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[
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s
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4
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[
5
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,
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6
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s
tiff
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[
6
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7
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Gu
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tr
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C
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tech
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[
8
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.
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[
9
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–
[
1
2
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q
u
a
l
it
y
o
f
l
i
f
e
[
1
4
]
.
Desp
ite
Gu
a
Sh
a
'
s
lo
n
g
h
is
to
r
y
an
d
wid
esp
r
e
ad
u
s
e
in
tr
ea
tin
g
m
u
s
cu
lo
s
k
eleta
l
d
i
s
ea
s
es,
it
s
m
ec
h
an
is
m
o
f
ac
tio
n
r
em
ain
s
u
n
clea
r
.
A
s
y
s
tem
atic
r
ev
ie
w
an
d
an
aly
s
is
o
f
cu
r
r
en
t
r
e
s
ea
r
ch
ar
e
u
r
g
e
n
tly
n
ee
d
ed
to
estab
lis
h
a
s
tr
o
n
g
er
s
cien
tific
f
o
u
n
d
atio
n
f
o
r
its
clin
ica
l
ap
p
licatio
n
.
T
h
is
s
tu
d
y
aim
ed
to
co
m
p
r
eh
e
n
s
iv
ely
e
v
alu
ate
th
e
ex
is
tin
g
liter
atu
r
e
o
n
t
h
e
im
p
a
ct
o
f
G
u
a
Sh
a
o
n
f
ascia.
W
e
will
s
u
m
m
ar
ize
th
e
ev
id
en
ce
s
u
p
p
o
r
tin
g
its
u
s
e,
ex
p
lo
r
e
p
o
ten
tial m
ec
h
a
n
is
m
s
o
f
ac
tio
n
,
an
d
p
r
o
p
o
s
e
f
u
tu
r
e
r
e
s
ea
r
ch
d
ir
ec
tio
n
s
.
2.
M
E
T
HOD
2
.
1
.
Sea
rc
h str
a
t
eg
y
a
nd
s
elec
t
io
n c
rit
er
ia
T
o
ass
ess
th
e
ef
f
ec
tiv
en
ess
a
n
d
s
af
ety
o
f
Gu
a
Sh
a
o
n
f
as
cia,
we
co
n
d
u
cted
a
s
y
s
tem
atic
r
ev
iew
f
o
llo
win
g
estab
lis
h
ed
g
u
id
eli
n
es.
T
wo
r
esear
ch
er
s
in
d
ep
en
d
en
tly
s
cr
ee
n
ed
s
tu
d
ies
ac
r
o
s
s
v
ar
io
u
s
d
atab
ases
,
in
clu
d
in
g
Sco
p
u
s
,
W
eb
o
f
Scien
ce
,
Pu
b
Me
d
,
an
d
C
o
ch
r
an
e
L
ib
r
ar
y
,
to
id
e
n
tify
r
elev
a
n
t
s
tu
d
ies
p
u
b
lis
h
ed
b
etwe
en
2
0
0
0
an
d
J
u
n
e
2
0
2
4
.
A
co
m
p
r
e
h
en
s
iv
e
s
ea
r
ch
s
tr
ateg
y
was
em
p
lo
y
ed
u
s
in
g
k
ey
wo
r
d
s
r
elate
d
to
"Gu
a
Sh
a
o
r
Scr
a
p
in
g
,
"
"f
asci
a
o
r
m
u
s
cu
lo
s
k
eleta
l
p
ain
o
r
in
f
lam
m
atio
n
,
"
an
d
"r
a
n
d
o
m
ized
co
n
tr
o
lled
tr
ial.
"
T
h
e
s
ea
r
ch
lan
g
u
ag
e
was r
estr
icted
to
E
n
g
lis
h
.
2
.
2
.
Study
s
elec
t
io
n
I
n
clu
s
io
n
c
r
iter
ia
in
th
is
s
tu
d
y
ar
e:
th
ese
ex
p
er
im
en
ts
m
u
s
t
b
e
ra
n
d
o
m
ize
d
c
o
n
tro
ll
e
d
tri
a
l
(
RCT
)
;
th
e
s
u
b
jects
m
u
s
t
b
e
h
u
m
an
;
o
n
e
o
f
th
e
in
ter
v
en
tio
n
m
eth
o
d
s
m
u
s
t
b
e
Gu
a
Sh
a;
an
d
th
e
m
ea
s
u
r
em
en
t
r
esu
lts
m
u
s
t
b
e
r
elate
d
to
in
d
icato
r
s
t
h
at
m
ay
ca
u
s
e
f
ascial
c
h
an
g
es,
s
u
ch
as n
eu
r
o
m
o
d
u
latio
n
o
r
b
lo
o
d
cir
c
u
latio
n
,
o
r
in
f
lam
m
atio
n
,
o
r
p
ain
p
er
ce
p
t
io
n
o
r
s
p
o
r
ts
p
e
r
f
o
r
m
an
ce
-
r
elate
d
r
esu
lts
.
E
x
clu
s
io
n
cr
iter
i
a
in
th
is
s
tu
d
y
ar
e:
a
n
im
al
ex
p
er
im
en
ts
,
ca
s
e
s
tu
d
ies,
r
ev
iew
ar
ticles
an
d
co
n
f
er
en
ce
ab
s
tr
ac
ts
wer
e
ex
clu
d
ed
;
s
tu
d
ies
with
o
n
ly
ab
s
tr
ac
ts
o
r
n
o
f
u
ll
tex
t;
s
tu
d
ies
with
a
f
lawe
d
m
eth
o
d
o
lo
g
y
o
r
q
u
esti
o
n
a
b
le
d
ata
in
teg
r
ity
.
I
n
itially
,
two
r
esear
ch
er
s
in
d
e
p
en
d
e
n
tly
c
o
n
d
u
cted
a
p
r
elim
in
ar
y
s
cr
ee
n
in
g
b
ased
o
n
titl
es
an
d
ab
s
tr
ac
ts
.
Su
b
s
eq
u
en
tly
,
f
u
ll
-
tex
t
r
ev
iews
o
f
p
o
ten
tial
ar
ticles
wer
e
p
er
f
o
r
m
ed
f
o
r
f
i
n
al
s
elec
tio
n
.
An
y
d
is
ag
r
ee
m
en
ts
wer
e
r
eso
lv
ed
th
r
o
u
g
h
d
is
cu
s
s
io
n
u
n
til
a
c
o
n
s
en
s
u
s
was
r
ea
ch
e
d
.
H
o
wev
er
,
if
co
n
s
en
s
u
s
co
u
l
d
n
o
t
b
e
r
ea
ch
e
d
af
te
r
d
is
cu
s
s
io
n
,
a
th
ir
d
r
e
v
iewe
r
was c
o
n
s
u
lted
to
d
ec
id
e
o
n
t
h
e
m
eth
o
d
o
l
o
g
ical
q
u
ality
o
f
th
e
in
clu
d
ed
tr
ials
.
2
.
3
.
