BACKGROUND: Renal osteodystrophy (ROD) is a skeletal pathology associated with chronic kidney disease-mineral and bone disorder (CKD-MBD) that is characterized by aberrant bone mineralization and remodeling. ROD increases the risk of fracture and mortality in CKD patients. The underlying mechanisms of ROD remain elusive, partially due to the absence of an appropriate animal model. To address this gap, we established a stable mouse model of ROD using an optimized adenine-enriched diet and conducted exploratory analyses through ribonucleic acid sequencing (RNA-seq). METHODS: Eight-week-old male C57BL/6J mice were randomly allocated into three groups: control group ( n = 5), adenine and high-phosphate (HP) diet group ( n = 20), and the optimized adenine-containing diet group ( n = 20) for 12 weeks. We assessed the skeletal characteristics of model mice through blood biochemistry, microcomputed tomography (micro-CT), and bone histomorphometry. RNA-seq was utilized to profile gene expression changes of ROD. We elucidated the functions of differentially expressed genes (DEGs) using gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and gene set enrichment analysis (GSEA). DEGs were validated via quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: By the fifth week, adenine followed by an HP diet induced rapid weight loss and high mortality rates in the mouse group, precluding further model development. Mice with optimized adenine diet-induced ROD displayed significant abnormalities in serum creatinine and blood urea nitrogen levels, accompanied by pronounced hyperparathyroidism and hyperphosphatemia. The femur bone mineral density (BMD) of the model mice was lower than that of control mice, with substantial bone loss and cortical porosity. ROD mice exhibited substantial bone turnover with an increase in osteoblast and osteoclast markers. Transcriptomic profiling revealed 1907 genes with upregulated expression and 723 genes with downregulated expression in the femurs of ROD mice relative to those of control mice. Pathway analyses indicated significant enrichment of upregulated genes in the sphingolipid metabolism pathway. The significant upregulation of alkaline ceramidase 1 ( Acer1 ), alkaline ceramidase 2 ( Acer2 ), prosaposin-like 1 ( Psapl1 ), adenosine A1 receptor ( Adora1 ), and sphingosine-1-phosphate receptor 5 ( S1pr5 ) were successfully validated in mouse femurs by qRT-PCR. CONCLUSIONS Optimized adenine diet mouse model may be a valuable proxy for studying ROD. RNA-seq analysis revealed that the sphingolipid metabolism pathway is likely a key player in ROD pathogenesis, thereby providing new avenues for therapeutic intervention.
Animals ; Mice ; Chronic Kidney Disease-Mineral and Bone Disorder/genetics* ; Male ; Disease Models, Animal ; Mice, Inbred C57BL ; Sphingolipids/metabolism* ; Transcriptome/genetics* ; Signal Transduction/genetics* ; X-Ray Microtomography ; Adenine

OBJECTIVE: To compare the diagnostic accuracy of supraspinatus muscle outlet X-ray film, oblique sagittal multislice helical CT (MSCT), and oblique sagittal MRI in the diagnosis of subacromial impingement syndrome (SIS). METHODS: A retrospective analysis was conducted on the imaging data of 106 patients diagnosed with SIS between January 2023 and December 2024. The cohort consisted of 32 males and 74 females, with ages ranging from 43 to 70 years (mean, 60.19 years). All patients underwent supraspinatus muscle outlet X-ray film, MSCT, and MRI scans, with MSCT further subjected to three-dimensional reconstruction. Two experienced radiologists independently evaluated the acromion morphology in each imaging modality using the Bigliani classification system. Inter-observer reliability was assessed via Kappa statistics. The CT three-dimensional reconstructions were used as the "gold standard". The overall consistency, Kappa values, sensitivity, and specificity of the three