Longitudinal serum proteome mapping reveals biomarkers for healthy ageing and related cardiometabolic diseases.

The blood proteome contains biomarkers of ageing and age-associated diseases, but such markers are rarely validated longitudinally. Here we map the longitudinal proteome in 7,565 serum samples from a cohort of 3,796 middle-aged and elderly adults across three time points over a 9-year follow-up period. We pinpoint 86 ageing-related proteins that exhibit signatures associated with 32 clinical traits and the incidence of 14 major ageing-related chronic diseases.

Oncolytic vaccinia virus armed with anti-CD47 nanobody elicit potent antitumor effects on multiple tumor models via enhancing innate and adoptive immunity.

Objective: Targeting CD47 for cancer immunotherapy has been studied in many clinical trials for the treatment of patients with advanced tumors. However, this therapeutic approach is often hampered by on-target side effects, physical barriers, and immunosuppressive tumor microenvironment (TME).

Methods: To improve therapeutic efficacy while minimizing toxicities, we engineered an oncolytic vaccinia virus (OVV) encoding an anti-CD47 nanobody (OVV-αCD47nb).

Noncanonical UPR factor CREB3L2 drives immune evasion of triple-negative breast cancer through Hedgehog pathway modulation in T cells.

The unfolded protein response (UPR) pathway is crucial for tumorigenesis, mainly by regulating cancer cell stress responses and survival. However, whether UPR factors facilitate cell-cell communication between cancer cells and immune cells to drive cancer progression remains unclear. We found that adenosine 3',5'-monophosphate response element-binding protein 3-like protein 2 (CREB3L2), a noncanonical UPR factor, is overexpressed and activated in triple-negative breast cancer, where its cleavage releases a C-terminal fragment that activates the Hedgehog pathway in neighboring CD8+ T cells.

Long-term outcome of endovascular thrombectomy in patients with acute ischemic stroke: a systematic review and meta-analysis.

Background: Randomized controlled trials have demonstrated the efficacy and safety of endovascular thrombectomy (EVT) in patients with acute large vessel occlusion stroke. However, its long-term benefits remain uncertain. Therefore, this study aimed to investigate the long-term clinical outcomes of EVT.

Optimized BCMA/CS1 bispecific TRuC-T cells secreting IL-7 and CCL21 robustly control multiple myeloma.

Introduction: Challenges remain in reducing antigen escape and tumor recurrence while CAR-T cell therapy has substantially improved outcomes in the treatment of multiple myeloma. T cell receptor fusion construct (TRuC)-T cells, which utilize intact T cell receptor (TCR)-CD3 complex to eliminate tumor cells in a non-major histocompatibility complex (MHC)-restricted manner, represent a promising strategy. Moreover, interleukin-7 (IL-7) is known to enhance the proliferation and survival of T cells.

Integral-Omics: Serial Extraction and Profiling of Metabolome, Lipidome, Genome, Transcriptome, Whole Proteome and Phosphoproteome Using Biopsy Tissue.

The integrative multiomics characterization of minute amounts of clinical tissue specimens has become increasingly important. Here, we present an approach called Integral-Omics, which enables sequential extraction of metabolites, lipids, genomic DNA, total RNA, proteins, and phosphopeptides from a single biopsy-level tissue specimen. We benchmarked this method with various samples, applied the workflow to perform multiomics profiling of tissues from six patients with colorectal cancer, and found that tumor tissues exhibited suppressed ferroptosis pathways at multiomics levels.

Efficacy of dupilumab with concomitant topical calcineurin inhibitors treatment for preschool children with atopic dermatitis: a retrospective cohort study.

Background/objective: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease that typically occurs in childhood/infancy and is associated with complications like extracutaneous atopic morbidity. Providing systemic treatment for pediatric AD patients with unmet comprehensive medical needs remains challenging. We present a cohort study describing the efficacy and safety of dupilumab combined with topical calcineurin inhibitors (TCI) in children with moderate-to-severe atopic dermatitis under the age of 6 years.

