Targeting long non-coding RNA H19 in Subchondral Bone Osteocytes Alleviates Cartilage Degradation in Osteoarthritis.

INTRODUCTION: Emerging evidence suggests long non-coding RNA (lncRNA) H19 is associated with osteoarthritis (OA) pathology. However, how H19 contributes to OA has not been reported. This study aims to investigate the biological function of H19 in OA subchondral bone remodeling and OA progression. METHODS: Clinical joint samples and OA animal models induced by medial meniscus destabilization (DMM) surgery were used to verify the causal relationship between osteocyte H19 and OA subchondral bone and cartilage changes. MLO-Y4 osteocyte cells subjected to fluid shear stress were used to verify the mechanism underlying H19-mediated mechano-response. Finally, the antisense oligonucleotide (ASO) against H19 was delivered to mice knee joints by magnetic metal-organic framework (MMOF) nanoparticles in order to develop a site-specific delivery method for targeting osteocyte H19 for OA treatment. RESULTS: Both clinical OA subchondral bone and wildtype mice with DMM-induced OA exhibit aberrant higher subchondral bone mass with more H19 expressing osteocytes. On the contrary, osteocyte-specific deletion of H19 mice is less vulnerable to DMM-induced OA phenotype. In MLO-Y4 cells, H19-mediated osteocyte mechano-response through PI3K/AKT/GSK3 signals activation by EZH2-induced H3K27me3 regulation on PP2A inhibition. Targeted inhibition of H19 (using ASO-loaded MMOF) substantially alleviates subchondral bone remodeling and OA phenotype. DISCUSSION: In summary, our results provide new evidence that the elevated H19 expression in osteocytes may contribute to aberrant subchondral bone remodeling and OA progression. H19 appears to be required for the osteocyte response to mechanical stimulation, and targeting H19 represents a new promising approach for OA treatment.

Nicotinamide mononucleotide enhances fracture healing by promoting skeletal stem cell proliferation.

The process of skeletal regeneration initiated by stem cells following injury, especially in fractures, is significantly impaired by aging and adverse factors. Nicotinamide mononucleotide (NMN), a critical endogenous precursor of nicotinamide adenine dinucleotide (NAD), has garnered extensive attention for its multifaceted regulatory functions in living organisms and its wide-ranging therapeutic potential. However, whether NMN contributes to trauma-induced skeletal regeneration remains unclear. Methods: The transverse femoral shaft fracture model was employed to evaluate the potential advantages of NMN administration for overall repair during the initial fracture stages in male mice through micro-CT analysis, histochemistry, and biomechanical testing. The pro-proliferative function of NMN on skeletal stem cells (SSCs) was investigated through flow cytometry, qRT-PCR, NAD content measurement, and cell proliferation assay. Results: In this study, we observed that the administration of NMN during the initial phase of fracture in mice led to a larger callus and corresponding improvement in micro-CT parameters. NMN enhances the cartilaginous component of the callus by elevating the NAD content, consequently accelerating subsequent endochondral ossification and the fracture healing process. Subsequent analyses elucidated that NMN was beneficial in promoting the expansion of diverse stem cells in vivo and in vitro potentially via modulation of the Notch signaling pathway. Moreover, the depletion of macrophages profoundly obstructs the proliferation of SSCs. Conclusion: Our discoveries provide a potential strategy for enhancing fracture healing through stimulation of callus SSC proliferation at an early stage, shedding light on the translational value of NMN as an enhancer for skeletal regeneration and highlighting the pivotal role of macrophage-stem cell interactions in governing the regenerative influence of NMN on stem cells.

How is parental psychological control associated with adolescent mental health in economically disadvantaged areas? The serial mediating role of psychological reactance and problematic smartphone use.

