Related Factors Mining of Diabetes Complications Based on Manifold-Constrained Multi-Label Feature Selection.

The primary cause of mortality among individuals with diabetes stems from complications. Identifying related factors for these complications holds immense potential for early prevention. Previous research predominantly employed traditional machine-learning techniques to establish prediction models utilizing medical indicators for related factor selection. However, uncovering the intricate correlations among complication labels and identifying similar characteristics among medical indicators has been challenging. We propose a novel embedded multi-label feature selection approach called LCFSM(Label Cosine and Feature Similar Manifold) to address the issue. LCFSM introduces manifold constraints into the objective function to uncover risk factors associated with diabetes complications. Label cosine similarity is set to optimize feature weights, forming label manifold constraints. Similarly, feature manifold constraints are established to utilize feature kernel similarity in optimizing feature weights. LCFSM formulates an objective function based on the l2,1 regularized Least Squares and previous manifolds constraints, employing the Sylvester equation for convergence assurance. The experimental evaluation compares LCFSM against eight baselines, demonstrating superior performance in top-10 feature selection and feature stacking.LCFSM is applied to identify primary risk factors for diabetes complications. Related factors involve Electromyogram, Urine Routine Protein Positive, etc, offering valuable insights for early treatment.

Suppression of IRF9 Promotes Osteoclast Differentiation by Decreased Ferroptosis via STAT3 Activation.

Osteoporosis is a chronic disease that endangers the health of the elderly. Inhibiting osteoclast hyperactivity is a key aspect of osteoporosis prevention and treatment. Several studies have shown that interferon regulatory factor 9 (IRF9) not only regulates innate and adaptive immune responses but also plays an important role in inflammation, antiviral response, and cell development. However, the exact role of IRF9 in osteoclasts has not been reported. To elucidate the role of IRF9 in osteoclast differentiation, we established the ovariectomized mouse model of postmenopausal osteoporosis and found that IRF9 expression was reduced in ovariectomized mice with overactive osteoclasts. Furthermore, knockdown of IRF9 expression enhanced osteoclast differentiation in vitro. Using RNA sequencing, we identified that the differentially expressed genes enriched by IRF9 knockdown were related to ferroptosis. We observed that IRF9 knockdown promoted osteoclast differentiation via decreased ferroptosis in vitro and further verified that IRF9 knockdown reduced ferroptosis by activating signal transducer and activator of transcription 3 (STAT3) to promote osteoclastogenesis. In conclusion, we identified an essential role of IRF9 in the regulation of osteoclastogenesis in osteoporosis and its underlying mechanism.

Early onset age increases the risk of musculoskeletal damage in patients with type 2 diabetes.

Introduction: It's not clear whether there are differences in musculoskeletal damage and body composition among different age groups of type 2 diabetes. Therefore, the purpose of this study is to analyze the difference between early-onset type 2 diabetes (EOT2D) and non-early-onset type 2 diabetes (NOT2D) in musculoskeletal damage. Methods: A total of 964 patients with type 2 diabetes mellitus were selected by 1:1 propensity score matching, including 534 males and 430 females, with an average age of 52 ± 7 years and an average course of 10 ± 8.5 years. Bone mineral density and body composition were measured, and combined with biochemical tests, linear regression and binary logic regression were used to analyze the relationship between EOT2D, NOT2D and musculoskeletal damage. In addition, 414 patients with T2DM were selected according to whether they were hospitalized twice or not, and the median follow-up period was 44 months. COX survival analysis further elucidates the relationship between EOT2D, NOT2D and musculoskeletal damage. Results: Compared with patients with non-early-onset type 2 diabetes, A/G was negatively correlated with the age of onset, and had statistical significance. EOT2D has a higher risk of sarcopenia, osteoporosis and even musculoskeletal damage. With the prolongation of the course of the disease, the risk of muscle mass and/or bone mineral density decrease in EOT2D increases. Conclusion: EOT2D brings a greater risk of sarcopenia and/or osteoporosis, as well as a higher risk of reduced ASM and BMD. In addition, fat distribution may be more central.

Suppression of TLR4 prevents diabetic bone loss by regulating FTO-mediated m6A modification.

