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com J Tradit Chin Med 2013 August 15; 33(4): 444-448
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Clinical treatment of myasthenia gravis with deficiency of spleen
and kidney based on combination of disease with syndrome theory
Chao Jiang, Ping Liu, Yan Liang, Shaobo Qiu, Wenjing Bao, Jingsheng Zhang
aa
Chao Jiang, Ping Liu, Yan Liang, Shaobo Qiu, Traditional
Chinese Medicine Department of Longhua Hospital Affiliat-
ed to Shanghai University of TCM, Shanghai 200030, China
Wenjing Bao, Jingsheng Zhang, Neurological Medical De-
partment of the Hospital Affiliated to Liaoning University of
TCM, Shenyang 110032, China
Supported by a Key Project in Basic Research of Shanghai
Municipal Committee of Science (No. 10JC1414500); a
Planned Project in the TCM Fund of Scientific Research un-
der the Shanghai Municipal Health Bureau (2010J002B)
Correspondence to: Prof. Ping Liu, TCM Department of
Longhua Hospital Affiliated to Shanghai University of TCM,
Shanghai 200030, China. liuping23@sina.com
Telephone: +86-13681717058
Accepted: January 20, 2013
Abstract
OBJECTIVE: To study the use of Jianjining in the
treatment of myasthenia gravis (MG) patients with
a deficiency of both spleen and kidney via the theo-
ry on the combination of disease with syndrome.
METHODS: Sixty MG patients with a deficiency of
both spleen and kidney were randomly divided in-
to an treatment group (n=30) treated with Jianjin-
ing granules and Western Medicine (prednisone or
pyridostigmine bromide) and a control group (n=
30) treated with Jianjining granules. The dosage of
the three drugs was reduced over the course of
treatment. After 3 and 6 months of treatment, the
curative effect was evaluated with the muscle
weakness severity scale (MWSS).
RESULTS: The MWSS score after treatment de-
clined significantly in both groups. The score in the
treatment group was much lower than that in the
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ISSN 0255-2922
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CLINICAL STUDY
TOPIC
control group (P<0.05). The total effective rate was
63.33% (19/30) in the treatment group and 36.67%
(11/30) in the control group after 3 months of treat-
ment, and 80.00% (24/30) and 50.00% (15/30), re-
spectively, after 6 months of treatment. The obvi-
ous and total effective rates in the treatment group
were much higher than those in the control group
(P<0.05). After 6 months of treatment, there were
no obvious differences (P>0.05) in the obvious and
effective rates between the 2 groups. However,
the total effective rate in the treatment group
was much higher than that in the control group
(P<0.01).
CONCLUSION: Using the theory on the combina-
tion of disease with syndrome, we found that the
curative effect of Jianjining and Western Medicine
on MG patients with deficiency of both spleen and
kidney is worth further exploration.
© 2013 JTCM. All rights reserved.
Key words: Myasthenia gravis; Deficiency of spleen
and kidney; Jianjining; Combination of disease
with syndrome
INTRODUCTION
Myasthenia gravis (MG) is an autoimmune disease af-
fecting T-cell dependent and B-cell mediated locations
connecting nerves and muscles.1 Myasthenia and fa-
tigue, characteristics of MG, may originate from an au-
toimmune reaction mediated by antibodies against the
acetylcholine receptor (AchR), stimulated by inappro-
priate signal transmission between T-cells and B-cells at
the neuromuscular junction.2 Because of the complex
444 August 15, 2013 | Volume 33 | Issue 4 |
 Jiang C et al. / Clinical Study
pathogenesis of MG, only 20%-40% of MG patients
see curative effects without ideal therapy. MG is catego-
rized as a flaccidity syndrome in TCM. The kidney is
the origin of congenital constitution to store essence,
governs the bone, generates marrow, and acts as the
root of primordial Qi to dominate growth and develop-
ment. Therefore, insufficiency of kidney-essence or de-
ficiency of primordial Qi directly influences growth, de-
velopment, and muscular function, causing MG. The
spleen acts as the origin of the acquired constitution
and as the source of transporting Qi, blood, and fluids
to govern the muscles and limbs. A deficiency of both
spleen and stomach fails to transport nutrients and
nourish limbs, also causing MG. A congenital deficien-
cy cannot warm the spleen-yang, deficiency of
spleen-yang cannot generate and transport Qi, blood,
and fluids, and a deficiency of both Qi and blood can-
not nourish muscles, causing MG. Previous research
showed3,4 that MG develops mainly because of deficien-
cy in both spleen and kidney, which is most commonly
seen in clinical practice. Therefore, Jianjining granules
were created for treating MG with a deficiency of both
the spleen and kidney. The recipe consists of Huangqi
