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Background: Osteosarcoma and chondrosarcoma are common malignant bone tumors, and accurate differentiation between these two tumors is crucial for treatment strategies and prognosis assessment. However, traditional radiological methods face diagnostic challenges due to the similarity in imaging between the two., Methods: Clinical CT images and pathological data of 76 patients confirmed by pathology from January 2018 to January 2024 were retrospectively collected from Guizhou Medical University Affiliated Hospital and Guizhou Medical University Second Affiliated Hospital. A total of 788 radiomic features, including shape, texture, and first-order statistics, were extracted in this study. Six machine learning models, including Random Forest (RF), Extra Trees (ET), AdaBoost, Gradient Boosting Tree (GB), Linear Discriminant Analysis (LDA), and XGBoost (XGB), were trained and validated. Additionally, the importance of features and the interpretability of the models were evaluated through SHAP value analysis., Results: The RF model performed best in distinguishing between these two tumor types, with an AUC value close to perfect at 1.00. The ET and AdaBoost models also demonstrated high performance, with AUC values of 0.98 and 0.93, respectively. SHAP value analysis revealed significant influences of wavelet-transformed GLCM and First Order features on model predictions, further enhancing diagnostic interpretability., Conclusion: This study confirms the effectiveness of combining machine learning with radiomic features in improving the accuracy and interpretability of osteosarcoma and chondrosarcoma diagnosis. The excellent performance of the RF model is particularly suitable for complex imaging data processing, providing valuable insights for the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Long, Wang, Hu, Gao, Zhang, Ban and Tian.)

Objectives: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with varying symptoms and multi-organ damage. Relapse-remission cycles often persist for many patients for years with the current treatment. Improved understanding of molecular changes caused by SLE flare and intensive treatment may result in more targeted therapies., Methods: RNA sequencing was performed on peripheral blood mononuclear cells (PBMCs) from 65 SLE patients in flare, collected both before (SLE1) and after (SLE2) in-hospital treatment, along with 15 healthy controls (HC). Differentially expressed genes (DEGs) were identified among the three groups. Enriched functions and key molecular signatures of the DEGs were analysed and scored to elucidate the transcriptomic changes during treatment., Results: Few upregulated genes in SLE1 vs HC were affected by treatment (SLE2 vs SLE1), mostly functional in interferon signalling (IFN), plasmablasts and neutrophils. IFN and plasmablast signatures were repressed, but the neutrophil signature remained unchanged or enhanced by treatment. The IFN and neutrophil scores together stratified the SLE samples. IFN scores correlated well with leukopenia, while neutrophil scores reflected relative cell compositions but not cell counts., Conclusions: In-hospital treatment significantly relieved SLE symptoms with expression changes of a small subset of genes. Notably, IFN signature changes matched SLE flare and improvement, while enhanced neutrophil signature upon treatment suggested the involvement of low-density granulocytes (LDG) in disease development., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Metformin, an anti-diabetic drug, regulates blood glucose by affecting gut microbiotas. However, the potential mechanism underlying this effect remains unclear. This study aimed to evaluate the effect of metformin on glucose regulation, lipid levels, and the gut microbiota in rats with type 2 diabetes mellitus induced by a high-fat diet with streptozotocin., Research Design Methods: Thirty Wistar rats was using in this experiment. T2DM rats were administered 300 mg/kg metformin for 8 weeks. The glucose regulation, lipid levels, organ coefficients, and gut microbiotawere measured by 16S rDNA., Result: The metformin-gavaged rats exhibited significant improvements in blood glucose and serum lipid levels, accompanied by alterations in short-chain fatty acid levels and the intestinal microbiota (p < 0.05). In the diabetic rats, metformin potentially increased specific probiotics, thus improving the hypoglycaemic effects of the oral anti-diabetic drug. Further, damage to the liver and kidney was effectively alleviated in the metformin-gavaged rats., Conclusion: This study's findings demonstrate that metformin exerts a positive anti-diabetic effect in HFD- and STZ-induced T2DM rats. These findings potentially provide a basis for the recommended use of metformin as a reliable oral drug for T2DM owing to its positive effect on the intestinal microbiota., (© 2024. The Author(s).)

Background: Secondary osteoporosis is associated with type 2 diabetes mellitus (T2DM), and there is conflicting evidence regarding the relationship between insulin-like growth factor-1 (IGF-1) and bone mineral density (BMD) in different populations. The objective of this study was to investigate the relationship between serum IGF-1 levels and BMD in patients with T2DM., Method: A retrospective cross-sectional study was performed on a cohort of 363 patients with T2DM, comprising men aged over 50 and women who are postmenopausal. Those with no significant medical history or medication affecting BMD or IGF-1 were considered. Data analyzed included IGF-1 levels, markers of bone metabolism, and measurements of BMD. To account for age and gender variations, we calculated IGF-1 standard deviation scores (IGF-1 SDS) for further investigation., Results: A significant increase in BMD at lumbar spine (LS), femoral neck (FN), and total hip (TH) was observed as IGF-1 SDS tertiles rose. We revealed a nonlinear correlation between IGF-1 SDS and BMD at these sites, with a common inflection point identified at an IGF-1 SDS level of -1.68. Additionally, our multivariate piecewise linear regression analysis highlighted a positive association between IGF-1 SDS and BMD at LS, FN, and TH when IGF-1 SDS exceeded the inflection point (β 0.02, 95% CI 0.01, 0.04 for LS; β 0.02, 95% CI 0.01, 0.03 for FN; β 0.02, 95% CI 0.01, 0.03 for TH). Conversely, below the inflection point, this association was not significant (β -0.04, 95% CI -0.10, 0.01 for LS; β -0.04, 95% CI -0.08, 0.01 for FN; β -0.03, 95% CI -0.08, 0.01 for TH)., Conclusion: These findings reveal a nonlinear relationship between IGF-1 SDS and BMD in T2DM patients. Higher serum IGF-1 levels were connected to increased bone density only after surpassing a certain threshold., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhao, Li, Zhang, Zhang and Ban.)

