Effects of moxibustion on visceral hypersensitivity and colonic inflammatory response in mice with chronic ulcerative colitis. / è‰¾ç¸å¯¹æ ¢æ€§æºƒç–¡æ€§ç»“è‚ ç‚Žå°é¼ å† è„é«˜æ•åŠç»“è‚ ç»„ç»‡ç‚Žæ€§ååº”çš„å½±å“.

OBJECTIVES: To observe the effects of moxibustion at "Zusanli" (ST36) on the expression levels of tumor necrosis factor (TNF)-α, TNF receptor 1 (TNF-R1), p38 mitogen-activated protein kinase (P38 MAPK), and transient receptor potential vanilloid 1 (TRPV1) in the colon tissue of mice with chronic ulcerative colitis (UC), so as to explore the underlying mechanisms of moxibustion in improving visceral hypersensitivity in chronic UC. METHODS: Male C57BL/6J mice were randomly divided into normal group, normal with moxibustion (NM) group, model group, and model with moxibustion (MM) group, with 10 mice in each group. The chronic UC model was established by drinking 2.5% dextran sodium sulfate for 3 cycles. Mice in the NM and MM groups received moxibustion at ST36 for 20 min, 5 days per week with a 2-day break, for a total of 4 weeks. The disease activity index (DAI) score of each group was evaluated before and after treatment. The minimum volume threshold of abdominal wall retraction reflex (AWR) was measured to observe the intestinal sensitivity of mice. The colon length was measured. The pathological changes of colon tissue were observed by HE staining. The expression of mucin in colon goblet cells was detected by periodate Scheff staining. The intestinal fibrosis was observed by Masson staining. The number of trypsin-positive cells (i.e., mast cell) and the expression level of TNF-α in colon tissue were detected by immunofluorescence staining. The expression levels of TNF-R1, P38 MAPK and TRPV1 in colon tissue were detected by immunohistochemistry. RESULTS: Compared with the normal group after treatment, the model group showed increased DAI score (P<0.001), decreased AWR minimum volume threshold (P<0.01), shortened colon length (P<0.001), significant inflammatory infiltration in the colon tissue, reduced mucin secretion (P<0.01), increased collagen fiber deposition (P<0.001), and elevated expression levels of TNF-α, TNF-R1, P38 MAPK, and TRPV1 (P<0.001, P<0.01, P<0.05). Compared with the model group, the MM group showed decreased DAI score (P<0.01), increased AWR minimum volume threshold (P<0.001), elongated colon length (P<0.001), reduced inflammatory cell infiltration, improved integrity of mucosal glandular structure, enhanced mucin secretion (P<0.01), decreased collagen fiber deposition (P<0.001), decreased number of mast cells in the colon tissue (P<0.001), and decreased expression levels of TNF-α, TNF-R1, P38 MAPK, and TRPV1 (P<0.001, P<0.01, P<0.05). There were no significant differences in the above index between the NM group and the normal group. CONCLUSIONS: Moxibustion can reduce visceral hypersensitivity, alleviate inflammatory infiltration and fibrotic damage in the colon tissue of mice with chronic UC. These effects may be associated with the down-regulation of TNF-α, TNF-R1, P38 MAPK, and TRPV1 expression in colon.

Moxibustion influences hippocampal microglia polarization via IL-33/ST2 pathway in Alzheimer's disease mice. / è‰¾ç¸é€šè¿‡ç™½ç»†èƒžä»‹ç´ -33/ç”Ÿé•¿åˆºæ¿€è¡¨è¾¾åŸºå› 2è›‹ç™½é€šè·¯å½±å“é˜¿å°”èŒ¨æµ·é»˜ç— å°é¼ æµ·é©¬å°èƒ¶è´¨ç»†èƒžæžåŒ–.