Da
t
a
e
x
t
r
a
ct
i
o
n
A
s
tan
d
ar
d
ized
d
ata
ex
tr
ac
tio
n
f
o
r
m
wa
s
d
ev
elo
p
ed
,
an
d
two
au
th
o
r
s
in
d
ep
e
n
d
en
tly
r
ev
iewe
d
ea
ch
in
clu
d
ed
s
tu
d
y
an
d
ex
tr
ac
ted
d
etailed
in
f
o
r
m
atio
n
.
T
h
e
f
o
ll
o
win
g
asp
ec
ts
ar
e
:
s
tu
d
y
d
esi
g
n
(
m
u
s
t
b
e
an
R
C
T
f
ir
s
t
a
u
th
o
r
n
am
e,
p
u
b
licatio
n
y
ea
r
;
n
u
m
b
er
,
a
g
e,
an
d
c
h
ar
ac
ter
is
tics
o
f
p
ar
ticip
an
ts
;
i
n
ter
v
en
tio
n
m
eth
o
d
,
d
u
r
atio
n
,
an
d
f
r
eq
u
e
n
cy
;
o
u
t
co
m
e
m
ea
s
u
r
es
r
elate
d
to
p
o
ten
tial
f
ascial
ch
an
g
es
;
s
tu
d
y
co
n
clu
s
io
n
s
.
T
wo
in
d
ep
en
d
en
t
r
ev
iewe
r
s
ex
tr
ac
t
ed
d
ata
f
r
o
m
ea
c
h
in
clu
d
e
d
s
tu
d
y
u
s
in
g
a
s
tan
d
a
r
d
ized
f
o
r
m
,
th
en
co
m
p
a
r
ed
th
e
ex
tr
ac
ted
d
ata
a
n
d
r
eso
lv
e
d
an
y
d
is
cr
ep
an
cies th
r
o
u
g
h
d
is
cu
s
s
io
n
.
2
.
4
.
Da
t
a
qu
a
lity
a
s
s
ess
m
ent
R
elev
an
t
d
ata
was
ex
tr
ac
ted
f
r
o
m
th
e
in
clu
d
e
d
s
tu
d
ies
a
cc
o
r
d
in
g
to
a
p
r
e
-
d
ef
i
n
ed
f
o
r
m
at.
T
h
e
m
eth
o
d
o
l
o
g
ical
q
u
ality
o
f
th
e
in
clu
d
e
d
R
C
T
was
ev
alu
at
ed
u
s
in
g
th
e
PEDr
o
s
co
r
in
g
s
ca
le.
T
h
is
s
ca
le
is
k
n
o
wn
f
o
r
its
h
ig
h
r
eliab
ilit
y
(
I
C
C
=0
.
8
)
an
d
v
alid
ity
(
C
B
N
r
i
s
k
o
f
b
ias
to
o
l
=0
.
8
3
)
,
as
r
ep
o
r
te
d
b
y
Yam
ato
et
a
l
.
[
1
5
]
.
T
h
e
PED
r
o
s
ca
le
co
n
s
is
ts
o
f
1
1
item
s
,
ea
ch
s
co
r
ed
as
0
(
ab
s
en
t)
o
r
1
(
p
r
esen
t)
,
with
a
m
ax
im
u
m
to
tal
s
co
r
e
o
f
1
0
.
T
h
ese
item
s
ev
alu
ate
v
ital
asp
e
cts
o
f
R
C
T
d
esig
n
an
d
co
n
d
u
c
t,
in
clu
d
in
g
r
an
d
o
m
allo
ca
tio
n
o
f
p
ar
ticip
an
ts
,
co
n
ce
alm
en
t o
f
allo
ca
tio
n
f
r
o
m
p
ar
ticip
an
ts
an
d
r
esear
ch
er
s
,
b
a
s
elin
e
co
m
p
ar
ab
ilit
y
o
f
g
r
o
u
p
s
,
b
lin
d
in
g
o
f
p
ar
ticip
an
ts
an
d
o
u
tco
m
e
ass
ess
o
r
s
,
c
o
m
p
letio
n
o
f
all
ass
ig
n
ed
tr
ea
tm
en
ts
,
an
aly
s
is
o
f
d
r
o
p
o
u
ts
,
in
clu
s
io
n
o
f
at
least
o
n
e
r
elev
an
t
o
u
tco
m
e
m
ea
s
u
r
e;
r
ep
o
r
tin
g
o
f
ap
p
r
o
p
r
iate
s
tatis
t
ical
m
eth
o
d
s
;
P
r
e
s
e
n
t
a
t
i
o
n
o
f
p
o
i
n
t
e
s
t
i
m
a
te
s
a
n
d
c
o
n
f
i
d
e
n
c
e
i
n
t
e
r
v
al
s
;
c
li
n
ic
a
l
r
e
l
e
v
a
n
ce
o
f
f
i
n
d
i
n
g
s
.
G
e
n
er
a
l
l
y
,
h
i
g
h
e
r
s
c
o
r
e
s
i
n
d
i
c
a
t
e
b
e
t
te
r
m
e
t
h
o
d
o
l
o
g
i
c
a
l
q
u
a
l
i
t
y
.
F
o
l
l
o
wi
n
g
t
h
e
e
s
t
a
b
li
s
h
e
d
c
r
i
t
e
r
i
a
b
y
M
a
h
e
r
e
t
a
l
.
[
1
6
]
s
t
u
d
i
e
s
w
e
r
e
c
a
t
e
g
o
r
i
z
e
d
as
h
i
g
h
q
u
a
l
i
t
y
(
s
co
r
e
:
9
-
1
0
)
,
m
o
d
e
r
a
t
e
q
u
a
l
i
t
y
(
s
c
o
r
e
:
6
-
8
)
,
a
n
d
l
o
w
q
u
a
l
i
t
y
(
s
c
o
r
e
:
5
o
r
b
e
l
o
w
)
.
3.
RE
SU
L
T
S
3
.
1
.
L
it
er
a
t
ure
s
ea
rc
h r
esu
lt
s
Fo
r
th
is
s
tu
d
y
,
a
t
o
tal
o
f
9
4
r
elev
an
t
ar
ticles
wer
e
r
etr
iev
e
d
.
Af
ter
r
em
o
v
in
g
d
u
p
licate
a
r
ticles,
4
0
ar
ticles
r
em
ain
ed
.
Ab
s
tr
ac
ts
an
d
titl
es
wer
e
f
u
r
th
er
s
cr
ee
n
e
d
;
s
ix
an
im
al
ex
p
e
r
im
en
ts
,
1
4
s
y
s
tem
atic
r
ev
iews,
an
d
f
iv
e
ca
s
e
r
ep
o
r
ts
wer
e
ex
clu
d
ed
,
leav
i
n
g
1
5
ar
ticles.
