Discovery of Acupoints and Combinations with Potential to Treat Vascular Dementia: A Data ...

13 Pages·2015·1.6 MB·English

Hindawi Publishing Corporation
Evidence-Based Complementary and Alternative Medicine
Volume 2015, Article ID 310591, 12 pages
http://dx.doi.org/10.1155/2015/310591
Research Article
Discovery of Acupoints and Combinations with Potential to
Treat Vascular Dementia: A Data Mining Analysis
ShuweiFeng,1YulanRen,1ShilinFan,2MinyuWang,1TianxiaoSun,1
FangZeng,1PingLi,2andFanrongLiang1
1ChengduUniversityofTraditionalChineseMedicine,Chengdu,Sichuan610075,China
2SouthwestPetroleumUniversity,Chengdu,Sichuan610500,China
CorrespondenceshouldbeaddressedtoPingLi;[email protected];[email protected]
Received18December2014;Revised16February2015;Accepted30April2015
AcademicEditor:ZhixiuLin
Copyright©2015ShuweiFengetal.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense,
whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited.
The prevalence of vascular dementia (VaD) is high among the elderly. Acupuncture, a popular therapeutic method in China,
canimprovememory,orientation,calculation,andself-managingabilityinVaDpatients.However,inclinicalacupunctureand
acupunctureresearch,theselectionofacupointstotreatVaDremainschallenging.Thisstudyaimedtodiscoveracupointsand
acupointcombinationswithpotentialforVaDbasedondatamining.Afterdatabasesearchingandscreeningforarticlesonclinical
trialsevaluatingtheeffectsofacupunctureonVaD,238acupunctureprescriptionswereincludedforfurtheranalysis.Baihui(GV
20),Sishencong(EX-HN1),Fengchi(GB20),Shuigou(GV26),andShenting(GV24)appearedmostfrequentlyinthemodern
literatureandarepotentialacupointsforVaD.CombinationsbetweenBaihui(GV20),Sishencong(EX-HN1),Fengchi(GB20),
Shenting (GV 24), Shuigou (GV 26), and Zusanli (ST 36) were most frequent and represent potential combinations for VaD
treatment.TheseresultsprovideareferencefortheselectionandcombinationofacupointstotreatVaDinclinicalacupuncture
andacupunctureresearch.
1.Introduction Vasculardementia(VaD)referstocognitiveimpairment
caused by changes in theblood circulationofthebrain[5].
Theselectionofacupointsplaysacriticalroleinthetherapeu-
Its clinical manifestations include confusion or short-term
tic effects of acupuncture. However, the selection of proper
memoryproblems,wandering,gettinglostinfamiliarplaces,
acupoints remains challenging, contributing to the limited
walking with rapid and shuffling steps, losing bladder or
therapeutic effects and application of acupuncture. Data
bowel control, laughing or crying inappropriately, difficulty
mining has been used to discover potential acupoints from
infollowinginstructions,andproblemwithcountingmoney
theexpansiverelevantliterature.Thismethodhasbeenused
andconductingmonetarytransactions.Atthelatestage,VaD
tosuggestacupointsontheShaoyangMeridianformigraine
patients may have severe impairment of basic activities of
treatmentbasedontheirhighfrequencyintheliterature[1].
dailylivingandlackthecapacitytomakeappropriatedeci-
Basedontheresultsofdatamining,asubsequentclinicaltrial
sions regarding their choices and preferences [6]. A recent
confirmed that acupuncture was effective for the treatment
of migraine and that acupoints on the Shaoyang Meridian population-basedsurveyreportedthattheprevalenceofVaD
were more effective than acupoints on other meridians [2]. among individuals aged 65 years and older was 1.5% [7]. It
DatamininghasalsobeenusedtodiscoverpotentialChinese hasbeenpredictedthatdementiawillaffect80millionpeople
herbs for the effective treatment of specific diseases [3, 4]. worldwide by 2040 [8]. The annual cost of care per patient
Theseresultssupportdataminingasapromisingmethodto is estimated to be US$17,000–55,200 for severe dementia,
discoveracupointswithpotentialfortreatingdiseases. placingaheavyeconomicburdenonfamiliesandsociety[9].
2 Evidence-BasedComplementaryandAlternativeMedicine
Acupuncture, a primary therapeutic method in tradi-
tional Chinese medicine (TCM), can improve memory, 2121 records identified through database searching
orientation, calculation, and self-managing ability in VaD
(CNKI: 892, CBM: 1084, PubMed: 145)
patients [10–12]. The therapeutic effects of acupuncture
are achieved via multiple pathways, including antioxidative
effects, antiapoptotic effects, and neurotrophic effects [11,
13–15]. However, acupoint selection remains a challenge in
the use of acupuncture to treat VaD. According to our
preliminary statistics, more than 100 acupoints distributed
in13meridianshavebeenrecordedinthemodernliterature 238 acupuncture prescriptions included in data
for the treatment of VaD. The most effective acupoints for
mining and network analysis after screening
the treatment of VaD and the selection of acupoints for
combination remain to be elucidated, representing a major
limitationforclinicaltherapeuticeffectsandtheapplication
ofacupunctureforVaD.
To shed some light on the selection of acupoints and
acupointcombinationstotreatVaDinclinicalacupuncture
and acupuncture research, this study aimed to discover Data preprocessing: extraction of information about
acupointsandacupointcombinationsthathavepotentialto
titles, journals, interventions, and main acupoints
treatVaDviadatamining.
and standardization of acupoint names
2.MaterialsandMethods
Theflowofinformationthroughthevariousphasesofdata
miningisillustratedinFigure1.
