Effect of electroacupuncture on proBDNF/mBDNF and synaptic plasticity in rats with learning and memory impairment after cerebral ischemia-reperfusion. / ç”µé’ˆå¯¹è„‘ç¼ºè¡€å†çŒæ³¨å­¦ä¹ è®°å¿†éšœç¢å¤§é¼ æµ·é©¬è„‘æºæ€§ç¥žç»è¥å »å› å­è½¬åŒ–å’Œçªè§¦å¯å¡‘æ€§çš„å½±å“.

OBJECTIVES: To observe the effect of electroacupuncture (EA) at "Baihui" (GV20) and "Shenting" (GV24) on the rats' behavior and the transforming precursor of brain-derived neurotrophic factor (proBDNF) into mature brain-derived neurotrophic factor (mBDNF) in the hippocampus of rats with learning and memory impairment induced by cerebral ischemia-reperfusion (IR), so as to explore its mechanisms underlying improvement of learning and memory ability. METHODS: SD rats were randomly divided into blank, sham operation, model, and EA groups, with 6 rats in each group. The model of IR was established by occlusion of the middle cerebral artery. EA (1 Hz/20 Hz) was applied to GV24 and GV20 for 30 min, once daily for 14 days. The neurological function was evaluated according to the Zea Longa's score criteria 24 h after modeling and after intervention. Morris water maze test was used to detect the learning and memory function of the rats. TTC staining was used to evaluate the cerebral infarction volume on the affected side. The protein expression levels of proBDNF, mBDNF, tissue plasminogen activator (tPA), tyrosine kinase receptor B (TrkB) and p75 neurotrophin receptor (p75NTR) in hippocampal tissue were detected by Western blot. RESULTS: Compared with the sham operation group, the neurological function score, the percentage of cerebral infarction volume and the expression levels of proBDNF and p75NTR protein in hippocampus were increased (P<0.01), while the times of crossing the original platform and the total distance in the target quadrant, the expression levels of mBDNF, TrkB and tPA protein and the ratio of mBDNF/proBDNF were decreased (P<0.01, P<0.05) in the model group. Compared with the model group, the neurological function score, the percentage of cerebral infarction volume, and the expression levels of proBDNF and p75NTR protein in hippocampus were decreased (P<0.01, P<0.05), while the times of crossing the original platform, the total distance in the target quadrant, and the expression levels of mBDNF, TrkB and tPA protein and the ratio of mBDNF/proBDNF were increased (P<0.05, P<0.01) in the EA group. CONCLUSIONS: EA can alleviate learning and memory impairment in IR rats, which may be related to its function in up-regulating the expression of tPA protein and promoting the transformation of proBDNF to mBDNF, thus improving the synaptic plasticity.

Effect of electroacupuncture of Governor Vessel on mitochondrial fusion and proliferation and differentiation of neural stem cells in spinal cord injury rats. / ç”µé’ˆç£è„‰å¯¹è„Šé«“æŸä¼¤å¤§é¼ è„Šé«“ç»„ç»‡çº¿ç²’ä½“èžåˆåŠç¥žç»å¹²ç»†èƒžå¢žæ®–åˆ†åŒ–çš„å½±å“.

OBJECTIVES: To observe the effect of electroacupuncture (EA) at "Dazhui" (GV14) and "Jizhong"(GV6) of the Governor Vessel (GV) on mitochondrial fusion and neural stem cell (NSC) proliferation and differentiation in the spinal cord of rats with spinal cord injury (SCI), so as to investigate its mechanisms underlying improvement of SCI. METHODS: SD rats were randomly divided into sham operation, model and EA groups, with 15 rats in each group. The SCI model was established by using a precision impactor. EA (20 Hz/100 Hz, 1-2 mA) was applied to GV14 and GV6 for 30 min, once daily for 14 days. The rats' hindlimb locomotor function in each group was assessed using the Basso-Beattie-Bresnahan (BBB) locomotor scale. Histopathological changes of the injured spinal cord tissue and the number of neurons were evaluated after H.E. staining and Nissl staining. The expressions of Nestin, mitochondrial fusion-related protein optic atrophy-1 (OPA1) and NSC markers sex-determining region Y-box 2 (SOX2) in the injured spinal cord tissue were detected by immunofluorescence staining. The protein and mRNA expression levels of Nestin in the spinal cord tissue were detected by quantitative real-time PCR and Western blot, separately. RESULTS: Compared with the sham operation group, the BBB scores after modeling, and the number of neurons were significantly decreased (P<0.001), while the mean fluorescence intensity values of Nestin, SOX2 and OPA1, and the expressions of Nestin mRNA and protein considerably increased (P<0.001, P<0.01, P<0.05) in the model group. After EA intervention and in comparison with the model group, the BBB scores at the 7th and 14th day, the number of neurons, the mean fluorescence intensity values of Nestin, SOX2 and OPA1, and the expressions of Nestin mRNA and protein were strikingly increased (P<0.05, P<0.01, P<0.001) in the EA group. H.E. staining showed swollen, ruptured and necrotic neurons of the spinal cord, with a large number of vacuoles and severe inflammatory cell infiltration after modeling, which was relatively milder in the EA group. CONCLUSIONS: EA stimulation of GV14 and GV6 can promote the recovery of motor function in rats with SCI, which may be related to its effects in promoting mitochondrial fusion and enhancing the proliferation and differentiation of NSCs.