T
h
e
f
u
ll
tex
t
w
as
th
e
n
r
ev
iewe
d
;
th
r
ee
c
o
n
f
er
e
n
ce
ab
s
tr
ac
ts
,
two
n
o
n
-
r
an
d
o
m
ize
d
co
n
tr
o
lled
tr
ials
,
an
d
o
n
e
p
r
o
s
p
ec
tiv
e
s
tu
d
y
wer
e
ex
clu
d
e
d
,
an
d
n
in
e
ar
ticles
wer
e
in
clu
d
e
d
.
Data
e
x
tr
ac
tio
n
an
d
f
u
r
th
er
an
aly
s
is
o
f
th
e
i
n
clu
d
ed
ar
ticles
s
h
o
wed
th
at
all
ar
ticles
m
et
th
e
d
at
a
q
u
ality
ass
ess
m
en
t a
n
d
an
aly
s
is
s
tan
d
ar
d
s
,
as sh
o
wn
in
Fig
u
r
e
1
.
Evaluation Warning : The document was created with Spire.PDF for Python.
I
SS
N
:
2
2
5
2
-
8
8
0
6
I
n
t J Pu
b
lic
Hea
lth
Sci
,
Vo
l.
14
,
No
.
2
,
J
u
n
e
20
25
:
6
7
2
-
6
8
1
674
Fig
u
r
e
1
.
L
iter
atu
r
e
s
cr
ee
n
in
g
f
lo
w
ch
ar
t
3
.
2
.
Q
ua
lit
y
a
s
s
ess
m
ent
o
f
i
nclud
e
d RC
T
s
T
h
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Deta
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a
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1
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T
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P
r
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t
R
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s
[
1
3
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[
1
0
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[
1
7
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[
1
8
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[
1
4
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[
1
9
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[
1
2
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[
1
1
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[
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R
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To
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8
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Th
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3.
3
.
T
he
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ua
Sh
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2
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Ta
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2
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Ref
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l
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[
1
9
]
-
P
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8
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-
S
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int
f
lex
ibi
lity
G
u
a
S
h
a
t
h
e
r
a
p
y
h
a
s
b
e
e
n
p
r
o
p
o
s
e
d
a
s
a
m
e
a
n
s
t
o
e
n
h
a
n
c
e
m
u
s
c
l
e
a
n
d
j
o
i
n
t
f
l
e
x
i
b
i
l
i
t
y
.
B
y
p
u
r
p
o
r
t
e
d
l
y
d
i
s
r
u
p
t
i
n
g
f
a
s
c
i
a
l
a
d
h
e
s
i
o
n
s
a
n
d
i
n
c
r
e
a
s
i
n
g
f
a
s
c
i
a
l
e
l
a
s
t
i
c
i
t
y
,
i
t
m
a
y
f
a
c
i
l
i
t
a
t
e
i
m
p
r
o
v
e
d
r
a
n
g
e
o
f
m
o
t
i
o
n
.
S
u
p
p
o
r
t
i
n
g
t
h
i
s
n
o
t
i
o
n
,
s
t
u
d
i
e
s
h
a
v
e
d
e
m
o
n
s
t
r
a
t
e
d
t
h
a
t
G
u
a
S
h
a
t
h
e
r
a
p
y
,
b
e
y
o
n
d
i
t
s
p
a
i
n
-
r
e
l
i
e
v
i
n
g
e
f
f
e
c
t
s
,
c
a
n
p
o
s
i
t
i
v
e
l
y
i
n
f
l
u
e
n
c
e
t
h
e
f
u
n
c
t
i
o
n
o
f
a
s
s
o
c
i
a
t
e
d
r
e
g
i
o
n
s
.
F
o
r
i
n
s
t
a
n
c
e
,
i
m
p
r
o
v
e
m
e
n
t
s
h
a
v
e
b
e
e
n
o
b
s
e
r
v
e
d
i
n
f
o
o
t
f
u
n
c
t
i
o
n
a
m
o
n
g
i
n
d
i
v
i
d
u
a
l
s
w
i
t
h
p
l
a
n
t
a
r
f
a
s
c
i
i
t
i
s
[
1
2
]
,
m
o
t
o
r
f
u
n
c
t
i
o
n
i
n
P
a
r
k
i
n
s
o
n
'
s
d
i
s
e
a
s
e
[
2
0
]
,
a
n
d
n
e
c
k
o
r
l
o
w
b
a
c
k
f
u
n
c
t
i
o
n
i
n
p
a
t
i
e
n
t
s
w
i
t
h
c
h
r
o
n
i
c
n
e
c
k
a
n
d
l
o
w
b
a
c
k
p
a
i
n
[
1
0
]
,
[
1
1
]
,
[
1
3
]
,
[
1
4
]
.
T
h
e
s
e
f
i
n
d
i
n
g
s
s
u
g
g
e
s
t
a
p
o
t
e
n
t
i
a
l
r
o
l
e
f
o
r
G
u
a
S
h
a
t
h
e
r
a
p
y
i
n
a
d
d
r
e
s
s
i
n
g
f
u
n
c
t
i
o
n
a
l
l
i
m
i
t
a
t
i
o
n
s
a
s
s
o
c
i
a
t
e
d
w
i
t
h
m
u
s
c
u
l
o
s
k
e
l
e
t
a
l
c
o
n
d
i
t
i
o
n
s
.
3.
4
.
P
o
t
ent
ia
l
m
ec
ha
nis
m
s
o
f
G
ua
Sh
a
o
n t
he
f
a
s
cia
T
h
e
b
e
n
ef
its
o
f
Gu
a
Sh
a
th
er
a
p
y
,
esp
ec
ially
p
ain
r
elief
a
n
d
im
p
r
o
v
e
d
f
u
n
ctio
n
,
m
a
y
b
e
att
r
ib
u
ted
t
o
its
ef
f
ec
ts
o
n
t
h
e
f
ascial
s
y
s
tem
.
T
h
e
s
cr
ap
in
g
ac
tio
n
o
f
Gu
a
Sh
a
is
th
o
u
g
h
t
to
i
n
d
u
ce
m
u
ltip
le
p
h
y
s
io
lo
g
ica
l
ch
an
g
es
th
at
p
r
o
m
o
te
h
ea
lin
g
an
d
im
p
r
o
v
e
f
ascial
h
ea
lth
.
Alth
o
u
g
h
th
er
e
a
r
e
cu
r
r
en
tly
n
o
s
tu
d
ies
th
at
d
ir
ec
tly
ex
p
lo
r
e
t
h
e
ef
f
ec
t
o
f
Gu
a
Sh
a
o
n
f
ascia,
th
e
f
o
llo
win
g
m
ec
h
an
is
m
s
m
ay
ex
is
t.
On
e
p
o
ten
tial
m
ec
h
an
is
m
in
v
o
lv
es
im
p
r
o
v
ed
b
lo
o
d
cir
c
u
latio
n
.
