Destruction of vascular endothelial glycocalyx during formation of pre-metastatic niches.

A special microenvironment called the "pre-metastatic niche" is thought to help primary tumor cells migrate to new tissues and invade them, in part because the normal barrier function of the vascular endothelium is compromised. While the primary tumor itself can promote the creation of such niches by secreting pro-metastatic factors, the underlying molecular mechanisms are still poorly understood. Here, we show that the injection of primary tumor-secreted pro-metastatic factors from B16F10 melanoma or 4T1 breast cancer cells into healthy mice can induce the destruction of the vascular endothelial glycocalyx, which is a polysaccharide coating on the vascular endothelial lumen that normally inhibits tumor cell passage into and out of the circulation. However, when human umbilical vein endothelial cultures were treated in vitro with these secreted pro-metastatic factors, no significant destruction of the glycocalyx was observed, implying that this destruction requires a complex in vivo microenvironment. The tissue section analysis revealed that secreted pro-metastatic factors could clearly upregulate macrophage-related molecules such as CD11b and tumor necrosis factor-α (TNF-α) in the heart, liver, spleen, lung, and kidney, which is associated with the upregulation and activation of heparanase. In addition, macrophage depletion significantly attenuated the degradation of the vascular endothelial glycocalyx induced by secreted pro-metastatic factors. This indicates that the secreted pro-metastatic factors that destroy the vascular endothelial glycocalyx rely primarily on macrophages. Our findings suggest that the formation of pre-metastatic niches involves degradation of the vascular endothelial glycocalyx, which may hence be a useful target for developing therapies to inhibit cancer metastasis.

Lipid-mediated protein corona regulation with increased apolipoprotein A-I recruitment for glioma targeting.

Protein corona has long been a source of concern, as it might impair the targeting efficacy of targeted drug delivery systems. However, engineered up-regulating the adsorption of certain functional serum proteins could provide nanoparticles with specific targeting drug delivery capacity. Herein, apolipoprotein A-I absorption increased nanoparticles (SPC-PLGA NPs), composed with the Food and Drug Administration approved intravenously injectable soybean phosphatidylcholine (SPC) and poly (DL-lactide-co-glycolide) (PLGA), were fabricated for enhanced glioma targeting. Due to the high affinity of SPC and apolipoprotein A-I, the percentage of apolipoprotein A-I in the protein corona of SPC-PLGA NPs was 2.19-fold higher than that of nanoparticles without SPC, which made SPC-PLGA NPs have superior glioma targeting ability through binding to scavenger receptor class BI on blood-brain barrier and glioma cells both in vitro and in vivo. SPC-PLGA NPs loaded with paclitaxel could effectively reduce glioma invasion and prolong the survival time of glioma-bearing mice. In conclusion, we provided a good example of the direction of achieving targeting drug delivery based on protein corona regulation.

Hyaluronic acid-functionalized DDAB/PLGA nanoparticles for improved oral delivery of magnolol in the treatment of ulcerative colitis.

Dysfunction of the mucosal barrier as well as local inflammation are major challenges in the treatment of ulcerative colitis (UC). Mag, a natural compound derived from traditional Chinese medicine, has been shown to have anti-inflammatory and mucosal protection properties. However, its poor gastrointestinal stability as well as its insufficient accumulation in inflamed colonic lesions limit its potential use as an alternative therapeutic drug in UC. The present research involved the design and preparation of a hybrid nanoparticle system (LPNs) specifically targeting macrophages at the colonic site. This was achieved by electrostatically adsorbing HA onto positively charged lipid-polymer hybrid nanoparticles (HA-LPNs). The prepared HA-LPNs exhibited a rounded morphology and a narrow size distribution. In vitro, the anti-inflammatory efficacy of Mag-HA-LPNs (which control levels of the pro-inflammatory cytokines NO, IL-6 and TNF-α) was assessed in RAW 264.7 cells. Analysis by flow cytometry and fluorescence microscopy demonstrated increased cellular uptake through HA/CD44 interaction. As expected, Mag-HA-LPNs was found to effectively increased colon length and reduced DAI scores in DSS-treated mice. This effect was achieved by regulating the inflammatory cytokines level and promoting the restoration of the colonic mucosal barrier through increased expression of Claudin-1, ZO-1 and Occludin. In this study, we developed an efficient and user-friendly delivery method for the preparation of HA-functionalized PLGA nanoparticles, which are intended for oral delivery of Mag. The findings suggest that these HA-LPNs possess the potential to serve as a promising approach for direct drug delivery to the colon for effective treatment of UC.

