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Chinese Medical Journal 2012;125(23):4301-4306

Meta analysis
Risk of cardiovascular disease and all-cause mortality among
diabetic patients prescribed rosiglitazone or pioglitazone: a
meta-analysis of retrospective cohort studies
CHEN Xin, YANG Li and ZHAI Suo-di
Keywords: cardiovascular risk; meta-analysis; pioglitazone; rosiglitazone; cohort study
Background The difference of cardiovascular effects between rosiglitazone and pioglitazone treatment for diabetic
patients has not been thoroughly studied. We performed a meta-analysis to compare the risk of cardiovascular adverse
effects in patients with type 2 diabetes treated with rosiglitazone compared to pioglitazone.
Methods The Cochrane Library, PubMed, and Embase were searched to identify retrospective cohort studies
assessing cardiovascular outcomes with rosiglitazone and pioglitazone. Meta-analysis of retrospective cohort studies
was conducted using RevMan 5.0 software to calculate risk ratios.
Results Of the 74 references identified, eight studies involving 945 286 patients fit the inclusion criteria for the analysis.
The results of meta-analyses showed that, compared with pioglitazone, rosiglitazone therapy significantly increased the
risk of myocardial infarction (risk ratios (RR) 1.17, 95% confidence interval (CI) 1.041.32; P=0.01), the risk of heart
failure (RR 1.18, 95% CI 1.021.36; P=0.03), and total mortality (RR 1.13, 95% CI 1.081.20; P <0.000 01).
Conclusion Compared with pioglitazone, rosiglitazone was associated with an increased risk of myocardial infarction,
heart failure, and all-cause mortality in diabetic patients.
Chin Med J 2012;125(23):4301-4306

osiglitazone and pioglitazone, the only marketed

thiazolidinediones (TZDs), are oral hypoglycaemic
agents that have been shown to improve glycaemic
control and may act to slow the progression of beta cell
failure. In May 2007, a meta-analysis of data from 42
randomized controlled clinical trials found an increased
risk of myocardial infarction (MI) and death from
cardiovascular causes in relation to the use of
rosiglitazone.1 However, several meta-analyses did not
come to the same conclusion. Moreover, the results of the
Rosiglitazone Evaluated for Cardiac Outcomes and
Regulation of Glycemia in Diabetes (RECORD) trial,
which was once considered to be the strongest evidence
evaluating the cardiovascular safety of rosiglitazone,
showed no significant increase in these events with
rosiglitazone compared to metformin or sulfonylurea in
2009.2 On the other hand, a meta-analysis of 19
randomised controlled trials with pioglitazone found a
statistically significant reduction in the composite
outcome of nonfatal MI stroke, and all-cause mortality.3
Thus, the cardiovascular risk data for rosiglitazone and
benefits of pioglitazone are less than conclusive and an
intriguing disparity between the drugs has emerged,
suggesting an intraclass variation in TZD effects. The
debate about the TZDs effects on cardiovascular health of
has gone on for years; especially in the case of
rosiglitazone.4-8 This debate is set against a background of
a lack of sufficient data and uncertainty about the
cardiovascular safety differences between the two types
of TZDs, mainly due to limitations in the randomised,
controlled trials to date, such as short duration and small

sample size.9
In contrast, surveillance data routinely collected through
general practice are able to capture information on drugs
and events in a wide range of patients as they present for
clinical care. That is to say, cohort studies provide data on
real-life use, rare outcomes, and long-term effects that are
undetectable in randomised controlled trials.10 With large
healthcare utilisation databases being used more and
more frequently, active surveillance in the form of
retrospective cohort studies can provide evidence of risk
that is not necessarily provided by randomised controlled
trials.11 Therefore, the comparison of cardiovascular
events in diabetic patients treated with rosiglitazone and
pioglitazone in the same cohort study can illustrate the
differential cardiovascular outcomes of these two
medications, which may provide strong evidence in the
debate on TZD safety.
The cardiovascular risks of rosiglitazone and pioglitazone
have been compared with one another in several
observational studies. A meta-analysis of these cohort
studies in type 2 diabetic patients was conducted to
compare the risk of myocardial infarction, heart failure,
and all-cause mortality between rosiglitazone and
DOI: 10.3760/cma.j.issn.0366-6999.2012.23.025
Department of Pharmacy, Peking University Third Hospital,
Beijing 100191, China (Chen X, Yang L and Zhai SD)
Correspondence to: Prof. ZHAI Suo-di, Department of Pharmacy,
Peking University Third Hospital, Beijing 100191, China (Tel &
Fax: 86-10-82266686. Email: zhaisuodi@163.com)

