Optimized lipid nanoparticles (LNPs) for organ-selective nucleic acids delivery in vivo.

Nucleic acid therapeutics offer tremendous promise for addressing a wide range of common public health conditions. However, the in vivo nucleic acids delivery faces significant biological challenges. Lipid nanoparticles (LNPs) possess several advantages, such as simple preparation, high stability, efficient cellular uptake, endosome escape capabilities, etc., making them suitable for delivery vectors. However, the extensive hepatic accumulation of LNPs poses a challenge for successful development of LNPs-based nucleic acid therapeutics for extrahepatic diseases. To overcome this hurdle, researchers have been focusing on modifying the surface properties of LNPs to achieve precise delivery. The review aims to provide current insights into strategies for LNPs-based organ-selective nucleic acid delivery. In addition, it delves into the general design principles, targeting mechanisms, and clinical development of organ-selective LNPs. In conclusion, this review provides a comprehensive overview to provide guidance and valuable insights for further research and development of organ-selective nucleic acid delivery systems.

Seeking Cells, Targeting Bacteria: A Cascade-Targeting Bacteria-Responsive Nanosystem for Combating Intracellular Bacterial Infections.

Intracellular bacteria pose a great challenge to antimicrobial therapy due to various physiological barriers at both cellular and bacterial levels, which impede drug penetration and intracellular targeting, thereby fostering antibiotic resistance and yielding suboptimal treatment outcomes. Herein, a cascade-target bacterial-responsive drug delivery nanosystem, MM@SPE NPs, comprising a macrophage membrane (MM) shell and a core of SPE NPs. SPE NPs consist of phenylboronic acid-grafted dendritic mesoporous silica nanoparticles (SP NPs) encapsulated with epigallocatechin-3-gallate (EGCG), a non-antibiotic antibacterial component, via pH-sensitive boronic ester bonds are introduced. Upon administration, MM@SPE NPs actively home in on infected macrophages due to the homologous targeting properties of the MM shell, which is subsequently disrupted during cellular endocytosis. Within the cellular environment, SPE NPs expose and spontaneously accumulate around intracellular bacteria through their bacteria-targeting phenylboronic acid groups. The acidic bacterial microenvironment further triggers the breakage of boronic ester bonds between SP NPs and EGCG, allowing the bacterial-responsive release of EGCG for localized intracellular antibacterial effects. The efficacy of MM@SPE NPs in precisely eliminating intracellular bacteria is validated in two rat models of intracellular bacterial infections. This cascade-targeting responsive system offers new solutions for treating intracellular bacterial infections while minimizing the risk of drug resistance.

Dual α-globin and truncated EPO receptor knockin restores hemoglobin production in α-thalassemia-derived red blood cells.

Alpha-thalassemia is an autosomal recessive disease with increasing worldwide prevalence. The molecular basis is due to mutation or deletion of one or more duplicated α-globin genes, and disease severity is directly related to the number of allelic copies compromised. The most severe form, α-thalassemia major (αTM), results from loss of all four copies of α-globin and has historically resulted in fatality in utero . However, in utero transfusions now enable survival to birth. Postnatally, patients face challenges similar to ß-thalassemia, including severe anemia and erythrotoxicity due to imbalance of ß-globin and α-globin chains. While curative, hematopoietic stem cell transplantation (HSCT) is limited by donor availability and potential transplant-related complications. Despite progress in genome editing treatments for ß-thalassemia, there is no analogous curative option for patients suffering from α-thalassemia. To address this, we designed a novel Cas9/AAV6-mediated genome editing strategy that integrates a functional α-globin gene into the ß-globin locus in αTM patient-derived hematopoietic stem and progenitor cells (HSPCs). Incorporation of a truncated erythropoietin receptor transgene into the α-globin integration cassette dramatically increased erythropoietic output from edited HSPCs and led to the most robust production of α-globin, and consequently normal hemoglobin. By directing edited HSPCs toward increased production of clinically relevant RBCs instead of other divergent cell types, this approach has the potential to mitigate the limitations of traditional HSCT for the hemoglobinopathies, including low genome editing and low engraftment rates. These findings support development of a definitive ex vivo autologous genome editing strategy that may be curative for α-thalassemia.