Purpose: Substantial evidence has established a strong association between non-alcoholic fatty liver disease (NAFLD), type 2 diabetes mellitus (T2DM) and insulin resistance (IR). Insulin resistance metabolic score (METS-IR) is a new and more effective comprehensive indicator for measuring IR. Our aim was to investigate the relationship between METS-IR and NAFLD in T2DM population., Patients and Methods: This cross-sectional study included 1097 adult patients with T2DM. Anthropometric measurements and biochemical indicators were collected, and the NAFLD was diagnosed by ultrasound. The METS-IR was calculated. Based on the presence of NAFLD, the population was divided into non-NAFLD and NAFLD groups. The relationship between METS-IR and NAFLD was evaluated., Results: Compared with the non-NAFLD group, the METS-IR was higher in the NAFLD group (P < 0.001). The incidence rate of NAFLD increased across the quartiles of the METS-IR (P < 0.001). Spearman correlation analysis showed that METS-IR was positively correlated with NAFLD (Correlation Coefficient: 0.441, P < 0.001). The binary logistic regression analysis indicated that METS-IR was independently associated with NAFLD (OR: 1.120, 95% CI 1.080-1.161). Furthermore, the area under the receiver operating characteristic curve of the METS-IR was 0.781 (95% CI 0.746-0.817) and relatively higher than other evaluation variables., Conclusion: In patients with T2DM, METS-IR is closely associated with NAFLD, and might be a valuable predictor of NAFLD. Further research is needed to verify this association., Competing Interests: The authors declare that they have no competing interests in this study., (© 2024 Ma et al.)

The goal of our research is to elucidate and better assess placental function in rats with preeclampsia through an innovative application of ultrasound-based radiomics. Using a rat model induced with L-NAME, we carefully investigated placental dysfunction via microstructural analysis and immunoprotein level assessment. Employing the Boruta feature selection method on ultrasound images facilitated the identification of crucial features, consequently enabling the development of a robust model for classifying placental dysfunction. Our study included 12 pregnant rats, and thorough placental evaluations were conducted on 160 fetal rats. Distinct alterations in placental microstructure and angiogenic factor expression were evident in rats with preeclampsia. Leveraging high-throughput mining of quantitative image features, we extracted 558 radiomic features, which were subsequently used to construct an impressive evaluation model with an area under the receiver operating curve (AUC) of 0.95. This model also exhibited a remarkable sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 88.7%, 91.5%, 90.2%, 90.4%, and 90.0%, respectively. Our findings highlight the ability of ultrasound-based radiomics to detect abnormal placental features, demonstrating its potential for evaluating both normative and impaired placental function with high precision and reliability., (© 2024. The Author(s).)

Metabolic dysfunction associated fatty liver disease (MAFLD) is a common cause of liver disease in children and adolescents. The relationship between insulin resistance (IR) and MAFLD in children with short stature remains largely unknown. The present study was to investigate the relationship between the triglyceride-glucose (TyG) index and alanine aminotransferase (ALT) levels in children with short stature. A total of 1754 children with short stature were enrolled. Anthropometric, biochemical and hormonal indexes were collected through physical measurement examinations and laboratory tests. A nonlinear association was found between the TyG index and ALT. The inflection point of the curve was at a TyG index of 8.24. In multivariate piecewise linear regression, only when the TyG index was greater than 8.24 was there a significant positive association between the TyG index and ALT (β 5.75, 95% CI 3.30, 8.19; P < 0.001). However, when the TyG index was less than 8.24, there was no significant association between the TyG index and ALT (β -0.57, 95% CI -1.84, 0.71; P = 0.382). This study demonstrated a nonlinear relationship between TyG index and ALT in children with short stature. This finding suggests that a high TyG index is associated with elevated ALT in children with short stature., (© 2024. The Author(s).)

Ankyrin repeat domain containing-protein 11 (ANKRD11), a transcriptional factor predominantly localized in the cell nucleus, plays a crucial role in the expression regulation of key genes by recruiting chromatin remodelers and interacting with specific transcriptional repressors or activators during numerous biological processes. Its pathogenic variants are strongly linked to the pathogenesis and progression of multisystem disorder known as KBG syndrome. With the widespread application of high-throughput DNA sequencing technologies in clinical medicine, numerous pathogenic variants in the ANKRD11 gene have been reported. Patients with KBG syndrome usually exhibit a broad phenotypic spectrum with a variable degree of severity, even if having identical variants. In addition to distinctive dental, craniofacial and neurodevelopmental abnormalities, patients often present with skeletal anomalies, particularly postnatal short stature. The relationship between ANKRD11 variants and short stature is not well-understood, with limited knowledge regarding its occurrence rate or underlying biological mechanism involved. This review aims to provide an updated analysis of the molecular spectrum associated with ANKRD11 variants, investigate the prevalence of the short stature among patients harboring these variants, evaluate the efficacy of recombinant human growth hormone in treating children with short stature and ANKRD11 variants, and explore the biological mechanisms underlying short stature from both scientific and clinical perspectives. Our investigation indicated that frameshift and nonsense were the most frequent types in 583 pathogenic or likely pathogenic variants identified in the ANKRD11 gene. Among the 245 KBGS patients with height data, approximately 50% displayed short stature. Most patients showed a positive response to rhGH therapy, although the number of patients receiving treatment was limited. ANKRD11 deficiency potentially disrupts longitudinal bone growth by affecting the orderly differentiation of growth plate chondrocytes. Our review offers crucial insights into the association between ANKRD11 variants and short stature and provides valuable guidance for precise clinical diagnosis and treatment of patients with KBG syndrome., (© 2024. The Author(s).)