OBJECTIVES: To observe the effect of moxibustion on the polarization of microglia towards M2 direction in Alzheimer's disease (AD) mice through the interleukin-33 (IL-33)/growth stimulating gene 2 protein (ST2) signaling pathway. METHODS: Five-month-old APP/PS1 male mice were randomly divided into model and moxibustion (Moxi) groups, and C57BL/6J mice of the same age were as the control group, with 9 mice in each group. In the Moxi group, moxibustion was applied at "Baihui" (GV20) and "Yongquan" (KI1) for 30 min, once a day, 5 days a week for 4 weeks. The spatial learning memory ability was observed by the Morris water maze test. The relative expressions of IL-33 and ST2 in hippocampus were detected by Western blot. The positive expression of amyloid-ß (Aß), phosphorylated Tau (p-Tau), IL-33/ionized calcium binding adapter molecule 1(Iba-1), ST2/Iba-1, arginase 1 (Arg1)/Iba-1 and indu-cible nitric oxide synthase (iNOS)/Iba-1 in hippocampal CA1 region were detected by immunofluorescence. RESULTS: Compared with the control group, the escape latency of the mice in the model group was prolonged (P<0.001, P<0.01), the number of times to enter the effective area and the percentage of target quadrant swimming time were reduced (P<0.001), the positive expression of both Aß and p-Tau, the positive expression of iNOS/Iba-1 in the hippocampal CA1 region was increased (P<0.001), while the expression of IL-33 and ST2 protein in hippocampal tissue, the positive expression levels of IL-33/Iba-1, ST2/Iba-1 and Arg1/Iba-1 in hippocampal CA1 region were all decreased (P<0.05, P<0.001). After treatment, compared with the model group, the escape latency of the mice in the moxibustion group was shortened (P<0.001, P<0.01), the number of entries into the effective area and the percentage of target quadrant swimming time were increased (P<0.001), the positive expression of Aß and p-Tau in the hippocampal CA1 region, and the positive expression of iNOS/Iba-1 were decreased (P<0.001), while the expression of IL-33 and ST2 protein in the hippocampal tissue, the positive expression of IL-33/Iba-1, ST2/Iba-1 and Arg1/Iba-1 in hippocampal CA1 region were all increased (P<0.05, P<0.01, P<0.001). CONCLUSIONS: Moxibustion can improve the spatial learning and memory abilities, reduce the pathological deposition of Aß and p-Tau in APP/PS1 mice, which may be related to its function in up-regulating the IL-33/ST2 signaling pathway to regulate the polarization of microglia towards M2 direction.

Electroacupuncture alleviates ulcerative colitis by targeting CXCL1: evidence from the transcriptome and validation.

Background: We aimed to use transcriptomics, bioinformatics analysis, and core gene validation to identify the core gene and potential mechanisms for electroacupuncture (EA) treatment of ulcerative colitis (UC). Materials and methods: EA was performed in mice after induction of UC via dextran sodium sulfate. Body weight, disease activity index (DAI), colon length, and hematoxylin-eosin of the colon tissue were used to evaluate the effects of EA. Mice transcriptome samples were analyzed to identify the core genes, and further verified with human transcriptome database; the ImmuCellAI database was used to analyze the relationship between the core gene and immune infiltrating cells (IICs); and immunofluorescence was used to verify the results. Results: EA could reduce DAI and histological colitis scores, increase bodyweight and colon length, and improve the expression of local and systemic proinflammatory factors in the serum and colon of UC mice. Eighteen co-differentially expressed genes were identified by joint bioinformatics analyses of mouse and human transcriptional data; Cxcl1 was the core gene. EA affected IICs by inhibiting Cxcl1 expression and regulated the polarization of macrophages by affecting the Th1 cytokine IFN-γ, inhibiting the expression of CXCL1. Conclusions: CXCL1 is the target of EA, which is associated with the underlying immune mechanism related to Th1 cytokine IFN-γ.

Matrix metalloproteinases are key targets of acupuncture in the treatment of ulcerative colitis.

The aim of this study was to elucidate the key targets of acupuncture in the colon of ulcerative colitis (UC) mice model using full-length transcriptome sequencing. 2.5% dextran sodium sulfate (DSS)-induced colitis mice were treated with or without acupuncture. Intestinal pathology was observed, and full transcriptome sequencing and bioinformatic analysis were performed. The results demonstrated that acupuncture treatment reduced the UC symptoms, disease activity index score, and histological colitis score and increased body weight, colon length, and the number of intestinal goblet cells. In addition, acupuncture can also decrease the expression of necrotic biomarker phosphorylates mixed lineage kinase domain-like pseudo kinase (p-MLKL). Full-length transcriptome analysis indicated that acupuncture reversed the expression of 987 of the 1918 upregulated differentially expressed genes (DEGs), and 632 of the 1351 downregulated DEGs induced by DSS. DEGs regulated by acupuncture were mainly involved in inflammatory responses and intestinal barrier pathways. The protein-protein interaction network analysis revealed that matrix metalloproteinases (MMPs) are important genes regulated by acupuncture. Gene set enrichment analysis revealed that extracellular matrix (ECM)-receptor interaction was an important target of acupuncture. In addition, alternative splicing analysis suggested that acupuncture improved signaling pathways related to intestinal permeability, the biological processes of xenobiotics, sulfur compounds, and that monocarboxylic acids are closely associated with MMPs. Overall, our transcriptome analysis results indicate that acupuncture improves intestinal barrier function in UC through negative regulation of MMPs expression.