Mental stress-induced myocardial ischemia detected by global longitudinal strain and quantitative myocardial contrast echocardiography in women with nonobstructive coronary artery disease.

BACKGROUND: The utility of radionuclide myocardial perfusion imaging including positron emission tomography (PET) for diagnosing mental stress-induced myocardial ischemia (MSIMI) is clinically restricted. This study aims to assess the diagnostic performance of novel echocardiographic techniques, including automated strain and quantitative myocardial contrast echocardiography (MCE) with dedicated software and deep neural network (DNN) model, for MSIMI detection. The secondary objective was to explore the correlation between changes in myocardial blood flow (MBF) and MSIMI. METHODS: 72 female patients aged 18 to 75 with angina and nonobstructive coronary artery disease (ANOCA), and 23 healthy controls were prospectively recruited. Both echocardiography with contrast agent and PET imaging were performed during structured mental stress testing. MSIMI was defined as a summed difference score ≥3 on PET. Echocardiographic parameters including left ventricular global longitudinal strain (LVGLS), ß and A×ß were obtained, and their trends during mental stress testing were observed. ΔGLS, ß reserve and A×ß reserve were respectively calculated. RESULTS: 32 ANOCA patients (44%) and 1 control (4%) were diagnosed with MSIMI (P<0.01). For ANOCA patients with MSIMI, LVGLS, ß and A×ß declined to varied extent during mental stress testing compared to those without MSIMI and the controls (P<0.05). Bland-Altman plots demonstrated good consistency between ß reserve and A×ß reserve output by the DNN model and iMCE software. Receiver operating characteristic (ROC) curve analyses showed that ΔGLS, ß reserve and A×ß reserve demonstrated favorable ability to predict MSIMI, especially the combination of A×ß reserve using iMCE analysis and ΔGLS (area under the curve [AUC] 0.94, sensitivity 83%, specificity 97%). CONCLUSIONS: Novel technologies in echocardiography exhibit the potential to be a clinical alternative to cardiac PET for effectively detecting MSIMI. Attenuated MBF response during structured mental stress testing was correlated with MSIMI, providing a reasonable explanation for the chest discomfort persisting in ANOCA women.

Comprehensive single-cell analysis reveals heterogeneity of fibroblast subpopulations in ovarian cancer tissue microenvironment.

Background: Ovarian cancer, as a highly malignant tumor, features the critical involvement of tumor-associated fibroblasts in the ovarian cancer tissue microenvironment. However, due to the apparent heterogeneity within fibroblast subpopulations, the specific functions of these subpopulations in the ovarian cancer tissue microenvironment remain insufficiently elucidated. Methods: In this study, we integrated single-cell sequencing data from 32 ovarian cancer samples derived from four distinct cohorts and 3226 bulk RNA-seq data from GEO and TCGA-OV cohorts. Utilizing computational frameworks such as Seurat, Monocle 2, Cellchat, and others, we analyzed the characteristics of the ovarian cancer tissue microenvironment, focusing particularly on fibroblast subpopulations and their differentiation trajectories. Employing the CIBERSORTX computational framework, we assessed various cellular components within the ovarian cancer tissue microenvironment and evaluated their associations with ovarian cancer prognosis. Additionally, we conducted Mendelian randomization analysis based on cis-eQTL to investigate causal relationships between gene expression and ovarian cancer. Results: Through integrative analysis, we identified 13 major cell types present in ovarian cancer tissues, including CD8+ T cells, malignant cells, and fibroblasts. Analysis of the tumor microenvironment (TME) cell proportions revealed a significant increase in the proportion of CD8+ T cells and CD4+ T cells in tumor tissues compared to normal tissues, while fibroblasts predominated in normal tissues. Further subgroup analysis of fibroblasts identified seven subgroups, with the MMP11+Fib subgroup showing the highest activity in the TGFß signaling pathway. Single-cell analysis suggested that oxidative phosphorylation could be a key pathway driving fibroblast differentiation, and the ATRNL1+KCN + Fib subgroup exhibited chromosomal copy number variations. Prognostic analysis using a large sample size indicated that high infiltration of MMP11+ fibroblasts was associated with poor prognosis in ovarian cancer. SMR analysis identified 132 fibroblast differentiation-related genes, which were linked to pathways such as platinum drug resistance. Conclusions: In the context of ovarian cancer, fibroblasts expressing MMP11 emerge as the primary drivers of the TGF-beta signaling pathway. Their presence correlates with an increased risk of adverse ovarian prognoses. Additionally, the genetic regulation governing the differentiation of fibroblasts associated with ovarian cancer correlates with the emergence of drug resistance.

