Electroacupuncture alleviates streptozotocin-induced diabetic neuropathic pain via suppressing phosphorylated CaMKIIα in rats.

Diabetic neuropathic pain (DNP) is a frequent complication of diabetes. Calcium/calmodulin-dependent protein kinase II α (CaMKIIα), a multi-functional serine/threonine kinase subunit, is mainly located in the surface layer of the spinal cord dorsal horn (SCDH) and the primary sensory neurons in dorsal root ganglion (DRG). Numerous studies have indicated electroacupuncture (EA) takes effect in various kinds of pain. In this research, we explored whether CaMKIIα on rats' SCDH and DRG participated in DNP and further explored the mechanisms underlying the analgesic effects of EA. The DNP model in rats was successfully established by intraperitoneal injection of streptozotocin. Certain DNP rats were treated with intrathecal injections of KN93, a CaMKII antagonist, and some of the DNP rats received EA intervention. The general conditions, behaviors, the expressions of CaMKIIα and phosphorylated CaMKIIα (p-CaMKIIα) were evaluated. DNP rats' paw withdrawal threshold was reduced and the expressions of p-CaMKIIα in SCDH and DRG were upregulated compared with the Normal group, while the level of CaMKIIα showed no significance. KN93 attenuated DNP rats' hyperalgesia and reduced the expressions of p-CaMKIIα. We also found EA attenuated the hyperalgesia of DNP rats and reduced the expressions of p-CaMKIIα. The above findings suggest that p-CaMKIIα in SCDH and DRG is involved in DNP. The analgesic effect of EA in DNP might be related to the downregulation of p-CaMKIIα expression level. Our study further supports that EA can be an effective clinical treatment for DNP.

A neural circuit associated with anxiety-like behaviors induced by chronic inflammatory pain and the anxiolytic effects of electroacupuncture.

AIMS: Negative emotions induced by chronic pain are a serious clinical problem. Electroacupuncture (EA) is a clinically proven safe and effective method to manage pain-related negative emotions. However, the circuit mechanisms underlying the effect of EA treatment on negative emotions remain unclear. METHODS: Plantar injection of complete Freund's adjuvant (CFA) was performed to establish a rat model of chronic inflammatory pain-induced anxiety-like behaviors. Adeno-associated virus (AAV) tracing was used to identify excitatory synaptic transmission from the rostral anterior cingulate cortex (rACC) to the dorsal raphe nucleus (DRN). Employing chemogenetic approaches, we examined the role of the rACC-DRN circuit in chronic pain-induced anxiety-like behaviors and investigated whether EA could reverse chronic pain-induced dysfunctions of the rACC-DRN circuit and anxiety-like behaviors. RESULTS: We found that chemogenetic activation of the rACC-DRN circuit alleviated CFA-induced anxiety-like behaviors, while chemogenetic inhibition of the rACC-DRN circuit resulted in short-term CFA-induced anxiety-like behaviors. Further research revealed that the development of CFA-induced anxiety-like behaviors was attributed to the dysfunction of rACC CaMKII neurons projecting to DRN serotonergic neurons (rACCCaMKII-DRN5-HT neurons) but not rACC CaMKII neurons projecting to DRN GABAergic neurons (rACCCaMKII-DRNGABA neurons). This is supported by the findings that chemogenetic activation of the rACCCaMKII-DRN5-HT circuit alleviates anxiety-like behaviors in rats with chronic pain, whereas neither chemogenetic inhibition nor chemogenetic activation of the rACCCaMKII-DRNGABA circuit altered CFA chronic pain-evoked anxiety-like behaviors in rats. More importantly, we found that EA could reverse chronic pain-induced changes in the activity of rACC CaMKII neurons and DRN 5-HTergic neurons and that chemogenetic inhibition of the rACCCaMKII-DRN5-HT circuit blocked the therapeutic effects of EA on chronic pain-induced anxiety-like behaviors. CONCLUSIONS: Our data suggest that the reversal of rACCCaMKII-DRN5-HT circuit dysfunction may be a mechanism underlying the therapeutic effect of EA on chronic pain-induced anxiety-like behaviors.

Electroacupuncture may alleviate diabetic neuropathic pain by inhibiting the microglia P2X4R and neuroinflammation.

