Numerical Simulation of the Evaporation Behavior of Fe-Mn Heterogeneous Powder in Selective Laser Melting Process.

Multi-material additive manufacturing using heterogeneous powders as raw materials is one of the important development directions of metal additive manufacturing technology. The evaporation behavior of heterogeneous powders in the selective laser melting (SLM) process has a significant influence on the accuracy of chemical composition control and the quality of the final product. In this paper, the fusion process of Fe20Mn (80 wt.% Fe and 20 wt.% Mn) heterogeneous powder, Fe and Mn elemental powders, and Fe20Mn pre-alloyed powder is numerically simulated using FLOW-3D® software and partially validated through SLM experimental results. The morphology and the characteristics of the flow field and temperature field in the melt pool for four kinds of powder materials are analyzed. The influence of the elemental evaporation behavior of different powders on the mass loss of the Mn element is discussed. The results show that the excessive accumulation of heat increases the maximum temperature of the melt pool, thus increasing mass loss. The Fe20Mn heterogeneous powder has a wider heat-affected zone and a higher peak value of temperature, nearly 400 K higher than that of the Fe20Mn pre-alloyed powders, which exhibits an intensive evaporation behavior. The mass loss of the Mn element obtained from the SLM experiment for Fe20Mn heterogeneous powders forming parts is more than the Fe20Mn pre-alloyed powders' forming parts for different laser powers, up to 17 wt.% at P = 120 W. This tendency is consistent with the numerical analysis of the effect of evaporation behavior of Fe-Mn heterogeneous powder during the SLM process. This study provides the necessary theoretical reference and process guidance for realizing the precise control of the SLM composition of a heterogeneous powder in multi-material additive manufacturing caused by evaporation behavior.

Development of a machine learning model for predicting pneumothorax risk in coaxial core needle biopsy (≤3 cm).

PURPOSE: The aim is to devise a machine learning algorithm exploiting preoperative clinical data to forecast the hazard of pneumothorax post-coaxial needle lung biopsy (CCNB), thereby informing clinical decision-making and enhancing perioperative care. METHOD: This retrospective analysis aggregated clinical and imaging data from patients with lung nodules (≤3 cm) biopsies. Variable selection was done using univariate analysis and LASSO regression, with the dataset subsequently divided into training (80 %) and validation (20 %) subsets. Various machine learning (ML) classifiers were employed in a consolidated approach to ascertain the paramount model, which was followed by individualized risk profiling showcased through Shapley Additive eXplanations (SHAP). RESULTS: Out of the 325 patients included in the study, 19.6% (64/325) experienced postoperative pneumothorax. High-risk factors determined were Cancer, Lesion_type, GOLD, Size, and Depth. The Gaussian Naive Bayes (GNB) classifier demonstrated superior prediction with an Area Under the Curve (AUC) of 0.82 (95% CI 0.71-0.94), complemented by an accuracy rate of 0.8, sensitivity of 0.71, specificity of 0.84, and an F1 score of 0.61 in the test cohort. CONCLUSION: The formulated prognostic algorithm exhibited commendable efficacy in preoperatively prognosticating CCNB-induced pneumothorax, harboring the potential to refine personalized risk appraisals, steer clinical judgment, and ameliorate perioperative patient stewardship.

Hypoxia preconditioning of adipose stem cell-derived exosomes loaded in gelatin methacryloyl (GelMA) promote type H angiogenesis and osteoporotic fracture repair.

