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1.
Alfonso J. Cruz-JentoftFederico Cuesta Triana Mari Carmen Gómez-CabreraAlfonso López-Soto Ferran MasanésPilar Matía Martín José Antonio Serra RexachDomingo Ruiz Hidalgo Antoni SalvàJosé Viña Francesc Formiga 《Revista espa?ola de geriatría y gerontología》2011,46(2):100
Sarcopenia is a common and prominent geriatric syndrome, of major interest for daily clinical practice of professionals working with older people. The number of affected individuals and its relation with disability, frailty, many chronic diseases, lifestyle and adverse outcomes are extremely relevant for geriatric care. Moreover, biological changes that lead to the loss of muscle mass and strength are intrinsically related to the mechanisms of aging. It is not therefore surprising that research in this field is growing exponentially in recent years, and sarcopenia has been placed in recent years in the forefront of research in geriatric medicine and gerontology.The Spanish Society of Geriatrics and Gerontology has recently created an Observatory of Sarcopenia, which aims to promote educational and research activities in this field. The first activity of the Observatory has been to offer the Spanish speaking scientific community a review of the current status of sarcopenia, that may allow unifying concepts and fostering interest in this promising field of geriatrics. 相似文献
2.
Jiayu Yin Zhiyuan Qian Yuqi Chen Yi Li Xiang Zhou 《Journal of cellular and molecular medicine》2020,24(9):4900-4912
Sarcopenia is an age‐related disease characterized by disturbed homeostasis of skeletal muscle, leading to a decline in muscle mass and function. Loss of muscle mass and strength leads to falls and fracture, and is often accompanied by other geriatric diseases, including osteoporosis, frailty and cachexia, resulting in a general decrease in quality of life and an increase in mortality. Although the underlying mechanisms of sarcopenia are still not completely understood, there has been a marked improvement in the understanding of the pathophysiological changes leading to sarcopenia in recent years. The role of microRNAs (miRNAs), especially, has been clearer in skeletal muscle development and homeostasis. miRNAs form part of a gene regulatory network and have numerous activities in many biological processes. Intervention based on miRNAs may develop into an innovative treatment strategy to conquer sarcopenia. This review is divided into three sections: firstly, the latest understanding of the pathogenesis of sarcopenia is summarized; secondly, increasing evidence for the involvement of miRNAs in the regulation of muscle quantity or quality and muscle homeostasis is highlighted; and thirdly, the possibilities and limitations of miRNAs as a treatment for sarcopenia are explored. 相似文献
3.
Carmen María Osuna-Pozo José Antonio Serra-Rexach José Viña María del Carmen Gómez-Cabrera Antoni Salvá Domingo Ruiz Ferrán Masanes Alfonso Lopez-Soto Francesc Formiga Federico Cuesta Alfonso Cruz-Jentoft 《Revista espa?ola de geriatría y gerontología》2014
Background
There are few systematic studies on the prevalence of sarcopenia using the new diagnostic criteria in different geriatric care settings.Objective
To estimate the prevalence of sarcopenia, using the European Working Group on Sarcopenia in Older People (EWGSOP) criteria in older subjects living in nursing homes and in those who attend geriatric outpatient clinics.Material and methods
A single country multicentre study in two samples of older subjects: patients cared for in outpatient geriatric clinics, and individuals living in nursing homes. Data collected will include demographic variables, medical history, medication, geriatric syndromes, functional status (assessment of basic and instrumental activities of daily living), mobility, cognitive status, comorbidity, quality of life, nutritional status, and laboratory parameters. For the diagnosis of sarcopenia, 4 m walking speed, handgrip strength, and body composition measured by bioelectrical impedance analysis will be assessed.Results
Using the EWGSOP algorithm, the prevalence of sarcopenia in an elderly Spanish population will be estimated. In addition, concordance and correlation between the three parameters included in the definition (muscle mass, muscle strength, and physical performance) will be analysed, using the different existing cut-off points, and examining the diagnostic accuracy of each. Finally, demographic, anthropometric and functional data that define subjects with sarcopenia will be investigated.Conclusions
The ELLI study should improve knowledge on the prevalence and characteristics of sarcopenia in older people in our population. 相似文献4.
