Application of conventional ultrasound coupled with shear wave elastography in the assessment of muscle strength in patients with type 2 diabetes.

Background: In patients with type 2 diabetes mellitus (T2DM), a decrease in muscle function may be related to changes in the biomechanical properties of skeletal muscles. However, the correlations between muscle function and the characteristics of muscle size and stiffness as measured by ultrasound in patients with T2DM are unclear. The aim of this study was to investigate the abilities of conventional ultrasound and shear wave elastography (SWE) to assess muscle properties in patients with T2DM and to correlate the findings with isokinetic muscle testing and functional tests. Methods: Sixty patients from the Department of Endocrinology in The Third Affiliated Hospital of Southern Medical University diagnosed with T2DM were recruited in this cross-sectional study from September 2021 to September 2022. T2DM was defined based on the American Diabetes Association criteria. The exclusion criteria were a history of injury or operation of the lower limb or clinical signs of neuromuscular disorders, any muscle-induced disease, and the presence of other types of diabetes mellitus. Thirty-five matched healthy volunteers were continuously included in the control group. SWE was used to measure the muscle stiffness of the quadriceps femoris [vastus lateralis (VL), rectus femoris (RF), vastus medialis (VM), vastus intermedius (VI)] and the biceps brachii (BB) in a relaxed position, and the shear wave velocity (SWV) values were recorded. Muscle size was measured using conventional ultrasound. The participants underwent isokinetic knee extension/flexion (60°/sec) to assess muscle strength and functional tests of physical performance, including the short physical performance battery, 30-s chair stand test, timed up-and-go test, and 6-meter walk test. All demographics and measured variables were compared using the independent samples t-test. Interclass correlation coefficient analysis was performed on the measurement data obtained by the two operators, and Pearson correlation coefficients were used to determine the relationships between variables. Results: Patients with T2DM exhibited worse physical performance (P<0.05) and weaker lower limb muscle strength (P<0.05) than did healthy controls, but their handgrip strength was comparable (P=0.102). Patients with T2DM had significantly decreased muscle thickness [RF thickness: 10.69±3.21 vs. 13.09±2.41 mm, mean difference =-2.40, 95% confidence interval (CI): -3.56 to -1.24, P<0.001; anterior quadriceps thickness: 23.45±7.11 vs. 27.25±5.25 mm, mean difference =-3.80, 95% CI: -6.33 to -1.26, P=0.004] and RF cross-sectional area (3.04±1.10 vs. 4.11±0.95 cm2, mean difference =-1.07, 95% CI: -1.49 to -0.64; P<0.001) compared to healthy controls. Smaller muscle size was associated with decreased muscle strength (r=0.44-0.69, all P values <0.001). Except for the BB (3.48±0.38 vs. 3.61±0.61 m/s, mean difference =-0.12, 95% CI: -0.35 to 0.11; P=0.257) and VI (2.59±0.34 vs. 2.52±0.23 m/s, mean difference =0.03, 95% CI: -0.06 to 0.18; P=0.299), the muscle stiffness in patients with T2DM was significantly decreased. For the patients with T2DM and healthy participants, the SWV of the RF was 1.66±0.23 and 1.83±0.18 m/s (mean difference =-0.17, 95% CI: -0.25 to -0.08; P<0.001), respectively; that of the VM was 1.34±0.15 and 1.51±0.16 m/s (mean difference =-0.17, 95% CI: -0.24 to -0.10; P<0.001), respectively; and that of VL was 1.38±0.19 and 1.53±0.19 m/s (mean difference =-0.15, 95% CI: -0.23 to -0.07; P<0.001), respectively. Excellent interobserver reliability of the SWV measurements on the muscle of T2DM patients was observed (all intraclass correlation coefficients >0.75; P<0.001). The SWV showed moderate correlations with muscle strength in the RF, VM, and VL (r=0.30-0.61; all P values <0.05). Conclusions: Ultrasound technology exhibits good reliability for repeated measurements of muscle size and stiffness. Reduced muscle stiffness as detected by SWE was demonstrated in patients with diabetes and was associated with decreased muscle strength and impaired functional activity.

A Randomized Clinical Trial of Intravenous Methylprednisolone With 2 Protocols in Patients With Graves Orbitopathy.