Diabetic neuropathic pain (DNP) is a common and destructive complication of diabetes mellitus. The discovery of effective therapeutic methods for DNP is vitally imperative because of the lack of effective treatments. Although 2 Hz electroacupuncture (EA) was a successful approach for relieving DNP, the mechanism underlying the effect of EA on DNP is still poorly understood. Here, we established a rat model of DNP that was induced by streptozotocin (STZ) injection. P2X4R was upregulated in the spinal cord after STZ-injection. The upregulation of P2X4R was mainly expressed on activated microglia. Intrathecal injection of a P2X4R antagonist or microglia inhibitor attenuated STZ-induced nociceptive thermal hyperalgesia and reduced the overexpression of brain-derived neurotrophic factor (BDNF), interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) in the spinal cord. We also assessed the effects of EA treatment on the pain hypersensitivities of DNP rats, and further investigated the possible mechanism underlying the analgesic effect of EA. EA relieved the hyperalgesia of DNP. In terms of mechanism, EA reduced the upregulation of P2X4R on activated microglia and decreased BDNF, IL-1ß and TNF-α in the spinal cord. Mechanistic research of EA's analgesic impact would be beneficial in ensuring its prospective therapeutic effect on DNP as well as in extending EA's applicability.

Research Trends on Acupuncture for Shoulder Pain Treatment Over the Past 15 Years: A Bibliometric Analysis.

Objective: Currently, acupuncture for shoulder pain has been widely used in clinical and scientific research worldwide, but the bibliometric literature on acupuncture for shoulder pain is still scarce. This study reviews the application of acupuncture in the treatment of shoulder pain over the past 15 years, to analyze the current state of research, research hotspots, and trends. The article can also provide a reference for future research. Methods: This paper searches the core collection of the Web of Science database for publications related to acupuncture therapy for shoulder pain between 2008 and 2022. And the data were visualized and analyzed using VOSviewer and CiteSpace for annual publications, countries, institutions, journals and co-cited journals, authors and co-cited authors, keywords, and emergent keywords. Results: A total of 135 papers were included, with an overall increasing trend in the number of annual publications. The country with the highest centrality in publishing articles is the United States (0.28). In terms of research institutions, Kyung Hee University has the highest number of publications (18). In terms of authors, Lewith George, Lind Klaus, MacPherson Hugh, Sherman Karen J, and Vickers Andrew J are the five most published authors. Vickers, Andrew J. is the most co-cited author (50 times). In terms of journals, PAIN has the highest number of publications (82) and co-cited frequency (232), while the highest impact factor was BMJ-BRIT MED J (96.216). "Acupuncture" was the most frequently mentioned keyword (65 times), with the keyword "protocol" appearing the most recently. Emerging keywords that are still in vogue are "stroke", "systematic review" and "stimulation". Conclusion: This study provides statistics on current research on the treatment of shoulder pain with acupuncture, which may be able to inform future research directions for all researchers and physicians, as well as facilitate closer communication and collaboration.

Electroacupuncture Inhibits Pain Memory and Related Anxiety-Like Behaviors by Blockading the GABAB Receptor Function in the Midcingulate Cortex.

Pain memory is commonly considered an underlying cause of chronic pain and is also responsible for a range of anxiety. Electroacupuncture (EA) has been shown to ameliorate pain memories and exert anti-anxiety effects. Previous research has indicated that GABAergic neurons and/or GABA receptors (GABARs) in the midcingulate cortex (MCC) have potential associations with chronic pain and anxiety. However, there is no known empirical research that has specifically studied the effects of EA on the GABAergic system in the MCC. Here, we used cross-injection of carrageenan to establish the pain memory rats model. Immunofluorescence were used to detect the excitability of GABAergic neurons within MCC. Von Frey filament, elevated zero maze, and open field tests were used to measure mechanical allodynia and anxiety-like behaviors, combined with chemogenetic and pharmacologic technologies. Finally, this study provides evidence that pain memories contribute to generalized negative emotions and that downregulating the activity of GABAergic neurons within MCC could block pain memories and reverse anxiety emotion. Specifically, GABABR is involved in pain memory and related anxiety-like behaviors. Activation of GABAergic neurons in the MCC did not reverse the effects of EA on pain memories and related anxiety-like behaviors, whereas these effects could be reversed by a GABABR agonist. These findings highlight the functional significance of GABABR in the EA-mediated attenuation of pain memories and related anxiety-like behaviors in rats.

