Targeted metabolomics reveals the aberrant energy status in diabetic peripheral neuropathy and the neuroprotective mechanism of traditional Chinese medicine JinMaiTong.

Diabetic peripheral neuropathy (DPN) is a common and devastating complication of diabetes, for which effective therapies are currently lacking. Disturbed energy status plays a crucial role in DPN pathogenesis. However, the integrated profile of energy metabolism, especially the central carbohydrate metabolism, remains unclear in DPN. Here, we developed a metabolomics approach by targeting 56 metabolites using high-performance ion chromatography-tandem mass spectrometry (HPIC-MS/MS) to illustrate the integrative characteristics of central carbohydrate metabolism in patients with DPN and streptozotocin-induced DPN rats. Furthermore, JinMaiTong (JMT), a traditional Chinese medicine (TCM) formula, was found to be effective for DPN, improving the peripheral neurological function and alleviating the neuropathology of DPN rats even after demyelination and axonal degeneration. JMT ameliorated DPN by regulating the aberrant energy balance and mitochondrial functions, including excessive glycolysis restoration, tricarboxylic acid cycle improvement, and increased adenosine triphosphate (ATP) generation. Bioenergetic profile was aberrant in cultured rat Schwann cells under high-glucose conditions, which was remarkably corrected by JMT treatment. In-vivo and in-vitro studies revealed that these effects of JMT were mainly attributed to the activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and downstream peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Our results expand the therapeutic framework for DPN and suggest the integrative modulation of energy metabolism using TCMs, such as JMT, as an effective strategy for its treatment.

Non-coding RNAs in diabetic peripheral neuropathy: their role and mechanisms underlying their effects.

Diabetic peripheral neuropathy (DPN) is a complication of diabetes with a high rate of disability. However, current clinical treatments for DPN are suboptimal. Non-coding RNAs (ncRNAs) are a type of RNAs that are not translated into proteins. NcRNAs perform functions that regulate epigenetic modifications, transcriptional or post-transcriptional regulators of proteins, and thus participate in the physiological and pathological processes of the body. NcRNAs play a role in the progress of DPN by affecting the processes of inflammation, oxidative stress, cellular autophagy or apoptosis. Therefore, ncRNAs treatment is regarded as a promising therapeutic approach for DPN. In addition, since some ncRNAs present stably in the blood of DPN patients, they are considered as potential biomarkers that contribute to early clinical diagnosis. In this paper, we review the studies on the role of ncRNAs in DPN in the last decade, and discuss the mechanisms of ncRNAs, aiming to provide a reference for the future research on the treatment and early diagnosis of DPN.

Sensitivity analysis of non-local damage in soft biological tissues.

Computational modeling can provide insight into understanding the damage mechanisms of soft biological tissues. Our gradient-enhanced damage model presented in a previous publication has shown advantages in considering the internal length scales and in satisfying mesh independence for simulating damage, growth and remodeling processes. Performing sensitivity analyses for this model is an essential step towards applications involving uncertain patient-specific data. In this paper, a numerical analysis approach is developed. For that we integrate two existing methods, that is, the gradient-enhanced damage model and the surrogate model-based probability analysis. To increase the computational efficiency of the Monte Carlo method in uncertainty propagation for the nonlinear hyperelastic damage analysis, the surrogate model based on Legendre polynomial series is employed to replace the direct FEM solutions, and the sparse grid collocation method (SGCM) is adopted for setting the collocation points to further reduce the computational cost in training the surrogate model. The effectiveness of the proposed approach is illustrated by two numerical examples, including an application of artery dilatation mimicking to the clinical problem of balloon angioplasty.

The association between soy isoflavone intake and menopausal symptoms after breast cancer diagnosis: a prospective longitudinal cohort study on Chinese breast cancer patients.