T
h
e
f
r
ictio
n
g
en
er
ate
d
b
y
G
u
a
Sh
a
m
a
y
in
cr
ea
s
e
b
lo
o
d
f
lo
w
to
th
e
tr
ea
ted
ar
ea
[
2
1
]
,
p
r
o
v
id
i
n
g
e
s
s
en
tial
n
u
tr
ien
ts
an
d
o
x
y
g
en
to
th
e
f
ascia
ti
s
s
u
e,
p
r
o
m
o
tin
g
tis
s
u
e
r
ep
air
,
an
d
p
o
ten
tially
r
e
d
u
cin
g
p
ain
.
On
th
e
o
th
er
h
a
n
d
,
Gu
a
Sh
a
m
a
y
s
tim
u
late
ly
m
p
h
atic
d
r
ain
ag
e
an
d
p
r
o
m
o
te
th
e
r
em
o
v
al
o
f
waste
an
d
in
f
l
am
m
ato
r
y
m
e
d
iato
r
s
f
r
o
m
t
h
e
f
ascia,
f
u
r
th
e
r
r
ed
u
cin
g
in
f
lam
m
atio
n
an
d
ac
ce
ler
atin
g
h
ea
lin
g
[
1
0
]
,
[
1
2
]
.
I
n
ad
d
itio
n
,
th
e
m
ec
h
a
n
ical
s
tim
u
latio
n
o
f
Gu
a
Sh
a
m
a
y
ac
tiv
ate
s
en
s
o
r
y
n
er
v
e
en
d
in
g
s
,
tr
ig
g
e
r
in
g
m
ec
h
an
is
m
s
th
at
in
h
ib
it
th
e
tr
an
s
m
is
s
io
n
o
f
p
ain
s
ig
n
als
[
1
3
]
.
Fin
ally
,
th
e
p
r
ess
u
r
e
ap
p
lied
d
u
r
in
g
s
cr
ap
in
g
m
ay
h
elp
lo
o
s
en
f
ascial
ad
h
esio
n
s
,
im
p
r
o
v
e
f
ascial
g
lid
in
g
f
u
n
ct
io
n
,
an
d
p
o
ten
tially
in
cr
ea
s
e
jo
in
t
m
o
b
ilit
y
[
1
0
]
.
I
t
is
im
p
o
r
tan
t
to
n
o
te
th
at
th
ese
m
ec
h
an
is
m
s
ar
e
s
till
b
ein
g
ex
p
lo
r
ed
,
a
n
d
f
u
r
th
er
r
esear
ch
is
n
ee
d
ed
to
u
n
d
er
s
tan
d
h
o
w
Gu
a
Sh
a
in
ter
ac
ts
with
f
ascia
th
o
r
o
u
g
h
ly
an
d
co
m
p
r
e
h
en
s
iv
ely
u
n
d
er
s
tan
d
h
o
w
Gu
a
Sh
a
in
t
er
ac
ts
with
f
ascia.
Ho
wev
er
,
th
e
r
esu
lts
o
f
th
is
r
ev
iew
s
u
g
g
est
a
r
ea
s
o
n
a
b
le
co
n
n
ec
tio
n
b
etwe
en
Gu
a
Sh
a
th
er
ap
y
a
n
d
im
p
r
o
v
em
en
ts
in
f
ascia
-
r
elate
d
d
is
o
r
d
er
s
.
4.
DIS
CU
SS
I
O
N
T
h
is
s
y
s
tem
atic
r
ev
iew
id
en
tifie
d
n
in
e
h
ig
h
-
q
u
ality
R
C
T
s
in
v
esti
g
atin
g
th
e
ef
f
ec
ts
o
f
Gu
a
Sh
a
th
er
ap
y
o
n
f
ascia
an
d
v
ar
io
u
s
h
ea
lth
co
n
d
itio
n
s
.
I
n
th
is
d
is
cu
s
s
io
n
,
we
will
ex
p
lo
r
e
th
e
m
ain
f
in
d
in
g
s
,
d
elv
e
in
to
p
o
ten
tial
m
ec
h
an
is
m
s
b
y
wh
ich
Gu
a
Sh
a
m
ay
af
f
ec
t
f
ascia,
cr
itically
ex
am
in
e
th
e
lim
itatio
n
s
o
f
th
e
cu
r
r
en
t e
v
id
en
ce
,
a
n
d
o
u
tlin
e
p
r
o
m
is
in
g
d
i
r
ec
tio
n
s
f
o
r
f
u
tu
r
e
r
esear
ch
.
4
.
1
.
E
v
idence
o
f
t
he
ef
f
ec
t
o
f
G
ua
Sh
a
o
n t
he
f
a
s
cia
Gu
a
Sh
a
a
p
p
ea
r
s
t
o
ex
e
r
t
th
er
ap
eu
tic
ef
f
ec
ts
t
h
r
o
u
g
h
v
ar
i
o
u
s
m
ec
h
an
is
m
s
,
in
clu
d
in
g
p
ain
r
ed
u
ctio
n
,
in
f
lam
m
atio
n
m
itig
atio
n
,
an
d
im
p
r
o
v
e
d
f
lex
ib
ilit
y
.
Hu
m
an
s
tu
d
ies
s
u
p
p
o
r
t
its
ef
f
ec
tiv
en
e
s
s
in
tr
ea
tin
g
p
ain
an
d
c
h
r
o
n
ic
co
n
d
itio
n
s
.
I
n
co
n
tr
ast,
an
im
al
s
tu
d
ies
s
u
g
g
est
Gu
a
Sh
a
m
a
y
e
n
h
an
ce
f
asci
al
b
lo
o
d
f
lo
w
an
d
s
tr
en
g
th
en
its
g
lid
in
g
ab
ilit
y
,
p
o
ten
tially
r
e
d
u
cin
g
f
ascial
in
f
lam
m
atio
n
a
n
d
p
ain
[
2
2
]
,
[
2
3
]
.
T
h
e
f
o
llo
win
g
s
d
is
p
lay
a
clo
s
er
lo
o
k
at
th
e
ev
i
d
en
ce
:
4
.
1
.
1
.
G
ua
Sh
a
ca
n r
eliev
e
p
a
in
Gu
a
Sh
a
f
u
n
ctio
n
s
as
a
m
y
o
f
ascial
r
elea
s
e
tech
n
iq
u
e,
em
p
l
o
y
in
g
a
Gu
a
Sh
a
to
o
l
t
o
s
cr
a
p
e
th
e
s
k
in
an
d
in
d
u
ce
p
etec
h
iae
ca
lled
"Sh
a.
"
R
esear
ch
er
s
ap
p
ly
th
e
to
o
l
alo
n
g
m
er
i
d
ian
s
in
a
s
in
g
le
d
ir
ec
tio
n
,
p
r
ess
in
g
with
s
u
f
f
icien
t
f
o
r
ce
(
1
-
1
.
2
5
k
g
)
to
r
ea
c
h
th
e
f
asci
a
lay
er
[
2
4
]
.
Sev
er
al
s
tu
d
ies
h
av
e
s
h
o
wn
th
at
Gu
a
Sh
a
is
Evaluation Warning : The document was created with Spire.PDF for Python.
