Beijing Xuanwu Traditional Chinese Medicine Hospital

Perivascular macrophages (PVMs) are increasingly recognized as key players in maintaining brain homeostasis, yet their role in maintaining neurovascular-metabolic homeostasis has not been fully explored. We hypothesized that PVM depletion compromises cerebrospinal fluid-interstitial fluid exchange through glymphatic system (GS) dysfunction, thereby exacerbating cortical hyperexcitability manifested as increased epilepsy susceptibility and seizure intensity. Using clodronate liposomes (CLOs), we achieved >85% PVM depletion in mice. Following pentylenetetrazole (PTZ) challenge, PVM-depleted mice exhibited anxiety-like behaviors (reduced center time, p < 0.05), impaired working memory (decreased spontaneous alternation, p < 0.05), and increased cortical hyperexcitability, including shorter seizure latency and elevated EEG total power (p < 0.05). Mechanistically, PVM loss led to dysregulation of extracellular matrix components (increased laminin and collagen IV), impairing perivascular space integrity and GS function (reduced CSF tracer clearance, p < 0.05). AQP4 inhibition with TGN-020 further exacerbated PTZ-induced EEG abnormalities (increased total power, p < 0.05). Analysis of human epileptic tissue confirmed elevated collagen IV deposition in the seizure focus (p < 0.05) and a trend toward increased PVM density (p = 0.0638). These results highlight PVMs as essential modulators of the glymphatic-metabolic axis, linking vascular health to brain excitability. Targeting the PVM-GS interface offers therapeutic potential for disorders involving vascular dysfunction and neuronal hyperexcitability.

BackgroundOsteoarthritis (OA) is a common disabling joint disorder traditionally attributed to mechanical wear. Emerging evidence shows that metabolic syndrome (MetS) and its components—obesity, hypertension, hyperglycemia, and dyslipidemia—are closely associated with OA onset and progression, suggesting that OA also has a metabolic-inflammatory nature.Main TextThis review highlights mechanisms linking each MetS component to OA. Obesity contributes not only by increasing joint load but also through adipokines such as leptin, resistin, and visfatin, which activate inflammatory pathways and promote cartilage degradation and synovitis. Hypertension may worsen OA via joint ischemia, oxidative stress, and renin–angiotensin system activation. Hyperglycemia damages cartilage and ligaments by promoting advanced glycation end product accumulation and oxidative stress. Dyslipidemia influences OA through cholesterol deposition and inflammatory responses. Metabolic inflammation and immunometabolic reprogramming further drive OA progression.ConclusionMetS and OA are interconnected through mechanical stress, adipokine activity, inflammatory signaling, and metabolic dysregulation. Future studies should clarify how MetS affects pain, subchondral bone remodeling, and other OA phenotypes, aiding the development of individualized, metabolism-targeted strategies for early intervention and comprehensive OA management.

Abstract Cancer screening can enable early detection and improve survival but a focus on single cancers limits cost-effectiveness. Here we present OMAFound (carcinOMA Finder foundation), a foundation model capable of simultaneous multi-cancer screening at both organ level and patient level using widely accessible non-contrast computed tomography (CT). The model was developed and tested on 325,197 CT volumes from 151,386 patients across 10 Chinese and international datasets, achieving performance comparable to mammography-based approaches for breast cancer detection and matching existing lung-specific models for lung cancer detection. In a prospective multi-centre cohort of 21,601 patients undergoing low-dose CT screening, OMAFound demonstrated balanced accuracy of 82.2% for breast cancer and 88.0% for lung cancer in females, while attaining 86.1% balanced accuracy for lung cancer detection in males. When assisted by OMAFound, 7 generalist radiologists showed improvement in sensitivity (mean increases of 38.9% for breast cancer, 16.0% for lung cancer and 21.3% at patient level), without compromising specificity. These findings highlight the potential of OMAFound as a multi-cancer screening tool to offer robust preventive medicine strategies with minimal costs.

