ITGB5 facilitates gastric cancer metastasis by promoting TGFBR2 endosomal recycling.

TGFBR2, a key regulator of the TGFß signaling pathway, plays a crucial role in gastric cancer (GC) metastasis through its endosomal recycling process. Despite its importance, the mechanisms governing this process remain unclear. Here, we identify integrin ß5 (ITGB5) as a critical mediator that promotes TGFBR2 endosomal recycling. Our study reveals elevated expression of ITGB5 in GC, particularly in metastatic cases, correlating with poor patient outcomes. Knockdown of ITGB5 impairs GC cell metastasis both in vitro and in vivo. Mechanistically, ITGB5 facilitates epithelial-mesenchymal transition mediated by TGFß signaling, thereby enhancing GC metastasis. Acting as a scaffold, ITGB5 interacts with TGFBR2 and SNX17, facilitating SNX17-mediated endosomal recycling of TGFBR2 and preventing lysosomal degradation, thereby maintaining its surface distribution on tumor cells. Notably, TGFß signaling directly upregulates ITGB5 expression, establishing a positive feedback loop that exacerbates GC metastasis. Our findings shed light on the role of ITGB5 in promoting GC metastasis through SNX17-mediated endosomal recycling of TGFBR2, providing insights for the development of targeted cancer therapies.

Young human plasma-derived extracellular vesicles rescue and reactivate IL-1ß and TNF-α treated chondrocytes.

Osteoarthritis (OA) is a degenerative disease that affects millions of individuals worldwide. Despite its prevalence, the exact causes and mechanisms behind OA are still not fully understood, resulting in a lack of effective treatments to slow down or halt disease progression. Recent research has discovered that extracellular vesicles (EVs) present in the circulation of young mice have a remarkable ability to activate musculoskeletal stem cells in elderly mice. Conversely, EVs derived from elderly mice do not exhibit the same potential, indicating that EVs obtained from young individuals may hold promise to activate aging cells in degenerative tissue. However, it remains unknown whether EVs derived from young individuals can also address cartilage degeneration caused by aging. In this study, we first evaluated EVs derived from young human plasma (YEVs) and EVs derived from old human plasma (OEVs) in an in vitro experiment using chondrocytes. The results revealed that YEVs effectively stimulated chondrocyte proliferation and migration, while OEVs from old plasma did not exhibit a similar effect. Given that OA represents a more complex inflammatory microenvironment, we further determine whether the benefits of YEVs on chondrocytes can be maintained in this context. Our findings indicate that YEVs have the ability to positively regulate chondrocyte function and protect them against apoptosis induced by IL-1ß and TNF-α in an in vitro OA model. Furthermore, we discovered that lyophilized EVs could be stored under mild conditions without any alterations in their physical characteristics. Considering the exceptional therapeutic effects and the wide availability of EVs from young plasma, they hold significant promise as a potential approach to activate chondrocytes and promote cartilage regeneration in early-stage OA.

In situ fabrication of an anisotropic double-layer hydrogel as a bio-scaffold for repairing articular cartilage and subchondral bone injuries.

Articular cartilage is a smooth and elastic connective tissue playing load-bearing and lubricating roles in the human body. Normal articular cartilage comprises no blood vessels, lymphatic vessels, nerves, or undifferentiated cells, so damage self-repair is very unlikely. The injuries of articular cartilage are often accompanied by damage to the subchondral bone. The subchondral bone mainly provides mechanical support for the joint, and the successful repair of articular cartilage depends on the ability of the subchondral bone to provide a suitable environment. Currently, conventional repair treatments for articular cartilage and subchondral bone defects can hardly achieve good results due to the poor self-repairing ability of the cartilage Here, we propose a bioactive injectable double-layer hydrogel to repair articular cartilage and subchondral bone. The hydrogel scaffold mimics the multilayer structure of articular cartilage and subchondral bone. Agarose was used as a common base material for the double-layer hydrogel scaffold, in which a sodium alginate (SA)/agarose layer was used for the repair of artificially produced subchondral bone defects, while a decellularized extracellular matrix (dECM)/agarose layer was used for the repair of articular cartilage defects. The double-layer hydrogel scaffold is injectable, easy to use, and can fill in the damaged area. The hydrogel scaffold is also anisotropic both chemically and structurally. Animal experiments showed that the surface of the new cartilage tissue in the double-layer hydrogel scaffold group was closest to normal articular cartilage, with a structure similar to that of hyaline cartilage and a preliminary calcified layer. Moreover, the new subchondral bone in this group exhibited many regular bone trabeculae, and the new cartilage and subchondral bone were mechanically bound without mutual intrusion and tightly integrated with the surrounding tissue. The continuous double-layer hydrogel scaffold prepared in this study mimics the multilayer structure of articular cartilage and subchondral bone and promotes the functional repair of articular cartilage and subchondral bone, favoring close integration between the newborn tissue and the original tissue.

