Efficacy, safety, and quality of life of dabrafenib plus trametinib treatment in Chinese patients with mutation-positive metastatic non-small cell lung cancer.

Background: Dabrafenib plus trametinib (Dab + Tram) is an approved targeted therapy in patients with mutated metastatic non-small cell lung cancer (NSCLC). Here, we report the efficacy, safety, and quality of life (QoL) results of Dab + Tram treatment in Chinese patients with mutation-positive metastatic NSCLC.

Methods: This is a single-arm, open-label, multicentre, phase II study (NCT04452877).

Macrocyclic Diterpenoids from Possessing Activity Towards Autophagic Flux.

Euphjatrophanes H-L (-), four new jatrophane-type and one new lathyrane-type diterpenoid, were isolated from , along with eight known diterpenoids (-). Their structures were established on the basis of extensive spectroscopic analysis and X-ray crystallographic experiments. All compounds were subjected to bioactivity evaluation using flow cytometry in autophagic flux assays with HM mCherry-GFP-LC3 cells, the human microglia cells which stably expressed the tandem monomeric mCherry-GFP-tagged LC3.

General anesthesia induces acute cell-free DNA methylation changes in peripheral blood.

Background: Short-term and long-term adverse events could occur after general anesthesia (GA) and the specific mechanism driving these effects has not yet been well-characterized. In this study, we aimed to evaluate the global effect of GA on DNA methylation in the cell-free DNA (cfDNA) of surgical lung-nodule patients.

Methods: This large retrospective cohort study enrolled 1,006 surgical lung nodule patients (529 pre-anesthesia, and 477 post-anesthesia).

Novel Biallelic Synonymous Exonic Variant in Affecting mRNA Splicing: Case Report.

Objectives: Chorea-acanthocytosis is an autosomal recessively inherited condition caused by loss-of-function pathogenic variants in . We identified a novel synonymous exonic variant leading to abnormal mRNA splicing in a patient with chorea-acanthocytosis.

Methods: A patient with focal epilepsy developed generalized chorea with orolingual dystonia, cognitive decline, and peripheral neuropathy, consistent with chorea-acanthocytosis.

Efficacy and safety of JMT103 in patients with unresectable or surgically-challenging giant cell tumor of bone: a multicenter, phase Ib/II study.

This was a multicenter, single-arm, open-label, phase Ib/II study (NCT04255576), aimed to evaluate the efficacy and safety of JMT103 in patients with unresectable or surgically-challenging giant cell tumor of bone (GCTB). JMT103 (2 mg/kg) was administered subcutaneously every four weeks, with loading doses on days 8 and 15. The primary endpoint was the objective tumor response rate (OTR) based on best response, defined as the proportion of patients who achieved elimination of at least 90% of the giant cells or radiologic complete or partial response per the modified Inverse Choi density/size (mICDS) or modified European Organization for Research and Treatment of Cancer (mEORTC) within 12 weeks.

Composite Hedges Nanopores codec system for rapid and portable DNA data readout with high INDEL-Correction.

Reading digital information from highly dense but lightweight DNA medium nowadays relies on time-consuming next-generation sequencing. Nanopore sequencing holds the promise to overcome the efficiency problem, but high indel error rates lead to the requirement of large amount of high quality data for accurate readout. Here we introduce Composite Hedges Nanopores, capable of handling indel rates up to 15.

IOP Reduction in Nonhuman Primates by Microneedle Injection of Drug-Free Hydrogel to Expand the Suprachoroidal Space.

Purpose: Expansion of the suprachoroidal space (SCS) by a hydrogel injection has been shown to reduce intraocular pressure (IOP) in rabbits as a potential treatment for ocular hypertension in glaucoma. Here, we evaluate the safety and efficacy of this approach in hypertensive and normotensive eyes in nonhuman primates.

Methods: A microneedle was used to inject a hyaluronic acid-based hydrogel or saline solution (control) into the SCS of cynomolgus monkey eyes that were either normotensive (n = 7 experimental; n = 2 control eyes) or had induced ocular hypertension (n = 6 experimental; n = 3 control eyes).