Sarcopenia, which is characterized by a progressive decrease of skeletal muscle mass and function with aging, is closely related
to several common diseases (such as cardiovascular and airway diseases) and functional impairment/disability. Strong genetic
determination has been reported for muscle mass and muscle strength, two most commonly recognized and studied risk phenotypes
for sarcopenia, with heritability ranging from 30 to 85% for muscle strength and 45–90% for muscle mass. Sarcopenia has been
the subject of increasing genetic research over the past decade. This review is designed to comprehensively summarize the
most important and representative molecular genetic studies designed to identify genetic factors associated with sarcopenia.
We have methodically reviewed whole-genome linkage studies in humans, quantitative trait loci mapping in animal models, candidate
gene association studies, newly reported genome-wide association studies, DNA microarrays and microRNA studies of sarcopenia
or related skeletal muscle phenotypes. The major results of each study are tabulated for easy comparison and reference. The
findings of representative studies are discussed with respect to their influence on our present understanding of the genetics
of sarcopenia. This is a comprehensive review of molecular genetic studies of gene identification for sarcopenia, and an overarching
theme for this review is that the currently accumulating results are tentative and occasionally inconsistent and should be
interpreted with caution pending further investigation. Consequently, this overview should enhance recognition of the need
to validate/replicate the genetic variants underlying sarcopenia in large human cohorts and animal. We believe that further
progress in understanding the genetic etiology of sarcopenia will provide valuable insights into important fundamental biological
mechanisms underlying muscle physiology that will ultimately lead to improved ability to recognize individuals at risk for
developing sarcopenia and our ability to treat this debilitating condition. 相似文献
5.
Guoyang Zhao 《Biological trace element research》2018,186(2):379-383
Sarcopenia has a high incidence among the elderly, with significant negative effects on the quality of life. The pathogenesis of sarcopenia is complex, and many factors are involved in its development and progression. Sarcopenia might be associated with iron accumulation given that (1) age-related iron accumulation was found in the skeletal muscle, (2) excess iron could cause skeletal muscle damage or atrophy, and (3) patients with sarcopenia showed higher levels of serum ferritin. Understanding the etiology and pathogenesis of sarcopenia would help to develop new treatment and preventive methods, thereby improving the quality of life of the elderly patients. 相似文献
6.
Sarcopenia, the age-related loss of muscle mass and strength, is a fundamental cause of frailty, functional decline and disability. In the year 2000, $18.5 billion in health care costs were directly attributable to sarcopenia. This economic burden will increase dramatically as the elderly population grows over the next decade. The primary causes of sarcopenia include a sedentary lifestyle and malnutrition. While resistance training appears to be a promising intervention, older individuals exhibit a blunted hypertrophic response to exercise stimuli. It has been posited that this decrement in regenerative capacity may be due to the loss of postprandial anabolism as well as an increase in reactive oxygen species. As such, a combination of resistance training and nutritional interventions may be a promising candidate in combating sarcopenia. Nevertheless, the mechanisms by which the manipulation of dietary variables may improve the sarcopenic condition are not well understood. To address this gap in extant knowledge, this review will examine the effects of protein, amino acid and/or antioxidant intake on sarcopenia both at rest and following resistance training exercise. 相似文献
7.
Sarcopenia is a geriatric syndrome in which there is a decrease of muscle mass and strength with aging. In age-related loss
of muscle strength, there are numerous observations supporting the assertion that neural factors mediate muscle strength.
A possible contributing cause may be that aging changes systemic extracellular heat shock protein (eHsp)72 activity. The present
study was designed to assess the plasma levels of eHsp72 in elderly people and to investigate its potential interaction with
components of sarcopenia. A total of 665 men and women participated in an official medical health examination and an integrated
health examination, including psychological and physical fitness tests. Blood samples were assayed for levels of plasma Hsp72,
serum C-reactive protein, interleukin 6, tumor necrosis factor α, and regular biomedical parameters. We found that higher
Hsp72 in plasma is associated with lower muscle mass, weaker grip strength, and slower walking speed, and may be a potential
biomarker of sarcopenia in elderly people. This finding was supported by other results in the present study: (1) older age
and shrinking body and lower hemoglobin levels, all of which characterize sarcopenia, were related to higher eHsp72 tertiles
and (2) the ORs of the highest tertile of eHsp72 for the lowest tertiles of muscle mass, grip strength, and walking speed
were 2.7, 2.6, and 1.8, respectively. These ORs were independent of age, sex, and the incidence of related diseases. Our results
would reveal that eHsp72 in plasma is linked to sarcopenia factors and is a potential biomarker or predictor of sarcopenia. 相似文献
8.
