Acupuncture and moxibustion for irritable bowel syndrome: An umbrella systematic review.

BACKGROUND: Irritable bowel syndrome (IBS) is a functional bowel disease characterized by abdominal pain or discomfort associated with altered bowel habits. Several clinical studies have demonstrated the effectiveness of acupuncture and moxibustion for IBS. Many systematic reviews of acupuncture and moxibustion for IBS have been published in recent years, but their results are not entirely consistent. OBJECTIVE: To evaluate the methodological, reporting, and evidence quality of systematic reviews of acupuncture and moxibustion for IBS. SEARCH STRATEGY: Systematic reviews of acupuncture and moxibustion for IBS published before February 20, 2023 were searched in eight databases: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Data, VIP Database for Chinese Technical Periodicals, and China Biology Medicine. The keywords used for literature search were acupuncture, moxibustion, systematic review, meta-analysis, and irritable bowel syndrome. INCLUSION CRITERIA: Systematic reviews and meta-analyses of randomized controlled trials of acupuncture and moxibustion for IBS were included. DATA EXTRACTION AND ANALYSIS: Relevant information was independently extracted by two investigators. The A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR 2), Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020), and Grading of Recommendations Assessment, Development and Evaluation (GRADE) were used to evaluate the methodological quality, reporting quality and evidence quality, respectively. RESULTS: A total of 342 studies were retrieved and 15 systematic reviews were included. The results of AMSTAR 2 showed low methodological quality in 2 studies and very low methodological quality in the remaining 13 studies, with main issues being failure to register a protocol, incomplete search strategy, not providing a list of excluded studies, incomplete consideration of the risk of bias in the included studies, and a failure to assess the publication bias. The results of PRISMA 2020 showed seriously deficient reporting quality of 2 studies, somewhat deficient reporting quality of 12 studies, and relatively complete reporting quality of 1 study, with the main problems being lack of a complete search strategy, non-availability of a list of excluded studies with justification for their exclusion, not conducting heterogeneity and sensitivity analyses, not evaluating the credibility of the evidence, and not registering the protocol. The results of GRADE showed that the quality of the evidence is low or very low. CONCLUSION: Most included systematic reviews interpreted findings to suggest that acupuncture and moxibustion have benefits for IBS. However, there is a need to improve the methodological, reporting and evidence quality of the systematic reviews. Larger, multicenter, rigorously designed randomized controlled trials and high-quality systematic reviews are required to obtain more robust evidence. PLEASE CITE THIS ARTICLE AS: Ma YY, Hao Z, Chen ZY, Shen YX, Liu HR, Wu HG, Bao CH. Acupuncture and moxibustion for irritable bowel syndrome: An umbrella systematic review. J Integr Med. 2024; 22(1): 22-31.

Acupoint Thread Embedding Combined With Wenshen Bugu Decoction for the Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptom Among Postmenopausal Breast Cancer Patients: Study Protocol of a Randomized Controlled Trial.

BACKGROUND: Aromatase inhibitors (AIs) are recommended as the preferred therapy for postmenopausal women with hormone receptor-positive (HR+) breast cancer. As a result, aromatase inhibitor-associated musculoskeletal symptom (AIMSS) have become a major problem leading to therapy discontinuation and decreased quality of life in patients receiving adjuvant AIs treatment. Multiple therapies have been attempted, but have yielded limited clinical results. This study will be performed to determine whether acupoint thread embedding (ATE) combined with Wenshen Bugu Decoction can effectively treat AIMSS, so as to improve the AIs medication compliance of postmenopausal breast cancer patients. METHODS: This study will utilize a randomized, 2 parallel groups controlled trial design. A total of 128 eligible postmenopausal breast cancer women with AIMSS will be randomized to receive a 12-week treatment with Wenshen Bugu Decoction alone (control group) or in combination with ATE (treatment group) in a 1:1 ratio. The primary outcome will be the 12 week Brief Pain Inventory Worst Pain (BPI-WP) score. The secondary outcome measures will include response rate, Brief Pain Inventory-Short Form (BFI-SF), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Functional Assessment of Cancer Therapy-Endocrine Symptom (FACT-ES), Functional Assessment of Cancer Therapy-Breast (FACT-B), bone marrow density (BMD), blood markers of bone metabolite, Morisky medication adherence scale-8 (MMAS-8), credibility and expectancy, and survival outcomes. DISCUSSION: This trial may provide clinical evidence that ATE combined with Wenshen Bugu Decoction can be beneficial for treating AIMSS among postmenopausal breast cancer survivors. Our findings will be helpful to enhance the quality of life and reduce the occurrence of AIs withdrawal.

[Progression and reflection on the mechanism study of acupuncture and moxibustion in treatment of Crohn's disease].

Crohn's disease (CD) is a common chronic non-specific gastrointestinal inflammatory disease. Studies showed that acupuncture-moxibustion (A&M) can effectively relieve the symptoms of CD and its clinical efficacy has been confirmed in patients. In this paper, by reviewing the relevant articles for the mechanism studies on CD treated with A&M in recent years, it is discovered that the effect mechanism of A&M on CD includes two aspects, i.e. the local regulation inside the intestines and the neuromodulation outside intestines. The former one refers to the regulation of intestinal microflora, intestinal epithelial cell function and the regulation of intestinal local immune cells. The latter points to the modulation of brain function effect and the modulation of "brain-gut axis" related neurotransmitters. This paper also introduces the differences in intervention modes and acupoint selection between clinical trial and animal experiment, the suggestions on elucidating the nerve-immunity mechanism for CD treatment with A&M in view of "brain-gut axis" system, and its prospects. It is anticipated that this review may be conductive to the effect mechanism research of A&M for CD so that the evidences may be provided for optimizing the clinical regimen of A&M in treatment of this disease.