Angle-Insensitive Ultrathin Broadband Visible Absorber Based on Dielectric-Semiconductor-Lossy Metal Film Stacks.

Ultrathin broadband absorbers with high efficiency, wide angular tolerance, and low fabrication cost are in demand for various applications. Here, we present an angle-insensitive ultrathin (<150 nm) broadband absorber with an average 96.88% (experiment) absorptivity in the whole visible range by utilizing a simple dielectric-semiconductor-lossy metal triple-layer film structure. The excellent broadband absorption performance of the device results from the combined action of the enhanced absorptions in the semiconductor and lossy metal layers exploiting strong interference effects and can be maintained over a wide viewing angle up to ±60°. Benefiting from the lossy metal providing additional absorption, our design reduces the requirement for the semiconductor's material dispersion and has great flexibility in the material selection of the metal layer. Additionally, the lithography-free nature of the proposed broadband visible absorber provides a high-throughput fabrication convenience, thus holding great potential for its large-area applications in various fields.

Nano wear particles and the periprosthetic microenvironment in aseptic loosening induced osteolysis following joint arthroplasty.

Joint arthroplasty is an option for end-stage septic arthritis due to joint infection after effective control of infection. However, complications such as osteolysis and aseptic loosening can arise afterwards due to wear and tear caused by high joint activity after surgery, necessitating joint revision. Some studies on tissue pathology after prosthesis implantation have identified various cell populations involved in the process. However, these studies have often overlooked the complexity of the altered periprosthetic microenvironment, especially the role of nano wear particles in the etiology of osteolysis and aseptic loosening. To address this gap, we propose the concept of the "prosthetic microenvironment". In this perspective, we first summarize the histological changes in the periprosthetic tissue from prosthetic implantation to aseptic loosening, then analyze the cellular components in the periprosthetic microenvironment post prosthetic implantation. We further elucidate the interactions among cells within periprosthetic tissues, and display the impact of wear particles on the disturbed periprosthetic microenvironments. Moreover, we explore the origins of disease states arising from imbalances in the homeostasis of the periprosthetic microenvironment. The aim of this review is to summarize the role of relevant factors in the microenvironment of the periprosthetic tissues, in an attempt to contribute to the development of innovative treatments to manage this common complication of joint replacement surgery.

Bone turnover biomarkers predict one-year all-cause mortality and walking ability in geriatric hip fracture patients.