Sarcopenia, defined as age‐associated decline of muscle mass and function, is a risk factor for mortality and disability, and comorbid with several chronic diseases such as type II diabetes and cardiovascular diseases. Clinical trials showed that nutritional supplements had positive effects on muscle mass, but not on muscle function and strength, demonstrating our limited understanding of the molecular events involved in the ageing muscle. Protein homeostasis, the equilibrium between protein synthesis and degradation, is proposed as the major mechanism underlying the development of sarcopenia. As the key central regulator of protein homeostasis, the mammalian target of rapamycin (mTOR) is proposed to be essential for muscle hypertrophy. Paradoxically, sustained activation of mTOR complex 1 (mTORC1) is associated with a loss of sensitivity to extracellular signaling in the elderly. It is not understood why sustained mTORC1 activity, which should induce muscle hypertrophy, instead results in muscle atrophy. Here, recent findings on the implications of disrupting protein homeostasis on muscle physiology and sarcopenia development in the context of mTOR/protein kinase B (AKT) signaling are reviewed. Understanding the role of these molecular mechanisms during the ageing process will contribute towards the development of targeted therapies that will improve protein metabolism and reduce sarcopenia. 相似文献
9.
Wonjong Yu Min-kyu Yang Dong Jun Sung Tae Jun Park Myungchul Kim Eustache Ntigura Sung Hea Kim Bokyung Kim Sang Woong Park Young Min Bae 《Biochemistry and Biophysics Reports》2022
As the geriatric population and life expectancy increase, the interest in preventing geriatric diseases, such as sarcopenia, is increasing. However, the causes of sarcopenia are unclear, and current diagnostic methods for sarcopenia are unreliable. We hypothesized that the changes in the expression of certain miRNAs may be associated with the pathophysiology of sarcopenia. Herein, we analyzed the miRNA expression profiles in the blood of young (3-months-old) healthy rats, old sarcopenic (17-months-old) rats, and age-matched (17-months-old) control rats. The changes in miRNA expression levels were analyzed using Bowtie 2 software. A total of 523 miRNAs were detected in the rat serum. Using scatter plots and clustering heatmap data, we found 130 miRNAs that were differentially expressed in sarcopenic rats (>2-fold change) compared to the expression in young healthy and age-matched control rats. With a threshold of >5-fold change, we identified 14 upregulated miRNAs, including rno-miR-133b-3p, rno-miR-133a-3p, rno-miR-133c, rno-miR-208a-3p, and rno-miR434-5p among others in the serum of sarcopenic rats. A protein network map based on these 14 miRNAs identified the genes involved in skeletal muscle differentiation, among which Notch1, Egr2, and Myocd represented major nodes. The data obtained in this study are potentially useful for the early diagnosis of sarcopenia and for the identification of novel therapeutic targets for the treatment and/or prevention of sarcopenia. 相似文献
10.
Esmee M. Reijnierse Marijke C. Trappenburg Morena J. Leter Gerard Jan Blauw Marian A. E. de van der Schueren Carel G. M. Meskers Andrea B. Maier 《PloS one》2015,10(8)
Objectives
Diagnostic criteria for sarcopenia include measures of muscle mass, muscle strength and physical performance. Consensus on the definition of sarcopenia has not been reached yet. To improve insight into the most clinically valid definition of sarcopenia, this study aimed to compare the association between parameters of malnutrition, as a risk factor in sarcopenia, and diagnostic measures of sarcopenia in geriatric outpatients.Material and Methods
This study is based on data from a cross-sectional study conducted in a geriatric outpatient clinic including 185 geriatric outpatients (mean age 82 years). Parameters of malnutrition included risk of malnutrition (assessed by the Short Nutritional Assessment Questionnaire), loss of appetite, unintentional weight loss and underweight (body mass index <22 kg/m2). Diagnostic measures of sarcopenia included relative muscle mass (lean mass and appendicular lean mass [ALM] as percentages), absolute muscle mass (total lean mass and ALM/height2), handgrip strength and walking speed. All diagnostic measures of sarcopenia were standardized. Associations between parameters of malnutrition (independent variables) and diagnostic measures of sarcopenia (dependent variables) were analysed using multivariate linear regression models adjusted for age, body mass, fat mass and height in separate models.Results
None of the parameters of malnutrition was consistently associated with diagnostic measures of sarcopenia. The strongest associations were found for both relative and absolute muscle mass; less stronger associations were found for muscle strength and physical performance. Underweight (p = <0.001) and unintentional weight loss (p = 0.031) were most strongly associated with higher lean mass percentage after adjusting for age. Loss of appetite (p = 0.003) and underweight (p = 0.021) were most strongly associated with lower total lean mass after adjusting for age and fat mass.Conclusion
Parameters of malnutrition relate differently to diagnostic measures of sarcopenia in geriatric outpatients. The association between parameters of malnutrition and diagnostic measures of sarcopenia was strongest for both relative and absolute muscle mass, while less strong associations were found with muscle strength and physical performance. 相似文献11.