Electroacupuncture Ameliorates Depression-Like Behaviors in Post-Stroke Rats via Activating AMPK-Mediated Mitochondrial Function.

Background: Post-stroke depression (PSD) is one of the most common complications of stroke. Electroacupuncture (EA) is an effective traditional Chinese medicine treatment for PSD, which is widely used in clinical settings. EA has a significant therapeutic effect against PSD, but the mechanism is still unclear. This study aimed to determine whether EA ameliorates depression-like behaviors in PSD rats by regulating the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)-mediated mitochondrial function. Methods: Middle cerebral artery occlusion (MCAO) and chronic unpredictable mild stress (CUMS) were used to develop a PSD rat model. To elucidate the role of AMPK in EA treatment, compound C, a selective inhibitor of AMPK, was injected into the lateral ventricle of rats before EA treatment. EA treatment was performed for 14 consecutive days for 30 min per day after PSD modeling. A modified Zea-Longa five-point scale scoring system was used to determine neurologic function in MCAO rats. Behavioral tests were conducted to evaluate depression-like phenotypes in rats. Depression-like behaviors were tested by sucrose preference test (SPT), novelty suppressed feeding test (NSFT), and open-field test (OFT). The structure and morphology of the prefrontal cortex were observed by histopathological hematoxylin-eosin (HE) and Nissl staining. The mitochondrial morphology and function were analyzed by colorimetry, chemiluminescence, Western blotting, and quantitative real-time polymerase chain reaction (qRT-PCR). Results: EA treatment successfully ameliorated depression-like behaviors, upregulated AMPK expression, and improved mitochondrial function. However, AMPK inhibition by Compound C exacerbated depression-like behaviors and aggravated neuronal and mitochondrial injury in PSD rats. Conclusion: EA treatment improved depression-like behaviors in PSD rats and promoted mitochondrial function by activating AMPK.

Needle retaining after electroacupuncture combined with cognitive training for post-stroke cognitive impairment: a multi-center randomized controlled trial. / ç”µé’ˆåŽç•™é’ˆè”åˆè®¤çŸ¥è®­ç»ƒæ²»ç–—è„‘å’ä¸­åŽè®¤çŸ¥åŠŸèƒ½éšœç¢ï¼šå¤šä¸­å¿ƒéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To compare the efficacy of needle retaining after electroacupuncture combined with cognitive training and electroacupuncture combined with cognitive training in the treatment of post-stroke cognitive impairment (PSCI). METHODS: A total of 206 patients with PSCI were randomized into a needle retaining group (103 cases, 9 cases dropped out) and an electroacupuncture group (103 cases, 6 cases dropped out). In addition to the conventional basic medical treatment and the rehabilitation treatment, in the needle retaining group, electroacupuncture at Shenting (GV 24) and Baihui (GV 20) was applied, with continuous wave of 50 Hz in the first 15 min and with disperse-dense wave of 2 Hz/50 Hz in the last 15 min, the needles were continuously retained for 1 h after electroacupuncture, during which cognitive training was adopted; in the electroacupuncture group, cognitive training was performed after the same electric stimulation exerted for 30 min, without additional needles retaining. The treatment was given once a day, 5 times a week for totally 8 weeks in the two groups. Before and after 8-week treatment, the TCM syndrome score was observed; before and after 4,8-week treatment, the scores of mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA) and ability of daily living were observed in the two groups. The clinical efficacy of the two groups was evaluated after 8-week treatment. RESULTS: After 8-week treatment, the TCM syndrome scores were increased compared with those before treatment in both groups (P<0.05); the TCM syndrome score in the needle retaining group was higher than that in the electroacupuncture group (P<0.05).After 4,8-week treatment, the scores of MMSE, MoCA and ability of daily living were increased compared with those before treatment in both groups (P<0.05); MMSE, MoCA scores after 4,8-week treatment and ability of daily living score after 8-week treatment in the needle retaining group were higher than those in the electroacupuncture group (P<0.05). The total effective rate was 90.4% (85/94) in the needle retaining group, which was superior to 82.5% (80/97) in the electroacupuncture group (P<0.05). CONCLUSIONS: Both needle retaining after electroacupuncture combined with cognitive training and electroacupuncture combined with cognitive training can effectively treat PSCI, improve the clinical symptom, cognitive function and ability of daily living in PSCI patients. Needle retaining after electroacupuncture combined with cognitive training has a better therapeutic effect.

Effect of acupuncture for patients with knee osteoarthritis: study protocol for a double-dummy randomized controlled trial.

