KRAS mutation promotes immune escape of lung adenocarcinoma via ZNF24/SLC7A5/PD-L1 axis.

Background: The imbalance of immune checkpoint molecules leads to immune escape of tumor cells. It has been established that KRAS mutation plays a key role in regulating PD-L1 expression of lung adenocarcinoma. However, the specific mechanism by which KRAS mutation regulates PD-L1 expression still needs further been clarified.

Immune Signatures Distinguish Pure and Mixed Sepsis in Critical COVID-19: A Retrospective Cohort Study.

Background: COVID-19-associated sepsis poses unique challenges in intensive care units (ICUs), where patients are often immunocompromised and prone to secondary bacterial infections. Differentiating immune phenotypes between pure viral and viral-bacterial sepsis is essential for timely diagnosis and personalized treatment.

Objective: To compare clinical characteristics, immune profiles, and outcomes between patients with pure COVID-19 sepsis and those complicated by confirmed secondary bacterial infection, and to identify immune markers capable of differentiating sepsis phenotypes.

A 1H-1,5-benzodiazepine derivative induces apoptosis in colorectal cancer cells by inhibiting JAK/STAT signaling pathway.

Colorectal cancer (CRC) is among the most common cancers worldwide, with limited pharmacological options currently. Benzodiazepine and its synthetic derivatives are now of interest as their bioactive attributes, especially their inhibitory effect on various cancer cell lines. Herein we designed and synthesized of a series of compounds, among which T0, a 1H-1,5-benzodiazepine derivative, which exhibited potential inhibitory activity against colorectal cell lines in vitro.

Immunophenotypic, cytogenetic, and mutational features of chronic lymphocytic leukemia/small lymphocytic lymphoma with atypical immunophenotype.

Flow cytometric analysis plays an important role in the diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Most CLL cases show a typical immunophenotype characterized by the expression of CD5, CD23, CD43, ROR1, and CD200, along with dim expression of B-cell markers. However, some show an atypical immunophenotype.

Global burden of major chronic respiratory diseases among older adults aged 55 and above from 1990 to 2021: Changes, challenges, and predictions amid the pandemic.

Objective: To characterize sex- and age-specific changes in the comprehensive burden of major chronic respiratory diseases (CRDs) and their attributable risk factors among adults aged ≥55 years globally, regionally, and nationally from 1990 to 2021 using the Global Burden of Disease (GBD) 2021 database.

Methods: Utilizing the GBD 2021 database, we performed in-depth analyses and preliminary projections of global, regional, and national burden trends for chronic obstructive pulmonary disease (COPD), asthma, and interstitial lung disease & pulmonary sarcoidosis (ILD&PS) through multi-model approaches including but not limited to Age-Period-Cohort (APC) models, Joinpoint regression, and Bayesian Age-Period-Cohort (BAPC) modeling.

Results: The overall global CRD burden among adults ≥55 years declined from 1990 to 2021.

Gut Microbiota Mediate Periampullary Cancer Through Extracellular Matrix Proteins: A Causal Relationship Study.

Recent studies have reported that gut microbiota may play a role in the occurrence and development of digestive system cancers. Periampullary cancer is a relatively rare digestive system cancer which lacks effective targeted therapy and specific drugs. The purpose of this study is to elucidate the relationship between periampullary cancer and gut microbiota.

Spread of the FAR-MRSA clone, a fusidic acid- and meticillin-resistant ST121, Europe, 2014 to 2024.

We describe the genetic characteristics of a fusidic acid- and meticillin-resistant (MRSA) clone widespread in Europe, based on whole genome sequences from 317 isolates. The clone is causing impetigo and other skin and soft tissue infections, primarily in young children. Comparison with publicly available ST121 sequences showed that the clone is clearly distinct from previously described ST121 clones.

Understanding the Role of Borohydride Doping in Electrochemical Stability of Argyrodite LiPSCl Solid-State Electrolyte.

This work elucidates the mechanism by which lithium borohydride (LiBH) doping into argyrodite-type LiPSCl (LBH-LPSCl) solid-state electrolyte (SSE) enhances electrochemical stability. State-of-the-art electrochemical performance is achieved with 5 wt% borohydride. Symmetric cells achieve critical current density (CCD) of 7.

Non-invasive monitoring of infections in chronic lung disease patients: a combined serology and HRCT imaging approach.

Background: Diagnosing infections in patients with chronic pulmonary diseases is challenging, particularly in settings where invasive diagnostic tools are limited. This study explores a non-invasive diagnostic approach, combining serological tests and high-resolution computed tomography (HRCT) imaging, to identify patients who may need further invasive evaluation for infection.

Methods: This retrospective study included patients with chronic pulmonary diseases from regional centers who experienced acute exacerbations that did not respond to antibacterial therapy, had positive sputum cultures for species, and lacked typical invasive radiological features on HRCT.

Understanding the gap between expectations and reality in decentralized clinical trials.

Decentralized clinical trials (DCTs) have gained long-standing interest, yet their adoption as a new paradigm remains uncertain even with broader acceptance from regulatory and industry. This study aims to unveil its evolutional trend, which helps answer what the current development stage DCT is located at as well as the underlying reasons. While DCTs' prime time has not arrived, we propose solutions to advance their sustainable implementation.

Concurrent or subsequent lymphomatous effusion in large B-cell lymphoma portends a dismal prognosis: A multi-institutional study.