(Radix Astragali Mongolici), Gouqizi (Fructus Lycii),
Heshouwu (Radix Polygoni Multiflori), Baizhu (Rhi-
zoma Atractylodis Macrocephalae), Shengma (Rhizoma
Cimicifugae Foetidae), and Danggui (Radix Angelicae Si-
nensis), Shanzhuyu (Fructus Corni), Yimucao (Herba
Leonuri), Zhishi (Fructus Aurantii Immaturus), Taizish-
en (Radix Pseudostellariae), as well as Fangfeng (Radix
Saposhnikoviae). The recipe nourishes the spleen and
kidney and lifts Yang Qi, and is therefore suitable for
MG. We previously showed that Jianjining granule can
improve the clinical symptoms of MG patients and
MG-related indexes in experimental animals suffering
from autoimmune MG with a deficiency of both
spleen and kidney.5-8 In this study, with a randomized
double-blind clinical experiment, we found that Jian-
jining and Western Medicine can more effectively im-
prove the clinical symptoms of MG patients with a de-
ficiency of both spleen and kidney than the Chinese
drug alone, thus providing a standardized model for ef-
fectively treating MG.
MATERIALS AND METHODS
General data
Sixty MG outpatients conforming to the inclusive stan-
dards came to the Longhua Hospital affiliated to
Shanghai University of TCM and the Hospital affiliat-
ed to Liaoning University of TCM from November
2010 to April 2012. The 60 MG patients aged 14-75
years were randomly divided into two groups. Among
the 30 patients in the treatment group were 12 females
and 18 males with an average age of (49±16) years and
an illness course of (28±24) months. Among the 30 pa-
tients in the control group were 13 females and 17
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males with an average age of (49±15) years and an ill-
ness course of (30±27) months. No patients with origi-
nal autoimmune diseases were recruited. Statistical
analysis showed that there were no obvious differences
(P>0.05) in age, sex, illness course, or other baseline da-
ta between the two groups, hence comparability. This
study was approved by the ethics examination commit-
tee of Longhua Hospital affiliated to Shanghai Univer-
sity of TCM. All patients signed a disclosure agree-
ment.
Inclusive standards
The diagnostic standard in Western Medicine for MG9
includes symptoms of fluctuated myasthenia in an elec-
tromyogram under repeated stimulation of nerves and
muscles. All patients were classified as I, IIA, or IIB in
the Osserman classification system. Flaccidity syn-
drome is considered the diagnostic standard in TCM.10
Patients with more than one major syndrome and one
minor syndrome or had a fur and pulse condition were
included.
Exclusive standards
Patients were excluded if they met any of the following
criteria: (a) osserman classification of III, IV, or V; (b)
familial MG, congenital MG, or MG caused by drugs
(such as penicillin or α-interferon); (c) pregnant or
breast-feeding women; (d) complications such as cere-
brovascular disease, renal insufficiency, disease of the
hematopoietic system, or mental illness; (e) allergic
constitution (sensitive to more than 2 foods or drugs);
(f ) taking part in a clinical experiment of other drugs
within the last month; and (g) patients given an intra-
venous injection with gamma globulin or a plasma re-
placement within the last three months.
Therapy
Jianjining granule and routine Western Medicine (pred-
nisone or pyridostigmine bromide) were used in the
treatment group. Jianjining granule consisted of
Huangqi (Radix Astragali Mongolici), Gouqizi (Fructus
Lycii), Heshouwu (Radix polygoni Multiflori), Baizhu
(Rhizoma Atractylodis Macrocephalae), Shengma (Rhi-
zoma Cimicifugae Foetidae) Taizishen (Radix Pseudostel-
lariae), Danggui (Radix Angelicae Sinensis), Shanzhuyu
(Fructus Corni), and other ingredients (Benxi Chinese
Drug Factory, Liaoning, China). Jianjining was taken
orally, one pack (10 g containing 7.4 g of crude drug) a
time, twice a day. Prednisone was taken orally, 60-80 mg
per day (Shanghai Sanwei Pharmaceutical Company,
China, H 31020867). Some patients took 60 g pyr-
idostigmine bromide orally, 4 times daily (Shanghai San-
wei Pharmaceutical Company, China, H31020867).
The Western Medicines were gradually reduced to
maintenance dosage upon improvement of symp-
toms.11 Jianjining granule (with the same dosage as the
treatment group) and placebo (taken orally, one pack a
time, twice a day) were taken in the control group. The
445 August 15, 2013 | Volume 33 | Issue 4 |
 Jiang C et al. / Clinical Study
placebo (with the same specifications as Jianjining),
contained bitter tincture and edible pigment and could
not be increased or decreased during treatment (Benxi
Chinese Drug Factory, Liaoning, China). During treat-
ment, the dosage of pyridostigmine bromide or predni-
sone could be gradually decreased according to the ill-
