Journal Pre-proof

An adaptive deep learning model to differentiate syndromes of infectious

fever in smart medicine

Zhuo Liu, Changchuan Bai, Hang Yu, Ying Zhu, Taihua Wu, Fanyu Bu

PII: S0167-739X(19)32184-3
DOI: https://doi.org/10.1016/j.future.2019.09.055
Reference: FUTURE 5221

To appear in: Future Generation Computer Systems

Received date : 15 August 2019

Revised date : 21 September 2019
Accepted date : 27 September 2019

Please cite this article as: Z. Liu, C. Bai, H. Yu et al., An adaptive deep learning model to
differentiate syndromes of infectious fever in smart medicine, Future Generation Computer
Systems (2019), doi: https://doi.org/10.1016/j.future.2019.09.055.

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 Journal Pre-proof

An Adaptive Deep Learning Model to Differentiate Syndromes of

Infectious Fever in Smart Medicine
Zhuo Liua,∗, Changchuan Baib,∗, Hang Yuc,∗, Ying Zhua,∗∗, Taihua Wua , Fanyu Bud
a
The First Affiliated Hospital of Dalian Medical University, Dalian, 116000, China.

of
b
Dalian Hospital of Traditional Chinese Medicine, Dalian, China.
c
Department of Computer Science, St. Francis Xavier University, Antigonish, B2G 2W5, Canada.
d
College of Computer and Information Management, Inner Mongolia University of Finance and Economics, Hohhot,
China.

pro
Abstract
Recently, smart medicine has been considered as a promising technique to treat the intractable
diseases by combining deep learning techniques with medical Internet of Things. As an important
re-
component in the integration of traditional and western medicine, smart medicine is particularly
effective to treat infectious fever. Before the cause of infectious fever diseases is ascertained, the
Chinese medicine intervention is able to alleviating symptoms and strive for time for the causes
detection. However, accurate syndrome differentiation, a difficult issue in infectious fever, is the
premise of the Chinese medicine intervention. This work presents a possible adaptive deep learn-
lP

ing model by integrating an adaptive dropout function into the stacked auto-encoder for computer-
aided syndrome differentiation in infective fever. Moreover, we summarize the main syndromes
and prescriptions in infectious fever. This work is expected to further the development of smart
medicine, especially smart Chinese medicine. More importantly, it points out a novel research
direction and medical technique in the treatment of infectious fever in clinic.
Keywords: Smart medicine, Medical Internet of Things, Deep learning, Infectious fever
a
urn

1. Introduction and reliable medical services by combining

medical techniques, artificial intelligence, big
At present, more and more wearable devices
data, cloud computing, and medical Internet of
are being developed such as bracelet, watch,
Things [5,6,7]. In the past two years, smart
wristband, and glasses and they are increas-
medicine, especially smart Chinese medicine,
ing the evolution of medical Internet of Things
has been presented and obtained several suc-
[1,2]. With the rapid proliferation of medical
cessful applications. For example, Zhang et al.
Jo