imaging modalities were calculated. Receiver operating characteristic (ROC) curves were plotted, and the area under the curve (AUC) was computed. RESULTS: The inter-observer reliability for supraspinatus muscle outlet X-ray film, oblique sagittal MSCT, and oblique sagittal MRI was moderate, with Kappa values of 0.62, 0.63, and 0.55, respectively. When compared to the CT three-dimensional reconstructions as the "gold standard", the overall consistency was 88.7% (94/106), 62.3% (66/106), and 58.5% (62/106), respectively. The supraspinatus muscle outlet X-ray film showed excellent consistency (Kappa=0.77), whereas the consistency of MSCT and MRI was lower (Kappa=0.34 and 0.29, respectively). In terms of diagnostic sensitivity and specificity, the supraspinatus muscle outlet X-ray film outperformed oblique sagittal MSCT and oblique sagittal MRI in distinguishing various acromion types. ROC analysis demonstrated that the AUC for the supraspinatus muscle outlet X-ray film was consistently higher than for oblique sagittal MSCT and oblique sagittal MRI, with the highest diagnostic performance observed for type Ⅲ hooked acromion (AUC=0.939). CONCLUSION Supraspinatus muscle outlet X-ray film provides the highest diagnostic accuracy for acromion classification in SIS patients, particularly in identifying type Ⅲ hooked acromion, which is strongly associated with SIS. Given its superior sensitivity and consistency, it should be considered the primary screening tool. MSCT and MRI serve as valuable supplementary modalities for complex cases and preoperative evaluation.
Humans ; Middle Aged ; Male ; Female ; Shoulder Impingement Syndrome/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Retrospective Studies ; Aged ; Adult ; Imaging, Three-Dimensional ; Sensitivity and Specificity ; Tomography, Spiral Computed/methods* ; Multidetector Computed Tomography/methods* ; Reproducibility of Results

Objective To observe the influence of functional ankle instability(FAI)on balance and lower limb explosive power. Methods A total of 26 male FAI participants,13 bilateral(bilateral group)and 13 left(left group),who regularly en-gaged in high-intensity exercise,were recruited at Harbin Sport University in May,2024.Meanwhile,13 unin-jured male participants who engaged in high-intensity exercise were recruited as control group.They were mea-sured the moving area of the left foot,right foot and body center of gravity standing on feet with the eyes opened and closed;as well as the sway angle,confidence ellipse diameter(maximum and minimum)to circle area ratio,sway ratio and confidence ellipse standing on single foot,with Gaitview plantar pressure analysis system.They were also tested with Y-balance test(YBT),and were measured flight time and center of gravity height during jumps single leg left/right drift,stiffness and counter movement jump using Opto-jump Optical Measurement of Motor Quality. Results There were significant differences among the groups in swing angle,confidence ellipse diameter(maximum and minimum)to circle area ratio,swing ratio and confidence ellipse as left-leg stance with eyes closed(F>3.300,P<0.05),which was the least in the control group(P<0.05).Swing angle,swing ratio and confidence ellipse were also different among the groups as right-leg stance with eyes closed(F>4.404,P<0.05),and they were less in the control group than in the bilateral group(P<0.05),and less in the left group than in the bilateral group(P<0.05),except swing angle.There was a significant difference in YBT results(F>3.649,P<0.05),which was the least in the bilateral group(P<0.05).There were significant differences in the flight time and center of gravity height during counter movement jump(F>7.458,P<0.01),which was the least in the bilateral group(P<0.05). Conclusion FAI may impair the static balance as single-leg stance with eyes closed,dynamic balance and lower limb ex-plosive power.

