Role of Exercise on Inflammation Cytokines of Neuropathic Pain in Animal Models.

Neuropathic pain (NP) resulting from a lesion or disease of the somatosensory system can lead to loss of function and reduced life quality. Neuroinflammation plays a vital role in the development and maintenance of NP. Exercise as an economical, effective, and nonpharmacological treatment, recommended by clinical practice guidelines, has been proven to alleviate chronic NP. Previous studies have shown that exercise decreases NP by modifying inflammation; however, the exact mechanisms of exercise-mediated NP are unclear. Therefore, from the perspective of neuroinflammation, this review mainly discussed the effects of exercise on inflammatory cytokines in different parts of NP conduction pathways, such as the brain, spinal cord, dorsal root ganglion, sciatic nerve, and blood in rat/mice models. Results suggested that exercise training could modulate neuroinflammation, inhibit astrocyte glial cell proliferation and microglial activation, alter the macrophage phenotype, reduce the expression of proinflammatory cytokines, increase anti-inflammatory cytokine levels, and positively modulate the state of the immune system, thereby relieving NP.

Demographic and clinical characteristics associated with failure of physical therapy in chronic low back pain: a secondary analysis from a randomized controlled trial.

BACKGROUND: The effect of physical therapy on pain and disability alleviation in patients with chronic low back pain (cLBP) has been demonstrated, but the risk factors for treatment failure remain unknown. AIM: To explore the associations of baseline demographic and clinical characteristics with treatment failure after physical therapy intervention for cLBP. DESIGN: A secondary analysis of a single-blind randomized clinical trial. SETTING: A rehabilitation hospital. POPULATION: A total of 98 patients with cLBP completed the 12-month measurement. METHODS: Patients were randomly grouped into 3-month therapeutic aquatic exercise or physical therapy modalities. The primary outcome was treatment failure, which was defined as a decrease in the numeric rating scale to less than 2.0 points at 12-month follow-up. Associations between baseline demographic and clinical characteristics with risk of treatment failure were assessed by logistic regressions. RESULTS: The pain intensity in the failure cases was alleviated after 3-month intervention but continuously increased at 6- and 12-month follow-up (P<0.05). Old age was significantly associated with an increased risk of treatment failure (adjusted OR 3.26, 95% CI 1.11-9.60). Compared with those receiving physical therapy modalities, the patients receiving therapeutic aquatic exercise had less risk of treatment failure (adjusted OR 0.19, 95% CI 0.08-0.47), and age (P=0.022) was a modifier for this association. CONCLUSIONS: Compared with younger ones, older patients with cLBP had a higher risk of treatment failure after physical therapy and gained a stronger benefit of long-term pain alleviation from therapeutic aquatic exercise. CLINICAL REHABILITATION IMPACT: Therapeutic aquatic exercise is an effective therapy for cLBP and more helpful for preventing treatment failure than physical therapy modalities, especially for older patients.

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.

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.

Repetitive transcranial magnetic stimulation regulates neuroinflammation in neuropathic pain.

Neuropathic pain (NP) is a frequent condition caused by a lesion in, or disease of, the central or peripheral somatosensory nervous system and is associated with excessive inflammation in the central and peripheral nervous systems. Repetitive transcranial magnetic stimulation (rTMS) is a supplementary treatment for NP. In clinical research, rTMS of 5-10 Hz is widely placed in the primary motor cortex (M1) area, mostly at 80%-90% RMT, and 5-10 treatment sessions could produce an optimal analgesic effect. The degree of pain relief increases greatly when stimulation duration is greater than 10 days. Analgesia induced by rTMS appears to be related to reestablishing the neuroinflammation system. This article discussed the influences of rTMS on the nervous system inflammatory responses, including the brain, spinal cord, dorsal root ganglia (DRG), and peripheral nerve involved in the maintenance and exacerbation of NP. rTMS has shown an anti-inflammation effect by decreasing pro-inflammatory cytokines, including IL-1ß, IL-6, and TNF-α, and increasing anti-inflammatory cytokines, including IL-10 and BDNF, in cortical and subcortical tissues. In addition, rTMS reduces the expression of glutamate receptors (mGluR5 and NMDAR2B) and microglia and astrocyte markers (Iba1 and GFAP). Furthermore, rTMS decreases nNOS expression in ipsilateral DRGs and peripheral nerve metabolism and regulates neuroinflammation.

