高雄荣民总医院

Gastric cancer (GC) remains a global health burden. While international guidelines share consensus, variations exist in disputed issues. The 2025 Taiwan Consensus and Management Guidelines for Gastric Cancer had just been released. We compared the key recommendations with established international guidelines. A multidisciplinary taskforce addressed key questions and recommendations using modified Delphi method and evidence-based approaches. The comparative review aimed to elucidate similarities and differences among guidelines from Taiwan, Japan, South Korea, China, Europe, and the US. Guidelines converge on absolute endoscopic resection criteria for early GC but differ in extended indications and perioperative approaches for locally advanced disease. Heterogeneity exists in biomarker assessment protocols, cutoff thresholds, and companion diagnostics. For metastatic disease, consensus exists on anti-HER2, anti-VEGF, immunotherapy, and biomarker-driven strategies, though oligo-metastatic definitions and intraperitoneal chemotherapy indications remain controversial. Optimal GC management requires integrating global evidence with regional contexts. The comparative review addresses heterogeneity among international guidelines, which helps harmonize management strategies as therapeutic standards evolve.

Controlling the behavior of mesenchymal stem cells (MSCs) through topographic patterns is an effective approach for stem cell studies. We, herein, reported a facile method to create a dopamine (DA) pattern on poly(dimethylsiloxane) (PDMS). The topography of micropatterned DA was produced on PDMS after plasma treatment. The grid-topographic-patterned surface of PDMS-DA (PDMS-DA-P) was measured for adhesion force and Young's modulus by atomic force microscopy. The surface of PDMS-DA-P demonstrated less stiff and more elastic characteristics compared to either nonpatterned PDMS-DA or PDMS. The PDMS-DA-P evidently enhanced the differentiation of MSCs into various tissue cells, including nerve, vessel, bone, and fat. We further designed comprehensive experiments to investigate adhesion, proliferation, and differentiation of MSCs in response to PDMS-DA-P and showed that the DA-patterned surface had good biocompatibility and did not activate macrophages or platelets in vitro and had low foreign body reaction in vivo. Besides, it protected MSCs from apoptosis as well as excessive reactive oxygen species (ROS) generation. Particularly, the patterned surface enhanced the differentiation capacity of MSCs toward neural and endothelial cells. The stromal cell-derived factor-1α/CXantiCR4 pathway may be involved in mediating the self-recruitment and promoting the differentiation of MSCs. These findings support the potential application of PDMS-DA-P in either cell treatment or tissue repair.

The classification of regulated cell death (RCD) has evolved from discrete, siloed pathways into an integrated network of metabolic and proteostatic checkpoints. For over a decade, the glutathione peroxidase 4 (GPX4)-dependent neutralization of lipid hydroperoxides on the plasma membrane was considered the primary defense against ferroptosis. However, the landmark discovery by Xia et al. [1] in Cell has identified a “non-canonical” ferroptosis pathway governed by the GPX1-OSBPL8 axis, which operates specifically at the endoplasmic reticulum (ER). By elucidating how the lipid transfer protein OSBPL8 recruits GPX1 to reduce peroxidized phosphatidic acid (PA-OOH), this research provides a definitive organelle-specific mechanism for lipid-driven cell death. For the field of apoptosis, this discovery is pivotal: it positions the ER as a central decision-making hub where ferroptotic lipid damage converges with intrinsic apoptotic signals via ER stress, the Unfolded Protein Response (UPR), and unregulated calcium dynamics. This commentary evaluates the mechanistic underpinnings of this non-canonical axis and explores the synergistic potential of targeting ER-localized death programs in oncology.

BACKGROUND:Obeldesivir is an oral nucleoside analog prodrug inhibitor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS:Nonhospitalized adults with risk factors for developing severe coronavirus disease 2019 (COVID-19) were enrolled ≤5 days from COVID-19 symptom onset and randomized 1:1 to receive obeldesivir 350 mg or placebo twice daily for 5 days. The primary end point was COVID-19-related hospitalization or all-cause death by day 29. Other end points included time to symptom alleviation by day 15, change in SARS-CoV-2 viral RNA copy number and infectious viral titer, and incidence of adverse events and laboratory abnormalities. RESULTS:Four hundred and sixty five participants were randomized and received ≥1 dose of study drug. Baseline characteristics were generally balanced between groups. Overall, 58% had received ≥1 COVID-19 vaccination, and 92% were seropositive for SARS-CoV-2 antibodies. COVID-19-related hospitalization or all-cause death by day 29 was reported in 0 of 211 (0%) participants with obeldesivir and 1 of 207 (0.5%) participants with placebo (log-rank P = .32). Time to COVID-19 symptom alleviation was numerically shorter with obeldesivir versus placebo. Obeldesivir reduced viral RNA copy number at day 5 and infectious titer at days 3 and 5 versus placebo. The safety profile was generally comparable across arms. CONCLUSIONS:Although underpowered in the context of a changing COVID-19 landscape, obeldesivir in nonhospitalized adults with targeted risk factors did not improve COVID-19-related hospitalization or all-cause death. Obeldesivir reduced viral RNA copy number and infectious titer, demonstrating its ability to inhibit SARS-CoV-2 replication, and resulted in numerically faster symptom alleviation. CLINICAL TRIALS REGISTRATION:NCT05603143; EudraCT 2022-002741-18.

Background: The modulation of brain dynamics by melatonin antidepressants in patients with major depressive disorder (MDD) remains unclear. Methods: Resting-state electroencephalographic (EEG) was recorded in 84 drug-free patients with MDD and 143 healthy controls. EEG data were collected at baseline and after 8-week agomelatine treatment. K-means clustering identified four canonical microstates (MS-A-D), and topographic analysis of variance assessed group differences. Results: At baseline, patients with MDD showed increased occurrence and coverage of MS-C and MS-D, along with a higher transition probability between these two states, compared to healthy controls. In contrast, the duration and coverage of MS-A and MS-B, as well as their transition probabilities, were reduced in the MDD group. Following treatment, patients with MDD exhibited increased MS-A coverage and a higher transition probability from MS-A to MS-B, while the transition probability between MS-C and MS-D decreased. Several microstate parameters were normalized to those of healthy controls. Notably, MS-B occurrence negatively correlated with baseline anhedonia severity, although no microstate measures predicted changes in anhedonia over time. Conclusions: This study demonstrates altered EEG microstate dynamics in patients with MDD and provides insights into the neural mechanisms underlying MDD. Microstate abnormalities may serve as potential clinical biomarkers for MDD.