1. science
2. medicine

Our reference: JEP 6989
P-authorquery-v9
AUTHOR QUERY FORM
Journal: JEP
Please e-mail or fax your responses and any corrections to:
E-mail: [email protected]
Article Number: 6989
Fax: +353 6170 9272
Dear Author,
Please check your proof carefully and mark all corrections at the appropriate place in the proof (e.g., by using on-screen
annotation in the PDF file) or compile them in a separate list. To ensure fast publication of your paper please return your
corrections within 48 hours.
For correction or revision of any artwork, please consult http://www.elsevier.com/artworkinstructions.
Any queries or remarks that have arisen during the processing of your manuscript are listed below and highlighted by flags in
the proof. Click on the ‘Q’ link to go to the location in the proof.
Location in
article
Q1
Q2
Q3
Q4
Query / Remark: click on the Q link to go
Please insert your reply or correction at the corresponding line in the proof
Please confirm that given names and surnames have been identified correctly.
As per the journal specification the abstract should be in the following format: Ethnopharmacological
relevance, Materials and methods, Results, and Conclusions. Please check and correct if necessary.
Please provide journal title for reference Chen and Xu (2003).
Please update references Lu et al. (in press) and Yan et al. (in press).
Thank you for your assistance.
G Model
ARTICLE IN PRESS
Journal of Ethnopharmacology xx (2011) xxx–xxx
Contents lists available at ScienceDirect
Journal of Ethnopharmacology
journal homepage: www.elsevier.com/locate/jethpharm
Graphical Abstract
An integrative approach of linking traditional Chinese medicine pattern
classification and biomedicine diagnosis
Journal of Ethnopharmacology xx (2011) xxx–xxx
Paern Classificaon in TCM
Disease diagnosis in biomedicine
Aiping Lu∗ , Miao Jiang, Chi Zhang, Kelvin Chan∗∗
Linkage between
TCM paern classificaon and diagnosis in
biomedicine
Historical evoluon on the integraon of the TCM paern
classificaon and disease diagnosis in biomedicine
Methodology of paern classificaon for diseases
Efficacy when integrang TCM paern classificaon and biomedical
disease diagnosis
Biological basis of TCM paern
TCM paern classificaon could lead new findings in biomedicine
JEP 6989 1
G Model
ARTICLE IN PRESS
JEP 6989 1–8
Journal of Ethnopharmacology xxx (2011) xxx–xxx
Contents lists available at SciVerse ScienceDirect
Journal of Ethnopharmacology
journal homepage: www.elsevier.com/locate/jethpharm
An integrative approach of linking traditional Chinese medicine pattern
classification and biomedicine diagnosis
1
2
3
Q1
Aiping Lu a,∗ , Miao Jiang a , Chi Zhang a , Kelvin Chan b,∗∗
4
a
5
b
China Academy of Chinese Medical Sciences, Beijing 100700, China
The University of Sydney, NSW 2006 and CompleMED University of Western Sydney, NSW 2560, Sydney, Australia
6
7
a r t i c l e
i n f o
a b s t r a c t
8
9
10
11
12
Q2 Article history:
Received 22 March 2011
Received in revised form 11 August 2011
Accepted 21 August 2011
Available online xxx
13
17
Keywords:
Pattern classification
Traditional Chinese medicine
Integrative medicine
18
1. Introduction
14
15
16
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
Traditional Chinese medicine (TCM) is a medical system with over 3000 years of continuous practice
experience and refinement through treatment observations. The TCM pattern classification (also defined
as Syndrome or Zheng differentiation) and treatment of ill health is the basis and the key concept of
the TCM theory. All diagnostic and therapeutic methods in TCM are based on the differentiation of TCM
pattern. TCM pattern can be considered as the TCM theoretical interpretation of the symptom profiles.
Pattern classification is often used as a guideline in disease classification in TCM practice and has been
recently incorporated with biomedical diagnosis, resulting in the increasing research interest of TCM
pattern among various disciplines of integrative medicine. This paper describes the historical evolution on
the integration of the TCM pattern classification and disease diagnosis in biomedicine, the methodology of
pattern classification for diseases, efficacy of TCM practice with integration of TCM pattern classification
and biomedical disease diagnosis, and the biological basis of TCM pattern. TCM pattern classification,
which may lead to new findings in biological sciences, was also discussed.
© 2011 Published by Elsevier Ireland Ltd.
Traditional Chinese medicine (TCM) is a healthcare-focused
medical system with its rich experience over 3000 years of continuous practice and refinement through observations, testing and
critical thinking in treating ill-health. TCM management of health
can be characterized as holistic with the emphasis on regulating the
integrity of the human body functions and the interaction between
human individuals and their environments. TCM applies multiple
therapeutic methods for patient management such as, life-style
adjustment of diet, treatments with prescribed herbal formulas
apart from the application of acupuncture and other nonchemical
interventions such as tuina (medical massage) and taichi.
TCM pattern classification (also called as Syndrome or Zheng differentiation) is the basic unit and the key concept in TCM theory.
All diagnostic and therapeutic methods in TCM are based on the
differentiation of TCM pattern, and this concept has been used for
thousands of years in China (Chen and Xu, 2003; Ma et al., 2010).
TCM pattern can be considered as the TCM theoretical interpretation of the symptom profiles of a disease but not only an assemblage
of disease symptoms. It is also used as a guideline in disease clas-
∗ Corresponding author. Tel.: +86 10 64067611; fax: +86 10 84032881.
∗ ∗ Corresponding author. Tel.: +61 2 91141485; fax: +61 2 46203291.
E-mail addresses: [email protected] (A. Lu), [email protected]
(K. Chan).
sification in TCM practice. For example, patients suffering from
the same disease may be categorized into different TCM patterns,
whereas different diseases may be categorized as the same TCM
pattern.
