Novel positioning guiders accurately assist in situ acetabular reconstruction for patients undergoing pelvic bone tumor resection.

PURPOSE: Acetabular reconstruction in situ after extensive pelvic resection is technically challenging. The aim of this study was to investigate the feasibility of positioning guiders for acetabular reconstruction following pelvic tumor resection and the clinical benefit brought by the approach. METHODS: The study included patients who underwent acetabular reconstruction following periacetabular tumor resection using a modular hemipelvic prosthesis. In the guider-assisted group (n = 14), guiders were designed and applied to assist acetabular reconstruction. In the traditional operation group (n = 18), the patients underwent the same surgery but without the guiders. The displacement of the hip rotation center before and after surgery was calculated. The complications and the Musculoskeletal Tumor Society-93 scores were documented. RESULTS: The overall displacement of the hip rotation center was significantly reduced in the guider-assisted group compared with the traditional operation group (13.83 ± 4.06 vs. 22.95 ± 9.18 mm in P = 0.000, 95%CI 3.90-12.96), especially in the anteroposterior axis (3.77 ± 3.03 versus 13.51 ± 9.43 mm in P = 0.000, 95%CI 3.45-13.09). Guider-assisted acetabular reconstruction reduced the risk of prosthesis dislocation compared with the traditional operation (dislocation risks: 1/14, 7.1% vs. 4/18, 22.2%). CONCLUSION: Positioning guiders can effectively and conveniently help place the modular hemipelvic prosthesis at the native position, which might potentially reduce the risk of prosthesis dislocation. LEVEL OF EVIDENCE: Therapeutic level III.

USP18 Curbs the Progression of Metabolic Hypertension by Suppressing JAK/STAT Pathway.

Hypertension is a pathological state of the metabolic syndrome that increases the risk of cardiovascular disease. Managing hypertension is challenging, and we aimed to identify the pathogenic factors and discern therapeutic targets for metabolic hypertension (MHR). An MHR rat model was established with the combined treatment of a high-sugar, high-fat diet and ethanol. Histopathological observations were performed using hematoxylin-eosin and Sirius Red staining. Transcriptome sequencing was performed to screen differentially expressed genes. The role of ubiquitin-specific protease 18 (USP18) in the proliferation, apoptosis, and oxidative stress of HUVECs was explored using Cell Counting Kit-8, flow cytometry, and enzyme-linked immunosorbent assays. Moreover, USP18 downstream signaling pathways in MHR were screened, and the effects of USP18 on these signaling pathways were investigated by western blotting. In the MHR model, total cholesterol and low-density lipoprotein levels increased, while high-density lipoprotein levels decreased. Moreover, high vessel thickness and percentage of collagen were noted along with increased malondialdehyde, decreased superoxide dismutase and catalase levels. The staining results showed that the MHR model exhibited an irregular aortic intima and disordered smooth muscle cells. There were 78 differentially expressed genes in the MHR model, and seven hub genes, including USP18, were identified. USP18 overexpression facilitated proliferation and reduced apoptosis and oxidative stress in HUVECs treated with Ang in vitro. In addition, the JAK/STAT pathway was identified as a USP18 downstream signaling pathway, and USP18 overexpression inhibited the expression of JAK/STAT pathway-related proteins. Conclusively, USP18 restrained MHR progression by promoting cell proliferation, reversing apoptosis and oxidative stress, and suppressing the JAK/STAT pathway.

The effects of semaphorin 3A in bone and cartilage metabolism: fundamental mechanism and clinical potential.

Semaphorin 3A (Sema3A) is a neuroinformatic protein molecule with widespread expression across various tissues and organs. Recent investigations have unveiled its pivotal role in the skeletal system, primarily through its binding interactions with two co-receptors, neuropilin-1 (Nrp-1) and members of the plexin family. Prior research has confirmed the expression of Sema3A and its receptors in both osteocytes and chondrocytes. Beyond its expression patterns, Sema3A plays a multifaceted role in regulating bone and cartilage metabolism via employing diverse signaling pathways. Additionally, it engages in collaborative interactions with the immune and nervous systems, contributing to the pathophysiological processes underlying a spectrum of bone and joint diseases. In this paper, we undertake a comprehensive review of recent research developments in this field. Our objective is to deepen the understanding of Sema3A within the context of skeletal physiology and pathology. Furthermore, we aim to furnish a valuable reference for potential therapeutic interventions in the realm of bone and joint diseases.

