Search

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 (PTNFR1 < 0.05, PTRADD < 0.01, PRIP1 < 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.

Background: Moxibustion is increasingly used for treatment of irritable bowel syndrome (IBS). This study investigated the long-term effects of moxibustion for IBS with diarrhea (IBS-D). Methods: Patients with IBS-D were assigned to receive moxibustion or sham moxibustion (52 each, 3× per week, 6 weeks) and were followed up to 24 weeks. The acupoints were bilateral ST25 and ST36, body surface temperatures at acupoints were 43°C ± 1°C and 37°C ± 1°C for the moxibustion and sham groups, respectively. Primary outcome was changes in IBS Adequate Relief (IBS-AR) from baseline to 6 weeks. Secondary outcomes included the following: IBS symptom severity scale (IBS-SSS), Bristol stool form scale (BSS), IBS quality of life (IBS-QOL), and Hospital Anxiety and Depression Scale (HADS). Results: Based on an intention-to-treat analysis, the rate of IBS-AR in the moxibustion group was significantly higher than the sham group at 6 weeks (76.9% versus 42.3%; p 50 points in IBS-SSS of the treatment group was significantly higher than that of the sham ( p Conclusions: Moxibustion treatment benefits the long-term relief of symptoms in IBS-D patients. Trial registration: Clinical trials.gov (NCT02421627). Registered on 20 April 2015.

Electroacupuncture (EA) has been confirmed effectiveness in the treatment of irritable bowel syndrome (IBS), and P2XTo reveal the neurobiological mechanism that P2XThe IBS chronic visceral pain rat model was established according to the method of Al-Chaer et al. EA at the bilateral He-Mu points, including ST25 and ST37, was conducted for intervention. The behavioral studies, histopathology of colon, electrophysiology, immunofluorescence histochemistry, and real-time polymerase chain reaction assays were used to observe the role of P2XEA significantly reduced the behavior scores of the IBS rats under different levels (20, 40, 60, 80 mmHg) of colorectal distention stimulation and downregulated the expression levels of P2XEA can regulate the P2X

AIMS: Patients with Crohn′s disease (CD) are shown to have abnormal changes in brain structures. This study aimed to further investigate whether these patients have abnormal brain activities and network connectivity. METHODS: Sixty patients with CD and 40 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (fMRI) scans. Amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity (FC) were used to assess differences in spontaneous regional brain activity and functional connectivity. RESULTS: Compared to the HCs, patients with CD showed significantly higher ALFF values in hippocampus and parahippocampus (HIPP/paraHIPP), anterior cingulate cortex, insula, superior frontal cortex and precuneus. The ALFF values were significantly lower in secondary somatosensory cortex (S2), precentral gyrus, and medial prefrontal cortex. Functional connectivities between left HIPP and left inferior temporal cortex, and right middle cingulate cortex, HIPP, and fusiform area were significantly lower. The functional connectivities between right HIPP and right inferior orbitofrontal cortex and left HIPP were also significantly lower. CONCLUSION: Patients with CD showed higher or lower spontaneous activity in multiple brain regions. Altered activities in these brain regions may collectively reflect abnormal function and regulation of visceral pain and sensation, external environmental monitoring, and cognitive processing in these patients. Lower functional connectivity of the hippocampus-limbic system was observed in these patients. These findings may provide more information to elucidate the neurobiological mechanisms of the disease.

