Efficacy and safety of KN026 and docetaxel for HER2-positive breast cancer: a phase II clinical trial.

Background: The standard first-line treatment for human epidermal growth factor receptor 2 (HER2)-positive recurrent/metastatic breast cancer currently includes pertuzumab plus trastuzumab and docetaxel. This study aimed to evaluate the effectiveness of KN026, an anti-HER2 bispecific antibody, plus docetaxel in first-line treatment of HER2-positive recurrent/metastatic breast cancer.

Methods: This open-label, single-arm, phase II study enrolled patients with HER2-positive recurrent/metastatic breast cancer in 19 centers across China from December 30, 2019 to May 27, 2021.

Parental burnout and parent-child relationship: the role of harsh parenting in couples.

Parental burnout is a prominent topic in current family research, with proven detrimental effects on the well-being of both parents and children. However, the specific mechanism by which parenting burnout impacts the parent-child relationship within families remains unclear. Furthermore, there is limited research exploring whether parenting burnout has a direct impact on the parent-child relationship.

Anemonin suppresses sepsis-induced acute lung injury by inactivation of nuclear factor-kappa B and activation of nuclear factor erythroid 2-related factor-2/heme oxygenase-1 pathway.

Sepsis-induced acute lung injury (ALI) is a common acute and severe reason of death in the intensive care unit. Although the pathogenesis is complicated and multifactorial, elevated inflammation and oxidative stress are considered as fundamental mechanisms for the progression of ALI. Anemonin is a natural compound with diverse biological properties including anti-inflammatory and anti-oxidative effects.

Norepinephrine (NE) promotes activated B cells to identify and kill effector CD8 T cells through FasL/Fas pathway in spleen mononuclear cells isolated from experimental autoimmune encephalomyelitis (EAE).

It has been reported that the nervous system can regulate immune reactions through various mechanisms. However, the role of splenic sympathetic nerve activity in the autoimmune reactions during the pathogenesis of experimental autoimmune encephalomyelitis (EAE) remained unclear. Here, we blocked the activity of the splenic sympathetic nerve and found that the number of adaptive immune cells, such as CD4 T cells, CD8 T cells and B cells, were upregulated.

Association between ESR1 and COL1A1 gene polymorphisms and skeletal fluorosis in Tibetan, Kazakh, Mongolian and Russian populations, China.

Background: Skeletal fluorosis is a chronic metabolic bone disease caused by excessive accumulation of fluoride in the bones. Previous studies have found that when the intake of tea fluoride is similar, the prevalence of skeletal fluorosis varies greatly among different ethnic groups, which may be related to different genetic backgrounds. Single nucleotide polymorphisms (SNPs) of estrogen receptor 1 (ESR1) and collagen type 1 α1 (COL1A1) were strongly associated with bone metabolism as well as bone growth and development, but their association with the risk of skeletal fluorosis has not been reported.

Left Atrial Mechanics and Atrioventricular Coupling in Hypertension With Supra-Normal Left Ventricular Ejection Fraction.

Objectives: Supra-normal left ventricular ejection fraction (snLVEF) represents a heterogeneous group with distinct prognoses. Left atrial (LA) strain, measured by speckle tracking echocardiography (STE), is a validated prognostic indicator. This study aimed to evaluate LA and left ventricular (LV) mechanical strains in hypertensive patients with snLVEF.

Immunoinfiltration Analysis of Mitochondrial Damage-Related Genes in Lung Adenocarcinoma and Construction of a Classification and Prognostic Model Integrated With WGCNA and Machine Learning Algorithms.

Background: Lung adenocarcinoma (LUAD) exhibits molecular heterogeneity, with mitochondrial damage affecting progression. The relationship between mitochondrial damage and immune infiltration, and Weighted Gene Co-expression Network Analysis (WGCNA)-derived biomarkers for LUAD classification and prognosis, remains unexplored.

Aims: The objective of our research is to identify gene modules closely related to the clinical stages of LUAD using the WGCNA method.

Cardiomyocyte-specific long noncoding RNA Trdn-as induces mitochondrial calcium overload by promoting the mA modification of calsequestrin 2 in diabetic cardiomyopathy.