As one of the main items of complementary and alternative medicine, the practice of TCM has increased dramatically in
recent decades (Eisenberg et al., 1998). However, the study of
TCM still encounters serious challenges due to the almost irreconcilable differences from the conventional orthodox medicine
(OM) (Fontanarosa and Lundberg, 1998). There are at least two
major differences between TCM and OM: patient classification and
intervention methodology. In patient classification, TCM uses pattern classification based on TCM information (obtained from direct
observation of patients’ external features, auscultation & olfaction,
interrogation or questioning and pulse detection and palpation)
while OM uses disease diagnosis based on pathological examinations of individual organ functions and receptors malfunctions. As
to the intervention: In TCM, establishing the therapeutic principles and general rules is of initial importance; this is followed
by the formulation of prescriptions containing Chinese material
medica (CMM) and other therapeutic measures because the latter
depends on the former for guidance. The outcome of a treatment
will indicate whether or not the diagnosed pattern and the CMM
prescription therapy are correct. The basic steps of the four TCM
examination techniques help to confirm the signs and symptoms
that, in turn, serve as means to work out the CMM prescriptions. Finally, the therapy directs the formulation of a specific
0378-8741/$ – see front matter © 2011 Published by Elsevier Ireland Ltd.
doi:10.1016/j.jep.2011.08.045
Please cite this article in press as: Lu, A., et al., An integrative approach of linking traditional Chinese medicine pattern classification and
biomedicine diagnosis. J. Ethnopharmacol. (2011), doi:10.1016/j.jep.2011.08.045
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
G Model
JEP 6989 1–8
2
ARTICLE IN PRESS
A. Lu et al. / Journal of Ethnopharmacology xxx (2011) xxx–xxx
30
Without Pattern
classification
25
With Pattern
classification
20
15
10
5
0
Before
2000
20002001
20022003
20042005
20062007
20082009
Fig. 2. The publications in Chinese about clinical trials on Dan Shen Di Wan (a TCM
product). The data were obtained from CBM database.
Fig. 1. The published papers in Chinese about TCM pattern classification. The data
were obtained from CBM database (till February 17 of 2011).
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
prescription. These essential steps are interlinked, interconnected
and indispensable in TCM practice.
In OM practice symptomatic treatments mainly aim at relieving patients’ complaints or main symptoms with pharmaceutical
drugs and surgery in severe cases, based on disease diagnosis to
provide specific chemical components acting on targeted receptors
or enzyme components at molecular levels. This paper attempts
to illustrate that the appropriate linking of TCM pattern classification with OM disease diagnosis can provide a better understanding
of the incorporation of TCM pattern classification into OM disease
diagnosis.
2. History of integration of TCM pattern classification and
disease diagnosis in biomedicine
In China, the integration of TCM pattern classification with disease diagnosis in biomedicine was proposed in the early 1960s by
Zhu (1962). In 1980s, the Chinese Association of Integration of TCM
and Western medicine was setup with the objectives of improving the integration of TCM with OM, in which the incorporation
of the TCM pattern classification into disease diagnosis in OM is
one of the tasks. The integration of the TCM pattern classification
and biomedical disease diagnosis has then been reported in the
English journals. Table 1 shows that there is a tendency in the TCM
pattern classification research, from the TCM concept to the biological basis, from clinical trial to innovation in biomedicine, from
clinical trial on herbal medicine to on biomedicine therapy, from
general biological basis exploration to the exploration with systems
biology approach. The clinical trial with the TCM pattern classification will help to provide improvement with more innovation in
biomedicine.
Since the 1980s we witnessed the changing situation of clinical studies with the TCM pattern classification in diseases in China.
TCM practitioners or integrative medicine practitioners in China
focused on clinical observations with TCM pattern classification
in diseases. From CMB (Chinese BioMedical Literature Database
at http://sinomed.imicams.ac.cn/index.jsp), there were more than
50,000 papers published on clinical observations with TCM pattern classification in different diseases. Fig. 1 shows the papers an
increase in the number of publications annually. Of these papers,
429 types of diseases linked with 190 categories of TCM pattern
have been treated with TCM interventions integrated with the TCM
pattern classification. Top 50 diseases treated in this manner and
top 50 TCM patterns classified in the 429 diseases are summarized
in Tables 2 and 3.
From Tables 2 and 3, it can be concluded that TCM pattern classification has been widely incorporated into the treatment of many
types of diseases know in biomedicine identified in OM practice.
Because of the complexity in RCTs with TCM pattern classification; there were few RCT publications in the Chinese language
journals. However, in recent years the observation detects an
increase of publications in RCTs with inclusion of TCM pattern classification. For example, a total of 171 RCT publications in Chinese
language journal on Dan Shen Di Wan (a TCM proprietary product for treatment of angina pectoris) was observed and more RCTs
were reported after 2006 (Fig. 2). A total of 381 papers on clinical
study were found in the Pubmed-cited journals with pattern classification (or syndrome differentiation) (till July 31 of 2010). Most
of them were published in Chinese language journals with English
abstracts, and only 44 published in English with full papers. Of these
33 were published after 2005, and 11 from 1983 to 2004. About 10
types of diseases with the TCM pattern differentiation were studied in the 12 RCTs from 2002 to 2009 (Jiang et al., 2010a). A total
of 11 RCTs showed that TCM was effective in the treatment of the
diseases or in the alleviation of symptoms, with one study failing
to confirm the efficacy. No study reported negative results.
Presently in China, governmental authorities only strongly fund
high quality clinical studies with strict regulations and guidelines
on TCM clinical trials. Researchers are required to pay more attention to the quality of clinical trials with proper protocols. It has
been estimated that there are more than 50 TCM clinical trials
ongoing that are sponsored by the National Key Technology R&D
Program in China [http://www.most.gov.cn/eng/programmes1/
200610/t20061009 36224.htm]. Among them, more than half
includes interventions based on the TCM pattern classification. We
believe that more evidence-based clinical trials will confirm and
support the role of the TCM pattern classification in future clinical
studies on the efficacy assessment of TCM practice.
3. Method for TCM pattern classification for diseases
TCM pattern identification had been used as a basis for
developing treatment protocols in clinical trials. TCM syndromes
differentiate biomedical diseases into different patterns, and each
pattern comprises of symptom/signs that have their own unique
treatment protocol. The TCM pattern classification is mainly based
on symptoms (including self-reported signs), tongue and pulse
diagnosis, and it is difficult to interpret in OM terminology. This
could be the main reason why TCM pattern classification was not
incorporated into the biomedical disease diagnosis. For this reason
Please cite this article in press as: Lu, A., et al., An integrative approach of linking traditional Chinese medicine pattern classification and
biomedicine diagnosis. J. Ethnopharmacol. (2011), doi:10.1016/j.jep.2011.08.045
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
G Model
JEP 6989 1–8
ARTICLE IN PRESS
A. Lu et al. / Journal of Ethnopharmacology xxx (2011) xxx–xxx
3
Table 1
Important events in TCM pattern research published at first time in Medline or SCI indexed journals.