I
n
t J Pu
b
lic
Hea
lth
Sci
I
SS
N:
2252
-
8
8
0
6
Th
e
th
era
p
eu
tic
p
o
te
n
tia
l o
f G
u
a
S
h
a
o
n
fa
s
cia
:
e
vid
e
n
ce
a
n
d
p
o
s
s
ib
le
mec
h
a
n
is
ms
(
B
eib
e
i Wa
n
g
)
677
ef
f
ec
tiv
e
in
co
n
tr
o
llin
g
p
ain
.
Fo
r
ex
am
p
le,
G
u
a
Sh
a
ca
n
r
e
d
u
ce
th
e
in
te
n
s
ity
o
f
lo
wer
b
a
ck
an
d
c
h
r
o
n
ic
n
ec
k
p
ain
co
m
p
ar
ed
to
a
co
n
tr
o
l
g
r
o
u
p
[
1
0
]
,
[
1
1
]
,
[
1
3
]
.
I
t
is
wo
r
t
h
n
o
tin
g
t
h
at
s
im
ilar
p
h
y
s
ical
th
er
ap
y
a
p
p
r
o
ac
h
es,
s
u
ch
as
o
th
er
f
ascial
r
elea
s
e
tech
n
iq
u
es,
h
a
v
e
also
b
ee
n
s
h
o
wn
to
h
av
e
p
ain
-
r
eliev
in
g
ef
f
ec
ts
o
n
v
ar
io
u
s
co
n
d
itio
n
s
,
i
n
clu
d
in
g
m
y
o
f
asc
ial
p
ain
,
t
r
ig
g
er
p
o
in
t
s
en
s
itiv
ity
,
an
d
ch
r
o
n
ic
lo
w
b
ac
k
p
ai
n
[
2
5
]
–
[
2
8
]
.
T
h
ese
f
in
d
in
g
s
s
u
g
g
est
th
at
Gu
a
Sh
a
m
ay
s
h
ar
e
s
o
m
e
co
m
m
o
n
an
a
lg
esic
m
ec
h
an
is
m
s
with
o
th
er
m
y
o
f
ascial
r
elea
s
e
tech
n
iq
u
es,
p
r
o
v
id
i
n
g
ev
i
d
en
c
e
o
f
its
p
o
ten
tial to
r
elie
v
e
p
ai
n
.
4
.
1
.
2
.
G
ua
Sh
a
ca
n r
educe
infla
mm
a
t
io
n
Gu
a
Sh
a
m
ay
ex
er
t
its
an
ti
-
in
f
lam
m
ato
r
y
ef
f
ec
ts
th
r
o
u
g
h
v
ar
io
u
s
m
ec
h
an
is
m
s
,
in
clu
d
in
g
th
e
p
o
ten
tial
f
o
r
im
p
r
o
v
e
d
b
lo
o
d
f
lo
w
to
th
e
f
ascia.
E
n
h
an
ce
d
b
lo
o
d
f
l
o
w
ca
n
d
eliv
er
ess
en
tial
n
u
tr
ien
ts
an
d
o
x
y
g
e
n
,
p
r
o
m
o
te
h
ea
lin
g
,
an
d
r
ed
u
ce
in
f
lam
m
atio
n
.
Ma
n
y
s
tu
d
ies
s
u
p
p
o
r
t
th
is
id
ea
,
s
h
o
win
g
r
ed
u
ce
d
p
ain
an
d
im
p
r
o
v
ed
r
an
g
e
o
f
m
o
tio
n
in
th
e
n
ec
k
,
s
h
o
u
l
d
er
s
,
n
ec
k
,
s
h
o
u
ld
er
s
,
a
n
d
b
ac
k
m
y
o
f
a
s
cial
ar
ea
af
ter
Gu
a
Sh
a
tr
ea
tm
en
t
[
2
9
]
.
An
im
al
s
tu
d
ies
p
r
o
v
id
e
f
u
r
th
er
in
s
ig
h
t
s
.
R
esear
ch
h
as
s
h
o
wn
th
at
Gu
a
Sh
a
ca
n
r
ed
u
ce
th
er
m
al
h
y
p
er
alg
esia
an
d
t
h
e
ex
p
r
ess
io
n
o
f
p
r
o
-
in
f
lam
m
ato
r
y
cy
to
k
in
es
in
t
h
e
s
er
u
m
o
f
r
a
ts
[
2
2
]
.
I
n
ad
d
itio
n
,
Gu
a
Sh
a
ca
n
s
ig
n
if
ican
tly
in
h
ib
it in
f
lam
m
ato
r
y
in
f
iltra
tio
n
i
n
th
e
lu
n
g
tis
s
u
e
o
f
R
R
8
-
in
f
ec
ted
m
ice
an
d
d
o
wn
-
r
eg
u
late
Ma
tr
ix
m
etallo
p
r
o
tein
ase
-
9
[
2
3
]
.
T
h
ese
f
in
d
in
g
s
,
c
o
u
p
led
with
ev
id
e
n
ce
th
at
Gu
a
Sh
a
im
p
r
o
v
es
m
icr
o
cir
cu
latio
n
[
2
4
]
,
s
u
g
g
es
t
th
at
Gu
a
Sh
a
m
ay
h
av
e
an
in
f
lam
m
ato
r
y
-
r
ed
u
cin
g
ef
f
ec
t.
Ho
wev
er
,
f
u
r
t
h
er
r
esear
ch
is
n
ee
d
ed
t
o
elu
cid
ate
th
e
s
p
ec
if
ic
an
ti
-
in
f
lam
m
at
o
r
y
m
ec
h
an
is
m
s
o
f
G
u
a
Sh
a.
4
.
1
.
3
.
G
ua
Sh
a
ca
n im
pro
v
e
f
lex
ibi
lity
F
a
s
ci
a
l
a
d
h
e
s
i
o
n
s
a
n
d
s
t
i
f
f
n
e
s
s
a
r
e
k
n
o
w
n
c
o
n
t
r
i
b
u
t
o
r
s
t
o
p
a
i
n
a
n
d
m
o
v
e
m
e
n
t
d
y
s
f
u
n
c
t
i
o
n
.
G
u
a
S
h
a
e
m
e
r
g
e
s
as
a
p
r
o
m
i
s
i
n
g
m
y
o
f
a
s
c
i
al
r
e
l
e
as
e
te
c
h
n
i
q
u
e
,
w
it
h
s
o
m
e
r
e
s
ea
r
c
h
e
r
s
s
u
g
g
e
s
ti
n
g
i
t
s
e
f
f
ec
t
i
v
e
n
es
s
i
n
i
m
p
r
o
v
i
n
g
f
l
e
x
i
b
i
l
i
t
y
f
o
r
s
e
d
e
n
t
a
r
y
i
n
d
i
v
i
d
u
a
l
s
a
n
d
p
a
t
i
e
n
ts
w
i
t
h
P
a
r
k
i
n
s
o
n
'
s
d
is
e
a
s
e
[
3
0
]
.
