Accepted Manuscript

Title: Acupoint herbal patching at Shenque (CV8) as an

adjunctive therapy for acute diarrhea in children: a systematic
review and meta-analysis

Authors: Zhe Liu, Ke-yu Yao, Hui-ru Wang, Yong-le Li,

Meng-ling Li, Jian-ping Liu, Shuang-qing Zhai

PII: S1876-3820(17)30009-4
DOI: http://dx.doi.org/doi:10.1016/j.eujim.2017.01.009
Reference: EUJIM 642

To appear in:

Received date: 22-11-2016

Revised date: 9-1-2017
Accepted date: 19-1-2017

Please cite this article as: Liu Zhe, Yao Ke-yu, Wang Hui-ru, Li Yong-
le, Li Meng-ling, Liu Jian-ping, Zhai Shuang-qing.Acupoint herbal patching
at Shenque (CV8) as an adjunctive therapy for acute diarrhea in children: a
systematic review and meta-analysis.European Journal of Integrative Medicine
http://dx.doi.org/10.1016/j.eujim.2017.01.009

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Acupoint herbal patching at Shenque
(CV8) as an adjunctive therapy for acute
diarrhea in children: a systematic review
and meta-analysis
Zhe Liua, Ke-yu Yaoa, Hui-ru Wanga, Yong-le Lib, Meng-ling Lia, Jian-ping Liuc*, Shuang-qing
Zhaia*

a School of Basic Medical Science, Beijing University of Chinese Medicine, Beijing 100029,
China
b College of Traditional Chinese Medicine, Inner Mongolia Medical University, Hohhot

010110, China
c Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine,

Beijing, 100029, China

*Corresponding author

Correspondence should be addressed to:

Shuang-qing Zhai, email:zsq2098@163.com
School of Basic Medical Science, Beijing University of Chinese Medicine
Jian-ping Liu, email:Jianping_l@hotmail.com
Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine
Address: Beijing University of Chinese Medicine
No. 11, Bei San Huan Dong Lu,
Chaoyang District,
Beijing 100029, China
Abstract
Introduction Acute diarrhea is one of the most frequent illnesses in Children and causes for
hospital attendance in developing countries. This systematic review and meta-analysis aims to
assess the beneficial effect and safety of acupoint herbal patching (AHP) at Shenque (CV8) as an
adjunctive therapy for acute diarrhea in children. Methods We searched published or registered
randomised clinical trials (RCTs) in seven databases (from their inception to September 30, 2016)
and three clinical trial registries that compared combined therapy of AHP applied at Shenque and
conventional treatments to conventional treatments. Data extraction and risk of bias assessment
were conducted by two independent reviewers. Stata 12.0 was used for statistical analyses.
Results 21 eligible studies involving 3560 children with acute diarrhea were included. All of the
RCTs were generally of poor methodological quality. Compared with conventional treatments
which included symptomatic treatment (fluid supplementation, nutritional management,
adsorbents, probiotics, et al.) and anti-infectious therapy ( antibiotics or antiviral drugs), AHP at
Shenque as adjuvant therapy reduced mean duration of diarrhea (MD=-36.49h, 95% confidence
interval -47.50 to -25.49) and decreased the risk of treatment failure (RR=0.21, 95% confidence
interval 0.17 to 0.27) at 72h after treatment began without report of serious adverse events.
Conclusions AHP applied at Shenque (CV8) as an adjunct therapy seemed to be a therapeutic
choice in the management of diarrhea in children. However, a robust conclusion could not be
drawn. Future clinical trials should be designed more rigorously.
Key words: topical application, Chinese herbs, diarrhea, children, randomized trials,
meta-analysis

