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Integrated Metabolomic and Transcriptomic Analysis Suggests Potential Therapeutic Mechanism of Shengxian Decoction in Hypobaric Hypoxia-Induced Pulmonary Hypertension in SD Rats

10 September 2026 at 18:00

Drug Des Devel Ther. 2026 Sep 5;20:603123. doi: 10.2147/DDDT.S603123. eCollection 2026.

ABSTRACT

BACKGROUND: High-altitude hypoxia can trigger maladaptive cardiopulmonary responses, with hypoxia-induced pulmonary hypertension (HPH) representing a major clinical challenge with limited therapeutic options. Shengxian Decoction (SXT), a classical traditional Chinese medicine formula for treating "qi deficiency and sinking", has shown clinical benefits, but the molecular pathways associated with its effects remain incompletely understood.

METHODS: Male Sprague-Dawley rats were exposed to simulated high altitude (5000 m; 404 mmHg, 10.8% O2) for 28 days and treated with SXT at three doses (1.8, 3.6, or 7.2 g/kg/day; n = 6/group). Integrated serum metabolomics (UHPLC-Q-TOF-MS) and lung transcriptomics (RNA-seq) were applied. Multivariate analysis, pathway enrichment, weighted gene co-expression network analysis, and cross-omics correlation were used for data integration. After randomization, allocation concealment and blinding were strictly implemented throughout all experimental procedures, with all interventions and outcome assessments performed by personnel blinded to group assignment until completion of data analysis.

RESULTS: Chronic hypoxia induced HPH with elevated mPAP, RVHI, RVWI and pulmonary vascular remodeling (increased WT% and WA%), while SXT dose-dependently ameliorated these abnormalities and restored hypoxia-disrupted metabolomic and transcriptomic profiles, with the high-dose group showing the most pronounced effect. Chronic hypoxia induced pronounced metabolic and transcriptional remodeling, with model animals clearly separated from controls in principal component analysis. Most differentially expressed genes exhibited downregulated expression, indicating global transcriptional suppression. SXT treatment dose-dependently restored both metabolomic and transcriptomic profiles, with the high-dose group most closely resembling controls. These pyruvate-proximal nodes may represent potential points of convergence through which SXT-associated metabolic and transcriptional alterations are coordinated. The relationships reported here are based on cross-omics associations, and causal inference will require further functional validation.

CONCLUSION: These findings suggest that SXT may ameliorate HPH partly through coordinated regulation of metabolic pathways and gene networks, particularly those related to energy metabolism, rather than fully explaining disease pathogenesis. The study provides multi-omics evidence supporting the traditional concept of "replenishing qi and elevating sunken qi" and identifies candidate metabolic biomarkers for further investigation. However, the results should be interpreted cautiously because of the relatively small sample size, the lack of functional validation experiments, and the exploratory nature of the biomarker findings. Further mechanistic and clinical studies are required to confirm these observations.

PMID:42719424 | PMC:PMC13557172 | DOI:10.2147/DDDT.S603123

The DreAM-plus integrative RNA switch enhances transient AAV expression and reduces side effects of gene editing

This study developed a multi-layer inducible RNA switch that achieves transient expression of gene-delivery vectors in hepatic and non-hepatic tissues. As an exemplary application, this RNA switch triggers pulsive expression of gene editors that reduces the off-target effects and immunotoxicity of gene editing.

Switchable single-atom catalysts for highly selective C–C coupling in direct methane oxidation

Nature Nanotechnology, Published online: 07 September 2026; doi:10.1038/s41565-026-02271-5

Single copper atoms on boron nanosheets dynamically and reversibly switch to clusters, enabling the direct conversion of methane to acetic acid with 97% selectivity and high activity without the requirement for carbon monoxide.