CONTEXT: Intravenous glucocorticoid (IVGC) is an accessible and affordable treatment for Graves orbitopathy (GO); the 4.5-g protocol is well studied, but many details of treatment protocols need to be clarified. OBJECTIVE: To compare the efficacy and safety of weekly and monthly protocol of IVGC in GO. METHODS: A prospective, randomized, observer-masked, single-center clinical trial, followed up to week 24, at the third affiliated hospital of Southern Medical University; 58 patients with active and moderate to severe GO, aged 18-60 years old, who had not received relevant treatment were included. The intervention was weekly protocol or monthly protocol of IVGC; both received a cumulative dose of methylprednisolone 4.5 g and had a duration of 12 weeks. The overall effective rate, improvement of quality of life (QOL) and signal intensity ratio (SIR) were measured. RESULTS: There was no significant difference in the effective rate between the 2 groups at week 12 and week 24 (86.21% vs 72.41%, P = .195; 86.21% vs 82.61%, P = .441), there was no significant difference in the improvement of clinical activity score, exophthalmos, soft tissue involvement, diplopia, and QOL. At week 24, the mean SIR and maximum SIR of the 2 groups were lower than those before treatment, and there were no statistically significant difference between the 2 groups. There was no significant difference in the incidence of adverse events between the 2 groups (31.03% vs 27.59%, P = .773). CONCLUSION: The efficacy and safety of the 2 protocols are comparable; the monthly protocol could be used as an alternative to the weekly protocol.

Systematic metabolomic studies identified adult adiposity biomarkers with acetylglycine associated with fat loss in vivo.

Obesity is associated with various adverse health outcomes. Body fat (BF) distribution is recognized as an important factor of negative health consequences of obesity. Although metabolomics studies, mainly focused on body mass index (BMI) and waist circumference, have explored the biological mechanisms involved in the development of obesity, these proxy composite measures are not accurate and cannot reflect BF distribution, and thus may hinder accurate assessment of metabolic alterations and differential risk of metabolic disorders among individuals presenting adiposity differently throughout the body. Thus, the exact relations between metabolites and BF remain to be elucidated. Here, we aim to examine the associations of metabolites and metabolic pathways with BF traits which reflect BF distribution. We performed systematic untargeted serum metabolite profiling and dual-energy X-ray absorptiometry (DXA) whole body fat scan for 517 Chinese women. We jointly analyzed DXA-derived four BF phenotypes to detect cross-phenotype metabolite associations and to prioritize important metabolomic factors. Topology-based pathway analysis was used to identify important BF-related biological processes. Finally, we explored the relationships of the identified BF-related candidate metabolites with BF traits in different sex and ethnicity through two independent cohorts. Acetylglycine, the top distinguished finding, was validated for its obesity resistance effect through in vivo studies of various diet-induced obese (DIO) mice. Eighteen metabolites and fourteen pathways were discovered to be associated with BF phenotypes. Six of the metabolites were validated in varying sex and ethnicity. The obesity-resistant effects of acetylglycine were observed to be highly robust and generalizable in both human and DIO mice. These findings demonstrate the importance of metabolites associated with BF distribution patterns and several biological pathways that may contribute to obesity and obesity-related disease etiology, prevention, and intervention. Acetylglycine is highlighted as a potential therapeutic candidate for preventing excessive adiposity in future studies.

Identification of PDXDC1 as a novel pleiotropic susceptibility locus shared between lumbar spine bone mineral density and birth weight.

An increasing number of epidemiological studies have suggested that birth weight (BW) may be a determinant of bone health later in life, although the underlying genetic mechanism remains unclear. Here, we applied a pleiotropic conditional false discovery rate (cFDR) approach to the genome-wide association study (GWAS) summary statistics for lumbar spine bone mineral density (LS BMD) and BW, aiming to identify novel susceptibility variants shared between these two traits. We detected 5 novel potential pleiotropic loci which are located at or near 7 different genes (NTAN1, PDXDC1, CACNA1G, JAG1, FAT1P1, CCDC170, ESR1), among which PDXDC1 and FAT1P1 have not previously been linked to these phenotypes. To partially validate the findings, we demonstrated that the expression of PDXDC1 was dramatically reduced in ovariectomized (OVX) mice in comparison with sham-operated (SHAM) mice in both the growth plate and trabecula bone. Furthermore, immunohistochemistry assay with serial sections showed that both osteoclasts and osteoblasts express PDXDC1, supporting its potential role in bone metabolism. In conclusion, our study provides insights into some shared genetic mechanisms for BMD and BW as well as a novel potential therapeutic target for the prevention of OP in the early stages of the disease development. KEY MESSAGES : We investigated pleiotropy-informed enrichment between LS BMD and BW. We identified genetic variants related to both LS BMD and BW by utilizing a cFDR approach. PDXDC1 is a novel pleiotropic gene which may be related to both LS BMD and BW. Elevated expression of PDXDC1 is related to higher BMD and lower ratio n-6/n-3 PUFA indicating a bone protective effect of PDXDC1.