Effects of comprehensive nursing intervention on pressure ulcer after traumatic brain injury surgery: A meta-analysis.

Pressure ulcers (PUs) are a common complication in postoperative patients with traumatic brain injury, and this study used a meta-analysis to assess the effects of comprehensive nursing applied in PUs intervention in postoperative patients with traumatic brain injury. A computerised systematic search of the PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Literature Database (CBM), VIP and Wanfang databases was performed to collect publicly available articles on randomised controlled trials (RCTs) on the effects of comprehensive nursing interventions in postoperative patients with traumatic brain injury published up to August 2023. Two researchers independently completed the search and screening of the literature, extraction of data and quality assessment of the included literature based on the inclusion and exclusion criteria. Meta-analysis was performed using RevMan 5.4 software. Twenty-eight articles were finally included, for a cumulative count of 2641 patients, of which 1324 were in the intervention group and 1317 in the control group. The results of the meta-analysis showed that, compared with conventional nursing, comprehensive nursing intervention helped to reduce the incidence of PUs in postoperative patients with traumatic brain injury (5.14% vs. 19.67%, odds ratio [OR]: 0.22, 95% confidence interval [CI]: 0.16-0.29, p < 0.00001) and reduced the incidence of postoperative complications (7.87% vs. 25.84%, OR: 0.22, 95% CI: 0.11-0.43, p < 0.0001), while increasing patient satisfaction (96.67% vs. 75.33%, OR: 9.5, 95% CI: 3.63-24.88, p < 0.00001). This study concludes that a comprehensive nursing intervention applied to postoperative patients with traumatic brain injury can significantly reduce the incidence of PUs and postoperative complications as well as improve nursing satisfaction, and it is recommended for clinical promotion. However, due to the limitations of the studies' number and quality, more high-quality, large-sample RCTs are needed to further validate the conclusions of this study.

Identification of Malassezia globosa as a Gastric Fungus Associated with PD-L1 Expression and Overall Survival of Patients with Gastric Cancer.

Background: Microbiotas affected the prognosis of cancer patients by regulating programmed death ligand-1 (PD-L1) expression. However, the relationship between gastric fungi and PD-L1 expression is still unclear in gastric cancer (GC). We aimed at exploring the association of gastric fungi with PD-L1 expression and overall survival in GC. Methods: A total of 61 GC patients were divided into the two groups based on the PD-L1 combined positive scores (CPS). Fungal profiling was performed by internal transcribed spacer rDNA sequencing, and the survival analyses were performed by Kaplan-Meier curves. Results: We observed a taxonomic difference of fungi between the PD-L1-High (CPS ≥ 10) and PD-L1-Low group (CPS < 10) by principal coordinates analysis (PCoA) (P = 0.014 for Bray-Curtis and P = 0.042 for Jaccard). Malassezia had a higher abundance in the PD-L1-High group compared to the PD-L1-Low group (P = 0.045). Malassezia globosa elevated significantly in the PD-L1-High group. GC patients with PD-L1 low expression and low abundance of Malassezia globosa had a longer overall survival (OS) than others (P = 0.047). Malassezia globosa was associated with PD-L1 expression (Odds Ratio = 3.509, 95% Confidence Interval: 1.056-11.656, P = 0.040). Malassezia globosa was associated with the tumor size (P = 0.031) and PD-L1 status (P = 0.024). GC patients with a high abundance of Malassezia globosa had shorter OS than others (P = 0.028). Malassezia globosa was an independent factor (Hazard Ratio = 3.080, 95% Confidence Interval: 1.140-8.323, P = 0.027) for OS after adjusting for tumor stage. Malassezia globosa was figured out to be associated with- fatty acid and lipid biosynthesis and degradation via LIPASYN pathway. Conclusions. Malassezia globosa was identified as a PD-L1 expression-associated gastric fungus and associated with OS of GC patients, which calls for more studies to further explore its potential in PD-L1/PD-1 targeted immunotherapy.

Effect of evidence-based nursing combined with exercise rehabilitation in patients with acute myocardial infarction after percutaneous coronary intervention.