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Chin Med J 2012;125(23):4301-4306

pioglitazone.
METHODS
Search strategy
The search strategy was designed to identify
observational cohort studies conducted in any country, in
people of any age, and aimed to compare cardiovascular
outcomes of both rosiglitazone and pioglitazone at the
same time. A computer-based literature search was
conducted up to July 2010 using the Cochrane library,
PubMed, and Embase. MeSH terms used to identify
articles included rosiglitazone, pioglitazone, cohort
study, and cardiovascular risk, as well as myocardial
infraction and heart failure. Additionally, we screened
the reference lists of selected researches and wrote to
authors for further detailed data. Although no language
restrictions were applied, the search results produced
studies published only in English. The literature search
was conducted by Chen and Zhai independently.
Inclusion criteria
All identified articles were reviewed according to
inclusion criteria before proceeding with further analysis.
The inclusion criteria were: (1) retrospective cohort study
in patients with diabetes mellitus; (2) studies that
compared rosiglitazone to pioglitazone with or without
other classes of oral antidiabetes drugs; (3) parameters
used to estimate cardiovascular risks, such as MI, heart
failure, or mortality. Studies were excluded if they were
not original research, were not available as full papers,
did not meet the three parameters mentioned above, or
were case-controlled studies.
Data extraction and quality assessment
Each potentially eligible study was independently
assessed by two qualified reviewers (Chen and Zhai) to
determine whether it met the inclusion criteria and to
assess its methodological quality. Conflict between the
reviewers was resolved through discussion, and if
consensus could not be reached, a third reviewer (Yang)
determined the outcome. The two reviewers
independently extracted data from each included study
using a standardised form. The characteristics of each
study were identified and extracted, including:
methodology, database, number of patients, intervention,
follow-up period, population characteristics, diagnostic
criteria of diabetes and outcomes. The outcome data
extracted were: number of patients treated with
rosiglitazone as well as those treated with pioglitazone,
number of events of each group.
The most important quality criteria for studies included:
prior cardiovascular outcome researches, reliability of
database researches used, comparability of population
characteristics between rosiglitazone groups and
pioglitazone groups, a follow-up period of at least one
year, and a clear definition of diabetes and outcomes.

Statistical analysis
RevMan version 5.0 (Cochrane Collaboration,
Copenhagen, Denmark) was used to combine results from
more than two separate trials. Statistical heterogeneity
among the studies was identified using the 2 test
(P=0.05). Random-effects models were applied when
heterogeneity was identified in a group of studies (P
0.10); otherwise, fixed-effects models were used. Since
the outcomes were dichotomous, risk ratios (RRs) were
calculated, and the range of the RRs was expressed as a
95% confidence interval (CI). P <0.05 was considered
statistically significant. Subgroup analysis was performed
to answer specific questions about particular patient
groups or types of interventions.
RESULTS
Study inclusion
The search of PubMed and Embase revealed 18 and 54
researches, respectively, of which 15 were relevant for
our study, while there was no relevant research from
Cochrane Library. Two studies were excluded from the
analysis based on the criterion for case control cohort
studies.12,13 One study were excluded because the data of
rosiglitazone and pioglitazone respectively were not
available. The other studies were excluded because the
original data relating to numbers of events were
unpublished. After attempting to contact corresponding
authors, three authors provided further data for analysis.
Finally, eight studies remained eligible for inclusion
(Table 1).14-21 Figure 1 shows search process and reasons
for excluding studies.
Study characteristics
Table 2 shows the main characteristics of the studies.
Most cohort studies were performed in the USA, one in
the UK, one in Canada, and one in Taiwan, China. Three
of the studies involved patients older than 65 years.14-16
Another study by Gerrits included patients older than 45
years,17 while the patients of Tzoulakis study were
between 35 and 90 years old.18 Only one study
specifically narrowed its population to newly diagnosed
diabetic patients.19 Unpublished data from Pantalones
study were added to our analysis.20 In all studies, the
rosiglitazone arm was compared with the pioglitazone
arm. Four studies were head-to-head cohorts of these two
TZD drugs.14-17 Four studies excluded patients that
received a prescription for insulin during TZD
treatment.14,16-18 Moreover, two studies compared
rosiglitazone and pioglitazone as monotherapy or in
combination, respectively.18,19
Data synthesis and sensitivity analysis
Myocardial infraction
A total of seven studies reported numbers of myocardial
infraction, and they showed statistical heterogeneity
across studies (Q-test P values=0.002); hence, a random
effects model was used for analysis. As showed in Figure
2, compared with patients given pioglitazone, patients

