Diclofenac Enhances the Response of BRAF Inhibitor to Melanoma Through ROS/p38/p53 Signaling.

BRAF inhibitors (BRAFi) represent a cornerstone in melanoma therapy due to their high efficacy. However, the emergence of resistance causes a significant challenge to their clinical utility. This study aims to investigate the potential of diclofenac as a sensitizer for BRAFi therapy in melanoma and to elucidate its underlying mechanism.

Remodeling and Characterization Analysis of Corticospinal Tract in Patients with Intracerebral Hemorrhage in the Basal Ganglia.

To investigate corticospinal tract (CST) injury and remodeling in patients with basal ganglia intracerebral hemorrhage (ICH) and explore the characterization capabilities of the corresponding parameters. In this prospective study, baseline, scale, and diffusion-weighted imaging (DWI) data were collected from patient cohorts. Participants were stratified into favorable (0-3 points) and unfavorable (4-6 points) prognosis groups, based on Modified Rankin Scale (mRS) after 3-6 months.

The impact of neoadjuvant therapy on the prognostic value of preoperative neutrophil-to-lymphocyte ratio for colorectal liver metastases: a multi-center cohort study.

Background: Neutrophil-to-lymphocyte ratio (NLR) is a promising prognostic marker for patients undergoing hepatectomy for colorectal liver metastases (CRLM). However, its prognostic value in patients receiving neoadjuvant therapy (NAT) has not been sufficiently addressed.

Methods: From 2013 to 2023, a cohort of 692 patients with CRLM receiving hepatectomy were enrolled in five centers.

SNHG16 alleviates pulmonary ischemia-reperfusion injury by promoting the warburg effect through regulating MTCH2 expression: experimental studies.

Background: Pulmonary ischemia-reperfusion injury (PIRI) is a major cause of fatality post-lung transplantation. Though some long non-coding RNAs (lncRNAs) have been studied in acute lung injury (ALI), their effects on PIRI remain undefined. The present study aims to explore the underlying mechanism of small nucleolar RNA host gene 16 (SNHG16) in PIRI.

Gut-derived lactic acid enhances tryptophan to 5-hydroxytryptamine in regulation of anxiety via .

The gut microbiota plays a pivotal role in anxiety regulation through pathways involving neurotransmitter production, immune signaling, and metabolic interactions. Among these, gut-derived serotonin (5-hydroxytryptamine, 5-HT), synthesized from tryptophan metabolism, has been identified as a key mediator. However, it remains unclear whether specific microbial factors regulate tryptophan metabolism to influence 5-HT production and anxiety regulation.

Modulating mTOR-dependent astrocyte substate transitions to alleviate neurodegeneration.

Traditional approaches to studying astrocyte heterogeneity have mostly focused on analyzing static properties, failing to identify whether subtypes represent intermediate or final states of reactive astrocytes. Here we show that previously proposed neuroprotective and neurotoxic astrocytes are transitional states rather than distinct subtypes, as revealed through time-series multiomic sequencing. Neuroprotective astrocytes are an intermediate state of the transition from a nonreactive to a neurotoxic state in response to neuroinflammation, a process regulated by the mTOR signaling pathway.

Privacy protection of sexually transmitted infections information from Chinese electronic medical records.

The comprehensive adoption of Electronic Medical Records (EMRs) offers numerous benefits but also introduces risks of privacy leakage, particularly for patients with Sexually Transmitted Infections (STI) who need protection from social secondary harm. Despite advancements in privacy protection research, the effectiveness of these strategies in real-world data remains debatable. The objective is to develop effective information extraction and privacy protection strategies to safeguard STI patients in the Chinese healthcare environment and prevent unnecessary privacy leakage during the data-sharing process of EMRs.

Nanomedicine-unlocked radiofrequency dynamic therapy dampens incomplete radiofrequency ablation-arised immunosuppression to suppress cancer relapse.