Interactions between nanoparticles and pathological changes of vascular in Alzheimer's disease.

Emerging evidence suggests that vascular pathological changes play a pivotal role in the pathogenesis of Alzheimer's disease (AD). The dysfunction of the cerebral vasculature occurs in the early course of AD, characterized by alterations in vascular morphology, diminished cerebral blood flow (CBF), impairment of the neurovascular unit (NVU), vasculature inflammation, and cerebral amyloid angiopathy. Vascular dysfunction not only facilitates the influx of neurotoxic substances into the brain, triggering inflammation and immune responses but also hampers the efflux of toxic proteins such as Aß from the brain, thereby contributing to neurodegenerative changes in AD. Furthermore, these vascular changes significantly impact drug delivery and distribution within the brain. Therefore, developing targeted delivery systems or therapeutic strategies based on vascular alterations may potentially represent a novel breakthrough in AD treatment. This review comprehensively examines various aspects of vascular alterations in AD and outlines the current interactions between nanoparticles and pathological changes of vascular.

Dual-responsive supramolecular photodynamic nanomedicine with activatable immunomodulation for enhanced antitumor therapy.

A major challenge facing photodynamic therapy (PDT) is that the activity of the immune-induced infiltrating CD8+ T cells is subject to the regulatory T lymphocytes (Tregs), leaving the tumor at risk of recurrence and metastasis after the initial ablation. To augment the antitumor response and reprogram the immunosuppressive tumor microenvironment (TME), a supramolecular photodynamic nanoparticle (DACss) is constructed by the host-guest interaction between demethylcantharidin-conjugated ß-cyclodextrin (DMC-CD) and amantadine-terminated disulfide-conjugated FFVLGGGC peptide with chlorin e6 decoration (Ad-ss-pep-Ce6) to achieve intelligent delivery of photosensitizer and immunomodulator for breast cancer treatment. The acid-labile ß-carboxamide bond of DMC-CD is hydrolyzed in response to the acidic TME, resulting in the localized release of DMC and subsequent inhibition of Tregs. The guest molecule Ad-ss-pep-Ce6 can be cleaved by a high level of intracellular GSH, reducing photosensitizer toxicity and increasing photosensitizer retention in the tumor. With a significant increase in the CTL/Treg ratio, the combination of Ce6-based PDT and DMC-mediated immunomodulation adequately achieved spatiotemporal regulation and remodeling of the TME, as well as improved primary tumor and in situ lung metastasis suppression with the aid of PD-1 antibody.

Nanotechnology for enhanced nose-to-brain drug delivery in treating neurological diseases.

Despite the increasing global incidence of brain disorders, achieving sufficient delivery towards the central nervous system (CNS) remains a formidable challenge in terms of translating into improved clinical outcomes. The brain is highly safeguarded by physiological barriers, primarily the blood-brain barrier (BBB), which routinely excludes most therapeutics from entering the brain following systemic administration. Among various strategies investigated to circumvent this challenge, intranasal administration, a noninvasive method that bypasses the BBB to allow direct access of drugs to the CNS, has been showing promising results. Nanotechnology-based drug delivery systems, in particular, have demonstrated remarkable capacities in overcoming the challenges posed by nose-to-brain drug delivery and facilitating targeted drug accumulation within the brain while minimizing side effects of systemic distribution. This review comprehensively summarizes the barriers of nose-to-brain drug delivery, aiming to enhance our understanding of potential physiological obstacles and improve the efficacy of nasal delivery in future trials. We then highlight cutting-edge nanotechnology-based studies that enhance nose-to-brain drug delivery in three key aspects, demonstrating substantial potential for improved treatment of brain diseases. Furthermore, the attention towards clinical studies will ease the regulatory approval process for nasal administration of nanomedicines targeting brain disease.