PURPOSE: To investigate the utility of serum C-terminal cross-linking telopeptides (ß-CTX) and procollagen type I N propeptide (PINP) for predicting one-year mortality and walking ability in Chinese geriatric hip fracture patients who underwent surgical interventions. METHOD: Elderly patients (≥ 60 years) who underwent surgical interventions for unilateral low-energy hip fracture from 2015 to 2020 in our center were included. Demographic data was retrospectively retrieved from the electronic medical database. The PINP and ß-CTX concentrations were measured before the surgery. The patients were divided into two groups according to the outcome of mortality and walking ability after hip surgery, respectively. ß-CTX and PINP were divided into four grades based on quartiles [Quartile(Q)1-4] for further analysis. All the variables with p < 0.1 in univariable analysis were included in a multivariable model. RESULTS: In univariable analysis, the levels of serum ß-CTX (p = 0.007) and PINP (p = 0.025) was associated with one-year mortality, while the association between levels of serum ß-CTX (p = 0.072) or PINP (p = 0.055) with one-year disability was marginally significant. After adjustment for confounders, the relative risk [OR (95 % CI), Q4 v sQ1, p-value] of one-year mortality and one-year disability were 7.28 (2.08-29.78, p = 0.003) and 3.97 (1.44-11.69, p = 0.009) for ß-CTX and 5.87 (1.70-23.80, p = 0.008) and 3.48 (1.30-9.93, p = 0.016) for PINP, respectively. The coefficient of determination, AUC and bias-corrected C-index of predictive models based on previously reported predictors were significantly improved after integrating ß-CTX or PINP. CONCLUSION: Higher serum ß-CTX and PINP are independently associated with an increased risk of one-year mortality and disability in patients with hip fractures. The application of BTMs improves the performance of currently available predictive models.

Stem cell therapy combined with core decompression versus core decompression alone in the treatment of avascular necrosis of the femoral head: a systematic review and meta-analysis.

INTRODUCTION: Accumulated clinical trials had been focused on stem cell therapy in combination of core decompression (CD) in the treatment of avascular necrosis of the femoral head (ANFH). Nonetheless, the results were inconclusive. Here, we performed a systematic review and meta-analysis of previous randomized controlled trials (RCTs) and retrospective studies to assess whether combined stem cell augmentation with CD improved the outcomes of ANFH compared with CD alone. METHODS: The current study included 11 RCTs and 7 retrospective studies reporting the clinical outcomes of a total of 916 patients and 1257 hips. 557 and 700 hips received CD and CD plus stem cell therapy, respectively. To compare CD with CD plus stem cell therapy, we examined the clinical evaluating scores, the occurrence of the femoral head, radiologic progression and conversion to total hip arthroplasty (THA). RESULTS: Only 10 studies reported significantly greater improvement in hip functions while combining stem cell procedure with CD. The pooled results in subgroup analysis indicated that stem cell group had a lower collapse rate on a mid-term basis (P = 0.001), when combined with mechanical support (P < 0.00001), and with extracted stem cells (P = 0.0002). Likewise, stem cell group had a lower radiographic progression rate at 2- to 5-year follow-up [P = 0.003], when combined with structural grafting (P < 0.00001), and with extracted stem cells (P = 0.004). Stem cell therapy resulted in an overall lower THA conversion rate (P < 0.0001) except that at a follow-up longer than 5 years. CONCLUSION: Stem cell therapy combined with core decompression was more effective in preventing collapse, radiographic progression and conversion to THA. Trial Registration The current protocol has been registered in PROSPERO with the registration number: CRD42023417248.

Preoperative Vitamin D Deficiency is Associated with Increased One-Year Mortality in Chinese Geriatric Hip Fracture Patients - A Propensity Score Matching Study.

Background: Vitamin D deficiency is a common comorbidity in geriatric hip fracture patients. However, there is still an ongoing debate regarding the influence of preoperative Vitamin D status on postoperative mortality in hip fracture patients. Methods: Elderly patients (≥60 years) who underwent surgical interventions for unilateral hip fracture from 2015 to 2020 in our center were included. We retrospectively retrieved the demographic data from the electronic medical database. Preoperative serum total 25-hydroxy-Vitamin D was set as the independent variable and patients were classified as the Vitamin D deficiency (<20ng/mL) and the control groups consequently. Clinical outcomes include all-cause mortality, walking ability, and major postoperative complications in the first postoperative year. Propensity score matching (PSM) was performed in a ratio of 1:1 in the two groups for further comparison. Results: A total of 210 patients were included and 121 patients (57.6%) were diagnosed with Vitamin D deficiency. Patients in the Vitamin D deficiency group were much older and therefore preferred peripheral nerve block, and had significantly higher proportions of females, preoperative dementia, higher ASA grade, and lower baseline serum albumin level. Overall, 79 patients were identified in the Vitamin D deficiency and control groups after PSM, respectively. Patients diagnosed with Vitamin D deficiency showed a significantly higher one-year mortality (21.5% vs 6.3%, P=0.011) and a much lower one-year independent walking rate (67.1% vs.84.8%, P=0.016) after the matching. Regarding the dataset before PSM and after PSM, the AUC for serum Vitamin D for predicting one-year mortality was 0.656 (P=0.006) and 0.695 (P=0.002), respectively. Conclusion: Our retrospective PSM-design study provides new evidence that Vitamin D deficiency was associated with a significantly higher mortality and poor walking ability in the first year after surgical intervention based on southern Chinese populations.