Introduction: Adolescent mental health has been an issue of global concern, and the mental health of adolescents in economically disadvantaged areas may require additional research. The research delves into factors associated with economically disadvantaged areas' adolescent mental health, employing family systems theory, self-determination theory, and psychological reactance theory. Specifically, the present study which was done in Jingzhou country, an economically disadvantaged area of Hunan Province, China, aimed to examine the link between parental psychological control and adolescent mental health, as well as the mediating roles of psychological reactance and problematic smartphone use in this relationship. Methods: A sample of 1300 Chinese middle school students (620 girls, mean age = 14.22 ± 1.29) completed self-reported measures of parental psychological control, psychological reactance, problematic smartphone use, and adolescent mental health. Results: Results showed that parental psychological control was negatively associated with adolescent mental health. Psychological reactance and problematic smartphone use mediated the association between parental psychological control and adolescent mental health, separately and serially. Discussion: The findings of the present study enrich the literature on parenting styles and adolescent mental health in economically disadvantaged areas, and this provides an intervention perspective to reduce the negative impact of poor parenting on adolescent mental health in economically disadvantaged areas.

Social Media and Adolescents' Prosocial Behavior: Evidence of the Interaction Between Short Videos and Social Value Orientation.

Background/Objective: Social media significantly influences adolescents' prosocial behavior. With smartphones becoming ubiquitous, short videos have emerged as the predominant social media format for adolescents. However, the effects of adolescents' engagement with short videos on their prosocial behavior remain uncertain. This study aims to address the problem of how short videos (content and consequences) affect prosocial behavior in adolescents, and simultaneously explores the differences of this effect among individuals with different social value orientations. Methods: The current study conducted two research laboratory experiments using the between-subject study design of two factors. Study 1 (N=148) reveals that viewing prosocial short videos significantly predicts adolescents' prosocial behavior more so than neutral short videos. The interaction between short video content and social value orientation on prosocial behavior illustrates that the encouraging impact of prosocial content is primarily evident in prosocial individuals, rather than in pro-self individuals. In Study 2 (N=152), we introduce new dimensions by assessing adolescents' response to varying consequences of the same prosocial behavior (ie, reward, punishment) within the short video context. Findings indicate that reward consequences significantly bolster adolescents' prosocial behavior, whereas punitive measures tend to adversely affect it. Furthermore, the interaction between the consequences of prosocial short videos and social value orientation suggests that prosocial individuals exhibit no significant behavioral difference between rewards and punishments; instead, the reward/punishment consequences notably influence the prosocial behavior of pro-self individuals. Conclusion: Short videos (content and consequences) and social value orientations interactively influence adolescents' prosocial behaviors. This study underscores the need to recognize individual differences in adolescents' use of short videos and its impact on their prosocial behavior, particularly highlighting the crucial role of their social value orientations. Practically, the research offers valuable insights for parents and professionals seeking to foster adolescents' prosocial behavior.

Impact of Pulmonary Artery Banding in Patients with Congenital Heart Disease and Pulmonary Hypertension.

Background: To evaluate the effectiveness of the surgical approach in patients with congenital heart disease and pulmonary hypertension (PH). Methods: This was a retrospective clinical review of patients with congenital heart disease and PH who underwent pulmonary artery banding (PAB) at our institution between January 2013 and January 2023. Results: We identified 219 patients (53.4% males) with a median age of 7 (4.0-15.0) months and a median weight of 6.8 (5.2-9.0) kg at the time of PAB. The median hospital stay was 7.0 (5.0-10.0) days. The in-hospital mortality rate was 4.6%. The median follow-up was 33.0 (17.0-61.0) months. Survival rates were 96.9 ± 2.5% at 60 months and 92.1 ± 6.9% at 120 months post-PAB. 43.8% of patients had a de-banding procedure, and 147 (79.0%) patients received a second-stage procedure (34.7% univentricular, 65.3% biventricular). The mortality rate between stages was 4.3%. 21 (9.6%) patients reached a third-stage procedure. The overall mortality rate was 9.1%. Conclusions: PAB is an acceptable strategy for patients with congenital heart disease complicated with PH. The results and outcomes of subsequent univentricular or biventricular procedures are generally good.

Repair of spinal cord injury by bone marrow mesenchymal stem cell-derived exosomes: a systematic review and meta-analysis based on rat models.