[Effect of electroacupuncture on Notch/NF-κB signaling pathway in colonic mucosa of mice with ulcerative colitis].

OBJECTIVE: To observe the protective effect of electroacupuncture (EA) on the intestinal mucosal barrier and its relationship with the Notch/NF-κB signaling pathway in mice with ulcerative colitis (UC), so as to explore its mechanism of treating UC. METHODS: Male C57BL/6J mice were randomized into control, model and EA groups, with 6 mice in each group. The UC model was established by giving the mice with 2% Dextran Sulfate Sodium (DSS) for 7 days. EA (2 Hz/15 Hz, 0.2 mA) was applied at bilateral "Zusanli" (ST36) for 30 min, once a day for 7 days. The disease activity indexes ï¼»DAI=(body weight index score+stool score+bleeding score)/3; 0-4 pointsï¼½ of mice were calculated. The morphological changes of colonic tissues of mice in each group were observed by HE staining, and serum contents of TNF-α and IL-6 were detected by ELISA. Claudin-1 protein expression in colon tissue was detected by immunofluorescence, while the protein expression levels of Muc-2, Notch-1, MMP-9 in colon tissue were detected by immunohistochemistry. The real-time PCR method was used to detect the expression levels of Notch-1, Hes-1, NF-κB, TLR-4 and AKT mRNA in colon tissues. RESULTS: After modeling, the DAI, serum TNF-α and IL-6 contents, Notch-1 and MMP-9 protein expression, the relative expression levels of Notch-1, Hes-1, NF-κB, TLR-4 and AKT mRNA in the colonic tissue were significantly increased (P<0.001, P<0.01) in the model group relevant to the control group. At the same time, Claudin-1 and Muc-2 protein expression were significantly reduced (P<0.01). After the EA intervention, the increased DAI score, TNF-α and IL-6 contents, Notch-1 and MMP-9 protein expression, the relative expressions of Notch-1, Hes-1, NF-κB, TLR-4 and AKT mRNA, and the decreased Claudin-1 and Muc-2 protein expression were all reversed compared with the model group (P<0.05, P<0.01, P<0.001). H.E. staining of the colonic tissue showed damage and infiltration of inflammatory cells in the model group, and those were significantly improved in the EA group. CONCLUSION: EA can promote the recovery of intestinal mucosal barrier function and reduce inflammatory reaction in UC mice, which may be associated with its effects in inhibiting the excessive activation of the Notch/NF-κB signaling pathway.

The Effects of Moxibustion on Learning and Memory and m6A RNA Methylation in APP/PS1 Mice.

Objectives: To study whether moxibustion can improve the learning and memory ability of APP/PS1 mice by reducing the pathological products Aß and Tau protein via decreasing N6-methyladenosine (m6A). Methods: APP/PS1 mice were randomly divided into model group (APP/PS1) and moxibustion group (APP/PS1+Mox). C57BL/6J mice were used as a control group (Control). Learning and memory abilities were assessed by the Morris water maze. Aß, Tau, phosphorylated Tau (p-Tau), and YTHDF1 proteins were detected in the mouse cortex and hippocampus by immunofluorescence and western blot. Altered m6A expression levels in hippocampal and cortical tissues were measured with the m6A RNA methylation quantification assay kit. RNA transcript levels of YTHDF1, METTL3, and FTO in the hippocampus and cortex were measured by q-PCR. Results: Moxibustion shortened the escape latency, increased the number of platform crossings, and increased the percentage of swimming time in the target quadrant of APP/PS1 mice. Meanwhile, moxibustion reduced the levels of Aß, Tau, and p-Tau proteins both in the hippocampal and cortical regions of APP/PS1 mice. In addition, the total amount of m6A in the hippocampal and cortical regions of APP/PS1 mice was significantly reduced after moxibustion. The expression of YTHDF1 in the hippocampal region of APP/PS1 mice increased and that in the cortical region decreased after moxibustion treatment. Conclusion: Moxibustion improves the learning and memory abilities and reduces the deposition of Aß and Tau protein pathological products in APP/PS1 mice. This may be related to the fact that moxibustion reduces the total amount of m6A and inhibits its binding enzyme YTHDF1 in the hippocampus and cortex of APP/PS1 mice.