The challenges posed by delayed atrophic healing and nonunion stand as formidable obstacles in osteoporotic fracture treatment. The processes of type H angiogenesis and osteogenesis emerge as pivotal mechanisms during bone regeneration. Notably, the preconditioning of adipose-derived stem cell (ADSC) exosomes under hypoxic conditions has garnered attention for its potential to augment the secretion and functionality of these exosomes. In the present investigation, we embarked upon a comprehensive elucidation of the underlying mechanisms of hypo-ADSC-Exos within the milieu of osteoporotic bone regeneration. Our findings revealed that hypo-ADSC-Exos harboured a preeminent miRNA, namely, miR-21-5p, which emerged as the principal orchestrator of angiogenic effects. Through in vitro experiments, we demonstrated the capacity of hypo-ADSC-Exos to stimulate the proliferation, migration, and angiogenic potential of human umbilical vein endothelial cells (HUVECs) via the mediation of miR-21-5p. The inhibition of miR-21-5p effectively attenuated the proangiogenic effects mediated by hypo-ADSC-Exos. Mechanistically, our investigation revealed that exosomal miR-21-5p emanating from hypo-ADSCs exerts its regulatory influence by targeting sprouly1 (SPRY1) within HUVECs, thereby facilitating the activation of the PI3K/AKT signalling pathway. Notably, knockdown of SPRY1 in HUVECs was found to potentiate PI3K/AKT activation and, concomitantly, HUVEC proliferation, migration, and angiogenesis. The culminating stage of our study involved a compelling in vivo demonstration wherein GelMA loaded with hypo-ADSC-Exos was validated to substantially enhance local type H angiogenesis and concomitant bone regeneration. This enhancement was unequivocally attributed to the exosomal modulation of SPRY1. In summary, our investigation offers a pioneering perspective on the potential utility of hypo-ADSC-Exos as readily available for osteoporotic fracture treatment.

Expert consensus on Prospective Precision Diagnosis and Treatment Strategies for Osteoporotic Fractures.

Osteoporotic fractures are the most severe complications of osteoporosis, characterized by poor bone quality, difficult realignment and fixation, slow fracture healing, and a high risk of recurrence. Clinically managing these fractures is relatively challenging, and in the context of rapid aging, they pose significant social hazards. The rapid advancement of disciplines such as biophysics and biochemistry brings new opportunities for future medical diagnosis and treatment. However, there has been limited attention to precision diagnosis and treatment strategies for osteoporotic fractures both domestically and internationally. In response to this, the Chinese Medical Association Orthopaedic Branch Youth Osteoporosis Group, Chinese Geriatrics Society Geriatric Orthopaedics Committee, Chinese Medical Doctor Association Orthopaedic Physicians Branch Youth Committee Osteoporosis Group, and Shanghai Association of Integrated Traditional Chinese and Western Medicine Osteoporosis Professional Committee have collaborated to develop this consensus. It aims to elucidate emerging technologies that may play a pivotal role in both diagnosis and treatment, advocating for clinicians to embrace interdisciplinary approaches and incorporate these new technologies into their practice. Ultimately, the goal is to improve the prognosis and quality of life for elderly patients with osteoporotic fractures.

C-arm CT guided percutaneous vertebroplasty for pain release in cancer patient with cervical 1 vertebral metastases: A case report.

OBJECTIVE: To evaluate the efficacy and treatment outcome of C-arm CT percutaneous vertebroplasty in the treatment of cervical 1 (C1) vertebral metastases. METHODS: This report recruited a male patient diagnosed with hepatocellular carcinoma and C1 vertebral metastases, who had suffered from severe neck pain symptoms and the analgesic showed little soothing effect. Under the guidance of C-arm CT, an 18G coaxial needle was used to puncture the left lateral mass of C1 vertebral metastases from lateral space between thyroid cartilage and the left carotid sheath, with 2 ml bone cement injected. RESULTS: Postoperative C-arm CT three-dimensional reconstruction scan showed that the bone cement was well filled and distributed in the left lateral mass of C1 vertebral body, and no leakage of bone cement was observed. The neck pain of the patients was significantly relieved one week after the operation. CONCLUSION: Under the guidance of C-arm CT, cement augmentation using percutaneous vertebroplasty in an anterior cervical direction could serve as a safe and effective pain relief approach for patients with C1 vertebral metastases.

Clinical efficacy of HAIC (FOLFOX) combined with lenvatinib plus PD-1 inhibitors vs. TACE combined with lenvatinib plus PD-1 inhibitors in the treatment of advanced hepatocellular carcinoma with portal vein tumor thrombus and arterioportal fistulas.