The Effect of Sow Maternal Behavior on the Growth of Piglets and a Genome-Wide Association Study.

Sows' maternal behavior is important for improving piglet survival and growth; thus, breeding for good mothering sows is necessary for pig production. However, there is little research on the genetic mechanism of maternal behavior. In this study, a comparative analysis of piglets' growth traits between good and bad maternal behavior groups and a genome-wide association study (GWAS) was performed to elucidate the impact of sows' maternal behavior on piglet growth and identify candidate genes and markers of sow's maternal behaviors. Comparing the growth traits of piglets between good and bad sows' maternal behavior groups, the results showed that the growth traits of piglets from sows with good maternal behavior were better than those from sows with bad maternal behavior and especially for the multiparous sows group, this comparative difference was significant. For the intensive study of the genetic mechanisms of sows' maternal behavior, a total of 452 sows were genotyped using the Illumina Porcine 50K SNP Chip, and 4 traits, including biting piglets (BP), crushing piglets (CP), trampling piglets (TP) and screaming test (ST), were examined. Using a GWAS, 20 single nucleotide polymorphisms (SNPs) were found to be associated with these traits. Within 1 Mb upstream and downstream of the significant SNPs screened, 138 genes were obtained. After pathway enrichment and gene annotation, HIP1, FZD9 and HTR7 were identified as important candidate genes affecting sows' maternal behaviors. These findings preliminarily elucidate the genetic basis of sows' maternal behavior traits and provide candidate genes and markers for molecular breeding in pigs.

Multifunctional Nanotheranostics for Dual-Modal Imaging-Guided Precision Therapy of Nasopharyngeal Carcinoma.

Currently, the low survival rate and poor prognosis of patients with nasopharyngeal carcinoma are ascribed to the lack of early and accurate diagnosis and resistance to radiotherapy. In parallel, the integration of imaging-guided diagnosis and precise treatment has gained much attention in the field of theranostic nanotechnology. However, constructing dual-modal imaging-guided nanotheranostics with desired imaging performance as well as great biocompatibility remains challenging. Therefore, we developed a simple but multifunctional nanotheranostic GdCPP for the early and accurate diagnosis and efficient treatment of nasopharyngeal carcinoma (NPC), which combined fluorescence imaging and magnetic resonance imaging (MRI) onto a single nanoplatform for imaging-guided subsequent photodynamic therapy (PDT). GdCPP had an appropriate particle size (81.93 ± 0.69 nm) and was highly stable, resulting in sufficient tumor accumulation, which along with massive reactive oxygen species (ROS) generation upon irradiation further significantly killed tumor cells. Moreover, GdCPP owned much stronger r1 relaxivity (9.396 mM-1 s-1) compared to clinically used Gd-DTPA (5.034 mM-1 s-1) and exhibited better T1WI MRI performance. Under dual-modal imaging-guided PDT, GdCPP achieved efficient therapeutic outcomes without causing any noticeable tissue damage. The results of in vitro and in vivo studies indicated that GdCPP may be a suitable candidate for dual-modal imaging-guided precision tumor therapy.

Influence factors on and potential strategies to amplify receptor-mediated nanodrug delivery across the blood-brain barrier.