Baseline Knee Pain Predicts Long-Term Response of Intra-Articular Steroid Injection in Symptomatic Knee Osteoarthritis: Data from OAI.

OBJECTIVE: The current study aims to investigate the factors that could predict response to intra-articular corticosteroid injection (IACI) in patients with knee osteoarthritis (KOA). METHODS: Data of participants were retrieved from the Osteoarthritis Initiative database. Participants with at least one IACI treatment on single or bilateral knees within the first 5 years of follow-up were retrospectively included. Demographic data, clinical and radiographic variables were collected at both baseline and the first follow-up after IACI treatment. Positive response to IACI treatment was defined as >20% reduction of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score from V0 to V1. All the variables with P < 0.2 after the comparison between the response and non-response groups were included in a multivariable logistic regression model to identify independent response predictive patient-specific valuables. Receiver operating characteristic curves were performed to establish the cutoff values of independent predictors. RESULTS: The current study included a total of 385 participants (473 knees), with 155 and 318 knees classified into the response group and non-response group, respectively. Those with satisfied responses to IACI treatment had significantly higher WOMAC pain score (P < 0.001), disability score (P = 0.002), and stiffness score (P = 0.015) at the baseline. Baseline WOMAC pain score showed significant association with positive response to IACI treatment in multivariate logistic analysis and the best cutoff value was 5 points. The rate of analgesics utilization was lower (P = 0.014) in the response group than the non-response group after the IACI treatment. CONCLUSION: KOA patients with a baseline WOMAC pain score ≥5 are more likely to benefit from IACI treatment.

HSP90ß promotes osteoclastogenesis by dual-activation of cholesterol synthesis and NF-κB signaling.

Heat shock protein 90ß (Hsp90ß, encoded by Hsp90ab1 gene) is the most abundant proteins in the cells and contributes to variety of biological processes including metabolism, cell growth and neural functions. However, genetic evidences showing Hsp90ß in vivo functions using tissue specific knockout mice are still lacking. Here, we showed that Hsp90ß exerted paralogue-specific role in osteoclastogenesis. Using myeloid-specific Hsp90ab1 knockout mice, we provided the first genetic evidence showing the in vivo function of Hsp90ß. Hsp90ß binds to Ikkß and reduces its ubiquitylation and proteasomal degradation, thus leading to activated NF-κB signaling. Meanwhile, Hsp90ß increases cholesterol biosynthesis by activating Srebp2. Both pathways promote osteoclastogenic genes expression. Genetic deletion of Hsp90ab1 in osteoclast or pharmacological inhibition of Hsp90ß alleviates bone loss in ovariectomy-induced mice. Therefore, Hsp90ß is a promising druggable target for the treatment of osteoporosis.

Anisotropic hydrogel fabricated by controlled diffusion as a bio-scaffold for the regeneration of cartilage injury.