1. Introduction

Despite a decline in mortality rate, diarrhea remains the second leading infectious causes of
death and accounts for 9.2% of all deaths [1] in children under 5. A child younger than 5 has
approximately 2.9 episodes of diarrhea each year. Acute diarrhea with duration of no more than
14 days is one of the most frequent childhood illnesses and causes for hospital attendance in
developing countries [2].Other direct consequences of childhood diarrhea include impaired
cognition development in resource-limited regions, growth faltering and malnutrition especially
when its prolonged [3-5].
Evidenced-based conventional treatments (CT) have been advocated worldwide which
include continued feeding, oral rehydration salts (ORS), Zinc as well as antibiotic for certain
bacterial diarrhea [6]. ORS can reduce mortality of diarrhea due to dehydration, but simple
replacement of lost fluid does not shorten the duration of diarrhea, while zinc supplementation
can reduce the course and severity of diarrhea. However, the size effects of supplementation can
be limited by several factors such as infants under breastfeeding and have enough maternal
stores of zinc, or geographical regions with low risk of zinc deficiency. Besides, zinc could arouse
adverse effect of vomiting [5]. ORS and zinc are symptomatic treatments regardless of pathogens
that cause diarrhea, whereas antibiotics are used to treat diarrhea due to certain bacteria with
great reduction of mortality as well as proportion of treatment failure [6]. Although acute
diarrhea in developing countries is usually infectious, the most common cause is virus, but not
bacteria. Antiviral treatment is not indicated except for severe infection or serious conditions like
children with low immune function. More approaches as adjunctive therapies to interventions
above have been investigated to shorten the duration of diarrhea as well as related symptoms
like vomiting and fever, and they are selected probiotics, adsorbents, antisecretory drugs,
antiemetics, et al [7]..
In China, an ancient therapy of acupoint herbal patching (AHP) at Shenque (CV8) (Fig. 1,
more figures on AHP at shenque were listed in appendix 1) has been in practice of Chinese
medicine for more than two thousand years [8], the earliest records of AHP at CV8 was found in
ancient Chinese medical texts Zaliao fang and wushier bingfang that were discovered in 1973 in
Mawangdui in a tomb which was sealed in 168 BCE under the Han dynasty. In Zaliao fang, there
was a prescription of AHP at CV8 for treating erectile dysfunction [9]. In wushier bingfang, there
were three prescriptions of AHP at CV8 for treating difficulty in urination [10] Later on, in the
classics of Huangdi Neijing and the Nan Jing, CV8 and its relation with the twelve regular
meridians and the zang fu organs were discussed, which gave theoretic guidance for choosing
CV8 to treat various diseases in clinical practice. This practice continued to evolve and reach its
highest popularity during the Qing dynasty as was shown in the book Li Yue Pian Wen (Wu Shi-Ji,
1864) [11].. Wu Shi-Ji concluded that the principles of treatment for both external and internal
application of Chinese herbal medicine (CHM) were the same, which suggests that herbs
prescribed for oral administration could also be applied externally. This statement became the
fundamental for transdermal treatment of CHM, and modern transdermal drug delivery systems
(TDDS) use the same concepts. However, as for transdermal treatment with CHM, herbs are not
simply applied to anywhere on the skin, but should be put at relevant acupuncture points. The
combination of acupoints stimulation and absorption of active ingredients of herbs penetrated
through skin contributed to the therapeutic effects [12-13].
The indications for AHP at CV8 gradually expanded throughout history, and peaked in Qing
dynasty (as was recorded in Li Yue Pian Wen), when the therapy was used for treating all kinds of
illnesses. Nowadays, plenty of clinical studies have been conducted to observe the therapeutic
effect of AHP at CV8 for various diseases, such as childhood diarrhea, bronchial asthma,
childhood dyspepsia, abdominal distension, ileus, functional urinary retention, ascites due to
cirrhosis, insomnia and dysmenorrheal. All the treatment was conducted under the guidance of
TCM theory [14].
In pediatrics, this old technique is most frequently used for treating diarrhea with popularity
[15]. As an external therapy, application of herbal patch is non-invasive and especially favorable
for sick children who cannot tolerate oral taking or intravenous administration of medicine. There
are both self-made navel pastes [16-17] and patent navel pastes [18-19] authorized by the
Chinese State of Food and Drug Administration as an adjuvant therapy to conventional
treatments of diarrhoea (such as ORS, zinc, diosmectite, probiotics).
In the theory of traditional Chinese medicine (TCM), spleen and stomach are responsible for
transportation and transformation of food and drinks that we intake. Diarrhea is a disease mainly
associated with dysfunction of spleen and stomach. If the duration of diarrhea is prolonged, the
dysfunction of kidney would be involved [20]. The causative factors of diarrhea include
exogenous pathogenic factors, improper feeding, or a constant asthenia of the spleen and
stomach. When the dysfunction of spleen and stomach occur, there would be excessive
dampness and food stagnation, bringing about diarrhea [21]. Syndrome differentiation
(bianzheng) is made according to the causative factors, general symptoms and property of stools.
The five common syndrome patterns include dyspeptic diarrhea, wind-cold diarrhea,
dampness-heat diarrhea, spleen-deficiency diarrhea and diarrhea due to deficiency of spleen and
kidney [22].Under the guidance of syndrome differentiation, the correspondent therapeutic
methods and prescriptions of herbs are prescribed. Unlike herbs for oral administration, herbal
medicaments for topical use prefer aromatic herbs which are warm in property or herbs with
dissipating action, since they promote absorption of drugs through skin and flow of qi and blood
[23].
Conventionally, the mixed herbs are ground into powder, filled into the navel (intact skin),
covered with gauze and fixed with adhesive plaster. Or mix the powder with binder like vinegar to
form paste formulations and pasted at Shenque. Prepared plasters or pounded fresh herbs are
also common pharmaceutical dosage forms of AHP at shenque [24-25] Time of plastering varies
from 6h to 24h per day. Close attention needs be paid to children with treatment of AHP at
shenque (CV8) to ensure theres no signs of irritation like blister, swollen of skin, et al. Every time
before changing the dressing, medicament should be remove the gently and skin be cleaned. [24]
Shenque is a special acupoint located in umbilicus which has connections with all the twelve
regular meridians and zang-fu (internal organs). Stimulation on Shenque can dredge meridians
and regulate function of zang-fu organs [26]. So a combination of selected herbal medicaments
and acupoint stimulation help to harmonize the targeted visceral system and thus to treat
diarrhea.
Recently, numerous clinical trials have assessed the effect of AHP at Shenque for acute
diarrhea in children [15]. But no available publication has been identified to summarize the
evidence and evaluate its effect and safety. We therefore conducted a systematic review to
investigate the unique therapy as an adjunctive for acute diarrhea in children.
2. Methods
This systematic review and meta-analysis were registered at International Prospective Register of
Systematic Reviews (CRD 42016050027) and was reported following Preferred Reporting Items
for Systematic Reviews and Meta-Analyses (PRISMA) Statement [27].
YKY and WHR independently searched the databases for published and ongoing trials,
manually searched the reference lists of eligible trials and relevant meta-analysis, and they
selected eligible studies. LZ and LML extracted the data. LZ and LYL conducted data analysis. Any
discrepancies were negotiated and resolved according to the original article or by seeking
settlement from ZSQ.
2.1 Search strategy and study selection
The following databases have been searched: Pubmed, Embase, Cochrane Central Register of
Controlled Trials, Chinese National Knowledge Infrastructure (CNKI), Chinese VIP Information
(VIP), Sinomed and Wanfang database for published trials from their inception to 30 September
2016. The World Health Organization (WHO) International Clinical Trial Registry Platform (ICTRP)
portal, websites of Chinese clinical trial registry (http://www.chictr.org.cn/) and international
clinical trial registry by U.S. National Institutes of Health (http://clinicaltrials.gov/) were searched
for ongoing registered clinical trials. The following search terms were used as Medical Subject
Headings (MeSH), title and abstract or keywords: (Shenque or umbilicus or umbilical or navel or
