Efficacy of electroacupuncture stimulating Shenmen(HT7),Baihui(GV20),Sanyinjiao(SP6)on spatial learning and memory deficits in rats with insomnia induced by para-chlorophenylalanine:a single acupoint vs combined acupoints

OBJECTIVE:To investiage the effect of electroacupuncture(EA)at a single acupoint of Shenmen(HT7),Baihui(GV20),Sanyinjiao(SP6)and at combined acupoints of Shenmen(HT7)and Baihui(GV20)and Sanyinjiao(SP6)on the PKA/CREB and BDNF/TrkB signaling,as well as neuroapoptosis and neurogenesis in hippocampus and elucidate the underlying mechanism of single and combined acupoints on ameliorating spatial learning and memory deficits in a rat model of primary insomnia.METHODS:Primary insomnia was modeled by intraperitoneal injection of para-chlorophenylalanine(PCPA)once daily for 2 d.EA was applied at Shenmen(HT7),Baihui(GV20),Sanyinjiao(SP6),or Shenmen(HT7)+Baihui(GV20)+Sanyinjiao(SP6)(combined)for 30 min daily for 4 d.Spatial learning and memory function was evaluated by the Morris water maze(MWM)test.Protein expressions of hippocampal cAMP-dependent protein kinase(PKA)-Cβ,phosphorylated cAMP-responsive element-binding protein(p-CREB),brainderived neurotrophic factor(BDNF),and tyrosine kinase receptor B(TrkB)were evaluated by Western blotting.Neuronal apoptosis in the hippocampus was detected with the transferase-mediated dUTP-X nick end labeling assay.Endogenous neurogenesis was examined with bromodeoxyuridine staining.The MWM test and hippocampal p-CREB,BDNF,and TrkB protein levels in the combined acupoints group were evaluated after the administration of a PKA-selective inhibitor(H89).RESULTS:Spatial learning and memory were significantly impaired in rats with insomnia.The spatial learning deficits were ameliorated in the Shenmen(HT7),Baihui(GV20),Sanyinjiao(SP6),and combined groups;this improvement was significantly greater in the combined group than the single acupoint groups.The spatial memory impairment was improved in the combined,Baihui(GV20),and Shenmen(HT7)groups,but not the Sanyinjiao(SP6)group.The expressions of PKA-Cβ,p-CREB,BDNF,and TrkB were decreased in rats with insomnia.All these proteins were significantly upregulated in the combined group.PKA/p-CREB protein levels were elevated in the Baihui(GV20)and Shenmen(HT7)groups,whereas BDNF/TrkB expression was upregulated in the Sanyinjiao(SP6)group.The staining results showed significant attenuation of hippocampal cell apoptosis and increased numbers of proliferating cells in the combined group,whereas the single acupoint groups only showed decreased numbers of apoptotic cells.In the combined group,the PKA inhibitor reversed the improvement of spatial memory and upregulation of pCREB expression caused by EA,but did not affect its activation of BDNF/TrkB signaling.CONCLUSIONS:EA at the single acupoints Baihui(GV20),Shenmen(HT7),or Sanyinjiao(SP6)had an ameliorating effect on the spatial learning and memory deficits induced by insomnia.EA at combined acupoints exerted a synergistic effect on the improvements in spatial learning and memory impairment in rats with insomnia by upregulating the hippocampal PKA/CREB and BDNF/TrkB signaling,facilitating neurogenesis,and inhibiting neuronal apoptosis.These findings indicate that EA at combined acupoints[(Baihui(GV20),Shenmen(HT7),and Sanyinjiao(SP6)]achieves a more pronounced regulation of hippocampal neuroplasticity than EA at single acupoints,which may partly explain the underlying mechanisms by which EA at combined acupoints exerts a better ameliorative effect on the cognitive dysfunction caused by insomnia.