Controlled fabrication of anisotropic materials has become a hotspot in materials science, particularly biomaterials, since the next generation of tissue engineering is based on the application of heterogeneous structures that can simulate the original biological complexity of the body. The current fabrication method of producing anisotropic materials involves expensive and highly specialized equipment, and not every conventional method can be applied to preparing anisotropic materials for corresponding tissue engineering. Anisotropic materials can be easily applied to a problem in tissue engineering: cartilage injury repairing. The articular cartilage consists of four spatially distinct regions: superficial, transitional, deep, and calcified. Each region has a specific extracellular matrix composition, mechanical properties, and cellular organization; this calls for the application of an anisotropic hydrogel. Controlled diffusion, under the assistance of buoyancy, has been considered a generalized method to prepare materials using a gradient. The diffusion of two solutions can be controlled through the difference in their densities. In addition to providing anisotropy, this method realizes the in situ formation of an anisotropic hydrogel, and simplifies the preparation process, freeing it from the need for expensive equipment such as 3D printing and microfluidics. Herein, an anisotropic hydrogel based on a decellularized extracellular matrix is fabricated and characterized. The as-prepared scaffold possessed specific chemical composition, physical properties, and physiological factor gradient. In vitro experiments ensured its biocompatibility and biological effectiveness; further in vivo experiments confirmed its application in the effective regeneration of cartilage injury.

AAV-mediated gene therapy produces fertile offspring in the Lhcgr-deficient mouse model of Leydig cell failure.

Leydig cell failure (LCF) caused by gene mutation results in testosterone deficiency and infertility. Serum testosterone levels can be recovered via testosterone replacement; however, established therapies have shown limited success in restoring fertility. Here, we use a luteinizing hormone/choriogonadotrophin receptor (Lhcgr)-deficient mouse model of LCF to investigate the feasibility of gene therapy for restoring testosterone production and fertility. We screen several adeno-associated virus (AAV) serotypes and identify AAV8 as an efficient vector to drive exogenous Lhcgr expression in progenitor Leydig cells through interstitial injection. We observe considerable testosterone recovery and Leydig cell maturation after AAV8-Lhcgr treatment in pubertal Lhcgr-/- mice. Of note, this gene therapy partially recovers sexual development, substantially restores spermatogenesis, and effectively produces fertile offspring. Furthermore, these favorable effects can be reproduced in adult Lhcgr-/- mice. Our proof-of-concept experiments in the mouse model demonstrate that AAV-mediated gene therapy may represent a promising therapeutic approach for patients with LCF.

Recent advances in soil remediation technology for heavy metal contaminated sites: A critical review.

With the increasing development of industry and urbanization, heavy metal contaminated sites have become progressively conspicuous, particularly by unreasonable emissions from electroplating, nonferrous metals smelting, mine tailing, etc. In recent years, soil remediation technologies for heavy metal contaminated sites have developed rapidly. New and effective remediation technologies have emerged successively, and more successful practical applications have appeared. Therefore, systematical summarization of the current progress is essential. As a result, in this paper, some mainstream soil remediation technologies for heavy metal contaminated sites, including physical remediation (soil thermal desorption and soil replacement), bioremediation (phytoremediation and microbial remediation), chemical remediation (chemical leaching, chemical stabilization, electrokinetic remediation-permeable reactive barrier, and chemical oxidation/reduction), as well as various combined remediation are comprehensively reviewed. The influencing factors, advantages, disadvantages, remediation mechanism, and practical applications are also deeply discussed. Besides, the corresponding remediation strategies are put forward for the remediation of heavily polluted sites such as the chemical industry, smelting, and tailing areas. Overall, this review will be beneficial for the in-depth understanding and provide references for the reasonable selection and development of soil remediation technology for heavy metal contaminated sites.

[Three-dimensional morphological study of the effect of false acetabulum on the femoral structure in Crowe type â £ developmental dysplasia of the hip].