Moxibustion improves experimental colitis in rats with Crohn's disease by regulating bile acid enterohepatic circulation and intestinal farnesoid X receptor.

OBJECTIVE: This study was conducted to explore the mechanism of intestinal inflammation and barrier repair in Crohn's disease (CD) regulated by moxibustion through bile acid (BA) enterohepatic circulation and intestinal farnesoid X receptor (FXR). METHODS: Sprague-Dawley rats were randomly divided into control group, CD model group, mild moxibustion group and herb-partitioned moxibustion group. CD model rats induced by 2,4,6-trinitrobenzene sulfonic acid were treated with mild moxibustion or herb-partitioned moxibustion at Tianshu (ST25) and Qihai (CV6). The changes in CD symptoms were rated according to the disease activity index score, the serum and colon tissues of rats were collected, and the pathological changes in colon tissues were observed via histopathology. Western blot, immunohistochemistry (IHC) and immunofluorescence were used to evaluate the improvement of moxibustion on intestinal inflammation and mucosal barrier in CD by the BA-FXR pathway. RESULTS: Mild moxibustion and herb-partitioned moxibustion improved the symptoms of CD, inhibited inflammation and repaired mucosal damage to the colon in CD rats. Meanwhile, moxibustion could improve the abnormal expression of BA in the colon, liver and serum, downregulate the expression of interferon-γ and upregulate the expression of FXR mRNA, and inhibit Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) mRNA. The IHC results showed that moxibustion could upregulate the expression of FXR and mucin2 and inhibit TLR4 expression. Western blot showed that moxibustion inhibited the protein expression of TLR4 and MyD88 and upregulated the expression of FXR. Immunofluorescence image analysis showed that moxibustion increased the colocalization sites and intensity of FXR with TLR4 or nuclear factor-κB p65. In particular, herb-partitioned moxibustion has more advantages in improving BA and upregulating FXR and TLR4 in the colon. CONCLUSION: Mild moxibustion and herb-partitioned moxibustion can improve CD by regulating the enterohepatic circulation stability of BA, activating colonic FXR, regulating the TLR4/MyD88 pathway, inhibiting intestinal inflammation and repairing the intestinal mucosal barrier. Herb-partitioned moxibustion seems to have more advantages in regulating BA enterohepatic circulation and FXR activation. Please cite this article as: Shen JC, Qi Q, Han D, Lu Y, Huang R, Zhu Y, Zhang LS, Qin XD, Zhang F, Wu HG, Liu HR. Moxibustion improves experimental colitis in rats with Crohn's disease by regulating bile acid enterohepatic circulation and intestinal farnesoid X receptor. J Integr Med. 2023; 21(2): 194-204.

Spinal cord astrocyte P2X7Rs mediate the inhibitory effect of electroacupuncture on visceral hypersensitivity of rat with irritable bowel syndrome.

This study explored the role of P2X7 receptors in spinal cord astrocytes in the electroacupuncture-induced inhibition of visceral hypersensitivity (VH) in rats with irritable bowel syndrome (IBS). Visceral hypersensitivity of IBS was intracolonically induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). Visceromotor responses to colorectal distension (CRD-20,40,60,80 mmHg) and abdominal withdrawal reflex scoring (AWRs) were recorded after electroacupuncture at bilateral Zusanli (ST36) and Sanyinjiao (SP6) acupoints to evaluate the analgesic effect of electroacupuncture on visceral pain in rats with IBS. Fluorocitric acid (FCA), an astrocyte activity inhibitor, was injected intrathecally before electroacupuncture intervention and AWRs were recorded. Western blot and real-time qPCR were used to detect the expression of NMDA and P2X7 receptor to observe the regulation effect of electroacupuncture on NMDA receptor in the spinal cord of rats with visceral hypersensitivity. Intrathecal injection of P2X7 agonist or antagonist was administered before electroacupuncture treatment. To observe the effect of P2X7 receptor in spinal astrocytes on the inhibition of visceral hyperalgesia by electroacupuncture, the changes of AWR score, NMDA receptor in the spinal cord, and GFAP expression in astrocytes were detected. Inflammation of the colon had basically subsided at day 21 post-TNBS; persistent visceral hypersensitivity could be suppressed by electroacupuncture. This analgesic effect could be inhibited by FCA. The analgesic effect, downregulation of NMDA receptor NR1 subunit, and P2X7 protein of electroacupuncture were all reversed by FCA. P2X7 receptor antagonist A740003 can cooperate with EA to carry out analgesic effect in rats with visceral pain and downregulate the expression of NR1, NR2B, and GFAP in spinal dorsal horn. However, the P2X7 receptor agonist BzATP could partially reverse the analgesic effect of EA, inhibiting the downregulatory effect of EA on the expression of NR1, NR2B, and GFAP. These results indicate that EA may downregulate the expression of the NMDA receptor by inhibiting the P2X7 receptor in the spinal cord, thereby inhibiting spinal cord sensitization in IBS rats with visceral pain, in which astrocytes are an important medium.

Acupuncture and moxibustion for treatment of Crohn's disease: A brief review.