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Chinese Medical Journal 2012;125(23):4301-4306

Table 1. Basic characteristics of included studies
References
Graham, 2010
Brownstein, 2010
Hsiao, 2009
Pantalone, 2009
Tzoulake, 2009
Juurlink, 2009
Winkelmayer, 2008
Gerrit, 2007

Country
USA
USA
China
USA
UK
Canada
USA
USA

Database

No. of patients

Population

Medicare Database
227 571
T2DM, above 65 years old
Partners Healthcare System
34 253
DM
Taiwans National Health Insurance
473 483
Newly diagnosed T2DM
Electronic health record derived clinical data at the
20 450
T2DM, no CV history
Cleveland Clinic
UK general practice research database
91 521
T2DM, 3590 years old
Ontario Public Drug Benefit Program, national
39 736
T2DM, above 65 years old
ambulatory care reporting system database
Medicare Beneficiaries
28 361
DM, above 65 years old
The Ingenix Research Database
29 911
T2DM
CV: cardiovascular. DM: diabetes mellitus. T2DM: type 2 diabetes mellitus.

Follow-up
(years)
3
7
5
8

Study period
20062009
20002006
20012005
19982006

7.1
3

19902005
20022008

5
1.21.3

20002005
20032006

given rosiglitazone had an increased risk of MI (RR 1.17;

95% CI 1.041.32, P=0.010). In the head-to-head studies,
the RR was 1.08 (95% CI 1.011.15, P=0.030).
Considering that the follow-up period of Gerrits study
was shorter than others, exclusion of this study from the
analysis gave an RR of 1.15 (95% CI 1.011.32,
P=0.040). For the studies that excluded patients treated
with insulin, the RR was 1.09 (95% CI 0.981.20,
P=0.11).
Heart failure
Since there was significant heterogeneity among the five
studies (P <0.0001, I2=84%) that reported the number of
heart failure events, the analysis used a random effects
model. The risk of heart failure was increased in the

Figure 1. Search process showing reasons for excluding studies.

Table 2. Patient characteristics of included studies

Rosiglitazone
References

Pioglitazone

Age (years)

Male (%)

Graham, 2010

74.4

39.2

No. of
patients
67 593

Brownstein,
2010
Hsiao, 2009

64.0

51.7

1879

Mono: 61.2
Multi: 55.4

Mono: 53.4
Multi: 52.6

61.4
Mono: 65.7
Multi: 64.5
72

45.5
Mono: 50.5
Multi: 53.6
53.1

76.3
58

Pantalone, 2009
Tzoulake, 2009
Juurlink, 2009
Winkelmayer,
2008
Gerrit, 2007

Age
(years)
74.4

Diagnostic criteria of
diabetes

Diagnostic criteria of cardiovascular

events

NA

AMI: ICD-9code410
CHF: ICD-9codes402x1, 404x3,428
AMI: ICD-9code410

40.5

No. of
patients
159 978

63.7

52.4

806

ICD-9code250.XX

49 624

Mono: 60.8
Multi: 54.6

Mono: 52.0
Multi: 53.2

12 010

ICD-9code250.XX

1079
18 082

61.6
64.8

48.3
54.3

1508
3816

ICD-9
READ CODE

22 785

72

52.1

16 951

NA

26.4

14 101

76.3

26.0

14 260

NA

57.2

15 104

Male (%)

58
58.8
14 807
ICD-9code250.XX
Mono: monotherapy. Multi: combination therapy.

AMI: ICD-9code410.XX, 411.XX

CHF: ICD-9codes428.XX402.01,
402.11402.91, 404.01, 404.11, 404.XX
ICD-9
READ CODE
AMI: ICD-10codeI20I21I22
CHF: ICD-10codesI50
NA
AMI: ICD-9code410

Figure 2. Comparison
myocardial infarction.

of

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Chin Med J 2012;125(23):4301-4306

Figure 3. Comparison of risk of

heart failure.