Incomplete radiofrequency ablation (iRFA) not only leaves residual tumor, but also render the residual tumor highly self-adaptable and immunosuppressive, consequently expediting residual tumor progression including relapse. To address it, radiofrequency dynamic therapy (RFDT) with identical trigger (namely radiofrequency) has been established and enabled by polyethylene glycol (PEG)-modified Fe-based single atom nanozyme (P@Fe SAZ). P@Fe SAZ can respond to radiofrequency field to produce reactive oxygen species (ROS), attaining the nanomedicine-unlocked low-temperature RFDT.

Predictive, preventive and personalized project of vascular cognitive impairment in China (P3): Study design and interim baseline patient characteristics of a Nationwide multicenter prospective registry.

Objectives: To outline the design of the P3 study and serve as a summary of the interim baseline patient characteristics.

Methods: P3 study is a multicenter, prospective cohort study targeting 1000 acute ischemic stroke (AIS) and cerebral small vessel disease (CSVD) patients with a 2-year follow-up from 80 participating hospitals across China. Comprehensive multimodal imaging, neuropsychological tests, and biological samples were collected prospectively on admission and follow-up visits.

Drug-phospholipid conjugate nano-assembly for drug delivery.

Phospholipid-based liposomes are among the most successful nanodrug delivery systems in clinical use. However, these conventional liposomes present significant challenges including low drug-loading capacity and issues with drug leakage. Drug-phospholipid conjugates (DPCs) and their assemblies offer a promising strategy for addressing these limitations.

Complexity of intrinsic brain activity in relapsing-remitting multiple sclerosis patients: patterns, association with structural damage, and clinical disability.

Functional plasticity has been demonstrated in multiple sclerosis (MS) studies. However, the intrinsic brain activity complexity alterations remain unclear. Here, using a coarse-graining time-series procedure algorithm, we obtained multiscale entropy (MSE) from a retrospective multi-centre dataset (208 relapsing-remitting MS patients and 228 healthy controls).

Disruption of seasonal influenza circulation and evolution during the 2009 H1N1 and COVID-19 pandemics in Southeastern Asia.

East, South, and Southeast Asia (together referred to as Southeastern Asia hereafter) have been recognized as critical areas fuelling the global circulation of seasonal influenza. However, the seasonal influenza migration network within Southeastern Asia remains unclear, including how pandemic-related disruptions altered this network. We leveraged genetic, epidemiological, and airline travel data between 2007-2023 to characterise the dispersal patterns of influenza A/H3N2 and B/Victoria viruses both out of and within Southeastern Asia, including during perturbations by the 2009 A/H1N1 and COVID-19 pandemics.

Xalnesiran with or without an Immunomodulator in Chronic Hepatitis B.

Background: Xalnesiran, a small interfering RNA molecule that targets a conserved region of the hepatitis B virus (HBV) genome and silences multiple HBV transcripts, may have efficacy, with or without an immunomodulator, in patients with chronic HBV infection.

Methods: We conducted a phase 2, multicenter, randomized, controlled, adaptive, open-label platform trial that included the evaluation of 48 weeks of treatment with xalnesiran at a dose of 100 mg (group 1), xalnesiran at a dose of 200 mg (group 2), xalnesiran at a dose of 200 mg plus 150 mg of ruzotolimod (group 3), xalnesiran at a dose of 200 mg plus 180 μg of pegylated interferon alfa-2a (group 4), or a nucleoside or nucleotide analogue (NA) alone (group 5) in participants with chronic HBV infection who had virologic suppression with NA therapy. The primary efficacy end point was hepatitis B surface antigen (HBsAg) loss (HBsAg level, <0.

Variables associated with cognitive function: an exposome-wide and mendelian randomization analysis.

Background: Evidence indicates that cognitive function is influenced by potential environmental factors. We aimed to determine the variables influencing cognitive function.

Methods: Our study included 164,463 non-demented adults (89,644 [54.

LncRNA MIR17HG drives cisplatin resistance partially via miR-138-5p/AKAP9 axis in cholangiocarcinoma.

Objectives: This study aims to discover the role of lncRNA MIR17HG, referred to as MIR17HG, in cisplatin resistance for cholangiocarcinoma (CCA).

Methods: QRT-PCR was conducted to measure the expression of MIR17HG in cisplatin-resistant/sensitive CCA cells and clinical CCA specimens. Log-rank test was used to analyze the survival curve.

