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.

Research progress and key scientific problems of traditional Chinese moxibustion

Moxibustion Moxibustion(written as“jiū(灸)”in Chinese),also known as“jiūruò(灸焫)”in ancient Chinese,was described in the ancient Chinese book Shuo Wen Jie Zi as having the meaning of burning and possessing the properties of fire,while sharing the same pronunciation as“jiǔ(久).”“Moxibustion is a method of curing diseases that uses lighted moxa to press and cauterize acupoints.”Moxibustion is a traditional external treatment method that involves the application of moxa wool or other materials,either directly or indirectly(such as through burning or fumigation),to stimulate specific points or areas on body surface.It is used for purposes such as prevention,treatment,rehabilitation,and health care.Moxibustion originated in ancient times,prevailed during the Qin and Han dynasties(221 B.C.E.–220 C.E.),experienced a period of decline during the Ming and Qing dynasties(1368–1912 C.E.),and was revitalized in the contemporary era.

OBSERVATIONS ON CLINICAL THERAPEUTIC EFFECT IN TREATING SOFT TISSUE IN|URIES BY ACUPUNCTURE,WITH PAIN THRESHOLD AND ELECTROMYOGRAPHY AS PARAMETERS

Soft tissue lesion is commonly seen in clinics,constituting more than half of the orthopediccases. Based on the syndrome differentiationtheory of traditional Chinese medicine(TCM),taking pain threshold and electromyography(EMG)as objective parameters on 120 soft tissueinjury cases divided into two groups for treat-ment,altogether 360 observations were recordedwith satisfactory results.

Acupuncture at Baihui and Dazhui reduces brain cell apoptosis in heroin readdicts

Acupuncture at Baihui （GV20） and Dazhui （GV14） reduces neuronal loss and attenuates ultra- structural damage in cerebral ischemic rats. However, whether acupuncture can treat addiction and prevent readdiction through changes to brain cell ultrastructure remains unknown. In this study, cell apoptosis was observed in the hippocampus and frontal lobe of heroin readdicted rats by electron microscopy. Immunohistochemical staining displayed a reduction in Bcl-2 ex- pression and an increase in Bax expression in the hippocampus and frontal lobe. After rats were given acupuncture at Baihui and Dazhui, the pathological damage in the hippocampus and frontal lobe was significantly reduced, Bcl-2 expression was upregulated and Bax expression was downregulated. Acupuncture exerted a similar effect with methadone, a commonly used drug for clinical treatment of drug addiction. Experimental findings suggest that acupuncture at Dazhui and Baihui can prevent brain cell apoptosis in heroin readdicted rats.

Electroacupuncture modulates the activity of the hippocampus-nucleus tractus solitarius-vagus nerve pathway to reduce myocardial ischemic injury