Cancer-associated fibroblast-secreted FGF7 as an ovarian cancer progression promoter.

BACKGROUND: Ovarian cancer (OC) is distinguished by its aggressive nature and the limited efficacy of current treatment strategies. Recent studies have emphasized the significant role of cancer-associated fibroblasts (CAFs) in OC development and progression. METHODS: Employing sophisticated machine learning techniques on bulk transcriptomic datasets, we identified fibroblast growth factor 7 (FGF7), derived from CAFs, as a potential oncogenic factor. We investigated the relationship between FGF7 expression and various clinical parameters. A series of in vitro experiments were undertaken to evaluate the effect of CAFs-derived FGF7 on OC cell activities, such as proliferation, migration, and invasion. Single-cell transcriptomic analysis was also conducted to elucidate the interaction between FGF7 and its receptor. Detailed mechanistic investigations sought to clarify the pathways through which FGF7 fosters OC progression. RESULTS: Our findings indicate that higher FGF7 levels correlate with advanced tumor stages, increased vascular invasion, and poorer prognosis. CAFs-derived FGF7 significantly enhanced OC cell proliferation, migration, and invasion. Single-cell analysis and in vitro studies revealed that CAFs-derived FGF7 inhibits the ubiquitination and degradation of hypoxia-inducible factor 1 alpha (HIF-1α) via FGFR2 interaction. Activation of the FGF7/HIF-1α pathway resulted in the upregulation of mesenchymal markers and downregulation of epithelial markers. Importantly, in vivo treatment with neutralizing antibodies targeting CAFs-derived FGF7 substantially reduced tumor growth. CONCLUSION: Neutralizing FGF7 in the medium or inhibiting HIF-1α signaling reversed the effects of FGF7-mediated EMT, emphasizing the dependence of FGF7-mediated EMT on HIF-1α activation. These findings suggest that targeting the FGF7/HIF-1α/EMT axis may offer new therapeutic opportunities to intervene in OC progression.

Comparison of three-dimensional heads-up system versus traditional microscopic system in medical education for vitreoretinal surgeries: a prospective study.

BACKGROUND: To compare the value and efficiency of the three-dimensional (3D) heads-up surgical system and traditional microscopic (TM) system in teaching and learning vitreoretinal surgeries. METHODS: Twenty ophthalmologists and scrub nurses were recruited as teachers, and 45 junior ophthalmology residents and trainee doctors, trainee nurses, and medical students were recruited as observers. Each teacher and observer were assigned to both a 3D-assisted and TM-assisted vitreoretinal surgery and then asked to complete satisfaction questionnaires for both surgical systems at the end of each surgery. RESULTS: The 3D heads-up surgical system was rated significantly higher in most of the subscales and overall satisfaction score by both teachers and observers (P < 0.05). However, ratings for instrument adjustment were significantly higher in the TM group compared to the 3D group for junior ophthalmology residents and trainee doctors (6.1 ± 1.7 vs. 8.8 ± 1.1, P < 0.001). CONCLUSIONS: The 3D heads-up surgical system has great didactical value in the medical education of vitreoretinal surgeries, but it is important to consider the specific needs of different learners when choosing between the two systems. TRIAL REGISTRATION: Not applicable.

In Situ Nanofiber Formation Blocks AXL and GAS6 Binding to Suppress Ovarian Cancer Development.