Age-related hearing impairment (ARHI) is becoming a more significant issue as geriatric population increases. Sarcopenia in older people is known to have a diverse health problem in various circumstances in recent studies. We assessed whether the decrease in muscle mass is related to ARHI. We used the 2010 data of the Korea National Health and Nutrition Examination Survey (KNHANES) to examine the associations between sarcopenia and ARHI. A total number of participants was 1,622 including 746 males and 876 females aged 60 years or older. Muscle mass was assessed as an appendicular skeletal muscle mass, and hearing loss was defined as the pure-tone averages (PTA) of test frequencies 0.5, 1, 2, 4 kHz at a threshold of 40 dB or higher in worse hearing side of the ear. Among 1,622 participants, 298 men and 256 women had hearing loss. Appendicular muscle mass (ASM), expressed as kg, was categorized in tertiles. In female population, after adjusting for age, smoking, drinking, amount of exercise, total body fat, education level, income level, and tinnitus, the odds ratio (OR) for hearing loss was 1.57 (95% confidence interval (CI) = 0.92–2.68) in the middle tertile and 1.79 (1.03–3.08) in the lowest tertile, compared with the highest tertile. P for trend in this model was 0.036. Controlling further for hypertension, diabetes mellitus, chronic kidney disease, and three types of noise exposure did not change the association. Larger muscle mass is associated with lower prevalence of hearing loss in elderly Korean females. 相似文献
12.
Molecular mechanisms involved in muscle wasting in cancer and ageing: cachexia versus sarcopenia 总被引:5,自引:0,他引:5
Argilés JM Busquets S Felipe A López-Soriano FJ 《The international journal of biochemistry & cell biology》2005,37(5):1084-1104
The aim of the present review is to summarize and evaluate the different mechanisms and catabolic mediators involved in cancer cachexia and ageing sarcopenia since they may represent targets for future promising clinical investigations. Cancer cachexia is a syndrome characterized by a marked weight loss, anorexia, asthenia and anemia. In fact, many patients who die with advanced cancer suffer from cachexia. The degree of cachexia is inversely correlated with the survival time of the patient and it always implies a poor prognosis. Unfortunately, at the clinical level, cachexia is not treated until the patient suffers from a considerable weight loss and wasting. At this point, the cachectic syndrome is almost irreversible. The cachectic state is often associated with the presence and growth of the tumour and leads to a malnutrition status due to the induction of anorexia. In recent years, age-related diseases and disabilities have become of major health interest and importance. This holds particularly for muscle wasting, also known as sarcopenia, that decreases the quality of life of the geriatric population, increasing morbidity and decreasing life expectancy. The cachectic factors (associated with both depletion of fat stores and muscular tissue) can be divided into two categories: of tumour origin and humoural factors. In conclusion, more research should be devoted to the understanding of muscle wasting mediators, both in cancer and ageing, in particular the identification of common mediators may prove as a good therapeutic strategies for both prevention and treatment of wasting both in disease and during healthy ageing. 相似文献
13.