Key event
Journal
Author
Years
Integration of TCM and Western medicine
Double blinded clinical trial in coronary heart disease with TCM intervention
Basic concept on TCM pattern classification
Review on TCM pattern of blood stasis
Biological basis focusing on TCM pattern of kidney deficiency
Biological basis focusing on TCM pattern
Linkage between TCM symptoms and biological parameters in gastritis
Integration of TCM pattern classification into disease diagnosis
TCM pattern and innovation in biomedicine
Clinical efficacy and TCM pattern classification in biomedical disease with RCT
Role of TCM pattern classification in biomedical sciences
TCM pattern help biomedicine for improvement of efficacy for biomedical disease
Omics based TCM pattern classification in biomedical disease
Safety evaluation based on TCM pattern classification in a biomedical disease
Medline, Chinese
Medline, Chinese
Medline, English
Medline, Chinese
Medline, English
SCI, English
SCI, English
SCI, English
SCI, English
SCI, English
SCI, English
SCI, English
SCI, English
SCI, English
Chen KJ
Chen KJ
No author listed
Chen KJ
Zhang Q
Chen ZQ
Li S
Jiang WY
Zha Q
Lu A
He Y
Lu C
van Wietmarschen H
Jiang M
1979 (Chen, 1979)
1982 (Chen, 1982)
1983 (No author listed, 1983)
1983 (Chen, 1983)
1990 (Zhang et al., 1990)
1999 (Chen et al., 1999)
2003 (Li et al., 2003)
2005 (Jiang, 2005)
2006 (Zha et al., 2006)
2009 (Lu and Chen, 2009)
2007 (He et al., 2007a)
2009 (Lu et al., 2009)
2009 (van Wietmarschen et al., 2009)
2010 (Jiang et al., 2010b)
Table 2
Top 50 TCM patterns in Chinese publications about TCM clinical studies.
Patterns (Zheng)
Qi deficiency
Blood stasis
Deficiency of the kidney
Damp-heat
Spleen deficiency
Blood deficiency
Yin deficiency of liver and kidney
Wind-cold
Yin deficiency
Cold-dampness
Qi stagnation
Hemoptysis
Qi depression to blood stasis
Wind heat
Blood heat
Pyrexia
Hematochezia
Cough
Asthenia of qi and blood
Yang deficiency
Bleeding Syndrome
Arthralgia syndrome
Spleen-kidney Yang deficiency
Asthenia syndrome
Bellyache
Total papers
20,286
19,065
12,600
9856
9088
3488
2016
1916
1876
1680
1620
1599
1452
1088
792
710
606
605
560
448
386
375
354
329
276
Patterns (Zheng)
Paper No.
Kidney-yang deficiency kidney-yang deficiency
Heat syndrome
Haematemesis
Deficiency-cold
Kidney-Yin deficiency
Constipation
Spleen Qi deficiency
Phlegm accumulation
Common influenza
Deficient cold of spleen and stomach
Night Sweats
Apoplexia
Liver heat
Liver-stomach disharmony
Edema
Xiaoke
Dysmenorrheal
Dyspnea
Jaundice
Vomit
Headache
Dyspepsia caused by improper diet
Phlegm syndrome
Cervical spondylosis
Dizziness
272
268
238
232
218
209
191
172
163
162
156
146
140
128
126
119
113
106
101
95
94
90
89
86
84
Table 3
Top 50 diseases published in Chinese about the clinical studies in TCM.
Diseases
Total number of paper
Diseases
Paper No.
Hemoptysis
Hematochezia
Hematuria
Hypertension
Diabetes
Pneumonia
Stenocardia
Abdominalgia
Albuminuria
Respiratory tract infection
Haematemesis
Hyperlipidaemia
Cerebral infarction
Constipation
Diarrhea
Blood hyperviscosity
Dyspnea
Cardiac failure
Asthma
Influenza
Infection
Aging
Nephrosis
Edema
Gastritis
1599
606
575
421
360
352
294
276
264
249
238
229
214
209
209
207
201
186
175
163
161
130
126
126
124
Dysmenorrheal
Prostatitis
Jaundice
Vomit
Cephalalgia (encephalalgia)
Nephrotic syndrome
Bronchitis
Vertigo
Osteoporosis
Arteriosclerosis
Myocardial infarction
Coma
Urinary tract infection
Anaphylaxis
Irritable bowel syndrome
Facial paralysisfacial paralysis
Migraine
Encephalorrhagia
Prostate hyperplasia
Hepatic tumor
Kidney failure
Depression
Arthralgia (arthrodynia)
Coronary heart disease
Dyspepsia
113
108
101
95
94
88
86
84
81
80
80
76
75
63
61
60
60
59
57
56
55
54
53
53
52
Please cite this article in press as: Lu, A., et al., An integrative approach of linking traditional Chinese medicine pattern classification and
biomedicine diagnosis. J. Ethnopharmacol. (2011), doi:10.1016/j.jep.2011.08.045
G Model
JEP 6989 1–8
4
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
208
209
210
211
212
213
ARTICLE IN PRESS
A. Lu et al. / Journal of Ethnopharmacology xxx (2011) xxx–xxx
TCM pattern classification becomes the most important factor to
be included in the incorporation process.
There is a wide variation of the differentiation of symptoms,
tongue and pulse diagnosis. Some of these are not closely related
to the disease diagnostic parameters, and are less focused upon
by biomedicine, such as thirst and turbid urine and yellow tongue
fur in some diseases (Lu et al., 2004). The quantification of TCM
patterns usually is based on the textbook or expert consensus. On
the other hand, statistical evaluation of the TCM pattern or pattern change can be obtained (Lu et al., 2008; Berle et al., 2010).
Although the symptoms, which are the key information for the
TCM pattern classification, are diversified in a disease, they can
be clustered into specific groups using bio-statistical approaches,
even though traditionally they are classified into groups based
on the TCM theory and clinical experiences. A multi-center RCT
study had shown that among 13 common symptoms of rheumatoid arthritis (RA), 5 are related to the joint, 8 are not related to
the joint. Symptoms clusters in 396 patients could be classified
into four factors (symptom combinations) with factor analysis. The
symptom combinations are very similar to the patterns differentiated by the TCM theory in RA patients, which divides the RA into
three basic patterns: cold, heat and deficiency patterns (He et al.,
2007a).
More instruments are being developed in the diagnosis of
tongue appearance and pulse feeling (Lu et al., 2008; Yan et al.,
2009; Berle et al., 2010; Xu et al., 2010). It is encouraging that
integration of TCM information in symptoms, signs, tongue appearance and pulse feeling will be the focus in the near future, and
TCM pattern classification would be based on objective examinations, which can further lead to more understanding with
biomedical aspects and the concepts can be used by other OM
scientists.
