IBI310 plus sintilimab vs. placebo plus sintilimab in recurrent/metastatic cervical cancer: A double-blind, randomized controlled trial.

Background: It remains unclear whether adding CTLA-4 blockade to PD-1/PD-L1 blockade improves clinical outcomes in cervical cancer (CC).

Methods: In this randomized, double-blind, placebo-controlled, phase 2 study (ClinicalTrials.gov: NCT04590599), patients with recurrent/metastatic CC (R/M CC) who experienced disease progression after or during platinum-based chemotherapy were enrolled from 37 centers across China and randomly assigned (1:1), stratified by PD-L1 expression and prior treatment lines, to receive either IBI310 plus sintilimab or placebo plus sintilimab intravenously every 3 weeks for 12 weeks, followed by sintilimab alone.

Frailty impacts all-cause mortality after endovascular abdominal aortic aneurysm repair: a retrospective cohort study.

Objective: This study aimed to evaluate the impact of frailty and inflammation on all-cause mortality in patients with abdominal aortic aneurysm (AAA) who underwent endovascular aneurysm repair (EVAR), and key risk factors were also explored.

Methods: A retrospective analysis was conducted on 174 patients with AAA who underwent EVAR at Beijing Hospital between 2016 and 2024. Frailty was assessed using the modified five-item Frailty Index (mFI-5).

3D imaging and pathological analysis of microglia in LPS-treated mice with light-sheet fluorescence microscopy.

Although two-dimensional (2D) histology and immunohistochemistry techniques have long been established and successfully applied to obtain structural information from tissues, recent advances in tissue clearing and expansion approaches combined with light sheet microscopy have led to the realization of three-dimensional (3D) nondestructive pathology, which may revolutionize our knowledge of the morphology of an organ or the whole body in its true state. Employing these 3D technologies, we obtained imaging data of microglia in whole hippocampus of mice. We established a simple procedure to analyze the 3D structures of microglia using the commercial software Amira.

Recent insights into the in vitro culture systems for mammalian embryos.

Mammalian early embryonic development is the cornerstone for a healthy life. Any aberrations during early embryonic development may lead to adverse pregnancy outcomes. Therefore, the comprehensive study of embryonic developmental events is essential for understanding biological and pathological pregnancy.

Fine-tuned programming of placenta trophoblast determines optimal maternal-fetal nutrient allocation.

Maternal health and fetal survival during pregnancy encapsulate a paradox of cooperation and competition. One particularly intriguing aspect of this paradox involves the optimal allocation of nutrients between the mother and fetus. Despite this, the precise mechanisms governing nutrient allocation remain elusive.

A novel and practical strategy for comprehensive differentiation and profiling of eight Curcumae varieties and their counterfeit from the Chinese market.

The Curcuma genus is extensively used in food, traditional medicine, and spice, however, nine closely related varieties are frequently misidentified, leading to mislabeling and adulteration. This study presents an innovative and practical strategy for precise differentiation of nine Curcumae varieties-eight authentic and one counterfeit. For the first time, comprehensive characterizations were conducted using LC-Orbitrap MS, and 702 non-volatiles were annotated, laying a groundwork for marker selection and identification.

Lipidomic characterization of polar and non-polar lipids in egg yolk and their anti-inflammatory and analgesic activities in zebrafish.

In this study, a technique that combines supercritical fluid extraction with ethanol extraction was employed to effectively fractionate egg yolk extracts into non-polar and polar lipids. By utilizing feature based molecular networking (FBMN) and MS-DIAL database search, 35 glycerolipids were identified in the supercritical extract (SE), and 70 glycerophospholipids in the ethanol extract (EE). Following the identification of lipids, a heatmap was generated using R software to visualize the abundance of lipids across both fractions.

Effectiveness of newly isolated bacteriophages targeting multidrug-resistant Extraintestinal Pathogenic Escherichia coli strain (TZ1_3) in food preservation and mice health modulation.

Bacteriophages are promising alternatives for combating multidrug-resistant bacterial infections. Two lytic bacteriophages, named P1 and P3, targeting pathogenic Escherichia coli (ExPEC; strain TZ1_3) were isolated and evaluated for their potential ability to control pathogenic numbers either in ExPEC-contaminated food or ExPEC-infected mice. Results showed that phages significantly reduced ExPEC numbers within 6 and 12 h in contaminated water, milk, beef, and chicken when applied at 10 plaque-forming units (PFU).

Tunable ion-release biodegradable nanoparticles enhanced pyroptosis for tumor immunotherapy.

