[Analysis and prospect of correlation between relative molecular weight and efficacy of polysaccharides from medicinal plant resources].

Polysaccharides from medicinal plant resources are a kind of polymers extracted from medicinal plants. They are complex long chains formed by different monosaccharides connected via glucosidic bonds. These polysaccharides usually have straight chain and branched chain structures, and their relative molecular weight changes greatly. Modern studies have shown that the biological activi-ty of polysaccharides from medicinal plant resources is closely related to their relative molecular weight. This paper first reviewed the preparation and detection methods of polysaccharides from medicinal plant resources with different relative molecular weights. Then, the paper summarized and analyzed the general experience of the correlation between efficacy and relative molecular weight of polysaccharides from medicinal plant resources with different molecular weights. It was considered that polysaccharides with large relative molecular weights(>100 kDa) play a leading role in immune regulation. Polysaccharides with medium relative molecular weights(10-100 kDa) play a leading role in immune regulation and the protection of the liver. Polysaccharides with small relative molecular weights(<10 kDa) play a leading role in anti-oxidation, regulation of intestinal flora, regulation of blood glucose and lipids, anti-fatigue, and the protection of nerves. Therefore, precise development of polysaccharides from medicinal plant resources based on relative molecular weight is expected to improve their biological activity and application value.

Specific molecular weight of Lycium barbarum polysaccharide for robust breast cancer regression by repolarizing tumor-associated macrophages.

The pro-tumorigenic M2-type tumor-associated macrophages (TAMs) in the immunosuppressive tumor microenvironment (TME) promote the progression, angiogenesis, and metastasis of breast cancer. The repolarization of TAMs from an M2-type toward an M1-type holds great potential for the inhibition of breast cancer. Here, we report that Lycium barbarum polysaccharides (LBPs) can significantly reconstruct the TME by modulating the function of TAMs. Specifically, we separated four distinct molecular weight segments of LBPs and compared their repolarization effects on TAMs in TME. The results showed that LBP segments within 50-100 kDa molecular weight range exhibited the prime effect on the macrophage repolarization, augmented phagocytosis effect of the repolarized macrophages on breast cancer cells, and regression of breast tumor in a tumor-bearing mouse model. In addition, RNA-sequencing confirms that this segment of LBP displays an enhanced anti-breast cancer effect through innate immune responses. This study highlights the therapeutic potential of LBP segments within the 50-100 kDa molecular weight range for macrophage repolarization, paving ways to offer new strategies for the treatment of breast cancer.

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.

A preliminary study for the clinical effect of one combinational physiotherapy and its potential influence on gut microbial composition in children with Tourette syndrome.

Introduction: Tourette syndrome (TS) is a chronic neuropsychiatric disorder with unknown causes and inadequate therapies. Inspired by the important roles of gut microbiota in some mental illnesses, the interactions between gut microbiota and TS via the gut-brain axis have gained more and more attention. This study aimed to characterize the gut microbial profiles in children with TS, and explore the clinical effects of one combinational physiotherapy and its potential influence on gut microbial composition. Methods: The gut microbial profiles were depicted based on the sequence data of 32 patients and 29 matched health children by 16S rDNA amplicon pyrosequencing. Thirty of thirty-two patients underwent uninterrupted two 10-day courses of combinational physiotherapy, which included a 60-minute cranial electrotherapy stimulation (CES) training followed by a 30-minute biofeedback training per session, 2 sessions a day. Results: Our results indicated that the gut microbial composition in children with TS was different from that in healthy controls. Multiple GBM neurotransmitter modules obtained through Picrust2 functional predictive analysis were significantly increased in patients, including Histamine degradation, Dopamine degradation, and DOPAC synthesis. Moreover, this combinational physiotherapy could significantly diminish tic activity, whose positive effects were first reported in children with TS. Lastly, different gut microbial compositions and predictive metabolic pathways were also observed between patients before and after this treatment, with lower abundances of the genera (e.g., Dorea) and significant decreases of GBM neurotransmitter modules (e.g. dopamine degradation) in patients after this treatment, indicating that improved clinical symptoms might be accompanied by an improvement of intestinal microenvironment. Discussion: Children with TS showed a cognizable gut microbial profile, and certain enriched bacteria with pro-inflammatory potential might induce neuroinflammatory responses. This combinational physiotherapy could significantly diminish tic activity, and the gut microbial compositions in patients after this treatment were different from those without any treatment, indicating the existence of bidirectional communication of the gut-brain axis in TS. But studies on the gut microbial characteristics in TS patients, the influences of gut microbiota on tic severity, the efficacy and safety of this treatment, and the bidirectional regulatory mechanism between brain signals and gut microbiota in TS still need to be explored.