omphalo or CV8 or abdomen or bellybutton or belly button) AND (acupoint sticking or acupoint
application or point application or external application or topical application or acupoint patching
or patching or patch or application or stick or sticking or paste or plaster or compress) AND
(diarrhea or diarrhoea or enteritis or enteritides) AND (child or children or childhood or infant or
infantile or pediatrics or paediatrics or toddler) AND random*. The above terms in Chinese were
adapted and searched in Chinese databases. (The detailed search strategy was listed in Appendix
2)
2.2 Inclusion/exclusion criteria
2.2.1 Type of study
Randomised controlled trials (RCTs) were eligible with no language restrictions.
2.2.2 Type of participants
Children under 5 years with acute diarrhea were included, including dysentery. Acute diarrhea is
defined as three or more loose or liquid stools per day with duration of less than 14 days
[3,28-29]. Dysentery is passage of stools with observable blood [29]. Etiological diagnosis is not
required, but if the study assessing diarrhea due to specific pathogens (e.g. rotavirus), it should
be laboratory confirmed before enrollment. Concomitant presence of other diseases was
excluded, such as pneumonia, rickets, anemia, et al.
2.2.3 Type of Interventions
Studies were eligible if both groups received conventional treatment, and the treatment group
had AHP at Shenque (CV8) as an adjunct, while the comparison group received additional
placebo or no AHP. Conventional treatments include western medicine therapy like ORS or
intravenous fluids, probiotics, mucosal protective agents, or anti-infective therapy.
Studies are excluded under following conditions: 1) Two groups comparing navel patching of
different formulas. 2) Interventions aided by equipment. 3) Conventional treatments included
other therapy of Traditional Chinese Medicine (TCM) like herbal decoctions, manipulation,
acupuncture, et al.
2.2.4 Type of outcome measures
Primary outcomes were duration of diarrhea, the proportion of treatment failure. Diarrhea
duration is defined as the time (hrs) from intervention began to the first formed stool followed by
a non-liquid stool, and returning to normal frequency of stool per day. Treatment failure is
verified as no change in the property of stools (loose or watery), the frequency of diarrhea (more
than 3 times per day) and the overall conditions (e.g. rehydration, vomiting, fever), or diarrhea
getting worse. Treatment failure rate was measured at 72h after interventions began. Secondary
outcomes were duration of hospital stay, stool frequency (number per day), stool output (volume
of stools), adverse events and all cause mortality. Adverse events [30] include serious adverse
events that is life-threatening, requiring longer hospitalization or requiring interventions to
prevent it, or non-serious adverse events causing discontinuation of treatment such as blister,
allergic events, abnormality of hepatic and renal function, or adverse events like rashes of skin.
Redundant published trials, poor data authenticity trials (suspected fraudulent,
incompatible data and conclusions) and trials with missing data not available from contacting the
authors were excluded.
2.2.5 Data Extraction
A structured data extraction form was designed for selected trials with following items: study
characteristics (author, year of publication, country, setting, quality of studies), baseline
characteristics of participants (sample size, diagnostic criteria, inclusion and exclusion criteria,
age, gender, duration of diarrhea, severity of diarrhea like vomiting, fever, degree of dehydration,
etc.), descriptions of interventions (syndrome differentiation, therapeutic methods, components
of herbal patch, doses, operation methods, conventional treatments), outcomes(diarrhea
duration[mean, SD], the proportion of treatment failure, stool frequency, stool output, duration
of hospital stay, all-cause mortality and adverse events) and other specific objectives(funding,
conflict of interest).
2.2.6 Risk of Bias Assessment
The quality of eligible studies was assessed by using risk of bias tools from Cochrane Handbook
Version 5.1.0. [31] The criteria mainly included random sequence generation, allocation
concealment, blinding of participants and personnel, blinding of outcome assessment,
incomplete outcome data, selective reporting and other sources of bias (comparable baseline
characteristic, sample size estimate, clear inclusion and exclusion criteria, funding, and conflict of
interest). Each item was assessed as having a low, unclear or high risk. The quality of eligible trials
were ranked as following three levels: high risk of bias (at least one item was ranked as high risk),
low risk of bias (all the items were ranked as low risk), unclear risk of bias (at least one item was
ranked as unclear risk). LZ and LML independently assessed the quality of trials and any
disagreements were resolved by ZSQ.
2.2.7 Data Analysis.
Stata (StataCorp, version 12.0) was applied for all statistical analyses. We regarded duration of
diarrhea, hospital stay, stool frequency and stool output as continuous variables, and the effect
estimate was reported as mean difference (MD) with a 95% confidence Interval (CI). For
proportion of treatment failure and all-cause mortality, we calculated an overall relative risk (RR)
with a 95% CI. The number of participants from each group was used as denominator in the
analysis.
Different trials may have different therapeutic methods for prescriptions of herbs. The
diversified therapeutic methods for AHP were deemed to be an important source of
heterogeneity, so subgroups were further analyzed by therapeutic methods. And trials with the
same therapeutic methods would be in a subgroup. The common therapeutic methods include
the method of warming the interior to dissipate cold (WIDC), the method of dispelling wind-cold
(DWC), the method of clearing heat (CH), the method of removing dampness (RD), the method of
invigorating spleen qi (ISQ), the method of astringing intestine (AI), the method of promoting
digestion (PD), the method of relieving pain (RP) or a combination of the methods above [22].
The I-squared statistic was used for statistical heterogeneity test. A fixed-effect model (FEM)
was applied for pooling data initially. If the value of I-squared was greater than 50%, which
indicated the existence of substantial heterogeneity, we would explore the cause for possible
source of heterogeneity, and a random-effect model (REM) was applied when appropriate.
Funnel plots were generated for detecting publication bias when more than ten trials were
identified for the same outcome. The funnel plots asymmetry was assessed using Begg and Egger
test, significant bias was defined as P-value <0.1. The trim-and-fill computation was used to
evaluate the effect of publication bias when interpreting the result [32].
3. Results
3.1 Study search and selection
We initially identified 1115 RCTs from 7 databases and 534 duplicate records were removed.
The remaining 581 records were screened, in which 371 records were excluded by reading titles
and abstracts, 210 records were assessed in full texts, an additional 189 records were excluded
for improper participants, irrelevant comparisons, uncertain diagnosis, uncertain or improper
diarrhea duration, poor data authenticity, redundant publications, not RCTS or missing data
unavailable from contacting the author. Twenty-one met the inclusion criteria and were included
in the systematic review (Fig. 2).
3.2 Description of studies
A total of 3560 participants enrolled in the studies with 1821 patients treated by AHP combined
with conventional treatments and 1739 by conventional treatments (except for one trial with
placebo plus conventional treatment as comparator). No trials reported dropout. All the trials
were conducted in China and reported in Chinese. All participants were children under 5 years
with acute diarrhea. All of the trials had two arms, except for one that had three arms, and two
of the three arms that met the inclusion criteria were included.
Six trials reported syndrome differentiation and twenty trials mentioned therapeutic
methods for utilization of herbal formulae. Three Chinese patent medicines approved by the
State Food and Drug Administration involved in the external application, one was Dinguier navel
paste especially made as adjunctive therapy for diarrhea in children, the other two were Yunnan
Baiyao and Kangenbei pills for enteritis, both of which were oral medicine, but were made for
external application on Shenque in the trials. The herbal patch for topical use in the rest 18 trials
was made by TCM doctors or hospital pharmacy. Conventional treatments were mainly
symptomatic therapy (including fluid supplementation, acid base disturbance correction,
water-electrolyte disturbance correction, febrifugal therapy, nutritional management, adsorbents,
probiotics, vitamin, calcium, antiemetic treatment) and anti-infectious therapy (antibiotics,
antiviral therapy).