Anexelekto (AXL) is an attractive molecular target for ovarian cancer therapy because of its important role in ovarian cancer initiation and progression. To date, several AXL inhibitors have entered clinical trials for the treatment of ovarian cancer. However, the disadvantages of low AXL affinity and severe off-target toxicity of these inhibitors limit their further clinical applications. Herein, by rational design of a nonapeptide derivative Nap-Phe-Phe-Glu-Ile-Arg-Leu-Arg-Phe-Lys (Nap-IR), a strategy of in situ nanofiber formation is proposed to suppress ovarian cancer growth. After administration, Nap-IR specifically targets overexpressed AXL on ovarian cancer cell membranes and undergoes a receptor-instructed nanoparticle-to-nanofiber transition. In vivo and in vitro experiments demonstrate that in situ formed Nap-IR nanofibers efficiently induce apoptosis of ovarian cancer cells by blocking AXL activation and disrupting subsequent downstream signaling events. Remarkably, Nap-IR can synergistically enhance the anticancer effect of cisplatin against HO8910 ovarian tumors. It is anticipated that the Nap-IR can be applied in clinical ovarian cancer therapy in the near future.

Iron Deficiency in Anemic Children Surviving Critical Illness: Post Hoc Analysis of a Single-Center Prospective Cohort in Canada, 2019-2022.

OBJECTIVES: Many children leave the PICU with anemia. The mechanisms of post-PICU anemia are poorly investigated, and treatment of anemia, other than blood, is rarely started during PICU. We aimed to characterize the contributions of iron depletion (ID) and/or inflammation in the development of post-PICU anemia and to explore the utility of hepcidin (a novel iron marker) at detecting ID during inflammation. DESIGN: Post hoc analysis of a single-center prospective study (November 2019 to September 2022). SETTING: PICU, quaternary center, Canada. PATIENTS: Children admitted to PICU with greater than or equal to 48 hours of invasive or greater than or equal to 96 hours of noninvasive ventilation. We excluded patients with preexisting conditions causing anemia or those admitted after cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Hematological and iron profiles were performed at PICU discharge on 56 participants of which 37 (37/56) were diagnosed with anemia. Thirty-three children (33/56; 59%) were younger than 2 years. Median Pediatric Logistic Organ Dysfunction score was 11 (interquartile range, 6-16). Twenty-four of the 37 anemic patients had repeat bloodwork 2 months post-PICU. Of those, four (4/24; 16%) remained anemic. Hematologic profiles were categorized as: anemia of inflammation (AI), iron deficiency anemia (IDA), IDA with inflammation, and ID (low iron stores without anemia). Seven (7/47; 15%) had AI at discharge, and one had persistent AI post-PICU. Three patients (3/47; 6%) had IDA at discharge; of which one was lost to follow-up and the other two were no longer anemic but had ID post-PICU. Eleven additional patients developed ID post-PICU. In the exploratory analysis, we identified a diagnostic cutoff value for ID during inflammation from the receiver operating characteristic curve for hepcidin of 31.9 pg/mL. This cutoff would increase the detection of ID at discharge from 6% to 34%. CONCLUSIONS: The burden of ID in children post-PICU is high and better management strategies are required. Hepcidin may increase the diagnostic yield of ID in patients with inflammation.

Robotic-assisted endoluminal gastric leiomyoma resection: a novel surgical technique for benign gastroesophageal junction tumors.

Gastric leiomyomas are rare, benign smooth muscle tumors that arise from the muscularis propria and can be found in any part of the stomach. The American College of Gastroenterologists recommends resection only for symptomatic leiomyomas, which can often present with bleeding, abdominal pain, or dyspepsia. Notably, symptomatic leiomyomas that arise at the gastroesophageal (GE) junction, especially those that are large, pose unique challenges. Specifically, total gastrectomy with esophagojejunostomy is often necessary, which can be associated with a compromised quality of life and possible complications such as anastomotic stricture or reflux esophagitis. In this context, we present the case of a young, male patient with a large symptomatic leiomyoma at the GE junction who was offered a robotic-assisted endoluminal leiomyoma resection. By placing endoluminal trocars and utilizing the Da Vinci® robot, we were able to carefully excise the tumor without perforating the stomach or causing GE junction stenosis. This allowed the patient to preserve his stomach and avoid a high-risk anastomosis. Another notable highlight of the case included the use of the endoscope as both a bougie and a source of insufflation. The patient had an uncomplicated postoperative course and a rapid recovery, highlighting the feasibility of this approach for patients with benign GE junction tumors.