[Objective]To investigate the effect and mechanism of Shuxuetong and its main component hirudin on the apoptosis of cerebellar granule neurons(CGNs)in Sprague-Dawley(SD)rats.[Methods]CGNs incubated in vitro for 7 days were divided into survival control group or 25 K group(cultured in medium containing 25 mmol/L KCL)and apopto-sis group or 5 K group(cultured in medium containing 5 mmol/L KCL).CGNs were separately treated with proportionally diluted and different concentrations of Shuxuetong(1/50,1/40,1/30,1/20 and 1/10)and the corresponding different con-centrations of hirudin(2,2.5,3.34,5 and 10 U/mL).Hoechst staining was performed to analyze the apoptosis.Western blot was used to detect the expression levels of Cleaved Caspase-3,Bim and VEGF.[Results]Hoechst staining showed that 5 K group had a higher apoptosis rate than 25 K group.In 25 K group,there was no significant change in the apoptosis rate between neurons treated with different concentrations of Shuxuetong and hirudin,but significant changes was found in 5 K group and the higher the concentration,the lower the apoptosis rate.Western blot results revealed that,compared with control neurons in 5 K group,Shuxuetong injection and hirudin treatments resulted in a decrease of Cleaved Caspase-3 and Bim expression,but an increase of VEGF protein.[Conclusions]Shuxuetong and its main component hirudin inhibits the apoptosis of CGNs through suppressing proapoptotic BH3-only protein Bim.

Objective:To analysis the molecular characteristics of chronic rhinosinusitis with nasal polyps (CRSwNP), to unravel its pathophysiological mechanisms, and to develop a prognostic model capable of effectively predicting postoperative recurrence.Methods:The data from three datasets (GSE198950, GSE179265, and GSE136825) were integrated, comprising 39 control cases, 16 cases of chronic rhinosinusitis without nasal polyps, and 89 cases of CRSwNP. Differential expression genes (DEGs) were identified based on adjusted P<0.05 and Log2FC>1. KEGG and GO enrichment analyses, as well as STRING node scoring, were conducted. Variable selection was performed using random forest and least absolute shrinkage and selection operator regression (LASSO), with key nodes identified through intersection analysis. Mann-Whitney U test was applied, and variables with P<0.05 were included in the model. A prognostic model for CRSwNP was constructed using logistic regression, externally validated using RNA-seq data, and evaluated with receiver operating characteristic (ROC) curve analysis to calculate the area under the curve (AUC). Results:This research illustrated both upregulated and downregulated DEGs in CRSwNP, activating pathways like neuroactive ligand-receptor interaction and IL-17 signaling, while inhibiting calcium signaling and gap junctions. Key nodes identified through random forest and LASSO, including G protein subunit γ4 ( U=3.00 P=0.028), Cholecystokinin ( U=0.50, P=0.006), Epidermal growth factor ( U=1.00 P=0.008), and Neurexin-1 ( U=0.00, P=0.004), showing statistical significance in external validation. The prognostic model, visualized in a line graph, exhibited high reliability (C-index=0.875,AUC=0.866). The ROC curve in external validation indicated its effectiveness in predicting postoperative recurrence (AUC=0.859). Conclusions:This study integrates multiple datasets on CRSwNP to provide a comprehensive description of its molecular features. The prognostic model, built upon key nodes identified through random forest and LASSO analyses, demonstrates high accuracy in both internal and external validations, thus providing robust support for the development of personalized treatment strategies for CRSwNP.

Objective:To explore the application value of histogram and texture feature analysis based on CT images in distinguishing long bone osteosarcoma (OS) from Ewing sarcoma (ES).Methods:A retrospective collection of 25 patients with long bone osteosarcoma and 25 patients with Ewing sarcoma confirmed by surgery and pathology in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Qilu Hospital of Shandong University and Nanjing Drum Tower Hospital, Nanjing University Medical School, from March 2018 to May 2023 was conducted. All patients were randomly divided into a training set (21 cases of OS and 19 cases of ES) and a validation set (4 cases of OS and 6 cases of ES) in an 8∶2 ratio. The region of interest (ROI) on CT images to extract texture feature parameters was manually sketched. Random forest and least absolute shrinkage and selection operator (LASSO) algorithm were used for feature screening. Logistic regression (LR), random forest (RF), support vector machine (SVM) and K-nearest neighbor (KNN) classifiers were used to establish models respectively. Receiver operating characteristic (ROC)curve was drawn and area under the curve (AUC) was calculated to evaluate the diagnostic efficiency of the four models.Results:A total of 100 texture parameters were extracted from CT images, and 8 feature parameters (maximum 3D diameter, 10th percentile, kurtosis, maximum pixel intensity value, inverse normalization, grayscale level variance, long range high grayscale emphasis, and low grayscale area emphasis) were obtained through screening. Four classifiers were used to establish models, and the AUC values of the four models (LR, RF, SVM, KNN) in the validation group were 0.92, 0.79, 0.83, and 0.73, respectively. LR and SVM classifier algorithm trains models had high diagnostic efficiency, with an accuracy of 90%, sensitivity of 83%, specificity of 100%, and AUC of 92% for the LR classifier validation set; the accuracy of SVM classifier validation set was 80%, sensitivity was 67%, specificity was 100%, and AUC was 83%.Conclusions:LR and SVM models have high value in distinguishing OS and ES.