Electroacupuncture Alleviates Diabetic Neuropathic Pain and Downregulates p-PKC and TRPV1 in Dorsal Root Ganglions and Spinal Cord Dorsal Horn.

Diabetic neuropathic pain (DNP) is a common complication of diabetes. Streptozotocin (STZ)-induced changes of protein in dorsal root ganglion (DRG) and spinal cord dorsal horn (SCDH) are critical for DNP genesis. However, which proteins change remains elusive. Here, the DNP model was established by a single intraperitoneal injection of STZ, accompanied by increased fasting blood glucose (FBG), decreased body weight (BW), and decreased paw withdrawal latency (PWL). Proteins change in L4-L6 DRGs and SCDH of rats were detected. Western blot and immunofluorescence results showed that expression levels of phosphorylated protein kinase C (p-PKC), transient receptor potential vanilloid-1 (TRPV1), Substance P (SP) and calcitonin gene-related peptide (CGRP) in the DRG and the SCDH of rats were increased after STZ injection. A preliminary study from our previous study showed that 2 Hz electroacupuncture (EA) effectively alleviates DNP. However, the analgesic mechanism of EA needs further elucidation. Here, EA at the bilateral Zusanli (ST36) and KunLun (BL60) acupoints was applied for one week, and to investigate the effect on DNP. EA reversed thermal hyperalgesia in DNP rats and downregulated the expression of p-PKC, TRPV1, SP, and CGRP in DRG and SCDH.

Dorsal root ganglia P2X4 and P2X7 receptors contribute to diabetes-induced hyperalgesia and the downregulation of electroacupuncture on P2X4 and P2X7.

Diabetic neuropathic pain (DNP) is highly common in diabetes patients. P2X receptors play critical roles in pain sensitization. We previously showed that elevated P2X3 expression in dorsal root ganglion (DRG) contributes to DNP. However, the role of other P2X receptors in DNP is unclear. Here, we established the DNP model using a single high-dose streptozotocin (STZ) injection and investigated the expression of P2X genes in the DRG. Our data revealed elevated P2X2, P2X4, and P2X7 mRNA levels in DRG of DNP rats. The protein levels of P2X4 and P2X7 in DNP rats increased, but the P2X2 did not change significantly. To study the role of P2X4 and P2X7 in diabetes-induced hyperalgesia, we treated the DNP rats with TNP-ATP (2',3'-O-(2,4,6-trinitrophenyl)-adenosine 5'-triphosphate), a nonspecific P2X1-7 antagonist, and found that TNP-ATP alleviated thermal hyperalgesia in DNP rats. 2 Hz electroacupuncture is analgesic against DNP and could downregulate P2X4 and P2X7 expression in DRG. Our findings indicate that P2X4 and P2X7 in L4-L6 DRGs contribute to diabetes-induced hyperalgesia, and that EA reduces thermal hyperalgesia and the expression of P2X4 and P2X7.

Analgesic effect of electroacupuncture on bone cancer pain in rat model: the role of peripheral P2X3 receptor.

Upregulation of P2X3 receptor (P2X3R) has been strongly implicated in nociceptive signaling including bone cancer pain (BCP). The present study, using rat bone cancer model, aimed to explore the role of P2X3R in regulating rat pain behavior under the intervention of electroacupuncture (EA). The BCP model was successfully established by injection with MRMT-1 breast cancer cell into the medullary cavity of left tibia for 3 × 104 cells/3 µL PBS in rats as revealed by obvious bone destruction, decreased paw withdrawal thresholds (PWTs), and reduced paw withdrawal latencies (PWLs). Western blot analyses showed that P2X3R expression was significantly upregulated in ipsilateral lumbar 4-6 (L4-6) dorsal root ganglia (DRG), but the difference not seen in spinal cord dorsal horn (SCDH). With the in-depth study of P2X3R activation, we observed that intrathecal injection of P2X3R agonist α,ß-meATP aggravated MRMT-1 induced BCP, while injection of P2X3R inhibitor A-317491 alleviated pain. Subsequently, we demonstrated that BCP induced mechanical allodynia and thermal hyperalgesia were attenuated after EA treatment. Under EA treatment, total P2X3R protein expression in ipsilateral DRGs was decreased, and it is worth mentioning that decreased expression of P2X3R membrane protein, which indicated that both the expression and membrane trafficking of P2X3R were inhibited by EA. The immunofluorescence assay showed that EA stimulation exerted functions by reducing the expression of P2X3R-positive cells in ipsilateral DRGs of BCP rats. Ca2+ imaging analysis revealed that the EA stimulation decreased the percentage of α,ß-meATP responsive neurons in DRGs and inhibited calcium influx. Notably, the inhibitory effect of EA on mechanical allodynia and nociceptive flinches was abolished by intrathecal injection of α,ß-meATP. These findings demonstrated EA stimulation ameliorated mechanical allodynia and thermal hyperalgesia in rat model of MRMT-1-induced BCP. EA exerts analgesic effect on BCP by reducing the overexpression and functional activity of P2X3R in ipsilateral DRGs of BCP rats. Our work first demonstrates the critical and overall role of P2X3R in EA's analgesia against peripheral sensitization of MRMT-1-induced BCP and further supports EA as a potential therapeutic option for cancer pain in clinic.