Norepinephrine (NE) and phenylephrine (PE) are routinely administered vasopressors used to maintain haemodynamic stability during caesarean section. Emerging evidence suggests that sustained infusion of these agents may disrupt maternal blood glucose regulation. This randomised controlled trial aims to compare the effects of NE and PE infusion on changes in postpartum blood glucose levels, insulin concentrations and insulin resistance in women after caesarean delivery. In this double-blind, randomised trial, 100 eligible parturients will receive prophylactic intravenous infusion of either NE or PE at a rate of 30 mL/hour immediately after subarachnoid anaesthesia, continuing until the end of surgery. The primary outcome is the difference between maternal preoperative and immediate postoperative blood glucose levels. Secondary outcomes include immediate and 6-hour postoperative insulin levels, as well as Homeostasis Model Assessment of Insulin Resistance. The Institutional Ethics Committee of Xuancheng People's Hospital approved the trial protocol (ID: 2025-yjky022-02). Findings will be published in an appropriate journal, and original data will be made available in November 2029 via the ResMan primary data-sharing platform of the China Clinical Trial Registry (http://www.medresman.org.cn). ChiCTR2500107683.

Fusarium root rot is recognized as a critical root disease responsible for significant reductions in tobacco yield and postharvest quality. It was caused by soil-borne pathogenic fungi of the genus Fusarium, with 11 species reported, among which F. oxysporum and F. solani are the main pathogens in China (Yang et al. 2024), but Fusarium asiaticum has not been previously reported until now at a global level in tobacco. In May 2024, field-grown tobacco (Nicotiana tabacum L.) plants exhibiting Fusarium root rot symptoms (approximately 5,000 m2 of 60,000 m2 surveyed) were observed in Xuancheng, Anhui Province, China (30.77°N, 118.84°E), with disease incidence of 2.52% to 14.35%, which was investigated in specific villages including Lianshumiao (3.71%), Xicun (4.62%), and Xizha (14.35%) in Huangdu Township; Yangliu Village (11.67%) in Yangliu Town; and Futian (2.52%) and Yanhe(3.82%) in Wenchang Town. Affected tobacco plants exhibited characteristic symptoms including brown to black lesions on the roots, epidermal sloughing in the root collar region, browning of xylem tissue, and chlorosis progressing to necrosis accompanied by wilting in mid-to-lower leaves. Under high soil moisture, root rot progressed rapidly, leading to plant death. To isolate the pathogen, thirty symptomatic roots (cv. Yunyan87) with typical and severe symptoms which were selected as representative isolates from a total of 242 diseased plants collected across 12 different fields were surface-sterilized (75% ethanol for 40 s, 5% NaClO for 1 min), rinsing with sterile distilled water. The roots were plated on PDA after cut into small pieces(5 mm×5 mm), and incubated at 28°C. Three isolates were obtained from three samples. Each isolate was obtained from a single spore and examined for morphological, molecular analyses and pathogenicity (The three strains used in this study are independent in origin but genetically closely related and phenotypically consistent isolates of Fusarium asiaticum. Given their high consistency in key traits such as species identity, colony morphology, and pathogenicity, so only strain A3 is covered in this report). Colonies on PDA displayed white aerial mycelium with white sporodochia, and began to produce red pigment after 7 days of culture. On carnation leat agar (CLA) medium, strain A3 produced macroconidia, which were falcate, 4–6 septate, measuring 45.4–50.6 × 3.7–4.5 μm (n=30) but no microconidia. Morphology matched Fusarium spp. (Leslie and Summerell. 2006). The total DNA of strain A3 was extracted from mycelium of the 7-day-old cultures by CTAB method (White et al. 1990). The ribosomal DNA internal transcribed spacer (ITS) region, elongation factor 1α (TEF-1α) and RNA polymerase II second largest subunit (RPB2) were amplified using primer pairs ITS1/ITS4 (White et al. 1990), EF1-728F/EF2R (Carbone and Kohn. 1999), and RPB2-5F/RPB2-7CR (Qiu et al. 2023) respectively, and sequenced. Neighbor-Joining analysis constructed by concatenating three sequences was carried out using MEGA 11. The obtained ITS (PV459639), TEF-1α (PV521975), and RPB2 (PV521974) sequences were 99.1 (511/516), 99.6% (757/760) and99.61% (1108/1112) identical to the corresponding DNA sequences of F. asiaticum strains (GenBank: ITS=KY272817, TEF-1α=PP404039, RPB2=PQ281488). Phylogenetic analysis confirmed clustering with F. asiaticum. Pathogenicity was verified by inoculating four-leaf-stage tobacco seedlings (cv. Yunyan 87) grown in sterile soil under controlled greenhouse conditions (25±2°C, 70% RH) with a 16-h light/8-h dark photoperiod. A total of 40 seedlings were used in the experiment. Twenty seedlings were inoculated via soil drenching with 20 mL of a conidial suspension (1×106 spores/mL) of Fusarium asiaticum prepared from a 7-day-old culture grown on PDA medium. Another twenty seedlings, serving as controls, were treated similarly with 20 mL of sterile water. The experiment was repeated third. Inoculated plants developed wilting and root discoloration within 7 days, while controls remained healthy. The pathogen was reisolated and confirmed as F. asiaticum via EF-1α sequencing. Although F. asiaticum has been reported on wheat(Zhang et al. 2025) , Ligusticum (Zhu et al. 2022), maize (Dong et al. 2021), corn (Jiang et al. 2023), Foxtail Millet (Kong et al. 2022) and rice(Chen et al. 2022) in Asia, this is the first report on tobacco. Given the economic importance of tobacco in China, this finding highlights the need for targeted management strategies against this emerging pathogen.