Objective: To explore the effect of false acetabulum on the development and anatomical morphology of proximal femur in Crowe type Ⅳ developmental dysplasia of the hip (DDH), providing a theoretical basis for the development of femoral reconstruction strategy and prosthesis selection for total hip arthroplasty. Methods: The medical records of 47 patients (54 hips) with Crowe type Ⅳ DDH between February 2008 and March 2020 were retrospectively analyzed, of which 21 patients (26 hips) were Crowe type Ⅳa (type Ⅳa group) and 26 patients (28 hips) were Crowe type Ⅳb (type Ⅳb group). There was no significant difference in general data such as gender, age, height, weight, body mass index, and side between the two groups ( P>0.05), which were comparable. The height of femoral head dislocation, the height of pelvis, and the proportion of dislocation were measured based on preoperative anteroposterior pelvic X-ray film. Based on the preoperative femoral CT scan data, the anatomical parameters of the femur and femoral medullary cavity were measured after three-dimensional reconstruction using Mimics19.0 software to calculate the canal fare index; and the femoral medullary cavity parameters were matched with the modular S-ROM prosthesis parameters. Results: The results of X-ray film measurement showed that the height of femoral head dislocation and the proportion of dislocation in type Ⅳa group were significantly higher than those in type Ⅳb group ( P<0.05). There was no significant difference in the height of pelvis between the two groups ( P>0.05). The results of CT three-dimensional reconstruction measurements showed that compared with the type Ⅳb group, the type Ⅳa group had less isthmus height, smaller femoral head, shorter femoral neck, narrower neck-shaft angle, increased anteversion angle, and higher greater trochanter, and the differences were significant ( P<0.05). There was no significant difference in the height of femoral head, femoral offset, and height difference between greater trochanter and femoral head between the two groups ( P>0.05). There was no significant difference in the mediolateral width (ML), anteroposterior width (AP), and diameter of the isthmus (Ci level) and the AP of the medullary cavity in the plane 40 mm distal to the most prominent point on the medial side of the lesser trochanter (C -40 level) ( P>0.05), and the size of medullary cavity was significantly smaller in type Ⅳa group than in type Ⅳb group at the other levels ( P<0.05). Compared with the type Ⅳb group, the difference between the outer diameter of the prosthetic sleeve and the diameter of the medullary cavity fitting circle in the plane where the center of femoral head rotation was located from the medial most prominent point of the lesser trochanter (C 0 level) in type Ⅳa group was smaller, and the proportion of negative values was greater ( P<0.05). The difference between the longest diameter of the prosthetic sleeve triangle and the ML of the medullary cavity in the plane 10 mm proximal to the most prominent point on the medial side of the lesser trochanter (C +10 level) in type Ⅳa group was smaller, and the proportion of negative values was greater ( P<0.05). Conclusion: False acetabulum has a significant impact on the morphology of the proximal femur and medullary cavity in patients with Crowe type Ⅳ DDH, and the application of three-dimensional reconstruction technique can accurately evaluate the femoral morphology and guide the selection of femoral prosthesis.

Contralateral advanced radiographic knee osteoarthritis predicts radiographic progression and future arthroplasty in ipsilateral knee with early-stage osteoarthritis.

PURPOSE: To explore whether the severity of contralateral knee osteoarthritis (OA) is associated with OA progression in ipsilateral knee with early OA. METHODS: Knees in early OA (Kellgren-Lawrence grade (KLG):1-2) with intact baseline demographic and clinical data were retrieved from OAI database and defined as target knees. The target knees were divided into the exposure group (contralateral knees KLG 3 to 4) and the control group (contralateral knees KLG 0 to 2). Both groups underwent propensity score matching (PSM) concerning demographic data, as well as radiographic and clinical outcomes at the baseline. The primary outcome was the upgrade of KLG in the target knee in the first 12 and 24 months. The secondary outcome was the incidence of knee arthroplasty in ipsilateral knee during the first 108 months. RESULTS: One thousand seven hundred fifty-two knees were included, with 449 in the exposure cohort and 1276 in the control cohort. Four hundred thirty-four knees in each group were matched after PSM. Target knees in the exposure cohort showed a significantly higher rate of radiographic progression in the first 12 months (12.9% vs. 5.1%, P < 0.001) and 24 months (19.6% vs. 8.1%, P < 0.001). As for the risk of future arthroplasty, a significant difference was also found between the two groups (7.8% vs. 4.0%, P = 0.02). Kaplan-Meier analysis showed that the 108-month accumulated knee survival rate was significantly lower in the exposure group (P = 0.01). CONCLUSION: The ipsilateral knee with early-stage OA is prone to have worse early to mid-, and long-term prognosis in the circumstance of contralateral radiographic advanced knee OA. Key Points •Identifying early knee osteoarthritis (OA) with a high risk of radiographic progression and future arthroplasty enables early personalized intervention. •This is a novel study to investigate the relationship between the risk of future arthroplasty and contralateral knee status. •Propensity score matching holds promise to minimize selection bias in observational studies. •Knees with early OA are prone to have a high risk of radiographic progression and future arthroplasty in the circumstance of contralateral advanced knee OA.