Factors associated with subgroups of fatigue in maintenance hemodialysis patients: a cross-sectional study.

OBJECTIVE: This study aimed to investigate affected factors for subgroups of fatigue and the degree of fatigue in maintenance hemodialysis (MHD) patients. METHODS: This study included 120 MHD patients. Questionnaires, pre- and post-dialysis clinical data, bioimpedance spectroscopy, and ultrasound assessment were involved. RESULTS: The prevalence of fatigue in participants was 83%, including 54% of patients with fatigue worsened by dialysis, 13% with fatigue lessened by dialysis, and 16% with undifferentiated fatigue. Based on multi-nominal logistic regression analysis, age was associated with worsened fatigue by dialysis (odds ratio (OR) = 1.06, 95% confidence interval (CI) 1.01-1.11, p = 0.019), lower post-dialysis phosphorus was associated with lessened fatigue by dialysis (OR = 0.03, 95% CI 0.001-0.981, p = 0.049), and there was an increasing trend of patients experiencing undifferentiated fatigue as the extracellular water / intracellular water (E/I) level increased (p for trend = 0.020). Based on multi-ordinal logistic regression analysis, age was also a significant predictor for more severe fatigue (OR = 1.042, 95% CI 1.008-1.059, p = 0.015). CONCLUSIONS: Different subgroups of fatigue in MHD patients have different affecting factors. Older patients were prone to worsened fatigue by dialysis, patients with lower post-dialysis phosphorus were prone to lessened fatigue by dialysis, and patients with higher E/I levels were prone to undifferentiated fatigue. Meanwhile, older patients are prone to suffer from more severe fatigue. However, more in-depth studies are needed to clarify the pathogenesis of fatigue in MHD patients.

[Effect of electroacupuncture invention on activities of PGC-1α/Irisin (FNDC5)/BDNF signaling in cerebral cortex, hippocampus and muscles in focal cerebral ischemic/reperfusion injury rats].

OBJECTIVE: To observe the effect of electroacupuncture(EA) on the expression of peroxisome proliferator-activated receptor gamma coactivators-1-alpha (PGC-1α), Irisin and brain-derived neurotrophic factor (BDNF) in the ischemic peripheral cortex, hippocampus and local skeletal muscle in rats with focal cerebral ischemic/reperfusion injury (CI/RI), so as to explore its underlying mechanism of improving of CI/RI. METHODS: Male SD rats were randomly divided into 3 groups: sham-operation, model and EA (11 rats in each group). The focal CI/RI model was established by middle cerebral artery occlusion (MCAO). EA (2 Hz /15 Hz, 2 to 4 mA) was applied to "Quchi" (LI11) and "Zusanli" (ST36) of the affected side for 20 min, once a day for 7 days. Zea-Longa's score and Balance Beam score were used to evaluate the neurological and motor functions. The infarcted volume of the brain was detected by using 2,3,5-triphenyltetrazolium chloride staining. The expression levels of PGC-1α, fibronectin type III domain-containing protein 5(FNDC5) and BDNF proteins in the ischemic peripheral cortex, hippocampus and local skeletal muscle were detected by Western blot. RESULTS: Compared with the sham-operation group, the Zea-Longa's score, Balance Beam score, percentage of cerebral infarct volume were notably increased (P<0.01), while the expression levels of PGC-1α, FNDC5 and BDNF proteins in the cerebral cortex and hippocampus (not in the local muscle) were significantly down-regulated in the model group (P<0.01, P<0.05). In comparison with the model group, the increase of Zea-Longa's score, Balance Beam score, percentage of cerebral infarct volume, and the decrease of expression levels of PGC-1α, FNDC5 and BDNF proteins in the ischemic peripheral cortex and that of BDNF in the hippocampus were reversed in the EA group (P<0.01, P<0.05). No significant changes were found in the expression levels of hippocampal PGC-1α and FNDC5 proteins in the hippocampus and those of PGC-1α, FNDC5 and BDNF proteins in the local muscle after EA intervention (P>0.05). CONCLUSION: EA can improve neurological and motor functions and reduce cerebral infarction volume in CI/RI rats, which may be related to its functions in activating PGC-1α/Irisin(FNDC5)/BDNF pathway in the cerebral cortex.