Acupoints combination correlates with activation of cerebral areas A functional MRI study

Acupoint combination is a method used for acupoint treatment of patients. Traditionally, acupoints are matched along the meridian distribution, which is a common rule in clinical practice, but the underlying mechanism remains unclear. Cerebral scans with functional magnetic resonance imaging （fMRI） have been used in the study of acupuncture and acupoint specifically. In this study, fMRI was used to detect the activation of the brain areas under different acupoints, matched along different meridians, to elucidate the acupoint combination via a modern medical approach. Forty healthy volunteers were randomly divided into the following groups： Waiguan point （SJ 5）, Waiguan （SJ 5） ＋ Zhigou （SJ 6） （2 acupoints come from the same meridian）, Waiguan （SJ 5） ＋ Neiguan （PC 6） （2 acupoints come from 2 meridians with the relationship of interior-exterior）, Waiguan （SJ 5） ＋ Yanglingquan （GB 34） （2 acupoints come from 2 meridians with the same name-Shaoyang Meridian）, and sham point groups （needling in different points on the right hand）. A real-time cerebral fMRI scan was simultaneously performed. The cerebral activation rate, and the number and strength of different regions of interest were compared among the groups. The fMRI cerebral imaging confirmed that there were some differences in the activation of cerebral areas by the needlings in SJ 5, and in combination with other acupoints. Needling at SJ 5 alone greatly activated the right cerebellum, while needling at both SJ 5 and different co-needling points activated different cerebral functional areas.

Cerebral mechanism of puncturing at He-Mu point combination for functional dyspepsia: study protocol for a randomized controlled parallel trial

Acupuncture is widely used to treat functional dyspepsia with satisfactory outcomes. Combination of the He and Mu acupoints is commonly used and has a synergistic effect on functional dyspepsia; however, its underlying mechanisms remain unclear. Therefore, a randomized controlled parallel clinical trial is currently underway at Chengdu University of Traditional Chinese Medicine, China. This trial is designed to explore the efficacy of and central responses to the He-Mu point combination in patients with functional dyspepsia using functional magnetic resonance imaging. A total of 105 patients with functional dyspepsia will be allocated into 3 groups： the low-He point group（puncturing at Zusanli（ST36））, Mu point group（puncturing at Zhongwan（CV12））, and He-Mu point combination group（puncturing at ST36 and CV12）. Every participant will receive 20 sessions of manual acupuncture for 4 weeks. The needles will be inserted perpendicularly to a depth of 1 to 2 cun. The angle of rotation and twisting will range from 90 to 180 degrees, while lifting and thrusting will range from 0.3 to 0.5 cm. The various manipulations will be performed 60 to 90 times per minute. The needles will remain in place for 30 minutes, during which manipulation will be applied every 10 minutes. Magnetic resonance imaging will be performed before and after 20 sessions of acupuncture. The primary outcome is symptom improvement according to the Chinese version of the Nepean Dyspepsia Index. Secondary outcomes include the Leeds dyspepsia questionnaire, Self-Rating Anxiety Scale, Self-Rating Depression Scale, Beck Anxiety Inventory, Beck Depression Inventory, and visual analogue scale scores before and after 10 and 20 sessions of acupuncture. Needle sensation and adverse events will be used to assess the therapeutic effects. This study will promote more widespread awareness of the benefits of acupoint combination in the clinical setting and provide a further explanation of the neuromechanism by which acupuncture at the He-Mu point combination for functional dyspepsia. Registration： Chinese Clinical Trial Registry, Chi CTR-IOR-15006402.

Analysis of the Effect of Combined DesensitizingAcupoints Therapy in Treating 419 Cases of Allergic Rhinitis Accompanied Asthma

Objective: To explore the effect of combined acupoint desensitizing therapy.Methods: A total of 419 cases of allergic rhinitis accompanied with asthma were treated by combined acupoint desensitizing therapy with positive allergen extract on acupoints of head and upper back region.Results: After 3 courses of treatment, skin test repeated with responding allergen extract showed that the scope of redness and swelling of skin were smaller than those before treatment,P < 0.01. The3H-TdR incorporation lymphocyte transformation rate, acidophil count, IgA, IgG level and E-rosette formation rate of acupoint desensitizing group were different significantly from those of the two control groups (the acupoint 0.85% normal saline injection group and the subcutaneous desensitizing group),P < 0.01 orP < 0.05. Follow-up study for over 3 years showed that the markedly effective rate of the acupoint desensitizing group was 68.73%, the effective rate 29.12% and total effective rate, 97.85%. The effect was higher than that of the two control groups, P<0.01.Conclusion: Combined acupoint desensitizing therapy is valuable and worthy of popularizing in treating patients of allergic rhinitis accompanied asthma.

