The efficacy is superior to the conventional warm-needling therapy.
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April 2013

[Changes in MLS-BAEP in newborn piglets with hypoxic-ischemic brain damage during selective moderate head cooling therapy].

Zhongguo Dang Dai Er Ke Za Zhi 2013 Jun;15(6):484-9

Department of Neonatology, Gynecology and Obstetrics Hospital, Fudan University, Shanghai, China.

Objective: To study the effect of selective moderate head cooling therapy on maximum length sequences brainstem auditory evoked potential (MLS-BAEP) in newborn piglets with hypoxic-ischemic brain damage.

Methods: Sixteen newborn piglets aged 5-7 day old were randomly divided into three groups: normothermic control (n=4), HI (n=6) and mild hypothermia-treated (n=6). HI was induced through temporary occlusion of both carotid arteries, followed by mechanical ventilation with low concentration of oxygen (FiO2=0.06) for 30 minutes. Mild hypothermia was induced by equipment via circulating water. MLS-BAER was recorded before HI and at 12 hours, 24 hours, 36 hours, 48 hours, 60 hours, 72 hours, 4 days, 7 days, 10 days, 13 days and 15 days after HI.

Results: Compared with the normothermic control group, all latencies and intervals tended to increase significantly at 72 hours in the HI group and reached peak values on day 7. From day 10, all latencies and intervals tended to decrease, but apart from wave I latency, still differed significantly from those of the normothermic control group. MLS-BAER variables did not reach normal values until day 15. Ⅲ latency, Ⅰ-Ⅲ interval and Ⅰ-Ⅴ interval were significantly reduced in the hypothermia-treated group between 60 and 7 days after HI compared with the HI group (P<0.05). V latency and Ⅲ-Ⅴ interval in the hypothermia-treated group were also reduced compared with the HI group between 72 hours and 7 days after HI (P<0.05).

Conclusions: Both peripheral and central auditory systems are disturbed by HI, which shows as a significant increase in MLS-BAER variables (all latencies and intervals) in newborn piglets. Involvement in central brainstem auditory system reaches a peak on day 7 after injury. MLS-BAER variables still cannot reach to normal values until day 15. Selective moderate head cooling therapy can significantly reduce brainstem damage induced by HI.
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June 2013

[Effects of the renal blood flow at different levels by transcutaneous electrical acupoint stimulation combined general anesthesia induced controlled hypotension].

Zhongguo Zhong Xi Yi Jie He Za Zhi 2012 Nov;32(11):1512-5

Lab for Acupuncture Neurobiology, Third Clinical College, Zhejiang University of Traditional Chinese Medicine, Hangzhou.

Objective: To observe the intervention of transcutaneous electrical acupoint stimulation (TEAS) on the renal blood flow at different levels of mean arterial pressure (MAP) in controlled hypotension.

Methods: Forty-two male beagle dogs were randomly divided into seven groups, i. e., the general anesthesia group, the 50% controlled group, the 40% controlled group, the 30% controlled group, the 50% experimental group, the 40% experimental group, and the 30% experimental group, 6 in each group. Beagles in the general anesthesia group were not treated with controlled hypotension, and the target MAP was achieved in those of the rest groups and maintained for 60 min. In the experimental groups, TEAS was applied to bilateral Hegu (LI4), Zusanli (ST36), Sanyinjiao (SP6), and Quchi (LI11) at 2/100 Hz with the stimulation strength of (4 +/- 1) mA starting from the stability of their physiological conditions to 60 min of maintaining the target MAP level. The changes of the renal blood flow were monitored at different time points using laser Doppler.

Results: From starting pressure control to the target MAP level, the renal blood flow was significantly lower in the 30% controlled group than in the general anesthesia group and the basic level of the same group (P < 0.05), while there was no obvious change in the 30% experimental group. In maintaining the blood pressure, the renal blood flow was significantly lower in the 50% controlled group, the 40% controlled group, the 30% controlled group, and the 30% experimental group than in the general anesthesia group (P < 0.05), while there was no obvious change in the 50% experimental group or the 40% experimental group. By the end of blood pressure recovery, the renal blood flow restored to the basic level in the 50% controlled group, the 50% experimental group, and the 40% experimental group (P > 0.05), while it was not restored to the basic level in the 40% controlled group, the 30% controlled group, and the 30% experimental group (P < 0.05).