For outcome measures, all the 21 trials reported proportion of treatment failure, of which
four trials were excluded because they didnt meet the definition of treatment failure as we
defined in the method section. Seven trials reported duration of diarrhea, two of which only gave
the mean value without standard deviation, and authors cannot be reached, so the data was
excluded from calculations. Only one trial reported stool frequency at 72h after intervention
began. No trials reported duration of hospital stay or stool output. Although treatment failure
rate was measured, no trial reported on the follow-up or all cause mortality. Ten trials reported
adverse events. No trials reported information on funding or conflict of interests. All studies
claimed comparable baseline regarding age, sex, course of diarrhea and severity of diarrhea.
(Table 1, Table 2)
3.3 Methodological quality
Four trials [17,33-35] out of 21 RCTs clarified method of sequence generation (referring to
random number table). One trial [34] used envelope for allocation concealment but no further
information on whether the envelope was sealed and opaque, so all trials had unclear risk for
allocation concealment. One trial [17] had unclear risk of bias for blinding since a placebo navel
patching was designed for control group, but no clear statement on blinding, while the rest 20
trials had one of the parallel-group receiving AHP, it was hard for blinding of participants and
personnel, and the outcomes were likely to be influenced by lack of blinding, so they all received
high risk for performance bias. No trials provided information on blinding of outcome assessment,
so detecting bias was unclear. No trials reported missing outcome data, thus they were assessed
as low risk for attrition bias. For reporting bias, two trials [36-37] reported one of the primary
outcomes incompletely so it was not possible for the meta-analysis, one trial [17] failed to
investigate primary outcomes and the above three trials were ranked as high risk, eight trials
[18,33-34,38-42] reported outcomes in the results in accordance with outcome measures in the
method section. Ten trials [16,35,43-50] which made no description of outcome measures in the
methods were ranked as unclear. No trial reported sample size estimate, funding or conflict of
interest, thus all trials were assessed as unclear risk for other bias. All eligible trials were assessed
as high or unclear risk of bias at the study level. (Fig. 3)
3.4 Effect estimate
We initially planned to conduct subgroup analysis by therapeutic methods of AHP. Although
nineteen included trials reported therapeutic methods, five [16,35,44,49-50] of the trials only
reported part of the therapeutic methods. For example, one trial [44] reported invigorating
spleen and removing dampness as therapeutic methods, however, from the components of
herbal patching, we deduced that the method of warming the interior and astringing intestine
was also utilized. In order to make a full understanding of the therapeutic methods, we made
deductions for those trials with inadequate or no report of therapeutic methods based on the
functions and dosages of the herbs for topical use. The deductions were conducted by two
reviewers (LZ and YKY), any disagreement was resolved by the third reviewer (ZSQ). Interestingly,
one trial [46] used Yunnan Baiyao as herbal medicament for topical application based on the
understanding of its modern pharmacological findings, which reported that Yunnan Baiyao could
inhibit bacteria and enhances immune function. So there was no deduction on the therapeutic
methods for this trial. The specific therapeutic methods were used as indexes for subgroup
analysis.
3.4.1 Duration of diarrhea
In a pooled analysis of five trials [16,18,34,42,50] investigating duration of diarrhea, the
combination of AHP and conventional treatments led to a greater mean reduction of diarrhea
duration than conventional treatments alone, with significant between-study heterogeneity
(MD=-36.49h, 95%CI -47.50~-25.49; I2=89.7% , P=0.000, REM). Effect estimate on duration of
diarrhea were consistent in direction. Subgroup analysis of two trials [18,42] showed that WIDC
plus ISQ plus conventional treatments comparing to conventional treatments could reduce
diarrhea duration with no significant between-study heterogeneity (MD -26.70h, 95%CI -34.74 to
-18.66, I2=42.8%, P=0.000). A pooled analysis of two trials [16,50] comparing WIDC plus ISQ plus
RD plus CH plus AI combined with conventional treatments to conventional treatments had a
greater reduction of diarrhea duration with no significant between-study heterogeneity
(MD=-34.03h, 95%CI -37.309 to -30.742, I2=0, P=0.000). WIDC plus CH plus RD combined with
conventional treatments to conventional treatments [34] was shown to be more effective in
reducing diarrhea duration (MD=-72.00h, 95%CI -85.36 to -58.64). There were significant
subgroup differences (P=0.00) [51], WIDC plus ISQ plus RD plus CH plus AI combined with
conventional treatments seemed to be more effective than WIDC plus ISQ in reducing diarrhea
duration, when each was compared to conventional treatments. (Table 3)
3.4.2 Rate of treatment failure
In a pooled analysis of 17 trials [18,33-41,43-49] assessing the proportion of treatment failure at
72h after treatment revealed that adjunctive AHP decreased the risk of treatment failure by 79%.
(RR=0.21, 95%CI 0.17 to 0.27; P=0.000). The size of the effect varies between studies but not the
direction. Further subgroup analysis was conducted by the therapeutic methods of included trials.
A pooled analysis of two trials [18,39] indicated that the treatment failure rate in WIDC plus ISQ
combined with conventional treatments was lower than that in conventional treatments (RR 0.11,
95%CI 0.03 to 0.34, P=0.000). A pooled analysis of 2 trials [33,41] revealed that CH plus RD
combined with conventional treatments decreased treatment failure rate by 75% (RR 0.25 95%CI
0.14 to 0.45, P=0.000). A pooled analysis of 3 trials [35,44,49] indicated that treatment failure
rate with WIDC plus ISQ plus RD plus AI plus conventional treatments was lower than that with
conventional treatments alone (RR 0.19, 95%CI 0.08 to 0.44, P=0.000). A pooled analysis of 2
trials [45,47] indicated that WIDC as adjunctive therapy to conventional treatments decreased
treatment failure rate by 87% (RR 0.13, 95%CI 0.08 to 0.22, P=0.000). A pooled analysis of 2 trials
[36,48] showed that WIDC plus RP plus PD as adjuncts decreased treatment failure rate by 76%
(RR 0.24, 95%CI 0.10 to 0.58, P=0.001). WIDC plus CH plus RD combined with conventional
treatments [34], WIDC plus RP combined with conventional treatments [43], DWC/CH+RD/ISQ
combined with conventional treatments [38], WIDC plus RP plus RC combined with conventional
treatments [37], Yunnan Baiyao combined with conventional treatments [46] and ISQ plus AI
combined with conventional treatments [40] were all shown to have lower treatment failure rate
than conventional treatments alone. Although the effect estimates varies between different
subgroups, the heterogeneity between subgroups was not significant (P=0.287), so its not
possible to conclude that therere any differences between effect estimates of subgroups. (Table
3)
The funnel plot of seventeen trials assessing treatment failure rate appeared asymmetrical,
indicating the existence of publication bias for included trials. Publication bias was confirmed on
Egger test (P=0.08, appendix 4), further analysis using trim-and-fill test indicated that publication
bias had no impact on the effect estimates (e.g. no trimming performed and data unchanged).
(Fig. 4
3.4.3 Stool frequency
One trial [17] reported stool frequency on day three, quantitative synthesis was not conducted.
The trial reported that the stool frequency was lower in AHP plus conventional treatments group
than that in placebo plus conventional treatments group (P<0.00001) .
3.4.4 Adverse events
Eleven trials (52.4%) didnt mention whether they had monitored adverse events (AEs) or not.
Five trials (23.8%) [17,33,35,38,42] reported no obvious AEs in the treatment group. Four trials
(19.0%) described AEs which included rashes of skin [26], slightly skin irritation by adhesive
plaster used for fixing the navel patching [38,42] or by causes undefined [42]. All the four trials
declared that AEs didnt influence the treatment and there was no incidence of dropout. One
trial [50] reported no AEs in combined treatment group, while the control group had one case
with indigitation that moved to the surgical department, 8 cases with abdominal distention and 2
transferred to constipation requiring further treatment. No trials reported serious AEs of AHP at
Shenque.
3.4.5 Herbs used for topical application at Shenque
Nineteen trials reported 41 herbs used for 100 frequencies, 5 kinds of herbs were included for
one topical application on average (ranging from 3 to 9), and twelve trials reported doses or
dosage proportion of herbs. The frequency of each herb was added up and the top 10 frequently
ued herbs were listed in table 4.

