NTPDase1-ATP-P2Y2Rs axis in the sciatic nerve contributes to acupuncture at "Zusanli" (ST36)-induced analgesia in ankle arthritis rats.

BACKGROUND: The efficacy of acupuncture at Zusanli (ST36) in alleviating lower-limb pain is widely acknowledged in clinical practice, while its underlying mechanism remains incompletely elucidated. Our previous research had revealed that the prompt analgesia induced by needling-ST36 was accompanied by expression alterations in certain exco-nucleotidases within the sciatic nerve. Building upon this finding, the current work focused on NTPDase1, the primary ecto-nucleotidase in the human body, which converts ATP into AMP. METHODS: A 20-min acupuncture was administered unilaterally at the ST36 on rats with acute ankle arthritis. The pain thresholds of the injured hind paws were determined. Pharmacological interference was carried out by introducing the corresponding reagents to the sciatic nerve. ATP levels around the excised nerve were measured using a luciferase-luciferin assay. Live calcium imaging, utilizing the Fura 2-related-F340/F380 ratio, was conducted on Schwann cells in excised nerves and cultured rat SCs line, RSC96 cells. RESULTS: The analgesic effect induced by needling-ST36 was impaired when preventing ATP degradation via inhibiting NTPDase1 activities with ARL67156 or Ticlopidine. Conversely, increasing NTPDase1 activities with Apyrase duplicated the acupuncture effect. Similarly, preventing the conversion of AMP to adenosine via suppression of NT5E with AMP-CP hindered the acupuncture effect. Unexpectedly, impeded ATP hydrolysis ability and diminished NTPDase1 expression were observed in the treated group. Agonism at P2Y2Rs with ATP, UTP, or INS365 resulted in anti-nociception. Contrarily, antagonism at P2Y2Rs with Suramin or AR-C 118925xx prevented acupuncture analgesia. Immunofluorescent labeling demonstrated that the treated rats expressed more P2Y2Rs that were predominant in Schwann cells. Suppression of Schwann cells by inhibiting ErbB receptors also prevented acupuncture analgesia. Finally, living imaging on the excised nerves or RSC96 cells showed that agonism at P2Y2Rs indeed led to [Ca2+]i rise. CONCLUSION: These findings strongly suggest that the analgesic mechanism of needling-ST36 on the hypersensation in the lower limb partially relies on NTPDase1 activities in the sciatic nerve. In addition to facilitating adenosine signaling in conjunction with NT5E, most importantly, NTPDase1 may provide an appropriate low-level ATP milieu for the activation of P2Y2R in the sciatic nerve, particularly in Schwann cells.

[Non-linear characteristic of acupoint resistance and its application].

Acupoint specificity is a key scientific issue in acupuncture and moxibustion. Acupoint electric resistance is a commonly-used biophysical index to study the functional specificity of acupoints. The non-linear characteristics of acupoint electric resistance have great impacts on the measured values, but it has been greatly ignored. By analyzing the non-linear characteristics of acupoint resistance and its application in the study of acupoint function specificity, a new idea of introducing chaos theory and technology into the study of acupoint function is proposed.

Mast Cell-Associated Serotonin in Acupoint Contributes to Acupuncture Analgesia in Arthritis Rats by Mediating ATP Release.

BACKGROUND: The activation of subcutaneous mast cells (MCs) helps to trigger the analgesic effect induced by acupuncture (AP), a traditional oriental therapy, that has been gradually accepted worldwide. This work aimed to reveal whether the serotonin (5-hydroxytryptamine, 5-HT) released from MCs plays an important role in this process, which has a controversial effect in the mechanism of pain. METHODS: In vivo tests, a 20-min session of AP was applied at Zusanli acupuncture point (acupoint) of acute ankle arthritis rats. Pain thresholds of the injured hindpaw were assessed to reflect the pain state, and the targeting substances in the interstitial space of the treated acupoint were sampled by microdialysis. In vitro experiments, exogenous 5-HT (exo-5-HT) was introduced to mediate adenosine triphosphate (ATP) release from cultured MCs. RESULTS: Needling promoted 5-HT accumulation at the Zusanli acupoint, which was prevented by sodium cromolyn. AP's analgesic effect was suppressed by the inhibition of 5-HT receptors at the acupoint, especially 5-HT1A subtype. In vitro tests, mechanical perturbation mimicking needling stimulation induced MCs to release 5-HT. 1 µM and 10 µM of exo-5-HT facilitated ATP release, which was restrained by blocking of 5-HT1 receptors rather than 5-HT3 receptors. As 5-HT, ATP and adenosine were also transiently accumulated in the treated acupoint during needling. Promoting ATP hydrolysis or activation adenosine A1 receptors duplicated AP analgesic effect. Finally, the inhibition of ATP receptors by suramin or pyridoxal phosphate-6-azo tetrasodium salt hydrate (PPADS) prevented AP analgesic effect. CONCLUSIONS: Our results suggest that MC-associated 5-HT release at acupoints contributes to AP analgesia, and the mediation of ATP secretion through 5-HT1A receptors might be the underlying mechanism at play. ATP could facilitate adenosine production or the propagation of needling signals.

