Association of persistent musculoskeletal pain with dementia risk score in adults aged 45 years or older: The China health and retirement longitudinal study.

BACKGROUND: Recent studies have confirmed an association between pain and dementia. Whether musculoskeletal pain in the spine, upper limbs, and lower limbs is associated with dementia risk remains unclear. The longitudinal effect of musculoskeletal pain on dementia risk also remains unclear. AIMS: This work aimed to investigate the association between musculoskeletal pain and dementia risk score. METHODS: We conducted cross-sectional and longitudinal analyses using data from the China Health and Retirement Longitudinal Study. Participants aged 45 years or older were recruited in 2011. A total of 10,759 participants with complete pain information at baseline were eligible for the cross-sectional analysis, and 5,855 were eligible for the longitudinal analyses. We utilized the Rotterdam Study Basic Dementia Risk Model (BDRM) to assess dementia risk. Generalized estimating equations were used to investigate the associations. RESULTS: Compared with participants without persistent musculoskeletal pain, those with persistent musculoskeletal pain (standardized, ß = 0.83; 95 % CI: 0.06, 1.61, p = 0.036), multisite pain (sites≧5; ß = 1.52; 95 % CI: 0.13, 2.91, p = 0.032), neck pain (ß = 2.33; 95 % CI: 0.41, 4.25, p = 0.018), back pain (ß = 2.12; 95 % CI: 0.43, 3.82, p = 0.014), waist pain (ß = 1.09; 95 % CI: 0.07, 2.11, p = 0.037), shoulder pain (ß = 1.74; 95 % CI: 0.46, 3.02, p = 0.008), wrist pain (ß = 2.72; 95 % CI: 0.42, 5.02, p = 0.021), and knee pain (ß = 1.91; 95 % CI: 0.70, 3.13, p = 0.002) had a higher BDRM score during 4 years of follow-up. CONCLUSIONS: Promoting the management of musculoskeletal pain may be beneficial in reducing the dementia risk score.

Physical therapy for acute and sub-acute low back pain: A systematic review and expert consensus.

OBJECTIVE: To review the effectiveness of different physical therapies for acute and sub-acute low back pain supported by evidence, and create clinical recommendations and expert consensus for physiotherapists on clinical prescriptions. DATA SOURCES: A systematic search was conducted in PubMed and the Cochrane Library for studies published within the previous 15 years. REVIEW METHODS: Systematic review and meta-analysis, randomized controlled trials assessing patients with acute and sub-acute low back pain were included. Two reviewers independently screened relevant studies using the same inclusion criteria. The Physiotherapy Evidence Database and the Assessment of Multiple Systematic Reviews tool were used to grade the quality assessment of randomized controlled trials and systematic reviews, respectively. The final recommendation grades were based on the consensus discussion results of the Delphi of 22 international experts. RESULTS: Twenty-one systematic reviews and 21 randomized controlled trials were included. Spinal manipulative therapy and low-level laser therapy are recommended for acute low back pain. Core stability exercise/motor control, spinal manipulative therapy, and massage can be used to treat sub-acute low back pain. CONCLUSIONS: The consensus statements provided medical staff with appliable recommendations of physical therapy for acute and sub-acute low back pain. This consensus statement will require regular updates after 5-10 years.

The roles of PARK gene family in myopathy.

The causative gene family of Parkinson's disease, PARK, plays important roles in the regulation of skeletal myopathy and is also involved in multiple biological processes, such as the modification of motor neurons, the transmission of nerve signals at the nerve-muscle junction, the regulation of skeletal muscle energy metabolism and mitochondrial quality, and the expression of myogenesis factors. PARK gene family regulates skeletal muscle mass, functions through a multi-level regulatory system, and plays a key role in the occurrence and development of skeletal myopathy. In this review, we summarize the structural characteristics, functions, and research of the PARK gene family in skeletal myopathy, providing a theoretical foundation and future research direction for in-depth study of the molecular mechanism for skeletal myopathy and giving references to further study on the role of PARK family in the development, the pathology, clinical diagnosis, and treatment of skeletal myopathy.

Comparative Transcriptome Profiling Reveals Changes of microRNAs Response to Exercise in Rats with Neuropathic Pain.