Figure 4. Comparison of risk of

all-cause mortality

rosiglitazone group compared to the pioglitazone group

(RR 1.18, 95% CI 1.021.36; P=0.03) (Figure 3). When
unpublished data for Pantalones study were included,
among the six studies, the difference between
rosiglitazone and pioglitazone was not significant (RR
1.14, 95% CI 0.981.32; P=0.08). Analysis of the four
studies that excluded patients on insulin combination
therapy found no difference between the two TZDs (RR
1.00, 95% CI 0.771.31; P=0.99)
All-cause mortality
All-cause mortality was reported in four studies. The RR
was 1.13 (95% CI 1.081.20; P <0.00001) (Figure 4).
After including data provided by the author of one study,
the risk of mortality remained significant in the
rosiglitazone group for the whole analysis (RR 1.13, 95%
CI 1.001.19; P <0.00001). Sensitivity analysis of studies
that did not involve insulin treatment showed more risk
with rosiglitazone (RR 1.16, 95% CI 1.081.24; P
<0.00001).
DISCUSSION
This meta-analysis compared the cardiovascular risks of
rosiglitazone and pioglitazone based on a total of eight
retrospective cohort studies. The risk of all three
outcomesMI,
heart
failure
and
all
cause
mortalitywere higher in the rosiglitazone group than in
the pioglitazone group. Moreover, the results of the main
analysis involving the whole population was significant,
and the results did not change with inclusion of the
unpublished data from one study or sensitivity analysis of
studies that did not involve insulin treatment, though part
of the analysis did not show significant differences. Our
findings suggest clear evidence for the cardiovascular
harm of rosiglitazone, which may have very important
consequences in clinical practice. Recently, the FDA
restricted rosiglitazone to a narrowed population, while

the EMA has suspended it. The results of our study

provide further evidence to support the decision. As far as
pioglitazone is concerned, the cardiovascular safety issue
has not been fully researched. Our study suggests that
pioglitazone does not present as high a risk as
rosiglitazone; however, it should also be used with
caution.
Though randomized controlled trials (RCTs) are the
golden standard for efficiency assessment of drugs, they
are not necessarily so for drug safety because of their
inadequate power to detect either multiple or rare adverse
events. Furthermore, the conditions under which drugs
are approved for market use are often different from the
settings in actual use. Take rosiglitazone for example, the
population of rosiglitazones RCTs are often younger than
the patients who are treated with it. Thus observational
studies are increasing in uptake because they reflect the
real-life utility of drugs, which can be far more useful to
drug safety assessment activities than generally
acknowledged. In recent years both FDA and EMA
consider observational researches as more appropriate
vehicle of exploring drug safety issues. Our study
assessed the difference in cardiovascular outcomes
between rosiglitazone and pioglitazone through a
meta-analysis of retrospective cohort studies. One of the
strengths of this study was that we combined the results
of cohort studies that reflected the differential effects of
cardiovascular outcomes between rosiglitazone and
pioglitazone during real-life use. To guard against
heterogeneity, we had strict inclusion criteria, including
that all the researches should be designed to study the
cardiovascular outcomes of patients treated with
anti-diabetic drugs, especially rosiglitazone or
pioglitazone as first-line treatment. We excluded
case-control studies because these will bring more
heterogeneity to the analysis. Moreover, of all of the
corresponding authors of the included studies, three

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Chinese Medical Journal 2012;125(23):4301-4306