Objective: This study aims to systematically evaluate the efficacy of bone marrow mesenchymal stem cell-derived exosomes (BMSCs-Exo) in improving spinal cord injury (SCI) to mitigate the risk of translational discrepancies from animal experiments to clinical applications. Methods: We conducted a comprehensive literature search up to March 2024 using PubMed, Embase, Web of Science, and Scopus databases. Two researchers independently screened the literature, extracted data, and assessed the quality of the studies. Data analysis was performed using STATA16 software. Results: A total of 30 studies were included. The results indicated that BMSCs-Exo significantly improved the BBB score in SCI rats (WMD = 3.47, 95% CI [3.31, 3.63]), inhibited the expression of the pro-inflammatory cytokine TNF-α (SMD = -3.12, 95% CI [-3.57, -2.67]), and promoted the expression of anti-inflammatory cytokines IL-10 (SMD = 2.76, 95% CI [1.88, 3.63]) and TGF-ß (SMD = 3.89, 95% CI [3.02, 4.76]). Additionally, BMSCs-Exo significantly reduced apoptosis levels (SMD = -4.52, 95% CI [-5.14, -3.89]), promoted the expression of axonal regeneration markers NeuN cells/field (SMD = 3.54, 95% CI [2.65, 4.42]), NF200 (SMD = 4.88, 95% CI [3.70, 6.05]), and the number of Nissl bodies (SMD = 1.89, 95% CI [1.13, 2.65]), and decreased the expression of astrogliosis marker GFAP (SMD = -5.15, 95% CI [-6.47, -3.82]). The heterogeneity among studies was primarily due to variations in BMSCs-Exo transplantation doses, with efficacy increasing with higher doses. Conclusion: BMSCs-Exo significantly improved motor function in SCI rats by modulating inflammatory responses, reducing apoptosis, inhibiting astrogliosis, and promoting axonal regeneration. However, the presence of selection, performance, and detection biases in current animal experiments may undermine the quality of evidence in this study.

Lespedeza bicolor Turcz. Honey Prevents Inflammation Response and Inhibits Ferroptosis by Nrf2/HO-1 Pathway in DSS-Induced Human Caco-2 Cells.

Lespedeza bicolor Turcz. (L. bicolor) honey, a monofloral honey, has garnered increased attention due to its origin in the L. bicolor plant. A previous study has shown that L. bicolor honey can ameliorate inflammation. In this study, we aimed to investigate the effects of L. bicolor honey extract and its biomarker (Trifolin) on DSS-induced ulcerative colitis (UC). Our results demonstrated that L. bicolor honey extract and Trifolin significantly increased the expression levels of the tight junction cytokines Claudin-1 and ZO-1. Additionally, they decreased the pro-inflammatory factors TNF-α and IL-6 and enhanced the antioxidant factors NQO1 and GSTA1. Based on metabolomic analyses, L. bicolor honey extract and Trifolin regulated the progression of UC by inhibiting ferroptosis. Mechanistically, they improved the levels of SOD and iron load, increased the GSH/GSSG ratio, reduced MDA content and ROS release, and upregulated the Nrf2/HO-1 pathway, thereby inhibiting DSS-induced UC. Moreover, the expression levels of ferroptosis-related genes indicated that they decreased FTL, ACSL4, and PTGS2 while increasing SLC7A11 expression to resist ferroptosis. In conclusion, our study found that L. bicolor honey improves DSS-induced UC by inhibiting ferroptosis by activating the Nrf2/HO-1 pathway. These findings further elucidate the understanding of anti-inflammatory and antioxidant activities of L. bicolor honey.

A novel sustainable photo/chemical magnetic nanomaterial effectively mitigates the allergenicity of phospholipase A2.