There is accumulating evidence showing that exercise therapy may play an active role in peripheral neuropathic pain (NP), but its mechanism is still unclear. Studies have found that microRNAs (miRNAs) may play a role in NP by regulating pain-related target genes. Therefore, we aimed to explore the changes of miRNA and mRNA of dorsal root ganglion (DRG) after NP in response to exercise with transcriptome technology. The chronic constriction injury (CCI) model was established, and rats were randomly allocated into three groups, namely, the sham-operated, CCI, and CCI-exercised groups. L4-L6 DRG tissue was taken for RNA-sequencing, and the differentially expressed genes (DEGs) were determined through bioinformatics analysis. Real-time PCR was used to confirm the accuracy. A total of 4 overlapping differentially expressed miRNAs and 186 overlapping differentially expressed mRNAs were identified in the two comparisons of the sham-operated group versus the CCI group and the CCI group versus the CCI-exercised group. Among these DEGs, miR-145-5p, miR-341, miR-300-5p, miR-653-5p, Atf3, Cacna2d1, Gal, and Ctss related to NP were validated by real-time PCR. DEGs between the CCI and CCI-exercised groups were enriched in HIF-1 signaling pathway, Rap1 signaling pathway, and neurotrophin signaling pathway. This study provides an understanding of the adaptive mechanisms after exercise of NP, and these DEGs in DRG might play a role in NP by stimulating the enriched pathways.

Network and pathway-based analysis of microRNA role in neuropathic pain in rat models.

The molecular mechanisms underlying neuropathic pain (NP) remain poorly understood. Emerging evidence has suggested the role of microRNAs (miRNAs) in the initiation and development of NP, but the specific effects of miRNAs in NP are largely unknown. Here, we use network- and pathway-based methods to investigate NP-induced miRNA changes and their biological functions by conducting a systematic search through multiple electronic databases. Thirty-seven articles meet the inclusion criteria. Venn analysis and target gene forecasting are performed and the results indicate that 167 overlapping target genes are co-regulated by five down-regulated miRNAs (rno-miR-183, rno-miR-96, rno-miR-30b, rno-miR-150 and rno-miR-206). Protein-protein interaction network analysis shows that 77 genes exhibit interactions, with cyclic adenosine monophosphate (cAMP)-dependent protein kinase catalytic subunit beta (degree = 11) and cAMP-response element binding protein 1 (degree = 10) having the highest connectivity degree. Gene ontology analysis shows that these target genes are enriched in neuron part, neuron projection, somatodendritic compartment and nervous system development. Moreover, analysis of Kyoto Encyclopedia of Genes and Genomes reveals that three pathways, namely, axon guidance, circadian entrainment and insulin secretion, are significantly enriched. In addition, rno-miR-183, rno-miR-96, rno-miR-30b, rno-miR-150 and rno-miR-206 are consistently down-regulated in the NP models, thus constituting the potential biomarkers of this disease. Characterizing these miRNAs and their target genes paves way for their future use in clinical practice.

A Bioinformatic Analysis of MicroRNAs' Role in Human Intervertebral Disc Degeneration.

Objectives The aim of our study was to ascertain the underlying role of microRNAs (miRNAs) in human intervertebral disc degeneration (IDD). Design Bioinformatic analysis from multiple databases. Methods Studies of the association of miRNAs and IDD were identified in multiple electronic databases. All potential studies were assessed by the same inclusion and exclusion criteria. We recorded whether miRNA expression was commonly increased or suppressed in the intervertebral disc tissues and cells of IDD subjects. We used String to identify biological process and cellular component pathways of differentially expressed genes. Results We included fifty-seven articles from 1,277 records in this study. This report identified 40 different dysregulated miRNAs in 53 studies, including studies examining cell apoptosis (26 studies, 49.06%), cell proliferation (15 studies, 28.3%), extracellular matrix (ECM) degradation (10 studies, 18.86%), and inflammation (five studies, 9.43%) in IDD patients. Three upregulated miRNAs (miR-19b, miR-32, miR-130b) and three downregulated miRNAs (miR-31, miR-124a, miR-127-5p) were considered common miRNAs in IDD tissues. The top three biological process pathways for upregulated miRNAs were positive regulation of biological process, nervous system development, and negative regulation of biological process, and the top three biological process pathways for downregulated miRNAs were negative regulation of gene expression, intracellular signal transduction, and negative regulation of biological process. Conclusions This study revealed that miRNAs could be novel targets for preventing IDD and treating patients with IDD by regulating their target genes. These results provide valuable information for medical professionals, IDD patients, and health care policy makers.