4. Efficacy of TCM practice with integration of TCM pattern
classification and biomedical disease diagnosis
Increasing numbers of medical researchers recognized that the
combination of disease diagnosis in biomedicine and pattern classification in TCM is essential for the clinical practice when TCM
is included as part of the treatment along side with the OM diagnostic approaches, and it has been a common practice model in
China since it focuses on a better assessment of clinical effect
(Manheimer et al., 2009). Over the past 50 years, clinical practice in TCM hospitals in China has applied both principles of
biomedical disease diagnosis and TCM pattern classification for
intervention/treatment of patients. A clinical investigation indicated that a more effective treatment rate could be achieved from
the RA patients with specific symptoms and co-diagnosed and
treated based on their TCM pattern classification (He et al., 2007a).
While clinical research on TCM has been conducted in China and the
West, much of this research was inadequate in delivering reliable
data. In 2008, a review of a total of 70 Cochrane systematic reviews
regarding TCM clinical research found most of the studies to be
inconclusive (Manheimer et al., 2009). Several reasons could be
identified: Most of trial protocols employed randomized controlled
trial (RCT) designs that were not suitable for TCM research, and
most of the investigations had not involved collaboration between
OM and TCM scientists. There was a failure to consider fundamental
concepts of TCM in terms of diagnosis. It is important to incorporate
the concepts of both OM and TCM into research protocols, necessitating collaboration between OM and TCM practitioners (Tsang,
2007).
Many meta-analyses on TCM clinical studies focused on the specific diseases, showed no evidence to prove the efficacy of TCM in
the treatment of the diseases because of lower quality of clinical
design (Chen and Hu, 2006; Zhu et al., 2008; Tu et al., 2009). Anecdotally, increasing number of patients were seeking help from TCM
for its better clinical outcomes. This suggests that TCM could have
a clinical effect; and it is necessary to assess the TCM clinical efficacy with better and innovative approaches. The RCT is considered
to be the methodology offering the highest level of evidence. However, different types of research approaches are needed to assess
different types of clinical problems. Observational studies and case
reports often are the only research method suitable for assessment
of TCM efficacy. TCM, being holistic in approach, it identifies and
treats syndromes rather than diseases. Recent RCTs on TCM have
been conducted and showed clinical efficacy in the treatment of
arthritis based on TCM pattern differentiation (Goldbach-Mansky
et al., 2009; Min et al., 2010; Tsang et al., 2010; Wang and He, 2010).
It is believed that the incorporation of TCM pattern classification
into disease diagnosis would greatly improve the efficacy of TCM
interventions.
Evaluation of TCM treatment efficacy should focus on a specific subgroup of patients with a specific disease, or a specific
herbal preparation with clinically proven effectiveness. Many system reviews currently on TCM efficacy showed that there were
no evidence to support the TCM intervention efficacy, and more
quality clinical trials of TCM were needed for collecting evidence
to support the TCM clinical application without focusing on the
TCM pattern classification. Based on our search on CMB (Chinese
BioMedical) Literature Database (in Chinese) and Pubmed database
(in English), there were 180 RCT about Danhong Injection (consisting of safflower and Salvia miltiorrhiza), which is commonly used
in the clinical practice in China for the activation of blood stasis
(based on TCM theory), and only two of them were based on TCM
pattern classification.
As TCM pattern classification focuses on further classification
of the patients into treatment sub-group, the treatment efficacy
would be improved if the responsive cases can be clarified from
non-responsive cases with the their TCM patterns. It has been
reported that the TCM pattern differentiation can specify the indications for the combination biomedical therapy in the treatment
of existing RA patients (Lu et al., 2009). A RCT was performed to
compare the symptomatic effects on patients with benign prostatic
hyperplasia (BPH) treated by two therapeutic approaches, the OM
and TCM, and the results showed that TCM is a potentially effective
treatment in improving the Quality of Life (QOL), prostate volumes
and maximum UFR for a subgroup of patients with BPH, and the
non-urethra related symptoms experienced by BPH patients could
be one of the parameters for further distinguishing the effects of
TCM and OM therapies (Li et al., 2010). The results suggest that it
may also be useful in defining specific indications for biomedical
therapies used to treat other diseases.
TCM psychotherapy is a special intervention and more clinical
experience proved that it could be used alone or in combination
to treat many diseases. TCM psychotherapy was recorded in many
ancient TCM books and has been applied in many mental diseases or
diseases with mental symptoms successfully for thousands of years.
Distinguished from modern psychotherapy, it integrated TCM theory basis with several therapeutic approaches such psychological
counseling and cognitive-behavioral techniques together, aiming
at the harmony of human body, mental and social status. Since
according to TCM theory, the human is regarded as a holistic system, there exist inner correlations between Zang-fu viscera and
various emotions, the regulation of one aspect will have effect
to the other aspect, and TCM psychotherapy focuses on not only
mental diseases, but also physical disorders during treatment. This
feature determines the high applicability of TCM psychotherapy
to the psychosomatic diseases, one good representative is female
menopausal syndrome. Modern clinical study, especially for the
randomized controlled trials (RCTs) conducting, usually ignores
Please cite this article in press as: Lu, A., et al., An integrative approach of linking traditional Chinese medicine pattern classification and
biomedicine diagnosis. J. Ethnopharmacol. (2011), doi:10.1016/j.jep.2011.08.045
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
230
231
232
233
234
235
236
237
238
239
240
241
242
243
244
245
246
247
248
249
250
251
252
253
254
255
256
257
258
259
260
261
262
263
264
265
266
267
268
269
270
271
272
273
274
275
276
277
278
279
G Model
JEP 6989 1–8
ARTICLE IN PRESS
A. Lu et al. / Journal of Ethnopharmacology xxx (2011) xxx–xxx
280
281
282
283
284
285
286
287
288
289
290
291
292
293
294
295
296
297
298
299
300
301
302
303
304
305
306
307
308
309
310
311
312
313
314
315
316
317
318
319
320
321
322
323
324
325
326
327
328
329
330
331
332
333
334
335
336
337
338
339
340
341
TCM psychotherapy due to the highly personalized therapeutic regimen and the difficulties in the fulfilling of the treatment, though
TCM based psychotherapy is an essential part of TCM therapeutics, and it has been widely used in many diseases and achieved
favorable outcomes, especially in those diseases signed with psychological symptoms (Wang et al., 2011). Therefore more clinical
trials should be focused on the effectiveness of TCM based psychotherapy.
5. Biological basis of TCM pattern
To illustrate the importance of TCM pattern in both the theory
and the practice of TCM, much effort has been paid to investigate its
biomedical basis. Previous study explored the biological basis of the
TCM pattern by applying general biological approaches. The results
included the linkage between sex hormones and Kidney deficiency
pattern in chronic nephritis (Zhang et al., 1990), linkage between
C-reactive protein and cold/hot pattern in RA (Zhao et al., 2006),
linkage between homeo-rheology and blood stasis pattern in cardiovascular diseases (Jia, 1989; Lin and Liao, 1990; Takeichi and
Sato, 1997), and linkage between gastric mucosal immune reactions and the TCM pattern in chronic gastritis (Lu et al., 2005).
