Associations between co-exposure to per- and polyfluoroalkyl substances and organophosphate esters and erythrogram in Chinese adults.

Erythrogram, despite its prevalent use in assessing red blood cell (RBC) disorders and can be utilized to evaluate various diseases, still lacks evidence supporting the effects of per- and polyfluoroalkyl substances (PFASs) and organophosphate esters (OPEs) on it. A cross-sectional study involving 467 adults from Shijiazhuang, China was conducted to assess the associations between 12 PFASs and 11 OPEs and the erythrogram (8 indicators related to RBC). Three models, including multiple linear regression (MLR), sparse partial least squares regression, and Bayesian kernel machine regression (BKMR) were employed to evaluate both the individual and joint effects of PFASs and OPEs on the erythrogram. Perfluorohexane sulfonic acid (PFHxS) showed the strongest association with HGB (3.68%, 95% CI: 2.29%, 5.10%) when doubling among PFASs in MLR models. BKMR indicated that PFASs were more strongly associated with the erythrogram than OPEs, as evidenced by higher group posterior inclusion probabilities (PIPs) for PFASs. Within hemoglobin and hematocrit, PFHxS emerged as the most significant component (conditional PIP = 1.0 for both). Collectively, our study emphasizes the joint effect of PFASs and OPEs on the erythrogram and identified PFASs, particularly PFHxS, as the pivotal contributors to the erythrogram. Nonetheless, further investigations are warranted to elucidate the underlying mechanisms.

Simulating liquefaction-induced resuspension flux in a sediment transport model.

Wave-induced liquefaction is a geological hazard under the action of cyclic wave load on seabed. Liquefaction influences the suspended sediment concentration (SSC), which is essential for sediment dynamics and marine water quality. Till now, the identification of liquefaction state and the effect of liquefaction on SSC have not been sufficiently accounted for in the sediment model. In this study, we introduced a method for simulating the liquefaction-induced resuspension flux into an ocean model. We then simulated a storm north of the Yellow River Delta, China, and validated the results using observational data, including significant wave heights, water levels, excess pore water pressures, and SSCs. The liquefaction areas were mainly distributed in coastal zones with water depths less than 12 m, and the simulated maximum potential soil liquefaction depth was 1.39 m. The liquefaction-induced SSC was separated from the total SSC of both liquefaction- and shear-induced SSCs by the model, yielding a maximum liquefaction-induced SSC of 1.07 kg·m-3. The simulated maximum proportion of liquefaction-induced SSC was 26.2% in regions with water depths of 6-12 m, with a maximum significant wave height of 3.4 m along the 12 m depth contour. The erosion zone at water depths of 8-12 m was reproduced by the model. Within 52.5 h of the storm, the maximum erosion thickness along the 10 m depth contour was enhanced by 33.9%. The model is applicable in the prediction of liquefaction, and provides a new method to simulate the SSC and seabed erosion influenced by liquefaction. Model results show that liquefaction has significant effects on SSC and seabed erosion in the coastal area with depth of 6-12 m. The validity of this method is confined to certain conditions, including a fully saturated seabed exhibiting homogeneity and isotropic properties, small liquefaction depth, residual liquefaction dominating the development of pore pressures, no influence by structures, and the sediment composed of silt and mud that experiences frequent wave-induced liquefaction.

Comparative effect of skeletal stem cells versus bone marrow mesenchymal stem cells on rotator cuff tendon-bone healing.

Background: Bone marrow mesenchymal stem cells (BMSCs) have immense potential in applications for the enhancement of tendon-bone (T-B) healing. Recently, it has been well-reported that skeletal stem cells (SSCs) could induce bone and cartilage regeneration. Therefore, SSCs represent a promising choice for cell-based therapies to improve T-B healing. In this study, we aimed to compare the therapeutic potential of SSCs and BMSCs for tendon-bone healing. Methods: SSCs and BMSCs were isolated by flow cytometry, and their proliferation ability was measured by CCK-8 assay. The osteogenic, chondrogenic, and adipogenic gene expression in cells was detected by quantitative real-time polymerase chain reaction (qRT-PCR). C57BL/6 mice underwent unilateral supraspinatus tendon detachment and repair, and the mice were then randomly allocated to 4 groups: control group (tendon-bone interface without any treatment), hydrogel group (administration of blank hydrogel into the tendon-bone interface), hydrogel + BMSCs group (administration of hydrogel with BMSCs into the tendon-bone interface), and hydrogel + SSCs group (administration of hydrogel with SSCs into the tendon-bone interface). Histological staining, Micro-computed tomography (Micro-CT) scanning, biomechanical testing, and qRT-PCR were performed to assay T-B healing at 4 and 8 weeks after surgery. Results: SSCs showed more cell proportion, exhibited stronger multiplication capacity, and expressed higher osteogenic and chondrogenic markers and lower adipogenic markers than BMSCs. In vivo assay, the SSCs group showed a better-maturated interface which was characterized by richer chondrocytes and more proteoglycan deposition, as well as more newly formed bone at the healing site and increased mechanical properties when compared to other there groups. qRT-PCR analysis revealed that the healing interface in the SSCs group expressed more transcription factors essential for osteogenesis and chondrogenesis than the interfaces in the other groups. Conclusions: Overall, the results demonstrated the superior therapeutic potential of SSCs over BMSCs in tendon-bone healing. The translational potential of this article: This current study provides valuable insights that SSCs may be a more effective cell therapy for enhancing T-B healing compared to BMSCs.