Effects of whole-body vibration exercise for non-specific chronic low back pain: an assessor-blind, randomized controlled trial.

OBJECTIVE: To confirm the benefits of whole-body vibration exercise for pain intensity and functional disability in patients with non-specific chronic low back pain. DESIGN: Single-blind randomized controlled trial. SETTING: Outpatient. SUBJECTS: Eighty-nine patients with non-specific chronic low back pain met the inclusion criteria, they were randomly allocated to either the intervention group (n = 45) or the control group (n = 44). INTERVENTION: The intervention group received whole-body vibration exercises three times a week for 12 weeks. The control group received general exercise protocol three times a week for 12 weeks. MAIN OUTCOMES: The primary outcome measures were pain intensity and functional disability measured by the visual analog scale scores and Oswestry Disability Index. The secondary outcome measures included lumbar joint position sense, quality of life (Short Form Health Survey 36) and overall treatment effect (Global Perceived Effect). RESULTS: A total of 84 subjects completed the 12-week study program. After 12 weeks, compared with the control group, the mean visual analog scale and Oswestry Disability Index scores decreased by additional 1 point (95% confidence interval (CI) = -1.22 to -0.78; P < 0.001), 3.81 point (95% CI, -4.98, -2.63; P < 0.001) based on adjusted analysis in the intervention group. And the intervention group provided additional beneficial effects for in terms of lumbar joint position sense (P < 0.05), quality of life (P < 0.05), and Global Perceived Effect (P = 0.012). CONCLUSION: The study demonstrated that whole-body vibration exercise could provide more benefits than general exercise for relieving pain and improving functional disability in patients with non-specific chronic low back pain.

Bibliometric Study of the Comorbidity of Pain and Depression Research.

Background: Comorbid pain and depression occur with high prevalence in clinical observations, and published academic journals about them have been increasing in number over time. However, few studies used the bibliometric method to analyze the general aspects of scientific researches on the comorbidity of pain and depression. The aim of this study is to systematically provide global scientific research in the comorbidity of pain and depression from 1980 to 2018. Methods: The published papers were searched between 1980 and 2018 in Web of Science. Publications related to comorbid pain and depression research were included. The language was restricted to English, and no species limitations were specified. Results: A total of 2,519 papers met the inclusion criteria in our study. The results revealed that the publications had a significant growth over time in the comorbidity of pain and depression research (P < 0.001) by linear regression analyses. The United States had the largest number of publications and citations and the highest value of H-index. According to subject categories of Web of Science, research areas of the 2,519 papers mainly focused on clinical neurology (28.78%), neurosciences (22.9%), and psychiatry (22.23%). In accordance with types of pain, headache (19.09%) was the most popular topic in the included papers on comorbid pain and depression research. Conclusions: The findings provide useful information for pain and depression researchers to detect new areas related to collaborators, cooperative institutions, popular topics, and research frontiers.

[Signaling pathways controlling skeletal muscle mass].

The skeletal muscle mass accounts for more than 40% of the body weight of healthy adults. The skeletal muscle not only plays an important role in physical activities but also affects the function of other organs as a secretory organ secreting multiple muscle factors. Therefore, it is important to maintain the normal quantity and function of skeletal muscle. Skeletal muscle mass is the basis of skeletal muscle function and is often affected by many factors such as exercise and disease. Resistance exercise training induces increased protein synthesis in skeletal muscle cells, while limb disuse, chronic obstructive pulmonary disease, heart failure, chronic kidney disease, cachexia, Duchenne muscular dystrophy and many other pathological conditions lead to decreased protein synthesis or enhanced protein degradation of skeletal muscle cells. The process of skeletal muscle hypertrophy involves changes in multiple signaling pathways, such as IGF-1/PI3K/Akt, myostatin and G protein. On the other hand, activations of the ubiquitin-proteasome system, IGF-1/Akt/FoxO, autophagy-lysosomal pathway, NF-κB, and the glucocorticoid-mediated signaling pathways play important roles in regulating muscle atrophy. These signaling pathways regulate skeletal muscle mass and are modulated by some different conditions. This review briefly summarizes the signaling pathways of skeletal muscle mass control.