Objectives: This study aims to elucidate the transcriptomic signatures and dysregulated pathways in patients with Systemic Lupus Erythematosus (SLE), with a particular focus on those persisting during disease remission., Methods: We conducted bulk RNA-sequencing of peripheral blood mononuclear cells (PBMCs) from a well-defined cohort comprising 26 remission patients meeting the Low Lupus Disease Activity State (LLDAS) criteria, 76 patients experiencing disease flares, and 15 healthy controls. To elucidate immune signature changes associated with varying disease states, we performed extensive analyses, including the identification of differentially expressed genes and pathways, as well as the construction of protein-protein interaction networks., Results: Several transcriptomic features recovered during remission compared to the active disease state, including down-regulation of plasma and cell cycle signatures, as well as up-regulation of lymphocytes. However, specific innate immune response signatures, such as the interferon (IFN) signature, and gene modules involved in chromatin structure modification, persisted across different disease states. Drug repurposing analysis revealed certain drug classes that can target these persistent signatures, potentially preventing disease relapse., Conclusion: Our comprehensive transcriptomic study revealed gene expression signatures for SLE in both active and remission states. The discovery of gene expression modules persisting in the remission stage may shed light on the underlying mechanisms of vulnerability to relapse in these patients, providing valuable insights for their treatment., (© 2024. The Author(s).)

KBG syndrome is a rare autosomal dominant condition characterized by multisystem developmental disorder, primarily caused by loss-of-function variants in ankyrin repeat domain-containing protein 11 (ANKRD11). Approximately 80 % of ANKRD11 variants associated with KBG syndrome, are frameshift and nonsense variants. Current insight into the pathogenesis of KBG syndrome resulting from ANKRD11 truncating variants remains limited. Here, we presented two members from a non-consanguineous Chinese pedigree both exhibiting characteristics fitting the KBG syndrome-associated phenotypic spectrum. Whole-exome sequencing identified a novel heterozygous frameshift variant in ANKRD11 (NM&#95;013275.6, c.2280&#95;2281delGT, p.Y761Qfs*20) in the proband. Sanger sequencing confirmed that the variant was inherited from her mother and co-segregated with KBG syndrome phenotype. In vitro functional assays revealed that the frameshift variant escaped nonsense-mediated mRNA decay, and resulting in a truncated protein with significantly increased expression levels compared to full-length ANKRD11. Immunofluorescence results demonstrated that truncated protein was predominantly expressed in the nucleus of HEK293 cells, while wild-type ANKRD11 was equally distributed in both the nucleus and cytoplasm. Moreover, the truncated protein significantly reduced CDKN1A / P21 -promoter luciferase activity in comparison to wild-type ANKRD11 protein, as well as a remarkably decrease in the endogenous CDKN1A/P2 1 mRNA level in HEK293 cells. These findings suggest a loss of transcriptional activation function and potentially a dominant-negative mechanism. Overall, our study expands the mutational spectrum of ANKRD11 gene and provides new insights into the pathogenic mechanism of KBG syndrome caused by ANKRD11 truncating variants., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Bone marrow stromal cell antigen 2 (BST2) is a type II transmembrane protein that serves critical roles in antiretroviral defense in the innate immune response. In addition, it has been suggested that BST2 is highly expressed in various types of human cancer and high BST2 expression is related to different clinicopathological parameters in cancer. The molecular mechanism underlying BST2 as a potential tumor biomarker in human solid tumors has been reported on; however, to the best of our knowledge, there has been no review published on the molecular mechanism of BST2 in human solid tumors. The present review focuses on human BST2 expression, structure and functions; the molecular mechanisms of BST2 in breast cancer, hepatocellular carcinoma, gastrointestinal tumor and other solid tumors; the therapeutic potential of BST2; and the possibility of BST2 as a potential marker. BST2 is involved in cell membrane integrity and lipid raft formation, which can activate epidermal growth factor receptor signaling pathways, providing a potential mechanistic link between BST2 and tumorigenesis. Notably, BST2 may be considered a universal tumor biomarker and a potential therapeutical target.