2.1.InclusionCriteriaforConsideringAcupoint
Data processing: analysis of frequencies of
PrescriptionsforDataMining
acupoints and meridians, confidence of acupoint
2.1.1.TypesofStudies. Clinicaltrialsevaluatingtheeffectof
TCMacupuncturewithorwithoutrandomizationmethods
combination, and network properties
were included. Trials with or without controls were also
included. The control interventions included no treatment,
Figure1:Flowofinformationthroughthedifferentphasesofdata
sham acupuncture, Western medicine, TCM herbs, non-
mining.
traditional acupuncture, and TCM acupuncture containing
anotheracupointprescriptionwhichisdifferentfromtheone
inobservationgroup.LanguagewasrestrictedtoChineseand
Westernmedicine,TCMherbs,nontraditionalacupuncture,
English.
and TCM acupuncture containing another acupoint pre-
scription which is different from the one in observation
2.1.2. Types of Participants. Clinical trials involving adult
group. If the studies compared the therapeutic effects of
participantsdiagnosedwithVaDwereincluded.
differentacupointprescriptions,themosteffectiveacupoint
prescriptionwasincluded.
2.1.3. Types of Interventions. Clinical trials evaluating TCM
acupuncture were included. Acupuncture can be used
alone or in combination with other types of interventions. 2.2.ExclusionCriteria
TCMacupunctureinvolvesinsertingneedlesintotraditional
meridian acupoints and extraordinary acupoints. Electrical 2.2.1. Types of Studies. Case reports, reviews, systematic
stimulation of the needles may be used. Trials using moxi- reviews,andmeta-analyseswereexcluded.
bustionaloneorasacointerventionwithacupuncturewere
alsoincluded. 2.2.2.TypesofParticipants. Trialsevaluatingthetherapeutic
effect of acupuncture for Alzheimer’s disease, traumatic
2.1.4. Effectiveness of Acupoint Prescriptions. Acupoint pre- dementia, and other subtypes of dementia were excluded.
scriptions for the disease and not particular syndromes Studiesonanimalswerealsoexcluded.
of VaD were included. There should be statistical differ-
ences in symptoms between before and after acupuncture. 2.2.3. Types of Interventions. Trials stimulating Ashi points
In a controlled trial, patients treated with acupuncture alonewereexcluded. Trialsofdryneedlingortriggerpoint
aloneorincombinationshouldreceivegreaterbenefitthan therapy, therapies that are based on principles of western
patientswhodonotreceiveacupuncturetherapy.Thecontrol anatomy and physiology, were excluded. Trials of laser
interventions included no treatment, sham acupuncture, acupunctureandnoninvasiveelectrostimulation(e.g.,using
Evidence-BasedComplementaryandAlternativeMedicine 3
electrodesontheskinratherthanneedlesormoxibustionto and support of acupoint combinations. According to the
stimulatetheacupoints)wereexcludedtolimitthefocusto definition of association rules mining [18], the following
TCM acupuncture. Trials evaluating acupressure, a form of canbeastatementofassociationrulesminingforacupoint
massage,wereexcludedaswell.Finally,trialsofmicropunc- combination. Let 𝐼 = {𝑖1,𝑖2,...,𝑖𝑚} be a set of acupoints.
turewereexcludedbecausemicropunctureisanontraditional Let𝐷beasetofacupointprescriptions,whereeachacupoint
acupuncturepracticethatisbased ontheprinciplethatthe prescription𝑇isasetofacupointssuchthat𝑇⊆𝐼.Associated
head(orear,nose,eye,abdomen,ankle,etc.)isamicrosystem witheachacupointprescriptionisauniqueidentifier,called
oftheentirebody. TID. An acupoint prescription 𝑇 contains 𝑋, a set of some
acupointsin𝐼,if𝑋 ⊆ 𝑇.Therule𝑋-𝑌hassupport 𝑠inthe
2.2.4. Effectiveness of Acupoint Prescriptions. Acupoint pre- acupointprescriptionset𝐷if𝑠%ofacupointprescriptionsin
scriptionsforaparticularsyndromeofVaDwereexcluded. 𝐷contain𝑋∪𝑌.
Acupoint prescriptions with no statistical improvement of
symptomswerealsoexcluded.Whenthetherapeuticeffects 2.6.3.MeasurementofNetworkProperties.Communitystruc-
ofdifferentacupointprescriptionswerecomparedinastudy, ture is a common characteristic of complex networks and
allacupointprescriptionsexceptthemosteffectiveonewere is characterized by more dense internal connections within
excluded. groups of nodes than with the rest of the network. In this
study, a hierarchical agglomeration was adopted to detect
2.3.SearchingMethodsforIdentificationofStudies communitystructureaccordingtoClausetetal.[19].Wealso
focusedoninvestigatingthesetofthemostinfluentialnodes
2.3.1.DataSources. PubMed(http://www.pubmed.com(1966
inacupointnetworksofVaD,definedasthenodeswiththe
to2012)),theChineseBioMedicineDatabase(CBM)(http:// highest 𝑘-core value [20]. The 𝑘-core method is predomi-
www.sinomed.ac.cn (1978 to 2012)), and China National
nantly used in analyzing social networks. We employed the
KnowledgeInfrastructure(CNKI)(http://www.cnki.net(1912 𝑘-coremethodtoobtainthecoresofdifferentacupoints.The
to2012))weresearchedformodernliteratureonacupuncture
𝑘-coremethodwasimplementedasfollows.First,all1-degree
treatmentforVaD.