The real-time detection of acupuncture-induced extracellular ATP mobilization in acupoints and exploration of its role in acupuncture analgesia.

Our and in vitro studies had confirmed that mechanosensitive ATP release and accumulation in acupoints was elicited by acupuncture (AP), which might be a pivotal step for triggering AP analgesia. But to date, the dynamics of extracellular ATP (eATP) in the interstitial space during AP process was poorly known, mainly due to the low temporal resolution of the current detection approach. This study attempted to capture rapid eATP signals in vivo in the process of needling, and further explored the role of this eATP mobilization in initiating AP analgesic effect. Ipsilateral 20-min needling was applied on Zusanli acupoint (ST36) of complete Freund's adjuvant (CFA)-induced ankle arthritis rats. Pain thresholds were assessed in injured-side hindpaws. eATP in the interstitial space was microdialyzed and real-time quantified by luciferin-luciferase assay at 1-min interval with the aid of the microfluid chip. We revealed in behavioral tests that modulation of eATP levels in ST36 influenced AP analgesic effect on ankle arthritis. A transient eATP accumulation was induced by needling that started to mobilize at 4 min, climbed to the peak of 11.21 nM within 3.25 min and gradually recovered. Such AP-induced eATP mobilization was significantly impacted by ankle inflammation, needling depth, needle manipulation, and the presence of local ecto-nucleotidases. This work reveals that needling elicits a transient eATP mobilization in acupoints, which contributes to initiating AP analgesia. This study will help us better understand the peripheral mechanism of AP analgesia and guide clinicians to optimize the needle manipulations to improve AP efficacy.

Low level light therapy/photobiomodulation for diabetic peripheral neuropathy: protocol of a systematic review and meta-analysis.

INTRODUCTION: Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes that strongly impact the patients' quality of life and working ability. Evidence indicated that low level light therapy (LLLT)/photobiomodulation might be effective for neuropathy. However, the effect of LLLT for DPN is not clear. The objective of this systematic review and meta-analysis is to determine the effects and safety of LLLT/photobiomodulation for DPN, in comparison with other methods such as sham light, no treatment, other active treatment and LLLT as an additional treatment compared with another treatment alone. METHODS AND ANALYSIS: We will search eight databases from their inception to the date before the review submission. Randomised controlled trials (RCTs) will be included. Two reviewers will independently extract data using a structured data extraction method and assess the risk of bias in the included studies. Data will be synthesised using standardised mean difference or risk ratio with 95% CIs for continuous and dichotomous data, respectively. The primary outcome will be change in pain and secondary outcomes will include global symptom improvement, functional impairment and disability, impairment of sensation, quality of life, nerve conduction, and adverse events. Sensitivity and subgroup analysis will be employed to explore the influence of possible clinical and methodological characteristics. Publication bias will be assessed using funnel plot. We will conduct meta-analysis with RevMan V.5.4 and evaluate quality of the evidence using GRADE approach. ETHICS AND DISSEMINATION: This study does not require ethics approval. Our findings will be disseminated in the peer-reviewed publications. PROSPERO REGISTRATION NUMBER: CRD42021276056.

[Bone proportional measurement on the chest and abdomen among 101 young females].

OBJECTIVE: To examine the bone proportional measurement standard on the chest and abdomen of modern women. METHODS: The height, weight and distances of bone proportional measurement chest and abdomen of 101 young females were measured. The height was divided by 75 to calculate the data of bone proportional measurement, and compared with the national standard published in 2006 and the ancient literature of Miraculous Pivot: Gudu. RESULTS: The bone proportional distances between two nipples and two coracoid processes of women were 8 cun and 12 cun respectively, which were in line with the 2006 national standard. The bone proportional distance from navel to superior margin of pubic symphysis (Qugu) was 6.5 cun, which was consistent with the ancient literature of Miraculous Pivot: Gudu. The bone proportional distance from suprasternal fossa to the middle point of xiphisternal synchondrosis (Qigu) was less than 9 cun, while the bone proportional distance from Qigu to navel was more than 8 cun, resulting in the ratio less than 9︰8. The bone proportional distance from suprasternal fossa to the middle point of xiphoid process was 9 cun, corresponding to the ratio of 9︰8 when comparing with the measurement from the middle point of xiphoid process to navel. CONCLUSION: The bone proportional distance measurement between two nipples and two coracoid processes of women should follow the 2006 national standard, and the bone proportional distance measurement from navel to superior margin of pubic symphysis should follow the standard of Miraculous Pivot: Gudu. The middle point of xiphisternal synchondrosis should be replaced by the middle point of xiphoid process.