Reducing the allergenicity of edible insects is crucial for the comprehensive utilization of insect resources. Phospholipase A2 (PLA2) exists in various edible insects and mammalian tissues, which can cause serious allergic reactions. Herein, we constructed a magnetic nanocomposite with photo/chemical synergistic capability to mitigate the allergenicity of PLA2. The formation of prepared nanocomposite was systematically confirmed using various techniques. The nanocomposite exhibited uniform diameters, abundant functional groups, excellent magnetic capabilities. An effective photo/chemical method was established to reduce the allergenicity of PLA2 in vitro. The feasibility of the method was demonstrated through circular dichroism, fluorescence spectrum and IgE-binding analysis. The allergenicity and IgE-binding effect of PLA2 were significantly reduced due to conformational changes after nanomaterial treatment. These results demonstrate the sensitivity and effectiveness a strategy for reducing PLA2 allergenicity, providing a basis for development of nanomaterials to reduce the risk of novel food allergies in response to edible insect products.

Photoinduced Asymmetric Formal Siloxycarbene Insertion into sp3 C-H Bonds Enabled by Chiral Phosphoric Acid.

We disclosed herein an enantioselective formal siloxycarbene insertion reaction enabled by chiral phosphoric acid and blue LED irradiation. This is the first time the asymmetric siloxycarbene insertion into an sp3 C-H bond under transition-metal free conditions has been realized. The reaction features good isolated yields (up to 92%), high enantioselectivity (up to 99:1 er), mild reaction conditions, and good compatibility. Moreover, this method also provides a green and efficient method to construct a chiral quaternary carbon center.

Reveal the mechanism of hepatic oxidative stress in mice induced by photo-oxidation milk using multi-omics analysis techniques.

INTRODUCTION: Photo-oxidation is recognized as a contributor to the deterioration of milk quality, posing potential safety hazards to human health. However, there has been limited investigation into the impact of consuming photo-oxidized milk on health. OBJECTIVES: This study employs multi-omics analysis techniques to elucidate the mechanisms by which photo-oxidized milk induces oxidative stress in the liver. METHODS: Mouse model was used to determine the effect of the gavage administration of milk with varying degrees of photo-oxidation on the mouse liver. The damage degree was established by measuring serum markers indicative of oxidative stress, and with a subsequent histopathological examination of liver tissues. In addition, comprehensive metabolome, lipidome, and transcriptome analyses were conducted to elucidate the underlying molecular mechanisms of hepatic damage caused by photo-oxidized milk. RESULTS: A significant elevation in the oxidative stress levels and the presence of hepatocellular swelling and inflammation subsequent to the gavage administration of photo-oxidized milk to mice. Significant alterations in the levels of metabolites such as lumichrome, all-trans-retinal, L-valine, phosphatidylglycerol, and phosphatidylcholine within the hepatic tissue of mice. Moreover, photo-oxidized milk exerted a pronounced detrimental impact on the glycerophospholipid metabolism of mice liver. The peroxisome proliferator-activated receptors (PPAR) signaling pathway enrichment appreciated in the animals that consumed photo-oxidized milk further supports the substantial negative influence of photo-oxidized milk on hepatic lipid metabolism. Gene set enrichment and interaction analyses revealed that photo-oxidized milk inhibited the cytochrome P450 pathway in mice, while also affecting other pathways associated with cellular stress response and lipid biosynthesis. CONCLUSION: This comprehensive study provides significant evidence regarding the potential health risks associated with photo-oxidized milk, particularly in terms of hepatic oxidative damage. It establishes a scientific foundation for assessing the safety of such milk and ensuring the quality of dairy products.

Simple "Door-Locking" Technique Using One Single-Row Anchor for Repairing Large Bony Bankart Lesions.

Large bony Bankart injuries are typically stabilized using screws or plates or multiple anchors. Here, the "door-locking" technique, using a single-row anchor, can provide effective fixation for massive bony Bankart injuries. This technique offers several advantages over open fixation surgery or other techniques that use more than 2 suture anchors, including simpler surgical procedures, lower medical costs, and satisfactory clinical outcomes.

Model Predictive Control for Speed-Dependent Active Suspension System with Road Preview Information.

This paper proposes a model predictive control (MPC) scheme based on linear parameter variation to enhance the damping control of speed-dependent active suspensions. The controller is developed by introducing a speed-dependent term, specifically front- and rear-wheel time delays, to the half-car model using the Padé approximation. Subsequently, the model is augmented with time-varying parameter dependence. An adaptive Kalman filter based on variance matching is employed to estimate system states affected by imprecise sensor measurement noise. Finally, a set of explicit control laws incorporating road preview information and available vehicle speed are determined offline using multi-parameter linear programming (mp-LP), simplifying online implementation to searching for optimal solutions in a lookup table. Simulation results demonstrate a significant improvement in active suspension control under changing vehicle speeds compared to passive control.