Observation of the effect of one-to-one education on high-risk cases of diabetic foot.

BACKGROUND: Diabetes is a common chronic disease, and its global incidence is on the rise. The disease is directly attributed to insufficient insulin efficacy/secretion, and patients are often accompanied by multiple complications. Diabetic foot is one of the most common complications of diabetes. Diabetic feet have ulcers and infections, which can eventually lead to amputation. Basic nursing care, such as lowering blood pressure and preventing foot skin infections in clinical nursing work, has positive significance for the prevention and control of diabetic feet. AIM: To explore the positive significance of one-to-one education in high-risk cases of diabetic foot. METHODS: This observation included 98 high-risk cases of diabetic foot in our hospital during the period from August 2017 to October 2019, and these patients were randomly divided into the basic nursing group and the one-to-one education group with 49 patients per group. The basic nursing group only received routine basic nursing, while the one-to-one education group gave patients one-to-one education on the basis of basic nursing. After nursing, the self-care ability and compliance behavior of the two groups were evaluated and compared between these two groups. The knowledge mastery of the patient and the satisfaction of nursing were accounted. RESULTS: The assessment results of patients (self-care responsibility, self-care skills, self-concept and self-care knowledge) were significantly higher in the one-to-one education group than in the basic nursing group. The scores of compliance behaviors (foot bathing, shoes and socks selection, sports health care) in the one-to-one education group were significantly higher than those in the basic nursing group. Patients in the one-to-one education group had a significantly higher level of knowledge mastery and satisfaction of nursing than the basic nursing group. CONCLUSION: One-to-one education for high-risk cases of diabetic foot is helpful to improve the cognition and self-care ability of patients with diabetic foot, to ensure that patients follow the doctor's advice of self-care and to improve their nursing satisfaction.

Enhanced Identification of Novel Potential Variants for Appendicular Lean Mass by Leveraging Pleiotropy With Bone Mineral Density.

Strong relationships have been found between appendicular lean mass (ALM) and bone mineral density (BMD). It may be due to a shared genetic basis, termed pleiotropy. By leveraging the pleiotropy with BMD, the aim of this study was to detect more potential genetic variants for ALM. Using the conditional false discovery rate (cFDR) methodology, a combined analysis of the summary statistics of two large independent genome wide association studies (GWAS) of ALM (n = 73,420) and BMD (n = 10,414) was conducted. Strong pleiotropic enrichment and 26 novel potential pleiotropic SNPs were found for ALM and BMD. We identified 156 SNPs for ALM (cFDR <0.05), of which 74 were replicates of previous GWASs and 82 were novel SNPs potentially-associated with ALM. Eleven genes annotated by 31 novel SNPs (13 pleiotropic and 18 ALM specific) were partially validated in a gene expression assay. Functional enrichment analysis indicated that genes corresponding to the novel potential SNPs were enriched in GO terms and/or KEGG pathways that played important roles in muscle development and/or BMD metabolism (adjP <0.05). In protein-protein interaction analysis, rich interactions were demonstrated among the proteins produced by the corresponding genes. In conclusion, the present study, as in other recent studies we have conducted, demonstrated superior efficiency and reliability of the cFDR methodology for enhanced detection of trait-associated genetic variants. Our findings shed novel insight into the genetic variability of ALM in addition to the shared genetic basis underlying ALM and BMD.

Identification and Functional Characterization of Metabolites for Bone Mass in Peri- and Postmenopausal Chinese Women.

CONTEXT: Although metabolic profiles appear to play an important role in menopausal bone loss, the functional mechanisms by which metabolites influence bone mineral density (BMD) during menopause are largely unknown. OBJECTIVE: We aimed to systematically identify metabolites associated with BMD variation and their potential functional mechanisms in peri- and postmenopausal women. DESIGN AND METHODS: We performed serum metabolomic profiling and whole-genome sequencing for 517 perimenopausal (16%) and early postmenopausal (84%) women aged 41 to 64 years in this cross-sectional study. Partial least squares regression and general linear regression analysis were applied to identify BMD-associated metabolites, and weighted gene co-expression network analysis was performed to construct co-functional metabolite modules. Furthermore, we performed Mendelian randomization analysis to identify causal relationships between BMD-associated metabolites and BMD variation. Finally, we explored the effects of a novel prominent BMD-associated metabolite on bone metabolism through both in vivo/in vitro experiments. RESULTS: Twenty metabolites and a co-functional metabolite module (consisting of fatty acids) were significantly associated with BMD variation. We found dodecanoic acid (DA), within the identified module causally decreased total hip BMD. Subsequently, the in vivo experiments might support that dietary supplementation with DA could promote bone loss, as well as increase the osteoblast and osteoclast numbers in normal/ovariectomized mice. Dodecanoic acid treatment differentially promoted osteoblast and osteoclast differentiation, especially for osteoclast differentiation at higher concentrations in vitro (eg,10, 100 µM). CONCLUSIONS: This study sheds light on metabolomic profiles associated with postmenopausal osteoporosis risk, highlighting the potential importance of fatty acids, as exemplified by DA, in regulating BMD.

