Limbic system plasticity after electroacupuncture intervention in knee osteoarthritis rats.

Knee osteoarthritis (KOA) is characterized by debilitating pain. Electroacupuncture (EA), a traditional Chinese medical therapy, has shown promise in KOA pain management. This study investigated the therapeutic potential of EA in KOA and its impact on limbic system neural plasticity. Sixteen rats were randomly assigned into two groups: EA group and sham-EA group. EA or sham-EA interventions were administered at acupoints ST32 (Futu) and ST36 (Zusanli) for three weeks. Post-intervention resting-state fMRI was scanned, assessing parameters including Amplitude of low frequency fluctuations (ALFF), regional homogeneity (ReHo), functional connectivity (FC) and nodal characterizations of network within limbic system. The results showed that EA was strategically directed towards the limbic system, resulting in discernible alterations in neural activity, FC, and network characteristics. Our findings demonstrate that EA had a significant impact on the limbic system neural plasticity in rats with KOA, presenting a novel nonpharmacological approach for KOA treatment.

Effects of electroacupuncture on imaging and behavior in rats with ischemic stroke through miR-212-5p.

BACKGROUND: Ischemic stroke is a serious disease leading to significant disability in humans worldwide. Increasing evidence suggests that some microRNAs (miRNAs) participate in the pathophysiology of ischemic stroke. A key role for MiR-212 has been found in neuronal function and synaptic plasticity. Ischemic stroke can be effectively treated with electroacupuncture (EA); however, there is a lack of understanding of the relevant mechanisms. In this study, we employed behavioral test and resting-state functional magnetic resonance imaging (rs-fMRI) to detect behavioral and brain function alterations in rats suffering from ischemic stroke. The efficacy of EA therapy and miR-212-5p's role in this process were also evaluated. METHODS AND RESULTS: Forty rats were randomly divided into the following groups: Sham, middle cerebral artery occlusion/reperfusion (MCAO/R), MCAO/R + EA, MCAO/R + EA + antagomir-negative control and MCAO/R + EA + antagomir-212-5p groups. Behavioral changes were assessed by Catwalk gait analysis prior to and after modeling. Rs-fMRI was performed at one week after EA treatment, amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) were calculated to reveal neural activity. Furthermore, neuronal apoptosis in the ischemic penumbra was analyzed using a TUNEL assay. Treatment with EA significantly improved the performance of rats in the behavioral test. The motor and cognition-related brain regions showed decreased ALFF and ReHo following focal cerebral ischemia-reperfusion, and EA treatment could reactivate these brain regions. Moreover, EA treatment significantly decreased MCAO/R-induced cell death. However, the transfection of antagomir-212-5p attenuated the therapeutic effect of EA. CONCLUSIONS: In conclusion, the results suggested that EA improved the behavioral and imaging outcomes of ischemic stroke through miR-212-5p.

Tuina therapy promotes behavioral improvement and brain plasticity in rats with peripheral nerve injury and repair.

INTRODUCTION: Tuina is currently one of the popular complementary and alternative methods of rehabilitation therapy. Tuina can improve patients' pain and mobility function. However, the underlying physiological mechanism remains largely unknown, which might limit its further popularization in clinical practice. The aim of this study is to explore the short-term and long-term changes in brain functional activity following Tuina intervention for peripheral nerve injury repair. METHODS: A total of 16 rats were equally divided into the intervention group and the control group. Rats in the intervention group received Tuina therapy applying on the gastrocnemius muscle of the right side for 4 months following sciatic nerve transection and immediate repair, while the control group received nerve transection and repair only. The block-design functional magnetic resonance imaging scan was applied in both groups at 1 and 4 months after the surgery. During the scan, both the injured and intact hindpaw was electrically stimulated according to a "boxcar" paradigm. RESULTS: When stimulating the intact hindpaw, the intervention group exhibited significantly lower activation in the somatosensory area, limbic/paralimbic areas, pain-regulation areas, and basal ganglia compared to the control group, with only the prefrontal area showing higher activation. After 4 months of sciatic nerve injury, the control group exhibited decreased motor cortex activity compared to the activity observed at 1 month, and the intervention group demonstrated stronger bilateral motor cortex activity compared to the control group. CONCLUSION: Tuina therapy on the gastrocnemius muscle of rats with sciatic nerve injury can effectively alleviate pain and maintain the motor function of the affected limb. In addition, Tuina therapy reduced the activation level of pain-related brain regions and inhibited the decreased activity of the motor cortex caused by nerve injury, reflecting the impact of peripheral stimulation on brain plasticity.