nodeswereremoved,andthenodeswerefurtherpruneduntil
no 1-degree nodes remained. The remaining nodes formed
2.3.2. Searching Strategy. The searching strategy used the
the 2-core node set. The pruning process was repeated in a
followingkeywords:(I)“acupuncture”OR“electroacupunc-
similar manner for other nodes in the network assigned to
ture” OR “moxibustion” OR “meridian” OR “acupoint”; (II)
thecorrespondingcores(denotedby𝑘s).Thenodeswiththe
“dementia”OR“vasculardementia”OR“Alzheimer’sdisease.”
largest 𝑘-core value were defined as the network core. The
The searching strategy included literature on acupuncture
treatmentforAlzheimer’sdisease(AD)becausethemodern degree of each acupoint was also analyzed to measure the
literatureonacupunctureforVaDoverlapswiththatonAD. involvementofthenodeinthenetwork.Thedegreerefersto
thenumberofnodestowhichafocalnodeisconnected[21].
2.4.DataCollection. Tworeviewersindependentlyscreened Betweennesscentralitywasalsousedtoanalyzeanacupoint’s
the title and abstract of every record retrieved from the centralityinthenetwork.Centralityisanimportantconcept
literature searches. All potentially relevant articles were for the analysis of networks, and betweenness centrality is
investigated as full text in English or Chinese. In cases of oneofthemostprominentmeasuresofcentrality.Itisused
disagreement, a trial was included or excluded based on to measure the degree to which a node is in a position of
discussionbetweenthetworeviewersorafterathirdreviewer brokerage by summing up the fractions of shortest paths
reviewed the information. For duplicate publications, the betweenotherpairsofverticesthatpassthroughit[22].
finalpublicationwasused.
3.Results
2.5. Data Preprocessing. Information about titles, journals,
interventions, and main acupoints was extracted using the 3.1. Overall Profile of Acupuncture Prescriptions. Database
self-establishedDataExcavationPlatformofAcupointSpeci- searching identified 892 records in CNKI, 1084 records in
ficity for data mining. Because acupoints have aliases, the CBM, and 145 records in PubMed. After screening, 238
names of acupoints were standardized according to Funda- acupuncture prescriptions in 238 articles were included.
mentalsofAcupuncture[16]. Amongthe238trials,185arecontrolledclinicaltrials(CCTs),
whiletheother53trialshavenocontrols.Thewholeviewon
thestudyqualityofthe185CCTswereshowninFigure2.
2.6.DataProcessing
2.6.1.FrequenciesofAcupoints. Thefrequenciesofacupoints, 3.2.FrequenciesofAcupointsandMeridians. Approximately
meridians, and acupoints on different body parts were 109 meridian-acupoints distributed over 13 meridians and
analyzed using the Data Excavation Platform of Acupoint 7 extraordinary acupoints have been recorded for 1400 and
Specificity. 133times,respectively,inmodernliteratureonacupuncture
treatment for VaD. The most frequently used meridian
2.6.2.AssociationRulesMining.AprioriAlgorithmforassocia- was the Governor Meridian (477 times). Other frequently
tionrulesmining[17]wasadoptedtoanalyzethefrequencies used meridians included the Gallbladder Meridian of Foot
4 Evidence-BasedComplementaryandAlternativeMedicine
Random sequence generation
Allocation concealment
Blinding of participants and personnel
Blinding of outcome assessment
Incomplete outcome data
Selective reporting
Another bias
0 20 40 60 80 100
(%)
Low risk
Unclear risk
High risk
Figure2:Wholeviewonthestudyqualityofthe185CCTs.
200
180
160
140
120
100
80
60
40
20
0
0) 1) 0) 6) 4) 6) 6) 6) 7) 3) 3) 3) 0) 3) 4) 9) 6) 4) 1) 3)
2Baihui (GV hencong (EX-HN 2Fengchi (GB 2Shuigou (GV 2Shenting (GV Neiguan (PC 3Zusanli (ST Sanyinjiao (SP Shenmen (HT Taixi (KI 1Benshen (GB 2Shenshu (BL 4Fenglong (ST Taichong (LV 1Dazhui (GV 3Xuanzhong (GB 1Fengfu (GV Hegu (LI 1Quchi (LI Yintang (EX-HN
Sis
Frequency
Figure3:The20mostfrequentacupointsandtheirfrequencies.
Shaoyang and the Stomach Meridian of Foot Yangming, times),upperlimbs(214times),backandlumbar(127times),
which were reported for 218 and 124 times, respectively. andchestandabdomen(43times)(Figures4(a)and4(b)).
Extraordinary acupoints were also frequently used. Baihui
(GV20),Sishencong(EX-HN1),Fengchi(GB20),Shuigou 3.4.FrequenciesofSpecificAcupoints. Specificacupointsrep-
(GV 26), and Shenting (GV 24), which were among the resented78ofthe116acupoints(67.24%).Specificacupoints
top five acupoints in frequency, were recorded for 176, 124, havebeenused1292times,representing84.28%ofthetotal
93, 86, and 84 times, respectively. The frequencies of each frequencyofallacupoints(Figures4(c)and4(d)).
meridianandacupointareshowninTable1.Thetwentymost
frequentlyusedacupointsareshowninFigure3. 3.5.FrequenciesandSupportofAcupointCombinations. Acu-
point combinations between Baihui (GV 20), Sishencong
3.3. Frequencies of Acupoints on Different Body Parts. Acu- (EX-HN 1), Fengchi (GB 20), Shenting (GV 24), Shuigou
pointsonthehead,face,andneckwereusedmostfrequently, (GV 26), and Zusanli (ST 36) were used most frequently.
with a total number of 42 acupoints and a total frequency The15mostfrequentlyusedacupointcombinationsandtheir
of766times,followedbyacupointsonthelowerlimbs(383 supportandconfidenceareshowninTable2.