ness condition. However, the dosage of Jianjining gran-
ule was kept constant in the 6 month course of treat-
ment.
Score of muscle weakness severity scale (MWSS)
We used the MWSS score to assess the physical state of
patients before treatment, after 3 months of treat-
ment, and after 6 months of treatment. The scale
was filled in by physicians and has eight items used
to assess the fatigue state of MG patients. "0" means
a normal state, "1" means a low state, "2" means a
moderate state, "3" means a severe state, and "4"
means the severest state, in which the patient cannot
move.12 The scores for the eight items are added up
to form the total score.
Standard of curative effect
In reference to the standard,13 the clinically relevant
score=(absolute score before treatment-absolute score
after treatment)/absolute score before treatment ×
100%. (a) Curative rate ≥95%, (b) basic curative rate=
81%-95% , (c) obvious effective rate=51%-80% , (d)
improved rate=26%-50% , and (e) ineffective rate ≤
25%. The total effective rate=curative rate+basic cura-
tive rate+obvious effective rate+improved rate. The cu-
rative effects before treatment, after 3 months of treat-
ment, and after 6 months of treatment were compared.
Evaluation of safety
Respiration, heart rate, and blood pressure were detect-
ed once a week. Blood samples, urine routine, stool
routine, hepatic and renal function, and electrocardio-
gram were examined before and after treatment.
Statistical methods
All the data were analyzed with SPSS 15.0 software
(produced by SPSS Corporation, Chicago, IL, USA).
A paired t-test was used to compare variables in each
group before and after treatment. A One-way analysis
of variance and Q test were used to compare variables
between groups. χ2 test was used to analyze variables
and classified variables in each group. P<0.05 was con-
sidered statistically significant.
Table 1 Comparison of MWSS scores between the two groups ( xˉ ±s)
Group n Before treatment
Treatment group 30 11±7a
Control group 30 127±7
Notes: treatment group treated with Jianjining granules and Western Medicine (prednisone or pyridostigmine bromide; control group
treated with Jianjining granules. MWSS: muscle weakness severity scale. aP>0.05, as compared with the datum before treatment in the con-
trol group; bP<0.05, as compared with the datum after 3 months of treatment in the control group; cP<0.05, as compared with the datum
before treatment in the same group; dP<0.01, as compared with the datum after 6 months of treatment in the control group.
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RESULTS
Comparison of accumulated MWSS scores between
groups before and after treatment
The accumulated MWSS scores after treatment in
both groups were significantly lower than those before
treatment (P<0.05). The MWSS score after 3 months
of treatment in the treatment group was lower than
that in the control group (P<0.05). There was a signifi-
cant difference (P<0.01, Table 1) between the two
groups after 6 months of treatment.
Comparison of curative effects between groups
The total effective rate, obvious effective rate, and im-
proved rate in the two groups are shown in Table 2. Af-
ter 3 months of treatment, there was no obvious differ-
ence (P>0.05) in improved rate between the two
groups. However, the obvious effective rate and the to-
tal effective rate in the treatment group were much
higher than those in the control group (P<0.05). After
6 months of treatment, there was no statistical differ-
ence (P>0.05) in obvious effective rate between the
two groups, but the total effective rate in the treatment
group was much higher than that in the control group
(P<0.01). MWSS scores after treatment in both groups
greatly declined with statistical difference (P<0.05) be-
tween the two groups.
Safety
There were no adverse reactions during the treatment
in the two groups.
DISCUSSION
The pathogenesis of autoimmune diseases, including
MG, is not yet clear and delays effective diagnosis and
treatment of MG. At present, MG is mainly treated
with non-specific immune-inhibitors, and cholinester-
ase-inhibitors are the first drugs chosen. This choice in-
fluences the progress of treating MG.14,15 Long-term
use of steroid drugs causes many side-effects, such as a
moonlike face, obesity, and baldness, negatively affects
the self-esteem of patients as well as psychological as-
pects and incurs large medical costs.16 However, there is
no effective measure to prevent and treat MG pa-
tients.17,18
Disease reflects the whole process of the occurrence
and development of a condition and syndrome reflects
a specific stage in the development of a condition. Syn-
After 3 months of treatment After 6 months of treatment
7±4bc 6±4cd
11±6 10±6
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 Jiang C et al. / Clinical Study