Acupuncture and Moxibustion Inhibited Intestinal Epithelial-Mesenchymal Transition in Patients with Crohn's Disease Induced by TGF- ß 1/Smad3/Snail Pathway: A Clinical Trial Study.

OBJECTIVE: To explore whether acupuncture combined with moxibustion could inhibit epithelialmesenchymal transition in Crohn's disease by affecting the transforming growth factor ß 1 (TGF- ß 1)/Smad3/Snail pathway. METHODS: Sixty-three patients with Crohn's disease were randomly divided into an observation group (31 cases) receiving moxibustion at 43 °C combined with acupuncture, and a control group (32 cases) receiving moxibustion at 37 °C combined with sham acupuncture using a random number table. Patients were treated for 12 weeks. Crohn's Disease Activity Index (CDAI) was used to evaluate disease activity. Hematoxylin-eosin staining and transmission electron microscopy were utilized to observe the morphological and ultrastructural changes. Immunohistochemistry was used to detect the expression of transforming growth factor ß 1 (TGF-ß 1), T ß R1, T ß R2, Smad3, Snail, E-cadherin and fibronectin in intestinal mucosal tissues. RESULTS: The decrease of the CDAI score, morphological and ultrastructural changes were more significant in observation group. The expression levels of TGF- ß 1, Tß R2, Smad3, and Snail in the observation group were significantly lower than those before the treatment (P<0.05 or P<0.01). After treatment, the expression levels of TGF-ß 1, TßR2, and Snail in the observation group were significantly lower than those in the control group (all P<0.05); compared with the control group, the expression of fibronectin in the observation group was significantly decreased, and the expression of E-cadherin was significantly increased (all P<0.05). CONCLUSIONS: Moxibustion at 43 °C combined with acupuncture may suppress TGF-ß 1/Smad3/Snail pathway-mediated epithelial-mesenchymal transition of intestinal epithelial cells in Crohn's disease patients by inhibiting the expression levels of TGF-ß 1, Tß R2, Smad3, and Snail. (Registration No. ChiCTR-IIR-16007751).

Traditional Chinese Medicine enhances absorption of lung lesions in corona virus disease 2019 patient.

OBJECTIVE: To study the possible role of traditional Chinese medicine (TCM) of Huangqi (Radix Astragali Mongolici), Gancao (Radix Glycyrrhizae), Jinyinhua (Flos Lonicerae), and Lianqiao (Fructus Forsythiae Suspensae) in absorption of lung lesions in Corona Virus Disease 2019 (COVID-19) patients. METHODS: A cohort of COVID-19 cases was recruited. During hospitalization, chest computed tomographic (CT) scan and real time polymerase chain reaction (RT-PCR) test were performed every three days. Comparison was held (Western Medicine, WM vs WM plus TCM) on absorption of lung lesions, time interval from admission to negative test result of RT-PCR (ATN), and medical expense. Multivariate cox regression models were built to identify the possible prognostic factor of delayed absorption of lung lesion. RESULTS: The medical expenditure (1163 ± 379 vs 1137 ± 498, P = 0.863) and ATN (13 ± 4 vs 10 ± 4, P = 0.055) were comparable between cases treated with WM plus TCM and cases only received WM. Multivariate cox regression model showed that cases receiving extra TCM had lower risk of delayed absorption of lung lesions [Hazard ratio = 0.24, 95% confidence Interval (0.06, 0.96), P = 0.043]. CONCLUSION: Compared to WM, the treatment of WM plus TCM facilitates the recovery of pulmonary infiltration on COVID-19 cases without significantly increasing medical expense.