Why Sample What You Can Enumerate? Exact Policy Optimization for Genomic Tool Selection

arXiv:2609.10221v1 Announce Type: new Abstract: Reinforcement learning over a frozen reasoner has become a common recipe for teaching a policy which external tools to invoke. We show that this recipe becomes structurally mismatched in specialist scientific settings where the complete tool-subset space is enumerable. There, a small set of recurring computational capabilities covers the domain, so the space of tool subsets is combinatorial yet small enough to enumerate, and GRPO still estimates an action expectation from a handful of sampled rollouts. Worse, the approximation degrades as training succeeds: as the policy concentrates on preferred subsets it resamples them, sampled rewards collide, and the group-normalized advantage vanishes. On genomic reasoning the fraction of questions yielding no reward signal rises from 0.2% under a uniform reference policy to 20.8% after GRPO training. As a remedy, we introduce FGPO (Full-Group Policy Optimization), which (1) scores every tool subset and optimizes the exact action expectation, so each update sees the complete action space, and (2) precomputes the reward of each question--subset pair into an exhaustive table, removing frozen-reasoner calls from the training loop entirely. Across five frozen reasoners and three genomic benchmarks, FGPO outperforms GRPO in all 15 settings by 6.75 points on average and up to 14.20, while a standard on-demand GRPO schedule would require 2.4 times as many frozen-reasoner reward evaluations and, on GenomeQA, FGPO cuts invoked tools per question from 2.36 to 1.40.

Research Status and Prospects of <em>Helicobacter pylori</em>-associated gastritis: From Mechanisms to Traditional Chinese Medicine Treatment

8 September 2026 at 18:00

Gastroenterol Res Pract. 2026 Sep 7;2026:3413458. doi: 10.1155/grp/3413458. eCollection 2026.

ABSTRACT

Helicobacter pylori-associated gastritis (HPAG) is a chronic inflammatory condition of the gastric mucosa caused by Helicobacter pylori infection, serving as the core etiological factor for peptic ulcers and gastric precancerous lesions. Given the persistently high global infection rates and the escalating burden of antibiotic resistance, conventional eradication therapies are encountering significant challenges. This article systematically delineates the molecular pathogenic mechanisms underlying HPAG, encompassing bacterial virulence factors, host immune responses, aberrant signaling pathways, oxidative stress, epigenetic regulation, and mucosal barrier damage. Building upon this foundation and in alignment with international mainstream diagnostic and therapeutic guidelines, we summarize the research progress of traditional Chinese medicine (TCM) interventions from a novel perspective of microecological homeostasis regulation. Specifically, we clarify the multifaceted roles of TCM monomers and formulas in immunomodulation, mucosal repair, and antibacterial synergism. By systematically synthesizing existing evidence from TCM studies, we construct a whole-course TCM intervention framework for HPAG that integrates "susceptibility prevention, active treatment, and posteradication repair." Furthermore, we critically analyze the current clinical translation bottlenecks and the limitations inherent in the "black-box" research paradigm of TCM monomers and formulas, and propose future research directions driven by multiomics technologies. This work provides both theoretical support and practical references for precise integrated Chinese and Western medicine diagnosis and treatment of HPAG.

PMID:42707495 | PMC:PMC13548316 | DOI:10.1155/grp/3413458

Research Status and Prospects of <em>Helicobacter pylori</em>-associated gastritis: From Mechanisms to Traditional Chinese Medicine Treatment

Gastroenterol Res Pract. 2026 Sep 7;2026:3413458. doi: 10.1155/grp/3413458. eCollection 2026.

ABSTRACT

Helicobacter pylori-associated gastritis (HPAG) is a chronic inflammatory condition of the gastric mucosa caused by Helicobacter pylori infection, serving as the core etiological factor for peptic ulcers and gastric precancerous lesions. Given the persistently high global infection rates and the escalating burden of antibiotic resistance, conventional eradication therapies are encountering significant challenges. This article systematically delineates the molecular pathogenic mechanisms underlying HPAG, encompassing bacterial virulence factors, host immune responses, aberrant signaling pathways, oxidative stress, epigenetic regulation, and mucosal barrier damage. Building upon this foundation and in alignment with international mainstream diagnostic and therapeutic guidelines, we summarize the research progress of traditional Chinese medicine (TCM) interventions from a novel perspective of microecological homeostasis regulation. Specifically, we clarify the multifaceted roles of TCM monomers and formulas in immunomodulation, mucosal repair, and antibacterial synergism. By systematically synthesizing existing evidence from TCM studies, we construct a whole-course TCM intervention framework for HPAG that integrates "susceptibility prevention, active treatment, and posteradication repair." Furthermore, we critically analyze the current clinical translation bottlenecks and the limitations inherent in the "black-box" research paradigm of TCM monomers and formulas, and propose future research directions driven by multiomics technologies. This work provides both theoretical support and practical references for precise integrated Chinese and Western medicine diagnosis and treatment of HPAG.