Crohn's disease (CD) is a kind of intestinal inflammatory disease that can affect any part of the gastrointestinal tract and the incidence rate of CD is gradually increasing worldwide. Acupuncture and moxibustion have unique curative effects on gastrointestinal diseases and can be new options for the treatment of CD.

Role of Bile Acids and Nuclear Receptors in Acupuncture in Improving Crohn's Disease.

Nuclear receptors (NRs) are ligand-dependent transcription factors that regulate the transcription of target genes. Bile acids (BAs) can be used as effector molecules to regulate physiological processes in the gut, and NRs are important receptors for bile acid signaling. Relevant studies have shown that NRs are closely related to the occurrence of Crohn's disease (CD). Although the mechanism of NRs in CD has not been clarified completely, growing evidence shows that NRs play an important role in regulating intestinal immunity, mucosal barrier, and intestinal flora. NRs can participate in the progress of CD by mediating inflammation, immunity, and autophagy. As the important parts of traditional Chinese medicine (TCM) therapy, acupuncture and moxibustion in the treatment of CD curative mechanism can get a lot of research support. At the same time, acupuncture and moxibustion can regulate the changes of related NRs. Therefore, to explore whether acupuncture can regulate BA circulation and NRs expression and then participate in the disease progression of CD, a new theoretical basis for acupuncture treatment of CD is provided.

LncRNA-miRNA-mRNA Network Analysis Reveals the Potential Biomarkers in Crohn's Disease Rats Treated with Herb-Partitioned Moxibustion.

Background: Long noncoding RNA (lncRNA) is receiving growing attention in Crohn's disease (CD). However, the mechanism by which herb-partitioned moxibustion (HPM) regulates the expression and functions of lncRNAs in CD rats is still unclear. The aim of our study is to identify lncRNA-miRNA-mRNA network potential biological functions in CD. Methods: RNA sequencing and microRNA (miRNA) sequencing were carried out to analyze lncRNA, miRNA and mRNA expression profiles among the CD rats, normal control rats, and CD rats after HPM treatment and constructed the potential related lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) networks. Then, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, protein-protein interaction (PPI) analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to explore potentially important genes in ceRNA networks. Results: A total of 189 lncRNAs, 32 miRNAs and 463 mRNAs were determined as differentially expressed (DE) genes in CD rats compared to normal control rats, and 161 lncRNAs, 12 miRNAs and 130 mRNAs were identified as remarkably DE genes in CD rats after HPM treatment compared to CD rats. GO analysis indicated that the target genes were most enriched in cAMP and in KEGG pathway analysis the main pathways included adipocytokine, PPAR, AMPK, FoxO and PI3K-Akt signaling pathway. Finally, qRT-PCR results confirmed that lncRNA LOC102550026 sponged miRNA-34c-5p to regulate the intestinal immune inflammatory response by targeting Pck1. Conclusion: By constructing a ceRNA network with lncRNA-miRNA-mRNA, PCR verification, and KEGG analysis, we revealed that LOC102550026/miRNA-34c-5p/Pck1 axis and adipocytokine, PPAR, AMPK, FoxO, and PI3K-Akt signaling pathways might regulate the intestinal immune-inflammatory response, and HPM may regulate the lncRNA LOC102550026/miR-34c-5p/Pck1 axis and adipocytokine, PPAR, AMPK, FoxO, and PI3K-Akt signaling pathways, thus improving intestinal inflammation in CD. These findings may be novel potential targets in CD.

Gut microbiome alterations in colitis rats after moxibustion at bilateral Tianshu acupoints.

BACKGROUND: The pathogenesis of ulcerative colitis (UC) is closely related to the gut microbiota. Moxibustion has been used to improve the inflammation and gastrointestinal dysfunctions in gastrointestinal disorders such as UC. In this study, we investigated whether moxibustion could improve the gut microbial dysbiosis induced by dextran sulphate sodium. METHODS: Twenty-five male rats were randomly assigned into five groups. The UC rat model was established by administering DSS solution. The rats in the moxibustion and normal rats with moxibustion groups were treated with moxibustion at Tianshu (bilateral, ST25) points, and the mesalazine group rats were treated with mesalazine once daily for 7 consecutive days. Disease activity index (DAI) and haematoxylin and eosin staining were used to evaluate the effect of moxibustion. Gut microbiota profiling was conducted by metagenomic high throughput sequencing technology. The gut microbiota composition, diversity and function were analyzed and compared using metagenomics methodologies. RESULTS: The DAI scores and histopathology scores in the moxibustion and mesalazine groups were significantly decreased compared with the UC group (P < 0.01). Moxibustion treatment increased abundance levels of Bacteroidetes, Actinobacteria, Ascomycota, Synergistetes and decreased abundance of Firmicutes, Proteobacteria. At the genus level, the abundance of Bacteroides, Bacteroides_bacterium_M7, Prevotella, Bacteroidales_bacterium_H2, were increased and Bacteroides_bacterium_H3, Parabacteroides, Porphyromonas, Alistipes, Parasutterella were decreased in the UC group in comparsion with those in the NG group. Moxibustion increased the abundance of Bacteroides and Bacteroides_bacterium_H3 and decreased Bacteroides_bacterium_M7, Prevotella, Bacteroidales_bacterium_H2. In UC group, the specie Bacteroides_massiliensis was negatively (P < 0.05) correlated with IL-23, Bacteroides_eggerthii_CAG109 and Bacteroides_eggerthii were negatively (P < 0.05) correlated with TGF-ß. And the species Prevotella_sp_CAG1031 and Bacteroides_bacterium_H2 were significant positively (P < 0.05) correlated with IL-23. In addition, compare with the normal group, genes involved in certain metabolic pathways, such as energy production and conversion, amino acid transport and metabolism, carbohydrate transport and metabolism, were under-represented in the UC group, and these changes in the metabolic pathways could be reversed by moxibustion treatment and mesalazine treatment. CONCLUSIONS: Our findings suggest that moxibustion treatment may protect the host from mucosal inflammation by modulating the intestinal microbiota community.