The Moxibustion-Induced Thermal Transport Effect Between the Heart and Lung Meridians With Infrared Thermography.

Objectives: By comparing the differences in the thermal transport effect between the heart and lung meridians induced by moxibustion, this study aimed to investigate the specificity of site-to-site associations on the body surface between different meridians. Methods: Eighty healthy participants were divided into the heart meridian intervention group and the lung meridian intervention group; moxibustion was performed at these two meridians, respectively. Baseline temperature and its change magnitude from baseline induced by moxibustion in 6 measuring sites of the heart and lung meridians were assessed by infrared thermography (IRT). Measuring sites included: Site 1 (Chize, LU5), Site 2 (midpoint of LU9 and LU5), Site 3 (Taiyuan, LU9), Site 4 (Shaohai, HT3), Site 5 (midpoint of HT7 and HT3), and Site 6 (Shenmen, HT7). Results: Forty participants (20 male and 20 female, 27.90 ± 0.52 years) were assigned to the heart meridian intervention group, and 40 participants (20 male and 20 female, 28.08 ± 0.54 years) were assigned to the lung meridian intervention group. In the lung meridian intervention group (moxibustion over LU5), the temperature of the distal sites in the lung meridian increased significantly at 5, 10, and 15 min compared with pre-moxibustion (P < 0.001). The temperature of Site 4 in the heart meridian, which was nearest to the moxibustion site, increased significantly compared with pre-moxibustion (P < 0.05), while the temperature in the distal sites of the heart meridian did not differ significantly during moxibustion. Regarding the comparison of temperature change magnitude from baseline (ΔT) between the two meridians, the ΔT of Site 2 in the lung meridian was significantly higher than Site 4 in the heart meridian at 5 and 10 min after moxibustion (P < 0.05), despite that Site 2 was more distal from the moxibustion site than Site 4. Similarly, the ΔT of Site 3 in the lung meridian was significantly higher than Site 5 and Site 6 in the heart meridian at 5, 10, and 15 min after moxibustion (P < 0.05). In the heart meridian invervention group, similar thermal transport effect between the two meridians was observed. The thermal transport effect of the distal sites along the heart meridian was more significant than that of the site closer to the moxibustion site but located in the lung meridian. Taken together, aforementioned results indicated that the moxibustion-induced thermal transport effect between the heart and lung meridians is generally more significant in the distal sites along the corresponding meridian than that in the closer sites of the other meridian. Conclusions: In the heart and lung meridians, the moxibustion-induced thermal transport effect is closely related to meridian routes, not just related to the absolute distance from the moxibustion site, thereby confirming the relative specificity of "site-to-site" associations on the body surface in these two meridians. Systematic Review Registration: https://clinicaltrials.gov/ct2/show/NCT05330403, identifier NCT05330403.

Biochemical and structural characterization of the cyanophage-encoded phosphate-binding protein: implications for enhanced phosphate uptake of infected cyanobacteria.

To acquire phosphorus, cyanobacteria use the typical bacterial ABC-type phosphate transporter, which is composed of a periplasmic high-affinity phosphate-binding protein PstS and a channel formed by two transmembrane proteins PstC and PstA. A putative pstS gene was identified in the genomes of cyanophages that infect the unicellular marine cyanobacteria Prochlorococcus and Synechococcus. However, it has not been determined whether the cyanophage PstS protein is functional during infection to enhance the phosphate uptake rate of host cells. Here we showed that the cyanophage P-SSM2 PstS protein was abundant in the infected Prochlorococcus NATL2A cells and the host phosphate uptake rate was enhanced after infection. This is consistent with our biochemical and structural analyses showing that the phage PstS protein is indeed a high-affinity phosphate-binding protein. We further modelled the complex structure of phage PstS with host PstCA and revealed three putative interfaces that may facilitate the formation of a chimeric ABC transporter. Our results provide insights into the molecular mechanism by which cyanophages enhance the phosphate uptake rate of cyanobacteria. Phosphate acquisition by infected bacteria can increase the phosphorus contents of released cellular debris and virus particles, which together constitute a significant proportion of the marine dissolved organic phosphorus pool.