Objective:To investigate the effects of compound Duzhong Jiangu Granules on joint function and gut microbiota in patients with Kashin-Beck disease.Methods:A single group pre- and post-experimental design was conducted, the patients with Kashin-Beck disease were selected as the subjects in Xunyi County, Xianyang City, Shaanxi Province; and treated with oral administration of compound Duzhong Jiangu Granules (12 g/bag, 1 bag/time, 3 times/day) for a period of 1 month. The improvement of joint function was evaluated using the joint dysfunction index scoring method before and after treatment. Morning stool samples of patients were collected and the changes in gut microbiota were analyzed before and after treatment using 16S rDNA sequencing technology.Results:A total of 87 patients with Kashin-Beck disease were included, including 44 males and 43 females; the age was (60.38 ± 7.12) years old, and the body mass index was (23.67 ± 3.59) kg/m 2. The comprehensive scores of joint dysfunction index for patients with Kashin-Beck disease before and after treatment were (7.27 ± 2.05) and (5.86 ± 2.01) points, respectively, and the difference was statistically significant ( t = 5.88, P < 0.001). The sequencing results of gut microbiota showed that there were statistically significant differences in the alpha diversity (chao1, observed species index) and beta diversity of gut microbiota in patients with Kashin-Beck disease before and after treatment ( Z = - 5.08, - 5.03, R = 0.09, P < 0.001). In the distribution of gut microbiota, Firmicutes was the dominant phylum, with relative abundances of 50.21% and 52.09% before and after treatment, respectively; the Bifidobacterium was the dominant bacterial genus, with relative abundances of 16.83% and 18.81% before and after treatment, respectively. At the genus level, a total of 17 gut microbiota genera were screened out, among which the relative abundances of Hafnia-Obesumbacterium, Gammaproteobacteria_unclassified, Acinetobacter, Pantoea, Leuconostoc, and Akkermanisia were significantly higher than before treatment ( Z = - 2.40, - 2.24, - 2.06, - 3.59, - 2.24, - 2.11, P < 0.05). The relative abundances of Dubosiella, Selenomonas, Anaeroplasma, Lachnospiraceae_ NK4A136_group, Rikenella, Prevotella, Megasphaera, Lactobacillus, Prevotella-9, Phascolarctobacterium, and Desulfovibrio were significantly lower than before treatment ( Z = - 9.38, - 2.61, - 2.18, - 8.43, - 2.45, - 2.46, - 2.49, - 7.29, - 2.29, - 2.55, - 2.08, P < 0.05). Conclusions:Compound Duzhong Jiangu Granules can effectively improve the joint function of patients with Kashin-Beck disease, and alter the diversity and richness of the gut microbiota community. It may reduce clinical symptoms in patients by regulating the structure of gut microbiota.