Diabetic cardiomyopathy (DCM) is a medical condition characterized by cardiac remodeling and dysfunction in individuals with diabetes mellitus. Sarcoplasmic reticulum (SR) and mitochondrial Ca overload in cardiomyocytes have been recognized as biological hallmarks in DCM; however, the specific factors underlying these abnormalities remain largely unknown. In this study, we aimed to investigate the role of a cardiac-specific long noncoding RNA, D830005E20Rik (Trdn-as), in DCM.

Lactobacillus gasseri prevents ibrutinib-associated atrial fibrillation through butyrate.

Ibrutinib, a widely used anti-cancer drug, is known to significantly increase the susceptibility to atrial fibrillation (AF). While it is recognized that drugs can reshape the gut microbiota, influencing both therapeutic effectiveness and adverse events, the role of gut microbiota in ibrutinib-induced AF remains largely unexplored. Utilizing 16S rRNA gene sequencing, fecal microbiota transplantation, metabonomics, electrophysiological examination, and molecular biology methodologies, we sought to validate the hypothesis that gut microbiota dysbiosis promotes ibrutinib-associated AF and to elucidate the underlying mechanisms.

Assessing the Efficacy of ChatGPT Prompting Strategies in Enhancing Thyroid Cancer Patient Education: A Prospective Study.

With the rise of AI platforms, patients increasingly use them for information, relying on advanced language models like ChatGPT for answers and advice. However, the effectiveness of ChatGPT in educating thyroid cancer patients remains unclear. We designed 50 questions covering key areas of thyroid cancer management and generated corresponding responses under four different prompt strategies.

Lerociclib plus fulvestrant in patients with HR+/HER2- locally advanced or metastatic breast cancer who have progressed on prior endocrine therapy: LEONARDA-1 a phase III randomized trial.

Lerociclib (GB491), a highly selective oral CDK4/6 inhibitor, has displayed anti-tumor activity and differentiated safety and tolerability profile in previous ph1/2 clinical trials. The LEONARDA-1, a randomized, double-blind, phase III study, was conducted to evaluate the efficacy and safety of lerociclib in HR+/HER2- locally advanced or metastatic breast cancer patients, who had relapsed or progressed on prior endocrine therapy. A total of 275 patients were randomized at 1:1 ratio to receive lerociclib (137 patients, 150 mg twice daily) or placebo (138 patients) plus fulvestrant.

Arsenic trioxide preconditioning attenuates hepatic ischemia- reperfusion injury in mice: Role of ERK/AKT and autophagy.

Background: Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI.

The global, regional, and national burden of type 2 diabetes mellitus attributable to low physical activity from 1990 to 2021: a systematic analysis of the global burden of disease study 2021.

Background: Low physical activity (LPA) is a leading risk factor for type 2 diabetes mellitus (T2DM). We examine the temporal and spatial trends in the burden of T2DM attributable to LPA at the global, regional, and country scales.

Methods: Data were obtained from the Global Burden of Disease Study 2021.

Unraveling the Therapeutic Potential of Sophora flavescens Aiton in Myocardial Infarction: An Integrative Approach Combining Bioinformatics, Network Pharmacology, and Experimental Validation.

Aims: This study aims to elucidate the relationship between potential MI targets and SFA's mechanism of action, providing a theoretical basis for clinical development of new drugs.

Background: Myocardial infarction (MI) has been identified as one of the major cardiovascular diseases with adverse consequences. Sophora flavescens Aiton (SFA) is indicated for the therapeutic treatment of MI.

Dietary carotenoid intakes and biological aging among US adults, NHANES 1999-2018.

Background: Carotenoids have been shown to have multiple health benefits, including antioxidant and anti-inflammatory. The data for the effect of dietary specific carotenoids on biological aging is limited. Our study aims to examine the association between dietary carotenoid intake levels and biological aging.

Protein molecular structures of USP53, NPY2R, and DCTN1-AS1 and impact on tumors: Analysis of prognostic biomarkers for diffuse large B-cell lymphoma.

In the past few years, three protein molecules-USP53, NPY2R, and DCTN1-AS1-have garnered significant attention in scientific research due to their potential implications in tumor development. Mass spectrometry and proteomics techniques were used to analyze the three-dimensional structure of these protein molecules and predict their active sites and functional domains. The effects of USP53, NPY2R and DCTN1-AS1 on biological behavior of tumor cells were studied by constructing gene knockout and overexpression cell models.