Acupuncture therapies for postherpetic neuralgia: a protocol for a systematic review and Bayesian network meta-analysis.

INTRODUCTION: Postherpetic neuralgia (PHN) is the most common sequela of herpes zoster, and it is often refractory to guideline-recommended treatments. Acupuncture therapy, a wildly applied complementary-alternative treatment, may help in the management of PHN. Diverse types of acupuncture therapy for PHN have been proposed, however, their comparative efficacies remain unclear. This study protocol plans to compare the efficacy and safety of different acupuncture therapies for PHN. METHODS AND ANALYSIS: Databases including MEDLINE, Embase, Cochrane Library, Web of Science, Chinese Biomedical Database, China National Knowledge Infrastructure, VIP Database, Wanfang Database, WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, Chinese Clinical Trial Register and OpenGrey will be searched from their inception to January 2022. Randomised controlled trials (RCTs) assessing the effectiveness of acupuncture therapy on the management of PHN will be selected. The primary outcome is pain intensity. Secondary outcomes include negative emotions, sleep condition, quality of life and adverse events. Reviewers will conduct study selection, data extraction and risk of bias assessment procedures. Then, standard pair-wised meta-analysis and Bayesian network meta-analysis will be performed (if applicable). The Confidence in Network Meta-Analysis application will be used to assess the confidence in the evidence for the primary outcome. ETHICS AND DISSEMINATION: All data used for this study will be extracted from published RCTs, thus, no ethical approval will be required. The results of this systematic review will be disseminated through peer-reviewed journal and conference presentation. PROSPERO REGISTRATION NUMBER: CRD42020219576.

[Effect of electroacupuncture and pretreatment of electroacupuncture on pain sensitization and expression of P2X7R in spinal dorsal horn in rats with diabetic neuropathic pain].

OBJECTIVE: To observe the occurrence time of neuralgia and the expression of purinergic ligand-gated ion channel 7 receptor (P2X7R) in the dorsal horn of the spinal cord after intraperitoneal injection of streptozotocin (STZ) in diabetic rats, and to explore the effect of electroacupuncture (EA) and pretreatment of EA on the heat pain threshold and expression of P2X7R in the spinal dorsal horn in rats with diabetic neuropathic pain (DNP), and to explore the possible mechanism of EA for DNP. METHODS: PartⅠ: Thirty male SD rats were randomly selected from 64 male SD rats as the control group; the remaining rats were given intraperitoneal injection of STZ (10 mg/mL) at a dose of 65 mg/kg to establish the diabetes model, and 30 rats were successfully modeled as the model group. The control group and the model group were divided into three subgroups respectively at 7, 14 and 21 days, with 10 rats in each subgroup. Body mass, fasting blood glucose (FBG) and thermal pain threshold were recorded at 7, 14 and 21 days after injection; the expression of P2X7R in spinal dorsal horn was detected by Western blot. PartⅡ: Eight SD rats were randomly selected from 35 male SD rats as the blank group, and the remaining 27 rats were given intraperitoneal injection of STZ (10 mg/mL) at a dose of 65 mg/kg to establish the diabetes model. The 24 rats with successful diabetes model were randomly divided into a DNP group, an EA group and a pre-EA group, 8 rats in each group. Fifteen to 21 days after STZ injection, the EA group received EA at "Zusanli" (ST 36) and "Kunlun" (BL 60), continuous wave, frequency of 2 Hz, 30 min each time, once a day; the intervention method in the pre-EA group was the same as that in the EA group. The intervention time was 8 to 14 days after STZ injection. The body mass, FBG and thermal pain threshold were recorded before STZ injection and 7, 14 and 21 days after STZ injection; the expression of P2X7R in spinal dorsal horn was detected by Western blot 21 days after injection. RESULTS: PartⅠ: Compared with the control group, in the model group, the body mass was decreased and FBG was increased 7, 14 and 21 days after STZ injection (P<0.01), and the thermal pain threshold was decreased 14 and 21 days after STZ injection (P<0.05), and the expression of P2X7R in spinal dorsal horn was increased 7, 14 and 21 days after STZ injection (P<0.05, P<0.01). PartⅡ: Compared with the blank group, in the DNP group, the body mass was decreased and fasting blood glucose were increased 7, 14 and 21 days after STZ injection (P<0.01). Compared with the DNP group, in the pre-EA group, the heat pain threshold was increased 14 and 21 days after STZ injection (P<0.05), while in the EA group, the heat pain threshold was increased 21 days after STZ injection (P<0.01), and the expression of P2X7R in the dorsal horn in the EA group and the pre-EA group was decreased (P<0.01). CONCLUSION: The diabetic neuropathic pain is observed 14 days after STZ injection. EA could not only treat but also prevent the occurrence of DNP, and its mechanism may be related to down-regulation of P2X7R expression in the dorsal horn of the spinal cord.