[Roles and mechanism of microRNAs in the regulation of skeletal muscle insulin resistance].

Insulin resistance is a common pathophysiological mechanism of obesity and type 2 diabetes mellitus. Skeletal muscle is one of the major target organs of insulin-mediated glucose uptake, metabolism and utilization, and it is the earliest and most important site of insulin resistance. Studies have shown that the impairments of glucose uptake, insulin signaling pathway and mitochondrial biosynthesis are closely related to skeletal muscle insulin resistance. When insulin resistance develops in skeletal muscle, multiple microRNAs (miRNAs) are up-regulated (miR-106b, miR-23a, miR-761, miR-135a, Let-7 and miR-29a) or down-regulated (miR-133a, miR-149 and miR-1). They participate in the regulation of skeletal muscle glucose uptake, insulin signaling pathway and mitochondrial biogenesis, and thus play important roles in the occurrence and development of skeletal muscle insulin resistance. Therefore, these miRNAs may serve as potential targets for the treatment of skeletal muscle insulin resistance or diabetes.

Co-existence of physical activity and sedentary behavior among children and adolescents in Shanghai, China: do gender and age matter?

BACKGROUND: There is limited evidence for the prevalence of the co-existence of physical activity (PA) and sedentary behavior (SED), and its correlates among children and adolescents. This study has two aims: 1) to investigate the prevalence of PA and SED, and their co-existence, and 2) to examine the associations between PA or SED, or both with gender and age among children and adolescents in Shanghai, China. METHODS: Using a cross-sectional study design (conducted from September to December 2014), 50,090 children and adolescents (10-18 years old, 50.4% boys) were included in this study. A self-reporting questionnaire was used to measure participants' sociodemographic characteristics, PA, and SED. Descriptive statistics were used to describe sample characteristics, the prevalence of PA and SED, and their co-existence. A Generalized Linear Model was conducted to explore the associations between the prevalence of PA and SED, and their co-existence with gender and age separately. RESULTS: Of the children and adolescents studied, only 18.4% met the guidelines for PA, 25.5% met the guidelines for SED, and 5.7% met the guidelines for both. Boys were more physically active (aOR = 1.43, 95% CI: 1.36-1.50), and girls were less sedentary (aOR = 1.29, 95%CI: 1.24-1.34). The prevalence of PA, SED, or both all declined as age increased (p < 0.001). Stratified analysis by gender revealed greater declining trends of meeting the PA or SED guidelines, or both in girls (all p < 0.005). CONCLUSION: Very few children and adolescents showed active lifestyles, and this was significantly related to age. Effective interventions aiming to promote PA and concurrently to limited SED among children and adolescents should be implemented as early as possible.

[Mechanism of the occurrence of sarcopenia in the elderly].

The decline in skeletal muscle mass and function with age is referred as sarcopenia. It is characterized by the muscle fiber's quality, strength, muscle endurance and metabolic ability decreasing as well as the fat and connective tissue growing. Previous studies have shown that sarcopenia in itself features decreased number and cross-sectional area of muscle fibers and the net degradation of protein, which results from the joint effects of multiple factors such as the exacerbation of inflammation, oxidative stress injury, mitochondrial dysfunction, abnormal autophagy and dysregulation of muscle quality regulatory factors. In this review, we systematically displayed the molecular mechanism of sarcopenia, which will be helpful to deepen our understanding of sarcopenia and provide potential targets for the prevention and treatment of sarcopenia.

[Macrophages depletion impairs skeletal muscle regeneration by regulating inflammation and oxidative stress levels].