Herb-partitioned moxibustion regulated the miRNA expression profile in the thyroid tissues of rats with experimental autoimmune thyroiditi.

OBJECTIVE: To observe the effect of herb-partitioned moxibustion (HPM) on the miRNA expression profile of thyroid tissue in experimental autoimmune thyroiditis (EAT) rats. METHODS: Rats were randomly divided into normal control (NC) group, EAT model (EAT) group, HPM group and western medicine (Med) group. EAT model rats were prepared by a combined immunization with complete and incomplete Freund's adjuvant emulsified with porcine thyroglobulin and iodine. Rats in the HPM group were treated with HPM, while rats in the Med group were treated with levothyrocine (1 µg/2 mL) by gavage. HE staining was used to observe the pathological morphological changes of thyroid tissue, ELISAs was uaed to detect the serum concentrations of TGAb, TPOAb, FT3, FT4, TSH. We then performed high-throughput miRNA sequencing to analyse the miRNA expression profiles in the thyroid tissues, followed by a bioinformatics analysis. RT-qPCR was used to verify the identified differentially expressed miRNAs. RESULTS: HPM improved the thyroid tissue morphology and reduced serum TPOAb, TGAb, TSH concentration in EAT rats (P < 0.05), but with no obvious effect on FT3 and FT4 concentration. While the TSH, FT3 and FT4 concentration was significantly changed in the Med group (P < 0.01 or P < 0.05) compared with that of EAT group. Sequencing results showed that a total of 17 miRNAs were upregulated, and 4 were downregulated in the EAT rats, in which the expression levels of miR-346 and miR-331-5p were reversed by HPM. The target genes of the miRNAs that regulated by HPM were associated with a variety of immune factors and immune signals. RT-qPCR verification showed that the expression of miRNA-346 and miRNA-331-5p was consistent with the sequencing results. CONCLUSIONS: HPM could regulate the the expression of miRNA-346 and miRNA-331-5p, then act on their target genes to immune and inflammation-related pathways, which may be one of the mechanisms of HPM on EAT rats.

[Spectrum and indications of acupuncture and moxibustion therapy based on bibliometric analysis].

OBJECTIVE: To analyze the literature of acupuncture and moxibustion for diseases in the recent 5 years, and discuss the spectrum and indications of acupuncture and moxibustion. METHODS: The literature on acupuncture and moxibustion for diseases in CNKI, Wanfang and VIP databases from January 1, 2015 to December 31, 2019 was searched, summarized and analyzed, and the disease spectrum was summarized. At the same time, the literature from 2015 to 2019 (group A), 1978 to 2005 (group B), and 1949 to 2005 (group C) was compared, and the indications of acupuncture and moxibustion therapy were summarized. RESULTS: There were 32 011 articles on acupuncture and moxibustion for diseases in the recent 5 years, including 377 kinds of indications. These indications can be mostly classified as neurology (9384), orthopedics and traumatology (7765), gastroenterology (3529) and obstetrics and gynecology (2283). The types of diseases were mostly gastroenterology (52 types), neurology (47 types), ophthalmology and otorhinolaryngology (47 types), and obstetrics and gynecology (42 types). The first-class indications of acupuncture and moxibustion therapy in the recent 5 years were hemiplegia, lumbar disc herniation, cervical spondylosis, knee osteoarthritis, insomnia, constipation and cerebrovascular diseases; the second-class were facial neuritis, shoulder pain and headache; the third-class were dysphagia, dysmenorrhea and depression; the forth-class were asthma, urinary retention, cerebral palsy, hypertension, dementia, side effects of radiotherapy and chemotherapy, infertility, allergic rhinitis, vertigo, shoulder-hand syndrome, diabetic neuropathy, herpes zoster, pain, hiccup, diarrhea, lumbar sprain and sciatica. CONCLUSION: Although the disease spectrum and indications of acupuncture and moxibustion therapy have changed to some extent in the recent 5 years, neurology and orthopedics and traumatology are still predominant, and the observation objects tend to transition from symptoms to diseases.

Influence of herb-partitioned moxibustion at Qihai (CV6) and bilateral Tianshu (ST25) and Shangjuxu (ST37) acupoints on toll-like receptors 4 signaling pathways in patients with ulcerative coliti.