Gender-Specific Risk Factors for Asymmetric Bone Density in Adult Degenerative Lumbar Scoliosis: A Retrospective Cohort Analysis.

BACKGROUND This study aimed to evaluate the performance of Hounsfield Unit (HU) value on the vertebral bone mineral density associated with adult degenerative lumbar scoliosis (ADLS) and to compare the HU and coronal height changes of the lumbar spine on the concave and convex sides. The secondary aim was to investigate the risk factors for increased asymmetric ratio of HU (ARH) by concave-to-convex. MATERIAL AND METHODS A total of 74 patients aged ≥50 years were retrospectively reviewed. The height and the HU values of the region of interest were measured and compared. Multiple linear regression and gender-stratified analyses were performed to explore risk factors. Restricted cubic spline (RCS) was used to visually assess the dose-effect relationship between the Cobb angle and ARH. RESULTS The heights on the concave sides were significantly lower while HU values were significantly higher than that of the convex side. Cobb angle (95% CI: 0.001 to 0.009, P=0.034) was positively correlated with the increased ARH, while apex orientation to the right (95% CI: -0.152 to -0.013, P=0.022) was negatively associated. Gender-stratified analyses showed age and apex vertebrae location are 2 additional risk factors in male patients but not in female patients. Cobb angle was identified by RCS as a risk factor both in males and females and the inflection points were 15 and 17.5, respectively. CONCLUSIONS HU values on the concave side are significantly higher than on the convex side, showing the asymmetrical bone mass distribution of ADLS patients. Several gender-related risk factors for increased ARH have been identified.

The role of taurine through endoplasmic reticulum in physiology and pathology.

Taurine is a sulfur-containing amino acid found in many cell organelles that plays a wide range of biological roles, including bile salt production, osmoregulation, oxidative stress reduction, and neuromodulation. Taurine treatments have also been shown to ameliorate the onset and development of many diseases, including hypertension, fatty liver, neurodegenerative diseases and ischemia-reperfusion injury, by exerting antioxidant, anti-inflammatory, and antiapoptotic effects. The endoplasmic reticulum (ER) is a dynamic organelle involved in a wide range of cellular functions, including lipid metabolism, calcium storage and protein stabilization. Under stress, the disruption of the ER environment leads to the accumulation of misfolded proteins and a characteristic stress response called the unfolded protein response (UPR). The UPR protects cells from stress and helps to restore cellular homeostasis, but its activation promotes cell death under prolonged ER stress. Recent studies have shown that ER stress is closely related to the onset and development of many diseases. This article reviews the beneficial effects and related mechanisms of taurine by regulating the ER in different physiological and pathological states, with the aim of providing a reference for further research and clinical applications.

Well-type thick-shell quantum dots combined with double hole transport layers device structure assisted realization of high-performance quantum dot light-emitting diodes.

Quantum dot (QD) light-emitting diodes (QLEDs) are promising for next-generation lighting and displays. Considering the optimization design of both the QD and device structure is expected to improve the QLED's performance significantly but has rarely been reported. Here, we use the thick-shell QDs combined with a dual-hole transport layer device structure to construct a high-efficiency QLED. The optimized thick-shell QDs with CdS/CdSe/CdS/ZnS seed/spherical quantum well/shell/shell geometry exhibit a high photoluminescence quantum yield of 96% at a shell thickness of 5.9 nm. The intermediate emissive CdSe layer with coherent strain ensures defect-free growth of the thick CdS and ZnS outer shells. Based on the orthogonal solvents assisted Poly-TPD&PVK dual-hole transport layer device architecture, the champion QLED achieved a maximum external quantum efficiency of 22.5% and a maximum luminance of 259955 cd m-2, which are 1.6 and 3.7 times that of thin-shell QDs based devices with single hole transport layer, respectively. Our study provides a feasible idea for further improving the performance of QLED devices.