The hippocampus is involved in the regulation of the autonomic nervous system,together with the hypothalamus and brainstem nuclei,such as the paraventricular nucleus and nucleus tractus solitarius.The vagus nerve-nucleus tractus solitarius pathway has an important role in cardiovascular reflex regulation.Myocardial ischemia has been shown to cause changes in the autonomic nervous system,affecting the dynamic equilibrium of the sympathetic and vagal nerves.However,it remains poorly understood how the hippocampus communicates with brainstem nuclei to regulate the autonomic nervous system and alleviate myocardial ischemic tissue damage.A rat model of acute myocardial ischemia（AMI） was made by ligating the left anterior descending branch of the coronary artery.Three days before ischemia,the hippocampal CA1 region was damaged.Then,3 days after ischemia,electroacupuncture（EA） at Shenmen（HT7）-Tongli（HT5） was performed（continuous wave,1 m A,2 Hz,duration of 30 minutes）.Cluster analysis of firing patterns showed that one type of neuron was found in rats in the sham and AMI groups.Three types of neurons were observed in the AMI ＋ EA group.Six types of neurons were found in the AMI ＋ EA ＋ Lesion group.Correlation analysis showed that the frequency of vagus nerve discharge in each group was negatively correlated with heart rate（HR）（P 〈 0.05,r =-0.424）,and positively correlated with mean arterial pressure（MAP）（P 〈 0.05,r = 0.40987） and the rate-pressure product（RPP）（P 〈 0.05,r = 0.4252）.The total frequency of the nucleus tractus solitarius discharge in each group was positively correlated with vagus nerve discharge（P 〈 0.01,r = 0.7021）,but not with hemodynamic index（HR： P 〉 0.05,r =-0.03263; MAP： P 〉 0.05,r =-0.08993; RPP： P 〉 0.05,r =-0.03263）.Some neurons（Neuron C） were negatively correlated with vagus nerve discharge,HR,MAP and RPP in the AMI ＋ EA group（vagus nerve discharge： P 〈 0.05,r =-0.87749; HR： P 〈 0.01,r =-0.91902; MAP： P 〈 0.05,r =-0.85691; RPP： P 〈 0.01,r =-0.91902）.Some neurons（Neurons C,D and E） were positively correlated with vagus nerve discharge,HR,MAP and RPP in the AMI ＋ EA ＋ Lesion group（vagus nerve discharge： P 〈 0.01,r = 0.8905,P 〈 0.01,r = 0.9725,P 〈 0.01,r = 0.9054; HR： P 〈 0.01,r = 0.9347,P 〈 0.01,r = 0.9089,P 〈 0.05,r = 0.8247; MAP： P 〈 0.05,r = 0.8474,P 〈 0.01,r = 0.9691,P 〈 0.01,r = 0.9027; RPP： P 〈 0.05,r = 0.8637,P 〈 0.01,r = 0.9407,P 〈 0.01,r = 0.9027）.These findings show that the hippocampus-nucleus tractus solitarius-vagus nerve pathway is involved in the cardioprotective effect of EA at the heart meridian.Some interneurons in the nucleus tractus solitarius may play a particularly important role in the cardiomodulatory process.

Extracellular signal-regulated kinase, substance P and neurokinin-1 are involved in the analgesic mechanism of herb-partitioned moxibustion

Herb-partitioned moxibustion can effectively mitigate visceral pain, a major symptom in inflammatory bowel disease, but the analgesic lnechanism is still unclear. Moreover, extracellular signal-regulated kinase, substance P, and neurokinin-1 are involved in formation of central hyperalgesia. Thus, we postulated that the analgesic effect of herb-partitioned moxibustion may be associated with these factors. Accordingly, in this study, we established an inflammatory bowel disease visceral pain model in rat by enema with a mixed solution of 5% trinitrobenzenesulfonic acid and 50% ethanol. Bilateral Tianshu （ST25） and Qihai （CV6） points were selected for herb-partitioned moxi- bustion. Our results showed that herb-partitioned moxibustion improved visceral pain and down-regulated extracellular signal-regulated kinase, substance P, and neurokinin-1 protein and mRNA expression in dorsal root ganglia. These results indicate that down-regulation of extracellular signal-regulated kinase, substance E and neurokinin-1 protein and mRNA may be a central mechanism for the analgesic effect of herb-partitioned moxibustion.

Effects of electroacupuncture on corticotropin-releasing hormone in rats with chronic visceral hypersensitivity