Evidence-BasedComplementaryandAlternativeMedicine 5
Table1:StatisticsofmeridiansandacupointsinthemodernliteratureonacupuncturetreatmentforVaD. AcupointsandtheirfrequenciesmberMeridianFrequencyNumberofacupointsBaihui(GV20)176,Shuigou(GV26)86,Shenting(GV24)84,Dazhui(GV14)27,Fengfu(GV16)23,Yintang(EX-HN3)16,Naohu(GV17)13,Shangxing(GV23)11,Mingmen(GV4)8,Yamen(GV15)5,Qiangjian(GV18)5,Qianding(GV21)4,Yaoyangguan(GV3)3,Zhiyang(GV9)3,Jinsuo(GV8)2,GV47726Shendao(GV11)1,Zhongshu(GV7)1,Taodao(GV13)1,Lingtai(GV10)1,Changqiang(GV1)1,Xuanshu(GV5)1,Yaoshu(GV2)1,Shenzhu(GV12)1,Jizhong(GV6)1,Houding(GV19)1,Xinhui(GV22)1Fengchi(GB20)93,Benshen(GB13)47,Xuanzhong(GB39)24,Shuaigu(GB8)7,Wangu(GB12)6,Toulinqi(GB15)6,Qubin(GB7)5,Xuanli(GB6)4,Naokong(GB19)4,Zuqiaoyin(GB44)3,YanglingquanGB21820(GB34)3,Yangbai(GB14)3,Hanyan(GB4)2,Qiuxu(GB40)2,Fengshi(GB31)2,Touqiaoyin(GB11)2,Xuanlu(GB5)2,Muchuang(GB16)1,Zhengying(GB17)1,Zhongdu(GB32)1Sishencong(EX-HN1)123,Taiyang(EX-HN5)4,Wailaogong(EX-UE8)2,Shiqizhui(EX-B8)1,BaxieEX-HN1337(EX-UE9)1,Anmian(EX-HN22)1,Yiming(EX-HN14)1Zusanli(ST36)72,Fenglong(ST40)40,Touwei(ST8)6,Lidui(ST45)2,Sibai(ST2)2,Futu(ST32)1,ST1247Renying(ST9)1Shenshu(BL23)43,Ganshu(BL18)12,Tianzhu(BL10)10,Pishu(BL20)8,Feiyang(BL58)8,Geshu(BL17)7,Xinshu(BL15)4,Zhiyin(BL67)2,Kunlun(BL60)2,Yuzhen(BL9)2,Tongtian(BL7)1,Chengjin(BL56)BL103151,Dazhu(BL11)1,Weizhong(BL40)1,Qucha(BL4)1Sanyinjiao(SP6)71,Xuehai(SP10)14,Taibai(SP3)8,Yinbai(SP1)2,Yinlingquan(SP9)1SP965Neiguan(PC6)73,Zhongchong(PC9)4,Daling(PC7)4,Jianshi(PC5)3,Laogong(PC8)2PC865Taixi(KI3)57,Dazhong(KI4)12,Yongquan(KI1)10,Zhaohai(KI6)8,Rangu(KI2)2KI835Shenmen(HT7)62,Shaochong(HT9)3,Jiquan(HT1)2HT673Hegu(LI4)20,Quchi(LI11)18,Shangyang(LI1)2,Shousanli(LI10)2,Binao(LI14)1,Jianyu(LI15)1,LI457Yingxiang(LI20)1Qihai(CV6)11,Zhongwan(CV12)10,Guanyuan(CV4)9,Danzhong(CV17)9,Shenque(CV8)4CV435Taichong(LV3)37,Dadun(LV1)3LV402Waiguan(TE5)6,Guanchong(TE1)2,Sizhukong(TE23)1,Jiaosun(TE20)1,Sidu(TE9)1TE115Shaoshang(LU11)3,Lieque(LU7)1LU42Shaoze(SI1)2,Yanggu(SI5)1SI32Total1,533116 GovernorMeridian;GB,GallbladderMeridianofFootShaoyang;EX-HN,extraordinaryacupoint;ST,StomachMeridianofFootYangming;BL,BladderMeridianofFootTaiyang;SP,SpleenMeridianofFootn;PC,PericardiumMeridianofHandJueyin;KI,KidneyMeridianofFootShaoyin;HT,HeartMeridianofHandShaoyin;CV,ConceptionVessel;LI,LargeIntestineMeridianofHandYangming;LV,LiverdianofFootJueyin;TE,TripleEnergizerofHandShaoyang;LU,LungMeridianofHandTaiyin;SI,SmallIntestineofHandTaiyang.Frequenciesofmeridiansrefertothetotalfrequenciesofacupointsonthemeridian.Numberofacupointsrefertothetotalnumberofacupointsonthesamemeridian.
Nu 1 2 3 4 5 6789 10 111213141516 GV,TaiyiMerisame
6 Evidence-BasedComplementaryandAlternativeMedicine
Table2:Statisticsofthe15mostfrequentlyusedacupointcombinationsinthetreatmentofVaD.