A randomized sham-controlled trial of manual acupuncture for infertile women with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex polygenic disease and is one of the most common endocrinological and reproductive disorders. The purpose of this study was to evaluate the efficacy of acupuncture combined with herbal medicine among infertile females with polycystic ovary syndrome (PCOS). METHOD: A total of 86 women with PCOS, experiencing infertility, were recruited and randomly assigned to receive either manual acupuncture (MA) or sham acupuncture (SA) twice per week for three menstrual cycles. Both groups received herbal medication. The evaluations were conducted after three menstrual cycles and 24 weeks' follow-up. RESULTS: The trial was completed by 79 (91.86%) of the 86 randomly selected patients. During this study, the pregnancy rate in the MA group (46.34%) was significantly higher than the SA group (18.42%), with a P-value of 0.008. Moreover, the ovulation rate of the MA group (58.14%) was higher than that of the SA group (45.74%), with a P-value of 0.046. The improvement rate of PCOS score and testosterone level showed a statistical difference between the two groups (P-values were <0.05). There were no other differences between the two groups. Sex hormones level, including E2, T, P, LH, and LH/FSH were significantly lower after intervention in the MA group (P-values were <0.05) compared with baseline, while only the progesterone level was reduced in the SA group (P-value = 0.008). CONCLUSION: Manual acupuncture combined with herbal medicine may be clinically useful for infertile women with PCOS in improving pregnancy and ovulation rate. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1800014997.

[International communication system of acupuncture-moxibustion based on OSI model].

Borrowing the open system interconnection (OSI) model of internet protocol and the 5W theory in communication studies, the links in the international communication of acupuncture-moxibustion can be classified into seven layers: physical layer, data link layer, network layer, transport layer, session layer, presentation layer and application layer, therefore it is built an OSI model of international communication system of acupuncture-moxibustion. It is pointed out that present international communication system of acupuncture-moxibustion is similar to the user datagram protocol (UDP) in internet technology. Evidence-based medicine (EBM) plays a key role to modernize acupuncture- moxibustion theory based upon its clinical effects. According to phenomenon-taking by classified analogy, it is found that the PICO model of EBM agrees pretty well with the "three-way handshakes" mechanism of the internet transmission control protocol (TCP), which is promising to construct an international discourse of acupuncture-moxibustion compatible with western medicine. Thus it will benefit to explore the scientific connotation of acupuncture-moxibustion theory and significantly improve the international prestige of acupuncture-moxibustion.

Acupuncture modulates extracellular ATP levels in peripheral sensory nervous system during analgesia of ankle arthritis in rats.

As an ancient analgesia therapy, acupuncture has been practiced worldwide nowadays. A good understanding of its mechanisms will offer a promise for its rational and wider application. As the first station of pain sensation, peripheral sensory ganglia express pain-related P2X receptors that are involved in the acupuncture analgesia mechanisms transduction pathway. While the role of their endogenous ligand, extracellular ATP (eATP), remains less studied. This work attempted to clarify whether acupuncture modulated eATP levels in the peripheral sensory nerve system during its analgesia process. Male Sprague-Dawley rats underwent acute inflammatory pain by injecting Complete Freund's Adjuvant in the unilateral ankle joint for 2 days. A twenty-minute acupuncture was applied to ipsilateral Zusanli acupoint. Thermal hyperalgesia and tactile allodynia were assessed on bilateral hind paws to evaluate the analgesic effect. eATP of bilateral isolated lumbar 4-5 dorsal root ganglia (DRGs) and sciatic nerves were determined by luminescence assay. Nucleotidases NTPDase-2 and -3 in bilateral ganglia and sciatic nerves were measured by real-time PCR to explore eATP hydrolysis process. Our results revealed that acute inflammation induced bilateral thermal hyperalgesia and ipsilateral tactile allodynia, which were accompanied by increased eATP levels and higher mechano-sensitivity of bilateral DRGs and decreased eATP levels of bilateral sciatic nerves. Acupuncture exerted anti-nociception on bilateral hind paws, reversed the increased eATP and mechanosensitivity of bilateral DRGs, and restored the decreased eATP of bilateral sciatic nerves. NTPDase-2 and -3 in bilateral ganglia and sciatic nerves were inconsistently modulated during this period. These observations indicate that eATP metabolism of peripheral sensory nerve system was simultaneously regulated during acupuncture analgesia, which might open a new frontier for acupuncture research.