4. Discussion
4.1 Main findings
Our result showed that, compared with conventional treatments, AHP as adjuvant therapy may
reduce duration of diarrhea and decrease the risk of treatment failure at 72h after treatment
began, with no serious adverse events. Those findings indicated that AHP at Shenque (CV8) as an
adjunctive therapy seems to be a therapeutic strategy in improving comprehensive management
of diarrhea in children.
According to TCM theory, combining disease with syndrome is a very common treatment
model for TCM, syndrome which mainly contains etiology, location, severity or stage of disease is
a summary of pathological nature. Syndrome differentiation is an integrated analysis of the
clinical information and it serves as guidance for therapeutic methods, and herbs are prescribed
in accordance with the therapeutic methods [52]. Herbs may vary among different trials, but the
core therapeutic methods are consistent. The common syndrome patterns of diarrhea include
wind-cold diarrhea, dampness-heat diarrhea, dyspeptic diarrhea, spleen-deficiency diarrhea and
diarrhea due to deficiency of spleen and kidney. As the syndrome of deficiency in spleen and
kidney is usually observed in chronic diarrhea, the former four syndrome patterns are more
common for acute diarrhea [21]. Only 28.6% (6/21) of included trials reported syndrome
differentiation and 66.7% gave adequate report of therapeutic methods. The corresponding
therapeutic methods for the first four syndromes could be the method of dispelling wind-cold
(DWC), the method of warming the interior to dissipate cold (WIDC), the method of clearing heat
(CH), the method of removing dampness (RD), the method of promoting digestion (PD), the
method of invigorating spleen qi (ISQ), and the method of astringing intestine (AI) [53]. Those
therapeutic methods are used individually or in combination to create individualized treatment
plans.
We considered that therapeutic methods are important source of between-study
heterogeneity and they may also lead to different degrees of effect estimates. So we conducted
subgroup analysis by different therapeutic methods. According to the pooled analysis of related
trials, WIDC plus ISQ plus RD plus CH plus AI combined with conventional treatments seemed to
be more effective than WIDC plus ISQ combined with conventional treatments in reducing
diarrhea duration, when each was compared to conventional treatments. The pooled analysis of
related trials for treatment failure rate showed that CH plus RD in combination with conventional
treatments, WIDC plus RP plus PD combined with conventional treatments, WIDC plus ISQ plus
RD plus AI combined with conventional treatments, WIDC combined with conventional
treatments and WIDC plus ISQ combined with conventional treatments could all effectively
reduce treatment failure rate at 72h after treatment began, when each was compared with
conventional treatments. Although the effect estimates between different subgroups are
different, the heterogeneity is not significant, so its not possible to conclude any differences
between different therapeutic methods for outcome of treatment failure rate.
We noticed that WIDC was the most frequently used therapeutic method (81%, 17/21) for
AHP at Shenque. This is consistent with the results of analyzing the herbs frequency. Wu Zhuyu,
Rou Gui and Ding Xiang as the three most frequently used herbs all have the function of warming
the interior to dissipate cold (WIDC). The method of WIDC and the top three herbs are mainly for
diarrhea due to cold or asthenia. Eight of the top ten frequently used herbs identified in our
review are consistent with analysis [54] of herbal medicaments for topical use for treating
diarrhea at Shenque from 650 ancient classics of TCM as well as clinical studies of umbilical
therapy (1991~2010). These top eight frequently used herbs are Ding Xiang, Wu Zhuyu, Rou Gui,
Hu Jiao, Cang Zhu, Wu Beizi, Mu Xiang and Huang Lian. Huang Lian (Coptidis Rhizoma) has the
function of clearing heat and removing dampness. Mu Xiang (Vladimiriae Radix) which is warm in
nature can regulate qi stagnation, remove dampness and relieve pain. Hu Jiao(Piperis Fructus)
warms the interior to dissipate cold, promotes digestion and relieves pain. Cang Zhu(Atractylodis
Rhizoma) invigorates spleen qi and removes dampness. Wu Beizi (Galla Chinensis) is mainly for
astringing intestine to stop diarrhea.
4.2 Possible mechanisms
Modern researches in transdermal drug delivery systems (TDDS) have already proved systematic
absorption through the skin after topical application of drugs [55]. AHP used the same concept as
TDDS, although the actual delivery method is different. For AHP, acupoints stimulation also
contributes to the therapeutic actions, and that lies one of the distinctive differences between
AHP and modern TDDS [13]. In our study, the very acupoint was Shenque (CV8) which belonged
to the Conception Vessel with connections to all the meridians as well as internal organs in TCM
theory. Meridians are pathways in which qi and blood of the body circulate, and they connect
internal organs with surface of the body [53]. Stimulation on Shenque can affect circulation of qi
and blood in meridians thus exerting direct influence on function of internal organs. A variety of
local and systematic diseases can be treated by placing herbal patching at Shenque [8].
From the anatomical findings, Shenque locates right on the navel. Navel has the thinnest
stratum corneum with no fat tissue underneath. The skin barrier function is weak and there is
abundant micro vessel structure under the skin which makes it a high sensitive location with
faster absorption rate of drugs [56]. A study found that the systemic bioavailability of investigated
drug by navel absorption was very close to the level by intravenous administration with an equal
dose, and was almost 1.6 times the level by forearm administration [57]. Experiment on animals
with diarrhea revealed that AHP on navel has positive influence on the energy metabolism, signal
transduction pathway and intestinal flora metabolism through methods of metabonomics [58].
Rou Gui(Cinnamomi Cortex), Ding Xiang(Caryophylli Flos) and Wu Zhuyu(Euodiae Fructus)
were most frequently used herbs in the included trials. Ethanolic extracts of those herbs were
proven to exhibit strongest depression on spontaneous contraction of isolated duodenum and
strong antimobility action on intestine, thus helping to arrest diarrhea [59].
4.3 Limitations
Although our findings exerted beneficial effect of AHP at Shenque for diarrhea in children, this
result of meta-analysis should be interpreted with caution since the included trials have
important limitations, and a confirmative conclusion concerning the efficacy and safety of AHP at
Shenque couldnt be drawn. Firstly, all the included trials had unclear or high risk of bias. Most of
included RCTs didnt report details on randomisation which may contribute to potential bias and
overestimation of intervention effect [60]. All the included trials reported positive results and a
funnel plot analysis showed the existence of publication bias, while negative results may be
selectively unreported thus were not included in the meta-analysis to justify the results. Secondly,
only 28.6% (6/21) of included trials reported syndrome differentiation, the information on
syndrome differentiation is important for potential users evaluation and application. Thirdly,
there were inadequate reports of adverse events in included trials (10/21, 47.6%), so a further
investigation on safety issues is still needed. Finally, although we had strict criteria for
participants, interventions and consistent time point as well as definition for outcome
assessment to ensure possible homogeneity, different severity of diarrhea, different
compositions of conventional treatments/herbal medicaments and varying doses of treatments
may lead to heterogeneity across studies.
4.4 Comparison with previous reviews
In 2013, a meta-analysis of 16 studies has assessed the effectiveness of acupoint herbal patching
(AHP) for childhood diarrhea in a Chinese journal [61], 12 out of 16 trials chose Shenque as the
acupoint for external application and only the overall effective rate was analyzed, which indicated
that AHP alone or in combination with conventional treatments (Chinese herbal medicine or
western medicine) were more effective than conventional treatments. While in our review, we
compared conventional treatments with or without herbal patching at shenque, and
conventional treatments only included western medicine. Besides, we have different search
strategy and more rigorous inclusion/exclusion criteria for participants and outcome assessment.
So 14 of the 16 trials in the meta-analysis were not included in our study. The deadline for
searching was 30 June of 2012 in that meta-analysis, and our review provided latest evidence
with additional trials.
4.5 Implications for future studies
Most of the included trials didnt follow the CONSORT statement. Report of methodology
was insufficient. We admit that a placebo of AHP at Shenque would be difficult, since herbs used
for external application usually have strong odor, while it is a bit hard for a placebo to mimic such
odor. For concerns of ethics, the guardians of suffering children with diarrhea might not be
willing to join a trial with possibility of entering a group with placebo. However, a placebo is
important for an acute and self-limiting disease like diarrhea to better evaluate the efficacy of
interventions. Furthermore, blinding of outcome assessment could be possible. Information on
sample size estimate, pharmaceutical industry funding or conflict of interest should be reported
to clarify the potential risk of bias. The possible biases above could lead to deviation from the
true value of intervention investigated. Future studies should pay more attention to monitor and
report adverse events which may provide us with more information on safety of the therapy.
Apart from ORS and continued feeding, zinc supplementation was also encouraged by WHO
guidelines for management and treatment of diarrhea in children [29]. We noticed that no
included trials gave zinc therapy as conventional treatment. On the other hand, 5 trials
[18,34,40,44-45] used ribavirin and 2 trials [16,42] used injection of Chinese herbal extraction
(Yanhuning) as anti-viral control interventions. Both of the drugs dont have indications for
diarrhea and are associated with specific adverse reactions [62-63]. The majority of diarrhea in
children is caused by virus, and usually has an acute and self-limiting course, so anti-viral drugs
are not recommended for treatment of diarrhea in children without other underlying diseases.
Zinc supplementation should be encouraged and the value of anti-viral drugs deserves more
research in infantile and childhood diarrhea.
For outcome measures, composite indexes (e.g. course of total recovery, effective rate of
diarrhea related symptoms, accumulated points of symptoms, course of total recovery) were
utilized by included trials, whereas objective outcomes were not reported adequately. Composite
indexes were subjective and diversified which made it impossible to undertake a pooling analysis
of outcomes and brought susceptibility of subjective bias. Besides, they were not international
recognized. Future trials may select more objective outcomes like duration of diarrhea, stool
frequency, stool output, duration of fever, vomiting, or hospital stay. Those outcomes are more
precise and internationally recognized in measuring and interpreting the efficacy of AHP at
Shenque for diarrhea in children.
5. Conclusions
AHP at Shenque may have the effect on reducing duration of diarrhea and decreasing the risk of
treatment failure without serious adverse events. WIDC was the most frequently used
therapeutic method for AHP at Shenque. Wu Zhuyu, Rou Gui, Ding Xiang were the most
frequently used herbs. However, due to the poor methodology of included RCTs, limited number
of included trials and inadequate report of AEs, a confirmative conclusion on efficacy and safety
of AHP at Shenque for diarrhea in children could not be drawn. More randomized controlled
trials with better methodological quality are warranted to support its use.