COMMENTS ON THE STUDY OF ACUPOINT COMBINATION AND REMEDIES FOR TREATMENT OF DIABETES MELLITUS WITH ACUPUNCTURE AND MOXIBUSTION

In the present paper, the author reviews the progresses in the study on acumoxi (acupuncture-moxi-bustion) treatment of diabetes mellitus (DM) from Chinese ancient classical works, Chinese and foreign journals. The therapeutic results reveal that acupuncture treatment of DM is effective in improving DM patients' symptoms via vagal-nerve reflex, regulation of neuroendocrine and immune functions. The author holds that ① correct selection of acupoints in accordance with syndrome differentiation and the related meridians and combined application of acupuncture and Chinese herbal medicines (for oral administration) are the key points for raising the therapeutic effect; and ② acupoint combination and curative methods need to be researched further.

Discussion on “analogical acupoints”

To point out that ＂analogical acupoint＂ is the acupoints with same indication effect by describing the concept of analogical acupoint, as well as its relationship with combination and prescription. ＂Analogical acupoint＂ is the basic element for acupoint combination, while the acupoint combination is the foundation of acupuncture prescription. Finally, to make future prospect for the research thought of ＂analogical acupoint＂.

基于复杂网络技术探讨针灸辅助体外受精-胚胎移植选穴规律

Objective To analyze the rules of acupoint selection in adjuvant interventions for in vitro fertilization-embryo transfer(IVF-ET)with acupuncture and moxibustion,with the use of complex network technology.Methods Articles on clinical trials of acupuncture and moxibustion for IVF-ET were searched in the China National Knowledge Infrastructure(CNKI),Wanfang,VIP,PubMed,and Web of Science databases from inception to January 31,2020.A database of acupoint prescriptions has been established.Descriptive analysis was conducted using Microsoft Excel 2019,association rule analysis was conducted using SPSS Modeler 18.0 Apriori algorithm,clustering analysis of high-frequency acupoints was performed using SPSS 25.0 Ward,and complex network analysis of acupoints was performed by using Gephi 0.9.2.Results A total of 124 clinical trials were included,and 187 acupoint prescriptions were extracted,for a total of 91 acupoints.The total frequency of using these acupoints was 1,296 times,with Sānyīnjiāo(三阴交SP6)used the most frequently.The acupoints were generally located around the conception vessel,spleen meridian,and stomach meridian,and they were mainly distributed in the lower extremities,chest,and abdomen.Considerable consideration was paid to the specific points.The association rule analysis showed that the highest correlation presented between Guānyuán(关元CV4)and Zĭgōng(子宫EX-CA1).Complex network k-core hierarchical analysis discovered that CV4,SP6,Xuèhăi(血海SP10),Hégŭ(合谷LI4),Tàichōng(太冲LR3),Qìhăi(气海CV6),and EX-CA1 were the core acupoints in adjuvant interventions with acupuncture-moxibustion for IVF-ET.Conclusion In adjuvant interventions with acupuncture-moxibustion,acupoints were commonly located around the conception vessel,spleen meridian,and stomach meridian,and the convergent point was particularly used as a specific point.The acupoints were selected to smooth the liver qi,remove stagnation,activate blood circulation,resolve stasis,and benefit the liver and kidney.“CV4→SP6→EX-CA1→ST36”were the core points,and CV4 was the core prescription in adjuvant treatments with acupuncture-moxibustion in IVF-ET.

Influence of different acupoint combinations on immediate effect of surface electromyography of patients with cervical spondylosis

Objective To observe the influence of different acupoint combinations on immediate effect of surface electromyography of patients with cervical spondylosis, and to explore the interactions and laws among different acupoint combinations. Methods Acupuncture in three kinds of different acupoint combinations was conducted on 90 patients with cervical spondylosis（three groups）： group A [distal point selection group： Kūnlún（昆仑 BL 60） and Hòuxī（后溪 SI 3）]; group B [local point selection group： Fēngchí（风池 GB 20） and Tiānzhù（天柱 BL 10）]; group C（distal and local point selection group： BL 60, SI 3, GB 20 and BL 10）. Self control before and after treatment was adopted to observe the mean value of surface electromyography（SEMG） amplitude, to measure the mean values of integrated electromyography（IEMG） and electromyography root mean square（RMS）, and to calculate the variation rate of electromyography amplitude of trapezius on the affected side of patients before and after acupuncture. The differences of influences of different acupoint combinations on immediate effect of surface electromyography were compared intra-group, and the differences among the three groups after acupuncture were also compared. Results According to the intragroup comparison before and after acupuncture, the differences of mean value of electromyography amplitude, variation rate of electromyography amplitude, IEMG and RMS were both statistically significant（all P〈0.05）. According to the inter-group comparison after acupuncture, the mean value of electromyography amplitude, variation rate of electromyography amplitude, IEMG and RMS varied in different degrees, however, the differences were not significant（all P〉0.05）; there was no significant difference in the total effective rate among the three groups（P〉0.05）. Conclusion Acupuncture treatment in different acupoint combinations can increase IEMG and RMS and reduce mean value of electromyography amplitude and variation rate of electromyography amplitude, enhance cervical vertebral stability and active contractility of muscle fiber, and improve the fatigue resistance of neck flexion; while, the therapeutic effect of acupuncture on cervical spondylosis has nothing to do with the distance or the number of selected acupoint.