Pharmacokinetics and Pharmacodynamics of Huanglian-Houpo Decoction Based on Berberine Hydrochloride and Magnolol Against H1N1 Influenza Virus.

BACKGROUND AND OBJECTIVES: Huanglian-Houpo decoction (HH), which is recorded in the famous traditional Chinese medicine monograph "Puji Fang," contains two individual herbs, Huanglian (Rhizoma coptidis) and Houpo (Magnoliae officinalis cortex). It was regularly used to treat seasonal epidemic colds and influenzas in ancient China. Our laboratory discovered that HH has a significant anti-H1N1 influenza virus effect. However, no pharmacokinetic and pharmacodynamic data concerning the anti-H1N1 influenza virus activity of HH are available to date. In the current study, the concentration-time profiles of two major components of HH, berberine and magnolol, in rat plasma were investigated. METHODS: An integrate pharmacokinetic approach was developed for evaluating the holistic pharmacokinetic characteristics of berberine and magnolol from HH. Additionally, the inhibition rate and levels of IFN-ß in MDCK cells infected by influenza virus were analyzed. Data were calculated using 3p97 with pharmacokinetic analysis. RESULTS: The estimated pharmacokinetic parameters were maximum plasma concentration (Cmax) 0.9086 µg/ml, area under the concentration-time curve (AUC) 347.74 µg·min/ml, and time to reach Cmax (Tmax) 64.69 min for berberine and Cmax = 0.9843 µg/ml, AUC= 450.64 µg·min/ml, Tmax = 56.86 min for magnolol, respectively. Furthermore, integrated pharmacokinetic and pharmacodynamic analysis showed that the highest plasma concentration, inhibition rate and interferon-ß (IFN-ß) secretion of HH first increased and then weakened over time, reaching their peaks at 60 min. The plasma concentration of HH is directly related to the anti-influenza virus effect. CONCLUSION: The results indicated that berberine and magnolol are the main active ingredients of HH related to its anti-influenza virus effect, which is related to the improvement of IFN-ß secretion.

The efficacy of bloodletting therapy in patients with acute gouty arthritis: A systematic review and meta-analysis.

BACKGROUND: Bloodletting therapy (BLT) is widely used to relieve acute gouty arthritis (AGA). However, limited evidence-based reports exist on the effectiveness and safety of BLT. This systematic review aims to evaluate the feasibility and safety of BLT in treating AGA. METHODS: Seven databases were exhaustively screened from the date of establishment to July 31, 2020, irrespective of the publication source and language. The included articles were evaluated for bias risk by using the Cochrane risk of bias assessment tool. All statistical analyses were done with Review Manager 5.3. RESULTS: Twelve studies involving 894 participants were included for the final analysis. Our meta-analysis revealed that BLT was highly effective in relieving pain (MD = -1.13, 95% CI [-1.60, -0.66], P < 0.00001), with marked alterations in the total effective (RR = 1.09, 95% [1.05, 1.14], P < 0.0001) and curative rates (RR = 1.37, 95%CI [1.17, 1.59], P < 0.0001). In addition, BLT could dramatically reduce serum C-reactive protein (CRP) level (MD = -3.64, 95%CI [-6.72, -0.55], P = 0.02). Both BLT and Western medicine (WM) produced comparable decreases in uric acid (MD = -18.72, 95%CI [-38.24, 0.81], P = 0.06) and erythrocyte sedimentation rate (ESR) levels (MD = -3.01, 95%CI [-6.89, 0.86], P = 0.13). Lastly, we demonstrated that BLT was safer than WM in treating AGA (RR = 0.36, 95%CI [0.13, 0.97], P = 0.04). CONCLUSION: BLT is effective in alleviating pain and decreasing CRP level in AGA patients with a lower risk of evoking adverse reactions.

Improvement of intestinal flora: accompany with the antihypertensive effect of electroacupuncture on stage 1 hypertension.