OBJECTIVE: To evaluate the efficacy of herb-partitioned moxibustion (HPM) at Qihai (CV6), Tianshu (ST25) and Shangjuxu (ST37) acupoints in relieving symptoms and the immune regulation of HPM on the toll-like receptors 4 (TLR4) signaling pathway in ulcerative colitis (UC) patients. METHODS: A randomized, single-blind study was conducted 63 patients to receive HPM or sham HPM treatment. The efficacy outcomes included scores of the Mayo, Baron, inflammatory bowel disease questionnaire (IBDQ), self-rating depression scale (SDS), self-rating anxiety scale (SAS). HE staining was used to observe the histopathological changes of the colon. The expression of inflammatory cytokines and TLR4 signaling pathway related molecules were determined by enzyme-linked immunosorbent assay and immunohistochemistry. RESULTS: Baron, SDS, SAS scores were significantly decreased in moxibustion group (P < 0.05), IBDQ score was significantly greater in the moxibustion group than in the sham moxibustion group (P < 0.05). Histopathology of mucosal biopsies showed that both two groups improved in mucosa after treatment. The expression levels of tumor necrosis factor-α, interleukin-2, interleukin-12, interferon-γ, and TLR4, lipopolysaccharide, myeloid differentiation factor 88, interleukin receptor associated kinase, tumor necrosis factor receptor associated factor 6 and nuclear factor kappa-B p65 were significantly lower in the moxibustion group than in the sham moxibustion group (P < 0.05). CONCLUSION: This study showed that HPM at Qihai?(CV6),?Tianshu?(ST25) and?Shangjuxu (ST37) acupoints is effective to relieve symptoms, anxiety, depression and improving life quality in UC patients, which may be related to the immune regulation of HPM on TLR4 signaling pathway.

[Effect of acupuncture-moxibustion on negative emotions and plasma tryptophan metabolism in patients with Crohn's disease at active stage].

OBJECTIVE: To observe the effect of acupuncture-moxibustion on negative emotions and plasma tryptophan (Trip)-kynurenine (Kyn) metabolism in the patients with Crohn's disease (CD) at the mild and moderate active stage. METHODS: A total of 66 CD patients were randomized into an observation group (33 cases, 1 case dropped off) and a control group (33 cases, 2 cases dropped off). In the observation group, acupuncture was applied in combination with moxibustion. In the control group, the sham-acupuncture was used in combination with sham-moxibustion. In both of the observation group and the control group, acupuncture was applied to Zhongwan (CV 12), Shangjuxu (ST 37), Sanyinjiao (SP 6), Gongsun (SP 4), Hegu (LI 4), Quchi (LI 11), Taixi (KI 3) and Taichong (LR 3), and moxibustion was applied to Tianshu (ST 25) and Zusanli (ST 36). The treatment was given once every two days, 3 times a week, totally for 12 weeks. Separately, before and after treatment, the score of the hospital anxiety-depression scale (HADS) and the score of intestinal core symptoms (degree of abdominal pain and frequency of diarrhea) were observed in the patients of the two groups. The concentration of plasma indoleamine 2,3-dioxygenase 1 (IDO1) and the ratios of Kyn/Trp, QuinA/Kyn, KynA/Kyn and KynA/QuinA were compared between the two groups. RESULTS: Compared with before treatment, the scores of HADS-A and HADS-D in the observation group and the score of HADS-A in the control group were all reduced after treatment (P<0.01, P<0.05). The scores of abdominal pain degree in the two groups and score of diarrhea frequency in the observation group were all reduced after treatment (P<0.001). After treatment, the reducing ranges of the score of HADS-A and the scores of abdominal pain degree and diarrhea frequency in the observation group were all larger than the control group (P<0.01, P<0.05). Compared with before treatment, the plasma IDO1 concentration in the two groups and the ratios of plasma Kyn/Trp and QuinA/Kyn in the observation group were all reduced after treatment (P<0.001, P<0.05, P<0.01), the ratios of plasma KynA/Kyn and KynA/QuinA were increased after treatment in the observation group (P<0.05, P<0.01). After treatment, the changes in IDO1 concentration and the ratios of plasma QuinA/Kyn and KynA/QuinA in the observation were larger than the control group (P≤0.01, P<0.05). In the observation group, the difference in the ratio of plasma KynA/Kyn before and after treatment was negatively related to the improvement value of HADS-D (r =-0.67, P<0.05). After treatment, plasma IDO1 concentration was positively related to HADS-A in the observation group (r =0.65, P<0.05). CONCLUSION: Acupuncture and moxibustion relieve the negative emotions of anxiety and depression in CD patients at mild and moderate active stage, which is probably related to the regulation of plasma Trp-Kyn metabolic pathway.

Herbal cake-partitioned moxibustion inhibits colonic autophagy in Crohn's disease via signaling involving distinct classes of phosphatidylinositol 3-kinases.