INTRODUCTION: A major challenge in treating central nervous system (CNS) disorders is to achieve adequate drug delivery across the blood-brain barrier (BBB). Receptor-mediated nanodrug delivery as a Trojan horse strategy has become an exciting approach. However, these nanodrugs do not accumulate significantly in the brain parenchyma, which greatly limits the therapeutic effect of drugs. Amplifying the efficiency of receptor-mediated nanodrug delivery across the BBB becomes the holy grail in the treatment of CNS disorders. AREAS COVERED: In this review, we tend to establish links between dynamic BBB and receptor-mediated nanodrug delivery, starting with the delivery processes across the BBB, describing factors affecting nanodrug delivery efficiency, and summarizing potential strategies that may amplify delivery efficiency. EXPERT OPINION: Receptor-mediated nanodrug delivery is a common approach to significantly enhance the efficiency of brain-targeting delivery. As BBB is constantly undergoing changes, it is essential to investigate the impact of diseases on the effectiveness of brain-targeting nanodrug delivery. More critically, there are several barriers to achieving brain-targeting nanodrug delivery in the five stages of receptor-mediated transcytosis (RMT), and the impacts can be conflicting, requiring intricate balance. Further studies are also needed to investigate the material toxicity of nanodrugs to address the issue of clinical translation.

Nano- and Microemulsions in Biomedicine: From Theory to Practice.

Nano- and microemulsions are colloidal systems that are widely used in various fields of biomedicine, including wound and burn healing, cosmetology, the development of antibacterial and antiviral drugs, oncology, etc. The stability of these systems is governed by the balance of molecular interactions between nanodomains. Microemulsions as a colloidal form play a special important role in stability. The microemulsion is the thermodynamically stable phase from oil, water, surfactant and co-surfactant which forms the surface of drops with very small surface energy. The last phenomena determines the shortage time of all fluid dispersions including nanoemulsions and emulgels. This review examines the theory and main methods of obtaining nano- and microemulsions, particularly focusing on the structure of microemulsions and methods for emulsion analysis. Additionally, we have analyzed the main preclinical and clinical studies in the field of wound healing and the use of emulsions in cancer therapy, emphasizing the prospects for further developments in this area.

The Gut Microbiota of Pregnant Rats Alleviates Fetal Growth Restriction by Inhibiting the TLR9/MyD88 Pathway.

Fetal growth restriction (FGR) is a prevalent obstetric condition. This study aimed to investigate the role of Toll-like receptor 9 (TLR9) in regulating the inflammatory response and gut microbiota structure in FGR. An FGR animal model was established in rats, and ODN1668 and hydroxychloroquine (HCQ) were administered. Changes in gut microbiota structure were assessed using 16S rRNA sequencing, and fecal microbiota transplantation (FMT) was conducted. HTR-8/Svneo cells were treated with ODN1668 and HCQ to evaluate cell growth. Histopathological analysis was performed, and relative factor levels were measured. The results showed that FGR rats exhibited elevated levels of TLR9 and myeloid differentiating primary response gene 88 (MyD88). In vitro experiments demonstrated that TLR9 inhibited trophoblast cell proliferation and invasion. TLR9 upregulated lipopolysaccharide (LPS), LPS-binding protein (LBP), interleukin (IL)-1ß and tumor necrosis factor (TNF)-α while downregulating IL-10. TLR9 activated the TARF3-TBK1-IRF3 signaling pathway. In vivo experiments showed HCQ reduced inflammation in FGR rats, and the relative cytokine expression followed a similar trend to that observed in vitro. TLR9 stimulated neutrophil activation. HCQ in FGR rats resulted in changes in the abundance of Eubacterium_coprostanoligenes_group at the family level and the abundance of Eubacterium_coprostanoligenes_group and Bacteroides at the genus level. TLR9 and associated inflammatory factors were correlated with Bacteroides, Prevotella, Streptococcus, and Prevotellaceae_Ga6A1_group. FMT from FGR rats interfered with the therapeutic effects of HCQ. In conclusion, our findings suggest that TLR9 regulates the inflammatory response and gut microbiota structure in FGR, providing new insights into the pathogenesis of FGR and suggesting potential therapeutic interventions.

Ultrasound-assisted pH-shifting to construct a stable aqueous solution of paprika oleoresin using egg yolk low-density lipoprotein as a natural liposome-like nano-emulsifier.