The objective of this study was to explore the roles of macrophages in the regeneration of injured skeletal muscle and the mechanisms involved. Mice were randomly divided into the following groups: muscle contusion (S), muscle contusion control (SCon), macrophages depleted (T) and macrophages depleted control (TCon) groups. Muscle contusion model was created by high-energy blunt injury. Macrophages depletion model was constructed by injection of clodronate-liposomes. Their gastrocnemius muscles were harvested at the time points of 1, 3, 7 and 14 d post-injury. The changes in skeletal muscle morphology were assessed by hematoxylin-eosin (HE) staining and Masson's trichrome staining. The mRNA and protein levels of inflammatory cytokines, chemokines and oxidative stress factors were analyzed by real-time polymerase chain reaction (RCR) and Western blotting, respectively. HE staining results showed that a small amount of regenerating myofibers were observed in the S group (14 d post-injury), whereas a large number of regenerating muscle fibers were observed in the T group. Quantitative analyses showed that the sizes of regenerating myofibers were significantly smaller in the T group as compared with the S group at 14 d post-injury (P < 0.05). At the same time, Masson staining results showed that macrophage depletion significantly increased the area of fibrosis as compared with the S group at 14 d post-injury (P < 0.01). The expression levels of inflammatory cytokines, chemokines, and oxidative stress factors were increased significantly after muscle injury. Moreover, macrophage depletion increased the expressions of inflammatory cytokines, chemokines and oxidative stress factors as compared with the S group during the later stage of injury (7-14 d post-injury). These results suggest that macrophages depletion can aggravate fibrosis and impair muscle regeneration, and inflammatory cytokines, chemokines and oxidative stress factors may be involved in this process.

[Fat deposition in skeletal muscle and its regulation].

Under normal condition, there are a few lipid droplets in skeletal muscle. But in skeletal muscle acute injury, muscular dystrophy, muscle atrophy, obesity, diabetes and other pathological conditions, the fat deposition in skeletal muscle increases, which implicate that the fat deposition may play an important role in the pathogenesis of these diseases. However, the mechanisms of development and regulation of fat deposition in skeletal muscle are not clear. Clarifying the key signaling pathways and regulatory factors that affect fat deposition in skeletal muscle, and exploring new ways to improve the fat deposition in skeletal muscle will not only help to deepen our understanding of the pathogenesis of these diseases, but also provide new ideas for the treatment of these diseases. This paper reviews the research progresses and main mechanisms of fat deposition in skeletal muscle.

PTP1B confers liver fibrosis by regulating the activation of hepatic stellate cells.

Liver fibrosis is a reversible wound-healing response to chronic hepatic injuries. Activation of hepatic stellate cells (HSCs) plays a pivotal role in the development of hepatic fibrosis. The currently accepted mechanism for the resolution of liver fibrosis is the apoptosis and inactivation of activated HSCs. Protein tyrosine phosphatase 1B (PTP1B), a prototype of non-receptor protein tyrosine phosphatase, is proved to be a vital modulator in cardiac fibrogenesis. However, the precise role of PTP1B on liver fibrosis and HSC activation is still unclear. Our study showed that the expression of PTP1B was elevated in fibrotic liver but reduced after spontaneous recovery. Moreover, stimulation of HSC-T6 cells with transforming growth factor-ß1 (TGF-ß1) resulted in a dose/time-dependent increase of PTP1B mRNA and protein. Co-incubation of HSC-T6 cells with PTP1B-siRNA inhibited the cell proliferation and activation induced by TGF-ß1. Additionally, both mRNA and protein of PTP1B were dramatically decreased in inactivated HSCs after treated with adipogenic differentiation mixture (MDI). Over-expression of PTP1B hindered the inactivation of HSC-T6 cells induced by MDI. These observations revealed a regulatory role of PTP1B in liver fibrosis and implied PTP1B as a potential therapeutic target.

Cognitive motor intervention for gait and balance in Parkinson's disease: systematic review and meta-analysis.