Transcriptomics and metabolomics revealed the pulmonary protective mechanism of Xixin-Ganjiang Herb Pair for warming the lungs to dissolve phlegm in COPD rats.

Xixin-Ganjiang Herb Pair (XGHP), a classic combination treatment to warm the lungs and dissolve phlegm, is widely used in the treatment of various pulmonary diseases. Chronic obstructive pulmonary disease (COPD) refers to a group of chronic obstructive airway diseases that can seriously harm human health. However, the effective components, targets, and pathways that underlie XGHP in the treatment of COPD remain unclear. Therefore, this study initially identified the effective components of XGHP through the use of UPLC-MS/MS and pharmacologic methods of traditional Chinese medicine. Secondly, transcriptomic analysis of the lung tissues of rats revealed the pharmacodynamic transcripts of each group, and metabolomics analysis revealed the differential metabolites associated with XGHP treatment. Finally, molecular docking of effective components with transcriptome genes was performed and western blotting was performed in order to determine the expression of related proteins in rat lung tissue. Overall, 30 effective components of XGHP were identified, including L-asarinin, 6-gingerol, sesamin, kaempferol, and quercetin. Transcriptomic studies demonstrated that expression of 386 genes recovered after XGHP treatment, and that they were mainly enriched in the oxidative phosphorylation and AMPK signaling pathways. According to the metabolomics studies, expression of eight metabolites differed between the COPD and the XGHP groups. These metabolites were mainly involved the biosynthesis of unsaturated fatty acids. Finally, the transcriptomic and metabolomics data were integrated. FASN and SCD in AMPK signaling pathway were directly linked to certain metabolites, including linoleic acid, palmitic acid, and oleic acid. These results indicate that XGHP can inhibit pAMPK expression and negatively regulate FASN and SCD expression during treatment of COPD in order to enhance the biosynthesis of unsaturated fatty acids and maintain energy homeostasis.

Modulation of Brain Network Topological Properties in Knee Osteoarthritis by Electroacupuncture in Rats.

Introduction: Osteoarthritis is a chronic, ongoing disease that affects patients, and pain is considered a key factor affecting patients, but the brain changes during the development of osteoarthritis pain are currently unclear. In this study, we used electroacupuncture (EA) to intervene the rat model of knee osteoarthritis and analyzed the changes in topological properties of brain networks using graph theory. Methods: Sixteen SD rat models of right-knee osteoarthritis with anterior cruciate ligament transection (ACLT) were randomly divided into electroacupuncture intervention group and control group. The electroacupuncture group was intervened on Zusanli (ST36) and Futu (ST32) for 20 min each time, five times a week for 3 weeks, while the control group was applied sham stimulation. Both groups were measured for pain threshold. The small-world properties and node properties of the brain network between the two groups after the intervention were statistically analyzed by graph theory methods. Results: The differences are mainly in the changes in node attributes between the two groups, such as degree centrality, betweenness centrality, and so on in different brain regions (P<0.05). Both groups showed no small-world characteristics in the brain networks of the two groups. The mechanical thresholds and thermal pain thresholds were significantly higher in the EA group than in the control group (P<0.05). Conclusion: The study demonstrated that electroacupuncture intervention enhanced the activity of nodes related to pain circuit and relieved pain in osteoarthritis, which provides a complementary basis for explaining the effect of electroacupuncture intervention on pain through graphical analysis of changes in brain network topological properties and helps to develop an imaging model for pain affected by electroacupuncture.

Effect of aging on the cerebral metabolic mechanism of electroacupuncture treatment in rats with traumatic brain injury.