In this study, a stable aqueous solution of paprika oleoresin (PO, the natural colorant extracted from the fruit peel of Capsicum annuum L) was constructed. The solubility of PO in an alkline aqueous solution (pH 10.95-11.10) increased rapidly. However, the aqueous solution of PO (pH 12.00) was unstable, obvious stratification was observed, and the color retention rate was only 52.99% after 28 days of storage. Chicken egg yolk low-density lipoprotein (LDL) was added combined with ultrasonic treatment to improve the stability of LDL-PO solution. The method could decrease the turbidity by 17.5 %, reduce the average particle size of the LDL-PO solution (13.9%), and enhance the interaction and combination of LDL and PO. The prepared PO aqueous solution was used in yogurt, egg white gel, fish balls and soymilk, and it could significantly improve the color of products and provided potential health benefits.

Co-delivery of microRNA-150 and quercetin by lipid nanoparticles (LNPs) for the targeted treatment of age-related macular degeneration (AMD).

Age-related macular degeneration (AMD) is characterized by choroidal neovascularization (CNV), which leads to severe vision loss in middle-aged and elderly patients. Current treatments for CNV show weak, transient efficacy, and they can cause several adverse effects. A potential new treatment is to use microRNA-150 (mR150), which regulates physiological and pathological angiogenesis by modulating the expression of CXCR4 at the post-transcriptional level. Here, we developed solid lipid nanoparticles that we modified with an Asp-Gly-Arg peptide to target endothelial cells during abnormal angiogenesis, then we co-loaded them with mR150 and the anti-angiogenic drug quercetin. The resulting nanoparticles had an average size around 200 nm and showed strong ability to target the fundus and inhibit CNV for up to two weeks in a mouse model without causing retinal toxicity. They significantly enhanced the uptake of mR150 in vitro compared to free mR150 or nanoparticles without peptide. Our study suggests that co-administration of mR150 and quercetin has potential for treating age-related macular degeneration and that nanoparticles modified with Asp-Gly-Arg peptide are an effective platform for the co-delivery of small-molecule and nucleic acid drugs via intravitreal injection.

Regulation of protein corona on liposomes using albumin-binding peptide for targeted tumor therapy.

Nanocarriers entering the body are usually coated by plasma protein, leading to a protein "corona" easily recognized by tissues and cells. Adjusting the composition of protein coronas may be an efficient way to change the properties and behavior of nanoparticles in vivo. In this study, we modified doxorubicin-loaded liposomes (Lip/DOX) with an albumin-binding domain (ABD) to prepare nanoparticles (ABD-Lip/DOX) that can specifically bind to albumin and form albumin-based protein coronas in vivo for targeted tumor therapy. The prepared liposomes were spherical with a particle size of about 100 nm. After incubating the liposomes with rat serum, the albumin content was eight times higher on ABD-Lip than on control liposomes. ABD-Lip significantly inhibited adsorption of IgG and complement activation in rat serum in vitro, while corona-coated ABD-Lip was internalized to a significantly greater extent than corona-coated control liposomes. In addition, ABD-Lip showed longer blood circulation time, higher tumor accumulation and greater antitumor efficacy than control liposomes in mice bearing 4 T1 tumors, while both liposome formulations showed similar biocompatibility. These results confirm that adjusting the component of protein coronas around nanoparticles can improve their therapeutic efficacy.

Dramatic improvement in the mechanical properties of polydopamine/polyacrylamide hydrogel mediated human amniotic membrane.

Human amniotic membrane (hAM) is a promising material for tissue engineering due to several benefits, including desirable biocompatibility, stem cell source, antibacterial activity, etc. However, because of its low elasticity, the clinical application of hAM is severely restricted. To solve this issue, we employed polydopamine/polyacrylamide (PDA/PAM) hydrogels to toughen hAM. The test results indicated that the PDA/PAM hydrogel can enhance the toughness of hAM dramatically due to the formation of abundant chemical bonds and the strong mechanical properties of the hydrogel itself. Compared to pure hAM, the break elongation and tensile strength of PDA/PAM-toughened hAM rose by 154.15 and 492.31%, respectively. And most importantly, the fracture toughness was almost 15 times higher than untreated hAM. In addition, the cytotoxicity of the PDA/PAM-coated hAM was not detected due to the superior biocompatibility of the chemicals used in the study. Treating hAM with adhesive hydrogels to increase its mechanical characteristics will further promote the application of hAM as a tissue engineering material.