Beneficial Effects and Potential Mechanisms of Tai Chi on Lower Limb Osteoarthritis: A Biopsychosocial Perspective.

Lower limb osteoarthritis (OA) is a chronic, multifactorial disease characterized by impaired physical function, chronic pain, compromised psychological health and decreased social functioning. Chronic inflammation plays a critical role in the pathophysiology of OA. Tai Chi is a type of classical mind-body exercise derived from ancient Chinese martial arts. Evidence supports that Tai Chi has significant benefits for relieving lower limb OA symptoms. Using a biopsychosocial framework, this review aims to elucidate the beneficial effects of Tai Chi in lower limb OA and disentangle its potential mechanisms from the perspective of biology, psychology, and social factors. Complex biomechanical, biochemical, neurological, psychological, and social mechanisms, including strengthening of muscles, proprioception improvement, joint mechanical stress reduction, change of brain activation and sensitization, attenuation of inflammation, emotion modulation and social support, are discussed.

Epidemiology of Musculoskeletal Injuries in the Navy: A Systematic Review.

Objectives: This study aimed to critically review the results of recent studies that investigated the epidemiology of noncombat-related musculoskeletal injuries (MSIs) in the Navy. Methods: A systematic search was conducted of three major databases (Pubmed, Embase, and Cochrane) to identify epidemiological studies on MSIs in the Navy. Study selection and risk of bias assessment were conducted. Results: The overall prevalence of MSIs ranged from 12.69% to 48.81%. And the prevalence of head and face injuries, upper extremity injuries, spine injuries, chest injuries, and lower extremity injuries were 0.11%-0.66%, 0.53%-11.47%, 0.75%-12.09%, 0.43%-0.95%, and 0.4%-21.17%, respectively. For the specific MSIs, the incidence ranged from 0.03/1000 person-years to 32.3/1000 person-years in the Navy and Marines. The ankle-foot, lumbopelvic, knee and lower leg, and shoulder were identified as the most frequent location for MSIs. Conclusion: This systematic review summarized that the Navy population had a high prevalence of MSIs. And different risk factors for MSIs varied from different anatomic locations. This systematic review also provided valuable information on MSIs for sports medicine specialists.

Non-invasive brain neuromodulation techniques for chronic low back pain.

Structural and functional changes of the brain occur in many chronic pain conditions, including chronic low back pain (CLBP), and these brain abnormalities can be reversed by effective treatment. Research on the clinical applications of non-invasive brain neuromodulation (NIBS) techniques for chronic pain is increasing. Unfortunately, little is known about the effectiveness of NIBS on CLBP, which limits its application in clinical pain management. Therefore, we summarized the effectiveness and limitations of NIBS techniques on CLBP management and described the effects and mechanisms of NIBS approaches on CLBP in this review. Overall, NIBS may be effective for the treatment of CLBP. And the analgesic mechanisms of NIBS for CLBP may involve the regulation of pain signal pathway, synaptic plasticity, neuroprotective effect, neuroinflammation modulation, and variations in cerebral blood flow and metabolism. Current NIBS studies for CLBP have limitations, such as small sample size, relative low quality of evidence, and lack of mechanistic studies. Further studies on the effect of NIBS are needed, especially randomized controlled trials with high quality and large sample size.

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.

Efficacy of Therapeutic Aquatic Exercise vs Physical Therapy Modalities for Patients With Chronic Low Back Pain: A Randomized Clinical Trial.