An L-shaped association between lymphocyte-to-monocyte ratio and erectile dysfunction in NHANES 2001-2004.

This study aimed to explore the relationship between the lymphocyte/monocyte ratio (LMR) and erectile dysfunction (ED) in adult men in the United States using a comprehensive dataset. A cross-sectional study design was used to analyze the relationship between the lymphocyte-to-monocyte ratio (LMR) and the prevalence of erectile dysfunction (ED) among adult male participants in the NHANES 2001-2004 dataset. Statistical analyses were performed to adjust for potential confounders and explore non-linear associations, with LMR categorized into quartiles to investigate the relationship with ED prevalence.

Association of dietary live microbe intake with all-cause and cardiovascular mortality in an older population: Evidence from NHANES 2003-2018.

Background: The relationship between dietary live microbe intake, non-dietary prebiotics/probiotics, and mortality in older adults remains unclear.

Methods: Participants from the National Health and Nutrition Examination Survey 2003-2018 were included. Participants were categorized into three groups based on estimated live microbe intake: low, medium, and high.

Identification of fatty acid anabolism patterns to predict prognosis and immunotherapy response in gastric cancer.

Gastric cancer (GC), one of the most common and heterogeneous malignancies, is the second leading cause of cancer death worldwide and is closely related to dietary habits. Fatty acid is one of the main nutrients of human beings, which is closely related to diabetes, hypertension and other diseases. However, the correlation between fatty acid metabolism and the development and progression of GC remains largely unknown.

Auto-RapTAC: A Versatile and Sustainable Platform for the Automated Rapid Synthesis and Evaluation of PROTAC.

The tedious synthesis and limited throughput biological evaluation remain a great challenge for discovering new proteolysis targeting chimera (PROTAC). To rapidly identify potential PROTAC lead compounds, we report a platform named Auto-RapTAC. Based on the modular characteristic of the PROTAC molecule, a streamlined workflow that integrates lab automation with "click chemistry" joint building-block libraries was constructed.

Successful Treatment of Rosacea by Trephination combined with Photodynamic Therapy: A case report.

Rosacea is a chronic, inflammatory dermatological condition primarily affecting the central face, including the cheeks, nose, chin, and forehead[1]. It presents with erythema, phymatous changes, papules, pustules, and telangiectasia. The pathogenesis of rosacea is still unknown.

Tenecteplase Thrombolysis for Stroke up to 24 Hours After Onset With Perfusion Imaging Selection: The CHABLIS-T II Randomized Clinical Trial.

Background: Whether it is effective and safe to extend the time window of intravenous thrombolysis up to 24 hours after the last known well is unknown. We aimed to determine the efficacy and safety of tenecteplase in Chinese patients with acute ischemic stroke due to large/medium vessel occlusion within an extended time window.

Methods: Patients with ischemic stroke presenting 4.

CircMVP promotes METTL3 activation mediated CTNNB1 m6A modification in the inhibition of colorectal cancer in B7-H3 dependence antitumor immunity.

The effect of immunotherapy for colorectal cancer (CRC) is limited due to anti-tumor immunosuppression. Circular RNAs (circRNAs) are also associated with tumor immunity. The aim of this study was to clarify the regulatory relationship between circRNA and anti-tumor immunosuppression in CRC.

Sorafenib promotes Treg cell differentiation to compromise its efficacy via VEGFR/AKT/Foxo1 signaling in hepatocellular carcinoma.

Unlabelled: Our study revealed that sorafenib (Sora) induced the formation of an immunosuppressive tumor microenvironment in hepatocellular carcinoma (HCC) by promoting the differentiation of regulatory T (Treg) cells through VEGFR/AKT/Foxo1 signaling, leading to compromised Sora efficacy. Importantly, combination treatment with an anti-CD25 antibody or the Foxo1 inhibitor AS1842856 inhibited Treg cell differentiation and increased the therapeutic efficacy of Sora in HCC.