OBJECTIVE: To explore the effect of evidence-based nursing combined with exercise rehabilitation on cardiac function indices, self-care ability and incidence of adverse reactions in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI). METHODS: In this retrospective study, the medical records of 200 AMI patients undergoing PCI in Ganzhou People's Hospital from June 2020 to September 2021 were retrospectively analyzed, and the patients were divided into a control group (n=100) and a study group (n=100) according to the nursing methods after PCI. The cardiac function index, 6-minute walking distance (6MWD), behavioral self-management, physiological index, angina questionnaire and postoperative complications were compared between the two groups. RESULTS: After intervention, the study group exhibited significantly higher left ventricular ejection fraction and lower pro-B-type natriuretic peptide index than the control group (P<0.05). At 1, 3 and 6 months postoperative, the study group exhibited significantly longer 6MWD than the control group (P<0.05). At 3 and 6 months postoperative, the total Coronary Artery Disease Self-Management Scale scores except for emotional management were significantly higher in the study group than those in the control group (P<0.05). At 3- and 6-month postoperative visits, systolic and diastolic blood pressure, fasting blood glucose, total cholesterol, triglyceride and low-density lipoprotein in the study group were significantly lower than those in control group (P<0.05). The study group showed higher scores of Seattle Angina Questionnaire and lower incidence of complications than the control group (P<0.05). CONCLUSION: Evidence-based nursing combined with exercise rehabilitation can ameliorate cardiac function and physiological indices, increase treatment compliance and satisfaction, reduce the incidence of postoperative complications, and improve the quality of life in patients with AMI after PCI.

Remotely Temporal Scheduled Macrophage Phenotypic Transition Enables Optimized Immunomodulatory Bone Regeneration.

Precise timing of macrophage polarization plays a pivotal role in immunomodulation of tissue regeneration, yet most studies mainly focus on M2 macrophages for their anti-inflammatory and regenerative effects while the essential proinflammatory role of the M1 phenotype on the early inflammation stage is largely underestimated. Herein, a superparamagnetic hydrogel capable of timely controlling macrophage polarization is constructed by grafting superparamagnetic nanoparticles on collagen nanofibers. The magnetic responsive hydrogel network enables efficient polarization of encapsulated macrophage to the M2 phenotype through the podosome/Rho/ROCK mechanical pathway in response to static magnetic field (MF) as needed. Taking advantage of remote accessibility of magnetic field together with the superparamagnetic hydrogels, a temporal engineered M1 to M2 transition course preserving the essential role of M1 at the early stage of tissue healing, as well as enhancing the prohealing effect of M2 at the middle/late stages is established via delayed MF switch. Such precise timing of macrophage polarization matching the regenerative process of injured tissue eventually leads to optimized immunomodulatory bone healing in vivo. Overall, this study offers a remotely time-scheduled approach for macrophage polarization, which enables precise manipulation of inflammation progression during tissue healing.

The osteogenic response to chirality-patterned surface potential distribution of CFO/P(VDF-TrFE) membranes.

Piezoelectric poly(vinylidene fluoride-trifluoroethylene) has demonstrated an ability to promote osteogenesis, and biomaterials with a chirality-patterned topological surface could enhance cellular osteogenic differentiation. In this work, we created a chirality-patterned surface potential distribution of CoFe2O4/poly(vinylidene fluoride-trifluoroethylene (CFO/P(VDF-TrFE)) membranes to explore their osteogenic response under no change in surface chemical and topology, attempting to further strengthen the ability of the membranes to promote osteogenesis. The chirality-patterned surface potential distribution was established by microdomain contact polarization with the help of sinistral/dextral-patterned ITO interdigital microelectrodes. In the in vitro evaluations, the mesenchymal stem cells showed a positive response in osteogenic differentiation to CFO/P(VDF-TrFE) membranes with both sinistral- and dextral-patterned surface potential distributions, however, the dextral-patterned distribution gave a stronger response than the sinistral-patterned one. And the in vivo evaluation showed a response tend in new bone tissue formation similar to the in vitro evaluations. The stronger response in osteogenic differentiation and osteogenesis for the CFO/P(VDF-TrFE) membrane with the dextral-patterned distributions may be attributed to that the intense interaction of the cells with the electrophysiological microenvironment appears due to a correspondingly higher expression of integrin α5ß1, which significantly up-regulates the Arp2/3 complex expression, a crucial factor for cytoskeleton reorganization, possibly increases cytoskeleton contractility, and strengthens the transduction of the osteogenesis-related signaling cascade. This work proves that the chirality-patterns in surface potential distributions could provide an osteogenic response similar to a chirality-patterned topological surface.