It is still far from reaching a full understanding of the inherent
mechanism of the TCM pattern, as it is known that the scientific
evaluation of TCM into OM disease terminology is very difficult
using existing conventional methods (Lu et al., 2007; Wu et al.,
2008). In the exploration on the biological basis of TCM patterns,
Li et al. explored the molecular basis of TCM pattern within the
context of neuro-endocrine-immune (NEI) system (Li et al., 2006,
2007). Patients suffering from RA are found to experience an alteration of the NEI system (He et al., 2007a; Lu and Chen, 2009). Our
previous studies showed that there were some the distinct molecular signatures in discriminating the RA patients with traditional
Chinese medicine (TCM) cold pattern and heat pattern (Lu et al., in
press). These results suggest that a better knowledge of the main
biological processes involved at a given pattern in TCM could help
to choose the most appropriate treatment.
The advances of “Omics” revolution and methodology in modern life science, bioinformatics and systems biology have offered
an opportunity to integrate multi-dimensional and various types
of data, in the new era of the medical and biological sciences (Lu
et al., in press; Zheng et al., 2011). Capturing these unprecedented
opportunities and challenges, bioinformatics and systems biology
approaches are expected to open the way to a new convergence of
TCM and OM in both concept and methodology. Such observations
can be interpreted as follows: Prescribing Chinese herbal medicine
(often referred to as Chinese material medica, CMM) in the form
of composite formulae based on TCM pattern classification is the
key disease prevention/treatment regimen in TCM practice. The
human body is a complex and hugely interconnected system, which
is dynamically regulated within boundaries of cells, tissues and
organs to achieve homeostasis. The treatment strategy of prescribing TCM composite formulae is based on supporting the balancing
capabilities of the body (salutogenesis) to recover from an imbalanced state. In the formula, each CMM contains many compounds
that possess concerted actions (Chan and Lee, 2000; Chan, 2005). A
successful formula organizes these concerted actions derived from
different CMMs to create holistic, multi-target, multi-dimensional
pharmacological actions, which could be expressed by technology
derived from “omics’ and systems biology, to achieve personalized
therapy. Thus the advance of pharmcogenomics and systems biology has created the building blocks to measure the mechanisms of
composite CMM formulae by modern pharmacology methodology
(Wang et al., 2009).
5
6. TCM pattern classification could lead new findings in
biomedicine
TCM pattern classification would lead to new findings when
linked with biomedicine diagnosis since there should have some
differences between different TCM patterns in the same diseases as
diagnosis in OM. For example, the treatment of RA with TCM intervention in the later stage of the disease usually focuses on the blood
stasis and deficiency TCM pattern (Zhou et al., 2000; Wang et al.,
2010). While TCM blood stasis pattern shows some linkage with
platelet activity (Ma et al., 2009), the TCM deficiency pattern shows
some linkage with immune response (Yuan et al., 2010). Thus it is
reasonable to make the hypothesis that there is a positive correlation among IgA (reflecting immune response), platelet and cartilage
erosion (severe in late stage) in RA. The changes in peripheral IgA
level and platelet number positively correlated with the grade of
cartilage damage in active RA patients, thus supporting the hypothesis (Zha et al., 2006; He et al., 2007b). In the clinical practice, the
CMMs with activating blood stasis pattern, and those reinforcing
deficiency pattern and containing polysacharides or animal proteins were used for the treatment (Yang et al., 2003; Zhang et al.,
2010).
On the other hand, biomedical sciences not only help identify
the scientific basis for TCM pattern, it can also improve further
clarification of TCM pattern. For example, Kangxin capsule and
Tongxinluo capsule are two TCM products exist in the China market
for years, are used to target TCM Qi deficiency and blood stasis pattern in the treatment of angina pectoris. Our previous study found
that biomedical parameters such as LDL and blood pressure can be
used as indicators showing the efficacy of Tongxinluo capsule and
Kangxin capsule respectively in the treatment of angina pectoris
even though there are targeting same TCM pattern (Yan et al., in
press).
Another important concept in TCM is named as “Treating Different Diseases with the Same Therapy” (TDDST) has been applied
in TCM practice. Some patients with Rheumatoid Arthritis (RA) and
other with Coronary Heart Disease (CHD) can be treated with similar therapies. (For example, activation of blood stasis for RA patients
with TCM pattern of blood stasis.) This suggests that there could
be something commonly existing between RA and CHD conditions
according to TCM diagnosis within the context of imbalance in the
body functions biological networks or biological basis. In order to
substantiate such concepts, there exists a need to search for these
interlinking data from reliable databases. Presently in our leading research database the amount of biomedical data is growing
rapidly, it is possible to get relevant and meaningful information
through the techniques developed in the fields of data mining.
Our previous study proposed an hierarchical analysis algorithm
called discrete derivatives which is based on the frequencies of coconcurrent MeSH (The Medical Subject Headings) terms, we have
found some significant results which can support the concept of
TDDST, and also that the biological basis and biological networks
commonly existing in RA and CHD. These networks can be affected
by the basic CMMs, which are widely used in the TCM therapies on
both RA and CHD (Figs. 3 and 4).
Therefore TCM pattern classification, as a new approach to
identify the relevant diseases among patients into different TCM
categories will certainly contribute important concepts in the
innovation of integrative treatment of diseases with supporting
biomedical sciences.
7. Future perspectives
The principles of TCM pattern classification (obtained from
direct observation of patients’ external features, auscultation &
Please cite this article in press as: Lu, A., et al., An integrative approach of linking traditional Chinese medicine pattern classification and
biomedicine diagnosis. J. Ethnopharmacol. (2011), doi:10.1016/j.jep.2011.08.045
342
343
344
345
346
347
348
349
350
351
352
353
354
355
356
357
358
359
360
361
362
363
364
365
366
367
368
369
370
371
372
373
374
375
376
377
378
379
380
381
382
383
384
385
386
387
388
389
390
391
392
393
394
395
396
397
398
399
400
401
402
403
G Model
JEP 6989 1–8
6
ARTICLE IN PRESS
A. Lu et al. / Journal of Ethnopharmacology xxx (2011) xxx–xxx
Fig. 3. The con-concurrent MeSH terms between RA and coronary heart disease were obtained from PubMed (till July 30 of 2010). Here is a small part focusing on apoptosis,
inflammation and genotype and their con-concurrent MeSH terms. The results indicate that there might be a similarity on apoptosis, inflammation and genotype and their
networks between the pathogenesis of RA and coronary heart disease.