Objective: Aging has great influence on the clinical treatment effect of cerebrovascular diseases, and evidence suggests that the effect may be associated with age-related brain plasticity. Electroacupuncture is an effective alternative treatment for traumatic brain injury (TBI). In the present study, we aimed to explore the effect of aging on the cerebral metabolic mechanism of electroacupuncture to provide new evidence for developing age-specific rehabilitation strategies. Methods: Both aged (18 months) and young (8 weeks) rats with TBI were analyzed. Thirty-two aged rats were randomly divided into four groups: aged model, aged electroacupuncture, aged sham electroacupuncture, and aged control group. Similarly, 32 young rats were also divided into four groups: young model, young electroacupuncture, young sham electroacupuncture, and young control group. Electroacupuncture was applied to "Bai hui" (GV20) and "Qu chi" (LI11) for 8 weeks. CatWalk gait analysis was then performed at 3 days pre- and post-TBI, and at 1, 2, 4, and 8 weeks after intervention to observe motor function recovery. Positron emission computed tomography (PET/CT) was performed at 3 days pre- and post-TBI, and at 2, 4, and 8 weeks after intervention to detect cerebral metabolism. Results: Gait analysis showed that electroacupuncture improved the forepaw mean intensity in aged rats after 8 weeks of intervention, but after 4 weeks of intervention in young rats. PET/CT revealed increased metabolism in the left (the injured ipsilateral hemisphere) sensorimotor brain areas of aged rats during the electroacupuncture intervention, and increased metabolism in the right (contralateral to injury hemisphere) sensorimotor brain areas of young rats. Results: This study demonstrated that aged rats required a longer electroacupuncture intervention duration to improve motor function than that of young rats. The influence of aging on the cerebral metabolism of electroacupuncture treatment was mainly focused on a particular hemisphere.

Emerging Biopharmaceuticals from Pimpinella Genus.

Evolved over eons to encode biological assays, plants-derived natural products are still the first dawn of drugs. Most researchers have focused on natural compounds derived from commonly used Pimpinella species, such as P. anisum, P. thellungiana, P. saxifrage, and P. brachycarpa, to investigate their antioxidant, antibacterial, and anti-inflammatory properties. Ethnopharmacological studies demonstrated that the genus Pimpinella has the homology characteristics of medicine and food and mainly in the therapy of gastrointestinal dysfunction, respiratory diseases, deworming, and diuresis. The natural product investigation of Pimpinella spp. revealed numerous natural products containing phenylpropanoids, terpenoids, flavonoids, coumarins, sterols, and organic acids. These natural products have the potential to provide future drugs against crucial diseases, such as cancer, hypertension, microbial and insectile infections, and severe inflammations. It is an upcoming field of research to probe a novel and pharmaceutically clinical value on compounds from the genus Pimpinella. In this review, we attempt to summarize the present knowledge on the traditional applications, phytochemistry, and pharmacology of more than twenty-five species of the genus Pimpinella.

Indocyanine green derived carbon dots with significantly enhanced properties for efficient photothermal therapy.

A simple yet effective strategy to enhance the properties of traditional dye indocyanine green (ICG) in all aspects was proposed and demonstrated. Specifically, indocyanine green-derived carbon dots (ICGCDs) were synthesized from ICG via a simple hydrothermal treatment. The ICGCDs exhibited significantly enhanced thermal stability and anti-photobleaching compared to ICG. Furthermore, their photothermal properties were also notably strengthened, in which a wider functional pH range, 50% improvement in photothermal conversion efficiency and superior photothermal cyclability were achieved. Thanks to these superior properties, ICGCDs were demonstrated as efficient NIR bioimaging and photothermal agents in both in vitro and in vivo experiments. Most excitingly, the strategy demonstrated in this study is likely to have broad applications in other systems.

Combined robot motor assistance with neural circuit-based virtual reality (NeuCir-VR) lower extremity rehabilitation training in patients after stroke: a study protocol for a single-centre randomised controlled trial.