Internet of Things, smart medicine has made

[8] presented a unified smart Chinese medicine
remarkable progress [3,4]. In particular, smart
framework for computer-aided syndrome dif-
medicine was explored to offer the pervasive
ferentiation and prescription recommendation
on the edge-cloud computing platform. In ad-
∗
Zhuo Liu, Changchuan Bai, and Hang Yu are the
co-first authors.
dition, they proposed to use two deep learning
∗∗
Corresponding author: Ying Zhu. models for syndrome differentiation in hyper-
Preprint submitted to Future Generation Computer Systems September 20, 2019
 Journal Pre-proof
tension and spleen-stomach diseases [9,10].
Currently, smart Chinese medicine is a
significant component in the integration of
traditional Chinese medicine with western
medicine for treating infectious fever. Infec-
tious fever is caused by the invasion of various
pathogens such as bacteria, viruses, fungi, my-
coplasma, chlamydia, rickettsia, spirochetes,
and malaria [11]. In particular, the fever may
occur in the acute or chronic, localized or sys-
temic infection. From the point of view of
pathogenesis, the metabolites of pathogenic
microorganisms or their toxins act on white
blood cells to produce and release endogenous
heat sources. Their molecular weight is so s-
mall that they can directly act on the body tem-
perature regulation center through the blood-
re-
brain barrier. In this case, the temperature reg-
ulation point is raised, thus causing fever. In-
fectious fever is seriously threatening human
health. For example, during the past few years,
a large number of enterococci which can re-
lP
sist carbon, hydrogen, enzymes, and alkene
have emerged since the abuse of antibiotics
such as mepem and imiperem destroys the mi-
croecological balance in the intestine [12,13].
In particular, the infection of the enterococ-
ci may cause septicemia when the enterococ-
a
ci enters the blood. Moreover, the enterococ-
ci often leads to sepsis when it infects two or
urn
more human organs. Antagonism is the main
method of Western medicine in treating in-
fectious fever. For example, tigecycline and
polymyxin are usually used to treat the infec-
tion of the enterococci [14,15]. However, they
are not always effective. In this case, the infec-
tion of the enterococci will result in the death.
Jo
The speed of research and development of new
effective antibiotics is far behind that of bac-
terial mutation. When no effective antibiotics
can be developed to treat the infection of mu-
tant bacteria, human life is seriously threat-
ened. In this case, the intervention of tradition-
2
al Chinese medicine is neccessary. In addition,
there are more and more cases of fever of un-
known origin in the infectious fever at present
[16,17]. A lot of clinical experience shows that
the integration of traditional Chinese medicine
and western medicine is one of the most im-
portant ways for treating the fever of unknown
of
origin. In particular, during the examination
of pathogens, the traditional Chinese medicine
can be used to alleviate symptoms by bring-
ing down the fever. Therefore, the Chinese
pro
medicine is playing an important role in treat-
ing the infectious fever, especially the fever of
unknown origin, in the integration of tradition-
al Chinese medicine and western medicine.
The theory of traditional Chinese medicine
states that the toxin is caused by fever. Based
on a large volume of clinic experience, we
put forward a new theory of infectious fever,
which states that fever is caused by toxin. In
detail, the pathogenesis of the fever comes
from four respects. Firstly, the invasion of cold
causes the occlusion of Xuanfu, and thus lead-
ing to fever. Secondly, the external toxin is
latent in the body and then produces the fever.
Thirdly, toxin fever is caused by implication of
evil Qi and plague. Finally, the fever is caused
by internal toxin. Furthermore, we put forward
a new theory for syndrome differentiation and
treatment for infectious fever, the location by
three cardinal guides and zang-fu viscera, the
qualitative analysis by two-izations and qi and
blood, and the tendency determining by four
stages with deficiency and excess. In detail,
three cardinal guides includes exterior, interi-
or, and smi-exterior-interior, and zang-fu vis-
cera include heart and small intestine, lung and
large intestine, spleen and stomach, liver and
gallbladder, kidney and bladder, and pericardi-
um by heat and sanjiao. Two-izations include
cold and heat, and qi and blood states the qifen
and xuefen differentiation of infectious fever.
Four stages include latent stage, early stage,
 Journal Pre-proof
obvious stage of symptoms, and termination
stage. Moreover, each stage is divided into d-
eficiency syndrome and excess syndrome. By
this theory, the Chinese medicine aims to coor-
dinate yin and yang. For example, the Chinese
medicine restores ecological balance in intes-
tine by coordination yin and yang for treating
the invasion of enterococci. By the compre-
hensive application of Treatise on Epidemic
Febrile Diseases and Treatise on Febrile Dis-
eases, we put forward four therapeutic meth-
ods of sweating, dispersing, purging, and pre-