Background Long-term exposure to ambient fine particulate matter (PM_2.5) may increase the risk of diabetes, and a healthy diet can effectively control fasting blood glucose levels. However, it is unclear whether dietary factors have a moderating effect on the risk of diabetes associated with atmospheric PM_2.5 exposure. Objective To investigate the association between long-term exposure to PM_2.5 and diabetes in rural areas of Ningxia, and potential interaction of long-term exposure to atmospheric PM_2.5 and diet on diabetes. Methods The study subjects were selected from the baseline survey data of the China Northwest Cohort-Ningxia (CNC-NX) , a natural population cohort. A total of 13917 subjects were included, excluding participants with missing covariate information. We utilized the annual average ambient PM_2.5 concentration from 2014 to 2018 as the long-term exposure level. Logistic regression and multiple linear regression were employed to analyze the associations of long-term atmospheric PM_2.5 exposure with diabetes and fasting blood glucose levels. Stratification by frequency of vegetable consumption, frequency of fruit consumption, and salty taste was used to examine moderating effects on the diabetes risk associated with atmospheric PM_2.5 exposure. Results The mean age of the 13917 subjects was (56.8±10.0) years, and the prevalence of diabetes was 9.8%. Between 2014 and 2018, the average annual concentration of PM_2.5 was (38.10±4.67) μg·m⁻³. The risk (OR) of diabetes was 1.018 (95%CI: 1.005, 1.032) and the fasting blood glucose was increased by 0.011 (95%CI: 0.004, 0.017) mmol·L⁻¹ for each 1 μg·m⁻³ increase in PM_2.5 concentration. Compared to those who consumed vegetables < 1 time per week, individuals who consume vegetables 1-3 times per week and ≥4 times per week had a reduced risk of developing diabetes by 27.1% (OR=0.729, 95%CI: 0.594, 0.893) and 16.8% (OR=0.832, 95%CI: 0.715, 0.971) respectively. Similarly, when compared to those who consumed fruits <1 time per week, individuals who consumed fruits 1-3 times per week and ≥4 times per week exhibited a reduced risk of diabetes by 16.4% (OR=0.836, 95%CI: 0.702, 0.998) and 18.2% (OR=0.818, 95%CI: 0.700, 0.959) respectively. Fasting blood glucose decreased by 0.202 (95%CI: -0.304, -0.101) mmol·L⁻¹ in participants who ate vegetables 1-3 times per week. The effect of salty taste on diabetes and fasting blood glucose was not significant. The results of stratified analysis by dietary factors and PM_2.5 concentration showed that the risks of diabetes were increased in the low PM_2.5 pollution-low vegetable intake frequency group and the high PM_2.5 pollution-low vegetable intake frequency group compared with the low PM_2.5 pollution-high vegetable intake frequency group, with OR values of 3.987 (95%CI: 2.943, 5.371) and 1.433 (95%CI: 1.143, 1.796) respectively. The risk of diabetes was 50.1% higher in participants with high PM_2.5 pollution and low fruit intake frequency than in participants with low PM_2.5 pollution and high fruit intake frequency (OR=1.501, 95%CI: 1.171, 1.926). No interaction was found between salty taste and PM_2.5 on diabetes. Conclusion Long-term exposure to ambient PM_2.5 is associated with an increased fasting blood glucose and an elevated risk of diabetes in rural Ningxia population. Increasing the frequency of weekly consumption of vegetables or fruits may have a certain protective effect against diabetes occurrence, as well as a moderating effect on diabetes and fasting blood glucose levels associated with long-term exposure to atmospheric PM_2.5.