INTRODUCTION: Improving lower extremity motor function is the focus and difficulty of post-stroke rehabilitation treatment. More recently, robot-assisted and virtual reality (VR) training are commonly used in post-stroke rehabilitation and are considered feasible treatment methods. Here, we developed a rehabilitation system combining robot motor assistance with neural circuit-based VR (NeuCir-VR) rehabilitation programme involving procedural lower extremity rehabilitation with reward mechanisms, from muscle strength training, posture control and balance training to simple and complex ground walking training. The study aims to explore the effectiveness and neurological mechanisms of combining robot motor assistance and NeuCir-VR lower extremity rehabilitation training in patients after stroke. METHODS AND ANALYSIS: This is a single-centre, observer-blinded, randomised controlled trial. 40 patients with lower extremity hemiparesis after stroke will be recruited and randomly divided into a control group (combined robot assistance and VR training) and an intervention group (combined robot assistance and NeuCir-VR training) by the ratio of 1:1. Each group will receive five 30 min sessions per week for 4 weeks. The primary outcome will be Fugl-Meyer assessment of the lower extremity. Secondary outcomes will include Berg Balance Scale, Modified Ashworth Scale and functional connectivity measured by resting-state functional MRI. Outcomes will be measured at baseline (T0), post-intervention (T1) and follow-ups (T2-T4). ETHICS, REGISTRATION AND DISSEMINATION: The trial was approved by the Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Chinese Traditional Medicine (Grant No. 2019-014). The results will be submitted to a peer-reviewed journal or at a conference. TRIAL REGISTRATION NUMBER: ChiCTR2100052133.

A Bibliometric Analysis of Acupuncture Therapy in the Treatment of Primary Dysmenorrhea from 2001 to 2021.

Background: Acupuncture therapy has already extensively used in many countries around the world to treat primary dysmenorrhea. But there is no bibliometric analysis on this aspect. Therefore, the purpose of this study is to evaluate the research trends of acupuncture therapy in the treatment of primary dysmenorrhea through literature research from 2001 to 2021 by using Citespace 6.1.R1(64-bit) Basic. Methods: Relevant literature is extracted from the Web of Science database. CiteSpace conducts cooperative network analysis on the information of authors, countries and institutions, co-occurrence network analysis on keywords, and co-citation analysis on cited journals, cited authors and cited references. Results: A total of 189 publications were extracted from 2001 to 2021. The total numbers of publication have steadily increased over the past two decades, and we have identified the most active countries, institutions, journals and authors in the field of acupuncture for primary dysmenorrhea. The EVID-BASED COMPL ALT was the most productive journal, and the COCHRANE DB SYST REV with the highest IF. The first in the frequency and centrality is the journal of AM J OBSTET GYNECOL. The most productive country and institution are China and Beijing University Chinese Medicine. YANG J was the most prolific author and CHEN H had the highest citation counts. The centrality of cite references ranked the first conducted by Burnett M. The keyword of "primary dysmenorrhea" ranked first for research developments with the highest frequency. Conclusion: The research results of Metrology in this paper provide the current situation and trend of clinical research on primary dysmenorrhea acupuncture Therapy in recent twenty-one years, which is helpful for researchers to identify the hot spots in this field and explore new directions of future research.

Alteration of brain functional networks induced by electroacupuncture stimulation in rats with ischemia-reperfusion: An independent component analysis.

Motor dysfunction is the major sequela of ischemic stroke. Motor recovery after stroke has been shown to be associated with remodeling of large-scale brain networks, both functionally and structurally. Electroacupuncture (EA) is a traditional Chinese medicine application that has frequently been recommended as an alternative therapy for ischemic stroke and is reportedly effective for alleviating motor symptoms in patients. In the present study, the effect of EA on the alterations of functional resting state networks (RSNs) was explored after middle cerebral artery occlusion/reperfusion (MCAO/R) injury using resting-state functional MRI. Rats were randomly assigned to three groups, including the sham group, MCAO/R group and MCAO/R+EA group. The ladder rung walking test was conducted prior to and after modeling to assess behavioral changes. RSNs were identified based on the independent component analysis (ICA) performed on the fMRI data from groups. EA treatment effectively reduced the occurrence of contralateral forelimb foot faults. Furthermore, our results suggested the disrupted function of the whole-brain network following ischemic stroke and the modulatory effect of acupuncture. The sensorimotor network (SMN), interoceptive network (IN), default mode network (DMN) and salience network (SN) were related to the therapeutic effect of EA on stroke recovery. Collectively, our findings confirmed the effect of EA on motor function recovery after cerebral ischemia reperfusion and shed light on the assessment of EA intervention-induced effects on brain networks. This study provides neuroimaging evidence to explain the therapeutic effects of EA in ischemic stroke and will lay the groundwork for further studies.