Background: Significant differences have been observed in the efficacy of recombinant human growth hormone (rhGH) treatment for short children. The present study aimed to identify the genetic etiology of short stature and to assess the role of molecular diagnosis in predicting responses to rhGH treatment., Methods: A total of 407 short children were included in the present study, 226 of whom received rhGH treatment. Whole-exome sequencing (WES) was conducted on short children to identify the underlying genetic etiology. Correlations between molecular diagnosis and the efficacy of rhGH treatment were examined., Results: Pathogenic or likely pathogenic mutations were identified in 86 of the 407 patients (21.1%), including 36 (41.9%) novel variants. Among the multiple pathways affecting short stature, genes involved in fundamental cellular processes (38.7%) play a larger role, especially the RAS-MAPK pathway. In general, patients without pathogenic mutations responded better to rhGH than those with mutations. Furthermore, patients with hormone signaling pathway mutations had a better response to rhGH, while those with paracrine factor mutations had a worse response to rhGH., Conclusions: This study highlights the utility of WES in identifying genetic etiology in children with short stature. Identifying likely causal mutations is an important factor in predicting rhGH response., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: This study was performed to investigate the effectiveness of the combination of letrozole and recombinant human growth hormone (rhGH) to improve the predicted adult height (PAH) and final adult height (FAH) of Chinese short pubertal boys., Methods: In total, 171 Chinese short pubertal boys were recruited for this study. 96 of them received letrozole (2.5 mg/d) combined with rhGH (33.3-66.6 μg/kg.d), and the others received rhGH alone. Follow-up visits were conducted at 1, 3, 6, 9, and 12 months or regularly after the first treatment. During each visit, plasma samples were collected for clinical tests and biomedical analyses, all of which were performed according to standard protocols. This study was registered at www.chictr.org.cn under ID number ChiCTR1900026142., Results: After receiving treatment for at least 3 months, 68 boys (91 %) in the rhGH therapy group and 90 (94 %) in the letrozole combined with rhGH (letrozole+rhGH) therapy group achieved an increase in PAH, with the latter treatment leading to a more effective slowing of bone age (BA) advancement. Moreover, the increased PAH showed a significant positive correlation with treatment time in both groups, and letrozole+rhGH increased the PAH to a greater degree than rhGH alone (p=0.0023). And letrozole+rhGH not only slowed the increase in BA more efficiently than rhGH therapy alone (p=0.0025), but also achieved a higher FAH (p=0.0078)., Conclusions: Letrozole combined with rhGH treatment is a promising therapy to increase the PAH and FAH of Chinese short pubertal boys., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Evidence regarding the relationship between sleep duration and blood pressure is controversial. Therefore, the aim of this study was to investigate the relationship between sleep duration and blood pressure in children with short stature., Methods: A total of 1,085 participants with short stature were enrolled from the Affiliated Hospital of Jining Medical University in China. The variables involved in this study included sleep duration, anthropometric indicators and biochemical parameters. Sleep duration was evaluated in a face-to-face interview., Results: The average age of the 1,085 selected participants was 10.2 ± 3.5 years old, and approximately 763 (70.32%) of them were male. The results of adjusted linear regression showed that sleep duration was negatively associated with systolic blood pressure z scores (SBP-Z) and diastolic blood pressure z scores (DBP-Z) after adjusting for confounders (β -0.07, 95% CI -0.13, -0.01 P  = 0.038; β -0.05, 95% CI -0.10, -0.01 P  = 0.035, respectively). A nonlinear relationship was detected between sleep duration and blood pressure, including SBP-Z, DBP-Z and mean arterial pressure z scores (MAP-Z). The inflection point of the nonlinear relationship between sleep duration and SBP-Z is 10 h, and the inflection point of DBP-Z and MAP-Z is 8 h., Conclusion: This study revealed a nonlinear relationship between sleep duration and blood pressure in children with short stature. The findings suggest that the optimal sleep duration in children with short stature was 8-10 h, and sleep durations either too short or too long were associated with increased blood pressure levels., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Zhao, He, Zhang, Chu and Ban.)

Background: Short stature is a common human trait. More severe and/or associated short stature is usually part of the presentation of a syndrome and may be a monogenic disease. The present study aimed to identify the genetic etiology of children with short stature of unknown origin., Methods: A total of 232 children with short stature of unknown origin from March 2013 to May 2020 were enrolled in this study. Whole exome sequencing (WES) was performed for the enrolled patients to determine the underlying genetic etiology., Results: We identified pathogenic or likely pathogenic genetic variants in 18 (7.8%) patients. All of these variants were located in genes known to be associated with growth disorders. Five of the genes are associated with paracrine signaling or cartilage extracellular matrix in the growth plate, including NPR2 (N = 1), ACAN (N = 1), CASR (N = 1), COMP (N = 1) and FBN1 (N = 1). Two of the genes are involved in the RAS/MAPK pathway, namely, PTPN11 (N = 6) and NF1 (N = 1). Two genes are associated with the abnormal growth hormone-insulin-like growth factor 1 (GH-IGF1) axis, including GH1 (N = 1) and IGF1R (N = 1). Two mutations are located in PROKR2, which is associated with gonadotropin-releasing hormone deficiency. Mutations were found in the remaining two patients in genes with miscellaneous mechanisms: ANKRD11 (N = 1) and ARID1A (N = 1)., Conclusions: The present study identified pathogenic or likely pathogenic genetic variants in eighteen of the 232 patients (7.8%) with short stature of unknown origin. Our findings suggest that in the absence of prominent malformation, genetic defects in hormones, paracrine factors, and matrix molecules may be the causal factors for this group of patients. Early genetic testing is necessary for accurate diagnosis and precision treatment., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The aim of this study was to explore the relationship between serum uric acid (SUA) and the triglyceride-glucose (TyG) index, which is a more effective indicator of insulin resistance. The study participants included 1700 children and adolescents with short stature who were recruited at the Affiliated Hospital of Jining Medical University in China between March 2013 and April 2021. A positive association between SUA levels and the TyG index was detected by univariate analysis (p < 0.001). Furthermore, a nonlinear relationship was detected between SUA and the TyG index, whose point was 6.55 mg/dL. There was a positive association between SUA and the TyG index when the SUA level was greater than 6.55 mg/dL (β 0.17, 95% CI: 0.07, 0.27; P < 0.001). However, we did not observe a significant relationship between SUA and the TyG index when the SUA level was less than 6.55 mg/dL (β 0.02, 95% CI: - 0.01, 0.05; P = 0.091). In addition, a stratified analysis was performed to appraise changes in this relationship for different sexes. The relationship between SUA and the TyG index in males and females is consistent with that in the general population, showing a nonlinear relationship. However, the inflection points of SUA level were significantly higher in males than in females, and the inflection points were approximately 6.72 and 5.88 mg/dL, respectively. This study revealed a nonlinear relationship between SUA and the TyG index in children with short stature. The nonlinear relationship remained in gender stratification analysis, but the inflection point of SUA level was higher in men. Further studies are needed to establish a causal relationship between SUA levels and the TyG index in children with short stature., (© 2023. Springer Nature Limited.)