Predictive value of different site-specific MRI-based assessments of bone quality for cage subsidence among patients undergoing oblique lumbar interbody fusion.

OBJECTIVE: The aim of this study was to investigate the predictive value of different site-specific MRI-based assessments of bone quality for cage subsidence among patients undergoing oblique lumbar interbody fusion (OLIF) with or without posterior internal fixation. METHODS: The authors retrospectively reviewed the records of patients who underwent OLIF between 2017 and 2022. Endplate bone quality (EBQ), mean vertebral bone quality (MVBQ), and vertebral bone quality (VBQ) scores were measured using preoperative non-contrast-enhanced T1-weighted MRI of the lumbar spine. Logistic regression analysis was used to identify factors associated with cage subsidence. Receiver operating characteristic curve analysis was used to evaluate the value of different site-specific MRI-based assessments of bone quality in predicting cage subsidence. RESULTS: Of the 124 patients who underwent OLIF, subsidence was found in 42 (33.9%). The VBQ, MVBQ, and EBQ scores were higher in the subsidence group than in the no-subsidence group. In the stand-alone OLIF (SA-OLIF) group, logistic regression analysis showed that the EBQ score was significantly associated with subsidence (OR 13.656, 95% CI 2.561-72.806; p = 0.002). Furthermore, the areas under the curve (AUCs) for using the VBQ, MVBQ, and EBQ scores and T-score to predict cage subsidence were 0.684, 0.683, 0.745, and 0.685, respectively. In the OLIF with posterior internal fixation (OLIF-PF) group, logistic regression analysis showed that the MVBQ score was significantly associated with subsidence (OR 8.301, 95% CI 2.064-33.385; p = 0.003). The AUCs for using the VBQ score, MVBQ score, and T-score to predict cage subsidence were 0.757, 0.774, and 0.685, respectively. CONCLUSIONS: There are significant differences in the predictive value of different site-specific bone quality assessments for cage subsidence among patients undergoing OLIF. For SA-OLIF, the EBQ score is recommended, while for OLIF-PF, the VBQ score is preferable.

The magnetic resonance imaging-based vertebral bone quality scoring system: A novel method to evaluate endplate changes in patients with primary single-level disk herniation and Modic changes.

OBJECTIVES: This study aimed to investigate differences in vertebral fat distribution and bone density between patients with and without Modic changes (MCs) using a magnetic resonance imaging (MRI)-based vertebral bone quality (VBQ) scoring system. PATIENTS AND METHODS: In this retrospective study, 189 patients (95 males, 94 females; mean age: 54±2.2 years; range, 18 to 82 years) with primary single-level disk herniation were reviewed between June 2021 and June 2022. The patients were divided into the MC group (n=99) and the non-MC (NMC) group (n=90). The subcutaneous fat tissue thickness and bone mineral density were determined. The system consisted of two scores: the VBQ score, which reflected the fatty infiltration within the vertebral body, and the endplate bone quality (EBQ) score, which reflected the signal intensity (SI) of the upper and lower endplates. The EBQ score is a novel measurement that we introduced in this study. The VBQ and EBQ were measured and scored using MRI scans. The mean SI of the upper and lower endplates (endplate SI)/the bone marrow SI (marrow SI) was measured. RESULTS: There was a considerable difference in subcutaneous fat tissue thickness between the MC and NMC groups (1.40 vs. 1.16 cm, p=0.01). The EBQ scores of the L4 and L5 vertebrae and endplate SI/marrow SI of all vertebral body levels were significantly higher in the MC group. CONCLUSION: The occurrence of MCs in the lumbar spine may be associated with abnormal fat distribution. The distribution of vertebral fat in patients with MCs is distributed earlier in the upper and lower endplates of the vertebral body, and this trend is not observed in patients without MC. The thickness of subcutaneous fat tissue is a key factor in the occurrence of MCs.

Efficacy and Safety of High-Viscosity Bone Cement in Percutaneous Vertebroplasty for Kummell's Disease.