Importance: Therapeutic aquatic exercise is frequently offered to patients with chronic low back pain, but its long-term benefits are unclear. Objective: To assess the long-term effects of therapeutic aquatic exercise on people with chronic low back pain. Design, Setting, and Participants: This 3-month, single-blind randomized clinical trial with a 12-month follow-up period was performed from September 10, 2018, to March 12, 2019, and the trial follow-up was completed March 17, 2020. A total of 113 people with chronic low back pain were included in the experiment. Interventions: Participants were randomized to either the therapeutic aquatic exercise or the physical therapy modalities group. The therapeutic aquatic exercise group received aquatic exercise, whereas the physical therapy modalities group received transcutaneous electrical nerve stimulation and infrared ray thermal therapy. Both interventions were performed for 60 minutes twice a week for 3 months. Main Outcomes and Measures: The primary outcome was disability level, which was measured using the Roland-Morris Disability Questionnaire; scores range from 0 to 24, with higher scores indicating more severe disability. Secondary outcomes included pain intensity, quality of life, sleep quality, recommendation of intervention, and minimal clinically important difference. Intention-to-treat and per-protocol analyses were performed. Results: Of the 113 participants, 59 were women (52.2%) (mean [SD] age, 31.0 [11.5] years). Participants were randomly allocated into the therapeutic aquatic exercise group (n = 56) or the physical therapy modalities group (n = 57), and 98 patients (86.7%) completed the 12-month follow-up. Compared with the physical therapy modalities group, the therapeutic aquatic exercise group showed greater alleviation of disability, with adjusted mean group differences of -1.77 (95% CI, -3.02 to -0.51; P = .006) after the 3-month intervention, -2.42 (95% CI, -4.13 to -0.70; P = .006) at the 6-month follow-up, and -3.61 (95% CI, -5.63 to -1.58; P = .001) at the 12-month follow-up (P < .001 for overall group × time interaction). At the 12-month follow-up point, improvements were significantly greater in the therapeutic aquatic exercise group vs the physical therapy modalities group in the number of participants who met the minimal clinically important difference in pain (at least a 2-point improvement on the numeric rating scale) (most severe pain, 30 [53.57%] vs 12 [21.05%]; average pain, 14 [25%] vs 11 [19.30%]; and current pain, 22 [39.29%] vs 10 [17.54%]) and disability (at least a 5-point improvement on the Roland-Morris Disability Questionnaire) (26 [46.43%] vs 4 [7.02%]). One of the 56 participants (1.8%) in the therapeutic aquatic exercise group vs 2 of the 57 participants (3.5%) in the physical therapy modalities group experienced low back pain and other pains related to the intervention. Conclusions and Relevance: The therapeutic aquatic exercise program led to greater alleviation in patients with chronic low back pain than physical therapy modalities and had a long-term effect up to 12 months. This finding may prompt clinicians to recommend therapeutic aquatic exercise to patients with chronic low back pain as part of treatment to improve their health through active exercise rather than relying on passive relaxation. Trial Registration: Chinese Clinical Trial Registry: ChiCTR1800016396.

Protein Tyrosine Phosphatase 1B (PTP1B): Insights into its New Implications in Tumorigenesis.

In vivo, tyrosine phosphorylation is a reversible and dynamic process governed by the opposing activities of protein tyrosine kinases and phosphatases. Defective or inappropriate operation of these proteins leads to aberrant tyrosine phosphorylation, which contributes to the development of many human diseases, including cancers. PTP1B, a non-transmembrane phosphatase, is generally considered a negative regulator of the metabolic signaling pathways and a promising drug target for type II diabetes and obesity. Recently, PTP1B is gaining considerable interest due to its important function and therapeutic potential in other diseases. An increasing number of studies have indicated that PTP1B plays a vital role in the initiation and progression of cancers and could be a target for new cancer therapies. Following recent advances in the aspects mentioned above, this review is focused on the major functions of PTP1B in different types of cancer and the underlying mechanisms behind these functions, as well as the potential pharmacological effects of PTP1B inhibitors in cancer therapy.

The role of circular RNAs in neuropathic pain.

Neuropathic pain (NP) results from a lesion or disease of the nervous system and accompanied by chronic pain, leading a serious public health issue and economic burden. In terms of the NP mechanisms remaining poorly understood, circular RNAs (circRNAs), owing to their high stability and evolutionary conservation, are expected to be used as potential therapeutic targets or diagnostic biomarkers. In this review, we concisely discuss the characteristics and biological functions of circRNAs. As emerging evidence we reviewed, deregulation of circRNAs (e.g., circ-Filip1l, circHIPK3, ciRS-7, circRNA.2837, circ-Ankib1 and circAnks1a) were involved in NP development. It suggested that specific circRNAs modulated through sponging their target miRNAs and thus regulated the homologous downstream mRNAs and proteins in neuropathic pain. These findings provide a theoretical basis for circRNAs use as biomarkers and therapeutic targets in neuropathic pain.

Interactions Among lncRNA/circRNA, miRNA, and mRNA in Musculoskeletal Degenerative Diseases.