venting for bringing down the fever
Syndrome differentiation is the premise and
core of the Chinese medicine [18] for treating
the infectious fever. However, it is hard for the
traditional Chinese medicine to accurately dif-
re-
ferentiate the syndromes of the infectious fever
because of the complexity of the infectious
fever. On the one hand, the infectious fever
has many different syndromes. On the oth-
er one hand, some different syndromes have
lP
the similar symptoms, which poses a great
challenge on syndrome differentiation. Smart
Chinese medicine provides a new solution for
syndrome differentiation by integrating vari-
ous machine learning techniques into the tra-
ditional Chinese medicine. In this work, we
a
present a promising deep learning model by
combining an adaptive dropout function with
urn
the stacked auto-encoder for syndrome differ-
entiation of the infectious fever in the future
work. The adaptive dropout function is used
to set the activation of neurons in each hidden
layer of the deep learning model. To validate
the presented model, we summarize the main
syndromes of the infectious fever. This work
Jo
is expected to further the development of the
smart Chinese medicine.
Overall, the paper has three contributions:
• We put forward a new theory for syn-
drome differentiation and treatment of in-
3
fectious fever in the traditional Chinese
medicine. The presented theory is three-
fold: (1) fever being caused by toxin; (2)
the location by three cardinal guides and
zang-fu viscera, the qualitative analysis
by two-izations and qi and blood, and the
tendency determining by four stages with
of
deficiency and excess; (3) four therapeu-
tic methods of sweating, dispersing, purg-
ing, and preventing for treating infectious
fever.
pro
• We present a promising deep learning
model that integrates an adaptive func-
tion into the stacked auto-encoder for au-
tomatical computer-aided syndrome dif-
ferentiation of infectious fever.
• We summarize the main syndromes of in-
fectious fever by two methods of syn-
drome differentiation that are sanjiao syn-
drome differentiation and syndrome d-
ifferentiation by weifen, qifen, yingfen,
and xuefen.
The paper is organized into four sections in
the following. Section 2 presents the related
work on smart Chinese medicine and Section
3 describes the proposed deep learning mod-
el. The main syndromes of infectious fever are
summarized in Section 4 and the future work
is discussed in Section 5.
2. Related Work
Smart Chinese medicine was developed to
offer the computer-aided syndrome differen-
tiation and prescription recommendation by
combining data mining, machine learning,
cloud computing, and medical Internet of
Things with the theory of the traditional Chi-
nese medicine. In particular, data mining and
machine learning are used to mine and sum-
marize the successful clinic experience of a
 Journal Pre-proof
large number of experts in traditional Chinese
medicine. Once the clinic experience is mod-
eled and parameterized, the young or unex-
perienced doctors of the traditional Chinese
medicine can be helped with syndrome differ-
entiation and prescription recommendation, e-
specially for the difficult and complicated dis-
eases. Moreover, smart Chinese medicine pro-
vides a bridge for the treatment of complex
diseases by the integration of traditional Chi-
nese medicine with western medicine. In par-
ticular, with the smart Chinese medicine plat-
form, the doctors without the experience in the
traditional Chinese medicine can differentiate
the syndromes and write a prescription by the
theory of the traditional Chinese medicine.
Zhang et al. [8] presented a unified smart
re-
Chinese medicine framework for computer-
aided syndrome differentiation and prescrip-
tion recommendation based on the edge-cloud
platform, as shown in Figure 1.
a lP
urn
Figure 1: The unified smart Chinese medicine frame-
Jo
work.
The framework consists of three layers in-
cluding the edge layer, the network layer, and
the cloud layer. In the edge layer, the pa-
tient’s symptoms are collected by inquiry and
tongue inspection are collected. The network
4
layer is responsible for uploading the patien-
t’s symptoms to the cloud layer. Most algo-
rithms and models are implemented on cloud
for syndrome differentiation and prescription
recommendation or re-organization. In addi-
tion, the main companied symptoms are rec-
ognized and the prescription re-organization is
of
also implemented on cloud.
From the framework, syndrome differentia-
tion is the fundamental step for implementing
the smart Chinese medicine. In particular, a
pro
stacked auto-encoder was presented for poten-
tial syndrome differentiation of hypertension
which is a common disease all over the world.
The stacked auto-encoder is composed of two
hidden layers, as shown in Figure 2 [9].
Figure 2: The stacked auto-encoder for syndrome dif-
ferentiation of hypertension.
Each layer is an auto-encoder, as shown in
Figure 3.
The auto-encoder is defined by the follow-
ing forward pass:
h = fθ (W (1) x + b(1) ). (1)
y = gθ (W (2) h + b(2) ). (2)
The parameters of each auto-encoder are
trained by the back-propagation algorithm
[19].
 Journal Pre-proof