Number Acupointcombination Frequency Support(%)
1 Baihui(GV20),Sishencong(EX-HN1) 98 41.18
2 Baihui(GV20),Fengchi(GB20) 81 34.03
3 Baihui(GV20),Shuigou(GV26) 72 29.83
4 Baihui(GV20),Shenting(GV24) 70 29.41
5 Baihui(GV20),Zusanli(ST36) 62 26.05
6 Sishencong(EX-HN1),Fengchi(GB20) 60 25.21
7 Baihui(GV20),Sanyinjiao(SP6) 57 23.95
8 Baihui(GV20),Neiguan(PC6) 54 22.69
9 Sishencong(EX-HN1),Shuigou(GV26) 51 21.43
10 Sishencong(EX-HN1),Baihui(GV20),Fengchi(GB20) 51 21.43
11 Baihui(GV20),Shenmen(HT7) 51 21.43
12 Sishencong(EX-HN1),Shenting(GV24) 49 20.59
13 Sishencong(EX-HN1),Neiguan(PC6) 46 19.33
14 Baihui(GV20),Taixi(KI3) 46 19.33
15 Sishencong(EX-HN1),Baihui(GV20),Shuigou(GV26) 43 18.07
Supportreferstothepercentageofacupointprescriptionscontainingtheacupointcombination.
3.6. Community Structure. Community detection resulted (GV24)arepotentialacupointsfortreatingVaD.Intermsof
in the division of the 116 acupoints into 5 communities. meridian,acupointsontheGovernorMeridianhavepoten-
Nodesofthesamecolorbelongtothesamecommunity.The tialfortreatingVaD.Fromtheperspectiveofcombinations,
communitystructureisshowninFigure5(a). combinations between such acupoints as Baihui (GV 20),
Sishencong(EX-HN1),Fengchi(GB20),Shenting(GV24),
3.7.Acupoint𝐾-CoreNetwork. Thelargest𝑘-corevaluewas Shuigou (GV 26), and Zusanli (ST 36) have potential for
19.Atthisvalue,therewere28nodes,correspondingtoHegu treating VaD. In addition, acupoints on the head, face, and
(LI 4), Quchi (LI 11), Zusanli (ST 36), Fenglong (ST 40), neck have more potential for VaD than acupoints on other
Sanyinjiao(SP6),Xuehai(SP10),Shenmen(HT7),Tianzhu regions of the body. Specific acupoints have more potential
(BL 10), Xinshu (BL 15), Ganshu (BL 18), Shenshu (BL 23), thannonspecificacupoints.Specificacupoints,withspecific
Taixi(KI3),Dazhong(KI4),Neiguan(PC6),Benshen(GB
names,areagroupofacupointsonfourteenmeridianswith
13),Fengchi(GB20),Xuanzhong(GB39),Taichong(LV3),
specifictherapeuticeffects.Therearetentypesofspecificacu-
Mingmen(GV4),Dazhui(GV14),Yamen(GV15),Fengfu
points, Five-Shu acupoints, Yuan-Primary acupoints, Luo-
(GV16),Baihui(GV20),Shenting(GV24),Shuigou(GV26),
Connecting acupoints, Xi-Cleft acupoints, Lower He-Sea
Guanyuan(CV4),Sishencong(EX-HN1),andYintang(EX-
acupoints, Back-Shu acupoints, Front-Mu acupoints, eight
HN3),asshowninFigure5(b).
influential acupoints, eight confluent acupoints connecting
theeightextrameridians,andconvergentacupoints.
3.8. Degree. The top 20 acupoints in degree are shown
Communitydetectiondividedtheacupointsinto5com-
in Figure 6(a). Baihui (GV 20), Sishencong (EX-HN 1),
munities.Acupointswithinthesamecommunityhavesome
Fengchi (GB 20), Shenting (GV 24), and Neiguan (PC 6)
characteristicsincommon.Bluenodes(CommunityA)were
hadthehighestdegrees,withvaluesof89,76,68,67,and65,
respectively. allJing-Wellacupoints.Yellownodes(CommunityB)wereall
acupointsonthefaceandhead.Mostgreennodes(Commu-
3.9.BetweennessCentrality. Thetop20acupointsinbetween- nityC)wereacupointsonthefourlimbs.Mostpurplenodes
ness centrality are shown in Figure 6(b). Yongquan (KI 1), (CommunityD)wereacupointsbelongingtoGovernorVes-
Baihui(GV20),andSishencong(EX-HN1)hadthehighest sel.Mostrednodes(CommunityE)werespecificacupoints
betweennesscentrality. or acupoints with specific therapeutic effects, and only this
community contained Bach-Shu acupoints and acupoints
on the abdomen. Acupoints within the same community
4. Discussion
were more densely connected with each other compared
4.1. Potential Acupoints and Combinations for VaD. In this with acupoints from different communities, indicating that
study, acupoints and combinations with potential for treat- an acupoint was more often used with acupoints within
ing VaD were discovered. These results may provide some thesamecommunitycomparedwithacupointswithinother
reference for the selection of acupoints in treatment for communities.