PURPOSE: This study investigated the association between soy isoflavone intake and menopausal symptoms (MPS) among Chinese women with early stage breast cancer in a prospective cohort study. METHODS: In an on-going prospective cohort study that involved 1462 Chinese women with early stage breast cancer, MPS were assessed at 18, 36 and 60 months after cancer diagnosis using the validated menopausal rating scale (MRS) questionnaire. Daily soy food intake for the previous 12 months was assessed at the same time using a validated food frequency questionnaire. The associations between MPS and soy isoflavone intake were evaluated in multivariable logistic regression analyses. RESULTS: The prevalence of MPS was almost the same during the first 60 months after cancer diagnosis, which were 64.5%, 65.2%, and 63.9% at 18, 36, and 60 months, respectively. Patients with MPS tended to be younger than those without MPS. The intake of soy isoflavones was not associated with the total score of MRS at 18-month follow-up [highest vs lowest tertile, odds ratio (OR) = 1.00, 95% CI 0.75-1.34]. Similarly, no significant association was noted at 36-month (OR = 1.25, 95% CI 0.92-1.69) and 60-month (OR = 1.21, 95% CI 0.84-1.74) follow-up. With regards to specific domain within MRS, the risk of symptoms presenting in somatic domain was higher among breast cancer patients who were in the highest tertile of soy isoflavone intake at 36 months post-diagnosis (OR = 1.44, 95% CI 1.07-1.94, P-trend = 0.02), compared with the lowest tertile, where a stronger significant association was noted among patients who were younger than 60 years (OR = 1.52, 95% CI 1.05-2.20, P-trend = 0.03) and pre-menopausal (OR = 3.81, 95% CI 1.85-8.11, P-trend < 0.01). CONCLUSION: The present study provided further evidence that soy isoflavone consumption was not associated with MPS among Chinese breast cancer patients. In fact, patients with higher intake of soy isoflavone have increased risk of experiencing somatic symptoms.

Comparison of Biomechanical Performance of Five Different Treatment Approaches for Fixing Posterior Pelvic Ring Injury.

Background: A large number of pelvic injuries are seriously unstable, with mortality rates reaching 19%. Approximately 60% of pelvic injuries are related to the posterior pelvic ring. However, the selection of a fixation method for a posterior pelvic ring injury remains a challenging problem for orthopedic surgeons. The aim of the present study is to investigate the biomechanical performance of five different fixation approaches for posterior pelvic ring injury and thus provide guidance on the choice of treatment approach in a clinical setting. Methods: A finite element (FE) model, including the L3-L5 lumbar vertebrae, sacrum, and full pelvis, was created from CT images of a healthy adult. Tile B and Tile C types of pelvic fractures were created in the model. Five different fixation methods for fixing the posterior ring injury (PRI) were simulated: TA1 (conservative treatment), TA2 (S1 screw fixation), TA3 (S1 + S2 screw fixation), TA4 (plate fixation), and TA5 (modified triangular osteosynthesis). Based on the fixation status (fixed or nonfixed) of the anterior ring and the fixation method for PRI, 20 different FE models were created. An upright standing loading scenario was simulated, and the resultant displacements at the sacroiliac joint were compared between different models. Results: When TA5 was applied, the resultant displacements at the sacroiliac joint were the smallest (1.5 mm, 1.6 mm, 1.6 mm, and 1.7 mm) for all the injury cases. The displacements induced by TA3 and TA2 were similar to those induced by TA5. TA4 led to larger displacements at the sacroiliac joint (2.3 mm, 2.4 mm, 4.8 mm, and 4.9 mm), and TA1 was the worst case (3.1 mm, 3.2 mm, 6.3 mm, and 6.5 mm). Conclusions: The best internal fixation method for PRI is the triangular osteosynthesis approach (TA5), followed by S1 + S2 screw fixation (TA3), S1 screw fixation (TA2), and plate fixation (TA4).

Three-dimensional numerical simulation of soft-tissue wound healing using constrained-mixture anisotropic hyperelasticity and gradient-enhanced damage mechanics.

Healing of soft biological tissues is the process of self-recovery or self-repair after injury or damage to the extracellular matrix (ECM). In this work, we assume that healing is a stress-driven process, which works at recovering a homeostatic stress metric in the tissue by replacing the damaged ECM with a new undamaged one. For that, a gradient-enhanced continuum healing model is developed for three-dimensional anisotropic tissues using the modified anisotropic Holzapfel-Gasser-Ogden constitutive model. An adaptive stress-driven approach is proposed for the deposition of new collagen fibres during healing with orientations assigned depending on the principal stress direction. The intrinsic length scales of soft tissues are considered through the gradient-enhanced term, and growth and remodelling are simulated by a constrained-mixture model with temporal homogenization. The proposed model is implemented in the finite-element package Abaqus by means of a user subroutine UEL. Three numerical examples have been achieved to illustrate the performance of the proposed model in simulating the healing process with various damage situations, converging towards stress homeostasis. The orientations of newly deposited collagen fibres and the sensitivity to intrinsic length scales are studied through these examples, showing that both have a significant impact on temporal evolutions of the stress distribution and on the size of the damage region. Applications of the approach to carry out in silico experiments of wound healing are promising and show good agreement with existing experiment results.