Flavor Chemical Research on Different Bee Pollen Varieties Using Fast E-Nose and E-Tongue Technology.

Bee pollen, derived from various plant sources, is renowned for its nutritional and bioactive properties, aroma, and taste. This study examined the bee pollen with the highest yield in China obtained from four plant species, namely Brassica campestris (Bc), Nelumbo nucifera (Nn), Camellia japonica (Cj), and Fagopyrum esculentum (Fe), using fast e-nose and e-tongue technology to analyze their flavor chemistry. Results showed substantial differences in scent profiles among the varieties, with distinct odor compounds identified for each, including n-butanol, decanal, and ethanol, in Bc, Nn, and Cj, respectively. The primary odorants in Fe consist of E-2-hexen-1-ol and (Z)-3-hexen-1-ol. Additionally, e-tongue analysis revealed seven distinct tastes in bee pollen samples: AHS, PKS, CTS, NMS, CPS, ANS, and SCS, with variations in intensity across each taste. The study also found correlations between taste components and specific odor compounds, providing insights for enhancing product quality control in bee pollen processing.

Does Proximal Adductor Canal Block Provide Better Analgesic Efficacy than Distal Adductor Canal Block in Patients Undergoing Knee Arthroplasty: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

To compare the analgesic efficacy and adverse events of proximal versus distal ACB for adults undergoing knee arthroplasty, we searched PubMed, Cochrane, Web of Science, and Embase to identify all eligible randomized controlled trials (RCTs). The study quality of the RCTs was evaluated using the Cochrane risk of bias assessment tool. Heterogeneity among studies was examined by Cochrane Q test. Our primary outcomes were pain intensity at rest/during movement and morphine consumption. Statistical analyses were conducted by RevMan Software. Seven eligible studies involving 400 subjects were included in this meta-analysis with 202 participants in the proximal ACB group and 198 participants in the distal ACB group. The results demonstrated that proximal ACB provided significantly better pain relief at rest at 2 h (SMD -0.27, 95% CI -0.54 to -0.01, four trials, 222 participants, I2 = 0, p = 0.04) and 24 h (SMD -0.28, 95% CI -0.48 to -0.08, seven trials, 400 participants, I2 = 0, p = 0.006) following the surgery. We found no evidence of a difference in postoperative pain intensity at other timepoints. Furthermore, we noted no evidence of a difference in cumulative morphine consumption and occurrence of adverse events. Proximal ACB provides better pain relief and comparable adverse effects profile compared with distal ACB. The analgesic benefit offered by proximal ACB, however, did not appear to extend beyond the first 24 h. The overall evidence level was mostly low or very low, which requires more well-organized multicenter randomized trials in the future.

Integrative transcriptomic and proteomic profile revealed inhibition of oxidative phosphorylation and peroxisomes during renal interstitial fibrosis.

Effective therapies of chronic kidney disease (CKD) are lacking due to the unclear molecular pathogenesis. Previous single omics-studies have described potential molecular regulation mechanism of CKD only at the level of transcription or translation. Therefore, this study generated an integrated transcriptomic and proteomic profile to provide deep insights into the continuous transcription-translation process during CKD. The comprehensive datasets identified 14,948 transcripts and 6423 proteins, 233 up-regulated and 364 down-regulated common differentially expressed genes of transcriptome and proteome were selected to further combined bioinformatics analysis. The obtained results revealed reactive oxygen species (ROS) metabolism and antioxidant system due to imbalance of mitochondria and peroxisomes were significantly repressed in CKD. Overall, this study presents a valuable multi-omics analysis that sheds light on the molecular mechanisms underlying CKD. SIGNIFICANCE: Chronic kidney disease (CKD) is a progressive and irreversible condition that results in abnormal kidney function and structure, and is ranked 18th among the leading causes of death globally, leading to a significant societal burden. Hence, there is an urgent need for research to detect new, sensitive, and specific biomarkers. Omics-based studies offer great potential to identify underlying disease mechanisms, aid in clinical diagnosis, and develop novel treatment strategies for CKD. Previous studies have mainly focused on the regulation of gene expression or protein synthesis in CKD, thereby compelling us to conduct a meticulous analysis of transcriptomic and proteomic data from the UUO mouse model. Here, we have performed a unified analysis of CKD model by integrating transcriptomes and protein suites for the first time. Our study contributes to a deeper understanding of the pathogenesis of CKD and provides a basis for subsequent disease management and drug development.