This study aimed to evaluate the clinical efficacy of hepatic arterial infusion chemotherapy (HAIC) combined with lenvatinib and PD1 inhibitors vs. transarterial chemoembolization (TACE) combined with lenvatinib and PD1 inhibitors in the treatment of unresectable hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) and artery-portal shunts (APFs). HCC Patients with PVTT and APFs who received HAIC in combination with PD1 inhibitor or TACE in combination with lenvatinib and PD1 inhibitor from March 2019 to May 2023 in Zhongshan People's Hospital were included. The objective response rate (ORR), disease control rate (DCR), median overall survival (mOS), median progression-free survival (mPFS), median duration of response (mDOR), and adverse events (AEs) were assessed. A total of 95 patients were enrolled in this study, including 34 cases in the HAIC+L+P group and 61 cases in the TACE+L+P group. According to the RECIST1.1, the ORR was 52.9% and 27.9%, and the DCR was 100% and 88.5%, respectively (P values =0.03 and < 0.001, respectively). The mOS of HAIC+L+P group and TACE+L+P group were 25.00 and 19.30 months, respectively (P=0.035). The mPFS of the two groups were 21.74 and 8.74 months, respectively (P=0.0066). The mDOR of the two groups was 20.43 and 9.13 months, respectively (P=0.067). Compared with TACE in combination with lenvatinib and PD-1 inhibitors, HAIC (FOLFOX) in combination with lenvatinib and PD-1 inhibitors can improve tumor response and prolong OS, PFS, and DOR in HCC patients with PVTT and APFs.

Isolated bronchial hemangioma causing recurrent hemoptysis: A case report.

RATIONAL: The development of bronchial hemangioma in adults is rare, and massive hemoptysis due to diffuse vascular proliferation of bronchial hemangioma is fatal. PATIENT CONCERNS: A case of a 29-year-old woman kept massive hemoptysis even after being underwent repeated interventional embolization for recurrent massive hemoptysis. Eventually, the patient was performed the operation of right upper lung lobectomy and bronchial hemangioma with extracorporeal membrane oxygenation support and was followed up for 4 years without recurrent hemoptysis. DIAGNOSES: Bronchial hemangioma. CONCLUSION: For patients with bronchial angiomas bonded with bronchial artery-pulmonary arteriovenous fistulae, the early surgical resection is recommended if bronchial artery embolization (BAE) is considered ineffective.

Association of low-level lead exposure with all-cause and cardiovascular disease mortality in US adults with hypertension: evidence from the National Health and Nutrition Examination Survey 2003-2010.

BACKGROUND: To explore the association of low-level lead exposure with all-cause mortality and cardiovascular disease (CVD) mortality among hypertensive patients. METHODS: This cohort study enrolled 6453 adults with hypertension from the National Health and Nutrition Examination Survey 2003-2010 and followed mortality information through December 31, 2019. The baseline population were divided into four groups based on quartiles of blood lead levels (Q1: < 1.2 µg/dL, Q2: 1.2-1.6 µg/dL, Q3: 1.7-2.4 µg/dL, Q4: 2.5-4.9 µg/dL). The correlation of blood lead levels to mortality was investigated by Kaplan-Meier survival curves, restricted cubic spline (RCS), proportional hazard regression model, and subgroup analysis. RESULTS: During a median follow-up period of 136 (interquartile range 113, 164) months, a total of 1943 (30.1%) deaths were documented, among which 553 (28.5%) were due to CVD. Blood lead showed a linear dose-response relationship with all-cause and CVD mortality. After adequate adjusting for confounders, the risk of all-cause death rose by 23% for each unit increase in continuous variable blood lead (hazard ratio (HR): 1.23; 95% confidence interval (CI):1.16-1.30). When blood lead was a quartile group variable, participants in the Q 4 group had a 73% higher risk of death than those in the Q 1 group (HR:1.73; 95% CI: 1.43-2.10; P for trend < 0.001). The association for CVD mortality was analogous. The concordant results were achieved in the subgroup analysis. CONCLUSION: Elevated blood lead levels were strongly associated with an increased all-cause and CVD mortality in adults with hypertension, even at the reference range of blood lead.

Maintaining hypoxia environment of subchondral bone alleviates osteoarthritis progression.