// Chunhui Bao 1, * , Peng Liu 2, * , Yin Shi 3 , Luyi Wu 1 , Xiaoming Jin 4 , Xiaoqing Zeng 5 , Jianye Zhang 6 , Di Wang 1 , Huirong Liu 3 and Huangan Wu 1 1 Key Laboratory of Acupuncture and Immunological Effects, Shanghai University of Traditional Chinese Medicine, Shanghai, China 2 Life Sciences Research Center, School of Life Sciences and Technology, Xidian University, Xi’an, China 3 Outpatient Department, Shanghai Research Institute of Acupuncture and Meridian, Shanghai University of Traditional Chinese Medicine, Shanghai, China 4 Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, Indiana, USA 5 Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, China 6 Department of Radiology, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, China * These authors contributed equally to this work Correspondence to: Huangan Wu, email: wuhuangan@126.com Huirong Liu, email: lhr_tcm@139.com Keywords: magnetic resonance imaging, Crohn’s disease, gray matter, brain, pain Received: June 16, 2017 Accepted: September 08, 2017 Published: September 22, 2017 ABSTRACT Increasing evidence indicates that abnormal pain processing is present in the central nervous system of patients with Crohn’s disease (CD). The purposes of this study were to assess changes in gray matter (GM) volumes in CD patients in remission and to correlate structural changes in the brain with abdominal pain. We used a 3.0 T magnetic resonance scanner to examine the GM structures in 21 CD patients with abdominal pain, 26 CD patients without abdominal pain, and 30 healthy control subjects (HCs). Voxel-based morphometric analyses were used to assess the brain GM volumes. Patients with abdominal pain exhibited higher CD activity index and lower inflammatory bowel disease questionnaire scores than those of the patients without abdominal pain. Compare to HCs and to patients without abdominal pain, patients with abdominal pain exhibited lower GM volumes in the insula and anterior cingulate cortex (ACC); whereas compare to HCs and to patients with abdominal pain, the patients without abdominal pain exhibited higher GM volumes in the hippocampal and parahippocampal cortex. The GM volumes in the insula and ACC were significantly negatively correlated with daily pain scores. These results suggest that differences exist in the brain GM volume between CD patients in remission with and without abdominal pain. The negative correlation between the GM volumes in the insula and ACC and the presence and severity of abdominal pain in CD suggests these structures are closely related to visceral pain processing.

Crohn’s disease (CD), a chronic inflammatory bowel disease, involved in brain structural and functional changes, including the amygdala. Amygdala is a key structure in the limbic system and its related circuits are implicated in processing of emotion, pain and sensory. However, limited study of the amygdala is elucidated in CD. This study mainly investigated altered functional connectivity (FC) of the amygdala in CD patients during resting-state. Magnetic resonance imaging scans were acquired from 42 CD patients and 35 healthy controls (HCs). Whole amygdala bilaterally were selected as regions of interest (ROIs). Voxel-based morphometry and FC methods were applied to investigate the differences of structure or intrinsic connectivity of the amygdala between the two groups, separately. Pearson correlations were performed to explore relationships between the clinical characteristics and neuroimaging findings in CD patients. Based on the whole amygdala bilaterally as ROIs, compared with HCs, CD patients showed no statistical differences of grey matter destiny but exhibited decreased FC between the amygdala and insula, parahippocampus, as well as anterior middle cingulate cortex/dorsal anterior cingulate cortex. CD patients had negative correlation between the disease duration and amygdala-insula connectivity. In the patient group, patients with higher anxiety or depression scores revealed increased FC of the amygdala with thalamus and orbitofrontal cortex. Our results reveal that aberrant FC of the amygdala may be involved in processing of visceral pain and sensation, and emotion in CD. These findings may further enhance the understanding of neural mechanisms of CD.

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-1β, IL-18, and resistance-like molecule β 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.

To categorize and summarize the clinical and mechanism studies of the past 30 years on the treatment of Hashimoto’s thyroiditis (HT) with moxibustion, moxibustion plus medication, and acupuncture plus medication, etc., and to analyze the current problems. The clinical and laboratory studies related to the treatment of HT with acupuncture-moxibustion therapies published before June 2015 were retrieved from MEDLINE, Excerpta Medica Database (EMBASE), China National Knowledge Infrastructure (CNKI), Wanfang Academic Journal Full-text Database (Wanfang) and Chongqing VIP Database (CQVIP). Moxibustion, moxibustion plus medication, and acupuncture plus medication can produce certain therapeutic effects in treating HT. The research on the treatment of HT with acupuncture-moxibustion therapies is rather limited in the amount and content. In the future, standardization should be fortified, specific moxibustion research needs deepening, and the action mechanism of moxibustion should be emphasized.

Objective To observe the effect of moxibustion on learning and memory abilities, corticosterone and glucocorticoid receptor (GR) in subacute aging rats.