GLP-1/GLP-1R Signaling Regulates Ovarian PCOS-Associated Granulosa Cells Proliferation and Antiapoptosis by Modification of Forkhead Box Protein O1 Phosphorylation Sites.

As the major cause of female anovulatory infertility, polycystic ovary syndrome (PCOS) affects a great proportion of women at childbearing age. Although glucagon-like peptide 1 receptor agonists (GLP-IRAs) show therapeutic effects for PCOS, its target and underlying mechanism remains elusive. In the present study, we identified that, both in vivo and in vitro, GLP-1 functioned as the regulator of proliferation and antiapoptosis of MGCs of follicle in PCOS mouse ovary. Furthermore, forkhead box protein O1 (FoxO1) plays an important role in the courses. Regarding the importance of granulosa cells (GCs) in oocyte development and function, the results from the current study could provide a more detailed illustration on the already known beneficial effects of GLP-1RAs on PCOS and support the future efforts to develop more efficient GLP-1RAs for PCOS treatment.

Vaspin protects mouse mesenchymal stem cells from oxidative stress-induced apoptosis through the MAPK/p38 pathway.

The aim of the work was to study the influence of vaspin on oxidative stress-induced apoptosis of mouse mesenchymal stem cells (MSCs). MSCs originated from bone marrow of C57BL/6 mouse were treated with vaspin and/or H2O2 in a dose-dependent manner. Cellular viability detected by CCK-8 and cell apoptosis studied by flow cytometry and TUNEL assay were observed in these cells. The protein expressions of PI3K, p-PI3K, Akt, p-Akt, T-ERK1/2, p-ERK1/2, p38, p-p38, JNK, and p-JNK were tested by Western blot. Vaspin had no significant effect on cellular viability, but significantly reduced H2O2-induced apoptosis. Western blot assay showed that pretreatment with vaspin promoted the activation of p-p38. Inhibition of p38 by SB203580 suppressed the protective effect of vaspin on oxidative stress-induced apoptosis. Vaspin inhibits oxidative stress-induced apoptosis of MSCs via the activation of MAPK/p38 signaling pathway. These findings indicate that vaspin is prone to osteoporosis protection.

Establishment of magnetic resonance imaging 3D reconstruction technology of orbital soft tissue and its preliminary application in patients with thyroid-associated ophthalmopathy.

OBJECTIVE: Effective management of thyroid-associated ophthalmopathy (TAO) requires precise identification of the disease activity period as it is responsive to immunosuppressive treatment. Quantitative evaluations of orbital soft tissue are useful for analysing disease stages. We aimed to establish a method for orbital soft tissue volume calculation based on magnetic resonance imaging (MRI) data using 3D reconstruction technology. Furthermore, we validated the accuracy and precision of this method and investigated volume differences between patients with TAO and healthy individuals. MATERIALS AND METHODS: Using Mimics software for 3D reconstruction based on orbital MRI data, we quantitatively measured orbital fat volume (FV) and extraocular muscle volume (MV) using a manual phantom, and in patients with TAO and healthy volunteers (n = 10 each). The phantom was made using a combination of butter and chicken muscle and 2 observers measured its volume. Volume calculations were compared to a previously established standard volume. One observer measured a typical TAO case 10 times to calculate intra-observer variability while 3 observers independently measured 10 patients with TAO each to calculate interobserver variability. Orbital soft tissue volumes between 10 patients with TAO and 10 healthy individuals were compared. RESULTS: The precision of calculations for the phantom between the 2 observers varied from -4.60% to -2.78% for FV and between -4.13% to 0.71% for MV. Mean differences among repetitive calculations were lower than 4%, except during measurement of MV, which was 5.84%. The intraclass correlation coefficient varied from 0.976 to 0.996. FV was 15.53 ± 3.06 mL in patients with TAO and 11.32 ± 1.68 mL(P = .001)in healthy individuals, while MV was 3.19 ± 0.82 mL in patients with TAO and 2.45 ± 0.57 mL(P = .030)in healthy individuals. CONCLUSIONS: This method of calculating orbital soft tissue volumes based on MRI data and 3D reconstruction is both reliable and accurate as it yielded significant differences in tissue volume between patients with TAO and healthy individuals.