leads to the stagnation such as qi stagnation,

blood stagnation, and dampness stagnation,
and thus causing the spleen-stomach diseases.
Furthermore, Zhang et al. [10] pointed out the
most promising deep learning models includ-
ing multi-modal deep learning model and deep
computation model for syndrome differentia-

of
tion of spleen-stomach diseases, shown in Fig-
ure 4 and Figure 5.
Figure 3: Example of an auto-encoder.

pro
Furthermore, the authors summarized the
main symptoms and the companied symptom-
s of each syndrome of hypertension. Overal-
l, the primary symptoms of hypertension are
vertigo and headache. In detail, five common
re-
syndromes of hypertension are the stagnation
of liver qi with the primary symptoms, liv-
er fire flaring up with the primary symptom-
s and dysphoria, upper hyperactivity of liv-
er yang with the primary symptoms and two
lP

main symptoms of soreness and weakness of Figure 4: Example of a multi-modal deep learning mod-
el.
waist and knees and dysphoria with feverish
sensation in chest, palms and soles, deficien-
cy of yin and yang with the primary symptoms
and fear of cold and cold limbs, and abundant
phlegm-dampness with the primary symptom-
a

s and oppression in chest, and vomiting. The

corresponding primary prescriptions for each
urn

syndrome of hypertension are xiaochaihu de-

coction, longdan xiegan decoction, yiguan de-
coction, qiju dihuang decoction, and wendan
decoction. Other commonly added Chinese
herbs were summarized in this work.
Moreover, Zhang et al. [10] summarized the
promising deep learning models for syndrome
Jo

differentiation of spleen-stomach diseases. In

particular, they put forward the theory of
spleen-stomach diseases caused by stagnation.
The theory states the etiology and pathogen- Figure 5: Example of a deep computation model.
esis of the spleen-stomach diseases in modern
times. In detail, excessive eating and sedentary
5
 Journal Pre-proof

3. Potential Deep Learning Model for

Syndrome Differentiation of Infectious 
 1− ∫l (l− n )2
Fever √1
−∞
exp(− 2σ22 )dl n = 2k
σ 2π
y= ∫l (l− n+1
2
 1− √1 exp(− 2
)
)dl n = 2k + 1
σ 2π −∞ 2σ 2
In this section, we present a potential (4)
deep learning model for computer-aided syn- This distribution function is also monotoni-

drome differentiation of infectious fever by
integrating an adaptive dropout function into
the stacked auto-encoder. The stacked auto-
encoder is a promising model for syndrome
of
cally decreasing and its values are also in (0,1).
This function has been proved to be effective
to reduce the over-fitting of the deep compu-
tation model. More importantly, the adaptive

differentiation in smart Chinese medicine.
However, it often produces the over-fitting
when it is used for classification in complex
tasks. Aiming at this issue, Hinton et al. [20]
proposed a dropout model by setting the acti-
vation rate of each neuron in the hidden layer-
re-
s to 0.5. Although the dropout model could
reduce the over-fitting of the stacked auto-
encoder, it cannot always obtain the desirable
classification results since it always setts the
same activation rate in each hidden layer. To
lP
pro
dropout deep computation model based on this
distribution function has achieved a high clas-
sification accuracy in some experiments.
Therefore, we integrate the distribution
function into the stacked auto-encoder to
present an adaptive dropout stacked auto-
encoder which can be viewed as a special
case of the adaptive dropout deep computa-
tion model. Figure 6 shows an example of the
dropout stacked auto-encoder.

improve the classification accuracy, Bu et al.

[21] proposed an adaptive distribution function
to set the activation rate in different hidden lay-
ers. Let l denote the layer position and the ac-
tivation rate y of each neuron in the l-th hidden
layer is defined by:
a
urn

y{ = f (l) =
−0.1l + 0.05n + 0.5 n = 2k(k = 1, 2, ...) ,
−0.1l + 0.05n + 0.55 n = 2k − 1(k = 1, 2, ...)
(3)
where n is the total number of layers. Clearly,
the distribution function is monotonically de-
creasing and its values are always in (0,1).
Jo

More recently, Zhang et al. [22] proposed

another adaptive distribution function to set
the activation rate of each neuron in their pro-
posed deep computation model. In particular,
the activation rate y of the neuron in the l-th
layer is defined by:
Figure 6: Example of the dropout stacked auto-encoder.
In particular, the l-th hidden layer in the
adaptive dropout deep computation model is
shown in Figure 7.
6
 Journal Pre-proof

Algorithm 1: Adaptive Back-propagation.