BACKGROUND: Acupuncture has been used to relieve chronic pain in patients with knee osteoarthritis (KOA), but the evidence is contradictory. Therefore, we carefully designed a double-dummy randomized controlled trial (RCT) to explore the therapeutic effect of acupuncture for KOA. METHODS/DESIGN: A total of 138 eligible participants with KOA who consent to participate will be randomly divided into Groups A, B, and C in a ratio of 1:1:1. Participants in Group A will receive verum acupuncture and placebo gel, while those in Groups B and C will be treated with diclofenac diethylammon gel and sham acupuncture, sham acupuncture and placebo gel, respectively. The patients will receive 4 weeks of treatment, five times a week, including acupuncture treatment once a day for 30 min and gel treatment three times a day. The primary outcome will be the change of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at week 4. The secondary outcomes will include visual analog scale (VAS), Arthritis Quality of Life Measurement Scale Simplified Scale (AIMS2-SF), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI) and Credibility/Expectancy Questionnaire. The evaluation will be performed at baseline, week 4, 8, and 12 after randomization. DISCUSSION: This double-dummy RCT used diclofenac diethylammon gel as a positive control, and the completion of this trial will provide detailed and accurate evidence of the efficacy and safety of acupuncture for KOA. TRIAL REGISTRATION: China Clinical Trials Registry No.ChiCTR2100043947. Registered on September 24, 2020. https://www.chictr.org.cn/showproj.html?proj=122536 .

[Electroacupuncture improves learning and memory impairment and enhances hippocampal synaptic plasticity through BDNF/TRKB/CREB signaling pathway in cerebral ischemia-reperfusion injury rats].

OBJECTIVE: To observe the effect of electroacupuncture on brain-derived neurotrophin factor (BDNF) / tyrosine kinase receptor B (TRKB) / cyclic adenosine monophosphate response element binding protein (CREB) pathway, synaptic plasticity marker protein and synaptic ultrastructure in the hippocampus of rats with learning and memory impairment induced by cerebral ischemia reperfusion (IR), so as to explore its mechanisms underlying improvement of cognitive impairment after stroke. METHODS: SD rats were randomly divided into blank, sham operation, model, and EA groups, with 12 rats in each group. The model of IR was established by occlusion of the middle cerebral artery. EA (2 Hz/10 Hz, 1-3 mA) was applied to "Shenting" (GV24) and "Baihui" (GV20) for 30 min, once daily for 14 days. The neurological function was evaluated according to the Zea Longa's score criteria. Morris water maze test was used to detect the learning and memory function of the rats. Nissl staining was used to observe the pathological morphology of the hippocampus. Transmission electron microscopy was used to observe the ultrastructure of the syna-pse in the hippocampus, the synaptic gap width and postsynaptic dense substance (PSD) thickness were measured. Immunofluorescence staining was used to observe the positive expression levels of BDNF, PSD-95 and synaptophysin (SYN) in hippocampal CA1 region. The protein expression levels of BDNF, TRKB, CREB, PSD-95, and SYN in hippocampal tissue were detected by Western blot. RESULTS: Compared with the sham operation group, the neurological function score and escape latency (EL) were significantly increased (P<0.01), the times of crossing the original platform were decreased (P<0.01), the number of neurons in the CA1 area of the hippocampus was reduced, with incomplete morphology, widened synaptic gaps and significantly decreased PSD thickness (P<0.01), the positive expressions of BDNF, PSD-95, SYN and the protein expression levels of BDNF, TRKB, CREB, PSD-95, SYN were significantly decreased (P<0.01) in the model group. Compared with the model group, the neurological function scores and EL on the 12th and 13th day were decreased (P<0.01, P<0.05), the times of crossing the original platform were increased (P<0.01), the morphology of hippocampal CA1 neurons improved, the synaptic gaps was decreased (P<0.01), the PSD thickness was significantly increased (P<0.01), the positive expressions of BDNF, PSD-95, SYN, and the protein expression levels of BDNF, TRKB, CREB, PSD-95, SYN were increased (P<0.05, P<0.01) in the EA group. CONCLUSION: EA can alleviate cognitive impairment in IR rats, which may be related to its function in up-regulating the proteins of BDNF/TRKB/CREB pathway, promoting the expressions of synaptic plasticity marker proteins PSD-95 and SYN, thus improving the synaptic plasticity.

Association of Globodera rostochiensis (Nematoda) with Stunted and Chlorotic Potato Plants in Yunnan and Sichuan Provinces in China.

On a global basis, potato cyst nematodes (Globodera spp. Skarbilovich 1959 [Behrens 1975]) are one of the most serious soilborne pathogens in potato (Solanum tuberosum L.) production. In 2019 to 2020, 188 soil samples were taken from rhizosphere soil associated with the roots of stunted and chlorotic potato plants in the main potato-growing areas of Yunnan and Sichuan Provinces of China. Globodera rostochiensis Wollenweber 1923 (Skarbilovich 1959) was recovered from 112 of the samples. Nematode identification was as confirmed by morphometric, light microscopy, electron microscopy, and molecular methodologies. Population densities of G. rostochiensis ranged from 47.0 to 69.0 eggs/g of soil. A BLASTn homology search program was used to compare the sequences of populations of G. rostrochienses from Yunnan and Sichuan Provinces with populations of other Heteroderinae spp. and populations of G. rostochiensis from other nations. Although potato has been grown in China for at least 400 years and the nation produces more potato than any other country, potato cyst nematodes were not reported in China until 2022.

Bibliometric analysis: Research trends of acupuncture treatment to cognitive impairment in recent 15 years.