AIM: To investigate the effect of electroacupuncture on corticotropin-releasing hormone(CRH) in the colon, spinal cord, and hypothalamus of rats with chronic visceral hypersensitivity.METHODS: A rat model of chronic visceral hypersensitivity was generated according to the internationally accepted method of colorectal balloon dilatation. In the 7th week after the procedure, rats were randomly divided into a model group(MG), electroacupuncture group(EA), and sham electroacupuncture group(S-EA). After treatment, the abdominal withdrawal reflex(AWR) score was used to assess the behavioral response of visceral hyperalgesia. Immunohistochemistry(En Vision method), ELISA, and fluorescence quantitative PCR methods were applied to detect the expression of CRH protein and m RNA in the colon, spinal cord, and hypothalamus.RESULTS: The sensitivity of the rats to the colorectal distension stimulus applied at different strengths(20-80 mm Hg) increased with increasing stimulus strength, resulting in increasing AWR scores in each group. Compared with NG, the AWR score of MG was significantly increased(P < 0.01). After conducting EA, the AWR scores of the rats were decreased compared with MG rats. The relative expression of CRH m RNA in the colon, spinal cord, and hypothalamus of MG rats was significantly increased compared with NG rats(P < 0.01). CRH m RNA in the colon and spinal cord of EA and S-EA rats was decreased to varying degrees(P > 0.05) compared with normal rats(NG). However, the decrease in EA compared with MG rats was statistically significant(P < 0.01). The average optical density of CRH expression in the colon of the MG rats was significantly enhanced compared with NG(P < 0.05), while the average optical density of CRH expression in the EA and S-EA rats was significantly decreased compared with MG rats(P < 0.01, P < 0.05, respectively). Compared with MG rats, the CRH concentration in the spinal cord of EA rats was significantly reduced(P < 0.01), but there was no significant change in S-EA rats(P > 0.05).CONCLUSION: Electroacupuncture at the Shangjuxu acupoint was able to significantly reduce the visceral hypersensitivity in rats, and regulated the expression of CRH protein and m RNA in the colon, spinal cord and hypothalamus at different levels, playing a therapeutic role in this model of irritable bowel syndrome.

Interventional effect of electroacupuncture combined with medicine on monoamine neurotransmitters in hypothalamus of rats with ulcerative colitis

BACKGROUND： Ulcerative colitis （UC） is conventionally treated with sulfasalazine and other aminosalicylic acids. The symptoms of UC can be rapidly controlled, but high recurrence, severe adverse reactions and other shortages exist commonly. Whether electroacupuncture combined with medicine can make up these shortages remains unclear. OBJECTIVE： This study was to observe the regulatory effect of electroacupuncture combined with medicine on monoamine neurotransmitter in hypothalamus of rats with ulcerative colitis, and to analyze the pathogenesis of UC and the action pathway of electroacupuncture combined with medicine. DESIGN： A randomized controlled observation. SETTING： Shanghai Institute of Acupuncture and Meridian. MATERIALS： Thirty involved male SD rats of clean grade, weighing （200±20）g, were provided by the Experimental Animal Center, Shanghai University of Traditional Chinese Medicine. Sulfasalazine was produced in the Shanghai Sanwei Pharmaceutical Co., Ltd [certification No. （1995）002083]. METHODS： This study was carried out in the State Laboratory （grade 3） for Acupuncture and Immunology, Shanghai Institute of Acupuncture and Meridian. The involved 30 rats were randomized into 5 groups： normal group, model group, electroacupuncture group, medicine group and electroacupuncture combined with medicine group, with 6 rats in each group. Rats in the latter 4 groups were prepared into models of UC. In the electroacupuncture group, Zusanli（shuang） point was selected. Electro-acupuncture apparatus （G6805Ⅱ type） was connected to the point and used to stimulate it with continuous wave, frequency of 2 Hz, electrical intensity 4 mA, 20 minutes a day, for 14 days successively. In the medicine group, rats were intragastrically administrated with sulfasalazine, twice a day, 3 mL once, for 14 days successively. In the electroacupuncture combined with medicine group, rats were treated with electroacupuncture and medicine simultaneously as described in the previous two groups. Rats in the model group and normal control group were untouched except for being fixed. MAIN OUTCOME MEASURES： The levels of noradrenaline acid tartrate （NE）, 3-methoxy-4 hydroxyphenylglycol （MHPG）, dopamine hydrochloride （DA）, 3,4-dihydroxyphenylacetic acid （DOPAC）, 5-hydroxytryptamine （5-HT） hydrochloride, homovanillic acid （HVA） and 5-hydroxyindole acetic acid （5-HIAA） of rats in each group were detected by high-performance liquid chromatography （HPLC）-electrochemical method. RESULTS： All the 30 involved rats entered into the stage of final analysis. ①Detection of NE and MHPG levels： After treatment, NE level in the hypothalamus of rats was significantly higher in the electroacupuncture combined with medicine group, electroacupuncture group and medicine group was all significantly higher than that in the model group, respectively （P 〈 0.01）. After treatment, MHPG level in the metabolite of NE was very significantly higher in the electroacupuncture group than in the medicine group （P 〈 0.01）. ②Detection of DA and DOPAC levels： After treatment, DA level in the hypothalamus of rats was very significantly higher in the medicine group than in the model group （P 〈 0.01）. ③Detection of 5-HT, HVA and 5-HIAA levels： After treatment, 5-HIAA level in the hypothalamus of rats was significantly higher in the medicine group than in the model group （P 〈 0.05）. CONCLUSION： The abnormal synthesis and metabolism of monoamine neurotransmitter in the central nervous system is one of pathogenesis of UC. Electroacupuncture combined with medicine might reach its goal of treatment by regulating the monoamine neurotransmitter disorder in the hypothalamus of rats with UC.