Abnormal subchondral bone remodeling featured by overactivated osteoclastogenesis leads to articular cartilage degeneration and osteoarthritis (OA) progression, but the mechanism is unclear. We used lymphocyte cytosolic protein 1 (Lcp1) knockout mice to suppress subchondral osteoclasts in a mice OA model with anterior cruciate ligament transection (ACLT), and Lcp1-/- mice showed decreased bone remodeling in subchondral bone and retarded cartilage degeneration. For mechanisms, the activated osteoclasts in subchondral bone induced type-H vessels and elevated oxygen concentration, which ubiquitylated hypoxia-inducible factor 1 alpha subunit (HIF-1α) in chondrocytes and led to cartilage degeneration. Lcp1 knockout impeded angiogenesis, which maintained hypoxia environment in joints and delayed the OA progression. Stabilization of HIF-1α delayed cartilage degeneration, and knockdown of Hif1a abolished the protective effects of Lcp1 knockout. Last, we showed that Oroxylin A, an Lcp1-encoded protein l-plastin (LPL) inhibitor, could alleviate OA progression. In conclusion, maintaining hypoxic environment is an attractive strategy for OA treatment.

Bone-Targeted Exosomes: Strategies and Applications.

As the global population ages, bone-related diseases have increasingly become a major social problem threatening human health. Exosomes, as natural cell products, have been used to treat bone-related diseases due to their superior biocompatibility, biological barrier penetration, and therapeutic effects. Moreover, the modified exosomes exhibit strong bone-targeting capabilities that may improve efficacy and avoid systemic side effects, demonstrating promising translational potential. However, a review of bone-targeted exosomes is still lacking. Thus, the recently developed exosomes for bone-targeting applications in this review are focused. The biogenesis and bone-targeting regulatory functions of exosomes, the constructive strategies of modified exosomes to improve bone-targeting, and their therapeutic effects for bone-related diseases are introduced. By summarizing developments and challenges in bone-targeted exosomes, It is striven to shed light on the selection of exosome constructive strategies for different bone diseases and highlight their translational potential for future clinical orthopedics.

The association between serum albumin and long length of stay of patients with acute heart failure: A retrospective study based on the MIMIC-IV database.

BACKGROUND: The purpose of this article is to assess the relationship between serum albumin level and long length of stay (LOS) of inpatients with acute heart failure (AHF) in the intensive care unit (ICU). METHODS: We retrospectively analyzed data of 2280 patients with AHF from the medical information mart for intensive care IV (the MIMIC-IV) database. Multivariate logistic regression was performed to evaluate the association between serum albumin and long LOS, and the development of the predictive model was based on independent predictors of long LOS. RESULTS: According to the statistical results, A negative linear relationship was presented between albumin and long LOS of AHF patients in the ICU (P for trend <0.001), and serum albumin could predict long LOS (AUC 0.649, 95%CI 0.616-0.683, P <0.001). Based on independent predictors, including respiratory failure (OR 1.672, 95%CI 1.289-2.169, P<0.001), WBC (OR 1.046, 95%CI 1.031-1.061, P<0.001), creatinine (OR 1.221, 95%CI 1.098-1.257, P<0.001), glucose (OR 1.010, 95%CI 1.007-1.012, P<0.001), lactic acid (OR 1.269, 95%CI 1.167-1.381, P<0.001), and albumin (OR 0.559, 95%CI 0.450-0.695, P<0.001), identified by multivariable logistic regression analysis, we developed the nomogram to predict the probability of long LOS of AHF patients in the ICU. The nomogram accurately predicted the probability of long LOS (AUC 0.740, 95%CI 0.712-0.768, P<0.001). The calibration suggested the predictive probability was highly consistent with the actual probability of long LOS. Decision curve analysis (DCA) also suggested that the nomogram was applicable in the clinic. CONCLUSION: Serum albumin level was negatively associated with LOS among AHF patients. The predictive model based on serum albumin has predictive value for evaluating the length of stay in AHF patients.

Percutaneous microwave ablation and transcatheter arterial chemoembolization for serum tumor markers and prognostics of middle-late primary hepatic carcinoma.