Funding Source
This work was supported by National Key Basic Research and Development Program (973
Program) [No.2013CB532001]
Authors contribution
Designed the review: LZ, YKY, LYL, ZSQ. Searched and selected trials: YKY, WHR. Data extractions
and risk of bias assessment: LZ, LML, ZSQ. Data analyses: LZ, LYL. First draft of paper: LZ.
Substantial revisions to the paper: LJP, ZSQ.

Conflict of Interest
All authors declare that they have no conflict of interests.

Acknowledgements
Special thanks to Dr. Guo-yan Yang from Western Sydney University for her suggestion on
assessment of methodology quality; Dr. Hai-peng Chen from Tianjin University of Chinese
Medicine for his advice on the diagnosis of rotavirus enteritis; Dr. Yi-yun Ding and Dr. Qiong-jie
Fang from Beijing University of Chinese Medicine for her advice on the inclusion criteria; Dr. Shuo
Feng, Dr Xun Li and Professor Yu-tong Fei from Beijing University of Chinese Medicine for their
advice on outcome assessment; Yi-ting Yang from Beijing University of Chinese Medicine for her
help in assay polishing.
.
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Fig.1 Shenque
Fig. 2 Study selection flow diagram
Fig.3 Risk of bias summary
Fig.4 Funnel plot of treatment failure rate in 17 trials
 Table 1: Characteristics of the included studies

Study Sample size Sex(n) and age(year or month)( TG,CG) Course of Treatment
Total(TG,CG) diarrhea(day or
hour)(TG/CG)

Hou et al.2007[18] 90(50,40) TG(M:16/F:14) CG(M:26/F:14) 30h/31h TG:AH

(both group:0.5~2 y): CG:ST(FS/A
Wu et al.2010[34] 130(75,55) TG(M:41/F:34) CG(M:30/F:25) <2d: 11/15; TG:AH
TG(16.08.3m) CG(16.06.8m) 2~7d: 32/41; CG:ST(F
8~14d:12/19

Lao et al.2014[33] 180(90,90) TG(M:51/F:39) CG(M:54/F:36) 1-3d TG:A

TG(14.207.47m) CG14.508.63m CG:
He et al.2013[43] 360(180,180) TG(M:98/F:82) CG(M:93/F:87) 2.121.59d TG:AH
TG(1.51.2y) CG1.71.3y /2.231.74d CG:ST(FS

Wang et al.2010[44] 52(30/22) TG(M:16/F:14) CG(M:13/F:9) 48h TG:AH

(both group:0.5~1 y) CG:S
/WED
Zou et al. 2010[42] 120(60,60) TG (M:35/F:25) CG(M:38/F:28) 24~72h TG:
(both group 3~36m) C
Ji et al.2011[16] 160(60,60) TG(M:38/F:22) CG(M:35/F:25) 1.200.82d TG:AH
TG(13.378.72m) CG(12.568.58m /1.100.93d CG:ST

Qian et al.2015[38] 60(30/30) TG(M:17/F:13) CG(M:16/F:14) 3.1/3d TG:

(both group:0.5~3y) CG:ST(F
Zhang et al. 014[35] 90(45,45) (M:50/F:40) 2~7d TG:
(Both group: 4m~3y) CG: S
Li et al. 2007[37] 160(80,80) TG(M:45/F:35) CG(M:49/F:31) 1~5d TG:
(T:18m/C:19m) CG:ST(FS/W
Fu et al. 1997[45] 360(180,180) TG(M:102/F:78) CG(M:114/F:66) 63.3/65.8h TG:AH
<0.5y 30/43;0.5~1y 96/90; 1~3y 54/47 CG:ST(FS/W
Tan et al. 2012[46] 204(102,102) TG(M: 64/F: 38) CG(M:62/F:40) 2.51.5d/ TG:AH
(T:6~24m C:4~26m) CG:31d CG:ST(
Li et al.2014[39] 100(50/50) (M:28/F:22) CG(M:26/F:24) 3~6d AHP
(both group:0.5~3y) ST(FS/
Zhao et al. 2005[36] 116(64,52) TG(M:35/F:29)CG(M:29/F:23) 2.7d/2.8d TG:
(both group:2m~3y) CG:ST(FS/

Dong et al. 2012[50] 186(96,90) NR 1.6d(1~3d) TG:

(both group:3m~3y) CG: ST
Zeng et al. 2001[49] 102(52,50) TG (M:36/F:16) CG(M:38/F:12) 3.01.1d/ TG:
(1.2y /1.4y) 2.81.2d CG:ST(FS
Sun et al. 2008[47] 320(160,160) (M:200/F:120) 7~14d TG:AH
(3~24m) CG:ST(FS/W
Wu et al. 2014[40] 120(60,60) TG(M:33/F:27)CG(M:35/F:25) 2.5(0.5~3d) TG:AH
(both group:2m~3y) CG:ST(FT/