Acupuncture and related therapies for carpal tunnel syndrome: A protocol for systematic review and Bayesian network meta-analysis.

BACKGROUND: Carpal tunnel syndrome (CTS) is the most common peripheral nerve compression syndrome of the upper limb. Plenty of studies showed the effects of acupuncture therapy on relieving pain and improving functional status for CTS patients. Diverse types of acupuncture therapies have been used in the treatment for CTS, but their relative treatment effects are poorly understood. This study will evaluate the effects of different acupuncture and related therapies for CTS by conducting a systematic review and Bayesian network meta-analysis (NMA). METHODS: We will search randomized controlled trials (RCTs) of acupuncture and related therapies for CTS in MEDLINE (via PubMed), EMBASE, Web of Science, Cochrane Library, Chinese Biomedical Database, China National Knowledge Infrastructure, VIP Database, Wanfang Database, WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, Chinese Clinical Trial Register, and OpenGrey from inception to November 2021. Then, we will select eligible studies, extract data, and conduct risk of bias assessment using the Cochrane tool. Pairwise meta-analysis and Bayesian NMA will be performed in Stata 15.1 software and Aggregate Data Drug Information System 1.16.8 software. We will assess the quality of the evidence using the Confidence in Network Meta-Analysis application. RESULTS: In this study, the treatment effects and safety of different acupuncture and related therapies for CTS will be evaluated. CONCLUSION: This study will provide evidence for choosing the optimal acupuncture and related therapies in the treatment for CTS.

Status, reporting completeness and methodological quality of pilot randomised controlled trials in acupuncture: protocol for a systematic review.

INTRODUCTION: To date, there has been a lack of knowledge about the status, reporting completeness and methodological quality of pilot trials in the acupuncture field. Thus, this systematic review protocol aims to: (1) investigate publication trends and aspects of feasibility evaluated in acupuncture pilot trials; (2) identify the proportion of acupuncture pilot trials that lead to definitive trials and (3) assess the reporting completeness and methodological quality of pilot trials in acupuncture. METHODS AND ANALYSIS: Studies of acupuncture pilot randomised controlled trials published from 2011 to 2021 will be retrieved in seven databases in January 2022, including PubMed, Web of Science, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang Database and Chinese Biomedical Literature Database. The methodological quality and reporting completeness of all included studies will be assessed using the risk of bias 2.0 tool (RoB 2) and the Consolidated Standards of Reporting Trials (CONSORT) extension to randomised pilot and feasibility trials, respectively. For the primary analysis, publication trends, aspects of feasibility and the proportion of pilot trials that lead to definitive trials will be analysed. A quantitative analysis of the methodological quality and reporting completeness of the included trials will be implemented by calculating the percentage of items reported in each domain of RoB 2 and CONSORT. The secondary analysis will adopt a regression analysis to identify factors associated with the reporting completeness. ETHICS AND DISSEMINATION: Ethical approval is not required for this study. This study is planned to be submitted to a peer-reviewed academic journal.