Abnormal pain processing in the central nervous system may be related to abdominal pain in patients with Crohn's disease (CD). The purpose of this study was to investigate changes in resting-state brain activity in patients with CD in remission and its relationship with the presence of abdominal pain. Twenty-five patients with CD and with abdominal pain, 25 patients with CD and without abdominal pain, and 32 healthy subjects were scanned using a 3.0-T functional magnetic resonance imaging scanner. Regional homogeneity (ReHo) was used to assess resting-state brain activity. Daily pain scores were collected 1 week before functional magnetic resonance imaging. We found that patients with abdominal pain exhibited lower ReHo values in the insula, middle cingulate cortex (MCC), and supplementary motor area and higher ReHo values in the temporal pole. In contrast, patients without abdominal pain exhibited lower ReHo values in the hippocampal/parahippocampal cortex and higher ReHo values in the dorsomedial prefrontal cortex (all P < 0.05, corrected). The ReHo values of the insula and MCC were significantly negatively correlated with daily pain scores for patients with abdominal pain (r = -0.53, P = 0.008 and r = -0.61, P = 0.002, respectively). These findings suggest that resting-state brain activities are different between remissive patients with CD with and without abdominal pain and that abnormal activities in insula and MCC are closely related to the severity of abdominal pain.

To observe the effect of electroacupuncture (EA) and herbal cake-partitioned moxibustion on anxiety and depression in patients with Crohn’s disease (CD) in remission. Sixty CD cases were randomly allocated into an EA group (n=30) and an herbal cake-partitioned moxibustion group (n=30) using the random number table by the ratio of 1:1. In addition, 30 healthy subjects were included in a control group. Bilateral Tianshu (ST 25), Qihai (CV 6) and Zhongwan (CV 12) were used in the EA and herbal cakepartitioned moxibustion groups. The treatment was done 3 times a week, for a total of 12 weeks. The efficacy was evaluated using self-rating anxiety scale (SAS), self-rating depression scale (SDS) and traditional Chinese medicine (TCM) symptom scores. Before treatment, the SAS and SDS scores in CD patients were remarkably higher than those in healthy subjects. After EA or herbal cake-partitioned moxibustion treatment, the SAS and SDS scores were significantly decreased in both groups, showing significant intra-group differences (P 0.05). Both EA and herbal cake-partitioned moxibustion can significantly decrease abnormally high SAS and SDS scores in CD patients as well as TCM symptom scores. The two therapies share similar effects in alleviating common symptoms and improving anxiety and depression.

Crohn’s disease may cause excessive damage and repair in the intestinal epithelium due to its chronic relapsing intestinal inflammation. These factors may initiate the TGF-β 1-Smad pathway to activate the transcription factor of Snail, and the Snail-mediated pathway promotes the transformation of intestinal epithelial cells to mesenchymal cells, leading to intestinal fibrosis. Acupuncture and moxibustion have been demonstrated to prevent intestinal fibrosis in Crohn’s disease. However, it is not clear whether acupuncture and moxibustion can inhibit intestinal epithelial mesenchymal transformation in Crohn’s disease by affecting the TGF-β 1-Smad-Snail pathway. This study indicated that abnormal increased expressions of TGFβ1, TβR2, Smad3, and Snail were significantly downregulated by herbs-partitioned moxibustion at Tianshu (ST25) and Qihai (RN6) and acupuncture at Zusanli (ST36) and Shangjuxu (ST37). In addition, protein and mRNA levels of E-cadherin, the epithelial cell marker, were significantly increased. Protein and mRNA levels of fibronectin, the mesenchymal cell marker, were decreased in the intestinal tissue. Moreover, the number of mesenchymal cells in the intestinal mucosa can be reversely transformed to intestinal epithelial cells. Therefore, herbs-partitioned moxibustion combined with acupuncture can prevent intestinal epithelial mesenchymal transition by inhibiting abnormal expression of TGFβ1, TβR2, Smad3, and Snail in the TGF-β1-Smad-Snail pathway in Crohn’s disease.

Crohn's disease may cause excessive damage and repair in the intestinal epithelium due to its chronic relapsing intestinal inflammation. These factors may initiate the TGF-β 1-Smad pathway to activate the transcription factor of Snail, and the Snail-mediated pathway promotes the transformation of intestinal epithelial cells to mesenchymal cells, leading to intestinal fibrosis. Acupuncture and moxibustion have been demonstrated to prevent intestinal fibrosis in Crohn's disease. However, it is not clear whether acupuncture and moxibustion can inhibit intestinal epithelial mesenchymal transformation in Crohn's disease by affecting the TGF-β 1-Smad-Snail pathway. This study indicated that abnormal increased expressions of TGFβ1, TβR2, Smad3, and Snail were significantly downregulated by herbs-partitioned moxibustion at Tianshu (ST25) and Qihai (RN6) and acupuncture at Zusanli (ST36) and Shangjuxu (ST37). In addition, protein and mRNA levels of E-cadherin, the epithelial cell marker, were significantly increased. Protein and mRNA levels of fibronectin, the mesenchymal cell marker, were decreased in the intestinal tissue. Moreover, the number of mesenchymal cells in the intestinal mucosa can be reversely transformed to intestinal epithelial cells. Therefore, herbs-partitioned moxibustion combined with acupuncture can prevent intestinal epithelial mesenchymal transition by inhibiting abnormal expression of TGFβ1, TβR2, Smad3, and Snail in the TGF-β1-Smad-Snail pathway in Crohn's disease.