Optimal treatment approach for intracranial germinoma: a systematic review and meta-analysis.

Background: To determine the optimal treatment modality for intracranial germinoma (IG).

Materials And Methods: A search of Medline, Embase, Web of Science and Cochrane Library was conducted up to April, 2024. Pooled risk ratio (RR) and 95% confidence interval (CI) were calculated.

Exome sequencing identifies genes for socioeconomic status in 350,770 individuals.

Socioeconomic status (SES) is a critical factor in determining health outcomes and is influenced by genetic and environmental factors. However, our understanding of the genetic structure of SES remains incomplete. Here, we conducted a large-scale exome study of SES markers (household income, occupational status, educational attainment, and social deprivation) in 350,770 individuals.

Promoter Polymorphism (Allelic Variation) Affects Tacrolimus Treatment Efficacy by Modulating E2F6 Binding Affinity.

Background: Tacrolimus is widely used as a first-line immunosuppressant in transplant immunology; however, its clinical application is constrained by the narrow therapeutic index and considerable interindividual variability. In this study, we identified the potential regulatory role of a novel promoter polymorphism, rs4519508 C > T, in the tacrolimus pharmacodynamic pathway.

Methods: Dual-luciferase reporter assays and bioinformatic analysis were applied to assess the impact of allelic variation.

Osteoarthritis synovium as a nidus for monosodium urate crystal deposition inducing severe gout studied by label-free stimulated Raman scattering combined with synovial organoids.

Gout, a common chronic disease, is characterized by the formation and deposition of monosodium urate (MSU) crystal deposition in articular and nonarticular structures. Osteoarthritis (OA), the most prevalent type of arthritis, is a progressive degenerative joint disease. Previous clinical studies have reported that gout frequently affects OA joints; however, the underlying mechanism remains unidentified.

Intracranial Hypotension Mechanism and Implant Retention Procedure for Patients With Titanium Mesh Exposure.

Background And Objectives: The study aimed to investigate the potential pathogenesis and present an implant retention procedure for patients with titanium mesh exposure after cranioplasty.

Methods: The clinical data were obtained from 26 consecutive cases with titanium mesh exposure who underwent surgical treatment between 2018 and 2023. These patients' medical records, scalp photographs, operative notes, and outcomes were retrospectively analyzed.

Cerebrospinal fluid proteomics reveals the innate immunity and blood-brain barrier dysregulation in a patient with multidrug-resistant ventriculitis treated with intrathecal and intravenous polymyxin B.

is a major pathogen of nosocomial meningitis and ventriculitis. Due to very limited antibiotic treatment options, polymyxins are often used as a last-line therapy. To optimise polymyxin use in the intraventricular environment, cerebrospinal fluid (CSF) proteomics was employed to investigate host-pathogen-polymyxin interactions in a 69-year-old patient with multidrug-resistant ventriculitis treated with a combination of intrathecal (ITH; 50,000 IU q24h/q48h), intraventricular (IVT; 50,000 IU q48h), and intravenous (500,000 IU, q12h) polymyxin B.

Association between GRIN2B polymorphism and Parkinson's disease risk, age at onset, and progression in Southern China.

Background And Objectives: The role of N-methyl-D-aspartate receptor 2B (GRIN2B) single nucleotide polymorphisms (SNPs) in influencing the risk and progression of Parkinson's disease (PD) is still unclear. This study aimed to assess the impact of GRIN2B genotype status on PD susceptibility and symptom progression.

Methods: We enrolled 165 individuals with sporadic PD and 154 healthy controls, all of whom had comprehensive clinical data available at the start and during follow-up.

Effect of intravenous urokinase vs best medicine treatment on functional outcome for patients with acute minor stroke (TRUST): a randomized controlled trial.

Background: The benefits of intravenous thrombolysis in patients with acute minor stroke remain controversial. For the aim of providing a better therapeutic strategy, high-quality trials are required to validate the efficacy of thrombolytic medicine other than intravenous recombinant tissue plasminogen and tenecteplase. In the trial, we evaluate the efficacy and safety of urokinase (UK) in acute minor stroke.