Objectives: Acupuncture therapy has been used for cognitive impairment-related diseases, however, there are still few studies on the overall trend of acupuncture therapy on cognitive impairment based on bibliometric analysis. The purpose of this study was to explore the research trend of the impact of acupuncture on cognitive impairment in the past 15 years, analyze the research trends and hotspots, and provide new ideas and theoretical basis for future research directions. Methods: From the Web of Science Core Collection (WoSCC), the relevant literature on the treatment of cognitive impairment with acupuncture from 2007 to 2022 was retrieved. Then, based on the CiteSpace and VOSviewer software of the Java platform, the cooperation between countries and institutions in this field, the co-citation of journals and documents, and the cooperation between authors and authors, etc. were analyzed. In addition, the co-occurrence and burst analysis of keywords are also carried out, and a visual knowledge map is drawn. Results: As of August 08, 2022, a total of 394 records related to the treatment of cognitive impairment with acupuncture were identified. The analysis results show: The number and rate of annual publications have steadily increased, with some fluctuations from year to year. The countries that contribute the most to this field are China and the USA. Among them, Beijing University of Chinese Medicine and Capital Medical University are tied for first place in terms of the number of published papers. Tao Jing is the most prolific author and the number one cited author. Conclusions: The number of publications on acupuncture for cognitive impairment is expected to increase rapidly in future research, suggesting a bright future for the field. Future research hotspots will focus on pain, injury, protocol, diagnosis, guidelines, etc. It is also necessary to strengthen cross-regional and cross-country cooperation among various academic groups.

Electroacupuncture of Baihui and Shenting ameliorates cognitive deficits via Pten/Akt pathway in a rat cerebral ischemia injury model.

Cerebral ischemic stroke is a huge threat to the health and life of many people. Electroacupuncture (EA) at Baihui (GV20) and Shenting (GV24) acupoints can notably alleviate cerebral ischemia/reperfusion injury (CIRI). However, the molecular basis underlying the effectiveness of EA at the GV20 and GV24 acupoints for CIRI remains largely unknown. Our present study demonstrated that EA treatment at the GV20 and GV24 acupoints markedly alleviated middle cerebral artery occlusion/reperfusion (MCAO/R)-induced cognitive deficits and cerebral infarction in rats. Proteomics analysis revealed that 195 and 218 proteins were dysregulated in rat hippocampal tissues in the MCAO/R vs. sham group and thhhe EA vs. MCAO/R group, respectively. Moreover, 62 proteins with converse alteration trends in MCAO/R vs. sham and EA vs. MCAO/R groups were identified. These proteins might be implicated in the EA-mediated protective effect against MCAO/R-induced cerebral injury. GO enrichment analysis showed that 39 dysregulated proteins in the MCAO/R vs. sham group and 40 dysregulated proteins in the EA vs. MCAO/R group were related to brain and nerve development. Protein-protein interaction analysis of the abovementioned dysregulated proteins associated with brain and nerve development suggested that Pten/Akt pathway-related proteins might play major roles in regulating EA-mediated protective effects against MCAO/R-induced brain and nerve injury. Western blot assays demonstrated that Pak4, Akt3, and Efnb2 were expressed at low levels in the MCAO/R group vs. the sham group but at high levels in the EA group vs. the MCAO/R group. In conclusion, multiple proteins related to the protective effect of EA at the GV20 and GV24 acupoints against CIRI were identified in our study.

Acupuncture ameliorates breast cancer-related fatigue by regulating the gut microbiota-gut-brain axis.

Cancer-related fatigue (CRF) is the most common side effect of chemotherapy for breast cancer (BC). Acupuncture treatment has an anti-fatigue effect and can regulate gut microbiota disturbance in fatigue patients. Related studies have shown that the gut microbiota-gut-brain axis is closely related to the occurrence of CRF. In this study, we first investigated the alterations of acupuncture on fatigue-like behavior, gut microbiota, gut inflammation and neuroinflammation response, gut barriers, HPA axis, and serum metabolomics in CRF mice after BC chemotherapy. Then, the correlation analysis of gut microbiota and other indicators was discussed. Our results showed that acupuncture treatment could exert an anti-fatigue effect and ameliorate the gut barrier, gut inflammation, neuroinflammation, and dysfunction of the HPA axis in CRF mice after chemotherapy for BC. 16S rRNA sequencing showed that acupuncture treatment could enhance the abundance of Candidatus Arthromitus, Lactobacillus, and Clostridia_UCG-014_unclassified and decrease the abundances of Escherichia-Shigella, Burkholderia-Caballeronia-Paraburkholderia, and Streptococcus. Serum metabolomics analysis showed that acupuncture treatment could regulate the differential metabolites N-methylnicotinamide, beta-glycerophosphoric acid, geranyl acetoacetate, serotonin and phenylalanine, tyrosine and tryptophan biosynthesis, taurine and hypotaurine, and beta-alanine metabolic pathways. Correlation analysis indicated that there are certain correlations between gut microbiota and gut inflammation, neuroinflammation, gut barrier, HPA axis function and serum metabolites. In conclusion, our findings revealed that the anti-fatigue mechanism of acupuncture treatment may be closely related to the gut microbiota-gut-brain axis. This study also provided a new reference for basic and clinical research on CRF after breast cancer chemotherapy.