Effectiveness and functional magnetic resonance imaging outcomes of Tuina therapy in patients with post-stroke depression: A randomized controlled trial.

Objective: To investigate the effectiveness and functional magnetic resonance imaging (fMRI) outcomes of Tuina therapy in patients with post-stroke depression (PSD). Methods: This was a single-center, randomized, two-armed, controlled trial. Eighty-four patients with PSD were selected and randomly assigned to a Tuina therapy group or a routine rehabilitation control group. The patients underwent five 20-min treatment sessions per week over a period of 2 weeks. The primary outcome measure was change in Hamilton Depression Rating Scale (HAMD) score over the 2 weeks of intervention, whereas the secondary outcome measures were changes in Fugl-Meyer Assessment (FMA) score, Modified Barthel index (MBI), and Mini Mental State Examination (MMSE) score. Results: The Tuina group showed significantly improved HAMD scores compared to the routine rehabilitation control group (5.85, [2.54, 9.16]). For the secondary outcomes, the Tuina group showed better MMSE scores than the routine rehabilitation group (1.97, [1.19, 2.76]); however, there were no significant differences between the other secondary outcomes of both groups (P > 0.05). After 2 weeks, both groups showed a significant decrease in HAMD score compared to baseline. In addition, the Tuina group showed a significant decrease in MMSE score compared to baseline (2.35, [1.8, 2.9]); however, there were no significant differences in the MBI and FMA scores of the two group after the intervention (P > 0.05). Regarding fMRI results, the zALFF values of the right caudate nucleus, right putamen, right insula, left superior temporal gyrus, right parahippocampal gyrus, right hippocampus, left middle temporal gyrus, left angular gyrus, and left thalamus were higher in the Tuina group. In the Tuina group, the functional connectivity between the hippocampus and thalamus, and the thalamus and caudate nucleus, were significantly different (P <0.01). In addition, the zALFF value of the hippocampus was significantly negatively correlated with HAMD score. No serious adverse events were observed in both groups. Conclusion: Tuina therapy administered 10 times within 2 weeks is safe and can effectively relieve depression and improve cognitive function in patients with PSD. This finding may be closely related to the effect of Tuina therapy on the activation and functional connectivity of the hippocampus. Clinical Trial Registration: http://www.chictr.org.cn/showproj.aspx?proj=55151, identifier ChiCTR200003388.

Surface-based map plasticity of brain regions related to sensory motor and pain information processing after osteonecrosis of the femoral head.

Pain is one of the manifestations of hip disorder and has been proven to lead to the remodeling of somatotopic map plasticity in the cortex. However, most studies are volume-based which may lead to inaccurate anatomical positioning of functional data. The methods that work on the cortical surface may be more sensitive than those using the full brain volume and thus be more suitable for map plasticity study. In this prospective cross-sectional study performed in Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, China, 20 patients with osteonecrosis of the femoral head (12 males and 8 females, aged 56.80 ± 13.60 years) and 20 healthy controls (9 males and 11 females, aged 54.56 ± 10.23 years) were included in this study. Data of resting-state functional magnetic resonance imaging were collected. The results revealed that compared with healthy controls, compared with the healthy controls, patients with osteonecrosis of the femoral head (ONFH) showed significantly increased surface-based regional homogeneity (ReHo) in areas distributed mainly in the left dorsolateral prefrontal cortex, frontal eye field, right frontal eye field, and the premotor cortex and decreased surface-based ReHo in the right primary motor cortex and primary sensory cortex. Regions showing significant differences in surface-based ReHo values between the healthy controls and patients with ONFH were defined as the regions of interests. Seed-based functional connectivity was performed to investigate interregional functional synchronization. When the areas with decreased surface-based ReHo in the frontal eye field and right premotor cortex were used as the regions of interest, compared with the healthy controls, the patients with ONFH displayed increased functional connectivity in the right middle frontal cortex and right inferior parietal cortex and decreased functional connectivity in the right precentral cortex and right middle occipital cortex. Compared with healthy controls, patients with ONFH showed significantly decreased cortical thickness in the para-insular area, posterior insular area, anterior superior temporal area, frontal eye field and supplementary motor cortex and reduced volume of subcortical gray matter nuclei in the right nucleus accumbens. These findings suggest that hip disorder patients showed cortical plasticity changes, mainly in sensorimotor- and pain-related regions. This study was approved by the Medical Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine (approval No. 2018-041) on August 1, 2018.