To investigate the effect and mechanism of moxibustion in rats with ulcerative colitis.A rat colitis model was established by administering 4% dextran sulphate sodium solution. Seventy male rats were randomly divided into seven groups: Healthy controls (HC), ulcerative colitis model group (UC), UC with 7 d of moxibustion (UC-7), UC with 14 d of moxibustion (UC-14), UC with mesalazine gavage (UC-W), HC with 7 d of moxibustion (HC-7), HC with 14 d of moxibustion (HC-14). Moxibustion was applied to the bilateral Tianshu (ST25). Gut microbiome profiling was conducted by 16S rRNA amplicon sequencing, and PCR and ELISA determined the expression of inflammatory cytokines in colon mucosa and serum, respectively.Moxibustion treatment restored the colonic mucosa and decreased submucosal inflammatory cell infiltration in colitis rats. Rats treated with moxibustion and mesalazine had significantly lower levels of the dominant phyla Proteobacteria and the generaOur findings suggest that moxibustion exerts its therapeutic effect by repairing mucosal tissue damage and modulating the gut microbiome and intestinal mucosal immunity.

The branching enzyme (EC 2.4.1.18) catalyzes the formation of α-1,6 branch points in starch. In this study, the Geobacillus thermoglucosidans gene-encoding branching enzyme was expressed in Escherichia coli BL21 (DE3) and the protein was isolated and characterized. G. thermoglucosidans branching enzyme is a thermostable enzyme with an optimal reaction temperature of nearly 60°C and a half-life at 65°C of approximately 1.1 h. The activity of the recombinant enzyme is optimal at pH 7.5, with broad stability between pH 5.5 and 9.0. Its thermostability, relatively broad pH stability and optimal temperature near the temperature at which starch begins to gelatinize may make it easy to use in industrial production. Furthermore, the enzyme is activated by Mg2+, Ba2+, K+ and Na+ in a concentration-dependent manner and dramatically inhibited by Ni2+ and Co2+. Its substrate dependence, using amylopectin as the substrate, could be adequately fitted using the Michaelis-Menten equation, yielding a Km of 0.99 mg/ml. High-performance anion exchange chromatography results showed that the chain length distribution of branching enzyme-treated waxy corn starch is indistinguishable from that of the branching enzyme-treated common corn starch. This enzyme may therefore be a promising tool for the enzymatic modification of starch.

Crohn's disease (CD) has been reported to relate with the functional and structural alterations in several local brain regions. However, it remains unknown whether the possible abnormalities of information transmission and integration between brain regions are associated with CD. The purpose of this study was to investigate the topological alterations of brain functional networks and the potential relationships between the neuroimaging findings and CD clinical characteristics. 43 remissive CD patients and 37 matched healthy controls (HCs) were recruited to obtain their resting-state functional magnetic resonance imaging (fMRI) data. Independent component analysis was applied to decompose fMRI data for building brain functional networks. The local and global topological properties of networks and connectivity of brain regions were computed within each group. We then examined the relationships between the topological patterns and CD clinical characteristics. Compared to HCs, CD patients exhibited disrupted local and global topological patterns of brain functional networks including the decreased nodal graph metrics in the subcortical, sensorimotor, cognitive control and default-mode networks and dysfunctional interactions within and among these four networks. The connectivity strength of putamen negatively correlated with CD duration in patients. Moreover, CD patients with high level of anxiety and/or depression had altered local topological patterns associated with anterior cingulate cortex (ACC), medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC) compared to other patients. By revealing CD-related changes in topological patterns of brain functional networks, our findings provide further neuroimaging evidence on the pathophysiology of CD involved in pain, sensory, emotional and/or cognitive processing.