BACKGROUND: Autophagy is an evolutionarily conserved biological process in eukaryotic cells that involves lysosomal-mediated degradation and recycling of related cellular components. Recent studies have shown that autophagy plays an important role in the pathogenesis of Crohn's disease (CD). Herbal cake-partitioned moxibustion (HM) has been historically practiced to treat CD. However, the mechanism by which HM regulates colonic autophagy in CD remains unclear. AIM: To observe whether HM can alleviate CD by regulating colonic autophagy and to elucidate the underlying mechanism. METHODS: Rats were randomly divided into a normal control (NC) group, a CD group, an HM group, an insulin + CD (I + CD) group, an insulin + HM (I + HM) group, a rapamycin + CD (RA + CD) group, and a rapamycin + HM (RA + HM) group. 2,4,6-trinitrobenzenesulfonic acid was administered to establish a CD model. The morphology of the colonic mucosa was observed by hematoxylin-eosin staining, and the formation of autophagosomes was observed by electron microscopy. The expression of autophagy marker microtubule-associated protein 1 light chain 3 beta (LC3B) was observed by immunofluorescence staining. Insulin and rapamycin were used to inhibit and activate colonic autophagy, respectively. The mRNA expression levels of phosphatidylinositol 3-kinase class I (PI3KC1), Akt1, LC3B, sequestosome 1 (p62), and mammalian target of rapamycin (mTOR) were evaluated by RT-qPCR. The protein expression levels of interleukin 18 (IL-18), tumor necrosis factor-α (TNF-α), nuclear factor κB/p65 (NF-κB p65), LC3B, p62, coiled-coil myosin-like BCL2-interacting protein (Beclin-1), p-mTOR, PI3KC1, class III phosphatidylinositol 3-kinase (PI3KC3/Vps34), and p-Akt were evaluated by Western blot analysis. RESULTS: Compared with the NC group, the CD group showed severe damage to colon tissues and higher expression levels of IL-18 and NF-κB p65 in colon tissues (P < 0.01 for both). Compared with the CD group, the HM group showed significantly lower levels of these proteins (P IL-18 < 0.01 and P p65 < 0.05). There were no significant differences in the expression of TNF-α protein in colon tissue among the rat groups. Typical autophagic vesicles were found in both the CD and HM groups. The expression of the autophagy proteins LC3B and Beclin-1 was upregulated (P < 0.01 for both) in the colon tissues of rats in the CD group compared with the NC group, while the protein expression of p62 and p-mTOR was downregulated (P < 0.01 for both). However, these expression trends were significantly reversed in the HM group compared with the CD group (P LC3B < 0.01, P Beclin-1 < 0.05, P p62 < 0.05, and P m-TOR < 0.05). Compared with those in the RA + CD group, the mRNA expression levels of PI3KC1, Akt1, mTOR, and p62 in the RA + HM group were significantly higher (P PI3KC1 < 0.01 and P Akt1, mTOR, and p62 < 0.05), while those of LC3B were significantly lower (P < 0.05). Compared with the RA + CD group, the RA + HM group exhibited significantly higher PI3KC1, p-Akt1, and p-mTOR protein levels (P PI3KC1 < 0.01, P p-Akt1 < 0.05, and P p-mTOR < 0.01), a higher p62 protein level (P = 0.057), and significantly lower LC3B and Vps34 protein levels (P < 0.01 for both) in colon tissue. CONCLUSION: HM can activate PI3KC1/Akt1/mTOR signaling while inhibiting the PI3KC3 (Vps34)-Beclin-1 protein complex in the colon tissues of CD rats, thereby inhibiting overactivated autophagy and thus exerting a therapeutic effect.

Typical ulcerative colitis treated by herbs-partitioned moxibustion: A case report.

BACKGROUND: Ulcerative colitis (UC), also known as chronic nonspecific UC, is an inflammatory bowel disease characterized by diffuse colonic mucosal inflammation. The incidence and prevalence of UC have risen markedly, and the disease seriously affects the quality of life of patients, and poses a great burden on the world health care infrastructure and economy. CASE SUMMARY: We present a 60-year-old man who had ulcerative colitis for more than 10 years, with recurrent abdominal pain, bloody diarrhea with mucopurulent stool. The treatments with sulfasalazine, mesalazine, and traditional Chinese medicine were not effective, and herbs-partitioned moxibustion (HPM) was then applied at "Zhongwan" (RN12), "Tianshu"(ST25), and "Qihai" (RN6) once a day for about 30 min, 3 times per week, for 6 mo.His main clinical symptoms of abdominal pain, bloody diarrhea with mucopurulent stool gradually improved, and the mucosa had nearly healed, as observed under endoscopy by the 6th mo. The patient's condition was alleviated without relapsing during the subsequent 3-mo follow-up period. HPM showed a significant effect in the treatment of ulcerative colitis in this case, and the effect would help the patient to maintain remission for at least 3 mo. CONCLUSION: A series of symptoms of this UC patient significantly improved with the treatment of HPM.

[Tongdu Tiaoshen acupuncture method for mild cognitive impairment: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy of Tongdu Tiaoshen acupuncture method for mild cognitive impairment in the elderly. METHODS: A total of 96 patients were randomly divided into an observation group, a control group and a waiting group, 32 cases in each group. The patients in the observation group were treated with acupuncture at Baihui (GV 20), Shenting (GV 24), Yintang (GV 29) and Sishencong (EX-HN 1), etc, while the patients in the control group were treated with non-penetrating sham acupuncture at the same acupoints as the observation group. The treatment was given once every other day, three times a week for 8 weeks. The patients in the waiting group only received health guidance for 8 weeks. Montreal cognitive assessment scale (MoCA) and mini-mental state examination (MMSE) were used before and after 8-week treatment in all three groups. The observation group and the control group were followed up for 2 months and evaluated with MoCA and MMSE. RESULTS: The MoCA scores in the observation group after treatment and during follow-up were higher than before treatment (P<0.01), but there was no significant difference between follow-up and after treatment (P>0.05). The MoCA scores in the control group after treatment and during follow-up were higher than before treatment (P<0.01, P<0.05), and the MoCA score during follow-up was lower than after treatment (P<0.01). There was no significant difference before and after treatment in the waiting group (P>0.05). The difference before and after treatment in the observation group was higher than the control group and waiting group (P<0.01), while that in the control group was higher than the waiting group (P<0.01). The difference between follow-up and before treatment in the observation group was higher than the control group (P<0.01), and the improving between follow-up and after treatment was superior to the control group (P<0.01). The MMSE scores after treatment and during follow-up were higher than before treatment in the observation group (P<0.01), but there was no significant difference between the follow-up and after treatment (P>0.05). The MMSE scores after treatment and during follow-up were higher than before treatment in the control group (P<0.01), and the MMSE score during follow-up was lower than after treatment (P<0.01). There was no significant difference before and after treatment in the waiting group (P>0.05). The difference before and after treatment the observation group and control group was not significant (P>0.05), and those in the two groups were higher than the waiting group (P<0.01). The difference between follow-up and before treatment in the observation group was higher than the control group (P<0.01), and the difference between follow-up and after treatment was lower than the control group (P<0.01). CONCLUSION: Tongdu Tiaoshen acupuncture method could improve cognitive impairment in elderly patients with mild cognitive impairment.