Electroacupuncture treatment improves motor function and neurological outcomes after cerebral ischemia/reperfusion injury.

Electroacupuncture (EA) has been widely used for functional restoration after stroke. However, its role in post-stroke rehabilitation and the associated regulatory mechanisms remain poorly understood. In this study, we applied EA to the Zusanli (ST36) and Quchi (LI11) acupoints in rats with middle cerebral artery occlusion and reperfusion. We found that EA effectively increased the expression of brain-derived neurotrophic factor and its receptor tyrosine kinase B, synapsin-1, postsynaptic dense protein 95, and microtubule-associated protein 2 in the ischemic penumbra of rats with middle cerebral artery occlusion and reperfusion. Moreover, EA greatly reduced the expression of myelin-related inhibitors Nogo-A and NgR in the ischemic penumbra. Tyrosine kinase B inhibitor ANA-12 weakened the therapeutic effects of EA. These findings suggest that EA can improve neurological function after middle cerebral artery occlusion and reperfusion, possibly through regulating the activity of the brain-derived neurotrophic factor/tyrosine kinase B signal pathway. All procedures and experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine, China (approval No. PZSHUTCM200110002) on January 10, 2020.

Molecular Mechanism of Xixin-Ganjiang Herb Pair Treating Chronic Obstructive Pulmonary Disease-Integrated Network Pharmacology and Molecular Docking.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by high morbidity, disability, and mortality, which seriously threatens human life and health. Xixin and Ganjiang are classic herb pairs of Zhongjing Zhang, which are often used to treat COPD in China. However, the substance basis and mechanism of action of Xixin-Ganjiang herb pair (XGHP) in the treatment of COPD remain unclear. METHODS: On the website of TCMSP and the DrugBank, effective compounds and targets of XGHP were found. COPD targets were obtained from GeneCards, DisGeNET, and GEO gene chips. Intersecting these databases resulted in a library of drug targets for COPD. Then, intersection targets were used for protein-protein interaction (PPI) and pathway enrichment analysis. Finally, the binding activity between compounds and core genes was evaluated by molecular docking to verify the expression level of PTGS2 and PPARG in rats. RESULTS: Twelve effective compounds and 104 core genes were found in the intersection library, and kaempferol, sesamin, ß-sitosterol, PTGS2, and PPARG were particularly prominent in the network analysis. A total of 113 pathways were obtained and enrichment of the TNF signaling pathway, IL-17 signaling pathway, and C-type lectin receptor signaling pathway was particularly obvious. Molecular docking indicated that kaempferol, sesamin, and ß-sitosterol were closely related to PTGS2 and PPARG and were superior to aminophylline. Key compounds in XGHP could restrict the expression of PTGS2 in the lung tissues of COPD rats and promote the expression of PPARG. CONCLUSION: Inhibition of the expression of inflammatory factor PTGS2 and promotion of the expression of PPARG may be an effective target of XGHP in the treatment of COPD.

The efficacy of Tuina with herbal ointment for patients with post-stroke depression: study protocol for a randomized controlled trial.