G
u
a
S
h
a
a
p
p
e
a
r
s
to
h
a
v
e
a
s
i
m
i
l
a
r
e
f
f
e
c
t
o
n
f
l
e
x
i
b
il
i
t
y
a
s
m
a
s
s
a
g
e
,
a
c
u
p
u
n
c
t
u
r
e
,
a
n
d
o
t
h
e
r
m
y
o
f
a
s
c
i
a
l
r
e
l
e
a
s
e
te
c
h
n
i
q
u
e
s
.
R
es
e
a
r
c
h
o
n
t
h
e
s
e
l
f
-
m
y
o
f
a
s
c
ia
l
r
e
l
e
as
e
o
f
t
h
e
l
o
w
e
r
b
a
c
k
u
s
i
n
g
a
r
o
l
le
r
m
a
s
s
a
g
e
r
s
h
o
w
s
t
h
a
t
G
u
a
Sh
a
i
m
p
r
o
v
e
s
f
a
s
c
i
al
g
l
i
d
i
n
g
,
l
u
m
b
a
r
s
p
i
n
e
f
l
e
x
i
b
i
l
ity
,
a
n
d
a
b
d
o
m
i
n
a
l
m
u
s
c
l
e
s
t
r
e
n
g
t
h
c
o
m
p
a
r
e
d
t
o
s
t
a
t
i
c
s
t
r
e
t
c
h
in
g
[
3
1
]
.
S
u
p
p
o
r
t
i
n
g
t
h
i
s
n
o
t
i
o
n
,
r
a
n
d
o
m
i
z
e
d
c
l
i
n
i
ca
l
t
r
i
a
ls
h
a
v
e
s
h
o
w
n
t
h
a
t
l
u
m
b
a
r
f
a
s
c
i
a
s
t
r
et
c
h
i
n
g
i
m
p
r
o
v
e
s
h
a
m
s
t
r
i
n
g
m
o
b
i
l
i
t
y
[
3
2
]
.
S
i
m
i
l
a
r
l
y
,
p
e
r
c
u
s
s
i
v
e
m
as
s
a
g
e
t
h
e
r
a
p
y
h
a
s
b
e
e
n
s
h
o
w
n
t
o
e
n
h
a
n
c
e
t
h
e
f
l
e
x
i
b
i
li
t
y
o
f
th
o
r
a
c
o
l
u
m
b
a
r
f
a
s
c
i
a
[
3
3
]
.
A
d
d
i
t
i
o
n
a
l
l
y
,
s
t
u
d
i
es
h
a
v
e
s
h
o
w
n
t
h
at
s
e
l
f
-
m
y
o
f
a
s
ci
a
l
r
e
le
a
s
e
a
n
d
l
a
te
r
a
l
f
r
ic
t
i
o
n
m
a
s
s
a
g
e
t
h
e
r
a
p
y
e
f
f
e
c
t
i
v
e
l
y
i
m
p
r
o
v
e
h
a
m
s
t
r
i
n
g
f
l
e
x
i
b
i
l
i
t
y
[
3
4
]
.
T
h
e
p
r
e
s
s
u
r
e
a
n
d
f
r
i
c
t
i
o
n
a
p
p
l
i
e
d
d
u
r
i
n
g
G
u
a
S
h
a
m
a
y
m
e
c
h
a
n
i
c
a
l
l
y
d
is
r
u
p
t
f
as
c
i
al
a
d
h
e
s
i
o
n
s
,
p
r
o
m
o
t
i
n
g
b
e
tt
e
r
e
x
t
en
s
i
o
n
a
n
d
f
l
e
x
i
b
i
li
t
y
.
4
.
2
.
P
o
s
s
ibl
e
m
ec
ha
nis
m
s
o
f
G
ua
Sh
a
o
n t
he
f
a
s
cia
T
h
e
m
ec
h
a
n
is
m
s
b
y
wh
ich
Gu
a
Sh
a
af
f
ec
ts
f
ascia
ar
e
s
till
b
ein
g
ex
p
lo
r
ed
,
b
u
t
s
ev
er
al
p
o
ten
tial
p
ath
way
s
h
av
e
b
ee
n
p
r
o
p
o
s
ed
.
T
h
ese
in
clu
d
e:
4
.
2
.
1
.
E
nh
a
nced
blo
o
d c
ircul
a
t
io
n a
nd
f
a
s
cia
re
mo
delin
g
Fas
cia,
a
d
en
s
e
n
etwo
r
k
o
f
co
n
n
ec
tiv
e
tis
s
u
e,
p
lay
s
a
cr
itic
al
r
o
le
in
b
o
d
y
s
tr
u
ctu
r
e
a
n
d
m
o
v
em
en
t
[
3
5
]
.
Gu
a
Sh
a'
s
m
ec
h
an
ical
s
tim
u
latio
n
m
ay
in
f
lu
en
ce
f
a
s
cia
r
em
o
d
elin
g
an
d
b
lo
o
d
c
ir
cu
latio
n
th
r
o
u
g
h
s
ev
er
al
p
o
ten
tial
m
ec
h
an
is
m
s
.
First,
it
in
cr
ea
s
es
b
lo
o
d
f
lo
w
an
d
n
u
t
r
ien
t
d
eliv
er
y
.
T
h
e
s
cr
ap
in
g
ac
tio
n
o
f
th
e
Gu
a
Sh
a
to
o
l
in
d
u
ce
s
d
ilatio
n
o
f
f
ascial
ca
p
illar
ies,
en
h
an
ci
n
g
b
l
o
o
d
f
lo
w
an
d
d
eliv
e
r
in
g
ess
en
tial
n
u
tr
ien
ts
an
d
o
x
y
g
en
to
f
ascial
f
ib
r
o
b
last
s
[
2
4
]
.
T
h
is
im
p
r
o
v
ed
n
u
tr
ien
t
s
u
p
p
ly
m
ay
p
r
o
m
o
t
e
tis
s
u
e
r
ep
air
an
d
r
eg
en
er
atio
n
with
in
th
e
f
ascia.
I
n
ad
d
itio
n
,
e
n
h
an
ce
d
b
lo
o
d
f
lo
w
m
ay
a
f
f
ec
t
th
e
p
r
o
d
u
ctio
n
o
f
c
o
llag
en
an
d
elastin
,
wh
ich
ar
e
k
ey
co
m
p
o
n
en
ts
o
f
f
ascia
elasticity
an
d
f
lex
ib
il
ity
[
3
6
]
.
Seco
n
d
,
Gu
a
Sh
a
ca
n
en
h
an
ce
f
ib
r
o
b
last
ac
tiv
ity
.
T
h
e
m
ec
h
an
ical
s
tim
u
latio
n
o
f
G
u
a
Sh
a
ac
tiv
ates
f
ib
r
o
b
last
s
,
wh
ich
ar
e
r
esp
o
n
s
ib
le
f
o
r
p
r
o
d
u
cin
g
co
llag
e
n
an
d
elastin
,
th
e
m
ain
co
m
p
o
n
e
n
ts
o
f
f
ascia
[
3
7
]
.