Toll-like receptor-4 (TLR4) has been implicated in the development and progression of diabetic osteoporosis. However, the mechanisms underlying TLR4-regulated bone metabolism in diabetes are yet to be fully understood. Epigenetic modifications have been indicated as a possible mechanism leading to increased risk of osteoporosis and bone fracture. As N6-methyladenosine (m6A) is the most common epigenetic modification in eukaryotic mRNAs, we hypothesized that TLR4 regulates m6A modification in bone tissues of diabetic rats, thereby potentially explaining the pathogenesis of diabetic bone loss. m6A sequencing (m6A-seq) was performed in samples of the femur of TLR4-wild type (TLR4WT) and TLR4-knockout (TLR4KO) diabetic rats to identify genes with differential m6A modifications that may be associated with the bone loss phenotype. We found that in TLR4KO rats, the rapid weight loss of diabetic rats was prevented, and bone mineral density (BMD) was significantly increased. m6A-seq and Gene Ontology enrichment analysis revealed that m6A-modified genes in the femur of TLR4KO diabetic rats were associated with regulation of biological processes such as osteoclast differentiation. qRT-PCR analysis on the expression levels of the m6A-modified methyltransferases and demethylases demonstrated that only the m6A demethylase fat mass and obesity-associated protein（FTO）was decreased. Using an osteoclast cell model, we confirmed that TLR4-mediated osteoclast differentiation was induced by glycolipid toxicity via inhibition of FTO expression. Taken together, these results suggest that inhibition of TLR4 may prevent diabetic bone loss via regulation of FTO-mediated m6A modification.

Precedence of Bone Loss Accompanied with Changes in Body Composition and Body Fat Distribution in Patients with Type 2 Diabetes Mellitus.

Methods: A total of 596 patients with T2DM, including 308 male and 288 female patients, were included in the follow-up study; the median follow-up time was 2.17 years. We calculated the difference between the endpoint and the baseline of each body composition index and the annual rate. The research participants were divided into the increased body mass index (BMI) group, stable BMI group, and decreased BMI group. Some confounding factors were adjusted, such as BMI, fat mass index (FMI), muscle mass index (MMI), muscle/fat mass ratio (M/F), trunk fat mass index (TFMI), appendicular skeletal muscle mass index (ASMI), and appendicular skeletal muscle mass/trunk fat mass ratio (A/T). Results: The linear analysis showed that ΔFMI and ΔTFMI were negatively correlated with the change in femoral neck BMD (ΔFNBMD) and ΔMMI, ΔASMI, ΔM/F, and ΔA/T were positively correlated with ΔFNBMD. The risk of FNBMD reduction in patients with increased BMI was 56.0% lower than that in patients with decreased BMI; also, the risk in patients with stable M/F was 57.7% lower than that in patients with decreased M/F. The risk in the A/T increase group was 62.9% lower than that in the A/T decrease group. Conclusions: A reasonable muscle/fat ratio is still beneficial to maintaining bone mass. Maintaining a certain BMI value is conducive to maintaining FNBMD. Simultaneously, increasing the proportion of muscle mass and reducing fat accumulation can also prevent FNBMD loss.

The prebiotic properties of polysaccharides obtained by differentiated deproteinization methods from Flos Sophorae Immaturus on Lactobacillus fermentum.

The polysaccharides derived from various deproteinization methods were prepared from Flos Sophorae Immaturus (FSI) to investigate the prebiotic efficacy of Lactobacillus fermentum (L.f ). The implications of polysaccharides from FSI (PFSI) gained after purification performed by non-deproteinization and different deproteinization processes (Savage method, papain method, and TCA method) via one-factor optimization were firstly investigated for the influences on the growth of L.f. The utilization of carbohydrate sources and the synthesis of protein and lactate during its growth were analyzed, as well as the variations of LDH, SOD, and GSH- Px enzyme dynamics. The results showed that the one-factor optimization of the deproteinization process with the protein removal rate and polysaccharide retention rate as the indexes led to the optimal methods of the Sevage method with 5 elution times, papain method with 80 U/mL concentration, and TCA method with 2.5 ratio, respectively. In addition, the PFSI obtained with or without deproteinization purification had a certain effect on promoting L.f proliferation. Moreover, the PFSI gained by the third deproteinization purification, at a concentration of 10 g/L, significantly elevated L.f biomass and growth rate compared with the blank control, and the utilization of reducing sugars and the synthesis of protein and lactic acid were higher than the control (P < 0.05); improved LDH, SOD, and GSH-Px activity in L.f (P < 0.05), and the TCA method could be effectively applied to eliminate the proteins affecting FSI in probiotics, and PFSI may be a potentially beneficial prebiotic and intestinal reinforcer.