PMID:42707495 | PMC:PMC13548316 | DOI:10.1155/grp/3413458

Integrative Multi-Omics Mendelian Randomization Analysis Identifies NIT2 as a Potential Metabolic Risk Gene in Hepatocellular Carcinoma

J Gene Med. 2026 Sep;28(9):e70111. doi: 10.1002/jgm.70111.

ABSTRACT

BACKGROUND: Metabolic pathways are crucial in hepatocellular carcinoma (HCC) pathogenesis, but causal metabolic genes remain unclear. This study used Summary data-based Mendelian Randomization (SMR) and colocalization to identify metabolism-related genetic loci influencing HCC risk.

METHODS: Differentially expressed genes in hepatic malignancy phenotype versus normal tissues from TCGA and GTEx were analyzed. Metabolism-related candidates were examined via SMR and colocalization using multi-omics data: methylation (mQTL), expression (eQTL), and protein (pQTL) quantitative trait loci.

RESULTS: Multi-omics integration identified NIT2 as a key metabolic regulator for HCC. The cg13016775 locus of NIT2 was associated with elevated HCC risk at gene (OR = 1.618, 95% CI: 1.199-2.182) and protein (OR = 4.432, 95% CI: 1.783-11.018) levels. Colocalization supported a shared causal variant (PPH4 > 0.6), linking NIT2 to hepatocarcinogenesis via metabolic regulation.

CONCLUSIONS: This study provides multi-omics evidence for NIT2 as a potential causal gene in HCC, enhancing understanding of metabolic contributions to HCC pathogenesis and highlighting integrative genomics for uncovering causal relationships.

PMID:42681890 | PMC:PMC13534973 | DOI:10.1002/jgm.70111

Reflect-Guard: Enhancing LLM Safeguards against Adversarial Prompts via Logical Self-Reflection

arXiv:2605.24834v1 Announce Type: cross Abstract: Large language model (LLM) safety classifiers such as Llama Guard are effective at detecting overtly harmful prompts but remain vulnerable to adversarial jailbreak attacks that disguise malicious intent through role-play scenarios, fictional framing, and indirect requests. We present Reflect-Guard, a method that augments LLM-based safety classifiers with chain-of-thought self-reflection capabilities through parameter-efficient fine-tuning. Our approach distills analytical reasoning from GPT-4o-mini into structured reflection annotations, then trains Llama-Guard-3-8B via QLoRA to generate logical self-reflections before issuing safety verdicts. Using only 1000 training examples and updating just 0.5% of model parameters (~42M), Reflect-Guard achieves substantial improvements on two challenging benchmarks. On WildGuardTest, F1 score improves from 0.770 to 0.842 (+7.2 pp), with recall on adversarial prompts increasing from 0.513 to 0.921 (+40.8 pp). On JailbreakBench, the attack success rate drops from 10.3% to 1.8%, representing an 82.5% relative reduction. These gains are especially pronounced on adversarial inputs, where the explicit reasoning step enables the model to see through obfuscation techniques that defeat standard pattern-matching approaches. Our results demonstrate that teaching safety classifiers to reason about adversarial intent, rather than simply classify surface patterns, is a promising direction for robust LLM safety.