[Effect of electroacupuncture on mitochondrial function in mice with Parkinson's disease].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on behavior, tyrosine hydroxylase (TH), mitochondrial complexes Ⅰ-Ⅳ, mitochondrial membrane potential and mitochondrial ultrastructure of Parkinson's disease (PD) mice, so as to explore its mechanism underlying improvement of PD. METHODS: C57BL/6 mice were randomly divided into normal, model, medication (Madopar) and EA groups (n=11 in each group). PD model was duplicated by intraperitoneal injection of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP, 30 mg·kg-1·d-1) for consecutively 5 d. EA was performed on the chorea tremor areas on both sides of the head of mice for 15 min, once a day for 14 d. The behavioral changes of mice were observed. The expression of TH in substantia nigra compacta of midbrain was detected by immunohistochemistry. The activities of mitochondrial complexes Ⅰ-Ⅳ were measured. The changes of mitochondrial membrane potential were detected by JC-1 staining method. The ultrastructural changes of striatum mitochondria were observed by transmission electron microscope. RESULTS: After modeling, the mice showed obvious behavioral abnormalities such as tremor, vertical hair and tail warping, and the pole test time in the model group was significantly longer than that in the normal group (P<0.01). After 7 and 14 days of the treatment, the pole test time in the EA and medication groups was shorter than that in the model group (P<0.05，P<0.01). Compared with the normal group, the number of TH positive cells of the substantia nigra, the mitochondrial membrane potential and the activity of mitochondrial complex I were decreased significantly in the model group (P<0.01), and EA and medication intervention reversed these changes (P<0.01). The mitochondrial structure of mice in the model group was obviously damaged, and the damage of mitochondrial structure was alleviated and the number of damaged mitochondria was decreased in the EA and medication groups. CONCLUSION: EA can protect and promote the recovery of mitochondrial structure and function in MPTP-induced PD mice, which may play a neuroprotective effect on PD mice by improving mitochondrial dysfunction, balancing cell homeostasis and reducing dopaminergic neuron damage.

[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.

Effects of acupuncture treatment on motor function in patients with subacute hemorrhagic stroke: A randomized controlled study.

OBJECTIVE: The aim of this study was to evaluate the additional effects of acupuncture treatment on motor function in patients with subacute hemorrhagic stroke. DESIGN: One hundred and thirty-four patients with subacute hemorrhagic stroke were randomized to receive acupuncture treatment plus conventional treatment (treatment group) or conventional treatment only (control group). Acupuncture treatments were given in 24 sessions over 4 weeks, with 3-month follow-up period. Blinded evaluation was based on Fugl-Meyer Assessment, Barthel Index with an intention-to-treat analysis. For those patients who were able to walk, a three-dimensional gait analysis system was employed to objectively record spatiotemporal and kinematic parameters. RESULTS: Compared with control group, the treatment group showed a significantly greater over-time improvement in total Fugl-Meyer, lower-limb Fugl-Meyer, but not in upper-limb Fugl-Meyer and Barthel Index. The spatiotemporal parameters of velocity, step length, cadence, step width all showed significant difference between the 2 groups. The velocity in treatment group decreased unexpectedly at day 14, then increased sharply and overcame control group at day 28. The treatment group also showed a significantly greater increase in peak circumduction, peak hip hiking, hip range of motion, knee range of motion and a tendency for the ankle range of motion. CONCLUSIONS: Acupuncture may promote the motor function recovery of hemorrhagic stroke patients in subacute phase mainly by enhancing the lower limb ability. It probably diminishes the compensation strategies earlier to correct the abnormal gait pattern. Although this adjustment may result in a compromise in the improvement of gait velocity temporarily, patients would benefit from it in a long run.

Differences in Post-ischemic Motor Recovery and Angiogenesis of MCAO Rats Following Electroacupuncture at Different Acupoints.