Power Intelligent Terminal Intrusion Detection Based on Deep Learning and Cloud Computing.

Numerous internal and external intrusion attacks have appeared one after another, which has become a major problem affecting the normal operation of the power system. The power system is the infrastructure of the national economy, ensuring that the information security of its network not only is an aspect of computer information security but also must consider high-standard security requirements. This paper analyzes the intrusion threat brought by the power information network and conducts in-depth research and investigation combined with the intrusion detection technology of the power information network. It analyzes the structure of the power knowledge network and cloud computing through deep learning-based methods and provides a network interference detection model. The model combines the methods of abuse detection and anomaly detection, which solves the problem that the abuse analysis model does not detect new attack variants. At the same time, for big data network data retrieval, it retrieves and analyzes data flow quickly and accurately with the help of deep learning of data components. It uses a fuzzy integral method to optimize the accuracy of power information network intrusion prediction, and the accuracy reaches 98.11%, with an increase of 0.6%.

Direct Oral Anticoagulants vs. Vitamin K Antagonists in Atrial Fibrillation Patients at Risk of Falling: A Meta-Analysis.

Background: Direct oral anticoagulants (DOACs) and warfarin are usually used for people with atrial fibrillation (AF). However, for the AF patients at risk of falling, the effectiveness and safety outcomes of DOACs compared with warfarin remain unclear. Therefore, we performed a meta-analysis regarding the effectiveness and safety of DOACs vs. warfarin in AF patients at risk of falling. Methods: A search of the PubMed and Embase databases until November 2021 was performed. We included studies if they satisfied the following criteria: (1) study type: randomized clinical trials or observational cohort studies. (2) Comparisons: effectiveness and/or safety of DOACs (dabigatran, rivaroxaban, apixaban, or edoxaban) compared with warfarin. (3) Study data: the sample size, the number of events in the VKAs or DOACs groups, adjusted risk ratios (RRs), and 95% confidence intervals (CIs). (4) Study outcomes: stroke or systemic embolism (SSE), ischemic stroke, myocardial infarction (MI), all-cause death, and cardiovascular death; major bleeding, major or clinically relevant non-major (CRNM) bleeding, intracranial bleeding, gastrointestinal bleeding, and any bleeding. (5) Study population: patients at risk of falling. According to the Morse Fall Scale, the risk of falling relates to the history of falling, secondary diagnosis, ambulatory aids, intravenous therapy, type of gait, and mental status. In this meta-analysis, if the patient's MFS score is ≥25 points, he will be thought of as having the risk of falling. The adjusted risk ratios (RRs) and 95% confidence intervals (CIs) were pooled by a random-effects model with an inverse variance method. Results: Three cohort studies were included in our study. For the effectiveness outcomes, the use of DOACs was only associated with a significantly reduced risk of hemorrhagic stroke (RR = 0.28, 95%CI:0.10-0.75) compared with warfarin, but there were no significant differences in stroke or systemic embolism (SSE) (RR = 0.87, 95%CI:0.70-1.08), cardiovascular death (RR = 0.97, 95%CI:0.73-1.29) and all-cause death (RR = 0.90, 95%CI:0.72-1.11). For the safety outcomes, the use of DOACs was significantly associated with reduced risks of major or clinically relevant non-major bleeding (RR = 0.77, 95%CI:0.61-0.98) and intracranial bleeding (RR = 0.26, 95%CI:0.11-0.66) but not major bleeding (RR = 0.78, 95%CI:0.58-1.06). Conclusions: Compared with warfarin, the use of DOACs in AF patients at risk of falling is significantly associated with reduced risks of hemorrhagic stroke, major or clinically relevant non-major bleeding, and intracranial bleeding.

Conversion from Spanning External Fixation to Open Reduction Internal Fixation Contributes to Healing of Soft Tissues and Fractures in Open Distal Humeral Fractures.