Conclusion: TEAS combined general anesthesia in controlled hypotension could effectively improve the renal blood flow, thus protecting the kidney.
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November 2012

[Effects of transcutaneous electrical acupoint stimulation combined with general anesthesia for controlled hypotension on heart function and oxidation resistance of myocardium].

Zhongguo Zhen Jiu 2012 Oct;32(10):913-7

Zhejiang University of CM, Hangzhou 310053, China.

Objective: To investigate the intervention effect of transcutaneous electrical acupoint sitmulation (TEAS) on heart under limiting level of controlled hypotension.

Methods: Eighteen male Beagles were randomly divided into a general anesthesia group, a control group and an experimental group, 6 dogs in each group. All animals were applied with general anesthesia, and the animals of the control group and the experimental group were administered with combination of isoflurane and sodium nitroprusside (SNP) for controlled hypotension to 30% mean arterial pressure (30% MAP) of base line for 60 min. In the experimental group, TEAS (2 Hz/100 Hz, 6-8 mA) was applied to "Hegu" (LI4), "Zusanli" (ST 36), "Sanyinjiao" (SP 6) and "Quchi" (LI 11) from the beginning of physiological conditions stability to the end of maintained low MAP for 60 min. Creatine kinase isoenzymes MB (CK-MB) and lactate dehydrogenase (LDH) activity were detected at the base line and 2 h, 24 h, 48 h, 72 h after operation. Total superoxide dismutase (T-SOD) and malondialdehyde (MDA) in myocardium were observed at 72 h after operation.

Results: The peak of LDH arrived at 24 h after operation and then restored in 3 groups. Compared with basal level, the activity of LDH in controlled group at 72 h after operation was significantly increased (P < 0.05), and in the other two groups no obvious change (P > 0.05). The activity of CK-MB arrived to peak from 2 h to 24 h after operation, and then came back gradually in 3 groups. Compared with postoperative 72 h of the same group, the control group at 48 h significantly increased (P < 0.05), while the other two groups had no statistically significant difference (P > 0.05). The content of MDA at 72 h after operation in controlled group was higher significantly than that in the general anesthesia group and the experimental group (both P < 0.05).

Conclusion: TEAS combined with anesthesia for controlled hypotension can elevate myocardial effect of anti-oxide free radical, reduce the postoperative release of LDH and CK-MB, so as to produce myocardial protection.
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October 2012

[Effects of transcutaneous electrical acupoint stimulation combined general anesthesia in controlled hypotension at different levels on the liver blood flow ].

Zhongguo Zhong Xi Yi Jie He Za Zhi 2012 Jun;32(6):785-8

Department of Neurobiology, Third Clinical Medical School, Zhejiang University of Traditional Chinese Medicine, Hangzhou.

Unlabelled: OBJECTIVE To observe the changes of the liver blood flow in controlled hypotension by transcutaneous electrical acupoint stimulation (TEAS) combined general anesthesia, thus clarifying the mechanism of liver protection effect in acupuncture anesthesia combined with drugs.

Methods: Forty-two male beagles were randomly divided into seven groups, i.e. , the general anesthesia group, the 50% control group, the 50% experiment group, the 40% control group, the 40% experiment group, the 30% control group, and the 30% experiment group, 6 in each group. Beagles in the latter six groups were administered with isoflurane inhalation and intravenous dripping of sodium nitroprusside (SNP) for controlled hypotension. The mean arterial pressure (MAP) was lowered to 50%, 40%, and 30% basic MAP and lasted for 60 min. Beagles in the general anesthesia group was not treated with controlled hypotension. In the experiment groups, TEAS was applied to bilateral Hegu (LI4), Zusanli (ST36), Sanyinjiao (SP6), and Quchi (LI11) at 2/100 Hz with the stimulation strength of 4 +/- 1 mA. The TEAS started from the stability of physiological conditions to 60 min after maintaining the target MAP. The changes of blood flow of the liver tissue surface at corresponding time points were monitored by laser Doppler blood flow meter.