[Effect of electroacupuncture of Governor Vessel on expression of GAD67 and GABA-T in cerebral cortex of rats with post-stroke limb spasticity].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of Governor Vessel (GV) on the expressions of glutamate decarboxylase 67 (GAD67) and γ-aminobutyric acid transaminase (GABA-T) in the cerebral cortex of rats with post-stroke limb spasticity, so as to explore its mechanism underlying improvement of limb spasticity. METHODS: Twenty four male SD rats were randomly and equally divided into control, sham operation, model, and EA groups. The cerebral ischemia model was established by occlusion of the middle cerebral artery (MCAO). EA (100 Hz, 1-3 mA) was applied to "Dazhui"(GV14), "Jizhong"(GV6) and "Houhui"( anteromedial of transverse process of the sixth lumbar vertebra) for 30 min, once daily for 7 consecutive days. The neurologic deficit score (0-5 points) was evaluated according to Zea Longa's method, and the muscular tension severity (0-5 points) was assessed according to the modified Ashworth muscle tone rating scale, and the tension signals of the quadriceps ferroris of the affected limb were recorded using tonotransducer and BL-420F electrophysiological recorder. The expression levels of GAD67 and GABA-T proteins and mRNAs in the cerebral cortex were detected by immunohistochemistry, fluorescence quantitative real-time PCR and Western blot, separately. RESULTS: After modeling, the neurological deficit score, muscle tone score, and the expression levels of GABA-T mRNA and protein in cerebral cortex were significantly increased (P<0.01, P<0.05), tension signal value and the expression levels of GAD67 mRNA and protein in cerebral cortex were significantly decreased (P<0.01) in the model group relevant to the control and sham operation groups. Following the intervention, the neurological deficit score, muscle tone score, and expression levels of GABA-T mRNA and protein in cerebral cortex were significantly decreased (P<0.01), tension signal value and the expression levels of GAD67 mRNA and protein in cerebral cortex were significantly increased (P<0.01, P<0.05) in the EA group in contrast to the model group. CONCLUSION: EA stimulation of Governor Vessel can ameliorate the limb spasticity symptom in MCAO rats, which may be associated with its functions in increasing the expressions of GAD67 protein and mRNA and inhibiting the expressions of GABA-T protein and mRNA, thereby playing the inhibitory role of GABA.

Efficacy of manual acupuncture, electro-acupuncture, and warm acupuncture for knee osteoarthritis: study protocol for a randomized controlled trial.

BACKGROUND: Acupuncture is one of the most popular complementary and alternative treatments for knee osteoarthritis (KOA). There are many methods of acupuncture in the treatment of KOA, and the effects are different. According to our clinical observations and researches, it is found that manual acupuncture (MA), electro-acupuncture (EA), and warm acupuncture (WA) are used more frequently in the treatment of KOA, and the curative effects are satisfactory. However, there is currently a lack of efficacy comparison of efficacy between different acupuncture treatments, as well as a lack of standardized clinical research on the acupuncture treatment of KOA. Therefore, we will carry out a high-quality clinical randomized controlled trial to research the effect laws of MA, EA, and WA on KOA. METHODS/DESIGN: A total of 200 eligible participants with KOA will be randomly assigned to group A, B, C, or D in a ratio of 1:1:1:1. Patients in group A will receive MA, while those in group B, group C, and group D will be treated with EA, WA, and sham acupuncture (SA), respectively. Patients will be treated with acupuncture once a day, 30 min per session, 5 sessions per week for 4 weeks. The primary outcome is the change of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at week 4. The secondary outcomes include WOMAC, visual analog scale (VAS), Arthritis Quality of Life Measurement Scale Simplified Scale (AIMS2-SF), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), and Credibility/Expectancy Questionnaire. The evaluation will be performed at baseline and weeks 4, 8, and 12 respectively after randomization. DISCUSSION: This is a randomized controlled trial. We will observe the clinical effect of MA, EA, and WA on KOA to research the effect laws of these three acupuncture treatments on KOA and set up standardized treatment programs for acupuncture for KOA. TRIAL REGISTRATION: China Clinical Trials Registry ChiCTR2100049526. Registered on August 2, 2021.

Effect of Acupuncture on the Cognitive Control Network of Patients with Knee Osteoarthritis: Study Protocol for a Randomized Controlled Trial.

Purpose: Abnormal central nervous system function is the key central pathological factor leading to chronic pain in patients with knee osteoarthritis (KOA). Acupuncture can effectively relieve the pain of KOA patients. However, the central nervous mechanism of acupuncture treating KOA is not fully understood. This trial will use functional magnetic resonance imaging (fMRI) analysis techniques to investigate the potential central nervous mechanism of acupuncture treatment of KOA. Materials and Methods: A total of 108 patients will be randomized (in a 1:1:1 ratio) into three groups, this trial will include 4-week treatment, patients in groups A and B will receive 20 acupuncture and sham acupuncture sessions, respectively, patients in group C will not receive any intervention, and all patients will receive fMRI scans before and after the intervention. The Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) will be the primary clinical outcome. Then, we will explore the functional changes of the cognitive control network (CCN) in the brains of KOA patients through whole brain functional connectivity (FC) analysis and seed-based functional connectivity (sFC) analysis. Pearson correlation coefficient will be used to analyze the relationship between the improved value of the clinical correlation scale and the change of fMRI data. Discussion: This trial will analyze the efficacy of verum acupuncture, sham acupuncture and the waiting-list for KOA and explore the activity of the CCN in three groups of patients by fMRI, so as to reveal the central nervous mechanisms of acupuncture in the treatment of KOA. Study Registration: This study is approved by the Ethics Committee of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine (No: 2019HL-133-01) and registered in the Chinese Clinical Trial Registry, ChiCTR2000038554.