Clinical Outcomes in A Multi-center Cohort Involving 919 Patients with Hypertriglyceridemia-associated Acute Pancreatitis.

Objectives: Hypertriglyceridemia-associated acute pancreatitis (HTG-AP) is one of the most common etiologies of acute pancreatitis (AP) worldwide. Compared to other etiologies, patients with HTG-AP may develop more severe AP, but previous studies yielded controversial conclusion due to the lack of adequate adjustment for the confounders. Therefore, this study aimed to examine the possibility and risk factors of developing severe AP in HTG-AP.

Rare and common genetic variants underlying the risk of Hirschsprung's disease.

Hirschsprung's disease (HSCR) is a congenital enteric neuropathic disorder characterized by high heritability (>80%) and polygenic inheritance (>20 genes). The previous genome-wide association studies (GWAS) identified several common variants associated with HSCR and demonstrated increased predictive performance for HSCR risk in Europeans using a genetic risk score, there remains a notable gap in knowledge regarding Chinese populations. We conducted whole exome sequencing in a HSCR case cohort in Chinese.

Ferroptosis-related alternative splicing signatures as potential biomarkers for predicting prognosis and therapy response in gastric cancer.

Ferroptosis is linked to various tumor biological traits, and alternative splicing (AS), a crucial step in mRNA processing, plays a role in the post-transcriptional regulation of ferroptosis-related genes (FRGs). A least absolute shrinkage and selection operator (LASSO) penalized Cox regression analysis was utilized to build a prognostic signature based on 12 AS events (p < 0.05), which was validated in gastric cancer (GC) patients.

PD-L1 positive platelets mediate resistance to immune checkpoint inhibitors in patients with colorectal cancer.

Background: Programmed cell death ligand 1 (PD-L1) expression on immune cells is correlated with the efficacy of immune checkpoint inhibitor (ICI) therapy in various types of cancer. Platelets are important components of the tumour microenvironment (TME) and are widely involved in the development of many types of cancer including colorectal cancer (CRC). However, the role of PD-L1 positive platelets in ICI therapy for CRC remains unknown.

The highly conserved PIWI-interacting RNA CRAPIR antagonizes PA2G4-mediated NF110-NF45 disassembly to promote heart regeneration in mice.

Targeting the cardiomyocyte cell cycle is a promising strategy for heart repair following injury. Here, we identify a cardiac-regeneration-associated PIWI-interacting RNA (CRAPIR) as a regulator of cardiomyocyte proliferation. Genetic ablation or antagomir-mediated knockdown of CRAPIR in mice impairs cardiomyocyte proliferation and reduces heart regenerative potential.

The role of lipid metabolism in cognitive impairment.

Alzheimer's disease (AD), diabetic cognitive impairment (DCI), and vascular dementia (VD) are considered the most common causes of severe cognitive impairment in clinical practice. Numerous factors can influence their progression, and many studies have recently revealed that metabolic disorders play crucial roles in the progression of cognitive impairment. Mounting evidence indicate that the regulation of lipid metabolism is a major factor in maintaining brain homeostasis.

Potential and development of cellular vesicle vaccines in cancer immunotherapy.

Cancer vaccines are promising as an effective means of stimulating the immune system to clear tumors as well as to establish immune surveillance. In this paper, we discuss the main platforms and current status of cancer vaccines and propose a new cancer vaccine platform, the cytosolic vesicle vaccine. This vaccine has a unique structure that can integrate antigen and adjuvant carriers to improve the delivery efficiency and immune activation ability, which brings new ideas for cancer vaccine design.

Lipopolysaccharide-induced active telocyte exosomes alleviate lipopolysaccharide-induced vascular barrier disruption and acute lung injury via the activation of the miRNA-146a-5p/caspase-3 signaling pathway in endothelial cells.

Background: Lipopolysaccharide (LPS)-induced apoptosis of lung microvascular endothelial cells (ECs) is the main reason of lung edema and acute lung injury (ALI) in septic conditions. Telocytes (TCs) are a distinct type of interstitial cells found around the lung microvasculature, which may protect ECs through the release of shed vesicles. However, whether TCs protect against LPS-induced EC apoptosis and ALI has not been determined.