Elevated serum and urinary secreted protein acidic and rich in cysteine levels are novel biomarkers of kidney fibrosis severity.

Background: Interstitial fibrosis is the primary determinant of the progression of chronic kidney disease (CKD), and noninvasive identification of interstitial fibrosis is a major challenge. We aimed to explore the diagnostic value of secreted protein acidic and rich in cysteine (SPARC) in serum and urine in kidney fibrosis.

Methods: Single-cell transcriptome analysis was used to measure SPARC expression in healthy reference kidneys and those of patients with CKD.

Hydrogen sulfide-generating semiconducting polymer nanoparticles for amplified radiodynamic-ferroptosis therapy of orthotopic glioblastoma.

A variety of therapeutic strategies are available to treat glioblastoma (GBM), but the tumor remains one of the deadliest due to its aggressive invasiveness, restrictive blood-brain barrier (BBB), and exceptional resistance to drugs. In this study, we present a hydrogen sulfide (HS)-generating semiconducting polymer nanoparticle (PFeD@Ang) for amplified radiodynamic-ferroptosis therapy of orthotopic glioblastoma. Our results show that in an acidic tumor microenvironment (TME), HS donors produce large amounts of HS, which inhibits mitochondrial respiration and alleviates cellular hypoxia, thus enhancing the radiodynamic effect during X-ray irradiation; meanwhile, Fe is reduced to Fe by tannic acid in an acidic TME, which promotes an iron-dependent cell death process in tumors.

CircRNome-wide characterisation reveals the promoting role of circAATF in anti-PD-L1 immunotherapy of gallbladder carcinoma.

Circular RNAs (circRNAs) have been shown to play important roles in tumour development and tumour immunology. However, genome-wide characterisation of circRNAs and their roles in the immunology and immunotherapy of gallbladder carcinoma (GBC) has been lacking. We present a comprehensive characterisation of the circRNA landscape in GBC, revealing GBC-specific circRNAs.

Effectiveness and safety of adjunctive non-drug measures in improving respiratory symptoms among patients with severe COVID-19: A multicenter randomized controlled trial.

Background: The outbreak of coronavirus disease 2019 (COVID-19) infection posed a huge threat and burden to public healthcare in late 2022. Non-drug measures of traditional Chinese medicine (TCM), such as acupuncture, cupping and moxibustion, are commonly used as adjuncts in China to help in severe cases, but their effects remain unclear.

Objectives: To observe the clinical effect of TCM non-drug measures in improving respiratory function and symptoms among patients with severe COVID-19.

Clinical significance of gene expression and rs3219175 G > a polymorphism in cancer.

The inflammatory cytokine resistin, which is encoded by the gene, plays a variety of roles in cancer. This study aimed to assess the relationship between gene expression and cancer stage, survival prognosis, immune infiltration, and drug sensitivity, and whether the rs3219175 G > A polymorphism affected the expression of the gene and cancer risk. The clinical significance of gene expression and the rs3219175 polymorphism in cancer was analyzed by the GSCA platform, GTEx database and STATA software.

Longitudinal trajectories of blood glucose and 30-day mortality in patients with diabetes mellitus combined with acute myocardial infarction: A retrospective cohort analysis of the MIMIC database.

Background: Although blood glucose changes have been suggested to be a potential better target for clinical control than baseline blood glucose levels, the association of blood glucose changes with the prognosis in acute myocardial infarction (AMI) patients with diabetes mellitus (DM) is unclear. Herein, this study aimed to investigate association of short-term longitudinal trajectory of blood glucose with 30-day mortality in this population.

Methods: Data of AMI patients with DM were extracted from the Medical Information Mart for Intensive Care (MIMIC) database in 2003-2019 in this retrospective cohort study.

Inhalable cardiac targeting peptide modified nanomedicine prevents pressure overload heart failure in male mice.

Heart failure causes considerable morbidity and mortality worldwide. Clinically applied drugs for the treatment of heart failure are still severely limited by poor delivery efficiency to the heart and off-target consumption. Inspired by the high heart delivery efficiency of inhaled drugs, we present an inhalable cardiac-targeting peptide (CTP)-modified calcium phosphate (CaP) nanoparticle for the delivery of TP-10, a selective inhibitor of PDE10A.