Observation of curative effect on meridian theory-based extracorporeal shock wave therapy for non-specific low back pain: study protocol for a randomized controlled trial.

BACKGROUND: Non-specific low back pain (NLBP) is a major global socioeconomic burden, and the prevalence of NLBP is still on the rise. At present, there is no ideal drug to cure this disease. This may be the reason why patients often use complementary therapies. Among them, extracorporeal shock wave therapy (ESWT) has gradually received more attention and has become the main treatment method for NLBP. The purpose of this study is to provide scientific evidence for the effect and safety of meridian theory-based ESWT on NLBP. OBJECTIVE: This study aims to evaluate the effect and safety of meridian theory-based ESWT on NLBP. This study will also provide more high-quality experimental evidence for the clinical application of meridian theory-based ESWT for the treatment of NLBP in future. METHODS: The study design is a single-blind, multi-center, randomized controlled trial. 66 patients with NLBP, aged 18 to 60 years, will be randomly divided into two groups: the experimental group (N = 33), which will receive meridian theory-based ESWT application, and the control group (N = 33) which will receive conventional ESWT treatment. These two applications will be carried out twice a week for two weeks. The primary outcome will be the Visual Analog Scale (VAS), and the secondary outcomes will be Oswestry Disability Index (ODI), Surface Electromyography (sEMG), and Patient Health Questionnaire-15 (PHQ-15). All outcomes will be evaluated at baseline and after the intervention (7 days, 14 days). DISCUSSION: Results of this trial will contribute to providing rigorous clinical evidence for the efficacy and security of meridian theory-based ESWT for NLBP. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100051049. Registered on 10 September 2021, http://www.chictr.org.cn/showproj.aspx?proj=46316 .

The Clinical Observation and Mechanism of Acupuncture on Cancer-Related Fatigue of Breast Cancer Based on "Gut-Brain Axis": Study Protocol for a Randomized Controlled Trial.

Background. Cancer-related fatigue (CRF) is a painful, persistent feeling of physical and cognitive subjective fatigue related to cancer or cancer remedy. The occurrence of CRF may be related to the hypothalamic-pituitary-adrenaline (HPA) axis, inflammatory mediator theory, and gut microbiota. Moreover, acupuncture could play a vital part in the therapy of CRF. The study will evaluate whether acupuncture can improve fatigue symptoms of CRF patients after breast cancer chemotherapy by regulating the gut-brain axis. Methods/design. Seventy patients with CRF will be enrolled in this study, with 35 patients randomly assigned to each group. Blood and feces will be collected at the beginning and end of treatment. Piper fatigue scale, KPS score scale, and quality-of-life scale will be used to observe the changes of fatigue symptoms and life quality of CRF patients and to evaluate the effect of acupuncture on CRF. Then, the method of ELISA will be used to explore the regulatory effect of acupuncture on the HPA axis and inflammatory cytokines. Moreover, based on 16SrDNA, the changes of gut microbiota structure and flora of CRF patients will be observed. Ultimately, the correlation analysis of gut microbiota can be related to inflammatory cytokines, HPA axis, and clinical efficacy evaluation. Discussion. This study will identify the effect and the mechanism of acupuncture therapy in CRF. And it will offer an alternative treatment modality for the treatment of CRF after chemotherapy for breast cancer. Furthermore, it will also provide the clinical and theoretical bases for the extensive application of acupuncture therapy in tumor rehabilitation. Trial Status. Protocol version number and date: V2.0, 6 May 2021. The trial is registered with the Chinese Clinical Trial Registry on 20 June 2021 (trial identifier: ChiCTR2100047510).

[Effects of eye acupuncture on motor evoked potential and somatosensory evoked potential in patients with incomplete spinal cord injury based on neuroelectrophysiological technology].