PathMem: Toward Cognition-Aligned Memory Transformation for Pathology MLLMs

arXiv:2603.09943v2 Announce Type: replace Abstract: Computational pathology demands both visual pattern recognition and dynamic integration of structured domain knowledge, including taxonomy, grading criteria, and clinical evidence. In practice, diagnostic reasoning requires linking morphological evidence with formal diagnostic and grading criteria. Although multimodal large language models (MLLMs) demonstrate strong vision language reasoning capabilities, they lack explicit mechanisms for structured knowledge integration and interpretable memory control. As a result, existing models struggle to consistently incorporate pathology-specific diagnostic standards during reasoning. Inspired by the hierarchical memory process of human pathologists, we propose PathMem, a memory-centric multimodal framework for pathology MLLMs. PathMem organizes structured pathology knowledge as a long-term memory (LTM) and introduces a Memory Transformer that models the dynamic transition from LTM to working memory (WM) through multimodal memory activation and context-aware knowledge grounding, enabling context-aware memory refinement for downstream reasoning. PathMem achieves SOTA performance across benchmarks, improving WSI-Bench report generation (12.8% WSI-Precision, 10.1% WSI-Relevance) and open-ended diagnosis by 9.7% and 8.9% over prior WSI-based models.

High-fidelity identification of guest species in porous materials

Nature, Published online: 20 May 2026; doi:10.1038/s41586-026-10527-2

A reconstruction method based on Gaussian-apodized single-sideband electron ptychography removes artefacts to enable the high-fidelity identification of guest species in porous materials.

Pulmonary-Intestinal Axis: Shared Genetic Basis and Mediating Factors Identified Through Multi-Omics Analysis

Int J Chron Obstruct Pulmon Dis. 2026 Apr 7;21:561645. doi: 10.2147/COPD.S561645. eCollection 2026.

ABSTRACT

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a systemic condition with comorbidities beyond the lung (eg, cardiovascular and metabolic disorders), and gastrointestinal (GI) disorders are also common. The shared genetic basis of COPD-GI comorbidity and its mediating factors remain unclear. We hypothesized that COPD and GI diseases share pleiotropic genetic architecture implicating lipid-metabolic pathways, with smoking mediating part of the association.

METHODS: We analyzed publicly available European-ancestry GWAS summary statistics for COPD (Global Biobank Meta-analysis Initiative), 15 GI diseases (FinnGen), and smoking phenotypes (UK Biobank). Genetic correlation was estimated using linkage disequilibrium score regression (LDSC) and high-definition likelihood (HDL). Multi-trait analysis of GWAS (MTAG) boosted COPD discovery by leveraging genetically correlated GI traits. We integrated locus-to-gene mapping with multi-tissue expression quantitative trait loci (eQTL) and plasma protein quantitative trait loci (pQTL) evidence to prioritize shared loci, genes, and proteins. Bidirectional two-sample Mendelian randomization (MR) tested causal directions, and two-step mediation MR evaluated smoking.

RESULTS: COPD showed significant genetic correlation with nine GI diseases. We identified six comorbidity-associated loci (three with CADD > 12.37) and 13 unique candidate pleiotropic genes; APOE was supported by proteomic evidence. Enrichment analyses highlighted lipid-metabolism pathways. MR suggested COPD increases risk of gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), acute appendicitis, and gastric ulcer, while diverticular disease showed reverse causality toward COPD. Smoking partially mediated the COPD effect on GERD, acute appendicitis, and gastric ulcer.

CONCLUSION: COPD and multiple GI disorders share a distributed pleiotropic genetic basis within the broader systemic comorbidity spectrum of COPD. Multi-omics evidence supports a genomic pulmonary-intestinal axis in which lipid metabolism and smoking-related mechanisms contribute to COPD and GI comorbidity, providing targets for risk stratification and potential intervention.