Results: Between the beginning of hypotension and the maintaining stage of target low blood pressure, the liver blood flow of the 50% control group was significantly lower than the level of the general anesthesia group and the basic level at corresponding time points (P < 0.05). It was significantly reduced in the 50% experiment group only at 30-60 min of maintenance. Besides, in the early period of maintenance (10-30 min), it was significantly higher in the 50% experiment group than in the 50% control group at the same time points (P < 0.05). In this stage, there was no obvious increase in the liver blood flow in the 40% and 30% experiment groups. In the recovery phase of blood pressure (20-30 min), the liver blood flow of the 40% experiment group had been restored to the level of the 40% control group and the basic level, while it had not been restored in the general anesthesia group. In this stage, the similar changing tendency of the liver blood flow occurred in the 50% and 30% experiment groups and the 50% and 30% control groups.

Conclusions: Line to a high level of controlled hypotension (50%), TEAS liver protective effect was obviously embodied in the early step-down phase and the maintenance phase. Line-induced hypotension to a lower level (40%), TEAS liver protective effect was obviously embodied in the recovery phase.
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June 2012

[Meta-analysis of mild hypothermia for gestational age over 35-week newborns with hypoxic-ischemic encephalopathy].

Zhonghua Yi Xue Za Zhi 2012 May;92(20):1400-4

Department of Neonatology, Children's Hospital of Fudan University, Shanghai 201102, China.

Objective: To determine the effects of therapeutic hypothermia (TH) in encephalopathic asphyxiated newborn infants on mortality, long-term neurodevelopmental disability and side effects by summarizing the data of hypoxic-ischemic encephalopathy(HIE) newborns undergoing mild hypothermia using meta-analysis.

Methods: The standard searching strategy of the Neonatal Review Group as outlined in the Cochrane Library was used to retrieve all clinical literatures about TH on HIE. RevMan 5.1 software was used to perform the meta-analysis of target papers. The primary outcome measure was a combination of death and severe major neurodevelopmental disabilities at 18 - 24 months of age. Secondary outcomes included mortality, cerebral palsy (CP), neurodevelopmental delay, blindness, deafness and main side effects of cooling therapy.

Results: A total of 276 papers fulfilled the search strategy and 11 trials were included. Overall TH resulted in a statistically significant and clinically important reduction in the combined outcome of death or major neurodevelopmental disabilities to 18-24 months of age (RR = 0.76, 95%CI: 0.68 - 0.84, P < 0.01). Moreover, as compared with the control group, TH significantly decreased the incidence of mortality (RR = 0.76, 95%CI: 0.65 - 0.90, P < 0.01), psychomotor development index(RR = 0.69, 95%CI: 0.55 - 0.87, P < 0.01), mental development index (RR = 0.66, 95%CI: 0.53 - 0.83, P < 0.01), CP (RR = 0.70, 95%CI: 0.54 - 0.91, P < 0.01) and blindness (RR = 0.54, 95%CI: 0.33 - 0.90, P < 0.05)except for severe hearing loss (deafness) (RR = 0.69, 95%CI: 0.35 - 1.34, P = 0.3000) in survivors. Adverse effects included significant thrombocytopenia in the TH group (P = 0.0400) but without deleterious consequences. There were no significant differences in arrhythmia, coagulopathy, hypotension requiring inotropic supports, sepsis and pulmonary hypertension between the TH and control groups (all P > 0.05).

Conclusions: Mild hypothermia is effective in reducing death and major disabilities in infants with moderate-to-severe HIE without significant side effects. Infants presenting within the first hours after birth with the signs and symptoms of moderate-to-severe encephalopathy should be cooled in accordance with the established protocols of previous randomized controlled trials.
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May 2012

Cerebral palsy in children: movements and postures during early infancy, dependent on preterm vs. full term birth.