Zhang et al. 112(57,57) TG(M: 28/F:29) CG(M:31/F:26) 1~3d TG:AH

2014[41] (TG: 22.713.6m CG: 24.512.3m) CG:ST(FS/W
Wang et al. 2011[17] 324(175,149) TG(M: 93/F: 82) CG(M:77/F:72) <48h TG:
(TG: 14.9 7.0m CG: 15.7 7.3m) CG:ST(FS
+p
Li et al. 2012[48] 254(127,127)/0 (M:151/F:103) <7d TG:
(3m~5y) CG:ST(FS/W
FT
TG: treatment group; CG: control group; NR: not reported; M:male; F:female; AHP: herbal patching; ST:
symptomatic therapy; FS: fluid supplementation; ADC: acid base disturbance correction; WEDC water-electrolyte
disturbance correction; FT: febrifugal therapy; NM: nutritional management; AIT: anti-infectious therapy; A:
Adsorbents; P: probiotics; V: vitamin; C: calcium; AET: antiemetic treatment TE: treatment effect; DD: duration of
diarrhea; AR: adverse reactions; CTR: course of total recovery; CSTBN: course of stool test back to normal; APS:
accumulated points of symptoms; 3-day/7-day RNRR: Rotavirus Negative Reversion Rate on day-3/ day-7; CDSBN:
course of defecation state back to normal; ERS: effective rate of symptoms; DF: duration of fever; DDH: duration
of dehydration; SF: stool frequency; BT: blood test; ST: stool test; UT: urine test; LF: liver function; RF: renal
function; COI: course of overall improvement.
 Table 2: Detailed information on AHP at Shenque
Study Syndrome differentiation
therapeutic methods
Hou et al. 2007[18] NR
Wu et al. 2010[34] NR
Lao et al. 2014[33] Dampness-heat diarrhea
He et al.2013[43] NR
Wang et al. 2010[44] NR
Zou et al. 2010[42] NR
Ji et al. 2011[16] NR WIDC+ ISQ+RD+CH+AI
Qian et al. 2015[38] Wind-cold
diarrhea/dampness-heat
diarrhea/spleen-deficiency
diarrhea
Zhang et al. 2014[35] NR ISQ+RD+WIDC+AI
Li et al. 2007[37] NR
Fu et al. 1997[45] NR
Tan et al. 2012[46] NR
Li et al.2014[39] Wind-cold
Categories of Herbal formula/ingre
for AHP
WIDC+ ISQ Dingguier navel paste (Caryophylli Flos,
Piperis Longi Fructus)
WIDC+ CH+ RD Lun Xieting ointment( Borneolum, Euod
Cortex, Caryophylli Flos, Vladimiriae Rad
myristicae semen, et l) ;size/weight:6g
CH+RD Qingchang Zhixie powder(Atractylodis R
Flavescentis Radix, Coptidis Rhizoma, Zi
Praeparatum) proportion:(3:2:1:0.5)
Binder: vinegar, blend into paste ,fill the
plaster 1.5cm in diameter
WIDC+ RP Zhixie paste(Piperis Fructus, rhei radix e
radix, rehmanniae radix, Cinnamomi Co
notopterygii rhizoma et radix)
WIDC+ RD Zhixie paste(Euodiae Fructus, Vladimiria
Cortex, granati pericarpium, alpiniae ka
binder: vinegar; blended into paste, fixe
WIDC+ ISQ Dingguier navel paste(Caryophylli Flos, C
Longi Fructus)
Diarrheagranule (rosae laevigatae fru
chinensis fructus, Galla Chinensis, Euod
Rhizoma)equal part; binder: vinegar; siz
DWC/CH+RD/ISQ Wind-cold (Angelicae Dahuricae Radix, C
Caryophylli Flos) /dampness-heat(Copti
Flavescentis Radix, Vladimiriae Radix)/s
(Caryophylli Flos, Cinnamomi Cortex, Eu
vinegar, blend into paste , size/weight:2
Euodiae Fructus, Cinnamomi Cortex, Ca
Fructus, Litseae Fructus, Chebulae Fruct
pericarpium, Foeniculi Fructus. equal pa
fixed by adhesive plaster, size/weight: 2
WIDC+RP+RC Atractylodis Rhizoma, Cinnamomi Corte
proportion(5:5:1.5) ,ground into powde
into paste, fixed by adhesive plaster,
size/weight: cake-like
WIDC (Caryophylli Flos 2 parts, Foeniculi Fruc
1 part, Borneolum 0.3 part)Ground into
adhesive plaster and gauze
NR Yunnan Baiyao powder;Binder:75% ethy
0.2~0.3ml;Size/weight:2~4g, blended in
WIDC+ISQ Nuanqi patch (Caryophylli Flos, Euodiae
 diarrhea/dampness-heat Cortex, zingiberis rhizoma et al.) Propor
diarrhea patch (Vladimiriae Radix, Euodiae Fruct
Radix, puerariae lobatae radix et al.) Pro
vegetable oil, blended into paste ,size/w
fixed by patch
Zhao et al. 2005[36] NR WIDC+RP+PD (Euodiae Fructus 5 parts, Caryophylli F
rhizoma 3 parts, endothelium corneum
Ground into powder, binder: vinegar ,bl
adhesive plaster or bandage or Shangsh
Dong et al. 2012[50] Dampness-heat WIDC+ ISQ+RD+CH+AI (Euodiae Fructus, Galla Chinensis, Sop
diarrhea/dampness-cold Coptidis Rhizoma, Zingiberis Rhizoma Pr
diarrhea Fructus et al.)equal part,; ground into p
put into gauze bag
Zeng et al. 2001[49] NR WIDC+ISQ+RD+AI Galla Chinensis 15g, Euodiae Fructus 6g
6g,coptidis rhizoma 3g, Atractylodis Rhi
corneum gigeriae galli 1g, amomi fructu
yunnan baiyao 4g, ground into powder,
blended into paste, size/weight:2g, fixed
Sun et al. 2008[47] NR WIDC Euodiae Fructus 15g, ground into powd
rice 80% done, mix together, make it ca
diameter,1cm in height , fixed by adhes
warm by hot-water bog with acceptable
Wu et al. 2014[40] NR ISQ+AI Xiaoer Fuxie paste(NR)
Zhang et al. 2014[41] Dampness-heat diarrhea CH+RD Changyanning pill (euphorbiae humifus
chrysotricha (Palib.) Chun., Litsea rubes
herba, formosan sweet-gum) Binder: Va
per pill*3pills, ground into powder, blen
by gauze and adhesive plaster
Wang et al. 2011[17] Dampness-heat diarrhea ISQ+CH+RD Qingchang Zhixie powder(Coptidis Rhizo
sarcodactylis fructus 1 part, Sophorae F
Atractylodis Rhizoma 3 parts)
Placebo(sorghum, black rice, propotion
Binder: vinegar, blended and made like
Li et al.2012[48] NR WIDC+RP+PD Coptidis Rhizoma, Cinnamomi Cortex, C
Fructus, endothelium corneum gigeriae
Vladimiriae Radix, paeoniae radix alba,
borneol 3g, ground into powder, binder
paste, fixed by patch.
NR: not reported; WIDC: warm the interior to dissipate cold; DWC: dispel wind-cold; CH: clear
heat; RD: remove dampness; ISQ: invigorate spleen qi; AI: astringe intestine; PD: promote
digestion; RP: relieve pain; RC: relieve convulsion; Formula/ingredients of herbal patch1: The
plant names used in this section were non-scientific names referring to Pharmacopoeia of China
(2015), the correspondent scientific names were listed in Appendix 3.
 Table 3: Effect estimates of AHP at Shenque for diarrhea in children
Comparison and Outcomes No. of Total No. of Effect estimates[95% CI] P value
Trials participants
AHP+CT vs CT
1. Duration of diarrhea MD[95% CI]
1.1 WIDC+ISQ+CT vs CT
Hou, et al.2007 1 90 -30.00[-36.96,-23.04]
Zou, et al.2010 1 120 -21.60 [-31.92,-11.28]
Subgroup meta-analysis (REM, 2 210 -26.70 [-34.74,-18.66] 0.000
I2=42.8% )
1.2 WIDC+CH+RD+CT vs CT
Wu, et al.2010 1 130 -72.00 [-85.36,-58.64] 0.000
1.3 WIDC+ISQ+RD+CH+AI+CT vs CT
Ji, et al.2011 1 120 -28.80 [-40.18,-17.42]
Dong, et al.2012 1 186 -34.50 [-37.93,-31.07]
Subgroup meta-analysis 2 306 -34.03[-37.31,-30.74] 0.000
Meta-analysis [REM, I2=89.7%) 5 646 -36.49 [-47.50,-25.49] 0.000
2. Treatment failure RR[95% CI]
2.1 WIDC+CT vs CT
Fu et al.1997 1 360 0.12[0.06,0.25]
Sun et al.2008 1 320 0.14[0.06,0.33]
Subgroup meta-analysis 2 680 0.13[0.08, 0.22] 0.000
2.2 WIDC+ISQ+CT vs CT
Hou et al.2007 1 90 0.05[0.07,0.39]
Li et al.2014 1 100 0.20[0.05,0.87]
Subgroup meta-analysis 2 190 0.11[0.03,0.34] 0.000
2.3 CH+RD+CT vs CT
Lao et al.2014 1 180 0.23 [0.12,0.45]
Zhang et al.2014 1 114 0.33[0.10,1.17]
Subgroup meta-analysis 2 294 0.25[0.14,0.45] 0.000
2.4 WIDC+RP+PD+CT vs CT
Zhao et al.2005 1 116 0.16[0.04,0.71]
Li et al.2012 1 254 0.31[0.10,0.92]
Subgroup meta-analysis 2 370 0.24[0.10, 0.58] 0.001
2.5 WIDC+ISQ+RD+AI+CT vs CT
Zeng et al.2001 1 100 0.15[0.04,0.65]
Wang et al.2010 1 52 0.21[0.05,0.91]
Zhang et al.2014 1 90 0.22[0.05,0.97]
Subgroup meta-analysis 3 242 0.19[0.08, 0.44] 0.000
2.6 Yunnan Baiyao+CT vs CT
Tan et al.2012 1 204 0.21[0.10, 0.43] 0.000
2.7 ISQ+AI+CT vs CT
Wu et al.2014 1 120 0.18[0.06, 0.57] 0.004
2.8 WIDC+RP+CT vs CT
He et al.2013 1 360 0.47[0.26, 0.84] 0.010
2.9 WIDC+RP+RC+CT vs CT
Li et al.2007 1 160 0.27[0.09, 0.77] 0.014
2.10 WIDC+CH+RD+CT vs CT
Wu et al.2010 1 130 0.26[0.12, 0.61] 0.002
2.11 DWC/CH+RD/ISQ+CT vs CT
Qian et al.2015 1 60 0.17[0.02, 1.30] 0.088
Meta-analysis 17 2810 0.21[0.17, 0.27] 0.000
REM: random effects model; FEM: fixed effects model; CT: conventional treatments
Table 4: Herbs frequently used for acupoint herbal patching at Shenque
Chinese herbal medicine Frequency
Count %
Wu Zhuyu(Euodiae Fructus) 11 52.6%
Rou Gui(Cinnamomi Cortex) 11 52.6%
Ding Xiang(Caryophylli Flos) 10 42.9%
Huang Lian(Coptidis Rhizoma) 8 38.1%
Mu Xiang(Vladimiriae Radix) 5 26.3%
Ku Shen(Sophorae Flavescentis Radix) 5 26.3%
Hu Jiao(Piperis Fructus) 5 26.3%
Cang Zhu(Atractylodis Rhizoma) 4 19.0%
Wu Beizi(Galla Chinensis) 3 14.3%
Bing Pian(Borneolum) 3 14.3%