PMID:41978582 | PMC:PMC13070119 | DOI:10.2147/COPD.S561645

KLong: Training LLM Agent for Extremely Long-horizon Tasks

arXiv:2602.17547v2 Announce Type: replace Abstract: This paper introduces KLong, an open-source LLM agent trained to solve extremely long-horizon tasks. The principle is to first cold-start the model via trajectory-splitting SFT, then scale it via progressive RL training. Specifically, we first activate basic agentic abilities of a base model with a comprehensive SFT recipe. Then, we introduce Research-Factory, an automated pipeline that generates high-quality training data by collecting research papers and constructing evaluation rubrics. Using this pipeline, we build thousands of long-horizon trajectories distilled from Claude 4.5 Sonnet (Thinking). To train with these extremely long trajectories, we propose a new trajectory-splitting SFT, which preserves early context, progressively truncates later context, and maintains overlap between sub-trajectories. In addition, to further improve long-horizon task-solving capability, we propose a novel progressive RL, which schedules training into multiple stages with progressively extended timeouts. Experiments demonstrate the superiority and generalization of KLong, as shown in Figure 1. Notably, our proposed KLong (106B) surpasses Kimi K2 Thinking (1T) by 11.28% on PaperBench, and the performance improvement generalizes to other coding benchmarks like SWE-bench Verified and MLE-bench.

LLMs Judge Themselves: A Game-Theoretic Framework for Human-Aligned Evaluation

arXiv:2510.15746v2 Announce Type: replace-cross Abstract: Ideal or real - that is the question.In this work, we explore whether principles from game theory can be effectively applied to the evaluation of large language models (LLMs). This inquiry is motivated by the growing inadequacy of conventional evaluation practices, which often rely on fixed-format tasks with reference answers and struggle to capture the nuanced, subjective, and open-ended nature of modern LLM behavior. To address these challenges, we propose a novel alternative: automatic mutual evaluation, where LLMs assess each other's output through self-play and peer review. These peer assessments are then systematically compared with human voting behavior to evaluate their alignment with human judgment. Our framework incorporates game-theoretic voting algorithms to aggregate peer reviews, enabling a principled investigation into whether model-generated rankings reflect human preferences. Empirical results reveal both convergences and divergences between theoretical predictions and human evaluations, offering valuable insights into the promises and limitations of mutual evaluation. To the best of our knowledge, this is the first work to jointly integrate mutual evaluation, game-theoretic aggregation, and human-grounded validation for evaluating the capabilities of LLMs.

The Latent Space: Foundation, Evolution, Mechanism, Ability, and Outlook

arXiv:2604.02029v1 Announce Type: new Abstract: Latent space is rapidly emerging as a native substrate for language-based models. While modern systems are still commonly understood through explicit token-level generation, an increasing body of work shows that many critical internal processes are more naturally carried out in continuous latent space than in human-readable verbal traces. This shift is driven by the structural limitations of explicit-space computation, including linguistic redundancy, discretization bottlenecks, sequential inefficiency, and semantic loss. This survey aims to provide a unified and up-to-date landscape of latent space in language-based models. We organize the survey into five sequential perspectives: Foundation, Evolution, Mechanism, Ability, and Outlook. We begin by delineating the scope of latent space, distinguishing it from explicit or verbal space and from the latent spaces commonly studied in generative visual models. We then trace the field's evolution from early exploratory efforts to the current large-scale expansion. To organize the technical landscape, we examine existing work through the complementary lenses of mechanism and ability. From the perspective of Mechanism, we identify four major lines of development: Architecture, Representation, Computation, and Optimization. From the perspective of Ability, we show how latent space supports a broad capability spectrum spanning Reasoning, Planning, Modeling, Perception, Memory, Collaboration, and Embodiment. Beyond consolidation, we discuss the key open challenges, and outline promising directions for future research. We hope this survey serves not only as a reference for existing work, but also as a foundation for understanding latent space as a general computational and systems paradigm for next-generation intelligence.

Do Emotions in Prompts Matter? Effects of Emotional Framing on Large Language Models