Omega-3 Polyunsaturated Fatty Acids as a Protective Factor for Myopia.

Purpose: Animal models suggest omega-3 polyunsaturated fatty acids (PUFAs) may protect against myopia by modulating choroidal blood perfusion, but clinical evidence is scarce and mixed. We aimed to determine the causality between omega-3 PUFAs and myopia using Mendelian randomization (MR) analysis.

Design: Two-sample MR analysis.

Is It Still Beneficial to Monitor the Trough Concentration of Vancomycin? A Quantitative Meta-Analysis of Nephrotoxicity and Efficacy.

This study conducted a quantitative meta-analysis to investigate the association of vancomycin indicators, particularly area under the curve over 24 h (AUC) and trough concentrations (C), and their relationship with both nephrotoxicity and efficacy. Literature research was performed in PubMed and Web of Science on vancomycin nephrotoxicity and efficacy in adult inpatients. Vancomycin C, AUC, AUC/minimum inhibitory concentration (MIC), nephrotoxicity evaluation and treatment outcomes were extracted.

LncRNA DCRT Protects Against Dilated Cardiomyopathy by Preventing NDUFS2 Alternative Splicing by Binding to PTBP1.

Background: Dilated cardiomyopathy is characterized by left ventricular dilation and continuous systolic dysfunction. Mitochondrial impairment is critical in dilated cardiomyopathy; however, the underlying mechanisms remain unclear. Here, we explored the cardioprotective role of a heart-enriched long noncoding RNA, the dilated cardiomyopathy repressive transcript (DCRT), in maintaining mitochondrial function.

A potent Henipavirus cross-neutralizing antibody reveals a dynamic fusion-triggering pattern of the G-tetramer.

The Hendra and Nipah viruses (HNVs) are highly pathogenic pathogens without approved interventions for human use. In addition, the interaction pattern between the attachment (G) and fusion (F) glycoproteins required for virus entry remains unclear. Here, we isolate a panel of Macaca-derived G-specific antibodies that cross-neutralize HNVs via multiple mechanisms.

2024 Chinese Expert Consensus Guidelines on the Diagnosis and Treatment of Atrial Fibrillation in the Elderly, Endorsed by Geriatric Society of Chinese Medical Association (Cardiovascular Group) and Chinese Society of Geriatric Health Medicine (Cardiovascular Branch): Executive Summary.

The consensus guidelines of the Geriatric Society of Chinese Medical Association on the management of atrial fibrillation (AF) in the elderly was first published in 2011 and updated in 2016, with endorsement by Chinese Society of Geriatric Health Medicine. Since then, many important studies regarding the screening and treatment in the elderly population have been reported, necessitating this updated expert consensus guideline. The writing committee members comprehensively reviewed updated evidence pertaining to elderly patients with AF, and formulated this 2024 update.

Enhanced potency of an IgM-like nanobody targeting conserved epitope in SARS-CoV-2 spike N-terminal domain.

Almost all the neutralizing antibodies targeting the receptor-binding domain (RBD) of spike (S) protein show weakened or lost efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged or emerging variants, such as Omicron and its sub-variants. This suggests that highly conserved epitopes are crucial for the development of neutralizing antibodies. Here, we present one nanobody, N235, displaying broad neutralization against the SARS-CoV-2 prototype and multiple variants, including the newly emerged Omicron and its sub-variants.

LncRNA CHKB-DT Downregulation Enhances Dilated Cardiomyopathy Through ALDH2.

Background: Human cardiac long noncoding RNA (lncRNA) profiles in patients with dilated cardiomyopathy (DCM) were previously analyzed, and the long noncoding RNA CHKB (choline kinase beta) divergent transcript (CHKB-DT) levels were found to be mostly downregulated in the heart. In this study, the function of CHKB-DT in DCM was determined.

Methods: Long noncoding RNA expression levels in the human heart tissues were measured via quantitative reverse transcription-polymerase chain reaction and in situ hybridization assays.