Fig. 4. Radix Notoginseng (NG, San Qi in Chinese) and Radix Salivae Miltiorrhizae (SM, Dan Sheng in Chinese) are an herbal combination and commonly used for activation of
blood stasis in TCM practice. The con-concurrent MeSH terms on NG and SM were obtained from PubMed (till July 30 of 2010), which then incorporated into the con-concurrent
MeSH terms between RA and coronary heart disease to find out the overlapped con-concurrent MeSH term network. Here is a small part focusing on apoptosis, superoxide
dismutase and intercellular adhesion molecule-1 and their con-concurrent MeSH terms, which NG and SM have been reported to target on (Triangle: SM; Diamond: NG;
Hexagon: combined two herbs). The results indicate that NG and SM have shown their activity in the similar MeSH terms (targets) about apoptosis, superoxide dismutase,
intercellular adhesion molecule-1 and their con-concurrent MeSH terms, which are co-shared by both in RA and coronary heart disease.
Please cite this article in press as: Lu, A., et al., An integrative approach of linking traditional Chinese medicine pattern classification and
biomedicine diagnosis. J. Ethnopharmacol. (2011), doi:10.1016/j.jep.2011.08.045
G Model
JEP 6989 1–8
ARTICLE IN PRESS
A. Lu et al. / Journal of Ethnopharmacology xxx (2011) xxx–xxx
olfaction, interrogation or questioning and pulse detection and
palpation) provide a firm basis to classify patients into subtypes
for selection of specific therapy even though the subjective measurements such as tongue appearance and pulse diagnosis through
direct observation require standardization.
The development of objective measurements such as quality of life instruments to monitor patients reported outcomes
(Zhao and Chan, 2005) and systems biology technology that provide biomarker measurement during treatment intervention will
substantiate the subjective assessment of TCM pattern classification of diseases. These two aspects should be considered in the
development of integrative medicine including OM and TCM. Furthermore, investigations based on systems biology approaches on
mechanisms of actions of CMM formulae can be applied as holistic approach in analyzing the complexity of CMM formulae. This
approach has become an important direction for the elucidation of
mechanism of TCM herbal mixtures used in clinical management of
patients treated by both OM and TCM (Lu and Li, 2010). Therefore
systems biology and bioinformatics are useful tools to clarify the
molecular basis for the TCM pattern. Likewise, TCM pattern classification could provide innovation approaches to examine if holistic
nature provided by OM using modern biomedical sciences.
In summary, the incorporation of TCM pattern classification into
biomedical disease diagnosis will lead to a new era in the development of medical sciences to provide improving treatment efficacy
with specific indications of integrative therapy. Further classifying
patients suffering from diseases into TCM pattern categories before
therapy selection will lead to innovation of biomedicine based concepts for TCM pattern assessment.
404
405
406
407
408
409
410
411
412
413
414
415
416
417
418
419
420
421
422
423
424
425
426
427
428
429
430
431
432
Acknowledgements
433
437
This research is partly sponsored by the projects from the
National Science Foundation of China (Project Nos. 30825047 and
90709007) and National Eleventh Five Year Support Plan (Project
No. 2006BAI04A10).
438
References
439
Berle, C.A., Cobbin, D., Smith, N., Zaslawski, C., 2010. A novel approach to evaluate
Traditional Chinese Medicine treatment outcomes using pattern identification.
Journal of Alternative and Complementary Medicine 16, 357–367.
Chan, K., Lee, H., 2000. Chinese Herbal Medicine Concepts of prescriptions, Interactions between Chinese Herbal Medicinal Products and Orthodox Drugs.
Harwood Academic Publishers, The Gordon & Breach Publishing Group, ISBN
90-5702-413-6, pp. 43–48.
Chan, K., 2005. Chinese medicinal materials and their interface with Western medical concepts. Journal of Ethnopharmacology 96, 1–18.
Chen, J.X., Hu, L.S., 2006. Traditional Chinese medicine for the treatment of chronic
prostatitis in China: a systematic review and meta-analysis. Journal of Alternative and Complementary Medicine 12, 763–769.
Chen, K.J., 1979. On strengthening the combination of Chinese traditional and Western medicine in cardiovascular research. Zhonghua Xin Xue Guan Bing Za Zhi 7,
295 (in Chinese).
Chen, K.J., 1982. The therapeutic effect of purified coronary heart II tablets on 112
cases of angina pectoris by double blind method. Zhonghua Xin Xue Guan Bing
Za Zhi 10, 85–89 (in Chinese).
Chen, K.J., 1983. Trends in studies of activation of blood circulation and treatment
of stasis. Zhong Xi Yi Jie He Za Zhi 3, 134–139 (in Chinese).
Chen, K.J., Xu, H., 2003. The integration of traditional Chinese medicine and Western
medicine. 11, 225–235.
Chen, Z.Q., Chen, G.L., Li, X.W., Zhao, Y.Q., Shi, L.J., 1999. Plasma L-ENK, AVP, ANP and
serum gastrin in patients with syndrome of Liver-Qi-stagnation. World Journal
of Gastroenterology 5, 61–63.
Eisenberg, D.M., Davis, R.B., Ettner, S.L., Appel, S., Wilkey, S., Van Rompay, M., Kessler,
R.C., 1998. Trends in alternative medicine use in the United States, 1990–1997:
results of a follow-up national survey. Journal of American Medical Association
280, 1569–1575.
Fontanarosa, P.B., Lundberg, G.D., 1998. Alternative medicine meets science. Journal
of American Medical Association 280, 1618–1619.
Goldbach-Mansky, R., Wilson, M., Fleischmann, R., Olsen, N., Silverfield, J., Kempf, P.,
Kivitz, A., Sherrer, Y., Pucino, F., Csako, G., Costello, R., Pham, T.H., Snyder, C., van
der Heijde, D., Tao, X., Wesley, R., Lipsky, P.E., 2009. Comparison of Tripterygium
434
435
436
440
441
442
443
444
445
446
447
448
449
450
451
452
453
454
455
456
457
458
459
460
461
462
463
464
465
466
467
468
469
470
471
472
Q3
7
wilfordii Hook F versus sulfasalazine in the treatment of rheumatoid arthritis:
a randomized trial. Annals of Internal Medicine 151, 229–240.
He, Y., Lu, A., Zha, Y., Yan, X., Song, Y., Zeng, S., Liu, W., Zhu, W., Su, L., Feng, X.,
Qian, X., Lu, C., 2007a. Correlations between symptoms as assessed in traditional
Chinese medicine (TCM) and ACR20 efficacy response: a comparison study in
396 patients with rheumatoid arthritis treated with TCM or Western medicine.