Background: Since the triglyceride glucose (TyG) index can reflect insulin resistance, it has been proven to be an efficient predictor of glycolipid-metabolism-related diseases. Therefore, this study aimed to investigate the predictive value of the TyG index for visceral obesity (VO) and body fat distribution in patients with type 2 diabetes mellitus (T2DM)., Methods: Abdominal adipose tissue characteristics in patients with T2DM, including visceral adipose area (VAA), subcutaneous adipose area (SAA), VAA-to-SAA ratio (VSR), visceral adipose density (VAD), and subcutaneous adipose density (SAD), were obtained through analyses of computed tomography images at the lumbar 2/3 level. VO was diagnosed according to the VAA (> 142 cm 2 for males and > 115 cm 2 for females). Logistic regression was performed to identify independent factors of VO, and receiver operating characteristic (ROC) curves were used to compare the diagnostic performance according to the area under the ROC curve (AUC)., Results: A total of 976 patients were included in this study. VO patients showed significantly higher TyG values than non-VO patients in males (9.74 vs. 8.88) and females (9.59 vs. 9.01). The TyG index showed significant positive correlations with VAA, SAA, and VSR and negative correlations with VAD and SAD. The TyG index was an independent factor for VO in both males (odds ratio [OR] = 2.997) and females (OR = 2.233). The TyG index ranked second to body mass index (BMI) for predicting VO in male (AUC = 0.770) and female patients (AUC = 0.720). Patients with higher BMI and TyG index values showed a significantly higher risk of VO than the other patients. TyG-BMI, the combination index of TyG and BMI, showed significantly higher predictive power than BMI for VO in male patients (AUC = 0.879 and 0.835, respectively) but showed no significance when compared with BMI in female patients (AUC = 0.865 and 0.835, respectively)., Conclusions: . TyG is a comprehensive indicator of adipose volume, density, and distribution in patients with T2DM and is a valuable predictor for VO in combination with anthropometric indices, such as BMI., (© 2023. The Author(s).)

The current study evaluated the efficacy and safety of a denosumab biosimilar, QL1206 (60 mg), compared to placebo in postmenopausal Chinese women with osteoporosis and high fracture risk. At 31 study centers in China, a total of 455 postmenopausal women with osteoporosis and high fracture risk were randomly assigned to receive QL1206 (60 mg subcutaneously every 6 months) or placebo. From baseline to the 12-month follow-up, the participants who received QL1206 showed significantly increased bone mineral density (BMD) values (mean difference and 95% CI) in the lumbar spine: 4.780% (3.880%, 5.681%), total hip :3.930% (3.136%, 4.725%), femoral neck 2.733% (1.877%, 3.589%) and trochanter: 4.058% (2.791%, 5.325%) compared with the participants who received the placebo. In addition, QL1206 injection significantly decreased the serum levels of C-terminal crosslinked telopeptides of type 1 collagen (CTX): -77.352% (-87.080%, -66.844%), and N-terminal procollagen of type l collagen (P1NP): -50.867% (-57.184%, -45.217%) compared with the placebo over the period from baseline to 12 months. No new or unexpected adverse events were observed. We concluded that compared with placebo, QL1206 effectively increased the BMD of the lumbar spine, total hip, femoral neck and trochanter in postmenopausal Chinese women with osteoporosis and rapidly decreased bone turnover markers. This study demonstrated that QL1206 has beneficial effects on postmenopausal Chinese women with osteoporosis and high fracture risk., (© 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Purpose: Chronic low-grade systemic inflammation affects muscle protein metabolism. The dietary inflammatory index (DII®) is a tool designed to assess the inflammatory potential of the diet. The available data on the association between DII and sarcopenia are limited. We aimed to investigate the association of the DII with components of sarcopenia in individuals over 50 years of age., Methods: This cross-sectional study used the National Health and Nutrition Examination Survey (NHANES) 1999-2002 dataset. Body composition was measured, and isokinetic strength of the knee extensors (peak force) was evaluated. Low muscle mass and strength were defined using sex-specific thresholds. Energy-adjusted DII (E-DII™) scores were calculated using 24-h dietary recall data. Regression models were fit to evaluate the association between E-DII scores and low muscle mass and low muscle strength, alone and combined., Results: Mean age of study participants was 62.1 ± 9.5 years, and 138 participants (7.4%) belonged to the combination group of low muscle mass and low muscle strength. In multivariable-adjusted regression models, higher E-DII score was associated with lower appendicular skeletal muscle index (ASMI) (β =  - 0.03, P  < 0.001, P trend <0.001), and lower peak force (β =  -2.15, P  = 0.04, P trend = 0.01) and higher likelihood for these components combined (OR = 1.12, 95% CI 1.01-1.25, P = 0.03)., Conclusion: Higher E-DII score is associated with lower muscle mass and muscle strength, and increased likelihood for the combination of low muscle mass and low muscle strength in older adults. This has important implications for healthy aging., (© 2022. The Author(s).)