BACKGROUND: Electroacupuncture (EA) can promote nerve and vascular regeneration, confer neuroprotection, inhibit apoptosis and inflammatory reactions, reduce oxidative stress injury, regulate neurochemicals and inhibit the formation of brain oedema in cerebral ischemic. However, the precise site of EA stimulation in the treatment of cerebral ischemic is unclear. OBJECTIVE: In the present study, we investigated the effect of EA at the acupoints of different meridians in motor function recovery and the involvement of Vascular Endothelial Growth Factor (VEGF), phosphorylated Protein Kinase B (P-Akt), phosphorylated endothelial nitric oxide synthase (p-eNOS) and Platelet Endothelial Cell Adhesion Molecule-1(CD31) were examined in the peri-infarction cortex of rats. METHODS: The Middle cerebral artery occlusion (MCAO) model or sham surgery was performed in a total of Ninety male Sprague-Dawley rats. Rats were randomly divided into five groups: a sham group, a middle cerebral artery occlusion (MCAO) group, a Yang meridian group, a Yin meridian group and a combined Yang and Yin meridian group. EA stimulus was given during the middle cerebral artery occlusion. The neurobehavioural function was measured using Modified Neurological Severity Scores (mNSS), the rotarod test and the ladder rung walking test, and the protein expression of VEGF, P-Akt, p-eNOS in the peri-infarction cortex was detected by Western blot. Immunofluorescence was used to measure the vascular density of the peri-infarction cortex. RESULTS: EA at different meridian acupoints has no effect on the infarction volume, while EA at Yin meridian acupoints significantly promoted neurobehavioural functional recovery, increased the vascular density and enhanced protein kinase B/Endothelial nitric oxide synthase (Akt/eNOS) phosphorylation and VEGF expression. CONCLUSION: In the early stage of stroke, EA at Yin meridian acupoints can improve neurobehavioural functional recovery and the mechanism of this effect may be related to the enhanced expression of VEGF, P-Akt and p-eNOS in the peri-infarction cortex of rats.

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.

Effects of Acupuncture Treatment on Lower Limb Spasticity in Patients Following Hemorrhagic Stroke: A Pilot Study.

BACKGROUND AND PURPOSE: Lower limb spasticity is often a significant problem in stoke rehabilitation. The purpose of this study was to investigate the effects of acupuncture treatment on lower limb spasticity in patients following hemorrhagic stroke. METHODS: Fifty-nine patients following hemorrhagic stroke were randomized to receive acupuncture treatment combined with conventional treatment (treatment group [TG]) or conventional treatment only (control group [CG]). Acupuncture treatments were given in 24 sessions over 4 weeks. Blinded evaluation was based on Modified Ashworth Scale (MAS), short intracortical inhibition (SICI), and Hmax/Mmax ratio as the primary outcomes. In addition, Fugl-Meyer Assessment (FMA), Barthel Index (BI), motor evoked potential (MEP) and surface integrated electromyogram (IEMG) were employed as the secondary outcomes. All the evaluations were performed at 14 and 28 days after the start of the treatment. RESULTS: Compared with the CG, the TG showed a significantly greater over-time decrease in MAS for knee (p = 0.022) and ankle (p = 0.017), SICI (p = 0.000) and Hmax/Mmax ratio (p = 0.000). In all patients of TG, we found a greater improvement in lower-limb FMA and MEP but not in BI. IEMG show that TG obtained a greater reduction in spastic agonist muscles and a greater enhancement in spastic antagonist muscles. A significant correlation between a greater decrease in ankle MAS and a greater increase in SICI for spastic muscles was found (r = 0.390, p = 0.002). CONCLUSIONS: Acupuncture could improve the lower limb spasticity and motor function, thus providing a safe and economical approach for treating stroke patients. The potential mechanism underpinning the greater improvement may be attributed to a reshape of corticospinal plasticity induced by acupuncture.

Moxibustion treatment modulates the gut microbiota and immune function in a dextran sulphate sodium-induced colitis rat model.