Skeletal outcomes of patients with osteogenesis imperfecta during drug holiday of bisphosphonates: a real-world study.

Purpose: This study aimed to investigate the skeletal outcomes of patients with osteogenesis imperfecta (OI) who received bisphosphonate (BP) treatment and entered drug holiday after achieving an age- and sex-specific bone mineral density (BMD) reference. Methods: Patients with OI receiving BP treatment were enrolled when they entered drug holidays of BPs. The skeletal outcomes were evaluated in detail during the drug holiday, including BMD, X-ray of the bone, bone fracture incidence, and bone turnover biomarkers. The pathogenic mutations of OI were identified by next-generation sequencing and confirmed by Sanger sequencing. Results: A total of 149 OI patients (127 juveniles and 22 adults) who entered drug holidays after nearly 4 years of BP treatment were included. Areal BMD at the lumbar spine increased from 0.934 ± 0.151 to 0.990 ± 0.142 g/cm2 and was stable in the second (1.029 ± 0.176 g/cm2) and third years (1.023 ± 0.174 g/cm2) of BP drug holidays, and BMD at the femoral neck, trochanter, and total hip had no significant change, but it was gradually inferior to that of the same-gender juveniles in the second and third years of the drug holiday. BMD at the lumbar spine and proximal hip did not change and was inferior to that of the same-gender adults. The average time of fractures fluctuated from 0.18 to 0.08 per year in juveniles, while only one adult suffered from a fracture during BP drug holidays. Bone turnover markers were in the normal range, except for a mildly high level of ß-carboxy-terminal cross-linked telopeptide of type 1 collagen in the juvenile group. A total of 17 (11.4%) patients received BP retreatment because of bone loss during the drug holiday. OI type III and type IV and COL1A2 mutation were correlated to a longer duration of BP treatment to enter drug holidays (all p < 0.05). Old age at initial treatment (OR, 1.056) and OI type III (OR, 10.880) were correlated to a higher risk of BP retreatment. Conclusions: OI patients will undergo nearly 4 years of BP treatment to achieve drug holidays. During the 3 years of the drug holiday, the patients' BMD is stable, and fracture incidence does not increase significantly. Patients are more inclined to need retreatment during drug holidays owing to the late start of BP treatment and more severe OI phenotypes.

The Chemical Profiling and Anticancer Potential of Functional Polysaccharides from Flos Sophorae Immaturus.

Polysaccharides from Flos Sophorae Immaturus (FSI) are one of its pharmacological compounds that can perform effective activities. Aiming to extract the most effective polysaccharides against hepatocellular carcinoma (HCC), the polysaccharides were separated from FSI through ultrasonic microwave extraction, and the first comparison was carried out on the characterization of the structure and its cytotoxic properties on HCC SMMC 7721 cells of undeproteinized purified polysaccharides (PFSI-1) and papain-deproteinized polysaccharides (PFSI-2) from FSI. The findings indicated that PFSI-1 and PFSI-2 had characteristic absorption peaks of polysaccharides; PFSI-1 contained three monosaccharides and PFSI-2 contained ten; and SEM, AFM, and NMR were consistent with the verification of IR polysaccharide characteristics, suggesting probable additional latent activities. The pharmacotoxic effects of both PFSI-1 and PFSI-2 on SMMC 7721 cells (p < 0.05), attenuated the migration ability of SMMC 7721 cells (p < 0.05) and promoted apoptosis (p < 0.05), with an increase in G0/G1-phase cells and decrease in S-phase cells in the PFSI-1 as well as a decrease in G0/G1-phase cells, increase in S-phase cells, and decrease in apoptosis in the PFSI-2 (p < 0.05). The significant cytotoxic effect of PFSI-2 on SMMC 7721 cells (p < 0.05) and its protective effect on human hepatic L02 cells (HL-7702) at low concentrations (p > 0.05) could indicate its potential as a new drug for the treatment of HCC.

Antibacterial effect and mechanism of anthocyanin from Lycium ruthenicum Murr.