VaD, which may promote the therapeutic effects in clinical The19-corenetworkindicatedthat28acupoints,includ-
practice.TheresultssuggestthatBaihui(GV20),Sishencong ing Hegu (LI 4), Quchi (LI 11), Zusanli (ST 36), Fenglong
(EX-HN1),Fengchi(GB20),Shuigou(GV26),andShenting (ST40),Sanyinjiao(SP6),Xuehai(SP10),Shenmen(HT7),
Evidence-BasedComplementaryandAlternativeMedicine 7
45 900
40 800
35 700
30 600
25 500
20 400
15 300
10 200
5 100
0 0
Head, face, Lower Upper Back and Chest and Head, face, Lower Upper Back and Chest and
and neck limbs limbs lumbar abdomen and neck limbs limbs lumbar abdomen
Number Frequency
(a) Thenumbersofacupointsindifferentparts (b) Thefrequenciesofacupointsindifferentparts
40 800
35 700
30 600
25 500
20 400
15 300
10 200
5 100
0 0
Convergent acupoint Five-Shu acupoint Yuan-source point Luo-Connecting point Eight influential point Shu-Back point Eight confluent acupoints Front-Mu point Lower He-Sea point Nonspecifc point Convergent acupoint Five-Shu acupoint Yuan-source point Luo-Connecting point Eight influential point Shu-Back point Eight confluent acupoints Front-Mu point Lower He-Sea point Nonspecifc point
Number Frequency
(c) Thenumbersofdifferentkindsofacupoints (d) Thefrequenciesofdifferentkindsofacupoints
Figure4:Thefrequenciesandnumbersofacupointsindifferentbodypartsanddifferenttypesofacupoints.
Tianzhu (BL 10), Xinshu (BL 15), Ganshu (BL 18), Shenshu to 4 different communities, had higher betweenness cen-
(BL 23), Taixi (KI 3), Dazhong (KI 4), Neiguan (PC 6), trality.Yongquan(KI1),whichhadthehighestbetweenness
Benshen (GB 13), Fengchi (GB 20), Xuanzhong (GB 39), centrality,didnothavearelativelyhighdegree.However,it
Taichong(LV3),Mingmen(GV4),Dazhui(GV14),Yamen connectsJing-Wellacupointswithothertypesofacupoints,
(GV15),Fengfu(GV16),Baihui(GV20),Shenting(GV24), resulting in a high betweenness centrality. Acupoints with
Shuigou(GV26),Guanyuan(CV4),Sishencong(EX-HN1), higher betweenness centrality play an important role in
andYintang(EX-HN3)arecoreacupointsinthenetwork. connectingdifferenttypesofacupoints.Jing-Wellacupoints,
Baihui (GV 20), Sishencong (EX-HN 1), Fengchi (GB exceptYongquan(KI1),wereoftenusedwithotherJing-Well
20),Shenting(GV24),andNeiguan(PC6)hadthehighest acupointsonly.Yongquan(KI1)wasnotonlyusedwithother
degrees.Thisresultindicatesthatthese5acupointshavebeen Jing-Well acupoints but also with other types of acupoints,
combinedwithmoreacupointsthanotheracupoints.These such as other types of specific acupoints, nonspecific acu-
acupointshavespecifictherapeuticeffectsonVaD.Therefore, points,andacupointsonotherparts.Thehighbetweenness
theseacupointscanbeusedtogetherwithotheracupointsto centralitysuggestedthatYongquan(KI1)mayhavemultiple
enhancetherapeuticeffects. effectscomparedwithotherJing-Wellacupointsintreatment
Yongquan (KI 1), Baihui (GV 20), Sishencong (EX-HN of VaD. From the perspective of TCM theory, Jing-Well
1), Neiguan (PC 6), and Shenting (GV 24), which belonged acupoints can restore consciousness. Yongquan (KI 1) was
8 Evidence-BasedComplementaryandAlternativeMedicine
GV6
HT1
GV5 GV4
GV9 GV10 TE20
GV14
EX-B8 GV8 SP6
ST2 EX-HN22 BL56 EX-UE9
GV7 GV16
GV19 GV11 TE23
ST32 GB31 GV22
GV26 GV1 BL11
GV12 GV2 GB40 BL10
BL4 GV15 GV13 PC8 LI14 GB34
EX-HN14 GV20 TE9 BL40
GB39 CV6 SP9 ST36 GV3 GB17 BL60 GB32 GB16
LI11
ST9 CV8 LV3 BL18 CV12 LI15 LI10 TE5 LI4
EX-HN1 PC6 LU7 SI5 PC7 GB8 GB5
EX-HN5 BL9
SP3 ST40 EX-UE8 BL20 GB14
KI3 BL17 GB13 GV23 GB15
GV21
CV4 GB20 CV17 KI4 BL23 KI6 HT7 PC5 ST8 EX-HN3 GV17
BL15 SI1 GB19 LI20 GB7
SP10 BL58 SP1 GV24 GB6
GB12 BL7 GB4
KI2 LV1 ST45 KI1 TE1 GB11
GV18
HT9 LI1
GB44 PC9
BL67
LU11
(a) NetworkstructureofacupointsforthetreatmentofVaD
KI4
GV4 GB13
EX-HN3
CV4
GV24 GV16
KI3
GV14
EX-HN1 GB39
ST40
BL23 GV20 PC6
GV26
SP6
GV15
HT7 LI4
GB20
ST36
BL18 LI11
LV3
BL15
BL10 SP10
(b) 19-corenetwork
Figure5:(a)NetworkstructureofacupointsforthetreatmentofVaD.Bluenodes(CommunityA)areallJing-Wellacupoints.Yellownodes
(CommunityB)areallacupointsonthefaceandhead.Mostgreennodes(CommunityC)areacupointsonfourlimbs.Mostpurplenodes
(Community D) are acupoints belonging to Governor Vessel. Most red nodes (Community E) are specific acupoints or acupoints with
specifictherapeuticeffects,andonlythiscommunitycontainsBach-Shuacupointsandacupointsontheabdomen.Acupointswithinthe
samecommunityaremoredenselyconnectedwitheachotherthanacupointsfromdifferentcommunities.(b)19-corenetwork.Thereare28
acupointsinthe19-corenetwork.TheyarecoreacupointsinthetreatmentofVaD.