Objective: Rare large B-cell lymphomas (LBCLs) present with concurrent or subsequent lymphomatous effusion (solid-effusion LBCL, SE-LBCL), which may have an inferior prognosis compared with their noneffusion counterpart. In addition, the relationship between SE-LBCL and human herpesvirus 8-negative effusion-based LBCL (EB-LBCL) remains unclear.

Methods: We collected 141 cases of SE-LBCL and a control cohort of 101 cases of stage IV solid-only LBCL.

10PL8 and 2fPL8 inhibit gastric cancer cell proliferation by targeting degradation of CDK6 proteins to arrest the cell cycle.

Existing studies on PROTAC technology frequently rely on modifications and validation of already marketed drugs, which limits the exploration of non-drug-forming proteins and targets that do not have existing therapeutic agents. In contrast, utilizing easily synthesized combinatorial chemical databases that offer a broad selection of compounds presents a promising strategy for discovering new PROTAC molecules. In this study, virtual screening was conducted on a small molecule database created using combinatorial chemistry, which contains a total of 12,904 active molecules.

Investigation of the Efficacy and Safety of Xeligekimab (GR1501) in Patients with Moderate-to-Severe Plaque Psoriasis: A Multicenter, Randomized, Double-Blind Phase II Clinical trial.

Introduction: Psoriasis is a chronic inflammatory skin disease. This study evaluated the efficacy and safety of xeligekimab (GR1501), a novel anti-interleukin-17A (anti-IL-17A) monoclonal antibody, in Chinese patients with moderate-to-severe plaque psoriasis.

Methods: In this multicenter, randomized, double-blind, phase II trial, 199 patients were assigned (1:1:1:1) to receive placebo (n = 49) or xeligekimab 100 mg (n = 50), 150 mg (n = 49), or 200 mg (n = 51) every 4 weeks for 12 weeks.

Low CD25 in ALK+ Anaplastic Large Cell Lymphoma Is Associated with Older Age, Thrombocytopenia, and Increased Expression of Surface CD3 and CD8.

Background/objectives: Anaplastic lymphoma kinase (ALK)-positive (+) anaplastic large cell lymphoma (ALCL) is known to express CD25, but its significance has not been well studied.

Methods: In the present study, we identified 54 ALK+ ALCL patients with CD25 results available and investigated the significance of CD25 expression levels.

Results: Forty-two (78%) cases had high CD25 expressions, whereas low CD25 expressions were found in 12 (22%) cases.

Blastic Plasmacytoid Dendritic Cell Neoplasm Presenting With Bruise-Like Macules: Case Report and Literature Review.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive malignancy characterized by a high frequency of cutaneous lesions at diagnosis. We report a 16-year-old female with BPDCN presenting with bruise-like macules over her face, trunk, and extremities, without evidence of other organ involvement, and review six similar cases. Pediatric BPDCN typically has a more favorable prognosis compared to adult cases.

Pagoda-Shaped Adhesive Microneedles Loaded with Ketorolac for Aortic Dissection Treatment.

Aortic dissection is a serious health risk and has led to interest in creating effective drug treatments like ketorolac. However, conventional administration techniques lack specificity, which limits their effectiveness and may result in adverse effects. A microneedle patch system (MNPS) offers a minimally invasive, pain-free alternative with a high capacity for drug delivery, but there is still a gap in the direction of treating aortic dissection.

Tailoring a Functional Synthetic Microbial Community Alleviates Fusobacterium nucleatum-infected Colorectal Cancer via Ecological Control.

Polymorphic microbiomes play important roles in colorectal cancer (CRC) occurrence and development. In particular, Fusobacterium nucleatum (F. nucleatum) is prevalent in patients with CRC, and eliminating it is beneficial for treatment.

Esmolol improves sepsis outcomes through cardiovascular and immune modulation.

Background: Sepsis poses significant mortality risks. Esmolol, a β1-adrenergic blocker, may improve outcomes through cardiovascular and immune modulation. This study aims to evaluate the effects of Esmolol on survival rates, inflammatory markers, and immune function in sepsis patients.

Nanofibrous membrane/self-healing hydrogel double-layer nanocomposite dressings based on oxidized dextran and carboxymethyl chitosan loading ZIF-nanozyme for enhanced bacterial-infected diabetic wound healing.

Treatment of diabetic wounds at different stages remains a pressing challenge. By simulating the complex structure of natural skin, a multifunctional nanofibrous membrane/self-healing hydrogel double-layer nanocomposite dressing loading nanozyme was prepared to accelerate diabetic wound healing. The upper layer was prepared from a modified self-synthesized polyurethane (APU) nanofibrous membrane, and the bottom layer was made of an injectable self-healing hydrogel loaded with nanozyme based on oxidized dextran (ODex) and carboxymethyl chitosan (CMC).

Learning from the LEAP trial series: Optimizing clinical trial design for combination therapies.

The LEAP trial series examining the synergy of pembrolizumab and lenvatinib across various cancers has yielded mixed results, highlighting the need for a more detailed understanding of combination therapies. By learning from these trials, we aim to advance the clinical development of more effective combination strategies to improve patient outcomes.

Unusually Indolent CML: Absence of Complete Cytogenetic Response after 10 Years of Tyrosine Kinase Inhibitor Therapy.

Background: With BCR::ABL1 tyrosine kinase inhibitor (TKI) therapy, most patients with chronic-phase chronic myeloid leukemia (CML-CP) can achieve complete cytogenetic response (CCyR) within 6 months of therapy. However, no studies have investigated patients who do not achieve CCyR yet maintains stable disease on long-term TKI treatment. Here we investigated 30 CML-CP patients who did not achieve CCyR but remained free of blastic progression for at least 10-year while on TKI therapy.