OBJECTIVE: To observe the effects of eye acupuncture on motor evoked potential (MEP) and somatosensory evoked potential (SEP) in the patients with incomplete spinal cord injury so as to evaluate its clinical efficacy. METHODS: According to the random number table, 90 patients were divided into exercise therapy group, eye acupuncture group and eye acupuncture combined exercise therapy group (combined treatment group), 30 cases in each. In the exercise therapy group, patients were treated with the routine exercise and occupational therapy. Patients of the eye acupuncture group were treated with eye acupuncture at upper jiao region, lower jiao region, liver region and kidney region bilaterally. Patients of the combined treatment group were given the routine exercise and occupational therapy combined with eye acupuncture. All the treatments were conducted once daily, 7 days as one treatment course for 4 treatment courses. Before treatment and 4 weeks after treatment, the motor function, light touch sensation and pinprick sensation, injury grade and clinical efficacy were assessed separately, using the criteria developed by the American Spinal Injury Association. The modified Barthel index(MBI) was adopted to evaluate the activities of daily livings. By monitoring SEP and MEP, the neurophysiological conditions were assessed for spinal cord injury. RESULTS: The total effective rate was 56.7% (17/30), 66.7% (20/30) and 90.0% (27/30) in the exercise therapy group, the eye acupuncture group and the combined treatment group, respectively. The total effective rate in the combined treatment group was higher than those in the other two groups (P<0.05). Compared with those before treatment, the scores of motor function, light tough sensation and pinprick sensation were all increased after treatment in three groups (P<0.05), MBI score was increased in both the exercise therapy group and the combined treatment group (P<0.05), and the latency of SEP (N11, N20, N23, P38) and the Cortical (hand region), Csp, Cortical (leg region) and Lsp of MEP were all shortened in the three groups separately (P<0.05). After treatment, compared with the exercise therapy group, the score of motor function was increased (P<0.05), MBI score decreased (P<0.05) and MEP latency shortened (P<0.05) in the eye acupuncture group. After treatment, compared with the exercise therapy group and the eye acupuncture group, the scores of motor function, light touch sensation and pinprick sensation, as well as MBI score were all increased (P<0.05), and the latency of SEP (N11,N20,N23,P38) and MEP shortened (P<0.05) in the combined treatment group. CONCLUSION: In treatment of incomplete spinal cord injury, eye acupuncture combined with exercise therapy can significantly increase the excitability of sensory and motor nerve conduction in the spinal cord and cerebral cortex of patients, effectively promote the recovery of patients' motor and sensory function and improve the activities of daily living.

Effects of Optimized Acupuncture and Moxibustion Treatment on Depressive Symptoms and Executive Functions in Patients With Post-Stroke Depression: Study Protocol for a Randomized Controlled Trial.

Background: Post-stroke depression (PSD), a common neuropsychiatric comorbidity after stroke, has a negative impact on the functional recovery and quality of life of survivors. It lacks effective therapeutic drugs with good curative effects and few adverse reactions. Preliminary experiments have shown that the optimized acupuncture and moxibustion treatment (OAMT), including acupuncture, moxibustion, and auricular intradermal acupuncture, improved depressive symptoms and neurological deficits in patients with PSD. However, the evidence for its effectiveness is still insufficient. Hence, we designed this study to evaluate the efficacy and safety of the OAMT in the treatment of PSD and to explore its possible mechanism from the perspective of executive functions. Methods/Design: This is a randomized controlled trial, which comprises a total of 134 patients with PSD. Participants are randomized into intervention group and control group at a 1:1 ratio. All treatments are given five times per week for 4 weeks. The primary outcome is the severity of depression, which is evaluated by the Hamilton Depression Scale-17 (HAMD-17) and the Beck Depression Rating Scale (BDI). Secondary outcomes are executive abilities, which are measured by several neuropsychological tests, including the Stroop Color and Word Test (SCWT), the Trial Making Test (TMT), the Digit Symbol Substitution Test (DSST), and the Matrix Reasoning Test (MRT). All outcomes have been evaluated at baseline and weeks 4, 8, 12, and 20. At the same time, functional MRI (fMRI) is used to measure the functional connectivity in the cognitive control network (CCN) at baseline and 4 weeks after intervention. Discussion: This study aims to provide high-quality evidence for the efficacy and safety of the OAMT for treating PSD. In addition, this trial is the first trial to explore if the improvement condition of depression in the OAMT group is related to the improvement of executive functions and the favorable changes in the structure. Clinical Trial Registration: Chinese Clinical Trial Registry, identifier: ChiCTR2100048431.

The Comparative Effectiveness of Traditional Chinese Medicine Exercise Therapies in Elderly People With Mild Cognitive Impairment: A Systematic Review and Network Meta-Analysis.

Background: Mild cognitive impairment (MCI) in the elderly is a health problem worldwide. Studies have confirmed that traditional Chinese medicine (TCM) exercise therapies can improve MCI. However, which therapy is the best and their impacts on brain function remain controversial and uncertain. This study aims to compare and rank TCM exercise therapies for MCI in the elderly, and analyze their effects on brain function, in order to find an optimal intervention and provide a basis for clinical treatments decision-making. Methods: The Web of Science, PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Clinical Trials, China National Knowledge Infrastructure (CNKI), Wangfang database, China Science and Technology Journal Database, and Chinese Biomedical Medicine (CBM) were searched through October 28, 2021. Two researchers reviewed all the studies and extracted the data. The ADDIS software version 1.16.8 and the Bayesian hierarchical model were used for pair-wise meta-analysis and network meta-analysis, and the STATA software version 14.0 was used to draw the network evidence plots and funnel plots. Results: A total of 23 studies on 2282 participants were included in this study. In the pair-wise meta-analysis, TCM exercise therapies (Baduanjin exercise, Tai Chi, Liuzijue exercise and finger exercise) were superior to non-TCM exercise therapies (stretching and toning exercise, usual care, health education and routine daily activities) in terms of MMSE, MoCA and ADL outcomes. In the network meta-analysis, the MMSE outcome ranked Baduanjin exercise (78%) as the best intervention and Tai Chi (36%) as the second. The MoCA outcome ranked Baduanjin exercise (62%) as the best intervention. For the ADL outcome, Baduanjin exercise (60%) ranked the best, and followed by finger exercise (43%). Conclusion: TCM exercise therapies may improve the cognitive function in elderly patients with MCI. Among the four therapies included, the Baduanjin exercise may be the preferred therapy for MCI in the elderly, and its mechanism may be related to the regulation of cognitive-related brain function and structure. Systematic Review Registration: https://inplasy.com, identifier: INPLASY202070006.