Effects of moxibustion on heat-shock protein 70 expression in the spinal cord and colonic mucosa in a rat model of ulcerative colitis

Pathological changes in the colon are closely associated with the spinal cord, and innervation of spinal cord can regulate cellular functions. Our previous studies verified that moxibustion protects and restores the colonic mucosa, but the mechanisms of action remain unknown. The present study observed the effects of moxibustion and salicylazosulfapyridine on expression of heat-shock protein 70 （HSP70） and its mRNA in the spinal cord and colonic mucosa of ulcerative colitis rats. Results demonstrated that moxibustion and salicylazosulfapyridine increased HSP70 mRNA expression in the spinal cord and colonic mucosa of ulcerative colitis rats. The decreased transcriptional activity of HSP70 in the spinal cord and colonic mucosa might participate in damage to the colonic mucosa in ulcerative colitis rats. Moxibustion exerted protective effects on colonic mucosa by up-regulating HSP70 transcriptional activity in the spinal cord and colonic mucosa.

Accurate Assessment and Tracking the Process of Liver-Specific Injury by the Residual Tissue Activity of Carboxylesterase 1 and Dipeptidyl Peptidase 4

Accurately assessing and tracking the progression of liver-specific injury remains a major challenge in the field of biomarker research.Here,we took a retrospective validation approach built on the mutuality between serum and tissue biomarkers to characterize the liver-specific damage of bile duct cells caused by a-naphthyl isothiocyanate(ANIT).We found that carboxylesterase 1(CES1),as an intrahepatic marker,and dipeptidyl peptidase 4(DPP-IV),as an extrahepatic marker,can reflect the different pathophysiologies of liver injury.Levels of CES1 and DPP-IV can be used to identify liver damage itself and the inflammatory state,respectively.While the levels of the conventional serological biomarkers alkaline phosphatase(ALP),alanine aminotransferase(ALT),and aspartate aminotransferase(AST)were all concomitantly elevated in serum and tissues after ANIT-induced injury,the levels of bile acids decreased in bile,increased in serum,and ascended in intrahepatic tissue.Although the level of γ-glutamyl transpeptidase(γ-GT)changed in an opposite direction,the duration was much shorter than that of CES1 and was quickly restored to normal levels.Therefore,among the abovementioned biomarkers,only CES1 made it possible to specifically determine whether the liver cells were destroyed or damaged without interference from inflammation.CES1 also enabled accurate assessment of the anti-cholestasis effects of ursodeoxycholic acid(UDCA;single component)and Qing Fei Pai Du Decoction(QFPDD;multicomponent).We found that both QFPDD and UDCA attenuated ANIT-induced liver damage.UDCA was more potent in promoting bile excretion but showed relatively weaker anti-injury and antiinflammatory effects than QFPDD,whereas QFPDD was more effective in blocking liver inflammation and repairing liver damage.Our data highlights the potential of the combined use of CES1(as an intrahepatic marker of liver damage)and DPP-IV(as an extrahepatic marker of inflammation)for the accurate evaluation and tracking of liver-specific injury—an application that allows for the differentiation of liver damage and inflammatory liver injury.