C
o
llag
en
f
ib
er
s
p
r
o
v
id
e
a
s
tr
u
ctu
r
al
f
r
am
ewo
r
k
f
o
r
f
ascia,
wh
ile
e
last
in
f
ib
er
s
co
n
tr
ib
u
te
to
its
elasticity
an
d
f
lex
ib
ilit
y
[
3
6
]
,
[
3
8
]
.
Gu
a
Sh
a
m
a
y
af
f
ec
t th
e
b
alan
ce
b
etwe
en
c
o
llag
en
s
y
n
th
esis
an
d
d
eg
r
a
d
atio
n
b
y
im
p
r
o
v
in
g
b
lo
o
d
f
lo
w,
th
er
eb
y
af
f
ec
tin
g
th
e
th
ick
n
ess
an
d
elasticity
o
f
f
asc
ia.
F
i
n
a
l
l
y
,
r
e
s
ea
r
c
h
d
e
m
o
n
s
t
r
a
t
es
t
h
at
b
l
o
o
d
c
i
r
c
u
l
a
t
i
o
n
i
n
f
a
s
c
i
al
ti
s
s
u
e
m
a
y
p
l
a
y
a
k
ey
r
o
l
e
i
n
m
a
i
n
t
a
i
n
i
n
g
t
h
e
b
i
o
m
e
c
h
a
n
i
c
a
l,
p
r
o
p
r
i
o
c
e
p
t
i
v
e
,
a
n
d
n
o
c
i
c
e
p
t
iv
e
f
u
n
c
t
i
o
n
s
o
f
t
h
e
t
h
o
r
a
c
o
l
u
m
b
a
r
f
a
s
c
i
a
[
3
9
]
,
[
4
0
]
.
R
e
d
u
c
e
d
b
l
o
o
d
f
l
o
w
d
u
e
t
o
h
y
p
o
x
i
a
m
a
y
t
r
i
g
g
e
r
f
as
c
i
al
d
eg
e
n
e
r
a
t
i
o
n
,
c
h
a
r
a
c
te
r
i
z
e
d
b
y
s
t
i
f
f
n
e
s
s
,
f
i
b
r
o
s
i
s
,
o
r
t
h
i
c
k
e
n
i
n
g
[
4
1
]
.
G
u
a
S
h
a
c
o
u
ld
t
h
e
o
r
e
t
i
c
al
l
y
c
o
u
n
t
e
r
a
ct
t
h
ese
d
e
g
e
n
e
r
a
t
i
v
e
p
r
o
c
ess
e
s
b
y
p
o
t
e
n
t
i
a
ll
y
i
m
p
r
o
v
i
n
g
b
l
o
o
d
f
l
o
w
.
F
u
r
t
h
e
r
r
e
s
ea
r
c
h
i
s
n
e
e
d
e
d
t
o
e
x
p
l
o
r
e
t
h
e
l
i
n
k
b
e
t
we
e
n
G
u
a
S
h
a
a
n
d
f
as
c
i
a
l
d
e
g
e
n
e
r
a
t
i
o
n
.
4
.
2
.
2
.
I
m
pro
v
es ly
m
ph
circ
ul
a
t
io
n a
nd
re
du
ce
s
infla
m
m
a
t
io
n
Gu
a
Sh
a
h
as
an
ti
-
in
f
lam
m
ato
r
y
p
r
o
p
er
ties
,
wh
ich
m
ay
b
e
lar
g
ely
attr
ib
u
ted
to
its
ef
f
e
cts
o
n
th
e
ly
m
p
h
atic
s
y
s
tem
,
wh
ich
p
lay
s
a
v
ital
r
o
le
in
r
em
o
v
i
n
g
waste
an
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to
x
in
s
.
R
esear
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s
h
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ws
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at
t
h
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l
y
m
p
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a
t
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s
y
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te
m
is
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ti
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a
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e
li
m
i
n
a
ti
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g
w
a
s
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a
n
d
t
o
x
i
n
s
f
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o
m
t
h
e
b
o
d
y
.
B
y
r
e
s
h
a
p
i
n
g
t
h
e
c
a
p
i
ll
a
r
y
n
e
t
wo
r
k
,
Gu
a
Sh
a
en
h
an
ce
s
ly
m
p
h
atic
d
r
ain
ag
e,
p
r
o
m
o
tin
g
an
ti
-
in
f
lam
m
at
o
r
y
an
d
an
tio
x
i
d
an
t
ef
f
ec
ts
.
Her
e'
s
h
o
w
it
wo
r
k
s
:
Evaluation Warning : The document was created with Spire.PDF for Python.
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14
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No
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2
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J
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20
25
:
6
7
2
-
6
8
1
678
I
n
f
lam
m
atio
n
an
d
o
x
id
ativ
e
s
tr
ess
ca
n
tr
ig
g
er
th
e
p
r
o
d
u
ctio
n
o
f
h
em
e
o
x
y
g
en
ase
-
1
(
HO
-
1
)
,
a
n
e
n
zy
m
e
with
p
o
ten
t
an
tio
x
id
an
t,
an
ti
-
in
f
lam
m
ato
r
y
,
a
n
d
im
m
u
n
o
m
o
d
u
lato
r
y
p
r
o
p
er
ties
in
v
ascu
lar
ce
lls
[
4
2
]
.
Stu
d
ies
h
a
v
e
s
h
o
w
n
t
h
a
t
G
u
a
S
h
a
m
a
y
u
p
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g
u
l
a
t
e
H
O
-
1
,
r
e
f
l
e
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ti
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g
t
h
e
b
o
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y
'
s
a
n
t
i
o
x
i
d
a
n
t
r
es
p
o
n
s
e
[
4
3
]
.
I
n
a
d
d
i
t
i
o
n
,
r
e
s
t
r
i
ct
e
d
b
l
o
o
d
c
i
r
c
u
l
a
ti
o
n
m
a
y
l
e
a
d
t
o
i
n
f
l
a
m
m
a
t
i
o
n
d
u
e
t
o
a
l
a
c
k
o
f
o
x
y
g
e
n
[
4
4
]
,
a
n
d
G
u
a
S
h
a
c
a
n
i
n
d
i
r
e
c
t
ly
ad
d
r
ess
th
is
p
r
o
b
lem
b
y
im
p
r
o
v
in
g
b
lo
o
d
f
lo
w.
C
lin
ical
ev
id
en
ce
f
u
r
t
h
er
s
u
p
p
o
r
ts
th
e
ef
f
ec
tiv
en
ess
o
f
Gu
a
Sh
a
in
tr
ea
tin
g
jo
in
t
f
as
cial
in
f
lam
m
atio
n
in
th
e
n
ec
k
,
b
ac
k
,
a
n
d
f
ee
t
[
1
1
]
,
[
1
2
]
.
An
im
al
ex
p
er
im
en
ts
f
u
r
th
er
e
lu
cid
ated
th
e
an
ti
-
in
f
lam
m
ato
r
y
m
ec
h
a
n
is
m
o
f
Gu
a
Sh
a
.