authors out of eight studies responded to our request, one

author provided further unpublished data, allowing a
more detailed analysis. By the addition of data from
Pantalones study, the risk of all outcomes increased for
rosiglitazone compared with pioglitazone; probably
because the number of patients included in this study was
relatively small, so the result did not have much effect in
the analysis. As the Tzoulakis study implies that the risk
of heart failure favours rosiglitazone, and the risk of MI
and all cause mortality did not show significant difference
between the two TZDs, it is noticeable that the design of
this study was to compare those two drugs as one
category with metformin or SU. Thus the sample size of
TZDs was relatively small, especially for pioglitazone
which combined mono therapy and multi therapy as one
group.
The weaknesses of this meta-analysis included the
limitations of observational studies which brought
together biases from all of the cohort studies. The
differences of research characteristic reminded us that
cohort studies were less homogeneous without control
mechanism, such as the treatment intervention, patients
characteristic, sample size, follow-up period and control
group are all varied from each other. So the results of this
meta analysis were less compelling as analysis of RCTs.
To guard against this, the inclusion criteria were
strengthened and further sensitive analysis and subgroup
analysis were performed. Since the follow-up time of the
included studies varied, a sensitivity analysis was
performed after excluding one study with only a 1-year
follow-up. Finally, as we did not have access to the
patient characteristic data, further analysis of the risk
factors which contributed to the adverse outcomes could
not be performed.

evidence for the absolute risk of any outcome for either

rosiglitazone or pioglitazone, as there was no reference
group treated with medications other than those two
drugs, our results indeed showed that, compared to
pioglitazone, rosiglitazone was associated with an
increased risk of all outcomes for the whole population.
We also analyzed the risk of non-insulin treated patients,
and the differences in rates of myocardial infarction and
heart failure were not significant, suggesting that patients
treated with insulin and these two TZDs are at higher risk
of cardiovascular diseases. Moreover, previous studies
that reported an insignificantly increased risk of MI with
rosiglitazone were conducted in younger populations
(mean age, 5465 years). There is a possibility that the
difference in cardiovascular outcomes for the two TZDs
changes with increasing age. The progression of diabetes
increases sudden cardiac death, along with aging. Thus,
the influence of the drug was comparable when the events
were more common in both groups.
In conclusion, our meta-analysis of eight retrospective
cohort studies found that, compared with pioglitazone,
rosiglitazone was associated with an increased risk of MI,
heart failure, and all-cause mortality in diabetic patients.
Further analyses would be recommended to compare the
absolute risks of rosiglitazone and pioglitazone, as well as
a comparison of these two drugs with other antidiabetic
drugs of a different category, such as metformin or
glimepiride.
REFERENCES
1.

2.

Since diabetes mellitus is complicated by cardiovascular

diseases, the adverse effects of hypoglycaemic agents
cannot be sensitively detected through comparisons with
placebos or healthy volunteers. Only in the most natural
circumstances can a rare adverse effect of one drug be
detected in a large population, without any interference
due to the specific purpose of any clinical trial. On the
other hand, the comparison of rosiglitazone to any other
treatment, including insulin, oral hypoglycaemic agents,
or even placebo, resulted in great heterogeneity among
the studies involved in the previous meta-analysis.
Therefore, we chose retrospective cohort studies of
diabetic patients who were treated with the two TZDs in
order to provide direct evidence in otherwise comparable
patients. The studies we included were all cohort studies
that compared these two drugs directly, since there has
been no such previous randomised controlled trial. These
retrospective cohort studies provide the best evidence to
evaluate the safety profiles of these two drugs.

3.

4.

5.

6.

7.

Our results are consistent with a previously suggested,

relatively adverse cardiovascular safety profile for
rosiglitazone. Although our study was not able to provide

8.

Nissen SE, Wolski K. Effect of rosiglitazone on the risk of

myocardial infarction and death from cardiovascular causes.
N Engl J Med 2007; 356: 2457-2471.
Home PD, Pocock SJ, Beck-Nielsen H, Curtis PS, Gomis R,
Hanefeld M, et al. Rosiglitazone evaluated for cardiovascular
outcomes in oral agent combination therapy for type 2
diabetes (RECORD): a multicentre, randomised, open-label
trial. Lancet 2009; 373: 2125-2135.
Lincoff AM, Wolski K, Nicholls SJ, Nissen SE. Pioglitazone
and risk of cardiovascular events in patients with type 2
diabetes mellitus: a meta-analysis of randomized trials.
JAMA 2007; 298: 1180-1188.
Dahabreh IJ, Economopoulos K. Meta-analysis of rare
events: an update and sensitivity analysis of cardiovascular
events in randomized trials of rosiglitazone. Clin Trials 2008;
5: 116-120.
Khanderia U, Pop-Busui R, Eagle KA. Thiazolidinediones in
type 2 diabetes: a cardiology perspective. Ann Pharmacother
2008; 42: 1466-1474.
Rohatgi A, McGuire DK. Effects of the thiazolidinedione
medications on micro- and macrovascular complications in
patients with diabetes--update 2008. Cardiovasc Drugs Ther
2008; 22: 233-240.
Singh S, Loke YK, Furberg CD. Long-term risk of
cardiovascular events with rosiglitazone: a meta-analysis.
JAMA 2007; 298: 1189-1195.
Gerstein HC, Yusuf S, Bosch J, Pogue J, Sheridan P, Dinccag

4306

9.
10.