Journal of Clinical Rheumatology 13, 317–321.
He, Y., Zha, Q., Liu, D., Lu, A., 2007b. Relations between serum IgA level and cartilage
erosion in 436 cases of rheumatoid arthritis. Immunological Investigations 36,
285–291.
Jia, B.S., 1989. Relation of the level of platelet membrane glycoproteins, platelet
adhesion, platelet aggregation and traditional Chinese medicine syndrome patterns of coronary heart disease. Zhong Xi Yi Jie He Za Zhi 9, 717–719 (in Chinese).
Jiang, M., Yang, J., Zhang, C., Liu, B., Chan, K., Cao, H., Lu, A., 2010a. Clinical studies
with traditional Chinese medicine in the past decade and future research and
development. Planta Medica 76, 2048–2064.
Jiang, M., Zhao, J., Lu, A., Zha, Q., He, Y., 2010b. Does gastrointestinal adverse drug
reaction influence therapeutic effect in the treatment of rheumatoid arthritis?
Journal of Alternative and Complementary Medicine 16, 143–144.
Jiang, W.Y., 2005. Therapeutic wisdom in traditional Chinese medicine: a perspective
from modern science. Trends in Pharmacological Sciences 26, 558–563.
Li, S., Lu, A., Wang, Y., 2010. Symptomatic comparison in efficacy on patients with
benign prostatic hyperplasia treated with two therapeutic approaches. Complementary Therapies in Medicine 18, 21–27.
Li, S., Lu, A., Zhang, L., Li, Y.D., 2003. Anti-Helicobacter pylori immunoglobulin G (IgG)
and IgA antibody responses and the value of clinical presentations in diagnosis
of H. pylori infection in patients with precancerous lesions. World Journal of
Gastroenterology 9, 755–758.
Li, S., Wu, L., Zhang, Z., 2006. Constructing biological networks through combined
literature mining and microarray analysis: a LMMA approach. Bioinformatics
22, 2143–2150.
Li, S., Zhang, Z.Q., Wu, L.J., Zhang, X.G., Li, Y.D., Wang, Y.Y., 2007. Understanding
ZHENG in traditional Chinese medicine in the context of neuro-endocrineimmune network. IET Systems Biology 1, 51–60.
Lin, Q., Liao, J., 1990. Rules for differentiating symptoms and signs of the heart-qi
deficiency syndrome. Zhong Xi Yi Jie He Za Zhi 10, 78–81.
Lu, A., Chen, K.J., 2009. Integrative medicine in clinical practice: from pattern differentiation in traditional Chinese medicine to disease treatment. Chinese Journal
of Integrative Medicine 15, 152.
Lu, A.P., Ding, X.R., Chen, K.J., 2008. Current situation and progress in integrative
medicine in China. Chinese Journal of Integrative Medicine 14, 234–240.
Lu, A.P., Jia, H.W., Xiao, C., Lu, Q.P., 2004. Theory of traditional Chinese medicine
and therapeutic method of diseases. World Journal of Gastroenterology 10,
1854–1856.
Lu, A.P., Li, S., 2010. Principle and application of Chinese medicine syndrome differentiation and disease classification. Zhongguo Zhong Xi Yi Jie He Za Zhi 30,
84–86.
Lu, A.P., Zhang, S.S., Zha, Q.L., Ju, D.H., Wu, H., Jia, H.W., Xiao, C., Li, S., Jian, H., 2005.
Correlation between CD4, CD8 cell infiltration in gastric mucosa, Hplicobacter
pylori infection and symptoms in patients with chronic gastritis. World Journal
of Gastroenterology 11, 2486–2490.
Lu, C., Xiao, C., Chen, G., Jiang, M., Zha, Q., Yan, X., Kong, W., Lu, A., in press.
Cold and heat pattern of rheumatoid arthritis in traditional Chinese medicine: Q4
distinct molecular signatures identified by microarray expression profiles in
CD4-positive T cell. Rheumatology International.
Lu, C., Zha, Q., Chang, A., He, Y., Lu, A., 2009. Pattern differentiation in Traditional Chinese Medicine can help define specific indications for biomedical therapy in the
treatment of rheumatoid arthritis. Journal of Alternative and Complementary
Medicine 15, 1021–1025.
Lu, K., Karlberg, E.O., Storling, Z.M., Olason, P.I., Pedersen, A.G., Rigina, O., Hinsby,
A.M., Tümer, Z., Pociot, F., Tommerup, N., Moreau, Y., Brunak, S., 2007. A human
phenome-interactome network of protein complexes implicated in genetic disorders. Nature Biotechnology 25, 309–316.
Ma, T., Tan, C., Zhang, H., Wang, M., Ding, W., Li, S., 2010. Bridging the gap between
traditional Chinese medicine and systems biology: the connection of Cold Syndrome and NEI network. Molecular Biosystems 6, 613–619.
Ma, X.J., Yin, H.J., Chen, K.J., 2009. Differential gene expression profiles in coronary
heart disease patients of blood stasis syndrome in traditional Chinese medicine
and clinical role of target gene. Chinese Journal of Integrative Medicine 15,
101–106.
Manheimer, E., Wieland, S., Kimbrough, E., Cheng, K., Berman, B.M., 2009. Evidence
from the Cochrane Collaboration for Traditional Chinese Medicine therapies.
Journal of Alternative and Complementary Medicine 15, 1001–1014.
Min, Z.H., Zhou, Y., Zhang, H.M., 2010. Effect of treatment based on syndrome differentiation by Chinese medicine on post-traumatic elbow arthritis. Chinese
Journal of Integrative Medicine 16, 264–269.
No author listed, 1983. Lectures on essentials of traditional Chinese medicine.
VII. Differentiation of syndromes. Journal of Traditional Chinese Medicine 3,
67–72.
Takeichi, M., Sato, T., 1997. Computerized color analysis of xue yu (blood stasis) in
the sublingual vein using a new technology. The American Journal of Chinese
Medicine 25, 213–219.
Tsang, I.K., 2007. Establishing the efficacy of traditional Chinese medicine. Nature
Clinical Practice Rheumatology 3, 60–61.
Tsang, I.K., Huang, S.H., Koehler, B.E., 2010. Traditional Chinese Medicine: an opportunity for discovery. The Journal of Rheumatology 37, 1989–1990.