Inhibitory Effect of S100A11 on Airway Smooth Muscle Contraction and Airway Hyperresponsiveness

Objective S100A11 is a member of the S100 calcium-binding protein family and has intracellular and extracellular regulatory activities.We previously reported that S100A11 was differentially expressed in the respiratory tracts of asthmatic rats as compared with normal controls.Here,we aimed to analyze the potential of S100A11 to regulate both allergen-induced airway hyperresponsiveness(AHR)as well as acetylcholine(ACh)-induced hypercontractility of airway smooth muscle(ASM)and contraction of ASM cells(ASMCs).Methods Purified recombinant rat S100A11 protein(rS100A11)was administered to OVA-sensitized and challenged rats and then the AHR of animals was measured.The relaxation effects of rS100A11 on ASM were detected using isolated tracheal rings and primary ASMCs.The expression levels of un-phosphorylated myosin light chain(MLC)and phosphorylated MLC in ASMCs were analyzed using Western blotting.Results Treatment with rS100A11 attenuated AHR in the rats.ASM contraction assays showed that rS100A11 reduced the contractile responses of isolated tracheal rings and primary ASMCs treated with ACh.In addition,rS100A11 markedly decreased the ACh-induced phosphorylation of the myosin light chain in ASMCs.Moreover,rS100A11 also suppressed the contractile response of tracheal rings in calcium-free buffer medium.Conclusion These results indicate that S100A11 protein can relieve AHR by relaxing ASM independently of extracellular calcium.Our data support the idea that S100A11 is a potential therapeutic target for reducing airway resistance in asthma patients.

Effects of electroacupuncture at Fengchi(GB20)on motor function and GFAP/NeuN expression around the ischemic tissue of the motor cortex in MCAO rats

Objective:To investigate the potential mechanism of electroacupuncture(EA)at bilateral Fengchi(GB20)in treating cerebral ischemia-reperfusion injury and to provide a scientific basis for future experimental research and clinical applications.Methods:Forty male specific-pathogen-free Sprague-Dawley rats were randomly divided into four groups:a normal group,a normal with EA group,a model group,and a model with EA group,with 10 rats in each group.The normal group received no intervention.The normal with EA group received EA at bilateral Fengchi(GB20).The model group underwent middle cerebral artery occlusion(MCAO)using the suture.The model with EA group underwent MCAO and received EA at bilateral Fengchi(GB20).Cerebral blood flow was monitored using a laser Doppler cerebral blood flow meter.Neurologic damage was assessed using the neurologic deficit score,and motor ability was observed using the CatWalk gait system.The expression of glial fibrillary acidic protein(GFAP)and neuronal nuclei(NeuN)protein,the neuron markers,was detected by Western blotting.The protein expression levels of GFAP and NeuN,as well as the number of positive cells in the motor cortex,were detected using immunofluorescence.Results:Compared to the normal group,the cerebral blood flow values in the model group and the model with EA group decreased by more than 50%during the modeling process(P<0.01)and returned to pre-modeling levels after reperfusion(P>0.05).The neurologic deficit score increased(P<0.05),the average motor velocity decreased(P<0.05),GFAP protein expression and the number of positive cells in the motor cortex increased(P<0.05),and the NeuN protein expression and the number of positive cells decreased(P<0.05)in the model group.Compared to the model group,the neurologic deficit score decreased(P<0.05),the average motor velocity accelerated(P<0.05),GFAP and NeuN protein expression and the number of positive cells in the motor cortex increased(P<0.01)in the model with EA group.Conclusion:EA at bilateral Fengchi(GB20)can reduce neuronal loss and increase GFAP and NeuN protein expression in the motor cortex of rats after ischemia-reperfusion,improve the motor function after ischemic stroke,and accelerate the recovery of balance and stability of the affected limbs.