Input: Training
{ set, η, threshold }
Output: θ = W , b ; W (2) , b(2)
(1) (1)

of
1 y = f (l);
2 for trainingobject = 1, 2, ..., M do
Figure 7: The l-th hidden layer in adaptive dropout deep
3 for j = 1, 2, 3, ...m do
computation model.

pro
4 Use Eq.(1) to compute hi ;
5 Use Eq.(4) to compute y;
The parameters of each layer in the adaptive
6 mark{i} = rand(size(h) > y);
dropout stacked auto-encoder are trained by
7 h = h · ∗mark{i};
the adaptive back-propagation algorithm de-
8 for i = 1, 2, 3, ..., n do
scribed in Algorithm 1.
9 Use Eq.(2) to compute yi ;
In the adaptive back-propagation algorithm,
re-
the output of each hidden and output neuron 10 if J(θ) > threshold then
is computed on line 3-9, and the partial deriva- 11 for i = 1, 2, 3, ..., n do
(3)
tives are computed by the back-propagation al- 12 Compute σi [ ];
gorithm on lines 11-23. Finally, the parameter- 13 for j = 1, 2, 3, ...m do
s are updated by the gradient descent method (2)
Compute σj [13];
lP

14
on lines 25-26.
15 σ (2) = σ (2) ·
∗[ones(size(σ (2) , 1), 1)mark{i}];
4. Common Syndromes of Infectious Fever
16 for i = 1, 2, 3, ..., n do
(2) (2) (3)
In this paper, we summarize the common 17 ∆bi = ∆bi + σi ;
syndromes of the infectious fever by the syn- 18 for j = 1, 2, 3, ...m do
a

(2) (2) (3)

drome differentiation of weifen, qifen, y- 19 ∆wij = ∆wij + hj · σi ;
ingfen, and xuefen. In particular, there are t-
urn

wo common weifen syndromes namely wind- 20 for j = 1, 2, 3, ...m do

(1) (1) (2)
heat invading wei and wind-cold invading wei 21 ∆bj = ∆bj + σj ;
and there are five common qifen syndromes in- 22 for i = 1, 2, 3, ..., n do
(1) (1) (2)
cluding heat pathogen invading lung, heat in 23 ∆wji = ∆wji + xi · σj ;
chest and diaphragm, heat stagnation in gall-
bladder, heat invading lung and stomach, and 24 //Gradient Descent
heat pathogen in intestines. Four common y- 25 W = W − η × ( M1 ∆W );
Jo

ingfen syndromes are heat injuring yingyin, 26 b = b − η × ( M1 ∆b);

invasion of pericardium by heat, heat blocking
heart-mind, and internal blockade and external
collapse, and five common xuefen syndromes
are bleeding due to blood heat, flaring heat in
qifen and xuefen, stirring of wind due to liver-
7
 Journal Pre-proof
heat, blood-heat injuring yin, and heat mixing
with blood. Moreover, heat pathogen invad-
ing lung often causes the syndrome of exuber-
ance of lung heat and the syndrome of lung-
heat and fu-viscera excess. The syndrome of
heat in chest and diaphragm can be divided in-
to two syndromes namely heat lying depressed
in the chest and diaphragm and heat burning in
chest and diaphragm. Moreover, the syndrome
of heat pathogen in intestines can be divided
into two types namely heat binding in intestine
and intestinal heat and diarrhea.
Table 1 lists the prescription for treating
each syndrome of the infectious fever.
5. Conclusion
re-
With the increasing development of medi-
cal Internet of Things, smart Chinese medicine
has made a great progress for mining the clinic
experience of famous doctors of the tradition-
al Chinese medicine. To promote the develop-
lP
ment of smart Chinese medicine, we presented
a potential deep learning model for computer-
aided syndrome differentiation of infectious
fever in this study. Specially, the presented
model integrates an adaptive distribution func-
tion into the stacked auto-encoder to reduce
a
the over-fitting and to improve the classifica-
tion accuracy. Furthermore, we summarized
urn
the main syndromes of the infectious fever by
the syndrome differentiation of weifen, qifen,
yingfen, and xuefen. We will validate the per-
formance of the presented model for syndrome
differentiation of the infectious fever on a large
number of clinic cases in the future work.
Jo
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of
Table 1: Primary prescription for each syndrome of the infectious fever.
Syndrome of infectious fever Primary prescription