BACKGROUND: Primary hepatic carcinoma (PHC) has an insidious onset and is usually diagnosed in the middle and late stages. Although transcatheter arterial chemoembolization (TACE) is the preferred option for treating middle- and advanced-stage PHC, it has limited efficacy in killing tumor cells and poor long-term efficacy. TACE plus percutaneous microwave coagulation therapy (PMCT) is more effective than interventional therapy alone and can improve survival time. However, there are few reports on the effects of TACE and PMCT on serum marker levels and the prognosis of patients with advanced PHC. AIM: To investigate the effect of PMCT + TACE on serum tumor markers and the prognosis of middle-late PHC. METHODS: This retrospective study included 150 patients with middle-late PHC admitted to Zhongshan People's Hospital between March 2018 and February 2021. Patients were divided into a single group (treated with TACE, n = 75) and a combined group (treated with TACE + PMCT, n = 75). Before and after treatment, the clinical efficacy and serum tumor marker levels [carbohydrate antigen 19-9 (CA19-9), alpha-fetoprotein (AFP), and carcinoembryonic antigen (CEA)] of both groups were observed. The 1-year survival rates and prognostic factors of the two groups were analyzed. RESULTS: The combined group had 21 and 35 cases of complete remission (CR) and partial remission (PR), respectively. The single group had 13 and 25 cases of CR and PR, respectively. After 4 wk of treatment, the serum CA19-9, CEA, and AFP levels in the single and combined groups decreased, with the decrease in the combined group being more significant (P < 0.05). The 1-year survival rate of the combined group (80.00%) was higher than that of the single group (60.00%) (P < 0.05). The average survival time within 1 year in the combined group was 299.38 ± 61.13 d, longer than that in the single group (214.41 ± 72.97 d, P < 0.05). COX analysis revealed that tumor diameter, tumor number, and the treatment method were prognostic factors for patients with middle-late PHC (P < 0.05). CONCLUSION: TACE + PMCT is effective in treating patients with mid-late PHC. It reduces the levels of tumor markers, prolongs survival, and improves prognosis.

Prognostic value of TIGIT in East Asian patients with solid cancers: A systematic review, meta-analysis and pancancer analysis.

Background: T-cell immunoreceptor with Ig and ITIM domains (TIGIT) participates in tumor immune escape by delivering inhibitory signals to T cells. The purpose of this article was to assess the prognostic value of TIGIT and its immunological function in solid cancers. Methods: Three databases were searched for relevant articles. The main endpoints were overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS), and disease-free survival (DFS). Hazard ratios (HR) were pooled by using fixed-effects or random-effects models. Pancancer analysis of TIGIT was performed based on public online databases, mainly The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and UCSC Xena. The possible relationships between TIGIT expression and the tumor microenvironment (TME), infiltration of immune cells, immune-related genes, tumor mutation burden (TMB), and microsatellite instability (MSI) were revealed in this article. Results: Sixteen studies met the inclusion criteria. High expression of TIGIT was associated with worse OS [HR= 1.73, 95% confidence interval (CI) 1.50, 1.99], PFS (HR = 1.53, 95% CI [1.25, 1.88]), RFS (HR = 2.40, 95% CI [1.97, 2.93]), and DFS (HR= 6.57, 95% CI [0.73, 59.16]) in East Asian patients with solid cancers. TIGIT expression was positively correlated with immune infiltration scores and infiltration of CD8 T lymphocytes in all of the cancers included. TIGIT was found to be coexpressed with the genes encoding immunostimulators, immunoinhibitors, chemokines, chemokine receptors, and major histocompatibility complex (MHC), especially in gastroesophageal cancer. TMB and MSI were also associated with TIGIT upregulation in diverse kinds of cancers. Conclusion: High expression of TIGIT is associated with poorer prognosis in East Asian patients with solid cancers. TIGIT is a novel prognostic biomarker and immunotherapeutic target for various solid cancers because of its activity in cancer immunity and tumorigenesis.

Development and validation of a predictive model for adverse left ventricular remodeling in NSTEMI patients after primary percutaneous coronary intervention.