Background: To analyze and evaluate the clinical outcomes of using high-viscosity bone cement compared to low-viscosity bone cement in percutaneous vertebroplasty (PVP) for treatment of Kummell's disease. Methods: From July 2017 to July 2019, 68 Kummell's disease patients who underwent PVP were chosen and separated into 2 groups: H group (n = 34), were treated with high-viscosity bone cement and L group (n = 34), treated with low-viscosity bone cement during treatment. The operation time, number of fluoroscopy tests done, and amount of bone cement perfusion were recorded for both groups. Clinical outcomes were compared, by measuring their Visual Analog Scale (VAS), Oswestry Disability Index (ODI), Kyphosis Cobb's angle, vertebral height compression rate, and other complications. Results: High-viscosity group showed less operation time and reduced number of fluoroscopy tests than the low-viscosity group (P < 0.05). When compared to preoperative period, both groups' VAS and ODI scores were significantly reduced at 1 day and 1 year postoperatively (P < 0.05). The vertebral height compression rate and Cobb's angle were significantly lower (P < 0.05) in both groups after surgery compared with those before surgery (P < 0.05). The cement leakage rate in group H was 26.5%, which was significantly lower than that in group L, which was 61.8% (P < 0.05). Conclusions: High-viscosity and low-viscosity bone cement in PVP have similar clinical efficacy in reducing pain in patients during the treatment, but in contrast, high-viscosity bone cement shortens the operative time, reduces number of fluoroscopy views and vertebral cement leakage and improves surgical safety.

Systematic evaluation of vertebral bone quality score as an opportunistic screening method for BMD in spine surgery patients.

PURPOSE: This study aimed to evaluate and compare the predictive value of vertebral bone quality (VBQ) score for low BMD and osteoporosis. Furthermore, we sought to enhance diagnostic effectiveness by integrating VBQ with easily accessible patient-specific factors. METHODS: We retrospectively analyzed data from 180 patients. VBQ was obtained by preoperative MRI. Low BMD was classified as meeting the standards for either osteopenia or osteoporosis. The receiver operating characteristic curve analysis and multivariate logistic regression were used to detect the ability of variables to assess BMD. The z-test was used to compare the area under the curves of different variables. RESULTS: VBQ was more effective in identifying low BMD than osteoporosis (AUC, 0.768 vs. 0.613, p = 0.02). Elevated VBQ (OR 6.912, 95% CI 2.72-17.6) and low BMI (0.858, 0.76-0.97) were risk factors for low BMD, while the risk factor for osteoporosis was age (1.067, 1.02-1.12), not VBQ. ROC analysis showed that AUCs were 0.613 for VBQ and 0.665 for age when screening for osteoporosis. The combined variable of VBQ, sex, age, and BMI obtained by logistic regression significantly improved the efficacy of BMD screening, with an AUC of 0.824 for low BMD and 0.733 for osteoporosis. CONCLUSION: VBQ is better at detecting low BMD than identifying osteoporosis. The ability of VBQ to predict osteoporosis is limited, and a similar diagnostic efficacy can be achieved with age. Incorporating VBQ alongside demographic data enhances the efficiency of BMD assessment. With the development of artificial intelligence in medicine, this simple method is promising.

Dysregulation of sphingolipid metabolism in pain.

Pain is a clinical condition that is currently of great concern and is often caused by tissue or nerve damage or occurs as a concomitant symptom of a variety of diseases such as cancer. Severe pain seriously affects the functional status of the body. However, existing pain management programs are not fully satisfactory. Therefore, there is a need to delve deeper into the pathological mechanisms underlying pain generation and to find new targets for drug therapy. Sphingolipids (SLs), as a major component of the bilayer structure of eukaryotic cell membranes, also have powerful signal transduction functions. Sphingolipids are abundant, and their intracellular metabolism constitutes a huge network. Sphingolipids and their various metabolites play significant roles in cell proliferation, differentiation, apoptosis, etc., and have powerful biological activities. The molecules related to sphingolipid metabolism, mainly the core molecule ceramide and the downstream metabolism molecule sphingosine-1-phosphate (S1P), are involved in the specific mechanisms of neurological disorders as well as the onset and progression of various types of pain, and are closely related to a variety of pain-related diseases. Therefore, sphingolipid metabolism can be the focus of research on pain regulation and provide new drug targets and ideas for pain.

Finite difference-embedded UNet for solving transcranial ultrasound frequency-domain wavefield.

Transcranial ultrasound imaging assumes a growing significance in the detection and monitoring of intracranial lesions and cerebral blood flow. Accurate solution of partial differential equation (PDE) is one of the prerequisites for obtaining transcranial ultrasound wavefields. Grid-based numerical solvers such as finite difference (FD) and finite element methods have limitations including high computational costs and discretization errors. Purely data-driven methods have relatively high demands on training datasets. The fact that physics-informed neural network can only target the same model limits its application. In addition, compared to time-domain approaches, frequency-domain solutions offer advantages of reducing computational complexity and enabling stable and accurate inversions. Therefore, we introduce a framework called FD-embedded UNet (FEUNet) for solving frequency-domain transcranial ultrasound wavefields. The PDE error is calculated using the optimal 9-point FD operator, and it is integrated with the data-driven error to jointly guide the network iterations. We showcase the effectiveness of this approach through experiments involving idealized skull and brain models. FEUNet demonstrates versatility in handling various input scenarios and excels in enhancing prediction accuracy, especially with limited datasets and noisy information. Finally, we provide an overview of the advantages, limitations, and potential avenues for future research in this study.