Musculoskeletal degenerative diseases (MSDDs) are pathological conditions that affect muscle, bone, cartilage, joint and connective tissue, leading to physical and functional impairments in patients, mainly consist of osteoarthritis (OA), intervertebral disc degeneration (IDD), rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) are novel regulators of gene expression that play an important role in biological regulation, involving in chondrocyte proliferation and apoptosis, extracellular matrix degradation and peripheral blood mononuclear cell inflammation. Research on MSDD pathogenesis, especially on RA and AS, is still in its infancy and major knowledge gaps remain to be filled. The effects of lncRNA/circRNA-miRNA-mRNA axis on MSDD progression help us to fully understand their contribution to the dynamic cellular processes, provide the potential OA, IDD, RA and AS therapeutic strategies. Further studies are needed to explore the mutual regulatory mechanisms between lncRNA/circRNA regulation and effective therapeutic interventions in the pathology of MSDD.

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.

The Effects of Whole-Body Vibration Exercise on Anticipatory Delay of Core Muscles in Patients with Nonspecific Low Back Pain.

Objective: The objective of this study is to determine the effect of whole-body vibration (WBV) exercise on the anticipatory delay of core muscles in nonspecific low back pain (NSLBP) patients. Methods: Forty participants with NSLBP were randomly divided into the WBV group and the control group. The sEMG signals of deltoid, erector spines (ES), multifidus (MF), rectus abdominis (RA), and transversus abdominus/internal oblique muscles (TrA/IO) were recorded before and after the intervention in the weight-shifting task. The relative activation time of each muscle was calculated. Results: In the WBV group, the relative activation time of bilateral MF and bilateral TrA/IO was significantly reduced on shoulder flexion (right MF: P=0.014; left MF: P=0.011; right TrA/IO: P=0.008; left TrA/IO: P=0.026). As for shoulder abduction, except for the left TrA/IO and the left RA, the relative activation time of other muscles was significantly reduced (right ES: P=0.001; left ES: P < 0.001; right MF: P=0.001; left MF: P=0.009; right TrA/IO: P < 0.001; right RA: P=0.001). In the control group, there was no significant difference in the relative activation time of each muscle before and after the intervention (P > 0.05). Conclusions: WBV exercise can effectively alleviate the anticipatory delay of core muscles in NSLBP patients, but the long-term effects still need further study. This trial is registered with ChiCTR-TRC-13003708.

microRNA-Based Network and Pathway Analysis for Neuropathic Pain in Rodent Models.

Neuropathic pain (NP) is poorly managed, and in-depth mechanisms of gene transcriptome alterations in NP pathogenesis are not yet fully understood. To determine microRNA-related molecular mechanisms of NP and their transcriptional regulation in NP, PubMed, Embase, Web of Science and CINAHL Complete (EBSCO) were searched from inception to April 2021. Commonly dysregulated miRNAs in NP were assessed. The putative targets of these miRNAs were determined using TargetScan, Funrich, Cytoscape and String database. A total of 133 literatures containing miRNA profiles studies and experimentally verify studies were included. Venn analysis, target gene prediction analysis and functional enrichment analysis indicated several miRNAs (miR-200b-3p, miR-96, miR-182, miR-183, miR-30b, miR-155 and miR-145) and their target genes involved in known relevant pathways for NP. Targets on transient receptor potential channels, voltage-gated sodium channels and voltage-gated calcium channels may be harnessed for pain relief. A further delineation of signal processing and modulation in neuronal ensembles is key to achieving therapeutic success in future studies.

Association between ageing population, median age, life expectancy and mortality in coronavirus disease (COVID-19).

As of May 5, 2020, the number of confirmed coronavirus disease (COVID-19) cases has been more than 3.5 million with 243,540 deaths. We aimed to determine the associations between ageing population, median age, life expectancy at birth and COVID-19 mortality. The numbers of COVID-19 cases and deaths in the European region were obtained from the World Health Organization database. The data on percentage of the population aged 65 and over, median age and life expectancy at birth were extracted from the World Factbook of Central Intelligence Agency. A total of 56 countries/areas in the Europe reported COVID-19 cases and deaths (1,121,853 cases and 100,938 deaths) on April 20, 2020. The results showed significant positive associations between COVID-19 mortality and ageing population (r =0.274; P =0.021), median age (r =0.255; P=0.029), male median age (r =0.284; P =0.017), female median age (r =0.224; P=0.049), life expectancy at birth (r =0.336; P=0.006), male life expectancy at birth (r =0.342; P=0.005), female life expectancy at birth (r =0.312; P=0.01) in the 56 European countries/areas. This study illustrated that COVID-19 mortality was positively associated with ageing population, median age, and life expectancy at birth.