The inhibitory effects of the anthocyanin obtained from Lycium ruthenicum Murr were tested against several food-borne pathogens were evaluated, such as Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), Aspergillus niger and Penicillium sp. In general, anthocyanin had different antibacterial effect on different bacteria, and the best antibacterial effect on S. aureus, with minimal inhibitory concentration (MIC) of 3.125 mg/mL. Anthocyanin increased the surface hydrophobicity of S. aureus, discharged the intracellular K+, and reduced the total soluble protein, affecting protein synthesis. Fluorescent inverted microscope and flow cytometry (FCM) found a significant increase in fluorescence intensity and lethality relative to the control group, and the dead P3 region to 77.21%. The above suggested a correlation between the antibacterial mechanism of anthocyanin and cell membrane permeability integrity. Biofilm formation was evaluated by the crystal violet assay (CV), silver staining method and methyl thiazolyl tetrazolium (MTT). Scanning electron microscopy (SEM) showed that anthocyanins could change the structure of biofilm.

Improvement of Lipotoxicity-Induced Islet ß Cellular Insulin Secretion Disorder by Osteocalcin.

Background: Osteocalcin (OCN) has been proved to be closely related with the development of type 2 diabetes mellitus (T2DM). We aimed to study if OCN could improve the disorder of islet cell caused by lipotoxicity. Methods: Alizarin red staining was used to investigate the mineralization. Western blotting and ELISA methods were used to measure protein expression. Immunofluorescence staining was used to investigate the protein nuclear transfer. Results: High glucose and high fat inhibited the differentiation of osteoblast precursors. Overexpression of insulin receptor (InsROE) significantly promoted the Runx2 and OCN expression. The increase of insulin, Gprc6a, and Glut2 by osteoblast culture medium overexpressing insulin receptor was reversed by osteocalcin neutralizing antibody. Undercarboxylated osteocalcin (ucOC) suppressed the lipotoxic islet ß-cell damage caused by palmitic acid. The FOXO1 from intranuclear to extranuclear was also significantly increased after ucOC treatment compared with the group PA. Knockdown of Gprc6a or suppression of PI3K/AKT signal pathway could reverse the upregulation of GPRC6A/PI3K/AKT/FoxO1/Pdx1 caused by ucOC. Conclusion: OCN could activate the FOXO1 signaling pathway to regulate GLUT2 expression and improve the insulin secretion disorder caused by lipotoxicity.

Activation of osteoblast ferroptosis via the METTL3/ASK1-p38 signaling pathway in high glucose and high fat (HGHF)-induced diabetic bone loss.

Diabetes mellitus (DM) and osteoporosis are two common diseases that may develop as a cause-and-effect relationship since the incidence of osteoporotic fractures is significantly increased in DM patients. However, the pathophysiology of diabetic osteoporosis is yet to be clearly understood. Iron overload has been reported to lead to bone loss and closely related to osteoporosis. In this study, we hypothesized that high glucose and high fat (HGHF) may induce osteoblastic ferroptosis for the pathogenesis of diabetic osteoporosis and explored the possible molecular mechanisms behind. Using the diabetic rat model established by HGHF feeding with a subsequent intraperitoneal injection of a single low dose of streptozocin, we found that the serum ferritin level (a biomarker for body iron store) was significantly elevated in HGHF-fed rats and the expression of SLC7A11 and GPX4 (inhibitory marker proteins for ferroptosis) was markedly attenuated in the bone tissue of the rats with diabetic bone loss as compared to the normal rats. In an osteoblast cell model, treatment of pre-osteoblastic MC3T3-E1 cells with high glucose and palmitic acid (HGPA) not only suppressed osteoblast differentiation and mineralization but also triggered ferroptosis-related osteoblastic cell death. m6 A-seq revealed that m6 A methylation on ASK1 was 80.9-fold higher in HGPA-treated cells. The expression of p-ASK1 and p-p38 was also significantly elevated in the HGPA-treated cells. Knockout of METTL3 (methyltransferase-like 3), one of the major m6 A methyltransferases, in MC3T3-E1 cells not only abrogated HGPA-induced activation of ASK1-p38 signaling pathway but also attenuated the level of ferroptosis. Therefore, HGHF-induced ferroptosis in osteoblasts may be the main cause of osteoporosis in DM via activation of METTL3/ASK1-p38 signaling pathway, and inhibition of ferroptosis in osteoblasts may provide a potential therapeutic strategy for diabetic osteoporosis.