The explorationon on the characteristics of acupoint selection and the rule of acupoint combination in treatment of insomnia with acupuncture and moxibustion:Complex network analysis

Objective:To analyze the rule of acupoint combination of insomnia treated with modern acupuncturemoxibustion with complex network technology and further reveal the internal characteristics of acupoint combination.Methods:Using computer retrieval,the relevant clinical trials of acupuncture and moxibustion in treatment of insomnia were searched from China National knowledge Infrastructure(CNKI),Wanfang Data Knowledge Service Platform(Wanfang),VIP Chinese Journal Service Platform(VIP) and Pubmed Database in recent 5 years.The articles were screened according to the inclusion and exclusion criteria,and then the database was set up and the acupoint prescriptions of acupuncture and moxibustion were extracted.Using Excel 2016 software,the data were processed and the frequency analysis was conducted.With SPSS Modeler 18.0,the association rules were analyzed.Using Gephi 0.9.2,the community analysis and complex network analysis were conducted.Results:Finally,766 articles were eligible and 1276 acupoint prescriptions were extracted with 186 acupoints involved.The acupoints with the highest frequency of use were Shénmén(神门 HT7),Bǎihuì(百会GV20) and Sānyīnjiāo(三阴交SP6).The meridians with the highest frequency were bladder meridian and the governor vessel.The acupoints located on the head and foot were mostly selected.The specific points involved were the crossing points,five-shu points and yuan-source points.The main core paired points referred to HT7 and SP6,HT7 and GV20 as well as HT7 and Nèiguān(内关PC6).The meridians with the highest confidence level appeared among heart meridian of hand-shaoyin,spleen meridian of foot-taiyin and kidney meridian of foot-shaoyin.The modular analysis of complex network obtained 4 core communities and topology analysis obtained 35 core points.The main prescription was composed of HT7,GV20,SP6,Sìshéncōng(四神聪EX-HN1),PC6,Tàixī(太溪KI3),Zúsānlǐ(足三里ST36),Tàichōng(太冲LR3),Anmián(安眠EX-HN18),Yìntáng(印堂EX-HN3),Zhàohǎi(照海KI6),Shēnmài(申脉BL62) and Fēngchí(风池 GB20).Conclusion:Acupuncture-moxibustion therapy focuses on regulating the mind/spirit of the heart and brain,as well as of five zang organs.The general treatment principles are regaining consciousness and opening the orifice,replenishing yin and reducing yang,nourishing the heart and tranquilizing.The supplementary points are mostly the combination of distal and nearby points and the combination of the acupoints located in the upper and the lower parts of the body.The back-shu points and the front-mu points are generally used,while the crossing point as the specific point is especially applied.All of these summaries provide the reference and guidance for clinical application and scientific research.

Two Sets of Acupoint Combination of Similar Functions Engage Shared Neural Representation:A Functional Magnetic Resonance Imaging Study

Objective： To investigate whether the neural representations underlying alternating two acupoint combinations （ACs） are the same or not. Methods： In this functional magnetic resonance imaging study, two sets of analgesia ACs were utilized, including Waiguan （TE5） and Qiuxu （GB40） for Group A, and Neiguan （PC6） and Taichong （LR3） for Group B, which are the most commonly adopted in clinical treatment. Each group had 20 healthy subjects. An experinlental design was proposed, which consisted of a pre-needling resting phase, a needling phase and a post-needling resting phase. This paradigm optimally mimics the clinical protocol as well as focuses on both the stimulation and the resting periods. The results were subjected to general linear model analysis, conjunction analysis and the functional connectivity analysis. Results： The rostral anterior cingulated cortex was engaged in the initiative period of the acupuncture effect in both groups, and it was chosen as the seed region for the functional connectivity analysis for the following resting period. The results showed that several shared brain regions were involved in both groups, in particular the insula, amygdala and hypothalamus. Moreover, significant differences were located at the posterior cingulated cortex as revealed by a two sample t-test （P〈0.05, corrected）. Other regions showed no significant differences. This finding was further supported by the spatial correlation analysis that the two groups were significantly correlated （r=0.51, P〈0.01）. Conclusion： This preliminary research helps us understand the neurophysiological mechanisms of acupuncture when following clinical guidelines on ACs, as well as provides an important opportunity to develop better treatment strategies for reducing, or even preventing pain.