BACKGROUND: Increasing evidence have indicated the relationship between intestinal dysbiosis and hypertension. We aimed to evaluate the effect of the electroacupuncture (EA) on intestinal microbiota in patients with stage 1 hypertension. METHODS: 93 hypertensive patients and 15 healthy subjects were enrolled in this study. Applying a highly accurate oscillometric device to evaluate the antihypertensive effect of EA. 16S rRNA sequencing was used to profile stool microbial communities from Healthy group, Before treatment (BT) group and After treatment (AT) group, and various multivariate analysis approaches were used to assess diversity, composition and abundance of intestinal microbiota. RESULTS: In this study, EA significantly decreased the blood pressure (BP) of hypertensive patients. Higher abundance of Firmicutes and lower Bacteroidetes abundance were observed in the BT group compared to the Healthy group. And EA treatment significantly decreased the Firmicutes/Bacteroidetes ratio compared to the BT group. Moreover, at the genus level, there was an increased abundance of Escherichia-Shigella in patients with hypertension, while Blautia were decreased, and EA reversed these changes. CONCLUSIONS: Our study indicates that EA can effectively lower BP and improve the structure of intestinal microbiota which are correlate with the alteration of blood pressure by electroacupuncture. TRIAL REGISTRATION: Clinicaltrial.gov, NCT01701726. Registered 5 October 2012, https://clinicaltrials.gov/ct2/show/study/NCT01701726.

Mitochondrial Respiratory Chain and Its Regulatory Elements SIRT1 and SIRT3 Play Important Role in the Initial Process of Energy Conversion after Moxibustion at Local Skin.

OBJECTIVES: To study how thermal energy is converted after moxibustion at local skin from the view of mitochondrial respiratory chain and its key regulatory elements of sirtuins 1 (SIRT1) and sirtuins 3 (SIRT3). METHODS: Two moxibustion temperatures usually used in clinical practice (38°C and 46°C) were applied to Zusanli (ST36) acupoint for 30 minutes in C57BL/6J mice. Local skin samples were harvested at 30 min and 72 h after moxibustion intervention, respectively. The activity of mitochondrial respiratory chain complexes I-V was detected by spectrophotometry. The expression of SIRT1 and SIRT3 protein was detected by immunofluorescence staining or western blot. RESULTS: Moxibustion at 38°C triggered more significant increase of mitochondrial respiratory chain complexes I-V expression. However, the protein expression of SIRT1 and SIRT3 at 46°C showed more obvious enhancement. In addition, the effect of mitochondrial respiratory chain complexes I-V activity on local skin of ST36 acupoint was more obvious at 30 min after moxibustion, while the expression of SIRT1 and SIRT3 protein was more significant at 72 h after moxibustion. CONCLUSION: Mitochondrial respiratory chain and its key regulatory element proteins SIRT1 and SIRT3 play important role in the initial process of thermal energy conversion stimulated by different moxibustion temperatures in local skin.

[Effect of acupuncture and moxibustion on expression of signal transducers and activators of transcription 3 and hypoxia-inducible factor 1α in colon mucosa in ulcerative colitis mice].

OBJECTIVE: To investigate the effect of acupuncture or moxibustion of "Zusanli" (ST36) and "Guanyuan" (CV4) on expression of signal transducers and activators of transcription 3 (STAT3) and hypoxia-inducible factor 1α (HIF-1α) in colonic tissue in ulcerative colitis (UC) mice. METHODS: Thirty-two male Kunming mice were randomly divided into control, model, acupuncture and moxibustion groups (n=8 in each group). The UC model was induced by free drinking of 3% Dextran Sodium Sulfate for 7 days. Acupuncture or moxibustion was applied to ST36 or CV4 for 15 min, once daily for 5 days. The severity of UC was monitored using the disease activity index (DAI) which includes evaluation of weight loss, stool consistency, and presence of fecal blood. Histopathological changes of the colon mucosa were observed by H.E. staining. Immunohistochemistry and Western blot were employed to detect the expression of STAT3 and HIF-1α proteins in the colon mucosa tissue. RESULTS: After modeling, the DAI, immunoactivity and expression of STAT3 and HIF-1α in the colonic tissue were significantly increased in the model group relevant to the control group (P<0.01,P<0.05). Compared with the model group, the levels of DAI, STAT3 and HIF-1α considerably decreased in both acupuncture and moxibustion groups (P<0.05), and without significant differences between the two intervention groups in the levels of DAI, STAT3 and HIF-1α after the intervention (P>0.05). H.E. staining of the colonic tissue showed damage and infiltration of inflammatory cells in the model group, and reduction of the submucosal edema and infiltrated inflammatory cells in the acupuncture and moxibustion groups. CONCLUSION: Both acupuncture and moxibustion can improve UC in UC mice, which may be associated with its effects in down-regulating the expression of colonic STAT3 and HIF-1α proteins.

[Epidemiological characteristics of acupuncturists who are sensitive to stimulation of moxa smoke: a face-to-face sectional survey based on 733 participants].