Previous studies have demonstrated that acupuncture is beneficial to patients with Crohn’s disease (CD), but the mechanism underlying its therapeutic effects remains unclear. To identify the mechanism by which acupuncture treats CD, the balance between Th17 and Treg cells was assessed in CD patients. In this study, Ninety-two CD patients were randomly and equally assigned to a treatment group that were treated with herb-partitioned moxibustion and acupuncture or a control group with wheat bran-partitioned moxibustion and superficial acupuncture. The effect of these treatments on Th17 and Treg cells and their related molecular markers in the intestinal mucosa were detected before (week 0) and after (week 12) treatment. The results suggested that the ratio of Th17 and Treg cells was significantly decreased after treatment and that the levels of IL-17 and RORγt in the intestinal mucosa were obviously reduced, while the expression of FOXP3 was increased after treatment in both groups. In the treatment group, the expression of these molecules was more markedly regulated than the control group. In conclusion, moxibustion and acupuncture have been shown to regulate the ratio of Th17 and Treg cells in the intestinal mucosa of CD patients and restore the balance between these immune cell subsets.

Objective.To compare the impacts of electroacupuncture (EA) and mild moxibustion (Mox) on patients with irritable bowel syndrome (IBS).Method.Eighty-two IBS patients were randomly allocated into EA group (n=41) and Mox group (n=41) and received corresponding interventions for four weeks. Before and after the treatment, the Visual Analogue Scale for Irritable Bowel Syndrome (VAS-IBS) was used to evaluate the gastrointestinal symptoms and mental well-being; and the expression of serotonin (5-hydroxytryptamine, 5-HT), 5-HT3receptor (5-HT3R), and 5-HT4receptor (5-HT4R) in sigmoid mucosal tissue were detected.Results. Both EA and Mox can radically improve the total VAS-IBS score (P<0.05), and EA was found to be more effective in ameliorating the symptom of constipation, while Mox was found to be more effective in ameliorating the symptom of diarrhoea. The abnormal expressions of 5-HT, 5-HT3R, and 5-HT4R in both groups were significantly improved after the treatments (allP<0.05), and EA was superior to Mox in regulating the abnormally decreased 5-HT4R expression in IBS patients with constipation (P<0.05).Conclusion. Electroacupuncture and mild moxibustion were both effective in improving IBS symptoms and modulate abnormal expressions of 5-HT, 5-HT3R, and 5-HT4R in the colonic tissue.

To observe the effects and safety of clinical common symptoms of active Crohn's disease at the mild and moderate stages treated with acupuncture and moxibustion.One hundred and two patients were randomly divided into an observation group and a control group, 51 cases in each one. Herb-partition moxibustion and acupuncture were used in the observation group. Herbal cakes withAfter 12-week treatment, the eight symptoms were improved apparently (allHerb-partition moxibustion combined with acupuncture achieve safety and efficacy for mild and moderate Crohn's disease, and can improve the clinical common symptoms. Furthermore, their effects on abdominal pain (degree, frequency, time), diarrhoea (shape and frequency), fatigue and anorexia are better than those of bran-partition moxibustion and shallow acupuncture.

Acupuncture and moxibustion have been shown to be effective in treating Crohn's disease (CD), but their therapeutic mechanisms remain unclear. Here we compared brain responses to either electro-acupuncture or moxibustion treatment in CD patients experiencing remission. A total of 65 patients were randomly divided into an electro-acupuncture group (n = 32) or a moxibustion group (n = 33), and treated for 12 weeks. Eighteen patients in the electro-acupuncture group and 20 patients in the moxibustion group underwent resting-state functional magnetic resonance imaging at baseline and after treatment. Seed-based analysis was used to compare the resting-state functional connectivity (rsFC) between bilateral hippocampus and other brain regions before and after the treatments, as well as between the two groups. The CD activity index (CDAI) and inflammatory bowel disease questionnaire (IBDQ) were used to evaluate disease severity and patient quality of life. Electro-acupuncture and moxibustion both significantly reduced CDAI values and increased IBDQ scores. In the electro-acupuncture group, the rsFC values between bilateral hippocampus and anterior middle cingulate cortex (MCC) and insula were significantly increased, and the changes were negatively correlated with the CDAI scores. In the moxibustion group, the rsFC values between bilateral hippocampus and precuneus as well as inferior parietal lobe (IPC) were significantly elevated, and the changes were negatively correlated with the CDAI scores. We conclude that the therapeutic effects of electro-acupuncture and moxibustion on CD may involve the differently modulating brain homeostatic afferent processing network and default mode network (DMN), respectively.