BACKGROUND Open distal humeral fractures (DHFs) often lead to loss of elbow function, thereby seriously affecting patient quality of life. The aim of this study was to evaluate the treatment outcomes of 2 surgical techniques to determine the better method for repairing open DHFs. Both groups were treated with immediate debridement first, and then group I had only internal fixation (IF), while group II underwent initial external fixation (EF) followed by IF surgery. MATERIAL AND METHODS This retrospective study included 32 patients who had open DHFs between 2013 and 2018. Twelve patients underwent thorough debridement and temporary EF treatment and converted to IF as the ultimate treatment. Twenty patients were treated with immediate open reduction and internal fixation (ORIF). Data of final treatment outcomes were analyzed at the latest follow-up. A comparative analysis of radiological results, function observations, and complications was performed for the 2 surgical groups. RESULTS All DHFs and osteotomized olecranon united after a mean of 5.2±1.21 months. No significant differences were observed in other preoperative demographic data between the 2 groups. Moreover, there was no significant difference in postoperative complications, elbow range of motion, or fracture healing time between the 2 groups. CONCLUSIONS The evidence provided by our study highlights the efficacy of definitive IF in treating open DHFs, which is recommended whenever possible. Furthermore, the combination of EF and ORIF, according to the type of soft tissue damage, may be a promising treatment option with a low revision rate for patients with open DHFs.

Effect of high-quality nursing on postpartum hemorrhage and quality of life in puerperants with gestational hypertension.

OBJECTIVE: To observe the effect of high-quality nursing on puerperants with gestational hypertension. METHODS: In this study, 144 puerperants with gestational hypertension admitted to our hospital were included and divided into a research group and a control group according to the nursing method. The control group (n = 72) adopted the routine nursing and the observation group (n = 72) adopted the high-quality nursing. The rate of postpartum hemorrhage, the incidence of eclampsia, the amount of 1 d-postpartum hemorrhage, the quality of life (QOL), the psychological states, and the nursing satisfaction were compared between the two groups. RESULTS: The rate of postpartum hemorrhage, the incidence of eclampsia, and the amount of 1 d-postpartum hemorrhage of the patients in the observation group were significantly lower than those in the control group (all P < 0.05). After intervention, the scores of psychological states in both groups decreased, which dropped more in the observation group (all P < 0.05). The scores of physical function, overall health, social function, and emotional role in the observation group were significantly higher than those in the control group (all P < 0.05). The patients' satisfaction on nursing in the observation group was significantly higher than that in the control group (P < 0.05). CONCLUSION: High-quality nursing has certain advantages in improving postpartum hemorrhage and QOL in puerperants with gestational hypertension. It can also improve patients' negative emotions, life quality, and nursing satisfaction.

Anisotropic magneto-mechanical stimulation on collagen coatings to accelerate osteogenesis.

Mechanical stimulation has been considered to be critical to cellular response and tissue regeneration. However, harnessing the direction of mechanical stimulation during osteogenesis still remains a challenge. In this study, we designed a series of novel magnetized collagen coatings (MCCs) (randomly or parallel-oriented collagen fibers) to exert the anisotropic mechanical stimulation using oriented magnetic actuation during osteogenesis. Strikingly, we found the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) were significantly up-regulated when the direction of magnetic actuation was parallel to the randomly-oriented collagen coating surface, in contrast to the down-regulated capacity under the perpendicular magnetic actuation. Moreover, further exerting a parallel mechanical stimulation along the parallel-oriented collagen coating, which cells have been oriented by the oriented collagens, were not only able to up-regulate the osteogenic differentiation of BMSCs but also promote the new bone formation during osteogenesis in vivo. We also demonstrated the anisotropic magneto-mechanical stimulation for the osteogenic differences might be attributed to the stretching or bending tensile status of collagen fibers controlled by the direction of magnetic actuation, driving the α5ß1-dependent integrin signaling cascade. This study therefore got insight of understanding the directional mechanical stimulation on osteogenesis, and also paved a way for sustaining regulation of the biomaterials-host interface.

Corrigendum to 'Decellularized disc hydrogels for hBMSC tissue-specific differentiation and tissue regeneration' [Bioactive Materials 6 (2021) 3541-3556].

[This corrects the article DOI: 10.1016/j.bioactmat.2021.03.014.].

Spatiotemporal regulation of angiogenesis/osteogenesis emulating natural bone healing cascade for vascularized bone formation.