OBJECTIVE: To explore the epidemiologic characteristics of acupuncturists who are sensitive to stimulation of moxa smoke, which could provide further direction for safety protection of exerting moxibustion and to further verify the feasibility of internet survey. METHODS: A self-made questionnaire regarding body response to moxa smoke was established, which was used to conduct a face-to-face survey among acupuncturists who had performed long-term moxibustion. The Logistic regression model was used to analyze the factors affecting the stimulation response of acupuncturists and the epidemiological characteristics of acupuncturists was obtained. RESULTS: A total of 733 valid data was obtained. The multivariate Logistic regression analysis showed that the history of chronic respiratory disease was the main risk factor of stimulus response including cough, phlegm in the throat, asthma, dyspnea, shortness of breath and nasal dryness after exposure to moxa smoke (P<0.05, P<0.01). The risk of stimulus response such as cough, tearing and nasal dryness was higher in women than in men (P<0.05, P<0.01). The risk of dry eyes and eyes pain in smokers was higher than those in non-smokers (P<0.05). The risk of shortness of breath in those who were exposed to second-hand smoke was higher than those who were not exposed to second-hand smoke (P<0.05). The analysis of index trend line showed that the results of internet survey were similar to those of face-to-face survey. CONCLUSION: The stimulus response of acupuncturist after long-term exposure to moxa smoke is related to the history of chronic respiratory disease, being female, smoking or exposure of second-hand smoke, therefore more attention should be paid to those populations. In addition, the internet survey can be used for the epidemiological investigation of safety of moxa smoke.

Electroacupuncture Alleviated Referral Hindpaw Hyperalgesia via Suppressing Spinal Long-Term Potentiation (LTP) in TNBS-Induced Colitis Rats.

Although referred pain or hypersensitivity has been repeatedly reported in irritable bowel syndrome (IBS) patients and experimental colitis rodents, little is known about the neural mechanisms. Spinal long-term potentiation (LTP) of nociceptive synaptic transmission plays a critical role in the development of somatic hyperalgesia in chronic pain conditions. Herein, we sought to determine whether spinal LTP contributes to the referral hyperalgesia in colitis rats and particularly whether electroacupuncture (EA) is effective to alleviate somatic hyperalgesia via suppressing spinal LTP. Rats in the colitis group (induced by colonic infusion of 2,4,6-trinitrobenzenesulfonic acid, TNBS), instead of the control and vehicle groups, displayed evident focal inflammatory destruction of the distal colon accompanied not only with the sensitized visceromotor response (VMR) to noxious colorectal distension (CRD) but also with referral hindpaw hyperalgesia indicated by reduced mechanical and thermal withdrawal latencies. EA at Zusanli (ST36) and Shangjuxu (ST37) attenuated the severity of colonic inflammation, as well as the visceral hypersensitivity and referral hindpaw hyperalgesia in colitis rats. Intriguingly, the threshold of C-fiber-evoked field potentials (CFEFP) was significantly reduced and the spinal LTP was exaggerated in the colitis group, both of which were restored by EA treatment. Taken together, visceral hypersensitivity and referral hindpaw hyperalgesia coexist in TNBS-induced colitis rats, which might be attributed to the enhanced LTP of nociceptive synaptic transmission in the spinal dorsal horn. EA at ST36 and ST37 could relieve visceral hypersensitivity and, in particular, attenuate referral hindpaw hyperalgesia by suppressing the enhanced spinal LTP.

Comparison of the Efficacy between Conventional Moxibustion and Smoke-Free Moxibustion on Knee Osteoarthritis: A Randomized Controlled Trial.

OBJECTIVE: The aim of this study was to investigate the difference of efficacy between conventional moxibustion (CM) and smoke-free moxibustion (SM) for patients with osteoarthritis of the knee (KOA). METHODS: This is a multicentre, randomized, single blinded, parallel-group clinical trial. Patients with KOA were randomly allocated to CM group (69) and SM group (69) in 7 hospitals of China. Moxibustion treatment in 12 sessions over 4 weeks was administrated at 3 acupuncture points (EX-LE4, ST35, and ST36). Patients completed standard questionnaires at baseline and after 2 weeks, 4 weeks, 8 weeks, and 12 weeks. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) from the baseline to 4 weeks. The secondary outcomes include Visual Analogue Scale (VAS) and Patient Global Assessment score (PGA). RESULTS: Analyses showed that the WOMAC score improved in pain (95% CI,-0.1[-1.2 to 0.9], p=0.76), stiffness (95% CI,-0.1 [-0.5 to 0.3], p=0.71), and function (95% CI, 2.2 [-1.3 to 5.8], p=0.22) compared between the two groups at 4 weeks, as well as the VAS score (95% CI,0.1 [-0.3 to 0.6], p=0.60). Similar results presented at 8 and 12 weeks. No statistically significant difference was observed between CM and SM groups for outcome measurements. CONCLUSIONS: It suggested that smoke generated during moxibustion treatment does not affect the efficacy of moxibustion in the treatment of KOA, which should be taken into account to be removed for the sake of reducing environmental pollution or moxa smoke exposure of acupuncturists or patients. This trial is registered with Clinical Trials.gov, NCT02772055.