INTRODUCTION: To develop and validate clinical evaluators that predict adverse left ventricular remodeling (ALVR) in non-ST-elevation myocardial infarction (NSTEMI) patients after primary percutaneous coronary intervention (PCI). METHODS: The retrospective study analyzed the clinical data of 507 NSTEMI patients who were treated with primary PCI from the Affiliated Hospital of Xuzhou Medical University and the Second Affiliated Hospital of Xuzhou Medical University, between January 1, 2019 and September 31, 2021. The training cohort consisted of patients admitted before June 2020 (n = 287), and the remaining patients (n = 220) were assigned to an external validation cohort. The endpoint event was the occurrence of ALVR, which was described as an increase ≥ 20% in left ventricular end-diastolic volume (LVEDV) at 3-4 months follow-up CMR compared with baseline measurements. The occurrence probability of ALVR stemmed from the final model, which embodied independent predictors recommended by logistic regression analysis. The area under the receiver operating characteristic curve (AUC), Calibration plot, Hosmer-Lemeshow method, and decision curve analysis (DCA) were applied to quantify the performance. RESULTS: Independent predictors for ALVR included age (odds ratio (OR): 1.040; 95% confidence interval (CI): 1.009-1.073), the level of neutrophil to lymphocyte ratio (OR: 4.492; 95% CI: 1.906-10.582), the cardiac microvascular obstruction (OR: 3.416; 95% CI: 1.170-9.970), peak global longitudinal strain (OR: 1.131; 95% CI: 1.026-1.246), infarct size (OR: 1.082; 95% CI: 1.042-1.125) and left ventricular ejection fraction (OR: 0.925; 95% CI: 0.872-0.980), which were screened by regression analysis then merged into the nomogram model. Both internal validation (AUC: 0.805) and external validation (AUC: 0.867) revealed that the prediction model was capable of good discrimination. Calibration plot and Hosmer-Lemeshow method showed high consistency between the probabilities predicted by the nomogram (P = 0.514) and the validation set (P = 0.762) and the probabilities of actual occurrence. DCA corroborated the clinical utility of the nomogram. CONCLUSIONS: In this study, the proposed nomogram model enabled individualized prediction of ALVR in NSTEMI patients after reperfusion and conduced to guide clinical therapeutic schedules.

Development and Validation of a Clinical and Laboratory-Based Nomogram for Predicting Coronary Microvascular Obstruction in NSTEMI Patients After Primary PCI.

OBJECTIVE: Cardiac microvascular obstruction (CMVO) remains a severe complication in non-ST elevation myocardial infarction (NSTEMI) patients with reperfusion therapy. We aimed at developing and validating the nomogram to predict the possibility of CMVO after primary percutaneous coronary intervention (PCI) by integrating clinical and laboratory-based information. METHODS: A total of 325 patients undergoing primary PCI for NSTEMI were recruited and divided into the training cohort (n=226) and the validating cohort (n = 99). The development of the nomogram was based on independent predictors of CMVO, and these variables were selected by multivariable logistic regression analysis. RESULTS: Independent predictors contained in nomogram were identified by multivariable logistic regression analysis, and these independent predictors included neutrophils (OR 1.166, 95% CI 1.044-1.303, P<0.01), hemoglobin (OR 1.037, 95% CI 1.013-1.062, P<0.01), triglyceride (OR 1.343, 95% CI 1.059; 1.704, P=0.015), Killip grade (OR 2.190, 95% CI 1.065-4.503, P=0.033), high thrombus load (OR 3.146, 95% CI 1.424-6.952, P<0.01), no-reflow (OR 3.142, 95% CI 1.419-6.955, P<0.01) and ischemic postconditioning (OR 0.445, 95% CI 0.209-0.944, P=0.035). The nomogram accurately predicted the presentation of CMVO in both the training set and validating set (AUC, 0.835 and 0.881, respectively). The results predicted by nomogram were confirmed to be highly consistent with the results of DE-CMR, both the training and validating cohorts, by Calibration plot and Hosmer-Lemeshow test. Decision curve analysis (DCA) also suggested that the nomogram was applicable in the clinic. CONCLUSION: The nomogram showed good performance in predicting CMVO, and it could help clinicians optimize the clinical treatments to improve the prognosis of NSTEMI patients.

Diterbutyl phthalate attenuates osteoarthritis in ACLT mice via suppressing ERK/c-fos/NFATc1 pathway, and subsequently inhibiting subchondral osteoclast fusion.