Analysis on the rules of acupoint combination in treatment of pseudobulbar palsy based on co-occurrence relationship

Objective:To explore the rules of acupoint combination in acupuncture treatment of post-stroke pseudobulbar palsy(PBP),based on acupuncture prescriptions retrieved from literature and using complex network analysis.Methods:The articles were searched from China National Knowledge Infrastructure(CNKI),Wanfang and VIP databases as the source of data.The eligible articles were selected in accordance with inclusion and exclusion criteria.The relevant data were extracted to set up the acupoint prescription database in acupuncture treatment of PBP.By using co-occurrence relationship in acupoint prescriptions,the core acupoints and the combination rules were analyzed in acupuncture treatment of PBP.Results:A total of 194 articles were eligible finally,with 202 acupoint prescriptions extracted.19 core acupoints were collected in total,i.e.Liánquán(廉泉CV23),Fēngchí(风池GB20),Bǎihuì(百会GV20),Jīnjīn(金津EX-HN12),Yùyè(玉液EX-HN13),Fēngfǔ(风府GV16),Yǎmén(哑门GV15),Shuǐgōu(水沟GV26),Nèiguān(内关PC6),Fēnglóng(丰隆ST40),Wángǔ(完骨GB12),Sānyīnjiāo(三阴交SP16),Yìfēng(翳风TE17),Tōnglǐ(通里HT5),Tàichōng(太冲LR3),Hégǔ(合谷LI4),Hǎiquán(海泉EX-HN11),Jùquán(聚泉EX-HN10)and Yìntáng(印堂EX-HN3).The core acupoint groups were CV23-GB20,EX-HN12-EX-HN13 and GV26-PC6-SP6.Acupoints were mostly selected from governor vessel.The methods of acupoint combination included the combination of distal and nearby points,and the combination of the acupoints located in the front and on the back.Conclusions:In treatment of PBP with acupuncture,biaoben(manifestation and root cause)theory is emphasized,the methods for dispelling wind,resolving phlegm,regaining consciousness,and opening orifices are recommended.Moreover,the attentions are paid on spirit regulation,holistic adjustment,and syndrome differentiation in treatment.

Comparative study of ancient and modern literature for Láogōng(劳宫PC8)in the indications and combination rules

Objective:To explore the clinical application rules of Láogōng(劳宫PC8)by analyzing the comparison and contrast of the practice with this acupoint in ancient times and in present.Methods:Relevant literature before October 1,1949 was selected from Chinese Medical Code(Fifth Edition)and Compilation of Moden Chinese Medicine Journals and literature published after October 1,1949 was screened from China National knowledge Infrastructure(CNIK),Wanfang Data Knowledge Service Platform(Wanfang),VIP Chinese Journal Service Platform(VIP),Chinese BioMedine Database(CBM),Pubmed Database,and Web of Science.After screening,SQL Server database was established.The complex network analysis was conducted by using Gephi and the cluster analysis was performed by SPSS Statistics.Results:Before October 1,1949,Lráogōng(劳宫PC8),on a single use or with a match of Dàlíng(大陵PC7),Guānyuán(关元CV4),and Zúsānlǐ(足三里ST36),was mainly used for treating ozostomia and edema due to pregnancy.However,Láogōng(劳宫PC8),on a single use or with a match of Yǒngquán(涌泉KI1),Hégǔ(合谷L14)and Nèiguān(内关PC6)was commonly for the treatment of toothache and the sequelae after wind stroke after October 1 st,1949.Conclusion:Láogōng(劳宫PC8)is mainly used to treat local disorders or diseases pertaining to the pericardium meridian.The single-point therapy was commonly applied before October 1 st,1949,while a combination of other points is more common afterwards and the scope of indication expands,with its application for psychiatry disorders,pain diseases and emergent diseases.Acupoints on the same meridian of Láogōng(劳宫PC8),ying-spring points,the back-shu points and combination between and the upper and the lower are dominated in the selection of supplementary points.The supplementary acupoints with the highest frequency of use were specific acupoints,including five-shu points,yuan-source points,front-mu points,etc。