pro
wind-heat invading wei yinqiao powder or sangju drink
wind-cold invading wei daqionglong decoction
exuberance of lung heat mahuang xingren gancao shigao decoc-
tion
lung-heat and fu-viscera excess xuanbai chengqi decoction
heat lying depressed in the chest and di- zhizichi decoction
aphragm
re-
heat burning in chest and diaphragm liangge powder
heat stagnation in gallbladder huangqin decoction with soybean sauce
and radix scrophulariae
heat invading lung and stomach baihu decoction
heat binding in intestine tiaoweichengqi decoction
lP

intestinal heat and diarrhea gegenqinlian decoction

heat injuring yingyin qingying decoction
invasion of pericardium by heat qinggong decoction
heat blocking heart-mind qinggong decoction with angong ni-
uhuang pills or zhibao mini-pills
internal blockade and external collapse shenfu decoction or shengmai powder
a

with angong niuhuang pills or zhibao

mini-pills
urn

bleeding due to blood heat xijiao dihuang decoction

flaring heat in qifen and xuefen qingwenbaidu decoction
stirring of wind due to liver-heat lingjiaogouteng decoction
blood-heat injuring yin qinghao biejia decoction
heat mixing with blood taoren chengqi decoction
Jo

9
 Journal Pre-proof

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Sutskever, U. R. Salakhutdinov, Improving neural
networks by preventing co-adaptation of feature de-
a

tectors, 2012, arXiv preprint arXiv:1207.0580.

[22] F. Bu, Z. Chen, P. Li, T. Tang, Y. Zhang, A
high-order CFS algorithm for clustering big da-
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ta, Mobile Information Systems (2016) 4356127:1-

4356127:8.
[23] Q. Zhang, L. T. Yang, Z. Chen, P. Li, F. Bu, An
adaptive droupout deep computation model for in-
dustrial IoT big data learning with crowdsourcing
to cloud computing, IEEE Transactions on Indus-
trial Informatics 2018, 15(4)(2019) 2330-2337.
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Zhuo Liu obtained her B. M. degree from Dalian Medical University, China, in
2009. She is working towards her doctoral degree at Dalian Medical University.
Her research interest is Lung Cancer Fundamentals and Clinic.

Changchuan Bai is currently a chief physician in Dalian Hospital of Traditional

of
Chinese Medicine, China, and a guest professor in Beijing University of Chinese
Medicine. He is one of the first famous Chinese medicine doctors in China. His
research interests include Exogenous Fever Disease, Classical Prescriptions, and
Smart Chinese Medicine.

pro
Hang Yu is is working towards the B. Sc. honours degree in Computer Science at
re-
the Department of Computer Science in St. Francis Xavier University, Canada. His
research interests include Deep Learning and Smart Medicine.
lP

Ying Zhu is currently a full professor at the First Affiliated Hospital of

Dalian Medical University. Her research interests include Infectious fever and
a

Smart Medicine.
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Taihua Wu obtained his B. M. degree from Dalian Medical University, China, in

1993, and his Ph. D degree from Dalian Medical University, China, in 2001. He is
currently a full professor in Dalian Medical University, China. His research
interests include Respiration and Lung Cancer.
 Journal Pre-proof
Fanyu Bu is currently an assistant professor at Inner Mongolia University of
Finance and Economics. His research interests include Deep Learning and Internet
of Things.

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The authors declared that there is no conflict of interest.

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An adaptive deep learning for syndrome differentiation in infectious fever.
Main syndromes of infectious fever are summarized.
An adaptive dropout function is investigated to improve the effectiveness of
deep learning.

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