Relationship between onset age of type 2 diabetes mellitus and vascular complications based on propensity score matching analysis.

AIMS/INTRODUCTION: To assess the relationship between type 2 diabetes mellitus onset age and vascular complications in China. MATERIALS AND METHODS: A retrospective review of 3,568 patients with type 2 diabetes mellitus using a propensity score-matched (PSM) cohort analysis was carried out in two different age of onset groups (age 40 and 60 years). These groups were then subdivided into two groups, early-onset diabetes (EOD40 and EOD60; the onset age before 40 and 60 years, respectively) and late-onset diabetes (LOD40 and LOD60: the onset age after 40 and 60 years, respectively). Macrovascular and microvascular complications were analyzed before and after PSM. RESULTS: Patients categorized in both the early-onset disease (EOD) groups had a higher risk of developing macro- and microvascular complications before PSM. After PSM, no differences existed between the EOD and late-onset disease groups in the risk of macrovascular complications. Compared with the late-onset disease group, the odds ratio of having a microvascular complication of diabetic retinopathy, chronic kidney disease and diabetic peripheral neuropathy in the 40-year-old EOD group increased to 2.906, 1.967 and 1.672 (P < 0.05), respectively. The odds ratio of diabetic retinopathy and diabetic peripheral neuropathy in the 60-year-old EOD group was 1.763 and 1.675 (P < 0.05), respectively. CONCLUSIONS: The earlier the onset of type 2 diabetes mellitus, the higher risk of microvascular, but not necessarily macrovascular, complications. It is not too late to prevent diabetes at any age. Pre-emptive microvascular treatment or preventative measures in EOD patients who do not yet show symptoms, might be beneficial.

Additive Effect of Sarcopenia and Anemia on the 10-Year Risk of Cardiovascular Disease in Patients with Type 2 Diabetes.

OBJECTIVE: To investigate the association between sarcopenia and anemia and the 10-year cardiovascular disease risk in diabetic patients. METHODS: A cross-sectional study was conducted involving 4673 hospitalized patients (2271 men and 2402 women) with type 2 diabetes mellitus, with an average age of 60.66 ± 11.93 years, of whom 542 were followed up for a median follow-up period of 24 months. All participants underwent body composition measurements, and they were grouped by sex and presence of sarcopenia using the Framingham risk model to assess their 10-year cardiovascular risk. According to the changes in the cardiovascular risk during follow-up, the patients were divided into four groups: low-low, low-high, high-low, and high-high. RESULTS: The prevalence of anemia was higher in the sarcopenia group than in the nonsarcopenia group (11.5% vs. 24.1% for men, P < 0.001; 13.9% vs. 19.7% for women, P < 0.05), and the difference remained significant after adjusting for confounders. Patients with sarcopenia and without anemia had a 46.2% increased risk of high 10-year cardiovascular disease (CVD) (odds ratio (OR) = 1.462, 95% confidence interval (CI) 1.085-1.972, P = 0.013), and the risk was twofold higher in patients with sarcopenia and anemia than in those without (OR = 3.283, 95% CI 2.038-5.289, P < 0.001). In follow-up studies, sarcopenia was associated with an increased risk of CVD at 10 years, and a reduction in appendicular skeletal muscle mass index independently predicted the increased risk of CVD. CONCLUSION: Sarcopenia is associated with an increased risk of anemia, and the presence of both has an additive effect on the 10-year CVD risk in patients with type 2 diabetes. Loss of muscle mass can independently predict an increased CVD risk in diabetic patients.

Association of decreased muscle mass with reduced bone mineral density in patients with Graves' disease.