AIM: To investigate the effect and mechanism of moxibustion in rats with ulcerative colitis. METHODS: 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. RESULTS: 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 genera Saccharibacteria, Sphingomonas and Barnesiella than colitis rats, and they could restore the microbiome to levels similar to those observed in healthy rats. UC rats had reduced alpha diversity, which could be alleviated by moxibustion therapy, and UC-7 had a higher alpha diversity than UC-14. This finding suggests that short-term (7 d) but no longer term (14 d) moxibustion treatment may significantly affect the gut microbiome. The potential bacterial functions affected by moxibustion may be ascorbate and aldarate metabolism, and amino acid metabolism. Compared with HC group, the levels of the cytokines interleukin-12 (IL-12) (P < 0.05) and IL-6, IL-17, IL-23, interferon-γ, lipopolysaccharide, IgA, tumour necrosis factor-α and its receptors 1 (TNFR1) and TNFR2 (P < 0.01) were all increased, whereas anti-inflammatory cytokine IL-2 and IL-10 (P < 0.01) and transforming growth factor-ß (P < 0.05) were decreased in UC rats. These changes were reversed by moxibustion. CONCLUSION: Our findings suggest that moxibustion exerts its therapeutic effect by repairing mucosal tissue damage and modulating the gut microbiome and intestinal mucosal immunity.

Comparison of Electroacupuncture and Mild-Warm Moxibustion on Brain-Gut Function in Patients with Constipation-Predominant Irritable Bowel Syndrome: A Randomized Controlled Trial.

OBJECTIVE: To compare the effects of electroacupuncture (EA) and mild-warm moxibustion (Mox) therapies for constipation-predominant irritable bowel syndrome (C-IBS) patients. METHODS: Sixty C-IBS patients were assigned to 2 groups by simple randomized method, i.e. EA group (30 cases) and Mox group (30 cases). Both EA and Mox treatments were performed on bilateral Tianshu (ST 25) and Shangjuxu (ST 37) for 30 min each time, 6 times per week, for 4 consecutive weeks. The gastrointestinal symptoms and psychological symptoms of the two groups were scored before and after treatment. The effects on the corresponding functional brain areas, namely the anterior cingulate cortex (ACC), insular cortex (IC) and prefrontal cortex (PFC) were observed by functional magnetic resonance imaging (fMRI) before and after treatment. RESULTS: Compared with the Mox group, greater improvements in abdominal distension, defecation frequency, diffificulty in defecation and stool features were observed in the EA group (all P<0.01), both Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale scores were signifificantly decreased in the EA group (all P<0.01). Finally, decreased activated voxel values were observed in the ACC, right IC and PFC brain regions of EA group with 150 mL colorectal distension stimulation (P<0.05 or P<0.01). CONCLUSIONS: Both EA and Mox could signifificantly improve some of the most intrusive symptoms of C-IBS patients, and EA was more effective than Mox. The therapeutic effect of these two therapies might through modulating of the brain-gut axis function. (Registration No. ChiCTRTRC-11001349).

Immediate effect of scalp acupuncture on the gait of patients with subacute intracerebral haemorrhage analysed by three-dimensional motion: secondary analysis of a randomised controlled trial.

OBJECTIVE: To investigate the immediate effect of scalp acupuncture on walking pattern, using three-dimensional gait analysis (3D-GA), among patients in the subacute stage of intracerebral haemorrhage (ICH). METHODS: A subset of 30 patients with subacute ICH participating in a recently published randomised controlled trial who were able to walk independently were assessed by 3D-GA before and immediately after scalp acupuncture treatment (treatment group) or no intervention (control group) and the results presented here as a secondary analysis. The acupuncture manipulation was repeated three times with an interval of 5 min. Spatiotemporal and kinematic parameters during walking were collected and analysed using a 3D motion analysis system. RESULTS: After treatment, there were significant differences between the treatment and control groups in the spatiotemporal parameters of step length, velocity and cadence (p<0.05) and double-limb support. No significant difference was found in step width. When kinematic parameters were evaluated, the treatment group showed a significantly decreased peak pelvic anterior tilt angle and an increased hip extension angle after scalp acupuncture treatment, whereas the control group demonstrated no temporal changes. There were no significant changes in any other kinematic parameters in either group. CONCLUSIONS: As the first exploratory study to investigate the effect of the scalp acupuncture on gait performance in patients with subacute ICH, this secondary analysis of a recent randomised trial suggested an immediate effect of treatment on spatiotemporal parameters. Improvement in gait pattern may be associated with a decreased anterior tilt of the pelvis and augmented hip joint motion during walking. TRIAL REGISTRATION NUMBER: ChiCTR-TRC-08000225; Post-results.

Comparison of the analgesic effects between electro-acupuncture and moxibustion with visceral hypersensitivity rats in irritable bowel syndrome.

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.