Three-dimensional morphological analysis of true acetabulum in Crowe type IV hip dysplasia via standard-sized cup-simulated implantation.

Background: Acetabular reconstruction in Crowe type IV developmental dysplasia of the hip (DDH) can be a challenging procedure for surgeons. A high risk of acetabular revision has been reported to be associated with extremely small acetabular prostheses. However, to our knowledge, quantitative morphological and coverage evaluations of the true acetabulum in Crowe IV hips have been infrequently conducted. Useful bony landmarks for acetabular reconstruction can also facilitate satisfactory intraoperative implantation. The aim of the present study was to investigate the anatomical size, orientation angles, and 2/3-dimensional (2D/3D) coverage parameters of the true acetabulum in Crowe IV hips; evaluate the feasibility of standard cup (>44 mm) implantation at the true acetabulum in Crowe IV hips; and identify the optimal position and useful bony landmarks of the acetabular reaming center in Crowe IV hips. Methods: A total of 42 Crowe IV hips in 37 patients and 36 normal hips were included in this study. Based on pelvic 3D computed tomography (CT) reconstruction, anatomical size and integral volume of the true acetabulum were measured quantitatively. Through standard-size cup-simulated implantation, morphological assessments of the true acetabulum included Cup-CE, Cup-Sharp, acetabular anteversion angle, and thickness of the medial wall. Acetabular sector angles (ASAs) and the component coverage ratio were measured to provide coverage indices. Acetabular reconstruction was also performed at different vertical levels to measure medial bone stock and 3D component coverage. Bony landmarks for optimal component center location were also determined. Results: The anatomic shape and volume of the acetabular triangle were significantly smaller in Crowe IV hips. Compared with the control group, the dysplastic acetabulum was more anteverted and abductive, with a thicker medial wall. According to the true acetabulum, bone stock was relatively sufficient in the posterior direction and prominently deficient in the anterosuperior and superior direction. The average 3D component coverage reached 79.89% by standard-sized cup implantation, with the most satisfactory coverage achieved at the true acetabulum (at the level of 13.32 mm above the transverse acetabular ligament). Regarding the component opening plane, the optimal component center was located at the midpoint between the superolateral and posteroinferior points of the true acetabulum. Conclusions: The most satisfactory coverage was achieved at the level of the true acetabulum, of which the most prominent deficiency was mainly located in the anterosuperior and superior directions. The optimal component center was determined to be the midpoint between the superolateral and posteroinferior points of the true acetabulum.

Accurate Machine Learning Model to Diagnose Chronic Autoimmune Diseases Utilizing Information From B Cells and Monocytes.

Heterogeneity and limited comprehension of chronic autoimmune disease pathophysiology cause accurate diagnosis a challenging process. With the increasing resources of single-cell sequencing data, a reasonable way could be found to address this issue. In our study, with the use of large-scale public single-cell RNA sequencing (scRNA-seq) data, analysis of dataset integration (3.1 × 105 PBMCs from fifteen SLE patients and eight healthy donors) and cellular cross talking (3.8 × 105 PBMCs from twenty-eight SLE patients and eight healthy donors) were performed to identify the most crucial information characterizing SLE. Our findings revealed that the interactions among the PBMC subpopulations of SLE patients may be weakened under the inflammatory microenvironment, which could result in abnormal emergences or variations in signaling patterns within PBMCs. In particular, the alterations of B cells and monocytes may be the most significant findings. Utilizing this powerful information, an efficient mathematical model of unbiased random forest machine learning was established to distinguish SLE patients from healthy donors via not only scRNA-seq data but also bulk RNA-seq data. Surprisingly, our mathematical model could also accurately identify patients with rheumatoid arthritis and multiple sclerosis, not just SLE, via bulk RNA-seq data (derived from 688 samples). Since the variations in PBMCs should predate the clinical manifestations of these diseases, our machine learning model may be feasible to develop into an efficient tool for accurate diagnosis of chronic autoimmune diseases.