[Tracing the origin of wrist-ankle acupuncture based on huan in bamboo slip and silk medical books, maikou and the theory of origin, junction, branch and trunk].

The origin and basis of wrist-ankle acupuncture were discussed based on the theory of huan in bamboo slip and silk medical book Mai Fa (Pulse Method), theory of maikou, "meridian points", and theory of origin, junction, branch and trunk. The huan in bamboo slip and silk medical book Pulse Method is the wrist and ankle, and the position of wrist-ankle acupuncture is close to the huan. The theory of maikou reflects the pulse method which could be used not only in diagnosis but also in treatment, and the acupuncture points of wrist-ankle acupuncture are corresponding to the position and the main indications of maikou. The acupuncture points of wrist-ankle acupuncture are close to the locations and indications of "meridian points", as well as the points of Liu, Zhu and Xiaru of the theory of origin, junction, branch and trunk. The acupuncture points of wrist-ankle acupuncture are distributed in the range of "ben" in the theory of origin, junction, branch and trunk and five-shu points. The operation of wrist-ankle acupuncture is consistent with the theory of shallow needling at defensive-qi.

[Effect of electroacupuncture on morphine-conditioned place preference and activation of glutamatergic neurons in the ventromedial prefrontal cortex in rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Zusanli"(ST36) and "Sanyinjiao"(SP6) on conditioned place preference (CPP) and activation of glutamatergic neurons in the ventromedial prefrontal cortex (VMPFC) of morphine-addiction rats, so as to explore its mechanisms underlying detoxification. METHODS: Thirty male SD rats were randomly and equally divided into control, model and EA groups. The rats with acquisition of morphine-induced CPP received intraperitoneal injection of morphine (10 mg/kg) in the morphine-paired chamber, once daily for 3 consecutive days, and those of the control group received intraperitoneal injection of the same dose of normal saline in saline-paired chamber. Thirty minutes before CPP acquisition training, EA (2 Hz/100 Hz, 0.5 to 1.0 mA) was applied to ST36 and SP6 for 20 min every day. The double-labeled neurons of Fos/vesicular glutamate transporter 2 (VGLUT2) in the VMPFC were detected by using fluorescent immunohistochemistry. The discharges of the VMPFC neurons were recorded by using a multi-channel microarray electrophysiological system, followed by performing a z-score standardized processing. The ratio of firing rate frequency of rats in the morphine-paired chamber/saline-paired chamber was calculated, and further statistical analysis was conducted on the data based on the standardized z-scores. The neuronal firing characteristic of glutamatergic neuron is low frequency and wide wave. RESULTS: Compared with the control group, the score of morphine-induced CPP and numbers of Fos, VGLUT2-positive and Fos-VGLUT2 double-labeled positive cells were significantly increased in the model group (P<0.01，P<0.05). After EA and in comparison with the model group, the morphine CPP score and numbers of Fos, VGLUT2-positive and Fos-VGLUT2 double-labeled cells were significantly reduced in the EA group (P<0.01，P<0.05). The ratio of firing rate of the VMPFC neurons in the preference chamber and the percentage of inhibitory neurons as well as the z-score were considerably lower in the EA group than in the model group (P<0.001). CONCLUSION: EA can suppress morphine-induced seeking behavior in rats, which may be related to its inhibitory effect on glutamatergic neurons in the VMPFC.

[Application of unrestrained conscious rats with acute inflammatory ankle pain to study of acupuncture analgesia].