Apoptotic extracellular vesicles derived from hypoxia-preconditioned mesenchymal stem cells within a modified gelatine hydrogel promote osteochondral regeneration by enhancing stem cell activity and regulating immunity.

Due to its unique structure, articular cartilage has limited abilities to undergo self-repair after injury. Additionally, the repair of articular cartilage after injury has always been a difficult problem in the field of sports medicine. Previous studies have shown that the therapeutic use of mesenchymal stem cells (MSCs) and their extracellular vesicles (EVs) has great potential for promoting cartilage repair. Recent studies have demonstrated that most transplanted stem cells undergo apoptosis in vivo, and the apoptotic EVs (ApoEVs) that are subsequently generated play crucial roles in tissue repair. Additionally, MSCs are known to exist under low-oxygen conditions in the physiological environment, and these hypoxic conditions can alter the functional and secretory properties of MSCs as well as their secretomes. This study aimed to investigate whether ApoEVs that are isolated from adipose-derived MSCs cultured under hypoxic conditions (hypoxic apoptotic EVs [H-ApoEVs]) exert greater effects on cartilage repair than those that are isolated from cells cultured under normoxic conditions. Through in vitro cell proliferation and migration experiments, we demonstrated that H-ApoEVs exerted enhanced effects on stem cell proliferation, stem cell migration, and bone marrow derived macrophages (BMDMs) M2 polarization compared to ApoEVs. Furthermore, we utilized a modified gelatine matrix/3D-printed extracellular matrix (ECM) scaffold complex as a carrier to deliver H-ApoEVs into the joint cavity, thus establishing a cartilage regeneration system. The 3D-printed ECM scaffold provided mechanical support and created a microenvironment that was conducive to cartilage regeneration, and the H-ApoEVs further enhanced the regenerative capacity of endogenous stem cells and the immunomodulatory microenvironment of the joint cavity; thus, this approach significantly promoted cartilage repair. In conclusion, this study confirmed that a ApoEVs delivery system based on a modified gelatine matrix/3D-printed ECM scaffold together with hypoxic preconditioning enhances the functionality of stem cell-derived ApoEVs and represents a promising approach for promoting cartilage regeneration.

Characterization and genomic analysis of a broad-spectrum lytic phage PG288: A potential natural therapy candidate for Vibrio infections.

Vibrio parahaemolyticus, an important zoonotic pathogen, can cause severe diseases and even death in aquatic animals and humans. As the widespread use of antibiotics gradually diminishes their effectiveness, phages, which can selectively lyse bacteria, are garnering increased attention as a valuable alternative antibacterial strategy. This study characterized PG288, a lytic phage utilizing V. parahaemolyticus strain G855 as its host. Morphologically, the phage features a polyhedral head and a long, non-retractable tail. Bactericidal assays revealed that phage PG288 exhibited a strong lytic ability against V. parahaemolyticus strain G855 and demonstrated a broad host range, as evidenced by the ability to infect several distinct Vibrio species. The one-step growth curve indicated a latent period of approximately 50 min for phage PG288, with a burst size of roughly 92 PFU per cell. Additionally, phage PG288 exhibited remarkable stability within a temperature range of 20-50°C and a pH range of 4-10. Genomic analysis unveiled 105 ORFs within phage PG288, notably devoid of genes associated with antibiotic resistance, virulence, and lysogenic activity. Phylogenetic analysis conclusively identified it as a new member of the genus Mardecavirus within the class Caudoviricetes. In summary, this study contributes valuable insights to the phage database, presenting phage PG288 as a promising candidate for phage therapies against Vibrio infections.