Acupuncture for treating chronic stable angina pectoris associated anxiety and depression: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Despite that acupuncture is effective in treating anxiety, depression and chronic stable angina pectoris (CSAP), it remains unclear whether acupuncture can treat CSAP, anxiety and depression simultaneously. This systematic review and meta-analysis aimed to investigate the efficacy of acupuncture on CSAP-associated anxiety and depression. METHODS: Eight electronic databases were searched to identify eligible randomized controlled trials (RCTs) or controlled clinical trials (i.e. "acupuncture alone or combined with standard care" versus " sham acupuncture alone, sham acupuncture with standard care, or standard care alone") from their inception to January 2021, which included PubMed, Embase, Web of Science, the Cochrane Library, CBM, CNKI, VIP and Wanfang Database. Data were extracted and meta analyses were performed using the RevMan 5.3. Risk of bias (ROB) 2.0 was used for methodological quality assessment. GRADEprofiler 3.2.2 was used to rate the quality of evidence. RESULTS: Seven trials involving 893 subjects were included. Meta-analysis results showed that acupuncture combined with standard care was more effective in relieving anxiety and depression, reducing angina attack frequency, and angina pain intensity than sham acupuncture with standard care and standard care alone. In addition, the effect remained until 16 weeks after acupuncture. The safety of acupuncture for CSAP-associated anxiety and depression was also high. Nonetheless, the quality of evidence ranged from low to moderate. CONCLUSION: Acupuncture may be used as an adjunctive therapy to treat CSAP-associated anxiety and depression. However, more high-quality RCTs are required to confirm our findings.

Electroacupuncture Regulates Pain Transition Through Inhibiting PKCε and TRPV1 Expression in Dorsal Root Ganglion.

Many cases of acute pain can be resolved with few side effects. However, some cases of acute pain may persist beyond the time required for tissue injury recovery and transit to chronic pain, which is hard to treat. The mechanisms underlying pain transition are not entirely understood, and treatment strategies are lacking. In this study, the hyperalgesic priming model was established on rats to study pain transition by injection of carrageenan (Car) and prostaglandin E2 (PGE2). The expression levels of protein kinase C epsilon (PKCε) and transient receptor potential vanilloid 1 (TRPV1) in the L4-L6 dorsal root ganglion (DRG) were investigated. Electroacupuncture (EA) is a form of acupuncture in which a small electric current is passed between a pair of acupuncture needles. EA was administrated, and its effect on hyperalgesia and PKCε and TRPV1 expression was investigated. The PKCε-TRPV1 signaling pathway in DRG was implicated in the pain transition. EA increased the pain threshold of model animals and regulated the high expression of PKCε and TRPV1. Moreover, EA also regulated hyperalgesia and high TRPV1 expression induced by selective PKCε activation. We also found that EA partly increased chronic pain threshold, even though it was only administered between the Car and PGE2 injections. These findings suggested that EA could prevent the transition from acute to chronic pain by inhibiting the PKCε and TRPV1 expression in the peripheral nervous system.

Difference in Moxibustion-Induced Microcirculatory Responses between the Heart and Lung Meridians Assessed by Laser Doppler Flowmetry.

OBJECTIVE: By comparing the differences in microcirculatory responses of the heart and lung meridians induced by moxibustion on these two meridians, respectively, this study aimed to investigate the specificity for site-to-site association on body surface between different meridians. METHODS: Eighty healthy adults were enrolled and divided into the lung meridian intervention group and heart meridian intervention group in a ratio of 1 : 1. Three-channel laser Doppler flowmetry was used to monitor microcirculatory responses for the heart and lung meridians. Primary outcome was change of blood perfusion units (PU) of three measurement sites along the two meridians. RESULTS: In the lung meridian intervention group, following moxibustion performed at LU5 of the lung meridian, PU in the distal site of the lung meridian increased significantly. By contrast, the PU of HT3 in the heart meridian, which was nearest to the moxibustion site, did not change significantly. PU in the distal site of the heart meridian declined. Meanwhile, significant difference in PU change was detected between the distal site of the lung meridian and the other two control sites of the heart meridians during moxibustion and postmoxibustion. Alternatively, similar to the results of the lung meridian intervention group, the specificity of microcirculatory response between the heart and lung meridians was observed in the heart meridian intervention group. CONCLUSIONS: For the heart and lung meridians, the effect of moxibustion-induced microcirculatory response may be more related to meridian routes than the specific distance between two sites located at different meridians, thereby supporting possible specificity for site-to-site association on the body surface between these two meridians. Nevertheless, given that only two meridians and limited measurement sites were compared, all current findings are not sufficiently robust. Further research should be conducted to investigate more meridians and measurement sites.