Gradient-enhanced continuum models of healing in damaged soft tissues.

Healing of soft biological tissue is the process of self-recovering or self-repairing the injured or damaged extracellular matrix (ECM). Healing is assumed to be stress-driven, with the objective of returning to a homeostatic stress metrics in the tissue after replacing the damaged ECM with new undamaged one. However, based on the existence of intrinsic length scales in soft tissues, it is thought that computational models of healing should be non-local. In the present study, we introduce for the first time two gradient-enhanced constitutive healing models for soft tissues including non-local variables. The first model combines a continuum damage model with a temporally homogenized growth model, where the growth direction is determined according to local principal stress directions. The second one is based on a gradient-enhanced healing model with continuously recoverable damage variable. Both models are implemented in the finite-element package Abaqus by means of a user subroutine UEL. Three two-dimensional situations simulating the healing process of soft tissues are modeled numerically with both models, and their application for simulation of balloon angioplasty is provided by illustrating the change of damage field and geometry in the media layer throughout the healing process.

Stochastic analysis of a heterogeneous micro-finite element model of a mouse tibia.

Finite element (FE) analysis can be used to predict bone mechanical environments that can be used for many important applications, such as the understanding of bone mechano-regulation mechanisms. However, when defining the FE models, uncertainty in bone material properties may lead to marked variations in the predicted mechanical environment. The aim of this study is to investigate the influence of uncertainty in bone material property on the mechanical environment of bone. A heterogeneous FE model of a mouse tibia was created from micro computed tomography images. Axial compression loading was applied, and all possible bone density-modulus relationships were considered through stochastic analysis. The 1st and 3rd principal strains (ε1 and ε3) and the strain energy density (SED) were quantified in the tibial volume of interest (VOI). The bounds of ε1, ε3, and SED were determined by the bounds of the density-modulus relationship; the bone mechanical environment (ε1, ε3, and SED) and the bone density-modulus relationship exhibit the same trend of change; the relative percentage differences caused by bone material uncertainty are up to 28%, 28%, and 21% for ε1, ε3, and SED, respectively. These data provide guidelines on the adoption of bone density-modulus relationship in heterogeneous FE models.

Dietary changes in the first 3 years after breast cancer diagnosis: a prospective Chinese breast cancer cohort study.

BACKGROUND: The diagnosis of cancer can motivate patients to change their dietary habits. Evidence on changes in dietary intake before and after breast cancer diagnosis in Chinese women has been limited. PATIENTS AND METHODS: In an ongoing prospective cohort study which involved 1,462 Chinese women with early-stage breast cancer, validated food frequency questionnaire was used to assess prediagnostic dietary intake (using questionnaire to recall dietary intake before diagnosis, which completed at baseline, ie, 0-12 months after diagnosis) and postdiagnostic dietary intake at 18-month and 36-month follow-ups after diagnosis. This study quantitatively compared dietary intake across three time points before and after breast cancer diagnosis. RESULTS: Breast cancer patients significantly and continuously increased vegetables and fruits consumption, from 4.54 servings/day at prediagnosis to 5.19 and 5.59 servings/day at 18-month and 36-month follow-ups postdiagnosis, respectively (each compared to baseline, P<0.001). At 18-month follow-up postdiagnosis, the intake of whole grains, refined grains, eggs, and nuts increased significantly (P<0.001, each). Conversely, the consumption of red meat (P<0.001), processed meat (P<0.001), poultry (P<0.001), dairy products (P<0.001), soy foods (P=0.024), sugar drinks (P<0.001), and coffee (P<0.001) decreased significantly. Compared with prediagnosis diet, the assessment at 36-month follow-up postdiagnosis observed similar dietary changes. The magnitude of changes between two postdiagnosis dietary assessments was much smaller than comparisons made between each of these time points with that of prediagnosis intakes. Postdiagnosis changes in dietary intake occurred in parallel with changes in macronutrients, vitamins, and minerals. CONCLUSION: Chinese breast cancer patients reported significant and long-term changes in dietary intake after cancer diagnosis, which was in line with current dietary recommendation. The present findings suggested that a cancer diagnosis might be a stimulus for patients to take up health-protective changes; health care professionals should consider this as a window of opportunity to educate patients on healthy lifestyle. Further follow-up of this cohort would enable clinicians to determine whether such dietary changes could improve long-term outcomes.

Adherence to the World Cancer Research Fund/American Institute for Cancer Research Guideline Is Associated With Better Health-Related Quality of Life Among Chinese Patients With Breast Cancer.