Early Hum Dev 2012 Oct 12;88(10):837-43. Epub 2012 Jul 12.

Department of Rehabilitation, Children's Hospital of Fudan University, Shanghai, PR China.

Background: A deviant motor behaviour at age 3 to 5 months is predictive of cerebral palsy (CP). Particular features of the early motor repertoire even proved predictive of the degree of functional limitations as classified on the Gross Motor Function Classification System (GMFCS) in children with CP, born preterm.

Aims: We aimed to determine whether an association between the early motor repertoire and the GMFCS also holds true for children born at term.

Study Design: Longitudinal study.

Subjects: 79 infants (60 boys and 19 girls; 47 infants born at term; video recorded for the assessment of movements and posture at age 9 to 20 weeks postterm age) who developed CP.

Outcome Measures: The GMFCS was applied at age 2 to 5 years.

Results: Motor optimality at age 3 to 5 months showed a significant correlation with functional mobility and activity limitation as classified on the GMFCS at age 2 to 5 years in both children born at term (Spearman rho=-0.66, p<0.001) and born preterm (rho=-0.37, p<0.05). Infants born preterm were more likely to show normal movement patterns than infants born at term. A normal posture and an abnormal, jerky (yet not monotonous) movement character resulted in better levels of function and mobility. With the exception of one, none of the infants showed fidgety movements. A cramped-synchronised movement character, repetitive opening and closing of the mouth, and abnormal finger postures characterised children who would show a poor self-mobility later.

Conclusions: Assessing the quality of motor performance at 9 to 20 weeks postterm age (irrespective of the gestational age) improves our ability to predict later functional limitations in children with CP.
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http://dx.doi.org/10.1016/j.earlhumdev.2012.06.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3437561PMC
October 2012

Hypoxic ischaemic hypothermia promotes neuronal differentiation and inhibits glial differentiation from newly generated cells in the SGZ of the neonatal rat brain.

Neurosci Lett 2012 Aug 27;523(1):87-92. Epub 2012 Jun 27.

Institute of Pediatrics, Children's Hospital, Fudan University, 399 Wanyuan Road, Shanghai 201102, China.

Hypothermia is a potential therapy for cerebral hypoxic ischaemic injury in adults and neonates. The mechanism of the neuroprotective effects of hypothermia after hypoxia-ischaemia (HI) in the developing rat brain remains unclear. In this research, 7-day-old rats underwent left carotid artery ligation followed by the administration of 8% oxygen for 2 h. These rats were divided into hypothermic (rectal temperature, 32-33 °C for 24 h) and normothermic (36-37 °C for 24 h) groups immediately after HI. All rats were given 50 mg/kg/day 5-bromodeoxyuridine (BrdU) intraperitoneally at 4-6 days and sacrificed at 1 or 2 weeks after HI. We found a significant decrease in infarct volume and the neuron loss were also detected in the subgranular zone (SGZ) in the hypothermic group at 7 and 14 days after HI compared with the normothermic group. BrdU immunopositive cells were reduced greatly in the hypothermic group compared with the normothermic group. Hypothermia did not change the number of nestin-labelled cells in the ipsilateral SGZ at 1 and 2 weeks after HI. The differentiation of newly generated cells was assessed by double immunolabelling of BrdU with glial fibrillary acidic protein (GFAP), O4 or Neuronal Nuclei (NeuN). The ratio of BrdU(+)-GFAP(+) or BrdU(+)-O4(+) to total BrdU(+) staining decreased dramatically, but the ratio of BrdU(+)-NeuN(+) to total BrdU(+) staining increased significantly in the hypothermic group compared to the normothermic group at 2 and 6 weeks after HI. These results suggest that the reduction in neuron loss observed after mild hypothermia may be associated with enhanced neuronal differentiation and decreased glial differentiation in the SGZ after HI. These observations are noteworthy for clinical hypothermia therapy following cerebral HI injury during the perinatal period.
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http://dx.doi.org/10.1016/j.neulet.2012.06.054DOI Listing
August 2012
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