arXiv:2604.02236v1 Announce Type: new Abstract: Emotional tone is pervasive in human communication, yet its influence on large language model (LLM) behaviour remains unclear. Here, we examine how first-person emotional framing in user-side queries affect LLM performance across six benchmark domains, including mathematical reasoning, medical question answering, reading comprehension, commonsense reasoning and social inference. Across models and tasks, static emotional prefixes usually produce only small changes in accuracy, suggesting that affective phrasing is typically a mild perturbation rather than a reliable general-purpose intervention. This stability is not uniform: effects are more variable in socially grounded tasks, where emotional context more plausibly interacts with interpersonal reasoning. Additional analyses show that stronger emotional wording induces only modest extra change, and that human-written prefixes reproduce the same qualitative pattern as LLM-generated ones. We then introduce EmotionRL, an adaptive emotional prompting framework that selects emotional framing adaptively for each query. Although no single emotion is consistently beneficial, adaptive selection yields more reliable gains than fixed emotional prompting. Together, these findings show that emotional tone is neither a dominant driver of LLM performance nor irrelevant noise, but a weak and input-dependent signal that can be exploited through adaptive control.

Reproducible, Explainable, and Effective Evaluations of Agentic AI for Software Engineering

arXiv:2604.01437v1 Announce Type: cross Abstract: With the advancement of Agentic AI, researchers are increasingly leveraging autonomous agents to address challenges in software engineering (SE). However, the large language models (LLMs) that underpin these agents often function as black boxes, making it difficult to justify the superiority of Agentic AI approaches over baselines. Furthermore, missing information in the evaluation design description frequently renders the reproduction of results infeasible. To synthesize current evaluation practices for Agentic AI in SE, this study analyzes 18 papers on the topic, published or accepted by ICSE 2026, ICSE 2025, FSE 2025, ASE 2025, and ISSTA 2025. The analysis identifies prevailing approaches and their limitations in evaluating Agentic AI for SE, both in current research and potential future studies. To address these shortcomings, this position paper proposes a set of guidelines and recommendations designed to empower reproducible, explainable, and effective evaluations of Agentic AI in software engineering. In particular, we recommend that Agentic AI researchers make their Thought-Action-Result (TAR) trajectories and LLM interaction data, or summarized versions of these artifacts, publicly accessible. Doing so will enable subsequent studies to more effectively analyze the strengths and weaknesses of different Agentic AI approaches. To demonstrate the feasibility of such comparisons, we present a proof-of-concept case study that illustrates how TAR trajectories can support systematic analysis across approaches.

Bias Is a Subspace, Not a Coordinate: A Geometric Rethinking of Post-hoc Debiasing in Vision-Language Models

arXiv:2511.18123v2 Announce Type: replace-cross Abstract: Vision-Language Models (VLMs) have become indispensable for multimodal reasoning, yet their representations often encode and amplify demographic biases, resulting in biased associations and misaligned predictions in downstream tasks. Such behavior undermines fairness and distorts the intended alignment between vision and language. Recent post-hoc approaches attempt to mitigate bias by replacing the most attribute-correlated embedding coordinates with neutral values. However, our systematic analysis reveals three critical limitations of this coordinate-wise approach: feature entanglement, poor cross-dataset generalization, and incomplete bias removal. We find that bias is not localized to a few coordinates but is instead distributed across a few linear subspaces. To address these limitations, we propose $\textbf{S}$ubspace $\textbf{P}$rojection $\textbf{D}$ebiasing ($\textbf{SPD}$), a geometrically principled framework that identifies and removes the entire subspace of linearly decodable bias while reinserting a neutral mean component to preserve semantic fidelity. Extensive experiments across zero-shot classification, text-to-image retrieval, and image generation validate the effectiveness of SPD: our method achieves more robust debiasing with an average improvement of $18.5\%$ across four fairness metrics, while maintaining minimal loss in task performance compared to the best debiasing baseline.

Two-step clinical care pathway to predict MASLD-related advanced fibrosis and long-term outcomes in type 2 diabetes

Gut. 2026 Feb 9;75(3):576-587. doi: 10.1136/gutjnl-2025-337506.

ABSTRACT

BACKGROUND: Current guidelines recommend a two-step approach for risk stratification of metabolic dysfunction-associated steatotic liver disease (MASLD), starting with Fibrosis-4 index (FIB-4) followed by liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE).

OBJECTIVE: To evaluate this approach for predicting advanced fibrosis and liver-related events (LREs) in patients with type 2 diabetes (T2D).