Utility of auto fluorescence-guided biopsy in suspected lung cancer patients with bronchial mucosal lesions.

BACKGROUND: Bronchoscopy is currently the most common technique for lung cancer diagnosis. Patients suspected of malignancy often undergo bronchoscopic examination, and biopsy is routinely used in patients with visible bronchial lesions. However, it is difficult to differentially diagnose lung cancer in patients with bronchial mucosal lesions. Thus, this study was conducted to investigate the utility of fluorescence-guided biopsy in suspected lung cancer patients with bronchial mucosal lesions. METHODS: We conducted a retrospective study in a single screening center to assess the sensitivity and specificity of fluorescence-guided biopsy compared with white light bronchoscopy (WLB) in patients with bronchial mucosal lesions. RESULTS: A total of 301 patients with bronchial mucosal lesions were enrolled in this study. The sensitivity for patients with fluorescence-guided biopsy was 60.3 % (95 % confidence interval [CI]: 53.1 %-67.1 %), which was higher than that of patients with WLB alone (45.2 %, 95 % CI: 38.2-52.4 %) (P = 0.0026). Additionally, compared with the WLB group, the fluorescence -guided biopsy group was found to have a significantly higher specificity (100 %, 95 % CI: 95.5-100 % versus 69.6 %, 95 % CI: 59.6-78.1 %), positive predictive value (100 %, 95 % CI: 96.1-100 % versus 74.3 %, 95 % CI: 65.5-81.7 %) and negative predictive value (56.3 %, 95 % CI: 48.8-63.6 % versus 39.4 %, 95 % CI: 32.3-47.0 %). CONCLUSION: Fluorescence-guided biopsy can serve as an important adjunct to WLB for the differential diagnosis of lung cancer in patients with bronchial mucosal lesions.

The Canal Bone Ratio: A Novel Indicator for Opportunistic Osteoporosis Screening in Adult Spinal Deformity Patients through Radiographs.

STUDY DESIGN: Retrospective diagnostic study. OBJECTIVES: To evaluate the utility of quantitative assessment of bone density using proximal femoral morphological parameters based on full-spine X-rays. SUMMARY OF BACKGROUND DATA: CT and MRI are commonly utilized methods for opportunistic assessment of bone density. However, there is currently a lack of means to quantitatively assess bone density in adult spinal deformity (ASD) patients through radiographs. METHODS: Data collection involved medical records of ASD patients treated at our hospital. Patients were categorized into osteoporotic and non-osteoporotic groups based on DEXA T-scores. Demographic information, radiographic parameters (canal bone ratio, CBR; cortical bone thickness, CBT), Hounsfield units (HUs) and vertebral body quality (VBQ) score were compared. Pearson correlation analysis was conducted to assess the correlation between CBR, CBT, and T-scores. Multiple linear regression analysis identified independent predictors of bone density T-scores. Receiver operating characteristic (ROC) curves and area under the curve (AUC) calculations were performed to investigate the predictive performance for osteoporosis. RESULTS: A total of 102 patients were included, with the osteoporotic group showing larger CBR and smaller CBT compared to the non-osteoporotic group. Proximal femoral morphological parameters exhibited the strongest correlation with total hip T-scores. Advanced age (ß=-0.028, 95%CI=-0.054 to -0.002, P=0.032), low BMI (ß=0.07, 95%CI=0.014 to 0.126, P=0.015), and high CBR (ß=-7.772, 95%CI=-10.519 to -5.025, P<0.001) were identified as independent predictors of low bone density. ROC analysis demonstrated that CBR had a similar osteoporosis screening capability as HUs, followed by CBT and VBQ score. CONCLUSION: The utilization of CBR from full-spine X-rays is a simple and effective osteoporosis screening indicator for ASD patients, facilitating bone density assessments by spine surgeons for all attending patients.

Based on neural network cascade abnormal texture information dissemination of classification of patients with schizophrenia and depression.