Please cite this article in press as: Lu, A., et al., An integrative approach of linking traditional Chinese medicine pattern classification and
biomedicine diagnosis. J. Ethnopharmacol. (2011), doi:10.1016/j.jep.2011.08.045
473
474
475
476
477
478
479
480
481
482
483
484
485
486
487
488
489
490
491
492
493
494
495
496
497
498
499
500
501
502
503
504
505
506
507
508
509
510
511
512
513
514
515
516
517
518
519
520
521
522
523
524
525
526
527
528
529
530
531
532
533
534
535
536
537
538
539
540
541
542
543
544
545
546
547
548
549
550
551
552
553
554
555
556
557
558
G Model
JEP 6989 1–8
8
559
560
561
562
563
564
565
566
567
568
569
570
571
572
573
574
575
576
577
578
579
580
581
582
583
584
585
586
587
588
589
590
591
592
ARTICLE IN PRESS
A. Lu et al. / Journal of Ethnopharmacology xxx (2011) xxx–xxx
Tu, X., Huang, G., Tan, S., 2009. Chinese herbal medicine for dysfunctional uterine bleeding: a meta-analysis. Evidence Based Complementary and Alternative
Medicine 6, 99–105.
van Wietmarschen, H., Yuan, K., Lu, C., Gao, P., Wang, J., Xiao, C., Yan, X., Wang,
M., Schroën, J., Lu, A., Xu, G., van der Greef, J., 2009. Systems biology guided
by Chinese medicine reveals new markers for sub-typing rheumatoid arthritis
patients. Journal of Clinical Rheumatology 15, 330–337.
Wang, J., He, Q.Y., 2010. Thinking on how to construct the system of Chinese medicine
efficacy evaluation for coronary heart disease angina pectoris. Chinese Journal
of Integrative Medicine 16, 75–78.
Wang, J.S., van der Heijden, R., Spruit, S., Hankermeier, T., Chan, K., van der Greef,
J., Xu, G.W., Wang, M., 2009. Quality and safety of Chinese medicine herbal
medicines guided by a systems biology perspective. Journal of Ethnopharmacology 126, 31–41.
Wang, Q., Ren, X.J., Yao, S.L., Wu, H.D., 2010. Clinical observation on the endocrinal
and immune functions in subjects with yin-deficiency constitution. Chinese
Journal of Integrative Medicine 16, 28–32.
Wu, X., Jiang, R., Zhang, M.Q., Li, S., 2008. Network-based global inference of human
disease genes. Molecular Systems Biology 4, 189.
Wang, J., Li, Y., Ni, C., Zhang, H., Li, L., Wang, Q., 2011. Cognition research and constitutional classification in Chinese medicine. American Journal of Chinese Medicine
39, 651–660.
Xu, L., Meng, M.Q., Qi, X., Wang, K., 2010. Morphology variability analysis of wrist
pulse waveform for assessment of arteriosclerosis status. Journal of Medical
Systems 34, 331–339.
Yan, S.Y., Yao, C., Ding, X.R., Jiang, M., Lu, A. Systolic blood pressure and heart rat
were found for identifying the indications of two herbal formulas targeting on
TCM Qi deficiency and blood stasis pattern in the treatment of angina pectoris.
Chinese Journal of Integrative Medicine, in press.
Yan, Z., Wang, K., Li, N., 2009. Computerized feature quantification of sublingual veins from color sublingual images. Computer Methods and Programs in
Biomedicine 93, 192–205.
Yang, W., Ouyang, J., Zhu, K., Zhou, S., Peng, Z., 2003. TCM treatment for 40 cases
of rheumatoid arthritis with channel blockage due to yin deficiency. Journal of
Traditional Chinese Medicine 23, 172–174.
Yuan, G.Q., Jia, Z.H., Yang, H.T., Wu, S.Z., Gao, H.L., Wei, C., Zhu, H.M., Wu, Y.L.,
2010. Comfortable lifestyle-induced imbalance of neuro-endocrine-immunity
network: a possible mechanism of vascular endothelial dysfunction. Chinese
Journal of Integrative Medicine 16, 54–60.
Zha, Q., He, Y., Lu, Y., Lu, A., 2006. Relationship between platelet counts and cartilage
erosion in 436 cases of rheumatoid arthritis. Clinica Chimica Acta 371, 194–195.
Zhang, H., Wang, W.R., Lin, R., Zhang, J.Y., Ji, Q.L., Lin, Q.Q., Yang, L.N., 2010. Buyang
Huanwu decoction ameliorates coronary heart disease with Qi deficiency and
blood stasis syndrome by reducing CRP and CD40 in rats. Journal of Ethnopharmacology 130, 98–102.
Zhang, Q., Wu, Z., Feng, Y., Shi, J., 1990. Levels of sexual hormones in relation with
syndrome-differentiation of TCM in patients of chronic renal failure. Journal of
Traditional Chinese Medicine 10, 132–135.
Zhao, L., Chan, K., 2005. Building a bridge for integrating Chinese medicine into
conventional healthcare: observations drawn from the Chinese Quality of
Life Instrument development. The American Journal of Chinese Medicine 33,
897–902.
Zhao, L.H., Xiao, C., Yan, X.P., Wang, J.M., Zhang, Y.Z., Dong, Q.X., Lu, C., Lu, A., 2006.
Correlation between heat or cold syndrome and cytokine, and laboratory index
in women with early rheumatoid arthritis. Acta Universitatis Traditionis Medicalis Sinensis Pharmacologiaeque Shanghai 20, 21–24 (in Chinese).
Zheng, G., Jiang, M., He, X., Zhao, J., Guo, H., Chen, G., Zha, Q., Lu, A., 2011. Discrete
derivative: a data slicing algorithm for exploration of sharing biological networks between rheumatoid arthritis and coronary heart disease. BioData Mining
4, 18.
Zhou, X., Zhou, Z., Jin, M., Wang, H., Wu, M., Gu, Q., Wang, Z., Shang, W., 2000. Intermediate and late rheumatoid arthritis treated by tonifying the kidney, resolving
phlegm and removing blood stasis. Journal of Traditional Chinese Medicine 20,
87–92.
Zhu, L.C., 1962. Importance and relationship of disease differentiation in combination with syndrome differentiation. Journal of Traditional Chinese Medicine 4,
15–16 (in Chinese).
Zhu, X., Proctor, M., Bensoussan, A., Wu, E., Smith, C.A., 2008. Chinese herbal
medicine for primary dysmenorrhoea. Cochrane Database of Systematic
Reviews 16, CD005288.
Please cite this article in press as: Lu, A., et al., An integrative approach of linking traditional Chinese medicine pattern classification and
biomedicine diagnosis. J. Ethnopharmacol. (2011), doi:10.1016/j.jep.2011.08.045
593
594
595
596
597
598
599
600
601
602
603
604
605
606
607
608
609
610
611
612
613
614
615
616
617
618
619
620
621
622
623
624
625
626
627