Objective: To develop a multiplex PCR method for a rapid detection of Y chromosome-specific sequences in patients with Turner syndrome., Methods: Nine genes were selected from various regions of the Y chromosome for designing the primers, which included SRY, TBL1Y, TSPY on the short arm of the Y chromosome, DDX3Y, HSFY1, RPS4Y2 and CDY1 on the long arm of Y chromosome and SHOX in the short arm and SPRY3 in the long arm of the pseudoautosomal region (PAR) of X and Y chromosomes. A multiplex PCR method for the nine genes in Y chromosome was established and optimized. The sensitivity was tested by using different amounts of genomic DNA. A total of 36 patients with Turner syndrome and a patient with male dwarfism with karyotype of 46, X, +mar were examined by the multiplex PCR method for the existence of materials from the Y chromosome., Results: The optimization results of the multiplex PCR reaction system (50 μL) showed that when the final concentration of upstream and downstream of each pair of primers was 0.1 μM, the multiplex PCR reaction of the 9 pairs of primers clearly amplified the target with the expected band size, and there was no non-specific amplification. The bands were clearly visible when the amount of genomic DNA in the multiple PCR reaction system was as low as 1 ng. By using the method, we have examined the 36 patients with Turner syndrome. One patient with Turner syndrome with karyotype of 45,X[40]/47XYY[21] amplified specific seven genes on Y chromosome, 35 patients with Turner syndrome amplified only two target genes SHOX and SPRY3, but not the other seven specific genes on the Y chromosome, which was in keeping with the clinical manifestations of such patients., Conclusion: This study established a multiplex PCR reaction system with nine genes, which can quickly and accurately screen Y chromosome materials in patients with Turner syndrome. It has the advantages of low cost, simple operation, high specificity and rapid turn-around time, and can be used to detect Turner syndrome patients with Y chromosome material in time. The method has provided a diagnostic basis for preventive gonad resection to prevent malignant gonadal tumors.

Background: Growth hormone is an effective therapy for growth hormone deficiency (GHD) but with a rather variable individual sensitivity. It is unclear whether rare genetic variants may contribute to the differential GH responsiveness., Methods: The present study aims to investigate the molecular etiology of GHD in Chinese children and adolescents and evaluate the impact of rare variants on therapeutic efficacies of GH., Results: Twenty-one rare heterozygous variant were classified as promising uncertain significance (n = 14), pathogenic (n = 5) or likely pathogenic (n = 2) for 21 of the 93 GHD patients. After GHD patients harboring these rare variants were excluded, inter-individual variability in the response to GH therapy obviously reduced and the negative correlation between initiation age of treatment and height SDS change became stronger in the group without rare variants. Among rare variants, 7 (likely) pathogenic variants (7.5%, 7/93) involved a total of 6 genes not only associated with GH secretion (PROKR2, LZTR1), but also growth plate chondrocyte signaling (ACAN, FBN1, COL9A1) or genetic syndromes (PTPN11)., Conclusions: Rare genetic variants are an important factor contributing to differential GH responsiveness and genetic testing should be factored into accurate diagnosis and treatment decision making in the future., Clinical Trial Registration Number: ChiCTR1900026510., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: A higher body mass index (BMI) is associated with shorter telomeres. The loss of muscle mass with aging is associated with adverse outcomes. The appendicular skeletal muscle index (ASMI) is currently used to quantify muscle mass., Objective: We investigated the association of the ASMI with leukocyte telomere length in adult Americans., Methods: This cross-sectional study used the National Health and Nutrition Examination Survey (NHANES) 1999-2002 dataset. Body composition was measured by dual-energy X-ray absorptiometry. Low muscle mass was defined using sex-specific thresholds of the appendicular skeletal muscle mass index (ASMI). The telomere-to-single-copy gene ratio (T/S ratio) was converted to base pairs. Generalized linear models were performed to evaluate the association of ASMI with telomere length., Results: In multivariable adjustment regression models, higher ASMI was associated with longer telomeres in US adults (β = 70.2, P < 0.001, P trend<0.001). In participants with preserved muscle mass, the ASMI was related to longer telomere length (β = 75.1, P < 0.001), but not significantly in low muscle mass participants (β = 68.7, P = 0.30). Further subgroup analysis by a combination of age groups and muscle mass status showed positive association with young-preserved muscle mass (β = 82.6, P < 0.001), old-preserved muscle mass (β = 44.4, P = 0.12), young-low muscle mass (β = 135.4, P = 0.20), and old-low muscle mass (β = 52.7, P = 0.55). Because each additional year of chronological age was associated with telomeres that were 15.3 base pairs shorter, on average, this would equate to 5.4 fewer years of biological aging (82.6 ÷ 15.3) in the young-preserved muscle mass participants., Conclusions: A higher ASMI is associated with longer telomeres. The prevention of skeletal muscle loss has the potential to delay telomere shortening and account for less biological aging., Competing Interests: Conflict of interest All authors declare no conflicts of interests., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The purpose of this study was to investigate the relationship between systolic blood pressure (SBP) and uric acid (UA) in patients with idiopathic short stature (ISS). The present study was a cross-sectional study. A total of 210 Chinese children and adolescents with ISS were included, and their anthropometrics and biochemical parameters were measured. Growth hormone peak levels were assessed after provocation tests with L-dopa and insulin. The univariate analysis results showed a significant positive association between UA and SBP levels (P < 0.001). Furthermore, a non-linear relationship was detected between UA and SBP. In multivariate piecewise linear regression, the inflection point of UA was 4.13 mg/dl (95% CI 3.28, 6.65; P = 0.03), the levels of SBP increased with the increase in UA when the UA level was >4.13 mg/dl (β 2.63, 95% CI: 0.94, 4.31; P = 0.002). However, we did not observe a significant relationship between UA and SBP when the UA level was <4.13 mg/dl (β -2.72, 95% CI -6.89, 1.45; P = 0.202). Our study found a nonlinear relationship between UA and SBP in Chinese children and adolescents with ISS and showed that SBP levels were associated positively with the rise of UA levels when the UA levels reached the inflection point.