Cytokine-induced killer cells-mediated chlorin e6-loaded gold nanostars for targeted NIR imaging and immuno-photodynamic combination therapy for lung cancer.

Recently, cytokine-induced killer (CIK) cells have a broad application prospect in the comprehensive diagnosis and treatment of tumors owing to their unique characteristics of killing and targeting malignant tumors. Herein, we report a facile strategy for synthesis of monodisperse gold nanostars (GNSs) based on PEGylation and co-loaded with the photosensitizer chlorin e6 (Ce6) to form GNSs-PEG@Ce6 NPs. Then employing CIK cells loading the as-prepared GNSs-PEG@Ce6 NPs to fabricate a CIK cells-based drug delivery system (GNSs-PEG@Ce6-CIK) for lung cancer.

Efficacy of acupuncture treatment for breast cancer-related insomnia: study protocol for a multicenter randomized controlled trial.

Background: Insomnia is one of the most common symptoms among breast cancer patients, which can be present throughout all stages of breast cancer. As a non-pharmacological alternative treatment, acupuncture has been suggested to improve sleep situations in patients with cancer suffering from insomnia. However, there is a lack of well-designed, high-quality clinical evidence regarding the efficacy of acupuncture in the treatment of breast cancer-related insomnia.

GTF2H4 regulates partial EndMT via NF-κB activation through NCOA3 phosphorylation in ischemic diseases.

Partial endothelial-to-mesenchymal transition (EndMT) is an intermediate phenotype observed in endothelial cells (ECs) undergoing a transition toward a mesenchymal state to support neovascularization during (patho)physiological angiogenesis. Here, we investigated the occurrence of partial EndMT in ECs under hypoxic/ischemic conditions and identified general transcription factor IIH subunit 4 (GTF2H4) as a positive regulator of this process. In addition, we discovered that GTF2H4 collaborates with its target protein excision repair cross-complementation group 3 (ERCC3) to co-regulate partial EndMT.

Genetically proxied therapeutic inhibition of lipid-lowering drug targets and risk of rheumatoid arthritis disease: a Mendelian randomization study.

Objective: To evaluate the potential impact of consistent use of similar treatments over a long period; it is essential to investigate the potential correlation between genetic variations that influence the expression or function of pharmacological targets for reducing lipid levels and the risk of developing rheumatoid arthritis.

Methods: We used variants in the following genes to conduct Mendelian randomization analyses: HMGCR (encoding the target for statins), PCSK9 (encoding the target for PCSK9 inhibitors, such as evolocumab and alirocumab), and NPC1L1 (encoding the target for ezetimibe). Data from lipid genetics consortia (173,082 sample size) were used to weight variations according to their correlations with low-density lipoprotein cholesterol (LDL-C).

An integrated strategy of UPLC-Q-TOF-MS analysis, network pharmacology, and molecular docking to explore the chemical constituents and mechanism of Zixue Powder against febrile seizures.

Febrile seizures (FS) are the most common type of seizures for children. As a commonly used representative cold formula for resuscitation, Zixue Powder (ZP) has shown great efficacy for the treatment of FS in clinic, while its active ingredients and underlying mechanism remain largely unclear. This study aimed to preliminarily elucidate the material basis of ZP and the potential mechanism for the treatment of FS through ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS), network pharmacology, and molecular docking.

Metagenomic identification of pathogens and antimicrobial-resistant genes in bacterial positive blood cultures by nanopore sequencing.

Nanopore sequencing workflows have attracted increasing attention owing to their fast, real-time, and convenient portability. Positive blood culture samples were collected from patients with bacterial bloodstream infection and tested by nanopore sequencing. This study compared the sequencing results for pathogen taxonomic profiling and antimicrobial resistance genes to those of species identification and phenotypic drug susceptibility using traditional microbiology testing.

Three-dimensional echocardiography reveals early mitral valve alterations in hypertrophic cardiomyopathy genetic mutation carriers.

Background: The mitral valve undergoes structural modifications in response to cardiac functional changes, often predating cardiac decompensation and overt clinical signs. Our study assessed the potential of mitral valve morphological changes as early indicators for detecting carriers of hypertrophic cardiomyopathy (HCM)-associated gene mutations.