The Development of Chinese Assessment and Evaluation of Physical Literacy (CAEPL): A Study Using Delphi Method.

The aim of this study is to introduce the development of the Chinese Assessment and Evaluation of Physical Literacy (CAEPL), to present the theoretical model of the CAEPL, and to quantify the weight of each domain of the CAEPL. 34 experts took part in the Delphi survey, and 23 experts completed all the three rounds of the survey. Experts' opinions are used to develop the theoretical model of the CAEPL. The analytical hierarchy process (AHP) was employed for determining the weights of subdomains and items of the CAEPL. The CAEPL is a comprehensive model, including intention of physical activity (IPA), knowledge of physical activity (KPA), motor/sport skill (MSS), behavior of physical activity (BPA) and physical fitness (PF). Specific weights of IPA, KPA, MSS, BPA and PF are 17.25%, 16.23%, 27.01%, 23.72% and 15.79%, respectively. The CAEPL provides an important and useful instrument to measure and improve physical literacy (PL) among young Chinese people. Studies on the feasibility, reliability, validity and sensitivity of the CAEPL should be conducted to improve it in the future.

Uncovering the Mechanism of Astragalus membranaceus in the Treatment of Diabetic Nephropathy Based on Network Pharmacology.

BACKGROUND: Diabetic nephropathy (DN), characterized by hyperglycemia, hypertension, proteinuria, and edema, is a unique microvascular complication of diabetes. Traditional Chinese medicine (TCM) Astragalus membranaceus (AM) has been widely used for DN in China while the pharmacological mechanisms are still unclear. This work is aimed at undertaking a network pharmacology analysis to reveal the mechanism of the effects of AM in DN. Materials and Methods. In this study, chemical constituents of AM were obtained via Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), and the potential targets of AM were identified using the Therapeutic Target Database (TTD). DisGeNET and GeneCards databases were used to collect DN-related target genes. DN-AM common target protein interaction network was established by using the STRING database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out to further explore the DN mechanism and therapeutic effect of AM. The network diagrams of the active component-action target and protein-protein interaction (PPI) networks were constructed using Cytoscape software. RESULTS: A total of 16 active ingredients contained and 78 putative identified target genes were screened from AM, of which 42 overlapped with the targets of DN and were considered potential therapeutic targets. The analysis of the network results showed that the AM activity of component quercetin, formononetin, calycosin, 7-O-methylisomucronulatol, and quercetin have a good binding activity with top ten screened targets, such as VEGFA, TNF, IL-6, MAPK, CCL3, NOS3, PTGS2, IL-1ß, JUN, and EGFR. GO and KEGG analyses revealed that these targets were associated with inflammatory response, angiogenesis, oxidative stress reaction, rheumatoid arthritis, and other biological process. CONCLUSIONS: This study demonstrated the multicomponent, multitarget, and multichannel characteristics of AM, which provided a novel approach for further research of the mechanism of AM in the treatment of DN.

Mechanism of increased risk of insulin resistance in aging skeletal muscle.

As age increases, the risk of developing type 2 diabetes increases, which is associated with senile skeletal muscle dysfunction. During skeletal muscle aging, mitochondrial dysfunction, intramyocellular lipid accumulation, increased inflammation, oxidative stress, modified activity of insulin sensitivity regulatory enzymes, endoplasmic reticulum stress, decreased autophagy, sarcopenia and over-activated renin-angiotensin system may occur. These changes can impair skeletal muscle insulin sensitivity and increase the risk of insulin resistance and type 2 diabetes during skeletal muscle aging. This review of the mechanism of the increased risk of insulin resistance during skeletal muscle aging will provide a more comprehensive explanation for the increased incidence of type 2 diabetes in elderly individuals, and will also provide a more comprehensive perspective for the prevention and treatment of type 2 diabetes in elderly populations.