Ipsi- and Contralateral Moxibustion Generate Similar Analgesic Effect on Inflammatory Pain.

The aim of this study was to investigate whether contralateral moxibustion would generate a similar analgesic effect with ipsilateral moxibustion. Contra- and ipsilateral moxibustion were separately applied to Zusanli (ST36) acupoints of inflammatory pain mice. The analgesic effect was evaluated, respectively, by licking/biting time (LBT) of formalin-induced inflammatory pain and thermal withdrawal latency (TWL) of complete Freund's adjuvant- (CFA-) induced inflammatory pain. For formalin-induced pain, compared with formalin group, the total LBT of ipsi- and contralateral moxibustion reduced in both phase I and phase II, but there was no significant difference between ipsi- and contralateral moxibustion. For CFA-induced inflammatory pain, compared with CFA group, TWL of ipsi- and contra-Moxi groups increased immediately after moxibustion intervention; however there was no obvious difference between ipsi- and contralateral moxibustion at any timepoint. It indicated that contralateral moxibustion had a similar analgesic effect with ipsilateral moxibustion in both formalin- and CFA-induced pain. These results suggest that both ipsi- and contralateral moxibustion could be applied for pain relief.

[Acupuncture and Moxibustion and Immunity: the Actuality and Future].

Immunity reaction has been regarded as a key step for clinical acupuncture and moxibustion treatment. In the present paper, we review current situations about studies on acupuncture-moxibustion induced immunoregulation from 1) related project fundings of National Natural Science Foundation (NCFS) of China from 1989-2017; 2) papers published in SCI and Chinese medical journals from 2010-2018; 3) clinical conditions or disorders treated by acupuncture and moxibustion and their clinical therapeutic effects; 4) the commonly used acupoints for studying immune regulation functions; 5) some mechanisms of innate immunity and adaptive immunity involved; and 6) immune adjustment pathways involved. Moreover, in our future studies, we suggest to pay more attention to 1) the detailed cellular molecular mechanisms; 2) interactions among the immune cells, the immune cells and non-immune cells and cytokines responsible for regulation effects of acupuncture-moxibustion; 3) interrelationship of different systems as skin-brain axis, brain-intestinal axis, nerve-blood vessel unit of brain tissues, etc. involving acupuncture-moxibustion induced immunoregulation by using new techniques as proteomics, genomics, two-photon imaging technology, tracer technique, cryo-electronic microscope technology, etc.

[Moxibustion-induced Regional Changes of Histological Structure and Number of TNF-α in "Zusanli" (ST 36) in C 57 BL/6 J and TRPV 1-/- Mice].

OBJECTIVE: To observe whether the transient receptor potential vanilloid 1(TRPV 1) plays a role in moxibustion (Moxi)-induced regulation of local immune inflammatory response. METHODS: Fifteen C 57 BL/6 J and 15 TRPV 1-/- mice were randomly and respectively divided into blank control, Moxi-30 min and Moxi-72 h groups (5 mice/group). The Moxi intervention ([46±1] ℃) was applied to the left "Zusanli" (ST 36) for 30 min. The local tissue of the left ST 36 region was collected for observing the histological changes after H．E. staining, and for counting the number of tumor necrosis factor-α (TNF-α) immune-reaction (IR)-positive cells after immunofluorescence staining. RESULTS: In both C 57 BL/6 J and TRPV 1-/- mice, following Moxi, the local epidermis tissue was incomplete, with vague layers and arrangement of the stratum corneum (being thicker than control mice), and visible scar tissue. The corium layer was relatively looser in the structure, and the collagenous and elastic fibers were loosened in the arrangement or absence, with an abundant inflammatory cell infiltration, vascular dilation and congestion of blood vessels, and abnormal hyperplasia of hair follicles and sebaceous glands (but without marked structural changes of the subcutaneous tissue). In C 57 BL/6 J mice, compared with the control group, the numbers of TNF-α IR-positive cells were significantly increased in the epidermis of the Moxi-30 min group (P<0.05), and in the dermis of the Moxi-30 min and -72 h groups (P<0.01). In TRPV 1-/- mice, compared with the control group, the numbers of TNF-α IR-positive cells were also considerably increased in the epidermis of the Moxi-30 min group, and in the dermis of both Moxi-30 min and -72 h groups (P<0.01). Comparison between the two Moxi groups showed that the number of TNF-α positive cells was significantly lower in the dermis of the Moxi-72 h group than in that of the Moxi-30 min group in C 57 BL/6 J mice (P<0.01), and significantly lower in both the epidermis and dermis of the Moxi-72 h group than in those of the Moxi-30 min group in TRPV 1-/- mice (P<0.01)．. CONCLUSION: Moxibustion stimulation of ST 36 can induce structural changes of the regional epidermis and dermis of the skin and up-regulate the number of TNF-α IR-positive cells in both C 57 BL/6 J and TRPV 1-/- mice, which may contribute to its therapeutic effect via local TRPV 1-independent immunoregulation.