Characterization of the Binding Properties of Sorafenib to c-MYC G-Quadruplexes: Evidence for Screening Potential Ligands.

Sorafenib (Sor) is a multitarget kinase inhibitor used clinically to treat hepatocellular carcinoma and renal cancer. In this study, the interaction mechanism of Sor with c-MYC G-quadruplexes (G4) was investigated at the molecular level by computer-aided means and experiments. Molecular docking results predicted the binding of Sor to the groove of G4. Molecular dynamics (MD) simulations were used to evaluate the effect of ligand binding to G4. Ultraviolet (UV), fluorescence spectroscopy, and viscosity experiments showed that the binding site was in the groove. The UV and fluorescence titration results showed that compared with traditional G4 ligands represented by compound meso-tetra (N-methyl-4-pyridyl) porphine (TmPyP4), Sor has a lower affinity for G4. Likewise, results from fluorescence resonance energy transfer (FRET) experiments suggested that Sor could have a limited ability to stabilize G4, but it was not as prominent as that of TmPyP4. Time-resolved fluorescence spectroscopy again supported the results from steady-state fluorescence spectroscopy, indicating that a static quenching mechanism mainly drove the process. Studying the interaction mechanism of Sor and c-MYC may inspire the screening of new, selective c-MYC G4 ligands and provide ideas for the design of drugs with good stability, low toxicity, and specific targeting of G4.

Sensitive acid phosphatase assay based on light-activated specific oxidase mimic activity.

Acid phosphatase (ACP) is a key marker in the diagnosis of many diseases. However, exploiting a simple and sensitive sensor for the real-time quantitative analysis of ACP is still challenging. Herein, we attempted to develop a sensitive colorimetric sensing strategy for the detection of ACP based on light-activated oxidase mimic property of carbon dots (CDs). The synthesized CDs were proved to be capable of intrinsic light-activated oxidase mimic activity, which could generate reactive oxygen species to oxidize chromogenic substrate under ultraviolet light stimulation. Interestingly, this light-activated oxidase mimic behavior would be effectively suppressed by the antioxidant ascorbic acid (AA), a product from the hydrolysis of 2-phospho-L-ascorbic acid trisodium (AAP) mediated by ACP. Based on the above property, a facile and sensitive colorimetric sensing method for ACP was developed. Under the optimal conditions, the linear range for ACP 0.1-5.5 U/L, and the detection limit was 0.056 U/L. Compared with conventional nanozyme based ACP assay systems, the catalytic activity of light-activated nanozyme could be conveniently regulated by switching the light on and off, which made it easier to precisely control the extent of the reaction and ensured the accuracy of the assay. In addition, the proposed sensing system would be readout directly by the naked eye or smartphone-based RGB analysis system, and have been successfully applied to analyze diluted in diluted fetal bovine serum and urine samples spiked with ACP. All these results indicated that this approach holds good promise for future applications in clinical analysis and point-of-care (POC) biosensor platforms.

Quantitative lipidomic analysis of chicken egg yolk during its formation.