Intraperitoneally Delivered Mesenchymal Stem Cells Alleviate Experimental Colitis Through THBS1-Mediated Induction of IL-10-Competent Regulatory B Cells.

Mesenchymal stem cells (MSCs) show promising therapeutic potential in treating inflammatory bowel disease (IBD), and intraperitoneal delivery of MSCs have become a more effective route for IBD treatment. However, the underlying mechanisms are still poorly understood. Here, we found that intraperitoneally delivered MSCs significantly alleviated experimental colitis. Depletion of peritoneal B cells, but not macrophages, clearly impaired the therapeutic effects of MSCs. Intraperitoneally delivered MSCs improved IBD likely by boosting the IL-10-producing B cells in the peritoneal cavity, and a single intraperitoneal injection of MSCs could significantly prevent disease severity in a recurrent mouse colitis model, with lower proinflammation cytokines and high level of IL-10. The gene expression profile revealed that thrombospondin-1 (THBS1) was dramatically upregulated in MSCs after coculture with peritoneal lavage fluid from colitis mice. Knockout of THBS1 expression in MSCs abolished their therapeutic effects in colitis and the induction of IL-10-producing B cells. Mechanistically, THBS1 modulates the activation of transforming growth factor-ß (TGF-ß), which combines with TGF-ß receptors on B cells and contributes to IL-10 production. Blocking the interaction between THBS1 and latent TGF-ß or inhibiting TGF-ß receptors (TGF-ßR) significantly reversed the THBS1-mediated induction of IL-10-producing B cells and the therapeutic effects on colitis. Collectively, our study revealed that intraperitoneally delivered MSCs secreted THBS1 to boost IL-10+Bregs and control the progression and recurrence of colitis, providing new insight for the prevention and treatment of IBD.

Femur-tibia angle and patella-tibia angle: new indicators for diagnosing anterior cruciate ligament tears in magnetic resonance imaging.

BACKGROUND: Femur-tibia angle (FTA) and patella-tibia angle (PTA) are two MRI measurements that reflect the rotation of the knee joint. The purposes of this study were to assess whether FTA and PTA are associated with ACL tear and to explore their roles in ACL tear diagnosis. METHODS: FTA, PTA, ACL angle and anterior tibial subluxation were compared between the two matched groups: ACL tear group and control group (each n = 20). Diagnostic performance was evaluated in a consecutive 120-patient cohort who underwent MR imaging of the knee and subsequently had arthroscopy. Different measurements were assessed by area under the curve (AUC) of receiver operating characteristic (ROC) curve. RESULTS: FTA and PTA increased significantly in ACL tears group when compared to the control group (4.79 and 7.36 degrees, respectively, p < 0.05). In distinguishing complete ACL tear, ACL angle had the highest AUC of 0.906 while AUC of PTA and FTA were 0.849 and 0.809. The cutoff of FTA was 80 degrees with a sensitivity of 82% and specificity of 68%, while the cutoff of PTA was 91 degrees with a sensitivity of 82% and specificity of 74%. In distinguishing partial ACL tear, FTA and PTA had the highest AUCs of 0.847 and 0.813, respectively. The calculated cutoff of FTA was 84 degrees with a sensitivity of 90% and specificity of 81%, while the cutoff of PTA was 92 degrees with a sensitivity of 80% and specificity of 77%. CONCLUSION: FTA and PTA increased when ACL tears and they might be valuable in diagnosing ACL tears, especially in distinguishing partial ACL tear from intact ACL.