Pyroptosis is an effective strategy for inducing inflammatory responses in 'cold' tumors, boosting the efficacy of immunotherapy. Although biodegradable inorganic nanoparticles (BINPs) show great potential in pyroptosis by releasing ions to break intracellular homeostasis, the limited intracellular ion release efficiency restricts pyroptosis level and subsequent immune activation. Herein, by heterovalent substitution strategy, a series of NaZrF:x%Yb (NZF:x%Yb, x = 0, 9, and 18) BINPs with tunable intracellular ion release efficiency are synthesized for enhanced pyroptosis and tumor immunotherapy.

Peripheral blood lymphocyte subsets combined with fungal biomarkers in the diagnosis of invasive fungal infections complicated by sepsis.

Objective: To evaluate the lymphocyte subpopulations and the levels of (1, 3)-β-d-glucan (BDG) and galactomannan (GAL) in sepsis patients with secondary invasive fungal infections (IFIs), and to investigate the association between lymphocytes and IFIs.

Methods: A retrospective case-control study of 47 patients with sepsis complicated by IFIs, 50 sepsis patients, and 50 healthy controls was conducted. The correlation between lymphocyte subsets and BDG, GAL levels was analyzed using the Spearman correlation method, and the diagnostic efficacy of IFIs-related factors was assessed using the receiver operating characteristic curve (ROC) analysis.

NFE2-driven neutrophil polarization promotes pancreatic cancer liver metastasis progression.

Pancreatic cancer liver metastasis is an important factor leading to dismal prognoses. The details of adaptive immune remodeling in liver metastasis, especially the role of neutrophils, remain elusive. Here, combined single-cell sequencing with spatial transcriptomics results revealed that liver metastases exhibit more aggressive transcriptional characteristics and higher levels of immunosuppression compared with the primary tumor.

A novel approach for target deconvolution from phenotype-based screening using knowledge graph.

Deconvoluting drug targets is crucial in modern drug development, yet both traditional and artificial intelligence (AI)-driven methods face challenges in terms of completeness, accuracy, and efficiency. Identifying drug targets, especially within complex systems such as the p53 pathway, remains a formidable task. The regulation of this pathway by myriad stress signals and regulatory elements adds layers of complexity to the discovery of effective p53 pathway activators.

Characterizing Genetic-Predisposed Proteins Involving Insomnia by Integrating Genome-Wide Association Study Summary Statistics.

Large case-control genome-wide association studies (GWASs) have detected loci associated with insomnia, but how these risk loci confer disease risk remains largely unknown. By integrating brain protein quantitative trait loci (pQTL) (N = 376, N = 152) and expression QTL (eQTL) (N = 452) datasets, with the latest insomnia GWAS summary statistics (N = 109,548, N = 277440), we conducted proteome/transcriptome-wide association study (PWAS/TWAS) and Mendelian randomization (MR) analysis, aiming to identify causal proteins involving in the pathogenesis of insomnia. We also explored the bi-directional causality between insomnia and several common diseases.

Single-step retrosynthesis prediction via multitask graph representation learning.

Inferring appropriate synthesis reaction (i.e., retrosynthesis) routes for newly designed molecules is vital.

CDK14 regulates the development and repair of lung.

Cyclin-dependent kinases (CDK) 14 regulates cell cycle, tumor expansion by influencing the downstream targets of the canonical Wnt signaling pathway. However, the function of CDK14 during organ development and regeneration has not been investigated in genetically-modified animals. Here, we found that genetic ablation of Cdk14 influenced pulmonary vascular endothelial cells and alveolar epithelial cells during mice embryonic development as well as repair of lung after bleomycin or lipopolysaccharide induced injury.

Quality of life, pain, depression, fatigue and sleep in patients with remission or mild fibromyalgia: a comparison with remission or low disease activity rheumatoid arthritis and healthy controls.

Background: Fibromyalgia is a chronic condition marked by widespread pain and various accompanying symptoms. Compared to healthy individuals and other rheumatic disease patients, it leads to more severe symptoms and a lower quality of life. Whether fibromyalgia patients in a mild activity or remission stage still experience core symptoms remains unclear.

A novel dual fixation method for improving the reliable assessment of pulmonary vascular morphology in pulmonary hypertension rats.

This study introduced a novel dual fixation method for the pulmonary vasculature and lung tissue in pulmonary hypertension (PH) rats, addressing the limitations of traditional fixation methods that failed to accurately preserve the in vivo status of pulmonary vascular morphology. The modified method involved a dual fixation process, combining individualized ventilation support and vascular perfusion to simulate the respiratory motion, pulmonary artery pressure and right ventricular output of the rat under in vivo conditions. Utilizing a monocrotaline-induced PH rat model, this study compared the dual fixation with the traditional immersion fixation, focusing on the quantitative assessment of alveolar expansion degree, capillary patency, endothelial cell quantity and wall thickness of pulmonary vein and artery.