Effectiveness of Robotic Intervention on Improving Social Development and Participation of Children with Autism Spectrum Disorder - A Randomised Controlled Trial.

Evidence-based robotic intervention programmes for children with autism spectrum disorder (ASD) have been limited. As yet, there is insufficient evidence to inform therapists, teachers, and service providers on effectiveness of robotic intervention to enhance social development and participation of children with ASD in a real context. This study used a randomised controlled trial to test the efficacy of robotic intervention programmes in enhancing the social development and participation of children with ASD. 60 children with ASD were included. The participants were randomly assigned to the following groups: (1) robotic intervention programme (n = 20), (2) human-instructed programme (n = 20), and (3) control group (n = 20). Both the performance-based behavioural change in social communication and parent-reported change in social responsiveness were evaluated. The participants in the robotic intervention group demonstrated statistically significant changes in both the performance-based assessment and parent-reported change in social participation. Significant differences were found in the communication and reciprocal social interactions scores between the experimental group and the control and comparison groups in the performance-based assessment (p < 0.01). The effectiveness of robotic intervention programme to enhance the social communication and participation was confirmed. Future studies may also consider adding a maintenance phase to document how the effects of the intervention carry over to the participants over a longer period. (Clinical trial number: NCT04879303; Date of registration: 10 May 2021).

Type II Abernethy malformation with cystic fibrosis in a 12-year-old girl: A case report.

BACKGROUND: Abernethy malformation, also known as congenital extrahepatic portosystemic shunt, is an uncommon malformation resulting from aberrant development of the portal venous system. Cystic fibrosis (CF) is an autosomal recessive genetic disease caused by mutations in the CFTR gene. It mainly affects the exocrine glands of the respiratory, digestive and reproductive systems. It is considered extremely rare in the Asian population. We present a clinical case involving a pediatric patient of Asian descent who was diagnosed with Abernethy malformation and CF. CASE SUMMARY: A 12-year-old girl presented with a medical history of recurring respiratory infections and hemoptysis, and chest computed tomography (CT) showed bronchiectasis. Whole exome sequencing was performed for the patient, yielding findings that revealed a compound heterozygous variant of the CFTR gene: c.233_c.234insT/p.Trp79fsTer3 (maternal origin); c.2909G>A/p.Gly970Asp (paternal origin). CF was diagnosed. The physician's attention was drawn to the presence of splenomegaly during disease progression. Abdominal enhanced CT revealed splenomegaly, compression of the left kidney, and multiple tortuous dilated vascular shadows were seen at the splenic hilum, which flowed back into the left renal vein and portal vein, suggesting Abernethy malformation type II. Intraoperatively, the abnormal blood flow was seen to merge into the inferior vena cava through the left renal vein without hepatic processing, and the pathology of liver biopsy showed hypoplastic, dilated or absent portal vein branches, both of which supported the diagnosis of Abernethy malformation type II. This represents the initial documented instance of Abernethy malformation accompanied by a CFTR gene mutation in the existing body of literature. CONCLUSION: Coexisting Abernethy malformation and CF are rare. Detailed medical history information, abdominal enhanced CT, venography and genetic testing contribute to diagnosis as well as differential diagnosis.

Underestimated Subsequent Sensorineural Hearing Loss after Septicemia.

Background and Objectives: Hearing loss after septicemia has been found in mice; the long-term risk increased 50-fold in young adults in a previous study. Hearing loss after septicemia has not received much attention. The aim of this study was to assess the relationship between septicemia and subsequent hearing loss. Materials and Methods: Inpatient data were obtained from the Taiwan Insurance Database. We defined patients with sensorineural hearing loss and excluded patients under 18 years of age. Patients without hearing loss were selected as controls at a frequency of 1:5. The date of admission was defined as the date of diagnosis. Comorbidities in the 3 years preceding the date of diagnosis were retrieved retrospectively. Associations with hearing loss were established by multiple logistic regression and forward stepwise selection. Results: The odds ratio (OR) for the association between sepsis and hearing loss was 3.052 (95% CI: 1.583-5.884). Autoimmune disease (OR: 5.828 (95% CI: 1.906-17.816)), brain injury (OR: 2.264 (95% CI: 1.212-4.229)) and ischemic stroke (OR: 1.47 (95% CI: 1.087-1.988)) were associated with hearing loss. Conclusions: Our study shows that hearing loss occurred after septicemia. Apoptosis caused by sepsis and ischemia can lead to hair cell damage, leading to hearing loss. Clinicians should be aware of possible subsequent complications of septicemia and provide appropriate treatment and prevention strategies for complications.