Stu
d
ies
h
av
e
s
h
o
wn
th
at
Gu
a
Sh
a
ca
n
r
ed
u
ce
th
er
m
al
h
y
p
er
alg
esia
an
d
th
e
ex
p
r
ess
io
n
o
f
p
r
o
-
in
f
lam
m
ato
r
y
cy
t
o
k
in
es
(IL
-
1
β,
I
L
-
6
,
an
d
T
NF
-
α
)
in
t
h
e
s
er
u
m
o
f
r
ats
with
lu
m
b
ar
d
is
c
h
er
n
iatio
n
[
2
2
]
.
T
h
is
s
u
g
g
ests
th
at
Gu
a
Sh
a
m
ay
r
eg
u
late
in
f
lam
m
at
o
r
y
s
i
g
n
alin
g
p
ath
wa
y
s
,
co
n
tr
ib
u
tin
g
to
its
an
alg
esic
ef
f
ec
ts
.
I
n
an
o
th
er
s
tu
d
y
,
Gu
a
Sh
a
si
g
n
if
ican
tly
in
h
ib
ited
in
f
lam
m
ato
r
y
i
n
f
iltra
tio
n
in
th
e
lu
n
g
tis
s
u
e
o
f
R
R
8
-
in
f
ec
ted
m
ice
an
d
d
o
wn
r
eg
u
lated
m
atr
ix
m
etallo
p
r
o
tein
ase
-
9
(
MM
P
-
9)
[
2
3
]
.
Do
wn
r
eg
u
latio
n
o
f
MM
P
-
9
,
an
en
zy
m
e
in
v
o
l
v
ed
in
tis
s
u
e
b
r
ea
k
d
o
wn
an
d
in
f
la
m
m
atio
n
,
s
u
g
g
ests
th
at
Gu
a
S
h
a
m
ay
p
r
o
tect
ag
ain
s
t
lu
n
g
i
n
ju
r
y
.
Ov
er
all,
th
e
an
ti
-
in
f
lam
m
ato
r
y
ef
f
ec
ts
o
f
Gu
a
Sh
a
ar
e
s
u
p
p
o
r
ted
b
y
a
n
im
al
an
d
clin
ical
s
tu
d
ies.
G
u
a
Sh
a'
s
ab
ilit
y
to
en
h
an
ce
ly
m
p
h
atic
d
r
ai
n
ag
e,
u
p
r
eg
u
late
HO
-
1
,
an
d
m
o
d
u
la
te
in
f
lam
m
ato
r
y
s
ig
n
a
lin
g
p
ath
way
s
m
ay
b
e
p
ar
t
o
f
its
th
er
ap
eu
tic
ef
f
ec
ts
.
4
.
2
.
3
.
Reg
ula
t
e
nerv
es a
nd
r
eliev
e
pa
in
E
x
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to
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ical
s
tu
d
ies
r
ec
o
g
n
ize
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e
p
r
esen
ce
o
f
ab
u
n
d
an
t
s
en
s
o
r
y
n
e
r
v
es
in
f
ascia
[
3
9
]
.
I
t
is
esti
m
ated
th
at
th
e
en
tire
f
asc
i
a
n
e
t
w
o
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k
o
f
t
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h
u
m
a
n
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o
d
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a
s
a
p
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m
a
t
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y
2
5
0
m
i
l
li
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n
e
r
v
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n
d
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n
g
s
[
4
5
]
,
w
h
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c
h
h
as
l
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d
t
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f
as
c
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b
e
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.
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o
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u
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n
d
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n
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n
v
i
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o
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m
e
n
t
,
s
u
c
h
a
s
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e
m
p
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r
a
t
u
r
e
,
p
r
e
s
s
u
r
e
,
a
n
d
p
a
i
n
.
T
h
i
s
i
n
f
o
r
m
a
t
i
o
n
c
a
n
b
e
p
r
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c
e
s
s
e
d
b
y
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h
e
b
r
a
i
n
a
n
d
f
e
d
b
a
c
k
t
o
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e
m
u
s
c
l
e
s
t
o
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e
g
u
l
a
te
m
u
s
c
l
e
c
o
n
t
r
a
c
ti
o
n
a
n
d
r
e
l
a
x
a
t
i
o
n
[
4
5
]
,
m
a
k
i
n
g
f
a
s
c
i
a
t
h
e
m
o
s
t
p
r
o
s
p
e
r
o
u
s
s
e
n
s
o
r
y
t
i
s
s
u
e
i
n
t
h
e
h
u
m
a
n
b
o
d
y
.
T
h
e
G
ua
Sh
a
m
o
tio
n
o
f
Gu
a
Sh
a
s
tim
u
lates
n
er
v
e
en
d
in
g
s
o
n
th
e
s
k
in
,
wh
ic
h
s
en
d
s
ig
n
als
to
th
e
b
r
ain
to
r
eg
u
late
th
e
f
u
n
ctio
n
o
f
th
e
ce
n
tr
al
n
er
v
o
u
s
s
y
s
te
m
[
1
7
]
.
Gu
a
Sh
a
ca
n
s
tim
u
late
n
er
v
e
en
d
in
g
s
to
r
elea
s
e
n
eu
r
o
tr
an
s
m
itter
s
an
d
ac
ety
lch
o
lin
e,
an
d
t
h
ese
n
eu
r
o
tr
an
s
m
itter
s
ca
n
r
eg
u
late
th
e
ac
tiv
ity
o
f
m
u
s
cles
an
d
f
ascia
[
4
6
]
.
Gu
a
Sh
a
r
elea
s
es
en
d
o
r
p
h
in
s
,
a
n
atu
r
al
a
n
alg
esic
s
u
b
s
tan
ce
th
at
ca
n
r
eliev
e
p
ain
an
d
im
p
r
o
v
e
m
u
s
cle
to
n
e
[
4
7
]
.
Fo
r
ex
am
p
le,
Gu
a
Sh
a
ca
n
r
elea
s
e
en
d
o
r
p
h
in
s
an
d
ac
ety
lch
o
lin
e,
a
n
e
u
r
o
tr
an
s
m
itter
th
at
p
r
o
m
o
tes m
u
s
cle
co
n
tr
ac
tio
n
a
n
d
r
elax
atio
n
.
A
n
i
m
a
l
s
t
u
d
i
e
s
h
a
v
e
p
r
o
v
i
d
e
d
s
o
m
e
i
n
i
t
i
a
l
i
n
s
i
g
h
t
s
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n
t
o
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u
r
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l
m
e
c
h
a
n
i
s
m
s
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n
d
e
r
l
y
i
n
g
G
u
a
S
h
a
t
h
e
r
a
p
y
.
S
o
m
e
s
t
u
d
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a
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o
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t
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v
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t
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g
[
4
8
]
–
[
5
1
]
.
I
n
f
l
a
m
m
a
t
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o
n
w
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t
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p
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[
2
2
]
.
I
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G
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