[Influence of Moxa Smoke on Indoor Air Quality and Strategies for Its Control].

Moxibustion is an effective therapy for treatment of a lot of clinical problems, but the ignited moxa-induced smoke containing harmful substances may bring about indoor air pollution to affect both patients' and medical workers' health. However, there is no standards about controlling indoor air quality (IAQ) for moxibustion rooms in China. In the present study, the authors reviewed newly-published articles about some substances released from moxa smoke as inhalable particles (PM 10 and PM 2.5), formaldehyde, benzene, methylbenzene, xylene, bene[α]pyrene, total volatile organic compounds, CO, CO2, NO, SO2, NH3, O3, etc. some of which affect IAQ. On this account, the authors put forward some strategies for controlling IAQ in moxibustion clinics including setting united safe standards, enhancing ventilation, controlling moxibustion material quality and strengthening scientific research on the safety of moxa smoke control, fully playing the superiority of moxibustion therapy and reducing its unfavorable aspects in clinical practice in the future.

[Method of Epidemiological Study on the Clinical Safety of Moxa Smoke].

With the development of moxibustion use, increasing attention has focused on the safety of moxa smoke. Evaluation of the safety of moxa smoke has now become an urgent problem in moxibustion clinical practice. An epidemiological study could provide direct evidence of the safety of moxa smoke, but has not yet been comprehensively and systematically studied. In the present paper, the authors discuss the research methods used in epidemiological studies of the clinical safety of moxa smoke and some key problems regarding definition of the exposed population, the determination of exposure outcome, the choice of psychological measuring tool and the assessment of exposure level.

Comparison of the efficacy between conventional moxibustion and smoke-free moxibustion on knee osteoarthritis: study protocol of a randomized controlled trial.

BACKGROUND: Conventional moxibustion is a representative non-drug intervention in traditional Chinese medicine, and it has been reported to produce encouraging results and benefits in relieving symptoms and improving the quality of life for patients with knee osteoarthritis (KOA) in previous clinical trials and systematic reviews. Given that increasing concerns on the safety of generated smoke from conventional moxibustion have received much attention, smoke-free moxibustion is regarded as a potential alternative. However, whether smoke-free moxibustion would display a similar efficacy to that of conventional moxibustion still remains unclear. Therefore, this randomized controlled trial attempts to investigate the difference of efficacy between conventional moxibustion and smoke-free moxibustion in patients with KOA. METHODS/DESIGN: This is a multicenter, randomized, single-blinded, parallel-group clinical trial. A total of 138 eligible participants with KOA will be randomly allocated to two groups (conventional moxibustion group and smoke-free moxibustion group) in seven hospitals in China. Participants will receive 12 sessions of moxibustion treatment at three acupoints (EX-LE4, ST35, and ST36) over a period of 4 weeks (3 sessions per week). A smoke-removing device is placed at the top of the moxibustion device for the smoke-free moxibustion group (n = 69), while the conventional moxibustion group (n = 69) is treated with traditional moxibustion. The primary outcome measure will be the change of the global scale of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) from the baseline to 4 weeks. Secondary outcomes include the visual analog scale VASand Patient Global Assessment scores. Follow-up measurements will be performed on the 8th and 12th weeks after random allocation. DISCUSSION: This study will contribute to providing a solid foundation for the selection of moxibustion in clinical application as well as future research in moxibustion therapy. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02772055 . Registered on 12 May 2016.