Methods: We studied 505 participants: 189 without the pathogenic gene mutations and left ventricular hypertrophy (G-/LVH-), 149 carriers without LV hypertrophy (G+/LVH-), and 167 manifest HCM patients (G+/LVH+).

ESCRT-III Component CHMP4C Attenuates Cardiac Hypertrophy by Targeting the Endo-Lysosomal Degradation of EGFR.

Background: Cardiac hypertrophy and subsequent heart failure impose a considerable burden on public health worldwide. Impaired protein degradation, especially endo-lysosome-mediated degradation of membrane proteins, is associated with cardiac hypertrophy progression. CHMP4C (charged multivesicular body protein 4C), a critical constituent of multivesicular bodies, is involved in cellular trafficking and signaling.

Investigation of the Molecular Mechanisms Underlying the Therapeutic Effect of L. Essential Oil on Acute Lung Injury Using Gas Chromatography-Mass Spectrometry and Network Pharmacology.

Objective: The present study aimed to investigate the molecular mechanism through which essential oil treats acute lung injury (ALI) through network pharmacology, molecular docking, and assays.

Methods: Relevant ALI targets of the active ingredients of essential oil were predicted using the SwissTargetPrediction database and meta TarFisher database. These ALI targets were then screened using GeneCards and DisGeNET, and differentially expressed ALI target genes were identified using the Gene Expression Omnibus (GEO) database.

SIRT6 deficiency in endothelial cells exacerbates oxidative stress by enhancing HIF1α accumulation and H3K9 acetylation at the Ero1α promoter.

Background: SIRT6, an important NAD -dependent protein, protects endothelial cells from inflammatory and oxidative stress injuries. However, the role of SIRT6 in cardiac microvascular endothelial cells (CMECs) under ischemia-reperfusion injury (IRI) remains unclear.

Methods: The HUVECs model of oxygen-glucose deprivation/reperfusion (OGD/R) was established to simulate the endothelial IRI in vitro.

Gene-echocardiography: refining genotype-phenotype correlations in hypertrophic cardiomyopathy.

Aims: This study aims to clarify the association between hypertrophic patterns and genetic variants in hypertrophic cardiomyopathy (HCM) patients, contributing to the advancement of personalized management strategies for HCM.

Methods And Results: A comprehensive evaluation of genetic mutations was conducted in 392 HCM-affected families using Whole Exome Sequencing. Concurrently, relevant echocardiographic data from these individuals were collected.

Dynamics of cerebrospinal fluid pressure alterations and bilateral transverse-sigmoid sinus morphologies in Asian patients with venous pulsatile tinnitus.

Objective: This study was performed to investigate the dynamics of intracranial pressure (ICP) alterations and bilateral transverse-sigmoid sinus morphologies in patients with venous pulsatile tinnitus (PT).

Methods: This retrospective study involved 27 patients with venous PT associated with sigmoid sinus wall anomalies. ICP and ICP metrics were measured by cerebrospinal fluid manometry and internal jugular vein compression tests.

Guizhi Fuling capsule relieves memory deficits by inhibition of microglial neuroinflammation through blocking JAK2/STAT3 pathway in presenilin1/2 conditional double knockout mice.

Chronic neuroinflammation has been regarded as an important part of the pathological initiation of Alzheimer's disease (AD), which is associated with the regulation of microglial activation. Preventing microglial activation to inhibit neuroinflammation may become a potential target for the treatment of neurodegenerative diseases. Guizhi Fuling capsule (GZFL) has a strong repression on inflammatory responses.

Novel ginsenoside monomer RT4 promotes colitis repair in mice by regulating miR-144-3p/SLC7A11 signaling pathway.

Background: Ginsenoside RT4 (RT4) is a new biologically active compound extracted from ginseng that possesses numerous medicinal and pharmacological properties. However, its potential therapeutic effect of ginsenoside RT4 on ulcerative colitis remains unknown.

Methods And Results: In this study, we investigated the anti-inflammatory effects of ginsenoside RT4 and its underlying molecular mechanism in the treatment of ulcerative colitis mice induced with dextran sulfate sodium (DSS).