Background: The 2007 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) guideline provides recommendations for cancer prevention among cancer survivors. Limited data have examined whether guideline adherence is related to health-related quality of life (HRQoL) among Chinese patients with breast cancer. Methods: An ongoing prospective cohort study involving 1,462 Chinese women with early-stage breast cancer assessed exercise, diet, and body mass index (BMI) at baseline and at 18-months follow-up after diagnosis. Each assessment recorded patient habits within the previous 12 months. HRQoL was evaluated by the EORTC Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). We first compared the level of adherence to WCRF/AICR recommendations before and after cancer diagnosis. We then examined whether adherence to these recommendations after diagnosis was associated with HRQoL at 18 months. Results: The mean adherence score significantly increased from baseline (3.2; SD, 1.1) to 18-month follow-up (3.9; SD, 1.1; P<.001). Overall, increasing adherence to the WCRF/AICR guideline was associated with higher scores of global health status/quality of life (QoL; Ptrend=.011), physical (Ptrend<.001) and role functioning (Ptrend=.024), and lower scores for fatigue (Ptrend=.016), nausea and vomiting (Ptrend<.001), pain (Ptrend=.004), dyspnea (Ptrend=.030), loss of appetite (Ptrend=.007), and diarrhea (Ptrend=.020). Patients with cancer who met the BMI recommendation had higher scores for physical functioning (P=.001) and lower scores for fatigue (P=.024), pain (P<.001), and dyspnea (P=.045). Adherence to physical activity recommendation was associated with better scores of global health status/QoL (P<.001), physical functioning (P=.003), fatigue (P=.002), pain (P=.018), and dyspnea (P=.021). Higher adherence to diet recommendation was associated with lower scores of nausea and vomiting (Ptrend=.005), loss of appetite (Ptrend=.026), constipation (Ptrend=.040), and diarrhea (Ptrend=.031). Conclusions: Chinese patients with breast cancer made positive lifestyle changes early after cancer diagnosis. Increased adherence to WCRF/AICR recommendations after cancer diagnosis may improve HRQoL. Our data suggest that Chinese patients with breast cancer should follow the WCRF/AICR guideline to improve overall well-being.

Numerical Investigation on the Biomechanical Performance of Laparoscopic-Assisted Plate Used for Fixing Pelvic Anterior Ring Fracture.

Because of the minimal soft tissue injury, the laparoscopic-assisted internal fixation is a promising technique in fixing the pelvic anterior ring fracture. The aim of this study was to investigate the biomechanical performance of the laparoscopic-assisted plate by the finite element method. Four kinds of implants were investigated, that is, the laparoscopic-assisted plate (LAP), the percutaneous anterior pelvic bridge (PAPB), the transramus intraosseous screw (TIS), and the open reduction (OR). The stability of the implants was investigated under three loading cases, showing that when the LAP was used, the stress at the fracture site was smaller than that at other parts, while for other implants, the high stress was always around the fracture site. In conclusion, the LAP demonstrated a good biomechanical performance in fixing the pelvic anterior ring fracture and is a promising technique in clinical applications.

A minimally invasive posterior lumbar interbody fusion using percutaneous long arm pedicle screw system for degenerative lumbar disease.

The aim of this study is to evaluate the therapeutic efficacy of patients with lumbar degeneration and instability treated with percutaneous pedicle screw fixation and minimally invasive lumbar interbody fusion. Twenty-one patients were selected in our hospital from November, 2012 to March, 2013. The patients with an average age 55.62 years, including 8 vertebral spondylolisthesis, 4 lumbar intervertebral disc herniation, and 9 lumbar spinal canal stenosis cases. All the patients were managed to take the lumbar MRI and radiographs. The comparison of preoperative and postoperative (3 days, 2 weeks, 3 months) VAS and ODI score were analyzed. The results indicated that VAS scores were 7.14 ± 0.79 before operation, and 5.19 ± 0.81 in 3 days after operation, 4 ± 0.84 after 2 weeks, and 2.67 ± 0.66 after 3 months. The pain was relieved, and the postoperative VAS score was lower than that before treatment (P < 0.05). ODI score was 55.8 ± 11.4 before operation, 47.38 ± 9.38 after 3 days, 41.38 ± 8.09 after 2 weeks, 35.76 ± 4.50 after 3 months. ODI score was obviously decreased (P < 0.05). In conclusion, percutaneous pedicle screw fixation combined with minimally invasive interbody fusion is a safe, effective, feasible minimally invasive spine operation, with worthy for spreading.