Evidence-BasedComplementaryandAlternativeMedicine 9
100
90
80
70
60
50
40
30
20
10
0
0 1 0 4 6 6 4 6 6 7 4 3 6 0 3 3 3 0 9 1
GV2 X-HN GB2 GV2 PC SP GV1 GV2 GV1 HT LI KI ST3 ST4 LV GB1 X-HN BL1 GB3 LI 1
E E
Degree
(a) The20acupointswithhighestdegree
0.16
0.14
0.12
0.1
0.08
0.06
0.04
0.02
0
1 0 1 6 6 0 4 4 6 3 7 4 3 6 0 3 0 6 3 9
KI GV2 X-HN PC GV2 GB2 GV2 GV1 SP X-HN HT LI KI GV1 BL1 LV ST4 ST3 GB1 PC
E E
Betweenness centrality
(b) The20acupointswithhighestbetweennesscentrality
Figure6:The20acupointswithhighestdegreeandthe20acupointswithhighestbetweennesscentrality.
also used to tonify kidney in treatment of VaD. Therefore, ElectroacupunctureatBaihui(GV20),Dazhui(GV14),and
Yongquan (KI 1) is used not only with other Jing-Well Shenshu (BL 23) blocks expression of p53 and Noxa in the
acupoints but also with other types of acupoints, such as hippocampal CA1 region of VaD rats [26]. Acupuncture at
othertypesofspecificacupoints,nonspecificacupoints,and Baihui (GV 20) can improve neurogenesis via regulating
acupointsonotherparts. brain-derived neurotrophic factor (BDNF) and cyclic AMP
response element-binding protein (CREB). BDNF, which
4.2.UnderlyingMolecularMechanismoftheAcupointwiththe is essential for synaptic plasticity and is coupled to CREB
MostPotentialtoTreatVaD. Accordingtoourresults,Baihui activation [27], is important for long-term memory storage
(GV 20), which had the highest frequency, has the most [28].CREBisrequiredfortheproliferation,growth,survival,
potentialtotreatVaD.Asystematicreviewandmeta-analysis anddifferentiationofalltypesofcells.Inthebrain,theCREB
alsosuggestedthatBaihui(GV20)isaprincipalacupointfor andCRE-mediatedsystemisinvolvedinmemory,learning,
acuteintracerebralhemorrhage(ICH);inanimalmodelsof synaptic transmission, neuron survival, differentiation, and
acuteICH,therewasnodifferenceinefficacybetweenBaihui axon growth [29]. Acupuncture at Baihui (GV 20) signifi-
(GV20)aloneandBaihui(GV20)plusotheracupoints[23]. cantlyincreasesthelevelsofBDNF[15,30],CREBproteins,
Molecular biology studies have provided insights into CREB mRNA [30], and phosphorylated CREB, the active
themechanismsunderlyingtheeffectsofBaihui(GV20)in form of CREB [15]. The molecular mechanism underlying
VaD treatment, including antioxidant effects, antiapoptotic acupuncture at Baihui (GV 20) also involves cholinergic
effects, neurotrophic effects, reduced blood-brain barrier system regulation. Decreased cholinergic function in the
(BBB) permeability, and regulation of the cholinergic and brain can result in a decline in memory and cognitive
dopaminergic systems. Acupuncture at Baihui (GV 20) in function [31]. Acupuncture at Baihui (GV 20) significantly
combination with other acupoints decreases levels of 8- increasesthelevelsofcholineacetyltransferase(ChAT)and
󸀠
hydroxy-2 -deoxyguanosine,aproductofoxidativedamage restores the expression of choline transporter 1 (CHT1)
toDNAinducedbyfreeradicals,suggestingthatthebenefit and vesicular acetylcholine transporter (VAChT) [30]. The
of acupuncture is partly due to antioxidant effects [11]. dopaminergic system is also involved in the mechanism
AcupunctureexertstherapeuticeffectsonVaDviaantiapop- underlyingthetreatmentofVaDwithacupunctureatBaihui
tosis.Thetumorsuppressorsp53andNoxaareimportantin (GV 20). Dopamine is a key regulator in specific synaptic
regulatingapoptosisandmediatehypoxiccelldeath[24,25]. changes observed at certain stages of learningand memory
10 Evidence-BasedComplementaryandAlternativeMedicine
andofsynapticplasticity[32].AcupunctureatBaihui(GV20) 4.4.SingleAcupointorAcupointCombination.Acupointcom-
increasesdopaminelevelsinchroniccerebralhypoperfusion binations also influence the therapeutic effects of acupunc-
and ischemia-reperfusion injured rats [33]. In addition, ture. An acupoint combination is considered to have a
acupunctureatBaihui(GV20)andZusanli(ST36)preserves synergistic effect that enhances the therapeutic effect of
the integrity of the BBB, reducing BBB permeability. The acupuncture. For example, a lower prevalence of postoper-
BBBisconstructedoftightconjunctions,includingoccludin ative nausea and vomiting in patients treated with Neiguan
andclaudin-5,whichformtheendothelialbarrier.Reduced (PC6)plusHegu(LI4)wasobservedcomparedwiththose
expression of ZO-1, claudin-5, and occludin mRNA and treatedwithNeiguan(PC6)only[42].Inspiteofextensive
protein contributes to BBB breakdown and edema in the evidence suggesting a synergistic effect of acupoint combi-
ischemic brain [34]. Electroacupuncture at Baihui (GV 20) nation and supporting its use, some studies have reported
antagonistic effects [43–45]. An antagonistic effect occurs
and Zusanli (ST 36) reduces brain damage and related
whenoneacupointweakensthetherapeuticeffectofanother
behavioral deficits via upregulation of tight conjunction
acupoint[46].Forexample,electroacupuncturecanimprove
proteins,includingZO-1,claudin-5,andoccludin[35].These
gastrointestinal movement in rats. The effect of needling
findingsrevealpartsofthemolecularmechanismunderlying
Pishu (BL 20) alone was better than the effect of needling
acupunctureatBaihui(GV20)totreatVaD.