Background The impact of atmospheric fine particulate matter (PM_2.5) and ozone (O₃) on the mortality of circulatory system diseases cannot be ignored. However, whether the interaction between PM_2.5 and O₃ can affect population health is rarely reported and requires study. Objective To investigate the individual and interactive impacts of atmospheric PM_2.5 and O₃ on the mortality of circulatory system diseases in the population of Ningxia region. Methods The data of 119647 deaths due to circulatory system diseases, daily average concentrations of atmospheric pollutants, and meteorological data in Ningxia from 2013 to 2020 were retrieved. PM_2.5 was divided into low, medium, and high concentrations according to the primary and secondary national limits (35 and 75 μg·m⁻³) of the Ambient air quality standards. Similarly, O₃ was divided into low, medium, and high concentrations according to the national limits (100 and 160 μg·m⁻³). Using a generalized additive mixed model based on quasi Poisson distribution, the impacts of atmospheric PM_2.5 and O₃ as well as their interaction on the mortality of circulatory system diseases were analyzed using the population data of Ningxia region. Results During the target period, males and the ≥ 65 year group accounted for larger proportions of deaths due to circulatory system diseases (55.47% and 79.87% respectively). The daily average concentration of PM_2.5 (40.25 μg·m⁻³) exceeded the national primary limit. In the single pollution model, the highest cumulative lag effects for mortality from circulatory system diseases were PM_2.5 exposure over previous 1 d (lag01) and O₃ exposure for previous 2 d (lag02), and their excess risk (ER) values were 1.03% (95%CI: 0.67%, 1.40%) and 1.02% (95%CI: 0.57%, 1.50%), respectively. The results of concentration stratification analysis showed that the most significant risks of death from circulatory system diseases [ER (95%CI): 1.12% (0.32%, 1.92%) and 0.95% (0.13%, 1.79%) respectively] were found at medium PM_2.5 and O₃ concentrations. The interaction analysis revealed that under, a synergistic effect on the risk of death from circulatory system diseases was identified (relative excess risk due to interaction=3.08%, attributable proportion of interaction=2.90%, synergy index=1.89) when considering the coexistence of PM_2.5 and O₃ above the primary limit. As the concentrations of PM_2.5 and O₃ increased, the synergistic effect increased the risk of death from circulatory system diseases in the general population, men, women, and the ≥ 65 years group. Conclusion Both atmospheric PM_2.5 and O₃ can increase the risk of death from circulatory system diseases, and the two pollutants have a synergistic effect on the risk of death from circulatory system diseases.

BACKGROUND:At present,a large number of studies have found that Liuwei Dihuang Pill can be used to treat osteoporosis,but there are few related studies on the differentiation and mineralization of osteoblasts induced by wear particles using Liuwei Dihuang Pill. OBJECTIVE:To investigate the positive effect of different concentrations of Liuwei Dihuang Pill-containing serum on titanium particle-induced mouse MC3T3-E1 osteoblast in vitro osteolysis model. METHODS:Drug-containing serum was extracted after oral administration of Liuwei Dihuang Pill.The best concentration of Liuwei Dihuang Pill-containing serum and titanium particles on the viability of MC3T3-E1 cells was screened.MC3T3-E1 cells were divided into three groups.The blank group was given osteoblastic differentiation culture.The model group was given titanium particles(5 μg/mL)ossification culture.The drug-containing serum group was given titanium particles(5 μg/mL)+ Liuwei Dihuang Pill-containing serum(10%,15%and 20%doses).Osteoblast viability was detected by CCK-8 assay.Cell alkaline phosphatase activity was detected by alkaline phosphatase staining.Cell mineralization was detected by silver nitrate(Von Kossa)and alizarin red staining.Expression levels of bone differentiation-related genes Runx-2,Osterix,Ocn,Axin,Alp,and Opn were detected by qRT-PCR.Wnt/β-catenin signaling pathways β-catenin,p-GSK-3β,GSK-3β,Runx2 and Osterix protein expression levels were detected by western blot assay. RESULTS AND CONCLUSION:(1)Liuwei Dihuang Pill-containing serum culture reversed the decrease in alkaline phosphatase activity of MC3T3E-1 cells induced by titanium particles,increased the alizarin red staining and calcification of MC3T3E-1 cells,increased the expression of osteogenesis-related genes in MC3T3E-1 cells,and increased the expression of proteins related to the Wnt/β-catenin signaling pathway.(2)These findings indicate that Liuwei Dihuang Pill-containing serum can reverse the inhibitory effect of titanium particles on the differentiation and mineralization of osteoblasts,upregulate the expression of osteogenesis-related genes,and its mechanism is related to the regulation of Wnt/β-catenin signaling pathway,suggesting that Liuwei Dihuang Pill is expected to become an effective drug for preventing aseptic loosening of artificial joints.