Systemic lupus erythematosus (SLE), a worldwide autoimmune disease with high heritability, shows differences in prevalence, severity and age of onset among different ancestral groups. Previous genetic studies have focused more on European populations, which appear to be the least affected. Consequently, the genetic variations that underlie the commonalities, differences and treatment options in SLE among ancestral groups have not been well elucidated. To address this, we undertake a genome-wide association study, increasing the sample size of Chinese populations to the level of existing European studies. Thirty-eight novel SLE-associated loci and incomplete sharing of genetic architecture are identified. In addition to the human leukocyte antigen (HLA) region, nine disease loci show clear ancestral differences and implicate antibody production as a potential mechanism for differences in disease manifestation. Polygenic risk scores perform significantly better when trained on ancestry-matched data sets. These analyses help to reveal the genetic basis for disparities in SLE among ancestral groups.

Growth hormone (GH) secretion is related to many factors, such as weight and puberty, and the reproducibility of GH provocation tests is very poor. This study aimed to evaluate whether the triglyceride (TyG) index was associated with peak GH in children with short stature. This study included 1095 children with short stature divided into two groups based on peak GH level in GH provocation tests [GH deficiency (GHD) group = 733 children; non-GHD group = 362 children]. We found that the TyG index was significantly higher in the GHD group than in the non-GHD group (P < 0.001). A nonlinear relationship was detected between the TyG index and peak GH, whose point was 7.8. A significant negative association between the TyG index and peak GH was observed when the TyG index was greater than 7.8 (β - 2.61, 95% CI - 3.98, - 1.24; P < 0.001), whereas, the relationship between the TyG index and peak GH was not significant when the TyG index was lower than 7.8 (β 0.25, 95% CI - 1.68, 2.17; P = 0.799). There is a nonlinear relationship between the TyG index and peak GH, and a higher TyG index is associated with decreased peak GH in children with short stature.

Background: Elevated triglyceride (TG) levels are a biomarker for cardiovascular disease (CVD) risk. The correlation between serum uric acid (SUA) and TG concentrations in adults or obese children is well established. However, studies on SUA and TG in children with short stature are limited., Aim: To determine the relationship between SUA and TG levels in short children and adolescents., Method: This was a cross-sectional evaluation of a cohort of 1095 patients with short stature (720 males and 375 females). The related clinical characteristics, including anthropometric and biochemical parameters, were determined., Results: Smooth curve fitting, adjusted for potential confounders was performed, which indicated the existence of a non-linear relationship between these measures. Piecewise multivariate linear analysis revealed a significant positive relationship between SUA and TG at SUA concentrations over 7 mg/dL (β = 0.13, 95% CI: 0.05-0.22, P = 0.002) but no significant correlation at lower SUA levels (β = 0.01, 95% CI: 0.01-0.04, P = 0.799). Furthermore, a stratified analysis was performed to appraise changes in this relationship for different sexes and standard deviation levels of body mass index (BMI). The non-linear relationship remained consistent in males and females with BMI standard deviation scores (BMI SDS) ≥ 0, with inflection points of 6.71 mg/dL and 3.93 mg/dL, respectively. Within these two groups, SUA and TG levels showed a positive association when SUA levels were higher than the inflection point (β = 0.21, 95% CI: 0.11-0.31, P < 0.001 for males and β = 0.1, 95% CI: 0.03-0.17, P = 0.005 for females). However, a specific relationship was not observed at lower SUA levels. No significant relationships were found between SUA and TG levels in males and females with BMI SDS < 0., Conclusion: The present study identified the non-linear association of SUA and TG levels with short children and adolescents. This relationship was based on BMI status. This finding suggests that health status should be considered for short stature children with high SUA levels, especially in children with a high BMI standard deviation score.

Introduction: Insulin-like growth factor-I receptor (IGF1R) mediated survival signaling is a crucial mechanism for cellular endurance and a potential indicator of recuperation in deteriorating hearts., Objective: This study evaluates the impact of long-term exercise training in enhancing cardiac survival mechanism in D-galactose-induced toxicity associated aging rats., Methods: Forty-eight male SD-rats were segregated into 4 groups (n=9) and were named as control, exercise training groups, aging group and aging group with exercise training. Aging was induced by intraperitoneal (IP) D-galactose (150 mL/kg) injection for 8 weeks and for exercise training, the rats were left to swim in warm water for 60 min every day and 5 times/week. Western blotting of proteins from the left ventricles was performed to identify the modulations in the survival signaling. Tissue sections were analyzed to determine the extent of fibrosis and apoptosis., Results: Western-blot analysis performed on the excised left ventricles (LV) showed that proteins of the cardiac survival pathway including IGF1R and Akt and the pro-survival Bcl-2 showed significant decrease in the aging group, whereas the levels were restored in the aging rats subjected to exercise training. In addition, aging groups showed increased interstitial space and collagen accumulation. Further, TUNEL assay showed higher number of apoptotic cells in the LV of aging group, which was correlated with increase in the proteins involved in FAS-FADD-dependent apoptosis. However, these aging associated effects were ameliorated upon exercise training in the D-galactose-induced aging rats that showed elevated IGF1R/Akt signaling., Conclusion: The results suggest that IGFIR survival signaling cascadeis elevated in following long-term exercise training and thereby provide cardio-protective benefits in D-galactose induced aging rats., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Authors. Published by Elsevier B.V. on behalf of Cairo University.)