DESIGN: A prospective liver biopsy cohort of T2D patients with histologically confirmed MASLD from seven centres in China was used to assess diagnostic performance for advanced fibrosis. The international VCTE-Prognosis cohort, including T2D patients with MASLD who underwent VCTE at 16 centres in the USA, Europe and Asia, with longitudinal follow-up, was used to assess LREs, defined as hepatic decompensation or hepatocellular carcinoma.

RESULTS: 4781 participants were included. In the liver biopsy cohort (n=352; 22.2% with advanced fibrosis), applying LSM thresholds of <8 kPa and >12 kPa after FIB-4 classified patients into 63.4% low-risk, 9.4% intermediate-risk and 27.3% high-risk, with a correct classification rate of 71%. In the VCTE-Prognosis cohort (n=4429; median follow-up 51.3 (IQR 27.4-70.7) months), 140 (3.2%) patients developed LREs (110 (2.5%) with hepatic decompensation and 59 (1.3%) with hepatocellular carcinoma). The two-step approach classified 72.6%, 6.8% and 20.6% of patients into low-risk, intermediate-risk and high-risk groups, with corresponding 5-year cumulative LRE incidences of 0.7%, 0.9% and 11.8%. Refining classification of intermediate FIB-4 patients using LSM <10 kPa (low-risk) and >15 kPa (high-risk) reduced the intermediate-risk group to 5.6% while preserving predictive accuracy.

CONCLUSION: The non-invasive two-step approach of FIB-4 followed by LSM effectively stratifies MASLD-related advanced fibrosis and LREs risk in T2D. Applying LSM cut-offs of 10 and 15 kPa further optimises risk stratification for future LREs.

PMID:41911049 | DOI:10.1136/gutjnl-2025-337506

Effect of a Digital-Driven Physician-Pharmacist Collaborative Model for Diabetes in Primary Health Care: Cluster Randomized Trial

Background: Evidence-based physician-pharmacist collaborative clinics have demonstrated significant short-term benefits for patients with type 2 diabetes (T2D), but their long-term effectiveness remains unclear, especially in primary health care settings. Objective: This study aimed to explore the long-term effectiveness and cost-effectiveness of a novel, digital-driven, multifaceted physician-pharmacist collaborative model for managing patients with T2D in underresourced settings. Methods: We conducted a 12-month cluster randomized controlled trial from May 2021 to December 2022 across 6 primary health care settings in China. Guided by the theory of planned behavior, the intervention involved routine therapy from physicians along with pharmaceutical interventions from pharmacists. These were delivered through a combination of face-to-face visits and mobile health care. The intervention group received 4 face-to-face visits and biweekly remote education sessions over the 12 months. We conducted intention-to-treat analyses to estimate differences in clinical and behavior indicators between the intervention and control groups. Primary outcomes included glycosylated hemoglobin and 10-year atherosclerotic cardiovascular risk. Data were analyzed using adjusted generalized estimation equations. Results: This study included 574 patients (291 in the intervention group and 283 in the control group). Over 12 months, patients in the intervention group had significant reductions in hemoglobin A1c (–2.57 vs –1.96, respectively; P<.001; 95% CI –1.027 to –0.238) and 10-year atherosclerotic cardiovascular risk (–1.35 vs 0.01, respectively; P<.001; 95% CI –1.690 to –0.630) compared with the control group. Substantial improvements were also observed in several secondary outcomes, including fasting blood glucose, 2-hour postprandial blood glucose, waist circumference, waist-to-hip ratio, blood pressure, triglyceride, and total cholesterol. Total diabetes-related costs decreased, and patient satisfaction improved significantly in the intervention group. There were no significant differences in BMI, high-density lipoprotein, or low-density lipoprotein. Conclusions: These findings suggest that the physician-pharmacist collaborative model could improve the long-term quality and efficiency of T2D management and reduce medical costs in underresourced areas globally. Patients with T2D, especially those with central obesity or high cardiovascular risk, may benefit more from collaborative clinics. Trial Registration: Chinese Clinical Trial Registry ChiCTR2000031839; https://www.chictr.org.cn/showproj.html?proj=51910
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