Central sensitization and network hyperexcitability of the nociceptive system is a basic mechanism of neuropathic pain. We hypothesize that development of cortical hyperexcitability underlying neuropathic pain may involve homeostatic plasticity in response to lesion-induced somatosensory deprivation and activity loss, and can be controlled by enhancing cortical activity. In a mouse model of neuropathic pain, in vivo two-photon imaging and patch clamp recording showed initial loss and subsequent recovery and enhancement of spontaneous firings of somatosensory cortical pyramidal neurons. Unilateral optogenetic stimulation of cortical pyramidal neurons both prevented and reduced pain-like behavior as detected by bilateral mechanical hypersensitivity of hindlimbs, but corpus callosotomy eliminated the analgesic effect that was ipsilateral, but not contralateral, to optogenetic stimulation, suggesting involvement of inter-hemispheric excitatory drive in this effect. Enhancing activity by focally blocking cortical GABAergic inhibition had a similar relieving effect on the pain-like behavior. Patch clamp recordings from layer V pyramidal neurons showed that optogenetic stimulation normalized cortical hyperexcitability through changing neuronal membrane properties and reducing frequency of excitatory postsynaptic events. We conclude that development of neuropathic pain involves abnormal homeostatic activity regulation of somatosensory cortex, and that enhancing cortical excitatory activity may be a novel strategy for preventing and controlling neuropathic pain.

We report a systematic study on the effect of molecular weight (MW) on microphase separation of mixed poly(tert-butyl acrylate) (PtBA)/polystyrene (PS) brushes grafted on 172 nm silica particles. The brushes were synthesized by sequential surface-initiated atom transfer radical polymerization (ATRP) of tBA at 75 °C and nitroxide-mediated radical polymerization (NMRP) of styrene at 120 °C from silica particles functionalized with an asymmetric difunctional initiator bearing an ATRP initiator and an NMRP alkoxyamine. The MWs of the two polymers in each sample were controlled to be similar to each other. A series of mixed brush samples with different average MWs, from 13.8 to 33.1 kDa, but comparable overall grafting densities were made, and their microphase separation was studied by transmission electron microscopy (TEM). The TEM samples were prepared by drop-casting the dispersions of mixed brush-grafted particles in CHCl3 and also in water (stabilized by a surfactant) and staining the brushes with RuO4. W...

Polymer brush‐grafted particles (i.e., hairy particles) capable of undergoing direct, especially reversible, phase transfer from one liquid phase to another immiscible liquid phase in response to environmental changes have received growing interest due to their great potential in a wide variety of applications. This article is intended to review recent exciting advances in stimuli‐triggered phase transfer of hairy particles in liquid‐liquid biphasic systems. We start with a discussion of the mechanism of particle transfer across a liquid‐liquid interface and progress to the synthesis of polymer brushes grafted on particles and the transfer of hairy particles between two immiscible liquid phases induced by various external stimuli, including temperature, pH, ionic strength, light, and solvents. The applications of thermally triggered phase transfer of hairy particles in catalysis (thermoregulated phase transfer catalysis) are discussed, followed by a summary and our perspective on future development. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2014, 52, 1600–1619

Background: To investigate effects moxibustion exerts on A20 expression and regulation of intestinal epithelial tight junctions via the TNF-α-NF-κB-MLCK pathway in Crohn's disease (CD). Methods: C57BL/6 wild type (WT) and A20IEC−KO mice (48 each) were randomly divided into normal control (NC), model control (MC), mesalazine (MESA) and herbs-partitioned moxibustion (HPM) groups (12 mice per group). An experimental model of CD was established using 2, 4, 6 trinitrobenzene sulfonic acid. MESA and HPM mice were treated with MESA and HPM (at Tianshu (ST25) and Qihai (CV6)), respectively. In HPM group, moxa cones (0.5 cm in diameter and 0.3 cm in height) made of refined mugwort floss were placed on herbal cakes (medicinal formula dispensing [radix] Aconiti praeparata, [cortex] Cinnamomi, etc.) at Tianshu (ST25) and Qihai (CV6) and ignited. The moxa cones were ignited, and two moxa cones were used for each treatment once daily for 10 days. In MESA group, mice were fed MESA, which was prepared at a proportion of 1:0.0026, twice daily for 10 days. Results: Intestinal epithelial ultrastructure of WT HPM mice improved more than A20IEC−KO HPM mice compared to MC mice. WT HPM mice exhibited greater expression of A20 compared with MC mice (P