OBJECTIVE: To compare the analgesic effect of manual acupuncture(MA) stimulation of "Zusanli" (ST36) in rats with inflammatory pain under unrestrained conscious, restrained and general anesthesia conditions, so as to explore the applicability of unrestrained conscious model in the evaluation of acupuncture analgesia effect. METHODS: Male SD rats were divided into 5 groups: blank control (n=9), pain model (n=7), unrestrained conscious conditions+MA (n=6), restrained conditions+MA (n=6), and general anesthesia (GA)+MA(n=6). The acute pain model was established by injection of complete Freund's adjuvant (CFA) into the left ankle joint 48 h ahead of acupuncture. Subsequently, a single 20 min session of MA was applied to the left ST36. The mechanical and thermal pain thresholds (MPT and TPT) were determined before and after injection of CFA, and after MA stimulation. In order to evaluate the autonomic behavior activities, rats were randomly divided into blank control (n=11), pain model (n=11) and conscious-unrestrained conditions +MA (n=12) groups. The rats' exploratory movements were assessed by open field tests. RESULTS: Both MPT and TPT were significantly decreased after injection of CFA in the model group relevant to the blank control group (P<0.001), and significantly higher in the three MA groups than in the model group (P<0.001). Comparison among the three MA groups showed that both MPT and TPT were significantly higher in the conscious unrestrained conditions+MA group than in the restrained conditions+MA and GA+MA groups (P<0.05, P<0.01). Open filed tests showed that the total moving distance in the open field and wall climbing times were significantly lower in the model group than in the blank control group (P<0.01), and the wall climbing times were obviously more in the unstrained conditions+MA group than in the model group (P<0.05). The central area resistance time was significantly shorter in the model group than in the control group (P<0.05), and was moderately increased after MA despite no evident significance (P>0.05). No significant changes were found in the total moving distance after MA and in the central area moving distance after modeling and MA (P>0.05). CONCLUSION: MA has a better therapeutic effect in relieving pain and pain-induced depression-like behavior in conscious unrestrained rats than in restrained and GA rats, implying a higher applicability of unrestrained conscious pain model to the assessment of acupuncture analgesia.

Laser irradiation activates spinal adenosine A1 receptor to alleviate osteoarthritis pain in monosodium iodoacetate injected rats.

The analgesic role of the adenosine A1 receptor is thought to involve the modulation of the spinal N-methyl D-aspartate receptor-mediated nociceptive pathway, which is suggested to be an underlying mechanism in chronic pain. Knee osteoarthritis is a degenerative condition accompanied by chronic pain. We have demonstrated that 10.6-µm laser irradiation has an antinociceptive effect in the monosodium iodoacetate -induced knee osteoarthritis in rats. However, its mechanism of action has yet to be explored. In the present work, we investigate the mechanism of 10.6-µm laser irradiation mediated antinociception in the monosodium iodoacetate -induced knee osteoarthritis. Results showed that the 10.6-µm laser significantly reversed the monosodium iodoacetate -induced nociceptive behaviors for up to 28 days. Moreover, the up-regulation of the A1 receptor and the down-regulated phosphorylation of the N-methyl D-aspartate receptor 1 subunit of the N-methyl D-aspartate receptor were observed in the spinal cord dorsal horn in the monosodium iodoacetate injected rats treated by laser irradiation. Intrathecal injection of 8-cyclopentyl-1,3-dipropylxanthine markedly reversed the effects of laser irradiation, as evidenced both by behavioral pain tests and by levels of spinal phosphorylation of N-methyl D-aspartate receptor 1. These results suggest that the spinal A1 receptor contributes to the antinociceptive effects of 10.6-µm laser, at least in part by inhibiting phosphorylation of N-methyl D-aspartate receptor 1 in the monosodium iodoacetate -induced knee osteoarthritis pain.

CO2 Laser Moxibustion for Knee Osteoarthritis: Study Protocol for A Multicenter, Double-blind, Randomized Controlled Trial.