Shinya Ishii Tomoki Tanaka Masahiro Akishita Yasuyoshi Ouchi Tetsuo Tuji Katsuya Iijima for the Kashiwa study investigators 《PloS one》2014,9(11)
Recent epidemiological evidence suggests that effects of cardiovascular risk factors may vary depending on sex and age. In this study, we assessed the associations of metabolic syndrome (MetS) with sarcopenia and its components in older adults, and examined whether the associations vary by sex and age. We also tested if any one of the MetS components could explain the associations. We conducted a cross-sectional analysis of the baseline data from the cohort study conducted in Kashiwa city, Chiba, Japan in 2012 which included 1971 functionally-independent, community-dwelling Japanese adults aged 65 years or older (977 men, 994 women). Sarcopenia was defined based on appendicular skeletal muscle mass, grip strength and usual gait speed. MetS was defined based on the National Cholesterol Education Program’s Adult Treatment Panel-III criteria. The prevalence of sarcopenia was 14.2% in men and 22.1% in women, while the prevalence of MetS was 43.6% in men and 28.9% in women. After adjustment for potential confounders, MetS was positively associated with sarcopenia in men aged 65 to 74 years (odds ratio 5.5; 95% confidence interval 1.9–15.9) but not in older men or women. Among the sarcopenia components, MetS was associated with lower muscle mass and grip strength, particularly in men aged 65 to 74 years. The associations of MetS with sarcopenia and its components were mainly driven by abdominal obesity regardless of sex or age. In conclusion, MetS is positively associated with sarcopenia in older men. The association is modified by sex and age, but abdominal obesity is the main contributor to the association across sex and age. 相似文献
14.
An Yun Guo Kwok Sui Leung Parco Ming Fai Siu Jiang Hui Qin Simon Kwoon Ho Chow Ling Qin Chi Yu Li Wing Hoi Cheung 《Experimental Animals》2015,64(4):425-433
Sarcopenia is an age-related systemic syndrome with progressive deterioration in skeletal
muscle functions and loss in mass. Although the senescence-accelerated mouse P8 (SAMP8)
was reported valid for muscular ageing research, there was no report on the details such
as sarcopenia onset time. Therefore, this study was to investigate the change of muscle
mass, structure and functions during the development of sarcopenia. Besides the average
life span, muscle mass, structural and functional measurements were also studied. Male
SAMP8 animals were examined at month 6, 7, 8, 9, and 10, in which the right gastrocnemius
was isolated and tested for ex vivo contractile properties and fatigability while the
contralateral one was harvested for muscle fiber cross-sectional area (FCSA) and typing
assessments. Results showed that the peak of muscle mass appeared at month 7 and the onset
of contractility decline was observed from month 8. Compared with month 8, most of the
functional parameters at month 10 decreased significantly. Structurally, muscle fiber type
IIA made up the largest proportion of the gastrocnemius, and the fiber size was found to
peak at month 8. Based on the altered muscle mass, structural and functional outcomes, it
was concluded that the onset of sarcopenia in SAMP8 animals was at month 8. SAMP8 animals
at month 8 should be at pre-sarcopenia stage while month 10 at sarcopenia stage. It is
confirmed that SAMP8 mouse can be used in sarcopenia research with established time line
in this study. 相似文献
15.
ChunWei Li Kang Yu Ng ShyhChang GuoXun Li SongLin Yu HuiJun Liu Bo Yang ZiYao Li YongJie Zhao LongYu Xu Jing Xu LingJuan Jiang RongJi Liu XinYuan Zhang ShaoFei Li XiaoWei Zhang HaiYan Xie Kang Li YiXiang Zhan Min Cui HangBo Tao Yao Li GaoShan Liu KeMin Ni DongJing Li 《Cell proliferation》2021,54(4)
ObjectivesOur aim was to investigate the prevalence and predictive variables of sarcopenia.MethodsWe recruited participants from the Peking Union Medical College Hospital Multicenter Prospective Longitudinal Sarcopenia Study (PPLSS). Muscle mass was quantified using bioimpedance, and muscle function was quantified using grip strength and gait speed. Logistic regression revealed the relationships between sarcopenia and nutritional, lifestyle, disease, psychosocial and physical variables.ResultsThe prevalence of sarcopenia and sarcopenic obesity was 9.2%‐16.2% and 0.26%‐9.1%, respectively. Old age, single status, undernourishment, higher income, smoking, low physical activity, poor appetite and low protein diets were significantly associated with sarcopenia. Multiple logistic regression analysis showed that age was a risk factor for all stages of sarcopenia, and participants above 80 years were greater than fivefold more susceptible to sarcopenia, while lower physical activity was an independent risk factor. The optimal cut‐off value for age was 71 years, which departs from the commonly accepted cut‐off of 60 years. Female participants were greater than twofold less susceptible to sarcopenia than male participants. The sterol derivative 25‐hydroxyvitamin D was associated with fourfold lower odds of sarcopenia in male participants. Several protein intake variables were also correlated with sarcopenia. Based on these parameters, we defined a highly predictive index for sarcopenia.ConclusionsOur findings support a predictive index of sarcopenia, which agglomerates the complex influences that sterol metabolism and nutrition exert on male vs female participants. 相似文献
16.