Engineering approaches for growth factor delivery have been considerably advanced for tissue regeneration, yet most of them fail to provide a complex combination of signals emulating a natural healing cascade, which substantially limits their clinical successes. Herein, we aimed to emulate the natural bone healing cascades by coupling the processes of angiogenesis and osteogenesis with a hybrid dual growth factor delivery system to achieve vascularized bone formation. Basic fibroblast growth factor (bFGF) was loaded into methacrylate gelatin (GelMA) to mimic angiogenic signalling during the inflammation and soft callus phases of the bone healing process, while bone morphogenetic protein-2 (BMP-2) was bound onto mineral coated microparticles (MCM) to mimics osteogenic signalling in the hard callus and bone remodelling phases. An Initial high concentration of bFGF accompanied by a sustainable release of BMP-2 and inorganic ions was realized to orchestrate well-coupled osteogenic and angiogenic effects for bone regeneration. In vitro experiments indicated that the hybrid hydrogel markedly enhanced the formation of vasculature in human umbilical vein endothelial cells (HUVECs), as well as the osteogenic differentiation of mesenchymal stem cells (BMSCs). In vivo results confirmed the optimal osteogenic performance of our F/G-B/M hydrogel, which was primarily attributed to the FGF-induced vascularization. This research presents a facile and potent alternative for treating bone defects by emulating natural cascades of bone healing.

Current and future distribution of the deciduous shrub Hydrangea macrophylla in China estimated by MaxEnt.

Climate change has a significant impact on the growth and distribution of vegetation worldwide. Hydrangea macrophylla is widely distributed and considered a model species for studying the distribution and responses of shrub plants under climate change. These results can inform decision-making regarding shrub plant protection, management, and introduction of germplasm resources, and are of great importance for formulating ecological countermeasures to climate change in the future. We used the maximum entropy model to predict the change, scope expansion/reduction, centroid movement, and dominant climate factors that restrict the growth and distribution of H. macrophylla in China under current and future climate change scenarios. It was found that both precipitation and temperature affect the distribution of suitable habitat for H. macrophylla. Akaike information criterion (AICc) was used to select the feature combination (FC) and the regularization multiplier (RM). After the establishment of the optimal model (FC = QP, RM = 0.5), the complexity and over-fitting degree of the model were low (delta AICc = 0, omission rate = 0.026, difference between training and testing area under the curve values = 0.0009), indicating that it had high accuracy in predicting the potential geographical distribution of H. macrophylla (area under the curve = 0.979). Overall, from the current period to future, the potential suitable habitat of this species in China expanded to the north. The greenhouse effect caused by an increase in CO2 emissions would not only increase the area of high-suitability habitat in Central China, but also expand the area of total suitable habitat in the north. Under the maximum greenhouse gas emission scenario (RCP8.5), the migration distance of the centroid was the longest (e.g., By 2070s, the centroids of total and highly suitable areas have shifted 186.15 km and 89.84 km, respectively).

Mutational characteristics of bone metastasis of lung cancer.

BACKGROUND: Roughly 30-40% of lung cancer (LC) patients develop bone metastasis during the course of disease. The genetic differences between primary LC and matched bone metastasis are not yet fully understood. METHODS: A total of 40 LC patients with bone metastasis were collected and 450 targeted cancer-related genes were sequenced for genomic-alteration (GA) identification. RESULTS: Among the 40 LC patients, 33 had adenocarcinomas and 7 had squamous cell carcinomas. The metastatic sites of the 33 lung adenocarcinomas (LUADs) were the pelvis (6 patients), spine (16 patients), and limbs (11 patients). A total of 425 and 422 GAs were detected in the primary and metastatic lesions, respectively. The most common GAs were epidermal growth factor receptor (EGFR) mutations, which had mutation rates of 85.0% and 72.5% in the primary and metastatic lesions, respectively, and tumor protein 53 (TP53) mutations, which had mutation rates of 52.5% and 67.5% in the primary and metastatic lesions, respectively. Metastases to the pelvis and spine were most commonly accompanied by factor receptor substrate 2 (FRS2), cyclin-dependent kinase 4 (CDK4), and murine double minute 2 (MDM2) amplification, and cyclin-dependent kinase inhibitor 2A (CDKN2A) deletion. The concordance between primary lung squamous cell carcinoma (LUSC) and corresponding metastasis was significantly higher than that of primary LUAD and corresponding metastasis (P=0.033). Compared to limb and pelvis metastases, the shared mutation in spine metastasis was significantly lower (P=0.016 and P=0.023, respectively). In matched primary LUSCs and bone metastasis lesions, there was no significant difference in the distribution of the tumor mutational burden (TMB) (P=0.9). Conversely, a significant difference of the TMB distribution was detected in pairs of primary LUAD and corresponding bone metastasis lesions (P=0.021). CONCLUSIONS: The consistency of mutation patterns between primary LC lesions and matched bone metastases may vary in terms of metastatic sites, but is very high in general. There was a significant difference in the TMB between primary LUAD and matched bone metastatic lesions. Our findings contribute to molecular understandings of primary LC and matched bone metastatic lesions.