BACKGROUND: Knee osteoarthritis (OA) is a major cause of disability among the older adults. Few treatments are safe and effective. Moxibustion is commonly used in treating knee OA in Chinese medicine (CM). CO2 Laser moxibustion device is a substitute for traditional moxibustion, which mimics the effects of traditional moxibustion. More data are needed to support its application in knee OA. OBJECTIVE: ObjectiveThe trial aims to assess the effect and safety of CO2 laser moxibustion in patients with knee osteoarthritis compared with a sham control. METHODS: This is a protocol for a multicenter, randomized, double-blind, placebo-controlled trial. A total of 392 participants were recruited and assigned to the CO2 laser moxibustion group and sham laser moxibustion group with a 1:1 ratio at 6 outpatient clinics in Shanghai, China. Participants in both groups received treatment at the affected knee(s) at the acupuncture point Dubi (ST 35) and an Ashi point. There were 3 sessions per week for 4 weeks, and an additional 20-week follow-up. Primary outcomes were changes in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores at week 4. Secondary outcomes were WOMAC function score, stiffness score and overall score, VAS pain, Short-Form heath survey (SF-36), and patients' global assessment. The serum levels of cytokines involved in progress of knee OA were explored. Safety was assessed during the whole trial. Masking effectiveness was assessed by both participants and treatment providers.This is a protocol for a multicenter, randomized, double-blind, placebo-controlled trial. A total of 392 participants were recruited and assigned to the CO2 laser moxibustion group and sham laser moxibustion group with a 1:1 ratio at 6 outpatient clinics in Shanghai, China. Participants in both groups received treatment at the affected knee(s) at the acupuncture point Dubi (ST 35) and an Ashi point. There were 3 sessions per week for 4 weeks, and an additional 20-week follow-up. Primary outcomes were changes in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores at week 4. Secondary outcomes were WOMAC function score, stiffness score and overall score, VAS pain, Short-Form heath survey (SF-36), and patients' global assessment. The serum levels of cytokines involved in progress of knee OA were explored. Safety was assessed during the whole trial. Masking effectiveness was assessed by both participants and treatment providers. DISCUSSION: CO2 laser moxibustion device, designed as a substitute for CM moxibustion, is easy to use and control with no choking smoke and smell, and is a plausible method for double-blind research. This study would provide rigorous evidence for the effect and safety of CO2 laser moxibustion in treating knee OA (Trial registration No.: ISRCTN15030019).

Effect of Compound Laser Acupuncture-Moxibustion on Blood Glucose, Fasting Insulin and Blood Lipids Levels in Type 2 Diabetic Rats.

OBJECTIVE: To investigate the effect of compound laser acupuncture-moxibustion on blood glucose, fasting insulin and blood lipids levels in type 2 diabetes mellitus (T2DM) rats. METHODS: Forty male Wistar rats were randomly divided into 4 groups, including the normal group, model control group, laser group and sham laser group (n=10 per group). The rats in the normal group were fed with a standard diet. Rats in other groups were fed with a high-sugar and high-fat diet for 4 weeks, then intraperitoneally injected with 1% streptozotocin to induce T2DM model. The laser group was irradiated by 10.6 µm and 650 nm compound laser on bilateral Pishu (BL 20), Shenshu (BL 23) and Sanyinjiao (SP 6) for 5 min, 6 times a week for 5 weeks. The sham laser group received the same treatment as the laser group, but without laser output. The model control group and normal group were not treated. Blood glucose levels were measured before and after 1, 2, 3, 4 and 5 weeks of treatment. The serum levels of fasting insulin, total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were analyzed after the last treatment. RESULTS: The blood glucose levels in the model control group increased during the 5 weeks of treatment compared with the normal group (P<0.05), while those in the laser group were significantly lower than the model control group after weekly treatment (P<0.01 or P<0.05). After 1, 2 and 3 weeks of treatment, the blood glucose levels in the laser group decreased obviously compared with the sham laser group (P<0.01 or P<0.05). Compared with the normal group, the levels of fasting insulin, TC and LDL in the model control group notably increased (P<0.01 or P<0.05), while their levels in the laser group were significantly lower than the model control group after 5 weeks of treatment (P<0.05 or P<0.01). However, no statistically significant differences were observed in TG or HDL levels among the 4 groups (P>0.05). CONCLUSION: The compound laser acupuncture-moxibustion of 10.6 µm and 650 nm had positive effects on the regulation of hyperglycemia and insulin resistance in T2DM rats, which may be a potential treatment for T2DM, and also provide an alternative to the traditional acupuncture and moxibustion therapy.

[Analysis on the temperature-time curve in warm needling manipulation with acupuncture needles of different materials].