Exosomes derived from ovarian cancer cells regulate proliferation and migration of cancer-associated fibroblasts.

Cancer-associated fibroblast (CAF) is an essential risk factor for ovarian cancer. Exosomes can mediate cellular communication in the tumour microenvironment, but the interaction of tumour cell exosomes with CAF is less studied in Ovarian cancer. This study identified H19/miR-29c-3p/LOXL2-COL1A1 as a ceRNA regulatory network involved in regulating tumour matrix-associated signaling pathways associated with CAF. Cellular assays demonstrated that exosomes from ovarian cancer cell line SKOV3 significantly promoted the proliferation and migration of CAF. The results of mixed transplantation tumour experiments in nude mice showed that exosomes of SKOV3 significantly promoted tumour growth. Ovarian cancer tumour-derived exosomes can regulate CAF proliferation and migration through H19/miR-29c-3p/LOXL2-COL1A1. This study reveals the regulatory role of tumour exosomes on CAF, which may provide a theoretical basis for the development of therapeutic regimens targeting fibroblasts in ovarian cancer.

Biological and clinical implications of early-onset cancers: A unique subtype.

In recent years, the incidence of cancers is continuously increasing in young adults. Early-onset cancer (EOC) is usually defined as patients with cancers under the age of 50, and may represent a unique subgroup due to its special disease features. Overall, EOCs often initiate at a young age, present as a better physical performance but high degree of malignancy. EOCs also share common epidemiological and hereditary risk factors. In this review, we discuss several representative EOCs which were well studied previously. By revealing their clinical and molecular similarities and differences, we consider the group of EOCs as a unique subtype compared to ordinary cancers. In consideration of EOC as a rising threat to human health, more researches on molecular mechanisms, and large-scale, prospective clinical trials should be carried out to further translate into improved outcomes.

The Intention of Inhaled Medication Adherence Scale (IMAS): The Development of a New Instrument for Assessing Inhaled Medication Adherence Among Patients with Chronic Obstructive Pulmonary Disease (COPD) Using Theory of Planned Behavior.

Purpose: Inhaled medication adherence is an important issue for patients with chronic obstructive pulmonary disease (COPD) because adhering to inhaled medications could substantially improve their health. However, patients with COPD may not be always adhere to the prescribed inhaled medications. Therefore, understanding the underlying reasons for patients with COPD adhering to inhaled medications is important. The present study used Theory of Planned Behavior (TPB) as a theoretical framework to develop the Intention of Inhaled Medication Adherence Scale (IMAS) and assess its psychometric properties. Patients and Methods: After reviewing papers using the TPB to design psychometric scales and the TPB scale development guidelines, 28 items were generated for expert evaluation. Eight experts reported that the 28 items all had good content validity (content validity index ranged from 0.88 to 1.00 at item-level; and from 0.981 to 0.987 at scale-level) comprising four factors. Following initial development, 235 patients with COPD (mean age 73.12 years; 93.6% males) completed the IMAS via interview with a respiratory therapist and a research assistant. The four-factor structure of the IMAS was evaluated using confirmatory factor analysis (CFA). Results: Nine IMAS items were removed because of low factor loadings or offending estimates. The 19-item IMAS was confirmed as having a four-factor structure supported by the CFA results (comparative fit index=1.00; Tucker-Lewis index=1.00; root mean square error of approximation=0.00; standardized root mean square residual=0.06). Conclusion: The 19-item IMAS had satisfactory psychometric properties in construct validity. The 19-item IMAS is an instrument that could help healthcare providers understand potential factors associated with adherence to inhaled medications among people with COPD.