Relevance of superoxide dismutase type 1 to lipoid pneumonia: the first retrospective case-control study.

Background: Lipoid pneumonia (LP) is a rare disease caused by the accumulation of lipids and lipid-laden macrophages in the alveoli inducing damage. LP is difficult to differentiate from other similar diseases without pathological evidence, such as upper respiratory tract infection (URTI), pneumonia, cryptogenic organizing pneumonia (COP), pulmonary alveolar proteinosis (PAP), lung mucinous adenocarcinoma and pulmonary edema. Given the high misdiagnosis rate and limited statistical clinical and treatment data, there is an urgent need for novel indicators of LP.

Cortisol regulates neonatal lung development via Smoothened.

Background: Neonatal respiratory distress syndrome (NRDS), one of the main causes of neonatal death, is clinically characterized by progressive dyspnea and cyanosis 1 to 2 h after birth. Corticosteroids are commonly used to prevent NRDS in clinical. However, the protective mechanism of the corticosteroids remains largely unclear.

The Impact of a Human Bone Morphogenetic Protein-infused Nano-Bone Material Combined With Traditional Chinese Medicine Carthamus tinctorius on the Repair of Oral Bone Defects.

Background: The role of human bone morphogenetic protein-infused in combination with traditional Chinese medicine Carthamus tinctorius in repairing oral bone defects (OBD) was evaluated in this work.

Methods: An experiment was conducted on a rat OBD model, where rats were randomly rolled into Groups A, B, and C based on their different treatments. Micro-CT was utilized to measure jaw bone volume fraction (BV/TV) and bone mineral density (BMD) in rats, while a biomechanical testing machine assessed compressive strength of the jaw bone.

Exploring the synergistic effects of soil nutrients, rhizosphere fungi, and endophytic fungi on the shaping of root metabolites in Angelica sinensis (Oliv.) Diels.

The root of Angelica sinensis (Oliv.) Diels (Ang) is a bulk Chinese herbal medicine, and the microecological regulation is a sustainable means to enhance its quality. In this study, Angs at five bases (LZ, XZ, QS, PM, MZC) in Minxian County, Gansu Province were taken as the research objects.

Optimal age for mandibular distraction osteogenesis in craniofacial microsomia: A systematic review and meta-analysis.

Objective: This systematic review and meta-analysis aimed to determine the optimal timing for mandibular distraction osteogenesis in children with craniofacial microsomia based on long-term outcomes and relapse rates.

Methods: A comprehensive search of PubMed, Embase, Cochrane Library, and Web of Science was conducted for studies published up to September 2024. Eligible studies included children aged ≤16 years with CFM who underwent MDO, with follow-up duration exceeding one year.

Cervico-acromial Flap for Large Defects in Face and Neck Reconstruction: 34-year Experience.

Background: Extensive cervicofacial defects often lead to functional and aesthetic impairments. The pre-expanded cervico-acromial flap technique is reliable and cost-effective for addressing such defects.

Objective: To introduce our 34 years' experience on pre-expanded cervico-acromial flap technique, emphasizing key surgical techniques.

Safety and humoral immunogenicity of the ChAdOx1 nCoV-19 vaccine administered as a fourth dose booster following two doses of ChAdOx1 nCoV-19 and a third dose of BNT162b2 (COV009): A prospective cohort study.

Objectives: Evaluation of the safety and humoral immunogenicity of ChAdOx1 nCoV-19 as a fourth dose booster in individuals who have had two initial doses of the vaccine and a third dose of BNT162b2.

Methods: COV009 is a safety follow-up study of volunteers enroled in the pivotal pre-licensure ChAdOx1 nCoV-19. In this sub-study, 149 eligible participants were given a fourth dose of ChAdOx1 nCoV-19.

SiO-based inorganic nanofiber aerogel with rapid hemostasis and liver wound healing functions.

Non-compressible hemostasis and promoting tissue healing are important in soft tissue trauma repair. Inorganic aerogels show superior performance in rapid hemostasis or promoting tissue healing, but simultaneously promoting non-compressive hemostasis and soft tissue healing still remains a challenge. Herein, SiO-based inorganic nanofiber aerogels (M@SiO, M=Ca, Mg, and Sr) were prepared by freeze-drying the mixture of bioactive silicates-deposited SiO nanofibers and SiO sol.