Sang Ouk Chin Sang Youl Rhee Suk Chon You-Cheol Hwang In-Kyung Jeong Seungjoon Oh Kyu Jeung Ahn Ho Yeon Chung Jeong-taek Woo Sung-Woon Kim Jin-Woo Kim Young Seol Kim Hong-Yup Ahn 《PloS one》2013,8(3)
Background
The association between sarcopenia and cardiovascular disease (CVD) in elderly people has not been adequately assessed. The aim of this study was to investigate whether CVD is more prevalent in subjects with sarcopenia independent of other well-established cardiovascular risk factors in older Korean adults.Method
This study utilized the representative Korean population data from the Korea National Health and Nutrition Examination Survey (KNHANES) which was conducted in 2009. Subjects older than 65 years of age with appendicular skeletal muscle mass (ASM) determined by dual energy X-ray absorptiometry were selected. The prevalence of sarcopenia in the older Korean adults was investigated, and it was determined whether sarcopenia is associated with CVD independent of other well-known risk factors.Results
1,578 subjects aged 65 years and older with the data for ASM were selected, and the overall prevalence of sarcopenia was 30.3% in men and 29.3% in women. Most of the risk factors for CVD such as age, waist circumference, body mass index, fasting plasma glucose and total cholesterol showed significant negative correlations with the ratio between appendicular skeletal muscle mass and body weight. Multiple logistic regression analysis demonstrated that sarcopenia was associated with CVD independent of other well-documented risk factors, renal function and medications (OR, 1.768; 95% CI, 1.075–2.909, P = 0.025).Conclusions
Sarcopenia was associated with the presence of CVD independent of other cardiovascular risk factors after adjusting renal function and medications. 相似文献17.
18.
Robert B. Edgerton 《Culture, medicine and psychiatry》1984,8(1):25-48
Although mental retardation is largely a sociocultural phenomenon, anthropological interest in this field has been slow to develop. In recent years, anthropological concepts and methods have been used in study of the community adaptation of mentally retarded persons and societal reactions to them. As an illustration, research developments at the Mental Retardation Research Center, UCLA, are discussed. The need for expanded, collaborative research by social and biomedical scientists is examined. The research puzzles include the links between poverty, ethnicity, schools, families and mental retardation, as well as the nature of intelligence and adaptation. 相似文献
19.
Past the age of 50 years, aging individuals lose muscle mass at an approximate rate of 1-2% per year. This age-related muscle atrophy, termed sarcopenia, can have significant effects on individual health and quality of life and can also impact the socioeconomic status. Sarcopenia is due to both a decrease in the number of fibers and the atrophy of the remaining fibers. The mechanisms causing loss of fibers have not been clearly defined, but may likely involve apoptosis. Elevated levels of circulating tumor necrosis factor alpha (TNF-alpha) and adaptations in TNF-alpha signaling in aged skeletal muscle may be contributing factors for the activation of apoptosis. These adaptations may be fiber-type specific, which could explain the selective loss of type II fibers, vs. type I fibers, in the aging process. Caloric restriction, a proven antiaging intervention, is known to attenuate the loss of muscle mass and function with age. Furthermore, caloric restriction has been shown to attenuate the age-associated adaptations in TNF-alpha signaling in skeletal muscle, which may be a possible mechanism by which CR prevents apoptosis and the loss of muscle fibers with age. The potential role of TNF-alpha in the progression of sarcopenia will be discussed, as well as the effects of life-long caloric restriction on TNF-alpha signaling. 相似文献
20.
Wei Hong Qun Cheng Xiaoying Zhu Hanmin Zhu Huilin Li Xuemei Zhang Songbai Zheng Yanping Du Wenjing Tang Sihong Xue Zhibin Ye 《PloS one》2015,10(9)