AIM: This study aimed to determine the association of decreased muscle mass with reduced bone mineral density in patients with Graves' disease. METHODS: A total of 758 patients with Graves' disease at diagnosis (mean age 41.2 years) were enrolled for a cross-sectional study; of these, 287 were enrolled for a cohort study with a median follow-up of 24 months. Meanwhile, 1164 age- and sex-matched healthy controls were recruited. All participants underwent dual-energy x-ray absorptiometry and muscle mass index (ASMI) measurements. The changes in ASMI and bone mineral density (BMD) were calculated from the measurements made at a gap of 2 years. RESULTS: The BMD of patients with Graves' disease was still significantly lower after normalizing serum thyroid hormone levels compared with that of healthy controls. ASMI positively correlated with BMD in patients with Graves' disease (lumbar BMD, r = 0.210; femoral neck BMD, r = 0.259; hip BMD, r = 0.235; P < 0.001), and this relationship persisted after successful anti-thyroid therapy (lumbar BMD, r = 0.169; femoral neck BMD, r = 0.281; hip BMD, r = 0.394; P < 0.001). Low muscle mass was associated with low BMD (OR, 1.436; 95% CI, 1.026-2.010). Improving the muscle mass led to changes in the bone mass of the femoral neck (OR, 0.420; 95% CI, 0.194-0.911) and hip (OR, 0.217; 95% CI, 0.092-0.511) during the follow-up. However, this phenomenon was not observed in lumbar and bone turnover markers. CONCLUSIONS: The recovery of bone mass might be related to the recovery of the muscle mass. Patients with Graves' disease should be helped to regain their muscle mass and thus accelerate the recovery of bone mass while administering anti-thyroid therapy.

Research, development, and evaluation of the practical effect of a storage inflow and outflow management system for consumables in the endocrinology department of a hospital.

BACKGROUND: This study was designed for the research and development (R&D) and application of a storage inflow and outflow management system enabling departments to perform efficient, scientific, and information-based consumable management. METHODS: In the endocrinology department of a hospital, expert and R&D teams in consumable management were set up, and an information-based storage inflow and outflow management system for consumables was designed and developed. The system was operated on a personal computer and was divided into three modules: public consumables, bed consumables, and quality control management. The functions of the system included storage inflow and outflow, early warnings, response to user queries, and statistics on consumables. Data were derived from the hospital information system (HIS,ZHIY SOFTWARE HIS VERSION4.0) and a questionnaire survey. Economic indicators, work efficiency of consumable management, nurse burnout, consumable stockroom management, and staff satisfaction were compared under manual management, Excel-based management, and the consumable storage inflow and outflow management system. The results of the questionnaire were analysed using the R software, version 4.1.0. RESULTS: Dates were obtained from manual management, Excel-based management and the consumable storage inflow and outflow management system. Under these three methods, the daily prices of department consumables per bed were 53.43 ± 10.27 yuan, 38.65 ± 8.56 yuan, and 31.98 ± 7.36 yuan, respectively, indicating that the new management system reduced costs for the department. The time spent daily on consumable management was shortened from 119.5 (106.75, 123.5) min to 56.5 (48.5, 60.75) to 20 (17.25, 24.25) min. Nurses' emotional fatigue and job indifference scores, respectively, decreased from 22.90 ± 1.65 and 8.75 ± 1.25 under manual management to 19.70 ± 1.72 and 6.90 ± 1.37 under Excel-based management and to 17.20 ± 2.04 and 6.00 ± 1.30 under the novel system; the satisfaction of the warehouse keeper and collection staff, respectively, increased from 76.62% and 80.78% to 91.6% and 90.5% to 98.8% and 98.5% under the three successive systems. CONCLUSIONS: The storage inflow and outflow management system achieved produced good results in the storage and classification of consumables.

Association of sarcopenia with a higher risk of infection in patients with type 2 diabetes.

AIMS: This study aimed to determine whether patients with type 2 diabetes and sarcopenia had a higher risk of infection. STUDY DESIGNS: A cross-sectional study and a follow-up study were performed. METHOD: A total of 2562 patients were enrolled and assessed for body composition and infection status. They were classified into four groups according to body fat (BF) and muscle mass index (ASMI): obese, sarcopenic, sarcopenic obese, and normal. Among these, 275 patients were followed for a median follow-up period of 1.84 years to evaluate the relationship of changes in skeletal muscle with infection status. RESULTS: The sarcopenic and sarcopenic obese groups showed a higher risk of infection, an increase by 49.6% (OR = 1.496, 95% CI 1.102-2.031) and 42.4% (OR = 1.424, 95% CI 1.031-1.967) compared with the normal group, and also had a higher risk of respiratory infection, an increase by 56.0% (OR = 1.560, 95% CI 1.084-2.246) and 57.4% (OR = 1.574, 95% CI 1.080-2.293), respectively. Patients with the increased ASMI (OR = 0.079, 95% CI 0.021-0.298) represented a lower risk of infection than those with the decreased ASMI. Even a minor change (OR = 0.125, 95% CI 0.041-0.378) against age was beneficial to lowering the risk of infection. However, no association was found in the changes of body mass index and BF with infection status. CONCLUSIONS: Sarcopenia, especially in patients with diabetes who are also obese, increases the risk of infection. Maintaining or improving muscle mass is expected to reduce infections.