Pishu (BL 20) and Zusanli (ST 36) at the same time [44].
Therefore, whether the effect of acupoint combination is
4.3. Acupoints Selection in Treatment for VaD. The proper
better than a single acupoint still remains a question and
selectionofacupointsisessentialforthetherapeuticeffects
needstobefurtherstudied.
ofacupuncturebecauseacupointsarespecificwithregardto
Some studies have compared single acupoints and an
morphologicalstructure,biophysicalproperties,pathological
acupoint combination for the treatment of VaD. The thera-
response, and stimulating effects [36]. This specificity dif- peutic effect of needling Baihui (GV 20), Shuigou (GV 26),
ferentiatesacupointsfromnonacupointsaswellasdifferent and Shenmen (HT 7) in combination was better than the
acupointsfromoneanother.Thespecifictherapeuticeffects effects obtained by needling each alone [40]. In addition,
ofdifferentacupointshavebeenreportedformigraine[37], needling Baihui (GV 20), Shuigou (GV 26), and Shenmen
functionaldyspepsia[38],ischemicstroke[39],andsoforth. (HT 7) simultaneously activated more brain areas related
The specificity of acupoints for the treatment of VaD tointellectualactivitiescomparedwithneedlingeachalone,
has also been reported. Phosphorylated CREB levels were generatingamoreextensiveeffectonthebrain[41].Antago-
significantlyincreasedafteracupuncturetherapyofneedling nisticeffectsinacupuncturetherapyforVaDhavenotbeen
Baihui (GV 20) and Zusanli (ST 36) compared to sham reportedbutmayoccur.Mostacupunctureprescriptionsfor
acupuncture therapy of needling nonacupoints [15]. Baihui VaDcontainacupointcombinations,andtheuseofacupoint
(GV 20), Shuigou (GV 26), and Shenmen (HT 7) are all combinationsissupported.However,acupointcombinations
among the 10 acupoints with the most potential. A clinical should be selected carefully to avoid antagonistic effects. It
trial demonstrated that needling Baihui (GV 20), Shuigou ishardtotellwhetheracombinationofacupointswillexert
(GV26),andShenmen(HT7)werealleffectiveinimproving antagonisticeffectswithcurrentknowledgeorTCMtheory.
As abovementioned, acupoints with similar functions can
thesymptomsofVaD.However,theirtherapeuticeffectsdif-
exertantagonisticeffects.Therearemanyacupoints,andthe
fer.NeedlingBaihui(GV20)improvedcalculationabilityand
number of acupoint combinations will grow geometrically.
short-term memory and corrected the personality changes
To test the antagonistic effects of each combination one
ofVaDpatients,whileneedlingShuigou(GV26)improved
by one is an exhausting job. To avoid antagonistic effects
naming ability and short-term memory. The therapeutic
as possible, the acupoint prescriptions should be simplified
effects of needling Baihui (GV 20) and Shuigou (GV 26)
as possible. The general principle is to select acupoints
were superior to those of needling Shenmen (HT 7) [40].
with relatively better therapeutic effects and acupoints with
APETandSPECTstudyrevealedthatneedlingthesethree
multipleindicationsandnottoselectmanyacupoints.
different acupoints in VaD patients affected different brain
areas.NeedlingBaihui(GV20)activatedtheinnertemporal
4.5.Limitations. Thisstudyhaslimitationsasfollows.First,
system, the thalamencephalon system, and the prefrontal
otherfactorsthatinfluenceacupuncture,suchasmanipula-
corticalsystem.NeedlingShuigou(GV26)activatedthepre-
tionandtreatmentduration,werenotanalyzedinthisstudy.
frontalcorticalsystem.NeedlingShenmen(HT7)generated
These data can be further mined in future studies. Second,
an effect similar to but weaker than the effect generated by
largelyduetothelackoftreatmentbasedonsyndromediffer-
needlingShuigou(GV26)[41].Thesefindingsdemonstrate entiationanddifferentmethodsofsyndromedifferentiation
that different acupoints have different therapeutic effects in in modern literature, potential acupoints and combinations
acupuncturetreatmentforVaD.Consequently,theselection fordifferentsyndromesofVaDwerenotanalyzed.Although
ofacupoints,whichdirectlyinfluencesthetherapeuticeffects treatment based on syndrome differentiation is important
ofacupuncture,shouldbeconsideredcarefully.Accordingto andisoftenemphasizedinTCM,treatmentbasedondisease
ourresultsbasedondatamining,Baihui(GV20),Sishencong differentiationisequallyimportant.Third,therealtherapeu-
(EX-HN1),Fengchi(GB20),Shuigou(GV26),andShenting tic effects of acupoints and combinations on VaD cannot
(GV 24), which have higher frequencies in the modern be reflected by frequencies in the literature. However, these
literature,mayhavebettertherapeuticeffectsonVaD. resultssuggestsomepotentialacupointsandcombinationsto