Effect of mild moxibustion on intestinal microbiota and NLRP6 inflammasome signaling in rats with post-inflammatory irritable bowel syndrome.

BACKGROUND: About one-third of refractory irritable bowel syndrome (IBS) cases are caused by gastrointestinal (GI) infection/inflammation, known as post-infectious/post-inflammatory IBS (PI-IBS). Although it is known that intestinal microbiota and host NOD-like receptor family pyrin domain containing 6 (NLRP6) inflammsome signaling are closely related to PI-IBS and moxibustion has a therapeutic effect on PI-IBS, whether moxibustion regulates the intestinal flora and host NLRP6 events in PI-IBS remains unclear. AIM: To examine the regulatory effect of moxibustion on intestinal microbiota and host NLRP6 inflammatory signaling in PI-IBS. METHODS: Sprague-Dawley rats were divided into a normal control group, a model control group, a mild moxibustion group, and a sham mild moxibustion group. PI-IBS rats in the mild moxibustion group were treated with moxibusiton at bilateral Tianshu (ST 25) and Zusanli (ST36) for 7 consecutive days for 10 min each time. The sham group rats were given the same treatment as the mild moxibustion group except the moxa stick was not ignited. Abdominal withdrawal reflex (AWR) score was measured to assess the visceral sensitivity, and colon histopathology and ultrastructure, colonic myeloperoxidase (MPO) activity, and serum C-reactive protein (CRP) level were measured to evaluate low-grade colonic inflammation in rats. The relative abundance of selected intestinal bacteria in rat feces was detected by 16S rDNA PCR and the NLRP6 inflammsome signaling in the colon was detected by immunofluorescence, qRT-PCR, and Western blot. RESULTS: The AWR score was significantly decreased and the low-grade intestinal inflammation reflected by serum CRP and colonic MPO levels was inhibited in the mild moxibustion group compared with the sham group. Mild moxibustion remarkably increased the relative DNA abundances of Lactobacillus, Bifidobacterium, and Faecalibacterium prausnitzii but decreased that of Escherichia coli in the gut of PI-IBS rats. Additionally, mild moxibustion induced mRNA and protein expression of intestine lectin 1 but inhibited the expression of IL-1ß, IL-18, and resistance-like molecule ß by promoting the NLRP6 and reducing the mRNA and protein expression of apoptosis-associated speck-like protein containing CARD (ASC) and cysteinyl-aspartate-specific proteinase 1 (Caspase-1). The relative DNA abundances of Lactobacillus, Bifidobacteria, Faecalibacterium prausnitzii, and Escherichia coli in each group were correlated with the mRNA and protein expression of NLRP6, ASC, and Caspase-1 in the colon. CONCLUSION: These findings indicated that mild moxibustion can relieve low-grade GI inflammation and alleviate visceral hypersensitivity in PI-IBS by regulating intestinal microbes and controlling NLRP6 inflammasome signaling.

Herbs-partitioned moxibustion alleviates aberrant intestinal epithelial cell apoptosis by upregulating A20 expression in a mouse model of Crohn's disease.

BACKGROUND: A20 inhibits intestinal epithelial cell apoptosis in Crohn's disease, and herbs-partitioned moxibustion (HPM) has been demonstrated to be an effective treatment for Crohn's disease. However, the mechanism by which HPM reduces intestinal epithelial cell apoptosis in Crohn's disease has not been thoroughly elucidated to date. AIM: To elucidate whether HPM exerts its effects by upregulating A20 to affect intestinal epithelial cell apoptosis in a Crohn's disease mouse model. METHODS: In this study, mice with A20 deletion in intestinal epithelial cells (A20IEC-KO) were utilized to establish a Crohn's disease mouse model with 2,4,6-trinitrobenzene sulfonic acid (TNBS) administration, as well as wild-type mice. Mice were randomly divided into normal control (NC), model control (MC), mesalazine (MESA), and HPM groups. The morphology of the colonic mucosa was observed by hematoxylin-eosin staining, and serum endotoxin and apoptosis of epithelial cells were evaluated by enzyme-linked immunosorbent assay and terminal dUTP nick-end labeling assay accordingly. The protein expression levels of A20 and tumor necrosis factor receptor 1 (TNFR1)-related signaling molecules were evaluated by Western blot, and co-expression of A20 and TNFR1-associated death domain (TRADD) and co-expression of A20 and receptor-interacting protein 1 (RIP1) were observed by double immunofluorescence staining. RESULTS: The intestinal epithelial barrier was noted to have an improvement in the HPM group of wild-type (WT) mice compared with that in A20IEC-KO mice. Compared with A20 IEC-KO HPM mice, serum endotoxin levels and apoptosis percentages were decreased (P < 0.01), A20 expression levels were increased (P < 0.01), and expression of TNFR1, TRADDD, and RIP1 was decreased in the HPM group of WT mice (P TNFR1 < 0.05, P TRADD < 0.01, P RIP1 < 0.01). Both of the co-expression of A20/TRADD and A20/RIP1 showed a predominantly yellow fluorescence in the HPM group of WT mice, while a predominantly red fluorescence was noted in the HPM group of A20IEC-KO mice. CONCLUSION: Our findings suggest that HPM in treating Crohn's disease functions possibly via upregulation of the A20 expression level, resulting in downregulation of TNFR1, TRADD, and RIP1 to alleviate increased cell apoptosis in the intestinal epithelial barrier in Crohn's disease.