Clinical characteristics and outcomes of patients who underwent neonatal cardiac surgery: ten years of experience in a tertiary surgery center.

OBJECTIVE: To evaluate the outcomes after neonatal cardiac surgery at our institute, and identify factors associated with operative mortality. METHODS: We examined 224 neonates who underwent cardiac surgery at a single institution from 2013 to 2022. Relevant data, such as demographic information, operative details, and postoperative records, were gathered from medical and surgical records. Our primary focus was on the operative mortality. RESULTS: Median age and weight at surgery were 12 (7-20) days and 3.4 (3.0-3.8) kg, respectively. Overall mortality was 14.3% (32/224). Mortality rates showed improvement over time (2013-2017 vs. 2018-2022), with rates decreasing from 21.9% to 10.6% (p = 0.023). ECMO use, extubation failure, lactate > 4.8 mmol/l and VIS > 15.5 on 24 h after operation were significantly associated with operative mortality, according to multivariate logistic regression analysis. Patients admitted to the cardiac intensive care unit (CICU) before surgery and those with prenatal diagnosis showed lower operative mortality. Median follow-up time of 192 hospital survivors was 28.0 (11.0-62.3) months. 10 patients experienced late deaths, and 7 patients required reinterventions after neonatal cardiac surgery. Risk factors for composite end-point of death and reintervention on multivariable analysis were: surgical period (HR = 0.230, 95% CI 0.081-0.654; p = 0.006), prolonged ventilation (HR = 4.792, 95% CI 1.296-16.177; p = 0.018) and STAT categories 3-5 (HR = 5.936, 95% CI 1.672-21.069; p = 0.006). CONCLUSIONS: Our institution has observed improved surgical outcomes in neonatal cardiac surgery over the past five years with low mortality, but late death and reintervention remain necessary in some patients. The location and prenatal diagnosis prior to surgery may affect the outcomes of neonates undergoing congenital heart disease operations.

Incidence and risk factors of perioperative deep vein thrombosis in patients undergoing primary hip arthroplasty via the direct anterior approach.

BACKGROUND: Deep vein thrombosis (DVT) is a frequent complication following hip arthroplasty. There still has been a lack of studies analyzing the perioperative risk factors of DVT following hip arthroplasty via direct anterior approach (DAA). METHODS: Patients who underwent unilateral primary hip arthroplasty via DAA in our hospital from August 2015 to January 2022 were included. Patients' data, including demographic data, clinical features, past medical history, operative data, and laboratory data, were analyzed and compared between patients with and without DVT. Logistic regression analysis was conducted to identify the independent risk factors. Receiver operating characteristic (ROC) curve analysis was used to assess the best cutoff value of continuous variables with statistical significance. RESULT: A total of 651 patients were included. The incidence of DVT before and after hip arthroplasty was 12.7% and 6.7%, respectively. Logistic regression analysis indicated that age ≥ 65 years (OR 4.594, 95% CI 1.994-10.587), women (OR 2.331, 95% CI 1.285-4.227), and cerebral infarction (OR 1.984, 95% CI 1.138-3.460) were independent risk factors for preoperative DVT. And age ≥ 65 years (OR 4.859, 95% CI 1.062-22.226), tumor (OR 3.622, 95% CI 1.108-11.841), and preoperative D-dimer (OR 1.040, 95% CI 1.004-1.078) were risk factors for postoperative DVT. The ROC curve analysis showed that the best cutoff value of preoperative D-dimer for the diagnosis of postoperative DVT is 1.44 mg/L. CONCLUSIONS: The incidence of DVT in patients undergoing DAA hip arthroplasty was low and the occurrence of DVT before and after unilateral primary hip arthroplasty performed through DAA was related to multiple factors.