OBJECTIVE: To analyze the characteristics of the temperature-time curve in warm needling manipulation with the acupuncture needles made of copper, silver, gold and stainless steel and explore the applicable temperature range and most suitable needle materials of warm needling manipulation in clinical practice. METHODS: A total of 10 healthy subjects were included. Using the digital thermometer, with different moxibustion dose (1.2 g or 1.5 g, moxa), the temperature was measured at the site where the skin contacts with the needle body during the warm needling manipulation with stainless steel needle, copper needle, gold needle and sliver needle separately. The initial heat pain threshold (the temperature when hot feeling started) and the burning pain threshold (feeling very hot but tolerable) were recorded when using the different needles mentioned above. Through the subject questionnaire, the comfort degree, the heat sensation, the adverse reaction and the acceptability to warm needling manipulation with the different needles were investigated. RESULTS: During the warm needling manipulation, the initial heat pain threshold was (42.8±2.7) ℃ and the burning pain threshold was (46.7±2.9) ℃. The strongest warm stimulation was presented in the warm needling manipulation with 1.5 g moxa and silver needle and the highest temperature was (55.5±6.3) ℃, followed by (52.9±4.2) ℃ with 1.2 g moxa and silver needle, (46.6±3.7) ℃ with 1.5 g moxa and gold needle, (46.6±1.9) ℃ with 1.5 g moxa and copper needle, (43.1±1.5) ℃ with 1.2 g moxa and copper needle and (41.7±0.9) ℃ with 1.5 g moxa and stainless steel needle. The sequence of the maintaining time of the initial heat pain threshold over 43℃ was 480 s with silver needle and 1.5 moxa, 325 s with silver needle and 1.2 g moxa, 270 s with gold needle and 1.5 g moxa, 185 s with copper needle and 1.5 g moxa, 42 s with copper needle and 1.2 g moxa and 0 s with stainless steel needle and 1.5 g moxa successively. The heat score graded by the subjects to the warm needling manipulation with different needles, from high to low, was presented in the manipulation with 1.5 g moxa and silver needle, 1.2 g moxa and silver needle, 1.5 g moxa and copper needle, 1.5 g moxa and gold needle, 1.2 g moxa and copper needle and 1.5 g moxa and stainless steel needle. The VAS score was different significantly in comparison among the six needles in warm needling manipulation (P<0.001). The comfort degree of the subjects in the warm needling manipulation with silver needle and 1.5 g moxa was significantly lower than the warm needling manipulation with the other 5 materials (P<0.05). Three subjects complained that the warm needling manipulation with silver needle and 1.5 g moxa was too hot to be tolerable and the most of subjects were willing to accept warm needling manipulation with these 6 materials (acceptability 70.0% to 100.0%). Except blisters presented in 9 subjects after warm needling manipulation with silver needle and 1.5 g moxa, no severe adverse reaction occurred in warm needling manipulation with 6 materials. CONCLUSION: In the warm needling manipulation in the human body, the initial heat pain and the burning pain threshold were 43 ℃ and 47 ℃ respectively, which is the applicable temperature range of moxibustion in clinical practice. The warm needling manipulation with silver needle induces a quite strong heat stimulation and the discomfort may be caused when the temperature is exceeded to some threshold. The warm needling manipulation with copper needle generates the onset temperature, without inducing adverse reactions, e.g. discomfort and burning in the subjects.

Research on the Characteristics of Infrared Radiation Spectra at Zigong Acupoint within Menstrual Cycle of Healthy Female.

The purpose of this study was to observe the characteristics of infrared radiation spectrum of Zigong acupoint (EX-CA1) within the menstrual cycle of healthy female. We used highly sensitive infrared radiation spectrum detection system and phase-locked amplification technology to detect and analyse the infrared radiation spectrum from 1.5µm to 18µm of 32 healthy female before, during, and after menstruation at EX-CA1 and control points. The results showed that the total radiation intensity of left EX-CA1 was significantly higher than that of left control point (P <0.05) at the whole menstrual cycle, and the difference between right EX-CA1 and right control points was statistically significant before and after menstruation (P <0.05), no statistical difference during menstruation. Previous studies found that the radiation near 15µm was correlated with glucose metabolism. The results of this study showed that there were statistical differences in 10 wavelengths between left EX-CA1 and left control point from 14µm to 18µm, and there were statistical differences in 3 wavelengths on the right side (P <0.05). The left side is more prominent than the right side. The infrared radiation intensity of EX-CA1 decreased gradually with the change of cycle rhythm within menstrual cycle, but there was no statistical difference in this trend. There was no statistical difference in total radiation intensity between the right and left side of EX-CA1. Compared with the control points, the number of different wavelengths between left EX-CA1 and left control point during menstruation was significantly larger than that between right EX-CA1 and right control point (P <0.001). The results indicated that the energy of EX-CA1 was higher than control points. There was no difference in the radiation intensity between the right and left sides of EX-CA1 but there was acupoint laterality compared with nonacupoints. There was no significant rhythmic change in infrared radiation intensity of EX-CA1 during the menstrual cycle.

Altered white matter microstructure in patients with post-stroke depression detected by diffusion kurtosis imaging.