OBJECTIVE: We performed a systematic review and meta-analysis to assess the effect of cognitive motor intervention (CMI) on gait and balance in Parkinson's disease. DATA SOURCES: PubMed, Embase, Cochrane Library, CINAHL, Web of Science, PEDro, and China Biology Medicine disc. METHODS: We included randomized controlled trials (RCTs) and non RCTs. Two reviewers independently evaluated articles for eligibility and quality and serially abstracted data. A standardized mean difference ± standard error and 95% confidence interval (CI) was calculated for each study using Hedge's g to quantify the treatment effect. RESULTS: Nine trials with 181 subjects, four randomized controlled trials, and five single group intervention studies were included. The pooling revealed that cognitive motor intervention can improve gait speed (Hedge's g = 0.643 ± 0.191; 95% CI: 0.269 to 1.017, P = 0.001), stride time (Hedge's g = -0.536 ± 0.167; 95% CI: -0.862 to -0.209, P = 0.001), Berg Balance Scale (Hedge's g = 0.783 ± 0.289; 95% CI: 0.218 to 1.349, P = 0.007), Unipedal Stance Test (Hedge's g = 0.440 ± 0.189; 95% CI: 0.07 to 0.81, P =0.02). CONCLUSIONS: The systematic review demonstrates that cognitive motor intervention is effective for gait and balance in Parkinson's disease. However, the paper is limited by the quality of the included trials.

[The Role of Hepatocyte Growth Factor in Keletal Muscle Regeneration]

Skeletal muscle repair after injury includes three stages which are inflammation, repair and tissue remodeling. The ability of Skeletal muscle to regenerate in response to injury is solely dependen on the activation, proliferation and differentiation of satellite cells. After skeletal muscle injury, hepatocyte growth factor (HGF) can regular muscle satellite cell function in the manner of autocrine, paracrine or endocrine, thus affecting the regeneration of damaged skeletal muscle. Studies about the mechanism have shown that HGF may bind to its receptor, e-met, to start the relevant signaling pathways involved in skeletal muscle satellite cell activation, proliferation, differentiation and migration, which affects skeletal muscle regeneration process.

Effect of aerobic exercise and low carbohydrate diet on pre-diabetic non-alcoholic fatty liver disease in postmenopausal women and middle aged men--the role of gut microbiota composition: study protocol for the AELC randomized controlled trial.

BACKGROUND: Pre-diabetes and non-alcoholic fatty liver disease (NAFLD) are associated with an unhealthy lifestyle and pose extremely high costs to the healthcare system. In this study, we aim to explore whether individualized aerobic exercise (AEx) and low carbohydrate diet (LCh) intervention affect hepatic fat content (HFC) in pre-diabetes via modification of gut microbiota composition and other post-interventional effects. METHODS/DESIGN: A 6-month randomized intervention with 6-month follow-up is conducted from January 2013 to December 2015. The target sample size for intervention is 200 postmenopausal women and middle-aged men aged 50-65 year-old with pre-diabetes and NAFLD. The qualified subjects are randomized into 4 groups with 50 subjects in each group: 1 = AEx, 2 = LCh, 3 = AEx + LCh, and 4 = control. In addition, two age-matched reference groups (5 = pre-diabetes without NAFLD (n = 50) and 6 = Healthy without pre-diabetes or NAFLD (n = 50)) are included. The exercise program consists of progressive and variable aerobic exercise (intensity of 60 to 75% of initial fitness level, 3-5 times/week and 30-60 min/time). The diet program includes dietary consultation plus supplementation with a special lunch meal (40% of total energy intake/day) which aims to reduce the amount of carbohydrate consumption (30%). The control and reference groups are advised to maintain their habitual habits during the intervention. The primary outcome measures are HFC, serum metabolomics and gut microbiota composition. The secondary outcome measures include body composition and cytokines. In addition, socio-psychological aspects, social support, physical activity and diet will be performed by means of questionnaire and interview. DISCUSSION: Specific individualized exercise and diet intervention in this study offers a more efficient approach for liver fat reduction and diabetes prevention via modification of gut microbiota composition. Besides, the study explores the importance of incorporating fitness assessment and exercise in the management of patients with pre-diabetes and fatty liver disorders. If our program is shown to be effective, it will open new strategies to combat these chronic diseases. TRIAL REGISTRATION: Current Controlled Trials: ISRCTN42622771.

[Current developments in exercise immunology].

The aim of this review is to highlight the research and review papers that reflect the current developments in Exercise Immunology, including the interventions on immunosuppression after extreme performance, the effect of exercise on immunosenescence, and the immunomodulating role of exercise in stress and disease. We discuss the papers in accordance with these themes, summarizing their important contributions, and providing directions for future research.