This article reports on the synthesis of mixed homopolymer brushes grafted on silica particles composed of poly(e-caprolactone) (PCL), a chemically and biologically degradable polymer, and polystyrene (PS), a vinyl polymer, by sequential surface-initiated ring-opening polymerization (ROP) of e-caprolactone (eCL) at 75 °C and nitroxide-mediated radical polymerization (NMRP) of styrene at 120 °C. The silica particles were functionalized with an asymmetric difunctional initiator (Y-initiator) bearing a hydroxyl group, an initiator for ROP, and an alkoxyamine moiety, an initiator for NMRP. We found that for ROP, PCL with Mn,SEC values of ∼25 kDa and narrow polydispersity indexes (≤1.20) relative to PS standards can be reproducibly synthesized at 75 °C using tin(II) 2-ethylhexanoate as catalyst after the Y-initiator-functionalized silica particles and the catalyst were thoroughly dried. Both surface-initiated ROP and NMRP polymerizations were carried out in the presence of a free initiator. The polymer brushes were cleaved from silica particles using hydrofluoric acid, and the SEC analysis showed that the molecular weights of the grafted polymers were close to those of the free polymers formed from the free initiators. The overall grafting density of mixed PCL/PS brushes can be tuned from 1.24 to 0.40 chains per nm2 by varying the mass ratio of Y-initiator-terminated triethoxysilane to bare silica particles in the initiator immobilization step, though the grafting density of PS was always higher than that of PCL.

Three-dimensional (3D) morphology of hierarchically self-assembled mixed poly(tert-butyl acrylate) (PtBA)/polystyrene (PS) brush-grafted 67 nm silica nanoparticles cast from chloroform on a carbon-coated transmission electron microscopy (TEM) grid was directly visualized using electron tomography (i.e., 3D TEM). The number-average molecular weights for PtBA and PS were 22.2 and 23.4 kDa, and their grafting densities were 0.51 and 0.34 chains/nm2, respectively. For a dense monolayer of mixed brush-grafted silica particles, a rippled phase structure was observed, and the monolayer consisted of protruded top portions from large nanoparticles and a bottom continuous film. In the top protruded part of large nanoparticles, isolated cylindrical PS microdomains were formed in the PtBA matrix due to the low PS volume fraction (i.e., 37%). The morphology in the lower continuous film was strongly influenced by interparticle interactions via mixed polymer brushes. As a result, bicontinuous nanostructures instead of i...

Irritable bowel syndrome (IBS) is a worldwide disease with high morbidity. The effect of current treatment with Western medicine is not satisfactory. Although moxibustion treatment is widely used for gastrointestinal diseases, randomized controlled trials on the use of this treatment for IBS are limited. This study aims to evaluate the clinical efficacy and safety of moxibustion treatment in patients with diarrhea-predominant irritable bowel syndrome (IBS-D). A multi-center, randomized, single-blind and placebo-controlled trial is employed. 104 cases will be divided into two groups: (1) a mild-warm moxibustion group in which moxa stick is 3–5 cm away from acupuncture points and the skin temperature is maintained at 43 ± 1 °C; and (2) a placebo moxibustion group in which moxa stick is 8–10 cm away from acupuncture points and the skin temperature is maintained at 37 ± 1 °C. Moxibustion is performed on bilateral ST25 and ST36 in the two groups for 30 min each time, three times a week for 6 weeks. The patients are followed up at the 12th and 18th weeks. Adequate relief is used as a primary outcome measure; IBS symptom severity score, Bristol stool form scale, IBS quality-of-life questionnaire, and hospital anxiety and depression scale are used as secondary outcome measures. This study aims to demonstrate the safety and efficacy of moxibustion treatment for IBS-D, which may validate moxibustion as an effective therapy for treating IBS-D. ClinicalTrials.gov identifier NCT02421627 (8 April 2015).