Osteoarthritis (OA) is the most common arthritis with a rapidly increasing prevalence. Disease progression is irreversible, and there is no curative therapy available. During OA onset, abnormal mechanical loading leads to excessive osteoclastogenesis and bone resorption in subchondral bone, causing a rapid subchondral bone turnover, cyst formation, sclerosis, and finally, articular cartilage degeneration. Moreover, osteoclast-mediated angiogenesis and sensory innervation in subchondral bone result in abnormal vascularization and OA pain. The traditional Chinese medicine Panax notoginseng (PN; Sanqi) has long been used in treatment of bone diseases including osteoporosis, bone fracture, and OA. In this study we established two-dimensional/bone marrow mononuclear cell/cell membrane chromatography/time of flight mass spectrometry (2D/BMMC/CMC/TOFMS) technique and discovered that diterbutyl phthalate (DP) was the active constituent in PN inhibiting osteoclastogenesis. Then we explored the therapeutic effect of DP in an OA mouse model with anterior cruciate ligament transaction (ACLT). After ACLT was conducted, the mice received DP (5 mg·kg-1·d-1, ip) for 8 weeks. Whole knee joint tissues of the right limb were harvested at weeks 2, 4, and 8 for analysis. We showed that DP administration impeded overactivated osteoclastogenesis in subchondral bone and ameliorated articular cartilage deterioration. DP administration blunted aberrant H-type vessel formation in subchondral bone marrow and alleviated OA pain assessed in Von Frey test and thermal plantar test. In RANKL-induced RAW264.7 cells in vitro, DP (20 µM) retarded osteoclastogenesis by suppressing osteoclast fusion through inhibition of the ERK/c-fos/NFATc1 pathway. DP treatment also downregulated the expression of dendritic cell-specific transmembrane protein (DC-STAMP) and d2 isoform of the vacuolar (H+) ATPase V0 domain (Atp6v0d2) in the cells. In conclusion, we demonstrate that DP prevents OA progression by inhibiting abnormal osteoclastogenesis and associated angiogenesis and neurogenesis in subchondral bone.

CT-based radiomics to predict development of macrovascular invasion in hepatocellular carcinoma: A multicenter study.

BACKGROUND: Macrovascular invasion (MaVI) occurs in nearly half of hepatocellular carcinoma (HCC) patients at diagnosis or during follow-up, which causes severe disease deterioration, and limits the possibility of surgical approaches. This study aimed to investigate whether computed tomography (CT)-based radiomics analysis could help predict development of MaVI in HCC. METHODS: A cohort of 226 patients diagnosed with HCC was enrolled from 5 hospitals with complete MaVI and prognosis follow-ups. CT-based radiomics signature was built via multi-strategy machine learning methods. Afterwards, MaVI-related clinical factors and radiomics signature were integrated to construct the final prediction model (CRIM, clinical-radiomics integrated model) via random forest modeling. Cox-regression analysis was used to select independent risk factors to predict the time of MaVI development. Kaplan-Meier analysis was conducted to stratify patients according to the time of MaVI development, progression-free survival (PFS), and overall survival (OS) based on the selected risk factors. RESULTS: The radiomics signature showed significant improvement for MaVI prediction compared with conventional clinical/radiological predictors (P < 0.001). CRIM could predict MaVI with satisfactory areas under the curve (AUC) of 0.986 and 0.979 in the training (n = 154) and external validation (n = 72) datasets, respectively. CRIM presented with excellent generalization with AUC of 0.956, 1.000, and 1.000 in each external cohort that accepted disparate CT scanning protocol/manufactory. Peel9_fos_InterquartileRange [hazard ratio (HR) = 1.98; P < 0.001] was selected as the independent risk factor. The cox-regression model successfully stratified patients into the high-risk and low-risk groups regarding the time of MaVI development (P < 0.001), PFS (P < 0.001) and OS (P = 0.002). CONCLUSIONS: The CT-based quantitative radiomics analysis could enable high accuracy prediction of subsequent MaVI development in HCC with prognostic implications.

Multi-task deep learning network to predict future macrovascular invasion in hepatocellular carcinoma.