BACKGROUND: Post-stroke depression (PSD) is a common complication after stroke which hinders functional recovery and return to social participation of stroke patients. Efficacy of conventional drug therapies for patients with PSD is still uncertain. Therefore, many patients prefer to use complementary and alternative therapies for PSD. Tuina (traditional Chinese manual manipulation) with herbal ointment is an integration of manual therapy, and ointment is an important part of traditional Chinese medicine (TCM) therapy. Preliminary experiments have shown that the Tuina with herbal ointment can improve the mental state of patients with PSD. The purpose of this study is to observe and verify the efficacy of Tuina combined with herbal ointment for patients with post-stroke depression, and to lay a foundation for further research on its mechanism of action. METHODS/DESIGN: In this study, a randomized controlled trial will be conducted in parallel, including two intervention groups: Tuina with herbal ointment group and herbal ointment for control group. A total of 84 eligible participants will be randomly assigned to the groups in a 1:1 ratio. All participants will receive conventional antidepressant venlafaxine treatment (75 mg QD), on which they received two different interventions. The interventions for both groups will be carried out 5 times each week for a period of 2 weeks. The primary outcome will be the Hamilton Rating Scale for Depression (HAMD). Secondary outcomes will include transcranial magnetic stimulation (TMS), as well as 36-item Short-Form Health Survey (SF-36) and Treatment Emergent Symptom Scale (TESS). They will be assessed at the baseline, at the end of the intervention (2 weeks), and during the 1 month and 3 months of follow-up by repeated measures analysis of variance. The significance level is 5%. Adverse events will be monitored at each visit to assess safety. All outcomes will be assessed and analyzed by researchers blinded to the treatment allocation. The purpose of this study will focus on observing the efficacy of Tuina with herbal ointment for patients with post-stroke depression, and to explore further the mechanisms of its effects. DISCUSSION: This study may evaluate clinical application value and safety of Tuina with herbal ointment in PSD patients, which can provide basis for clinical research and mechanism exploration of PSD. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000033887 . Registered on 15 June 2020. DISSEMINATION: The results will be published in peer-reviewed journals and disseminated through the study's website and conferences.

Xiaoyaosan Improves Antibiotic-Induced Depressive-Like and Anxiety-Like Behavior in Mice Through Modulating the Gut Microbiota and Regulating the NLRP3 Inflammasome in the Colon.

Disturbance of the gut microbiota plays an essential role in mental disorders such as depression and anxiety. Xiaoyaosan, a traditional Chinese medicine formula, has a wide therapeutic spectrum and is used especially in the management of depression and anxiety. In this study, we used an antibiotic-induced microbiome-depleted (AIMD) mouse model to determine the possible relationship between imbalance of the intestinal flora and behavioral abnormalities in rodents. We explored the regulatory effect of Xiaoyaosan on the intestinal flora and attempted to elucidate the potential mechanism of behavioral improvement. We screened NLRP3, ASC, and CASPASE-1 as target genes based on the changes in gut microbiota and explored the effect of Xiaoyaosan on the colonic NLRP3 pathway. After Xiaoyaosan intervention, AIMD mice showed a change in body weight and an improvement in depressive and anxious behaviors. Moreover, the gut flora diversity was significantly improved. Xiaoyaosan increased the abundance of Lachnospiraceae in AIMD mice and decreased that of Bacteroidaceae, the main lipopolysaccharide (LPS)-producing bacteria, resulting in decreased levels of LPS in feces, blood, and colon tissue. Moreover, serum levels of the inflammatory factor, IL-1ß, and the levels of NLRP3, ASC, and CASPASE-1 mRNA and DNA in the colon were significantly reduced. Therefore, Xiaoyaosan may alleviate anxiety and depression by modulating the gut microbiota, correcting excessive LPS release, and inhibiting the immoderate activation of the NLRP3 inflammasome in the colon.

Research for improvement on the extract efficiency of lignans in traditional Chinese medicines by hybrid ionic liquids: As a case of Suhuang antitussive capsule.