[A novel method for quantitative measurement of orbital fat volume based on magnetic resonance images].

OBJECTIVE: To establish a new method for rapid and quantitative measurement of orbital fat volume based on magnetic resonance imaging (MRI) data. METHODS: We collected MRI data from normalized mold and patients with the diagnosis of thyroid-associated ophthalmopathy (TAO). The cross-sectional areas of the orbital fat on each MR image slice were measured to calculate the fat volume on each slice and then the total orbital fat volume. We recorded the time for completing the measurement and assessed the precision, reliability, repeatability and interoperator variations of the results. RESULTS: This MRI data-based method allowed precise measurement of the orbital fat volumes with an absolute value of the mean percentage difference <1%. This method was fast and the results showed a good repeatability (with CVs <1%), a high reliability (ICC=0.996, 95%CI: 0.985-0.999) and a high interoperator concordance (95%CI of the Bland-Altman: -0.54-0.90). CONCLUSION: The novel method we established for orbital fat volume measurement is rapid, accurate, reliable and reproducible with a low learning cost for clinical use.

[Calculation of orbital fat volumes for determining treatment timing for thyroid- associated ophthalmopathy].

OBJECTIVE: To analyze the relationship between orbital fat volume and the progression and prognosis of thyroid- associated ophthalmopathy (TAO) and determine the optimal treatment timing for TAO. METHODS: The clinical data were collected from 35 patients (70 orbits) with a definite diagnosis of TAO between January, 2016 and December, 2016. The correlation between orbital fat volume and the clinical parameters was evaluated. We also analyzed the correlation of the signal intensity ratio (SIR) of the extraocular muscles with the clinical parameters. The orbital fat volume was compared between patients with TAO and 12 control subjects. RESULTS: The orbital fat volume was significantly correlated with the duration of TAO (r=0.480, P<0.01), but showed no significant difference between patients with a disease course within 6 months and those with a disease course of 6 to 12 months (P=0.084). The patients with a disease course beyond 12 months had a significantly greater orbital fat volume than those with a disease course of 6 months (P<0.01) or 6 to 12 months (P<0.05). The orbital fat volume was correlated with the degree of proptosis (r=0.622, P<0.01), and an increase of exophthalmos by 1 mm was associated with a total orbital volume increment of 0.88 mL. The clinical activity score was correlated with the SIR of the extraorbital muscles (r=0.536, P<0.01) and levels of anti-thyroid-stimulating hormone receptor antibody (r=0.416,P<0.01). The orbital fat volume was significantly greater in TAO patients than in the healthy individuals (P<0.01). CONCLUSION: In patients with TAO, the peak increase of orbital fat volume occurs one year after the disease onset. Measurement of the orbital fat volume combined with SIR of the extraorbital muscles can serve as an indicator for determining the optimal timing for intervention of TAO and helps in the evaluation of prognosis of the patients.

Micro/Nanostructures and Mechanical Properties of Trabecular Bone in Ovariectomized Rats.

Bone mechanical properties encompass both geometric and material factors, while the effects of estrogen deficiency on the material and structural characteristics of bone at micro- to nanoscales are still obscure. We performed a series of combined methodological experiments, including nanoindentation assessment of intrinsic material properties, atomic force microscopy (AFM) characterization of trabecular (Tb) nanostructure, and Tb microarchitecture and 2D BMD. At 15 weeks after surgery, we found significantly less Tb bone mineral density (BMD) at organ (-27%) and at tissue level (-12%), Tb bone volume fraction (-29%), Tb thickness (-14%), and Tb number (-17%) in ovariectomy (OVX) rats than in sham operated (SHAM) rats, while the structure model index (+91%) and Tb separation (+19%) became significantly greater. AFM images showed lower roughness Tb surfaces with loosely packed large nodular structures and less compacted interfibrillar space in OVX than in SHAM. However, no statistically significant changes were in the Tb intrinsic material properties-nanoindentation hardness, elastic modulus, and plastic deformation-nanoindentation depths, and residual areas. Therefore, estrogen deprivation results in a dramatic deterioration in Tb micro/nanoarchitectures, 3D volumetric BMD at both organ and tissue levels, and 2D BMD, but not in the nanomechanical properties of the trabeculae per se.