Effects of acupuncture and moxibustion on chromatin remodeling-related enzymes in the colon tissue of rats with Crohn disease

Objective:To investigate the regulatory effects of acupuncture and moxibustion on chromatin remodeling complex core catalytic subunit of Brahma-related gene 1(Brg1),histone deacetylase(HDAC)3,HDAC9,and males absent on the first(MOF)in the colon tissue of rats with Crohn disease(CD).Methods:Using the random number table method,60 male Sprague-Dawley rats were divided into 5 groups,including a normal group,a model group,an acupuncture group,a medicinal cake-insulated moxibustion group,and an acupuncture-moxibustion group,with 12 rats in each group.CD rat models were prepared using 2,4,6-trinitrobenzene sulfonic acid(TNBS)in all groups except the normal group.The normal and model groups received no interventions.In the acupuncture group,rats were intervened with acupuncture at bilateral Zusanli(ST36)and Shangjuxu(ST37),20 min/session,once a day.The medicinal cake-insulated moxibustion group received medicinal cake-insulated moxibustion at Qihai(CV6)and bilateral Tianshu(ST25)with 2 cones per point per session,once a day.The acupuncture-moxibustion group received both acupuncture and moxibustion interventions simultaneously.Each intervention was performed for 10 consecutive days.Observations included general condition,disease activity,macroscopic damage,and pathological changes in the rat’s colon tissue.Realtime fluorescence quantitative polymerase chain reaction was used to measure the mRNA expression of chromatin remodeling-related enzymes Brg1,HDAC3,and HDAC9,while Western blotting detected the protein expression of Brg1,HDAC3,HDAC9,and MOF in rat’s colon tissue.Results:The model group showed significantly increased diarrhea score,occult blood score,macroscopic damage score of colon tissue,and colon macroscopic damage index(CMDI)score,as well as elevated mRNA expression levels of HDAC3 and HDAC9,protein expression levels of HDAC3,HDAC9,and MOF,and decreased mRNA and protein expression levels of Brg1 compared to the normal group(P<0.01).In contrast,compared to the model group,the diarrhea score,occult blood score,macroscopic damage score,CMDI score,mRNA expression levels of HDAC3 and HDAC9,and protein expression levels of HDAC3,HDAC9,and MOF were significantly reduced(P<0.05 or P<0.01),while the mRNA and protein expression levels of Brg1 were significantly increased(P<0.01)in the acupuncture group,the medicinal cake-insulated moxibustion group,and the acupuncture-moxibustion group.Conclusion:Both medicinal cake-insulated moxibustion and acupuncture,either used alone or in combination,can regulate the abnormal expression of chromatin remodeling-related enzymes Brg1,HDAC3,HDAC9,and MOF in the colon tissue,thus reducing colon inflammation in CD rats.

Regulatory role of electroacupuncture on satellite glial cell activity in the colon and dorsal root ganglion of rats with irritable bowel syndrome

OBJECTIVE:To investigate the role of satellite glial cells in irritable bowel syndrome(IBS)and the effect of electroacupuncture(EA)at the Tianshu(ST25)and Shangjuxu(ST37)combination.METHODS:A model for visceral hypersensitivity in IBS was induced through colorectal distension(CRD)stimulation.Clean-grade male Sprague-Dawley(SD)rats were randomly divided into four groups:a normal group(NG),a model group(MG),an electroacupuncture group(EA),and a glial cell inhibitor group(FCA).Bilateral EA(2/100 Hz,1 mA,30 min)was administered at the Tianshu(ST25)and Shangjuxu(ST37)in week 6.Abdominal withdrawal reflex(AWR)scores were used to assess the behavioral response associated with visceral hyperalgesia,while hematoxylin-eosin staining was employed to evaluate pathological changes in the colon.The protein and mRNA levels of glial fibrillary acidic protein(GFAP)in the colon and colon-related dorsal root ganglion(DRG)were analyzed using immun-ofluorescence,immunohistochemistry,Western blotting,real-time polymerase chain reaction.The impact of EA on electrophysiological properties of colon-related DRG neurons was observed through whole-cell patch clamp analysis.RESULTS:EA significantly reduced the visceral pain behavior scores in rats with IBS in response to graded(20,40,60,80 mm Hg)CRD stimulation.Additionally,EA downregulated the protein and mRNA expression levels of GFAP in the colon and colon-related DRG of rats with IBS.EA also regulated the resting membrane potential,rheobase and action potential of colon-related DRG neurons in rats with IBS.CONCLUSIONS:EA can regulate the excitatory properties of colon-related DRG neurons by downregulating the protein and mRNA expression of GFAP in the colon and colon-related DRG,indicating a potential neurobiological mechanism by which EA relieves visceral hypersensitivity in rats with IBS.