[Herbal cake-partitioned moxibustion improves intestinal epithelial barrier dysfunction by suppressing TNF-α-mediated apoptosis pathway of intestinal epithelium in rats with Crohn's disease].

OBJECTIVE: To observe the effect of herbal cake-partitioned moxibustion (Moxi) on tumor necrosis factor (TNF)-α/ TNF receptor 1 (TNFR1)-associated death domain (TRADD) / Fas-associated death domain (FADD) pathway-mediated apoptosis of intestinal epithelial cells in Crohn's disease (CD) rats, so as to explore its underlying mechanisms in the treatment of CD. METHODS: Forty-eight SD male rats were randomly divided into normal, model, Moxi and medication groups (n＝12 rats in each). The CD model was established by intra-annual perfusion of 2，4，6-trinitrobenzene sulfonic acid (TNBS) solution (TNBS∶50% alcohol＝2∶1, 3 mL/kg), once every 7 days, 4 times altogether. For rats of the Moxi group, moxibustion was given to "Tianshu" (ST25) and "Qihai" (CV6), two moxa-cones every time, once daily for 10 days. For rats of the medication group, intragastric perfusion of mesalazine solution was given twice daily for 10 days. After the treatment, the colonic epithelium tissue was sampled. The epithelial cells were purified and cultured to establish an in vitro intestinal epithelial barrier, and added with TNF-α (a pro-inflammatory factor, 100 ng/mL) in the culture medium for 24 h for making an increased epithelial permeability model. The permeability of intestinal epithelial cell barrier was evaluated by detecting the fluorescence yellow transmittance of the TNF-α-incubated cell medium. Western blot was used to detect the expression levels of TNFR1, TRADD, receptor-interacting protein 1 (RIP1), FADD and zinc finger protein A20 (A20, a ubiquitination enzyme for inhibiting activation of TRADD and RIP1) of the cultured intestinal epithelium cells. The apoptosis of the TNF-α-incubated intestinal epithelial cells was detected by flow cytometry. RESULTS: After modeling and compared with the normal group, the fluorescence yellow transmittance of intestinal epithelia cells, apoptosis rate, and expression levels of TNFR1, TRADD, and RIP1 proteins were significantly increased (P<0.001, P<0.01), and the expression of A20 was significantly decreased (P<0.01) in the model group. In comparison with the model group, the fluorescence yellow transmittance of intestinal epithelial cells, the apoptosis rate and expression levels of TRADD, RIP1 and FADD were remarkably down-regulated (P<0.001, P<0.01), and the expression of A20 was significantly up-regulated (P<0.01) in both the Moxi and medication groups. CONCLUSION: Herbal cake-partitioned moxibustion may down-regulate the permeability of intestinal epithelial barrier and the apoptosis of intestinal epithelial cells by way of suppressing TNF-α-mediated cellular apoptosis pathway of intestinal epithelium in CD rats.

Herb-partitioned moxibustion alleviates colon injuries in ulcerative colitis rats.

AIM: To observe the effect of herb-partitioned moxibustion (HPM) on expression of colonic cytokines in ulcerative colitis (UC) rats. METHODS: A UC rat model was established by protein immunization in combination with topical chemical stimulation. Rats in the HPM group (n = 8) received HPM at bilateral Tianshu (ST25) points. The gross injury and pathological scores of the colon were recorded. The expression profile of colonic cytokines was assayed using the protein microarray technique. Specific differential cytokines were selected and verified by ELISA. The corresponding UniProt Accessions of the differentially expressed cytokines were retrieved in the UniProt database. The pathways involved were analyzed with the help of the KEGG PATHWAY database. The DAVID database was used for functional cluster and pathway analysis. RESULTS: HPM improved colon injuries in UC rats, manifested by accelerated repair of ulcers and alleviation of inflammation, and the gross injury and pathological scores both significantly decreased (P < 0.01). Fold change > 1.3 or < 0.77 was taken as the screening standard. There were 77 down-regulated and 9 up-regulated differentially expressed colonic cytokines in the HPM group compared with the model group, and expression of 20 differed significantly (P < 0.05). Twelve of the 20 significantly differentially expressed cytokines [ß-catenin, interleukin-1 receptor 6 (IL-1R6), IL-1ß, B7-1, nerve growth factor receptor, AMP-activated protein kinase-α1, neuropilin-2, orexin A, adipocyte differentiation-related protein, IL-2, Fas and FasL] were up-regulated in the model group (n = 3, compared with the normal group) but down-regulated in the HPM group (n = 3, compared with the model group). Functional cluster analysis showed that the differentially expressed colonic cytokines in the HPM group regulated apoptosis and protein phosphorylation. KEGG pathway analysis showed that 52 down-regulated and 7 up-regulated differentially expressed colonic cytokines in the HPM group had pathways. The pathways that interacted between the cytokines and their receptors accounted for the largest proportion (28 of the down-regulated and 5 of the up-regulated cytokines). CONCLUSION: HPM promotes the repair of colon injuries in UC rats, which is related to the regulation of several abnormally expressed cytokines.