This study used MRI brain image segmentation to identify novel magnetic resonance imaging (MRI) biomarkers to distinguish patients with schizophrenia (SCZ), major depressive disorder (MD), and healthy control (HC). Brain texture measurements, including entropy and contrast, were calculated to capture variability in adjacent MRI voxel intensity. These measures are then applied to group classification in deep learning techniques and combined with hierarchical correlations to locate results. Texture feature maps were extracted from segmented brain MRI scans of 141 patients with schizophrenia (SCZ), 103 patients with major depressive disorder (MD) and 238 healthy controls (HC). Gray scale coassociation matrix (GLCM) is a monomer matrix calculated in a voxel cube. Deep learning methods were evaluated to determine the application capability of texture feature mapping in binary classification (SCZ vs. HC, MD vs. HC, SCZ vs. MD). The method is implemented by repeated nesting and cross-validation for feature selection. Regions that show the highest correlation (positive or negative). In this study, the authors successfully classified SCZ, MD and HC. This suggests that texture analysis can be used as an effective feature extraction method to distinguish different disease states. Compared with other methods, texture analysis can capture richer image information and improve classification accuracy in some cases. The classification accuracy of SCZ and HC, MD and HC, SCZ and MD reached 84.6%, 86.4% and 76.21%, respectively. Among them, SCZ and HC are the most significant features with high sensitivity and specificity.

Assessing peptic ulcer risk with the HAMPROW score in the general Chinese population.

The timely identification of individuals at high risk for peptic ulcers (PUs) is vital in preventing gastrointestinal bleeding after antiplatelet therapy. This study was designed to determine PU risk factors and develop a risk assessment model for PU detection in the general Chinese population. In a prospective dataset, clinical data from individuals undergoing gastroscopic evaluation between April 2019 and May 2022 were recorded. PUs were defined as mucosal defects exceeding 5 mm confirmed via gastroscopy. Participants were categorized into development (April 2019 to April 2021) and validation (May 2021 to May 2022) sets based on chronological order. LASSO-derived logistic regression analysis was employed to create a score, which was further validated via temporal validation. A total of 902 patients were ultimately enrolled, 204 (22.6%) of whom had PUs based on endoscopic findings. In the development cohort (n = 631), seven independent risk factors emerged: male sex (OR = 2.35, P = 0.002), white blood cell (WBC) count (OR = 1.16, P = 0.010), red blood cell (RBC) count (OR = 0.49, P < 0.001), globulin level (OR = 0.92, P = 0.004), albumin level (OR = 0.94, P = 0.020), pepsinogen I (PGI) level (OR = 1.01, P < 0.001), and positive Helicobacter pylori (HP) antibody (OR = 2.50, P < 0.001). Using these factors, a nomogram (HAMPROW score [hazard ratio (HP) antibody, albumin, male, PGI, RBC, globulin, and WBC]) was developed for individual PU prediction. The ability of the HAMPROW score to predict survival was confirmed with AUCs of 0.854 (95% CI 0.816-0.891) and 0.833 (95% CI 0.771-0.895) in the development and validation sets, respectively. In conclusion, the HAMPROW score can be used to screen for PUs effectively in the general Chinese population, facilitating personalized early detection of high risk of gastrointestinal bleeding before antiplatelet therapy.

A Combined Treatment of BMP2 and Soluble VEGFR1 for the Enhancement of Tendon-Bone Healing by Regulating Injury-Activated Skeletal Stem Cell Lineage.

BACKGROUND: Bone morphogenetic protein 2 (BMP2) is an appealing osteogenic and chondrogenic growth factor for promoting tendon-bone healing. Recently, it has been reported that soluble vascular endothelial growth factor (VEGF) receptor 1 (sVEGFR1) (a VEGF receptor antagonist) could enhance BMP2-induced bone repair and cartilage regeneration; thus, their combined application may represent a promising treatment to improve tendon-bone healing. Moreover, BMP2 could stimulate skeletal stem cell (SSC) expansion and formation, which is responsible for wounded tendon-bone interface repair. However, whether the codelivery of BMP2 and sVEGFR1 increases tendon enthesis injury-activated SSCs better than does BMP2 alone needs further research. PURPOSE: To study the effect of BMP2 combined with sVEGFR1 on tendon-bone healing and injury-activated SSC lineage. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 128 C57BL/6 mice that underwent unilateral supraspinatus tendon detachment and repair were randomly assigned to 4 groups: (1) untreated control group; (2) hydrogel group, which received a local injection of the blank hydrogel at the injured site; (3) BMP2 group, which received an injection of hydrogel with BMP2; and (4) BMP2 with sVEGFR1 group, which received an injection of hydrogel with BMP2 and sVEGFR1. Histology, micro-computed tomography, and biomechanical tests were conducted to evaluate tendon-bone healing at 4 and 8 weeks after surgery. In addition, flow cytometry was performed to detect the proportion of SSCs and their downstream differentiated subtypes, including bone, cartilage, and stromal progenitors; osteoprogenitors; and pro-chondrogenic progenitors within supraspinatus tendon enthesis at 1 week postoperatively. RESULTS: The repaired interface in BMP2 with sVEGFR1 group showed a significantly improved collagen fiber continuity, increased fibrocartilage, greater newly formed bone, and elevated mechanical properties compared with the other 3 groups. There were more SSCs; bone, cartilage, and stromal progenitors; osteoprogenitors; and pro-chondrogenic progenitors in the BMP2 with sVEGFR1 group than that in the other groups. CONCLUSION: Our study suggests that the combined delivery of BMP2 and sVEGFR1 could promote tendon-bone healing and stimulate the expansion of SSCs and their downstream progeny within the injured tendon-bone interface. CLINICAL RELEVANCE: Combining BMP2 with sVEGFR1 may be a good clinical treatment for wounded tendon enthesis healing.