AIM To observe whether there are differences in the effects of electro-acupuncture (EA) and moxibustion (Mox) in rats with visceral hypersensitivity. METHODS EA at 1 mA and 3 mA and Mox at 43 °C and 46 °C were applied to the Shangjuxu (ST37, bilateral) acupoints in model rats with visceral hypersensitivity. Responses of wide dynamic range neurons in dorsal horns of the spinal cord were observed through the extracellular recordings. Mast cells (MC) activity in the colons of rats were assessed, and 5-hydroxytryptamine (5-HT), 5-hydroxytryptamine 3 receptor (5-HT3R) and 5-HT4R expressions in the colons were measured. RESULTS Compared with normal control group, responses of wide dynamic range neurons in the dorsal horn of the spinal cord were increased in the EA at 1 mA and 3 mA groups (1 mA: 0.84 ± 0.74 vs 2.73 ± 0.65, P < 0.001; 3 mA: 1.91 ± 1.48 vs 6.44 ± 1.26, P < 0.001) and Mox at 43 °C and 46 °C groups (43 °C: 1.76 ± 0.81 vs 4.14 ± 1.83, P = 0.001; 46 °C: 5.19 ± 2.03 vs 7.91 ± 2.27, P = 0.01). MC degranulation rates and the expression of 5-HT, 5-HT3R and 5-HT4R in the colon of Mox 46 °C group were decreased compared with model group (MC degranulation rates: 0.47 ± 0.56 vs 0.28 ± 0.78, P < 0.001; 5-HT: 1.42 ± 0.65 vs 7.38 ± 1.12, P < 0.001; 5-HT3R: 6.62 ± 0.77 vs 2.86 ± 0.88, P < 0.001; 5-HT4R: 4.62 ± 0.65 vs 2.22 ± 0.97, P < 0.001). CONCLUSION The analgesic effects of Mox at 46 °C are greater than those of Mox at 43 °C, EA 1 mA and EA 3 mA.

Aim. To compare whether there is different effect between electroacupuncture (EA) and moxibustion (Mox) on visceral hypersensitivity (their analgesic effects) in constipation-predominant irritable bowel syndrome (C-IBS).Methods. EA at 1 mA and 3 mA and Mox at 43°C and 46°C were applied to the Shangjuxu (ST37, bilateral) acupoint in rats with C-IBS and normal rats. An abdominal withdrawal reflex (AWR) score was used to assess visceral hypersensitivity. Toluidine blue staining was used to assess mast cell (MC) activity in colon of rats. Immunochemistry was used to measure 5-HT and 5-HT4 receptor expression in the colon.Results. AWR scores in all EA (1 mA and 3 mA) and Mox (43°C and 46°C) treatment groups after colorectal distention (CRD) stimulation pressure of 20, 40, 60, and 80 mmHg were significantly lower than those of the model (MC) group (Pall < 0.01). The MC counts and degranulation rates in the colon of all EA and Mox treatment groups and the MC group were significantly higher than those of the NC group (Pall < 0.01). MC degranulation rates in the colon of all EA and Mox treatment groups were lower than those of the MC group (Pall < 0.05). 5-HT expression in colon of all EA and Mox treatment groups was significantly lower than that of the MC group (Pall < 0.01), and 5-HT4R expression in colon of both EA groups was significantly higher than that of the MC group (Pboth < 0.01).Conclusion. EA and Mox treatments may both ameliorate visceral hypersensitivity at different degree in rats with C-IBS, and EA treatment was better than Mox.

This study aimed to investigate changes in resting state brain activity in remissive Crohn’s Disease (CD) patients after electro-acupuncture or moxibustion treatment. Fifty-two CD patients and 36 healthy subjects were enrolled, and 36 patients were equally and randomly assigned to receive either electro-acupuncture or moxibustion treatment for twelve weeks. We used resting state functional magnetic resonance imaging to assess Regional Homogeneity (ReHo) levels, and Crohn’s Disease Activity Index (CDAI) and Inflammatory Bowel Disease Questionnaire (IBDQ) scores to evaluate disease severity and quality of life. The results show that (i) The ReHo levels in CD patients were significantly increased in cortical but decreased in subcortical areas, and the coupling between them was declined. (ii) Both treatments decreased CDAI, increased IBDQ scores, and normalized the ReHo values of the cortical and subcortical regions. (iii) ReHo changes in multiple cortical regions were significantly correlated with CDAI score decreases. ReHo changes in several subcortical regions in the electro-acupuncture group, and those of several cortical regions in the moxibustion group, were correlated with reduced CDAI. These findings suggest that both treatments improved cortex-subcortical coupling in remissive CD patients, but electro-acupuncture regulated homeostatic afferent processing network, while moxibustion mainly regulated the default mode network of the brain.