Exploring Active Compounds and Mechanisms of Angong Niuhuang Wan on Ischemic Stroke Based on Network Pharmacology and Molecular Docking.

Methods: The chemical ingredients of ANW were retrieved from TCMSP, TCMID, and literature. We predicted the potential targets of active ingredients by PubChem, Swiss Target Prediction, and STITCH databases. The targets related to ischemic stroke were retrieved using GeneCards, DisGeNET, DrugBank, TTD, and GEO databases. Subsequently, Venn diagrams were used to identify common targets of active ingredients and ischemic stroke. Protein-protein interaction (PPI) network was structured with STRING platform and Cytoscape 3.8.2. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of key targets were performed in the Metascape database. Finally, molecular docking was conducted by AutoDock Tools and PyMOL software. Results: A total of 2391 targets were identified for 230 active ingredients of ANW, and 1386 of them overlapped with ischemic stroke targets. The key active ingredients were mainly quercetin, ß-estradiol, berberine, wogonin, and ß-sitosterol, and the key targets were also identified, including IL-6, AKT1, MAPK3, PIK3CA, and TNF. The biological process (BP) results indicated that ANW may have therapeutic effects through response oxidative stress, inflammatory response, cellular response to lipid, and response to nutrient levels. Furthermore, the ingredients of ANW were predicted to have therapeutic effects on ischemic stroke via the HIF-1 signaling pathway, FoxO signaling pathway, chemokine signaling pathway, fluid shear stress and atherosclerosis, and neurotrophin signaling pathway. The molecular docking results all showed that the core ingredients were strong binding activity with the core targets. Conclusion: In conclusion, the bioinformatics and pharmacological results reveal that counteracting oxidative stress, suppressing inflammation, inhibiting the development of AS, and even protecting neurological function are critical pathways for ANW in the treatment of ischemic stroke. These results may help to elucidate the mechanism of ANW on ischemic stroke for experimental studies and clinical applications.

[Effect of moxibustion on M2 and P2X3 receptors of bladder tissue in rats with neurogenic bladder of detrusor areflexia after lumbar-sacral spinal cord injury].

OBJECTIVE: To observe the effect of moxibustion at "Guanyuan" (CV 4) and "Shenque" (CV 8) on acetylcholine (Ach), adenosine triphosphate (ATP) and muscarinic-type choline receptor (M2) and purine receptor P2X3 in bladder tissue in the rats with neurogenic bladder (NB) of detrusor areflexia after lumbar-sacral spinal cord injury and explore the underlying mechanism of moxibustion for promoting detrusor contraction. METHODS: Sixty SD rats were randomly divided into a model preparation group (n=45) and a sham-operation group (n=15). In the model preparation group, the modified Hassan Shaker spinal cord transection method was used to prepare the model of NB. In the sham-operation group, the spinal cord transection was not exerted except laminectomy and spinal cord exposure. Among the rats with successfully modeled, 30 rats were selected and divided randomly into a model group and a moxibustion group, with 15 rats in each one. On the 15th day after the operation, moxibustion was applied at "Guanyuan" (CV 4) and "Shenque" (CV 8) in the moxibustion group, 10 min at each acupoint, once a day. The consecutive 7-day treatment was as one course and the intervention for 2 courses was required. Urodynamic test was adopted to evaluate bladder function in rats. Using HE staining, the morphological changes in bladder tissue were observed. The content of Ach and ATP in bladder tissue was measured with biochemical method, and the protein and mRNA expression levels of M2 and P2X3 receptors in bladder tissue were detected with Western blot and real-time fluorescence quantification PCR method. RESULTS: Compared with the sham-operation group, the maximum bladder capacity, leakage point pressure and bladder compliance were increased in the rats of the model group (P<0.05). Compared with the model group, the maximum bladder capacity, the leakage point pressure and bladder compliance were decreased in the rats of the moxibustion group (P<0.05). In the model group, the detrusor fibres were arranged irregularly, bladder epithelial tissues were not tightly connected and cell arrangement was disordered, combined with a large number of vacuolar cells. In the moxibustion group, compared with the model group, the detrusor fibres were arranged regularly, bladder epithelial cells were well distributed and vacuolar cells were reduced. Compared with the sham-operation group, the content of Ach and ATP in bladder tissue was decreased (P<0.05), the protein and mRNA expression levels of M2 and P2X3 receptors were reduced (P<0.05) in the model group. In the moxibustion group, the content of Ach and ATP in bladder tissue was increased (P<0.05) and the protein and mRNA expression levels of M2 and P2X3 receptors were increased (P<0.05) as compared with the model group. CONCLUSION: Moxibustion at "Guanyuan" (CV 4) and "Shenque" (CV 8) may effectively improve bladder function in the rats with NB of detrusor areflexia after lumbar-sacral spinal cord injury and its underlying mechanism is related to promoting the release of Ach and up-regulating the expression of M2 receptor, thereby enhancing the release of ATP and increasing the expression of P2X3 receptor. Eventually, detrusor contraction is improved.