Mechanism of Circ_HECW2 regulating osteoblast apoptosis in osteoporosis by attenuating the maturation of miR-1224-5p.

BACKGROUND: Osteoporosis (OP) poses a significant clinical challenge with escalating morbidity. This study explores Circ_HECW2 expression in OP patients and its regulatory role in lipopolysaccharide (LPS)-induced osteoblast apoptosis. METHODS: Circ_HECW2 expression in OP patient serum and healthy controls was quantified using RT-qPCR. Diagnostic value of Circ_HECW2 for OP was assessed via ROC curve. Pearson's correlation model examined associations between indicators. Human osteoblasts HFOB1.19, treated with LPS, were analyzed for Circ_HECW2, pre-miR-1224, miR-1224-5p, and PDK2 mRNA levels. TUNEL assay determined cell apoptosis and Western blot assessed cleaved-caspase-3 protein levels. RNase R resistance assay and actinomycin D assay confirmed Circ_HECW2's cyclic structure. RNA pull-down and dual-luciferase reporter assay verified binding relationships between Circ_HECW2 and miR-1224 and between miR-1224-5p and PDK2. RESULTS: Circ_HECW2 exhibited elevated expression in OP patients with diagnostic significance and a negative correlation with lumbar T-score. LPS co-culture increased Circ_HECW2 expression in HFOB1.19 cells, significantly elevating apoptosis index and cleaved-caspase-3. Circ_HECW2 downregulation inhibited HFOB1.19 apoptosis, reduced pre-miR-1224 expression, and elevated mature miR-1224-5p. Circ_HECW2 bound to pre-miR-1224, and inhibiting miR-1224-5p reversed the effect of Circ_HECW2 downregulation on osteoblast apoptosis. miR-1224-5p targeted PDK2 transcription. CONCLUSION: Circ_HECW2, highly expressed in OP, holds diagnostic significance and reflects disease severity. Circ_HECW2 reduces mature miR-1224-5p by binding to pre-miR-1224, upregulating PDK2, and facilitating LPS-induced osteoblast apoptosis.

Treprostinil Effectiveness in Higher-Risk Pediatric Patients With Idiopathic and Heritable Pulmonary Arterial Hypertension.

BACKGROUND: Little is known about the effectiveness of treprostinil in higher-risk paediatric patients with various pulmonary arterial hypertension genotypes. This study was designed to investigate the prognosis of higher-risk paediatric patients with idiopathic or heritable pulmonary arterial hypertension (IPAH/HPAH) after treprostinil therapy. METHODS: Children with IPAH/HPAH who were stratified as higher risk and treated with treprostinil in our centre were included as the study cohort. Those who received only oral medications were included as the reference cohort. All patients in the study cohort received PAH-related genotyping. Survival was defined as no death. Event-free survival was defined as no death, Potts shunt, or atrial septostomy. RESULTS: Forty-nine children (median age 7.7 years [interquartile range (IQR) 4.2-11.5 years], 65% female) were included in the study cohort and 48 children were included in the reference cohort; 84% of the study cohort had genetic disorders after genetic testing with a dominance of BMPR2 and ACVRL1 mutations. After a median therapy duration of 5.56 months (IQR 2.66-11.12 months), all patients were alive with significant improvements in clinical characteristics. One-, 2-, and 3-year survival rates were 91%, 84%, and 69%, respectively with a median follow-up duration of 19.17 months (IQR 9.7-29.79 months), which was significantly superior to the reference cohort (P = 0.038). Multivariate Cox regression analysis identified World Health Organisation functional class after therapy as a predictor for survival. There was no significant difference in survival among patients with different genotypes. CONCLUSIONS: Treprostinil can significantly improve the prognosis in children with IPAH/HPAH who are at higher risk, despite genetic backgrounds.