Hyperpolarized Gas Imaging in Lung Diseases: Functional and Artificial Intelligence Perspective.

Pathophysiologic changes in lung diseases are often accompanied by changes in ventilation and gas exchange. Comprehensive evaluation of lung function cannot be obtained through chest X-ray and computed tomography. Proton-based lung MRI is particularly challenging due to low proton density within the lung tissue.

AGO2 Protects Against Diabetic Cardiomyopathy by Activating Mitochondrial Gene Translation.

Background: Diabetes is associated with cardiovascular complications. microRNAs translocate into subcellular organelles to modify genes involved in diabetic cardiomyopathy. However, functional properties of subcellular AGO2 (Argonaute2), a core member of miRNA machinery, remain elusive.

Logical Magic State Preparation with Fidelity beyond the Distillation Threshold on a Superconducting Quantum Processor.

Fault-tolerant quantum computing based on surface code has emerged as an attractive candidate for practical large-scale quantum computers to achieve robust noise resistance. To achieve universality, magic states preparation is a commonly approach for introducing non-Clifford gates. Here, we present a hardware-efficient and scalable protocol for arbitrary logical state preparation for the rotated surface code, and further experimentally implement it on the Zuchongzhi 2.

Novel Pan-ERR Agonists Ameliorate Heart Failure Through Enhancing Cardiac Fatty Acid Metabolism and Mitochondrial Function.

Background: Cardiac metabolic dysfunction is a hallmark of heart failure (HF). Estrogen-related receptors ERRα and ERRγ are essential regulators of cardiac metabolism. Therefore, activation of ERR could be a potential therapeutic intervention for HF.

Coating-Free Culture Medium for Establishing and Maintaining Human Induced Pluripotent Stem Cells.

Cell expansion of human pluripotent stem cells (hPSCs) commonly depends on Matrigel as a coating matrix on two-dimensional (2D) culture plates and 3D microcarriers. However, the xenogenic Matrigel requires sophisticated quality-assurance processes to meet clinical requirements. In this study, we develop an innovative coating-free medium for expanding hPSCs.

PROTAC targeting cyclophilin A controls virus-induced cytokine storm.

Cytokine storms caused by viruses are associated with elevated cytokine levels and uncontrolled inflammatory responses that can lead to acute respiratory distress syndrome. Current antiviral therapies are not sufficient to prevent or treat these complications. Cyclophilin A (CypA) is a key factor that regulates the production of multiple cytokines and could be a potential therapeutic target for cytokine storms.

Pharmaco-proteogenomic characterization of liver cancer organoids for precision oncology.

Organoid models have the potential to recapitulate the biological and pharmacotypic features of parental tumors. Nevertheless, integrative pharmaco-proteogenomics analysis for drug response features and biomarker investigation for precision therapy of patients with liver cancer are still lacking. We established a patient-derived liver cancer organoid biobank (LICOB) that comprehensively represents the histological and molecular characteristics of various liver cancer types as determined by multiomics profiling, including genomic, epigenomic, transcriptomic, and proteomic analysis.

Toxicokinetics of recombinant human fibroblast growth factor 21 for injection in cynomolgus monkey for 3 months.

Recombinant human fibroblast growth factor 21 (FGF-21) is a potential therapeutic agent for multiple metabolic diseases. However, little is known about the toxicokinetic characteristics of FGF-21. In the present study, we investigated the toxicokinetics of FGF-21 delivered via subcutaneous injection .

Late-Onset Anti-GABA Receptor Encephalitis: Clinical Characteristics and Outcomes Differing From Early-Onset Patients.

Background And Objectives: Existing evidence indicates anti-GABA receptor encephalitis (GABAR-E) seems to occur more commonly later in life, yet the age-associated differences in clinical features and outcomes are not well determined. This study aims to explore the demographic, clinical characteristics, and prognostic differences between late-onset and early-onset GABAR-E and identify predictors of favorable long-term outcomes.

Methods: This is an observational retrospective study conducted in 19 centers from China.