World Federation of Acupuncture-Moxibustion Societies(WFAS)Technical Benchmark of Acupuncture and Moxibustion:Filiform Needle

On December 31,2023,World Federation of Acupuncture-Moxibustion Societies(WFAS)officially issued Technical Benchmark of Acupuncture and Moxibustion:Filiform Needle.This technical benchmark clarifies terms and definitions,operating procedures and requirements,safety requirements,etc.The promulgation and implementation of this technical benchmark would provide a standard for acupuncture practitioners to apply filiform needle in clinical practice,and may play a positive role in the safe use and promotion of filiform needle.

Acupuncture-moxibustion in treating irritable bowel syndrome: How does it work?

Irritable bowel syndrome (IBS) is a functional intestinal disease characterized by abdominal pain or discomfort and altered bowel habits. It has drawn great attention because of its high prevalence, reoccurring symptoms, and severe influence on patients&#x02019; lives. Many clinical studies have demonstrated the efficacy of acupuncture-moxibustion in treating IBS. Increasing attention has been paid to research regarding the action mechanisms of acupuncture-moxibustion for IBS, and the adoption of modern techniques has achieved some progress. This article reviews the latest advances among action mechanism studies from the perspectives of gastrointestinal motility, visceral hypersensitivity, the brain-gut axis, the neuroendocrine system, and the immune system. It is shown that acupuncture-moxibustion can effectively regulate the above items, and thus, this treatment should have a high efficacy in the treatment of IBS. This article also identifies existing problems in current mechanism research and raises several ideas for future studies. Further revelations regarding these action mechanisms will promote the application of acupuncture-moxibustion in treating IBS.

Moxibustion eases chronic inflammatory visceral pain through regulating MEK, ERK and CREB in rats

AIM To investigate the effects of herb-partitioned moxibustion(HPM) on phosphorylation of mitogen-activated extracellular signal-regulated kinase(MEK)1, extracellular signal-regulated kinase(ERK)1/2 and c AMP response element binding protein(CREB) in spinal cord of rats with chronic inflammatory visceral pain(CIVP), and to explore the central mechanism of HPM in treating CIVP.METHODS Male Sprague-Dawley rats were randomized into normal, model, HPM, sham-HPM, MEK-inhibitor and dimethyl sulfoxide(DMSO) groups. The CIVP model was established using an enema mixture of trinitrobenzene sulfonic acid and ethanol. HPM was applied at bilateral Tianshu(ST25) and Qihai(CV6) acupoints in the HPM group, while in the sham-HPM group, moxa cones and herb cakes were only placed on the same points but not ignited. The MEK-inhibitor and DMSO groups received L5-L6 intrathecal injection of U0126 and 30% DMSO, respectively. Abdominal withdrawal reflex(AWR), mechanical withdrawal threshold(MWT) and thermal withdrawal latency(TWL) were applied for the assessment of pain behavior. The colonic tissue was observed under an optical microscope after hematoxylin-eosin staining. Expression of phosphor(p)MEK1, p ERK1/2 and p CREB in rat spinal cord was detected using Western blotting. The levels of MEK, ERK and CREB m RNA in rat spinal cord were detected using real-time polymerase chain reaction. RESULTS Compared with the normal group, the AWR scores were increased significantly(P < 0.01) and the MWT and TWL scores were decreased significantly(P < 0.05) in the model, sham-HPM and DMSO groups. Compared with the model group, the AWR scores were decreased significantly(P < 0.01) and the MWT and TWL scores were increased significantly in the HPM and MEK-inhibitor groups(P < 0.05). Compared with the sham-HPM and DMSO groups, the AWR scores were decreased significantly(P < 0.01) and the MWT and TWL scores were increased significantly(P < 0.05) in the HPM and MEK-inhibitor groups. Compared with the normal group, the expression of p MEK1, p ERK1/2 and p CREB proteins and the levels of MEK, ERK and CREB m RNA in rat spinal cord were increased significantly in the model, sham-HPM and DMSO groups(P < 0.01 or < 0.05). Compared with the model group, the expression of p MEK1, p ERK1/2 and p CREB proteins and the levels of MEK, ERK and CREB m RNA in rat spinal cord were reduced significantly in the HPM and MEK-inhibitor groups(P < 0.01 or < 0.05). Compared with the sham-HPM and DMSO groups, expression of p MEK1, p ERK1/2 and p CREB proteins and the levels of MEK, ERK and CREB m RNA in rat spinal cord were reduced significantly in the HPM and MEK-inhibitor groups(P < 0.01 or < 0.05). CONCLUSION HPM down-regulates protein phosphorylation of MEK1, ERK1/2 and CREB, and m RNA expression of MEK, ERK and CREB, inhibiting activation of the MEK/ERK/CREB signaling pathway in the spinal cord of CIVP rats, which is possibly a critical central mechanism of the analgesic effect of HPM.