Recently, efficient extraction of natural products from traditional Chinese medicines (TCMs) by green solvents is deemed an essential area of green technology and attracts extensive attentions. In this work, a green protocol for simultaneous ultrasonic-extraction of the native compounds with different polarities of TCMs by using a hybrid ionic liquids (HILs)-water system was reported for the first time. As a case study, three superior ILs (1-ethyl-3-methylimidazolium tetrafluoroborate ([EMIM][BF4]), 1-ethyl-3-methylimidazolium acetate ([EMIM][OAc]), and 1-allyl-3-methylimidazolium chloride ([AMIM]Cl)) were chosen as the compositions of the HILs system, and the TCMs Suhuang antitussive capsule (SH) containing different-polarity lignans was selected. Primarily, an ultra-performance liquid chromatography coupled to triple quadrupole tandem mass spectrometry (UPLC-QqQ-MS/MS) method in the multiple reaction monitoring (MRM) mode was established for qualitative and quantitative analysis of 18 lignans. After majorization by uniform design experiment, the HILs prepared with [AMIM]Cl, [EMIM][BF4], and [EMIM][OAc] at a volume ratio of 1:5:5 could simultaneously extract multi-polarity lignans compared to single IL. Subsequently, the conditions of ultrasonic extraction employing with HILs and traditional organic solvent were optimized by the response surface methodology, respectively. The results indicated that the extract efficiency of the HILs system for target compounds was significantly improved compared with the traditional organic solvent-extraction, i.e. the content of total lignans in ethanol system was up to 47 mg/g, while that in the HILs system was up to 69 mg/g, with an increasing of 47%. Additionally, 1H-NMR and 13C-NMR spectra were used to characterize the hydrogen-bond interactions in the HILs-lignan mixtures. Extraction with the HILs in TCMs is a new application schema of ILs, which not only avoids the use of volatile toxic organic solvents, but also shows the potential to be comprehensively applied for the extraction of bioactive compounds from TCMs.

Effectiveness and safety of acupuncture in the treatment of chronic severe functional constipation: A protocol for systematic review and meta-analysis.

BACKGROUND: Acupuncture has been widely used clinically to relieve chronic severe constipation. However, the efficacy of acupuncture in the treatment of chronic severe constipation is uncertain. The purpose of this study is to determine the effectiveness and safety of acupuncture in the treatment of chronic severe constipation. METHODS: Search PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure Database, Wanfang Database, China Science, and Technology Journal Database, China Biomedical Literature Database, and search related randomized controlled trials. Two reviewers will independently select studies, collect data, and evaluate methodological quality through the Cochrane Deviation Risk Tool. Revman V.5.3 will be used for meta-analysis. RESULTS: This study will evaluate the current status of acupuncture treatment for chronic severe constipation, aiming to illustrate the effectiveness and safety of acupuncture treatment. CONCLUSION: This study will provide a basis for judging whether acupotomy is effective in treating chronic severe constipation. INPLASY REGISTRATION NUMBER: INPLASY202070002.

Effectiveness of theta and gamma electroacupuncture for post-stroke patients on working memory and electrophysiology: study protocol for a double-center, randomized, patient- and assessor-blinded, sham-controlled, parallel, clinical trial.

BACKGROUND: Practitioners of complementary and alternative medicine have suggested that electroacupuncture (EA) could improve post-stroke cognitive impairment, based on the clinical evidence. This study protocol is aimed at showing the effectiveness of theta and gamma EA for post-stroke patients on working memory (WM) and electrophysiology. METHODS: After assessing their eligibility, 66 patients with stroke will be enrolled from two Chinese medicine hospitals and randomly divided into theta frequency EA group, gamma frequency EA group, and sham-EA group according to the ratio of 1:1:1. All patients will receive 20 sessions of EA procedures for 4 weeks. Patients in three groups will receive EA at two same acupoints in the head: Baihui (GV20) and Shenting (GV24). The frequency of the three groups of EA is set as follows: 6 Hz (theta-EA group), 40 Hz (gamma-EA group), and no current through the electrodes (sham EA). Patients and assessors will be blinded throughout the entire study. The primary outcome is the performance accuracy of 1-back task which is a frequently used measure of WM in cognitive neuroscience research contexts. Secondary outcome measures will include the response time of 1-back task, the Rivermead Behavioral Memory Test, Trail Making Test, Loewenstein Occupational Therapy Cognitive Assessment Scale, modified Barthel Index, and electroencephalogram (EEG) signals during 1-back tasks. A blinding index will be assessed. Data will be statistically analyzed by one-way ANOVA, at 5% of significance level. DISCUSSION: We expect this double-center, randomized, patient- and assessor-blinded, sham-controlled, parallel, clinical trial to explore the effectiveness of theta and gamma EA therapy, compared with sham EA, for post-stroke WM. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000031995 . Registered on 17 April 2020.