11.

12.

13.

14.

15.

Chin Med J 2012;125(23):4301-4306

N, et al. Effect of rosiglitazone on the frequency of diabetes
in patients with impaired glucose tolerance or impaired
fasting glucose: a randomised controlled trial. Lancet 2006;
368: 1096-1105.
Silverman SL. From randomized controlled trials to
observational studies. Am J Med 2009;122: 114-120.
Suissa S, Garbe E. Primer: administrative health databases in
observational studies of drug effects--advantages and
disadvantages. Nat Clin Pract Rheumatol 2007; 3: 725-732.
Yang W, Zilov A, Soewondo P, Bech OM, Sekkal F, Home
PD. Observational studies: going beyond the boundaries of
randomized controlled trials. Diabetes Res Clin Pract 2010;
88 (Suppl 1): S3-S9.
Loebstein R, Dushinat M, Vesterman-Landes J, Silverman B,
Friedman N, Katzir I, et al. Database evaluation of the effects
of long-term rosiglitazone treatment on cardiovascular
outcomes in patients with type 2 diabetes. J Clin Pharmacol
2010. doi: 10.1177/0091270010368281.
Koro CE, Fu Q, Stender M. An assessment of the effect of
thiazolidinedione exposure on the risk of myocardial
infarction in type 2 diabetic patients. Pharmacoepidemiol
Drug Saf 2008; 17: 989-996.
Juurlink DN, Gomes T, Lipscombe LL, Austin PC, Hux JE,
Mamdani MM. Adverse cardiovascular events during
treatment with pioglitazone and rosiglitazone: Population
based cohort study. BMJ 2009; 339: b2942.
Graham DJ, Ouellet-Hellstrom R, Macurdy TE, Ali F,
Sholley C, Worrall C, et al. Risk of acute myocardial
infarction, stroke, heart failure, and death in elderly medicare
patients treated with rosiglitazone or pioglitazone. JAMA
2010; 304: 411-418.

16.

17.

18.

19.

20.

21.

Winkelmayer WC, Setoguchi S, Levin R, Solomon DH.

Comparison of cardiovascular outcomes in elderly patients
with diabetes who initiated rosiglitazone vs pioglitazone
therapy. Arch Intern Med 2008; 168: 2368-2375.
Gerrits CM, Bhattacharya M, Manthena S, Baran R, Perez A,
Kupfer S. A comparison of pioglitazone and rosiglitazone for
hospitalization for acute myocardial infarction in type 2
diabetes. Pharmacoepidemiol Drug Saf 2007; 16: 1065-1071
Tzoulaki I, Molokhia M, Curcin V, Little MP, Millett CJ, Ng
A, et al. Risk of cardiovascular disease and all cause
mortality among patients with type 2 diabetes prescribed oral
antidiabetes drugs: retrospective cohort study using UK
general practice research database. BMJ 2009; 339: b4731
Hsiao FY, Huang WF, Wen YW, Chen PF, Kuo KN, Tsai YW.
Thiazolidinediones and cardiovascular events in patients with
type 2 diabetes mellitus: a retrospective cohort study of over
473 000 patients using the National Health Insurance
database in Taiwan. Drug Saf 2009; 32: 675-690.
Pantalone KM, Kattan MW, Yu C, Wells BJ, Arrigain S, Jain
A, et al. The risk of developing coronary artery disease or
congestive heart failure, and overall mortality, in type 2
diabetic patients receiving rosiglitazone, pioglitazone,
metformin, or sulfonylureas: a retrospective analysis. Acta
Diabetol 2009; 46: 145-154.
Brownstein, JS, Murphy SN, Goldfine AB, Grant RW, Sordo
M, Gainer V, et al. Rapid identification of myocardial
infarction risk associated with diabetes medications using
electronic medical records. Diabetes Care 2010; 33: 526-531.

(Received April 24, 2012)

Edited by GUO Li-shao