The aim of our study is to determine the pathological changes of white matter microstructure in patients with early post-stroke depression (PSD), and to investigate the association between white matter integrity examined by diffusion kurtosis imaging (DKI) and early PSD. Thirty-eight patients with acute cerebral infarction were selected, including 17 patients with depression (PSD group), and 21 patients without depression (N-PSD group). In addition, 20 normal healthy controls (NORM group) were selected. All were taken DKI scans. The white matter of the frontal lobe, temporal lobe, parietal lobe, occipital lobe, anterior limb of internal capsule, and posterior limb of internal capsule, in addition to the genu of corpus callosum and splenium of corpus callosum was selected as a region of interest (ROI). Selected parameters include fractional anisotropy (FA) and mean kurtosis (MK). Compared with N-PSD group and NORM group, FA value of the left frontal lobe and MK value of the bilateral frontal lobe, bilateral temporal lobe, and genu of corpus callosum in PSD group were decreased (P < 0.05). Our results indicated that the early PSD patients had white matter microstructure abnormalities in the frontal lobe, temporal lobe, and genu of corpus callosum. DKI provides a comprehensive brain imaging reference for detecting early microstructural damage of white matter in PSD patients, which can be used as an imaging biomarker to detect early PSD and its progression potentially.

[Brain regions responding to acupuncture stimulation of Zusanli (ST36) in healthy subjects analyzed on the basis of spontaneous brain activity].

OBJECTIVE: To determine the attributes of responses of the higher nerve center to acupuncture stimulation of Zusanli (ST36) on the basis of spontaneous brain activity, so as to explore the synchronization level of different brain rejoins after acupuncture. METHODS: All studies using fMRI to investigate the effect of acupuncture stimulation of ST36 and/or other acupoints on the human brain (at least 10 healthy subjects or patients in one group) published in journals from January of 1995 to January of 2018 were searched from databases of CNKI and PubMed by using keywords of acupuncture, electroacupuncture, and resting-state functional magnetic resonance images (rs-fMRI) or regional homogeneity (ReHo). Brain functional image data of acupuncture stimulation of ST36 and/or other acupoints were collected and analyzed with anisotropic effect size-signed differential mapping (AES-SDM) software (Meta-analysis), and those of acupuncture of simple ST36 analyzed as a subgroup. RESULTS: A total of 229 papers in Chinese and 109 in English were collected. According to our inclusive and exclusive standards, 11 papers containing 235 subjects were brought into analysis at last. Meta-analysis of brain image data of acupuncture at ST36 and/or other acupoints (comparison between pre- and post-acupuncture) revealed that the same brain regions (generality) which showed a significant increase in ReHo, are the right and left anterior cingulated gyrus, right caudate, left superior frontal gyrus, right middle frontal gyrus, and the right paracentral lobe, and those which showed a marked decrease of ReHo are the left mid-inferior occipital gyrus, left and right precentral and postcentral gyrus. The brain regions responding to acupuncture at ST36 only (specificity) are the right inferior parietal lobe, left middle inferior gyrus, right posterior lobe of cerebellum, and the left angular gyrus which displayed an increase of ReHo, and the right middle superior frontal gyrus which showed a decrease in ReHo. CONCLUSION: After acupuncturing at ST36, the relative generality and specificity of the central response in healthy subjects reflected as the location of the affected brain regions and the difference in the synchronization level of the corresponding spontaneous brain activities.

[Mechanisms of Acupuncture for Inflammatory Pain].

Although acupuncture, especially electroacupuncture (EA) is widely used to treat pain, its mechanisms have not been completely understood. In the present paper, we review the development of researches on the underlying mechanisms of EA in relieving inflammatory pain in recent years from a)peripheral inflammation-mediated immune response and neuro-immune interaction of receptors on primary nociceptors, b) crosstalk of neurotransmitters or neuromodulators, cellular signaling pathways, other related bioactive molecules, as well as glial activation in the dorsal horns of spinal cord, and c) supraspinal modulation of both sensory and affective components of pain. Inflammatory pain involves complex neuro-immune networks of neurons and non-neurons, various inflammatory mediators, neurotransmitters, neuromodulators and cellular signaling molecules in the peripheral and central nervous systems. Therefore, the analgesic mechanism of acupuncture still needs to be studied in depth at multi-levels and multi-targets, for instance, the reciprocal actions of peripheral opioid peptide, adenosine and TRPV 1 (which have been demonstrated to be involved in EA analgesia individually), the roles of spinal cord adenosine A 1 receptor (A 1 R) and A 2 R (for which fewer studies have been conducted), the interactions of classical neurotransmitters/neuromodulators/neuropeptides and their receptors, changes of intracellular molecules at transcriptional and translation levels, etc. during acupuncture analgesia. Furthermore, the mechanisms underlying reciprocal actions of neurotransmitters, neuromodulators and their receptors complicated in acupuncture-induced relief of pain affection in the higher brain regions also need to be explored further.