Background: Nurses play an important role in medical and health services but anxiety among those in this profession is widespread. Anxiety not only damages the physical and mental health of the individual, but also reduces the efficiency of their work and the quality of care, ultimately impacting on patient care. Therefore, it is necessary to elucidate the factors that lead to anxiety and explore measures to reduce the impact these factors have on nurses., Objective: The purpose of this study was to investigate the serial-multiple mediation of psychological capital (PsyCap), organizational commitment, job burnout, and anxiety among Chinese female nurses., Design: A cross-sectional stratified cluster sampling study., Participants: The study consisted of 1354 Chinese female nurses from two tertiary grade A hospitals in Heilongjiang Province, China., Methods: The Zung Self-Rating Anxiety Scale, the Chinese psychological capital questionnaire, the Chinese Maslach Burnout Inventory, and the Chinese Employee Organizational Commitment Questionnaire were used to gather data. Descriptive analysis, independent-samples T-test, one-way analysis of variance, Spearman correlation analyses, ordinary least-squares regression and the bootstrap method were used to analyze data., Results: The prevalence rate of anxiety among nurses was found to be 41.1%, and there were significant differences in anxiety symptoms in age (F = 15.54, p < 0.001) and marital status (F = 5.41, p < 0.001), but not education (F = 1.50, p = 0.224) among nurses. Overall, the serial-multiple mediation of organizational commitment and job burnout in the relationship between PsyCap and anxiety was found to be statistically significant., Conclusions: The results of the present study showed that positive PsyCap was sequentially associated with increased organizational commitment first, and then decreased job burnout, which was in turn related to reduced symptoms of anxiety among female nurses., (Copyright © 2018. Published by Elsevier Ltd.)

Introduction: Chronic hepatitis B (CHB) is still a public health problem and its mechanism remains unclear. In this study, we detect the skewness of T cell receptor beta chain variable gene (TCR Vβ) in peripheral blood lymphocytes (PBL) and the liver infiltrating lymphocytes (LIL) of patients with CHB; and hope to provide information for further research on the pathogenic mechanism of CHB., Material and Methods: Fifteen patients with CHB, ten healthy volunteers and three patients with liver cysts were recruited as the subjects. The usage of TCR Vβ of PBL and LIL were measured and compared; the associations of the TCR Vβ usage of PBL with some hematological indices, including human leukocyte antigen (HLA) alleles, percents of CD4+ and CD8+ T cells, sera levels of HBV-DNA and IFN-γ, were analyzed., Results: In PBL, Vβ12 and Vβ13.1 were the highest predominant usage genes which usage frequencies were all 46.7%; Vβ23 was the key limited usage gene (40.0%). In LIL, the mainly predominant and limited usage gene was Vβ13.1 (73.3%) and Vβ23 (46.7%), respectively. About half of the patients with CHB with HLA-DR9 or HLA-DR12 showed the predominant usage of Vβ5.2 or Vβ13.2. In patients with CHB, the percentage of CD4+ T cells was 33.41 ± 5.39 %, that of CD8+ T cells was 28.67 ± 6.77 %; the concentration of IFN-γ was 182.52 ± 44.16 pg/mL. Compared to the healthy controls, there were significant differences for these data (P &lt; 0.05). Neither ALT nor HBV-DNA was relative to the usage of TCR Vβ., Conclusions: PBL and LIL share the common sknewness of TCR Vβ genes, which probably relates to some hematological indices. However, the roles of such similarities and associations in the development of CHB need further study.

Objective: To evaluate the efficacy of internal application of Qigui Mixture (QM) and external application of Qigui Huoxue Lotion (QHL) in treating type 2 diabetic peripheral neuropathy (DNP) patients of qi-yin deficiency complicated phlegm-dampness blocking collaterals syndrome (QYD-PDBCS), and to primarily discuss its mechanism., Methods: Totally 62 DPN patients of QYD-PDBCS were randomly assigned to the treatment group (31 cases) and the control group (31 cases). All patients received routine comprehensive therapy. Patients in the control group took Mecobalamine Tablet, 500 microg each time, 3 times per day. Patients in the treatment group additionally took QM, 200 mL per day, twice daily. Besides, they had foot bath in QHL 10 - 15 min every evening for 3 months. The efficacy was assessed by Chinese medical symptom integrals and Toronto clinical scoring system (TCSS) before treatment, 2 and 3 months after treatment. The nerve conduction velocity was determined; the serum levels of total antioxidant capacity (T- AOC), malondialdehyde (MDA), and superoxide dismutase (SOD) were detected 2 and 3 months after treatment., Results: The total effective rates of Chinese medical symptom integrals and TCSS score were obviously higher in the treatment group than in the control group (P < 0.05). The nerve conduction velocity was significantly improved in the treatment group, when compared with before treatment (P < 0.01). There was statistical difference in the nerve conduction velocity difference of right median nerve motor branch, bilateral tibial nerve motor branches, bilateral common peroneal nerve motor branches, bilateral ulnar nerve sensory branches, and left tibial nerve sensory branch (P < 0.05). Compared with before treatment, serum levels of T-AOC and SOD significantly increased, and the level of MDA decreased significantly in the treatment group after 2 and 3 months of treatment (P < 0.01). But only the SOD level increased significantly in the control group (P < 0.01). There was no statistical difference in increased T-AOC level between the two groups after 2 months of treatment (P > 0.05), but there was statistical difference in increased SOD level and decreased MDA level (P < 0.05). There was statistical difference in increased T-AOC and SOD levels and decreased MDA level between the two groups after 3 months of treatment (P < 0.05). No adverse reaction occurred during the therapeutic course., Conclusions: The internal application of QM and external application of QHL combined with Mecobalamine in treating DPN was safe and effective, with more significant efficacy than using Mecobalamine alone. Its mechanism might be associated with resistance to oxidative stress.