Effect of Exosomes From Bone Marrow-Derived Mesenchymal Stromal Cells and Adipose-Derived Stromal Cells on Bone-Tendon Healing in a Murine Rotator Cuff Injury Model.

Background: Bone-tendon injury is characterized by poor self-healing. It is established that exosomes are favorable for tissue repair and regeneration. However, their effect on bone-tendon healing has not yet been determined. Purpose: To compare the effectiveness of exosomes derived from adipose-derived mesenchymal stromal cells (ADSC-Exos) and bone marrow-derived mesenchymal stromal cells (BMSC-Exos) on bone-tendon interface healing in murine rotator cuff injury model and explore the underlying mechanisms thereof. Study Design: Controlled laboratory study. Methods: A total of 63 male C57BL6 mice with rotator cuff injuries underwent surgery and were randomly assigned to a control group treated without exosomes (n = 21), an ADSC-Exos group (n = 21), or a BMSC-Exos group (n = 21). The mice were sacrificed 4 or 8 weeks after surgery, and tissues were collected for histologic examination and radiographic and biomechanical testing. For exosome tracing in vivo, mice were sacrificed 7 days after surgery. A series of functional assays (radiographic evaluation, proliferation assay, Alizarin Red staining, alkaline phosphatase staining and activity, Alcian blue staining, quantitative polymerase chain reaction analyses, and glycosaminoglycans quantification) were conducted to evaluate the effect of exosomes on the cellular behaviors of the BMSCs in vitro. A statistical analysis of multiple-group comparisons was performed by 1-way analysis of variance, followed by the Bonferroni post hoc test to assess the differences between the 2 groups. Results: The ADSCs and BMSCs were positive for surface markers CD29 and CD90 and negative for surface markers CD34 and CD45 and could differentiate into osteoblasts, chondrocytes, and adipocytes. Exosomes showed a cup- or sphere-shaped morphology and were positive for CD63 and TGS101. Local injection of ADSC-Exos and BMSC-Exos could recruit BMSCs and promote osteogenesis, chondrogenesis, and bone-tendon healing. In vitro, ADSC-Exos and BMSC-Exos could significantly promote the proliferation, migration, osteogenic differentiation, and chondrogenic differentiation ability of BMSCs. In vivo, ADSC-Exos and BMSC-Exos significantly accelerated bone-tendon injury healing, with no significant statistical difference between them. Conclusion: ADSC-Exos and BMSC-Exos exhibited similar therapeutic effects on bone-tendon healing in our murine animal model. Clinical Relevance: ADSC-Exos and BMSC-Exos may be used to develop a new cell-free therapy method for promoting rotator cuff injury repair.

Causal associations between modifiable risk factors and intervertebral disc degeneration.