BACKGROUND: The accumulation of lipids in egg yolk during its formation represents a knowledge gap between food science and animal science research to which researchers in either field have not paid sufficient attention. Therefore, the egg yolk samples during different periods of formation (yellow follicle, YF; small hierarchical follicles, SF; and the largest hierarchical follicle, LF) were prepared, and their fatty acid compositions and lipidomes were quantitatively compared. RESULTS: The fatty acid profiles and lipidomes of egg yolks at the three stages of formation were significantly different. The relative content of oleic acid and palmitic acid were increased, but that of the main polyunsaturated fatty acids (linoleic acid, linolenic acid and docosahexaenoic acid) was decreased in the SF period to the LF period. Among the 786 lipid molecular species identified, 150 and 46 differentially abundant lipids (DALs) were identified in the pairwise comparison of YF/SF (early stage of egg yolk formation) and SF/LF (late stage of egg yolk formation), respectively. Triglycerides and diglycerides, represented by TG(14:0/18:1/20:1) and DG(18:1/18:1/0:0), were decreased, whereas free fatty acids (especially free unsaturated fatty acids) were greatly increased during yolk formation. The changes in phospholipids were complex; the relative abundance of phosphatidylcholine [represented by PC(18:0/22:5)] decreased, whereas phosphatidylethanolamine [represented by PE(18:0/18:0)] increased. In addition, the relative abundance of lysophosphatidylcholine [represented by LPC(18:1/0:0)] was increased during egg yolk formation. CONCLUSION: The transport and accumulation of lipids into the egg yolk is dynamically adjusted during its formation, and the transport and timing of different lipid molecular species are different. © 2022 Society of Chemical Industry.

Factors associated with in-hospital mortality from free wall rupture after acute myocardial infarction.

BACKGROUND: Free wall rupture is a fatal and emergency complication of acute myocardial infarction. The factors associated with in-hospital mortality from free wall rupture remain unclear. OBJECTIVES: To investigate the factors associated with in-hospital mortality from free wall rupture. METHODS: We performed a single-center, retrospective study. We enrolled 111 consecutive patients with free wall rupture following acute myocardial infarction who were admitted to Fuwai Hospital from January 2005 to May 2021. The primary endpoint was in-hospital death. Clinical characteristics, laboratory data, and treatment modalities associated with in-hospital mortality were analyzed. RESULTS: Eighty-seven of the 111 study participants died in hospital. Multivariate Cox regression analysis showed that pericardiocentesis (hazard ratio [HR] 0.296, 95% confidence interval [CI] 0.094-0.929, p = 0.037), pericardial effusion at admission (HR 0.083, 95% CI 0.025-0.269, p<0.001), time interval between acute myocardial infarction and free wall rupture (HR 0.670, 95% CI 0.598-0.753, p<0.001), and previous myocardial infarction (HR 0.046, 95% CI 0.010-0.208, p<0.001) were independently associated with in-hospital mortality. CONCLUSIONS: Pericardiocentesis, pericardial effusion at admission, the acute myocardial infarction to free wall rupture time, and previous myocardial infarction are associated with a lower rate of in-hospital mortality from free wall rupture after acute myocardial infarction.

The comparative burden of brain and central nervous system cancers from 1990 to 2019 between China and the United States and predicting the future burden.

Background: Brain and central nervous system (CNS) cancers represent a major source of cancer burden in China and the United States. Comparing the two countries' epidemiological features for brain and CNS cancers can help plan interventions and draw lessons. Methods: Data were extracted from the Global Burden of Disease repository. The average annual percentage change (AAPC) and relative risks of cancer burdens were calculated using joinpoint regression analysis and age-period-cohort (APC) models, respectively. Moreover, a Bayesian APC model was employed to predict the disease burden over the next decade. Results: From 1990 to 2019, the number of incidences, deaths, and disability-adjusted life-years (DALYs) increased in China and the US, with a larger increase in China. Age-standardized incidence rates in China and the United States have shown an increasing trend over the past three decades, with AAPCs of 0.84 and 0.16%, respectively. However, the rates of age-standardized mortality and age-standardized DALYs decreased in both countries, with a greater decrease in China. Overall, age trends in cancer burden were similar for males and females, with two peaks in the childhood and elderly groups, respectively. The period and cohort effects on incidence showed an overall increasing trend in China and limited change in the US. However, the period effects for mortality and DALY were decreasing in both countries, while the cohort effects tended to increase and then decrease. Moreover, we predicted that the cancer burdens would continue to rise in China over the next decade. Conclusion: The burden of brain and CNS cancers is substantial and will continue to increase in China. Comprehensive policy and control measures need to be implemented to reduce the burden.