Transcranial pulse current stimulation improves the locomotor function in a rat model of stroke

Previous studies have shown that transcranial pulse current stimulation(tPCS) can increase cerebral neural plasticity and improve patients' locomotor function.However, the precise mechanisms underlying this effect remain unclear.In the present study, rat models of stroke established by occlusion of the right cerebral middle artery were subjected to tPCS, 20 minutes per day for 7 successive days.tPCS significantly reduced the Bederson score, increased the foot print area of the affected limbs, and reduced the standing time of affected limbs of rats with stroke compared with that before intervention.Immunofluorescence staining and western blot assay revealed that tPCS significantly increased the expression of microtubule-associated protein-2 and growth-associated protein-43 around the ischemic penumbra.This finding suggests that tPCS can improve the locomotor function of rats with stroke by regulating the expression of microtubule-associated protein-2 and growth-associated protein-43 around the ischemic penumbra.These findings may provide a new method for the clinical treatment of poststroke motor dysfunction and a theoretical basis for clinical application of tPCS.The study was approved by the Animal Use and Management Committee of Shanghai University of Traditional Chinese Medicine of China(approval No.PZSHUTCM190315003) on February 22, 2019.

Electroacupuncture at Tianshu (ST 25) for diarrhea-predominant irritable bowel syndrome using positron emission tomography Changes in visceral sensation center

Previous studies have demonstrated that electroacupuncture therapy is effective in the treatment of irritable bowel syndrome. However, the precise mechanism of this therapy is unknown. The present study served to investigate the effects of electroacupuncture therapy on treatment of patients with diarrhea-predominant irritable bowel syndrome （IBS）. We compared brain activation maps based on the changes of cerebral glucose metabolism obtained by 18-fluorodeoxyglucose positron emission tomography scanning under three conditions： resting, rectal balloon distension and rectal balloon distension plus electroacupuncture. Under the resting condition, compared with healthy controls, IBS patients displayed an increasing regional cerebral metabolic rate of glucose over a wide range： bilateral superior temporal gyrus, right middle occipital gyrus, superior frontal gyrus and bilateral middle frontal gyrus. However, there was no significant activity in the visceral pain center. Compared with the resting condition, under the rectal balloon distension condition, patients with IBS had a greater regional cerebral metabolic rate of glucose in the prefrontal cortex, left anterior cingulate cortex, postcentral gyrus, precentral gyrus and temporal gyrus. Under the rectal balloon distension plus electroacupuncture condition, stimulation by electroacupuncture at Tianshu （ST 25） manifested a decreased regional cerebral metabolic rate of glucose in the left cingulate gyrus, right insula, right caudate nucleus, fusiform gyrus and hippocampal gyrus. Electroacupuncture therapy relieved abdominal pain, distension or discomfort by decreasing glucose metabolism in the brain.

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 factorκB/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(PIL-18<0.01 and Pp65<0.05).There were no significant differences in the expression of TNF-αprotein 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(PLC3B<0.01,PBeclin-1<0.05,Pp62<0.05,and Pm-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(PPI3KC1<0.01 and PAkt1,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 pmTOR protein levels(PPI3KC1<0.01,Pp-Akt1<0.05,and Pp-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.