BACKGROUND: Models predicting future macrovascular invasion in hepatocellular carcinoma are constructed to assist timely interventions. METHODS: A total of 366 HCC cases were retrospectively collected from five Chinese hospitals between April 2007 and November 2016: the training dataset comprised 281 patients from four hospitals; the external validation dataset comprised 85 patients from another hospital. Multi-task deep learning network-based models were constructed to predict future macrovascular invasion. The discrimination, calibration, and decision curves were compared to identify the best model. We compared the time to macrovascular invasion and overall survival using the best model and related image heterogeneity scores (H-score). Then, we determined the need for a segmentation subnet or the replacement deep learning algorithm by logistic regression in screening clinical/radiological factors. Finally, an applet was constructed for future application. FINDINGS: The best model combined clinical/radiological factors and radiomic features. It achieved best discrimination (areas under the curve: 0·877 in the training dataset and 0·836 in the validation dataset), calibration, and decision curve. Its performance was not affected by the treatments and disease stages. The subgroups had statistical significance for time to macrovascular invasion (training: hazard ratio [HR] = 0·073, 95% confidence interval [CI]: 0·032-0·167, p < 0·001 and validation: HR = 0·090, 95%CI: 0·022-0·366, p < 0·001) and overall survival (training: HR = 0·344, 95%CI: 0·246-0·547, p < 0·001 and validation: HR = 0·489, 95%CI: 0·279 - 0·859, p = 0·003). Similar results were achieved when the patients were subdivided by the H-score. The subnet for segmentation and end-to-end deep learning algorithms improved the performance of the model. INTERPRETATION: Our multi-task deep learning network-based model successfully predicted future macrovascular invasion. In high-risk populations, besides the current first-line treatments, more therapies may be explored for macrovascular invasion.

Deep Learning-Based Prediction of Future Extrahepatic Metastasis and Macrovascular Invasion in Hepatocellular Carcinoma.

PURPOSE: For timely treatment of extrahepatic metastasis and macrovascular invasion (aggressive progressive disease [PD]) in hepatocellular carcinoma, models aimed at stratifying the risks of subsequent aggressive PD should be constructed. PATIENTS AND METHODS: After dividing 332 patients from five hospitals into training (n = 236) and validation (n = 96) datasets, non-invasive models, including clinical/semantic factors (ModelCS), deep learning radiomics (ModelD), and both (ModelCSD), were constructed to stratify patients according to the risk of aggressive PD. We examined the discrimination and calibration; similarly, we plotted a decision curve and devised a nomogram. Furthermore, we performed analyses of subgroups who received different treatments or those in different disease stages and compared time to aggressive PD and overall survival in the high- and low-risk subgroups. RESULTS: Among the constructed models, ModelCSD, combining clinical/semantic factors and deep learning radiomics, outperformed ModelCS and ModelD (areas under the curve [AUCs] for the training dataset: 0.741, 0.815, and 0.856; validation dataset: 0.780, 0.836, and 0.862), with statistical difference per the net reclassification improvement, the integrated discrimination improvement, and/or the DeLong test in both datasets. Besides, ModelCSD had the best calibration and decision curves. The performance of ModelCSD was not affected by treatment types (AUC: resection = 0.839; transarterial chemoembolization = 0.895; p = 0.183) or disease stages (AUC: BCLC [Barcelona Clinic Liver Cancer] stage 0 and A = 0.827; BCLC stage AB &B = 0.861; p = 0.537). Moreover, the high-risk group had a significantly shorter median time to aggressive PD than the low-risk group (training dataset hazard ratio [HR] = 0.108, p < 0.001; validation dataset HR = 0.058, p < 0.001) and poorer overall survival (training dataset HR = 0.357, p < 0.001; validation dataset HR = 0.204, p < 0.001). CONCLUSION: Our deep learning-based model successfully stratified the risks of aggressive PD. In the high-risk population, current guideline indicates that first-line treatments are insufficient to prevent extrahepatic metastasis and macrovascular invasion and ensure survival benefits, so more therapies may be explored for these patients.

Gate Alignment of Liquid Water Molecules in Electric Double Layer.

The behavior of liquid water molecules near an electrified interface is important to many disciplines of science and engineering. In this study, we applied an external gate potential to the silica/water interface via an electrolyte-insulator-semiconductor (EIS) junction to control the surface charging state. Without varying the ionic composition in water, the electrical gating allowed an efficient tuning of the interfacial charge density and field. Using the sum-frequency vibrational spectroscopy, we found a drastic enhancement of interfacial OH vibrational signals at high potential in weakly acidic water, which exceeded that from conventional bulk-silica/water interfaces even in strong basic solutions. Analysis of the spectra indicated that it was due to the alignment of liquid water molecules through the electric double layer, where the screening was weak because of the low ion density. Such a combination of strong field and weak screening demonstrates the unique tuning capability of the EIS scheme, and would allow us to investigate a wealth of phenomena at charged oxide/water interfaces.