Table 2 Comparison of curative effects between the two groups [n (%)]

Item Treatment group (n=30, %) Control group (n=30, %)
After 3 months After 6 months After 3 months After 6 months
of treatment of treatment of treatment of treatment
Curative rate 0 (0.00) 2 (6.67) 0 (0.00) 0 (0.00)

Basic curative rate 1 (3.33) 4 (13.33) 1 (3.33) 2 (6.67)

Obvious effective rate 5 (16.67)ac 9 (30.00)cd 1 (3.33) 6 (20.00)

Improved rate 13 (43.33)bc 9 (30.00)cd 9 (30.00) 7 (23.33)

Ineffective rate 11 (36.67) 6 (20.00) 19 (63.33) 15 (50.00)

<0 5 (16.67) 9 (30.00) 8 (26.67) 7 (23.33)

Total effective rate 19 (63.33)bc 24 (80.00)ce 11 (36.67) 15 (50.00)

Notes: after 3 months of treatment, P<0.05 as compared with the datum in the control group, P>0.05 as compared with the datum in the
a b

control group; cP<0.05 as compared with the datum before treatment in the same group; after 6 months of treatment, dP>0.05 as com-
pared with the datum in the control group, eP<0.05 as compared with the datum in the control group.
drome-differentiation in TCM and pathological pro-
cess in Western Medicine share similar characteristics
but are often neglected. Therefore, a pathological pro-
cess exists in different diseases, a disease has different
pathological stages, a syndrome appears in different dis-
eases, and a disease has different syndromes. In addi-
tion, disease and syndrome have compatible intensions
and extensions. Based on this, the combination of dis-
ease differentiation with syndrome differentiation is
widely accepted in the diagnosis and treatment of dis-
eases. Chen19-21 believes that the combination of diseas-
es with syndromes is a clinically optimized mode in the
combination of TCM with Western Medicine. He says
that we should form a clinically oriented mode by
"combination of disease with syndrome" and in "com-
bination of macro-differentiating syndrome with mi-
cro-differentiating disease". He claims that only by
combination of the two forms, can the state of a dis-
ease be accurately reflected and their clinical advantag-
es and complementation be better displayed to eventu-
ally work out the best therapy to treat patients. In this
study, we administered the Chinese drug Jianjining
granule for strengthening spleen and nourishing kid-
ney in addition to routine therapy in Western Medi-
cine, to treat MG patients with deficiency of both
spleen and kidney. This multi-centric, randomized,
double blind, and placebo controlled study confirmed
that the combination of TCM with Western Medicine
in the treatment group obviously enhanced the total ef-
fective rate to 63.33% after 3 months of treatment and
80% after 6 months of treatment with significant dif-
ference (P<0.05) from 36.67% and 50% , respectively,
in the control group. Jianjining, composed of Huangqi
(Radix Astragali Mongolici), Gouqizi (Fructus Lycii),
Heshouwu (Radix polygoni Multiflori), Baizhu (Rhi-
zoma Atractylodis Macrocephalae), Shengma (Rhizoma
Cimicifugae Foetidae) and other ingredients, is for nour-
ishing the spleen and kidney and lifting Yang Qi, and is
suitable for treating MG. In the recipe, Huangqi (Ra-
dix Astragali Mongolici) and Gouqizi (Fructus Lycii) are
for nourishing the spleen and kidney and lifting Yang
Qi, and are monarch drugs. Heshouwu (Radix polygoni
Multiflori) and Shanzhuyu (Fructus Corni) are for rein-
forcing liver and kidney and Taizishen (Radix Pseu-
dostellariae) and Baizhu (Rhizoma Atractylodis Macro-
cephalae) are for supplementing Qi, strengthening
spleen, and increasing the effect of monarch drugs, and
are minister drugs. Shengma (Rhizoma Cimicifugae
Foetidae) for elevating Yang Qi and helping monarch
drugs lift the declined Qi, Yimucao (Herba Leonuri Ja-
ponici) and Zhiqiao (Fructus Aurantii Submaturus) for
promoting the circulation of Qi and blood, and Dang-
gui (Radix Angelicae Sinensis) for regulating blood flow,
are adjuvant drugs. The combination of these drugs
can nourish the spleen and kidney, elevate Yang Qi, in-
vigorate the Qi of the spleen and stomach, nourish the
muscles, and generate marrow. In addition, our previ-
ous research5-8 has shown that Jianjining granules can
reduce the level of IFN-1, mRNA and serum AchRAb,
decrease MG severity, promote the growth of new axo-
ns at the neuromuscular junction, increase the quantity
of synaptic vesicles, and reduce damage to the synapse
in a rat model with experimental autoimmune MG
(EAMG). It can also effectively regulate the level of dif-
ferent EAMG-related proteins. The combination of dif-
ferentiating disease with differentiating syndrome and
the combination of TCM with Western Medicine can
achieve good curative effects on MG without adverse
reactions. However, in this study, a small quantity of
samples and short study time cannot explain any
long-term advantages of the combination of differenti-
ating disease with differentiating syndrome. To further
evaluate the effectiveness and accuracy of using the
combination of disease with syndrome to treat MG pa-
tients with a deficiency of both spleen and kidney, it is
necessary to increase the number of patients, extend
the length of the study, conduct randomized and dou-
ble blind comparisons, and provide an effective mea-
sure conforming to the state condition of China to
treat MG.

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 Jiang C et al. / Clinical Study
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