[Clinical efficacy and safety of moxibustion as adjuvant therapy for COPD in stable phase: a Meta-analysis].

OBJECTIVE: To systematically evaluate the efficacy and safety of conventional therapy combined with moxibustion in the treatment of chronic obstructive pulmonary disease (COPD) in stable phase based on Meta-analysis medicine. METHODS: The randomized controlled trials (RCTs) of moxibustion as adjuvant therapy for COPD were retrieved from the databases of CNKI, Wanfang, SinoMed, PubMed, Web of Science, Cochrane Library and Ebsco. RevMan5.3 software was used for Meta analysis, and the quality of evidence was evaluated according to GRADE standards. RESULTS: A total of 16 RCTs were included, involving 1425 patients. The results of Meta-analysis showed that: compared with the conventional treatment, ①the adjuvant therapy with moxibustion had advantages in reducing the number of acute exacerbations [MD=-0.31, 95%CI:-0.49--0.13, P=0.0006]; ②the adjuvant therapy with moxibustion improved lung function significantly [FEV1% (MD=4.00, 95%CI:2.63-5.37, P<0.000 01) and FEV1/FVC (MD=3.56, 95%CI:1.69-5.43, P=0.000 2)]; ③the adjuvant therapy with moxibustion could extend the 6 min walking distance (6WMD) (MD=35.00, 95%CI:18.02-51.99, P<0.000 1); ④the adjuvant therapy with moxibustion could improve the modified British Medical Research Council breathing questionnaire (mMRC) classification significantly (MD=-0.62, 95%CI:-1.18--0.05, P=0.03); ⑤no adverse reaction was reported in the included literature. CONCLUSION: The efficacy of moxibustion as adjuvant therapy for COPD in stable phase is better than that of simple conventional therapy. Due to insufficient clinical evidence and the limitations of this study, clinical safety is unclear and further evidence is needed to support the results.

[Discussion on "guiding meridian sinew qi along with meridian running course" in treatment of meridian sinew disorders].

It is to determine the effect mechanism and therapeutic method of the idea as "guiding meridian sinew qi along with meridian running course" for meridian sinew disorders so as to provide the reference for clinical treatment of these disorders. "Guiding meridian sinew qi along with meridian running course" is the summary for the approach to meridian sinew disorders by YANG Shang-shan, recorded in Huangdi Mingtang Jing (The Yellow Emperor's Acupoints Canon of Mingtang ), but the concrete statement on it had been lost. By investigating the existing ancient works, the authors discussed the specific meaning of jinqi (meridian sinew qi ), the relationship between jingjin (meridian sinew) and jingmai (meridian), the method of "guiding meridian sinew qi along with meridian running course" and its preferable acupoint selection for treatment of meridian sinew disorders with both the primary and the secondary considered.

The difference in heat transport characteristics of the heart and lung meridians: A comparative study of COPD patients and healthy subjects.

BACKGROUND: The vast majority of previous studies focused on the relationship between 1 meridian and 1 organ, and the comparison and specificity between 2 meridians is rarely explored. Thus, the aim of this study is to compare the heat transport characteristics between 2 different meridians and the specificity between them will also be investigated. METHODS: The Lung and Heart meridians are chosen for comparison of 2 different meridians. We will enroll 120 subjects and divide them into the healthy control group, chronic obstructive pulmonary disease (COPD) group and healthy intervention group, in a 1:1:1 ratio. Infrared thermography (IRT) will be used to assess the heat transport characteristics of the Heart and Lung meridians. The specificity for the meridian-visceral association will be investigated by comparing the difference in heat transport characteristic between the Heart and Lung meridians in the healthy control group and COPD group. Meanwhile, moxibustion will be given to subjects in the Heart meridian and Lung meridian respectively in the healthy intervention group to verify the specificity for the surface-surface association. RESULTS: The primary outcomes will be the temperature of corresponding sites along the Heart and Lung meridians. CONCLUSION: This study will verify the specificity between different meridians by comparing the difference in heat transport characteristic. The findings will guide the selection of acupoints to optimize the therapeutic effect of acupuncture and help determine whether IRT could be used to assist in the diagnosis of COPD. ETHICS AND DISSEMINATION: The study has been approved by the Third Affiliated Hospital of Zhejiang Chinese Medical University (Approval No. ZSLL-KY-2019-001G-01). TRIAL REGISTRATION NUMBERS: NCT04046588.