BACKGROUND: Intervertebral disc degeneration (IVDD) is a common degenerative condition, which is thought to be a major cause of lower back pain (LBP). However, the etiology and pathophysiology of IVDD are not yet completely clear. PURPOSE: To examine potential causal effects of modifiable risk factors on IVDD. STUDY DESIGN: Bidirectional Mendelian randomization (MR) study. PATIENT SAMPLE: Genome-wide association studies (GWAS) with sample sizes between 54,358 and 766,345 participants. OUTCOME MEASURES: Outcomes included (1) modifiable risk factors associated with IVDD use in the forward MR; and (2) modifiable risk factors that were determined to have a causal association with IVDD in the reverse MR, including smoking, alcohol intake, standing height, education level, household income, sleeplessness, hypertension, hip osteoarthritis, HDL, triglycerides, apolipoprotein A-I, type 2 diabetes, fasting glucose, HbA1c, BMI and obesity trait. METHODS: We obtained genetic variants associated with 33 exposure factors from genome-wide association studies. Summary statistics for IVDD were obtained from the FinnGen consortium. The risk factors of IVDD were analyzed by inverse variance weighting method, MR-Egger method, weighted median method, MR-PRESSO method and multivariate MR Method. Reverse Mendelian randomization analysis was performed on risk factors found to be caustically associated with IVDD in the forward Mendelian randomization analysis. The heterogeneity of instrumental variables was quantified using Cochran's Q statistic. RESULTS: Genetic predisposition to smoking (OR=1.221, 95% CI: 1.068-1.396), alcohol intake (OR=1.208, 95% CI: 1.056-1.328) and standing height (OR=1.149, 95% CI: 1.072-1.231) were associated with increased risk of IVDD. In addition, education level (OR=0.573, 95%CI: 0.502-0.654)and household income (OR=0.614, 95%CI: 0.445-0.847) had a protective effect on IVDD. Sleeplessness (OR=1.799, 95%CI: 1.162-2.783), hypertension (OR=2.113, 95%CI: 1.132-3.944) and type 2 diabetes (OR=1.069, 95%CI: 1.024-1.115) are three important risk factors causally associated with the IVDD. In addition, we demonstrated that increased levels of triglycerides (OR=1.080, 95%CI:1.013-1.151), fasting glucose (OR=1.189, 95%CI:1.007-1.405), and HbA1c (OR=1.308, 95%CI:1.017-1.683) could significantly increase the odds of IVDD. Hip osteoarthritis, HDL, apolipoprotein A-I, BMI and obesity trait factors showed bidirectional causal associations with IVDD, therefore we considered the causal associations between these risk factors and IVDD to be uncertain. CONCLUSIONS: This MR study provides evidence of complex causal associations between modifiable risk factors and IVDD. It is noteworthy that metabolic disturbances appear to have a more significant effect on IVDD than biomechanical alterations, as individuals with type 2 diabetes, elevated triglycerides, fasting glucose, and elevated HbA1c are at higher risk for IVDD, and the causal association of obesity-related characteristics with IVDD incidence is unclear. These findings provide new insights into potential therapeutic and prevention strategies. Further research is needed to clarify the mechanisms of these risk factors on IVDD.

MRI­based vertebral bone quality score is a comprehensive index reflecting the quality of bone and paravertebral muscle.

BACKGROUND: Recently, vertebral bone quality (VBQ) score has been shown to predict bone mineral density (BMD) and spine-related postoperative complications. However, in clinical work, we found that patients with higher VBQ scores also had more severe paravertebral muscle degeneration. PURPOSE: To explore the ability of the VBQ score to evaluate BMD and paravertebral muscle quality. STUDY DESIGN/SETTING: Retrospective single-center cohort. PATIENT SAMPLE: Patients in the spinal surgery department of our hospital. OUTCOME MEASURES: Bone mineral density and T-score were measured by dual-energy X-ray absorptiometry (DXA). The Picture Archiving and Communication Systems (PACS) measured the cross-sectional area (CSA) of the paravertebral muscles. Image J software was used to measure the degree of fat infiltration (DFF) of the paraspinal muscle. METHODS: Patients who underwent lumbar MRI and DXA simultaneously within two weeks were enrolled. The VBQ score was calculated using T1-weighted lumbar MRI images. Firstly, BMD-related and muscle-related parameters of patients with different VBQ scores were compared. Then, the correlation coefficients between the VBQ score and the parameters of BMD and paravertebral muscle were calculated. Finally, multivariate linear analysis was used to compare the contribution of each variable to the VBQ score. RESULTS: A total of 101 patients were eventually included in this study for analysis. When the VBQ score was greater than 3.0, the patients were mostly female, older, less likely to smoke, and had lower BMD. Interestingly, we found that patients with VBQ scores greater than 3.0 had smaller CSA of the paravertebral muscles (ES: 17.53±3.36 vs 19.13±3.97, p=.032; total: 29.59±5.27 vs 34.12±7.02, p<.001) and higher DFF (MF: 22.47±5.93 vs 19.64±5.28, p=.015; ES: 17.71±4.67 vs 15.74±4.62, p=.038; PM: 13.70±3.32 vs 11.33±3.02, p<.001; average: 17.96±3.78 vs 15.57±3.42, p=.001). The VBQ score was negatively correlated with the CSA (MF: r=-0.316, p=.001; ES: r =-0.388, p=.001; PM: r=0.388, p=.001) and positively correlated with the DFF (MF: r=0.344, p<.001; ES: r=0.439, p<.001; PM: =0.416, p<.001). In multivariate linear analysis, BMD, total CSA, and average DFF determined the value of the VBQ score, and the contribution of paravertebral muscle was higher than that of BMD (BMD: r=-0.203, p=.024; total CSA: r=-0.294, p=.003; average DFF: r=0.261, p=.011). CONCLUSIONS: This study is the first to find a positive association between the VBQ score and paravertebral muscle degeneration, and this association may be independent of BMD. VBQ can reflect the quality of bone and paravertebral muscle, which is its special advantage in clinical application.