Sustained zinc release in cooperation with CaP scaffold promoted bone regeneration via directing stem cell fate and triggering a pro-healing immune stimuli.

Metal ions have been identified as important bone metabolism regulators and widely used in the field of bone tissue engineering, however their exact role during bone regeneration remains unclear. Herein, the aim of study was to comprehensively explore the interactions between osteoinductive and osteo-immunomodulatory properties of these metal ions. In particular, the osteoinductive role of zinc ions (Zn2+), as well as its interactions with local immune microenvironment during bone healing process, was investigated in this study using a sustained Zn2+ delivery system incorporating Zn2+ into ß-tricalcium phosphate/poly(L-lactic acid) (TCP/PLLA) scaffolds. The presence of Zn2+ largely enhanced osteogenic differentiation of periosteum-derived progenitor cells (PDPCs), which was coincident with increased transition from M1 to M2 macrophages (M[Formula: see text]s). We further confirmed that induction of M2 polarization by Zn2+ was realized via PI3K/Akt/mTOR pathway, whereas marker molecules on this pathway were strictly regulated by the addition of Zn2+. Synergically, this favorable immunomodulatory effect of Zn2+ further improved the osteogenic differentiation of PDPCs induced by Zn2+ in vitro. Consistently, the spontaneous osteogenesis and pro-healing osteoimmunomodulation of the scaffolds were thoroughly identified in vivo using a rat air pouch model and a calvarial critical-size defect model. Taken together, Zn2+-releasing bioactive ceramics could be ideal scaffolds in bone tissue engineering due to their reciprocal interactions between osteoinductive and immunomodulatory characteristics. Clarification of this synergic role of Zn2+ during osteogenesis could pave the way to develop more sophisticated metal-ion based orthopedic therapeutic strategies.

Decellularized Disc Hydrogels for hBMSCs tissue-specific differentiation and tissue regeneration.

Tissue specificity, a key factor in the decellularized tissue matrix (DTM), has shown bioactive functionalities in tuning cell fate-e.g., the differentiation of mesenchymal stem cells. Notably, cell fate is also determined by the living microenvironment, including material composition and spatial characteristics. Herein, two neighboring tissues within intervertebral discs, the nucleus pulposus (NP) and annulus fibrosus (AF), were carefully processed into DTM hydrogels (abbreviated DNP-G and DAF-G, respectively) to determine the tissue-specific effects on stem cell fate, such as specific components and different culturing methods, as well as in vivo regeneration. Distinct differences in their protein compositions were identified by proteomic analysis. Interestingly, the fate of human bone marrow mesenchymal stem cells (hBMSCs) also responds to both culturing methods and composition. Generally, hBMSCs cultured with DNP-G (3D) differentiated into NP-like cells, while hBMSCs cultured with DAF-G (2D) underwent AF-like differentiation, indicating a close correlation with the native microenvironments of NP and AF cells, respectively. Furthermore, we found that the integrin-mediated RhoA/LATS/YAP1 signaling pathway was activated in DAF-G (2D)-induced AF-specific differentiation. Additionally, the activation of YAP1 determined the tendency of NP- or AF-specific differentiation and played opposite regulatory effects. Finally, DNP-G and DAF-G specifically promoted tissue regeneration in NP degeneration and AF defect rat models, respectively. In conclusion, DNP-G and DAF-G can specifically determine the fate of stem cells through the integrin-mediated RhoA/LATS/YAP1 signaling pathway, and this tissue specificity is both compositional and spatial, supporting the utilization of tissue-specific DTM in advanced treatments of intervertebral disc degeneration.