Gastric cancer (GC) is one of the most common and deadly types of cancer worldwide. In China, it is the most frequently occurring digestive tract tumour. Compared to traditional chemotherapeutic regimens centred on platinum and fluorouracil, immunotherapy has become one of the most important treatments for gastric cancer. Immune checkpoint inhibitors (ICIs) have the potential to benefit patients in the long term, but their development is limited by a high rate of resistance. To improve the efficacy of ICIs, it is important to understand the resistance mechanism in GC patients. In this paper, we review the resistance mechanisms of ICI in gastric cancer patients from four aspects: tumour immunity, immunosuppressed TME, tumour cells, and microbial populations.Additionally, we discuss new strategies and ideas to address ICI resistance in gastric cancer patients.

BackgroundPrevious studies have shown that astrocytes can transfer healthy mitochondria to dopaminergic (DA) neurons, which may serve as an intrinsic neuroprotective mechanism in Parkinson’s disease (PD). LRRK2 G2019S is the most common pathogenic mutation associated with PD. In this study, we explored whether mitochondrial transfer is influenced by genetic and environmental factors and whether dysfunction in this process is one of the mechanisms of the pathogenic LRRK2 G2019S mutation.MethodsDA neurons and astrocytes were differentiated from induced pluripotent stem cells generated from the peripheral blood of a healthy individual and a PD patient carrying the LRRK2 G2019S mutation. A coculture system of astrocytes and DA neurons was established to explore the pathogenic mechanisms of LRRK2 G2019S.ResultsExposure to the environmental toxin rotenone impaired mitochondrial transfer from astrocytes to DA neurons. Compared with the co-culture system from the healthy participant, the co-culture system harboring the LRRK2 G2019S mutation experienced more pronounced damage. Specifically, STX17 was colocalized with the mitochondrial outer membrane marker TOM20, and its knockdown caused damage to mitochondrial transfer. Drp1 interacted with STX17. LRRK2 G2019S-mutant astrocytes exhibited markedly increased phosphorylation of Drp1 at Ser616 upon rotenone exposure. Moreover, the degree of colocalization of STX17 with TOM20 decreased. The Drp1 phosphorylation inhibitor DUSP6 restored the colocalization of STX17 and TOM20, as well as the mitochondrial transfer efficiency and neuronal survival.ConclusionsThe impairment of mitochondrial transfer is a potential pathogenic mechanism associated with LRRK2 G2019S mutation. The molecular mechanisms of mitochondrial transfer were observed to occur through a Drp1-STX17-dependent pathway. Notably, inhibitors for Drp1 Ser616 phosphorylation may offer neuroprotection through mitigating mitochondrial transfer impairments. This study provides novel insights into the pathogenesis of PD and the development of new therapeutic targets.Graphical abstractSupplementary InformationThe online version contains supplementary material available at 10.1186/s40035-025-00525-1.