Background & Aims: Sora is the first-line drug for advanced HCC.

Identification of a broad-inhibition influenza neuraminidase antibody from pre-existing memory B cells.

Identifying broadly reactive B precursor cells and conserved epitopes is crucial for developing a universal flu vaccine. In this study, using influenza neuraminidase (NA) mutant probes, we find that human pre-existing NA-specific memory B cells (MBCs) account for ∼0.25% of total MBCs, which are heterogeneous and dominated by class-unswitched MBCs.

NECTIN-4-redirected T cell Antigen Coupler T cells bearing CD28 show superior antitumor responses against solid tumors.

Introduction: T cell Antigen Coupler (TAC) T cells harness all signaling subunits of endogenous T cell receptor (TCR) to trigger T-cell activation and tumor cell lysis, with minimal release of cytokines. Some of the major obstacles to cellular immunotherapy in solid tumors include inefficient cell infiltration into tumors, lack of prolonged cellular persistence, and therapy-associated toxicity.

Methods: To boost the cytotoxic potential of TAC-T cells against solid tumors, we generated a novel NECTIN-4-targeted TAC-T variant, NECTIN-4 TAC28-T, which integrated the co-stimulatory CD28 cytoplasmic region, and compared the anti-tumor activities between NECTIN-4 TAC-T cells and NECTIN-4 TAC28-T cells in vitro and vivo.

Comprehensive Mass Spectral Libraries of Human Thyroid Tissues and Cells.

Thyroid nodules are a common endocrine condition with an increasing incidence over the decades. Data-independent acquisition has been widely utilized in discovery proteomics to identify disease biomarkers and therapeutic targets. To analyze the thyroid disease-related proteome in a high-throughput, reproducible and reliable manner, we introduce thyroid-specific peptide spectral libraries.

Efficacy and safety of low-dose TBI combined MAC regimen for HSCT in high-risk AML patients with active disease.

Background: The management of high-risk acute myeloid leukaemia (AML) remains challenging, highlighting the need for innovative conditioning strategies beyond current regimens.

Methods: In the present single-arm study, a FACT regimen comprised of low-dose total body irradiation (TBI) with fludarabine, cytarabine and cyclophosphamide was employed to treat cytogenetically high-risk AML patients exhibiting pre-transplant active disease. This clinical trial is registered in the Chinese Clinical Trial Registry with the registration number ChiCTR2000035111.

Primary hepatic epithelioid hemangioendothelioma: a case report.

Epithelioid hemangioendothelioma is a low-grade malignant tumor of vascular origin. The rarity of hepatic epithelioid hemangioendothelioma (HEHE) makes the diagnosis and treatment of this entity challenging. We report a case of a 69-year-old female patient who suffered from HEHE and complained of abdominal distension pain with dizziness and appetite loss for more than half a month.

Association of the EAT-Lancet diet, serial measures of serum proteome and gut microbiome, and cardiometabolic health: a prospective study of Chinese middle-aged and elderly adults.

Background: The EAT-Lancet diet was reported to be mutually beneficial for the human cardiometabolic system and planetary health. However, mechanistic evidence linking the EAT-Lancet diet and human cardiometabolic health is lacking.

Objectives: We aimed to investigate the role of blood proteins in the association between the EAT-Lancet diet and cardiometabolic health and explore the underlying gut microbiota-blood protein interplay.

Guidance Documents for Off-Label Drug Use Management for Chinese Health Care Institutions: A Scoping Review.

Background: Off-label drug use (OLDU) is a common practice in health care institutions, and numerous guidance documents have been developed to guide the management of OLDU in China. This scoping review aims to compare these documents and identify existing issues.

Methods: PubMed, EMbase, three Chinese databases, the National Public Service Platform for Standards Information and the official websites of pharmaceutical-related associations were searched to identify guidance documents relevant to the management of OLDU for Chinese health care institutions.