Clinical, Biochemical, Radiological, and Genetic Analyses of a Patient with VCP Gene Variant-Induced Paget's Disease of Bone.

Paget's disease of bone (PDB) is a rare metabolic bone disorder, which is extremely rare in Asian population. This study aimed to investigate the phenotypes and the pathogenic mutations of woman with early-onset PDB. The clinical features, bone mineral density, x-ray, radionuclide bone scan, and serum levels of alkaline phosphatase (ALP), procollagen type 1 N-terminal propeptide (P1NP), and ß-carboxy-terminal cross-linked telopeptide of type 1 collagen (ß-CTX) were measured in detail. The pathogenic mutations were identified by whole-exon sequencing and confirmed by Sanger sequencing. We also evaluated the effects of intravenous infusion of zoledronic acid on the bones of the patient and summarized the phenotypic characteristics of reported patients with mutation at position 155 of the valosin-containing protein (VCP). The patient only exhibited bone pain as the initial manifestation with vertebral compression fracture and extremely elevated ALP, P1NP, and ß-CTX levels; she had no inclusion body myopathy and frontotemporal dementia. The missense mutation in exon 5 of the VCP gene (p.Arg155His) was identified by whole-exome sequencing and further confirmed by Sanger sequencing. No mutation in candidate genes of PDB, such as SQSTM1, CSF1, TM7SF4, OPTN, PFN1, and TNFRSF11A, were identified in the patient by Sanger sequencing. Rapid relief of bone pain and a marked decline in ALP, P1NP, and ß-CTX levels were observed after zoledronic acid treatment. Previously reported patients with VCP missense mutation at position 155 (R155H) always had myopathy, frontotemporal dementia, and PDB, but the patient in this study exhibited only PDB. This was the first report of R155H mutation-induced early-onset in the VCP gene in Asian population. PDB was the only manifestation having a favorable response to zoledronic acid treatment. We broadened the genetic and clinical phenotype spectra of the VCP mutation.

Relationship between Hyponatremia and Peripheral Neuropathy in Patients with Diabetes.

OBJECTIVES: Hyponatremia is a common complication of diabetes. However, the relationship between serum sodium level and diabetic peripheral neuropathy (DPN) is unknown. This study was aimed at investigating the relationship between low serum sodium level and DPN in Chinese patients with type 2 diabetes mellitus. METHODS: A retrospective study was performed on 1928 patients with type 2 diabetes between 2010 and 2018. The multivariate test was used to analyze the relationship between the serum sodium level and the nerve conduction function. A restricted cubic spline was used to flexibly model and visualize the relationship between the serum sodium level and DPN, followed by logistic regression with adjustment. RESULTS: As the serum sodium level increased, the prevalence of DPN had a reverse J-curve distribution with the serum sodium levels (69.6%, 53.7%, 49.6%, 43.9%, and 49.7%; P = 0.001). Significant differences existed between the serum sodium level and the motor nerve conduction velocity, sensory nerve conduction velocity, part of compound muscle action potential, and sensory nerve action potential of the participants. Compared with hyponatremia, the higher serum sodium level was a relative lower risk factor for DPN after adjusting for several potential confounders (OR = 0.430, 95%CI = 0.220-0.841; OR = 0.386, 95%CI = 0.198-0.755; OR = 0.297, 95%CI = 0.152-0.580; OR = 0.376, 95%CI = 0.190-0.743; all P < 0.05). Compared with low-normal serum sodium groups, the high-normal serum sodium level was also a risk factor for DPN (OR = 0.690, 95%CI = 0.526-0.905, P = 0.007). This relationship was particularly apparent in male participants, those aged <65 years, those with a duration of diabetes of <10 years, and those with a urinary albumin - to - creatinine ratio (UACR) < 30 mg/g. CONCLUSIONS: Low serum sodium levels were independently associated with DPN, even within the normal range of the serum sodium. We should pay more attention to avoid the low serum sodium level in patients with type 2 diabetes mellitus.