Changhai Hospital

Microglia, lipids, and their interaction are found to play important roles in post-stroke immunity. Microglia are sensitive to detect environment change in injured brain. Activated microglia undergo phenotypical remodeling and trigger complex signal cascades to regulate immune responses after stroke. Lipids including peripheral lipid metabolism and lipid droplet biogenesis are involved in the control of microglia functions, such as activation, phagocytosis, proliferation, and pro-inflammation. In this review, we explore new scope of microglia and lipids in immune regulation of stroke. Implication of peripheral lipid metabolism after stroke is mentioned and advances in microglia-lipid interaction are discussed. We give a special focus on how diet and gut microbiome influence neuroinflammation system via gut-brain axis, and how these processes associate with the risk and outcome of stroke. Moreover, we reviewed the therapeutic targets related to lipid metabolism and microglial modulation after stroke. These can provide a prospective strategy for more efficient and safer treatment for ischemic and hemorrhagic stroke.

Robot-assisted partial nephrectomy (RAPN) represents the preferred minimally-invasive approach for localized renal tumors. Increasing attention has focused on optimizing parenchymal preservation, with enucleation proposed as a potentially advantageous strategy. This study aimed to compare perioperative and functional outcomes of enucleation versus enucleoresection in a large, contemporary multicenter RAPN cohort. Data were extracted from the multicentric and multicontinental European Association of Urology Young Academic Urologists (EAU-YAU) Renal Cancer Working Party database. Patients undergoing RAPN between 2015 and 2024 with clearly documented resection technique (enucleation vs enucleoresection) were included. The resection technique was chosen based on the surgeon's preference. Perioperative, pathological, and renal functional outcomes were evaluated. Acute kidney injury (AKI - defined according to the AKIN classification) and chronic kidney disease (CKD) worsening served as primary endpoints. Logistic regression and Cox proportional hazards models were used to assess the association between surgical technique and the risk of AKI and CKD progression; Kaplan-Meier curves were used to depict time-to-event and functional outcomes, while longitudinal eGFR analyses were performed to evaluate renal function trends over time. Among 1260 patients, 527 (42%) underwent enucleation and 733 (58%) enucleoresection. Adoption of both techniques remained stable over time. Baseline characteristics were comparable. Enucleoresection was associated with longer ischemia time, higher intraoperative complication rates, and a lower positive surgical margin rate (5.2% vs 8.3%, p=0.003). Postoperative AKI occurred more frequently after enucleoresection (18% vs 3%, p<0.001), although eGFR recovery was similar at a median follow-up of 12 vs 25 months. In the overall cohort and among patients with baseline CKD stages 1-2, enucleation was associated with a lower risk of CKD progression (p<0.001). Enucleation during RAPN offers a parenchyma-sparing approach with potential functional advantages, particularly in patients with preserved baseline renal function. This benefit must be balanced against a slightly higher risk of positive margins, reinforcing the necessity of thoughtful case selection and standardized surgical technique.

High-grade meningiomas remain clinically challenging due to their aggressive behavior and limited therapeutic options. Although mutations and dysregulation of KMT2 family members have been implicated in various cancers, their functional significance in meningioma remains unclear. While NF2 alterations are the most common drivers of meningioma pathogenesis, the mechanisms regulating NF2 transcription in NF2-intact tumors are poorly understood. Here, we demonstrate that KMT2C expression is markedly reduced in high-grade meningiomas and that loss of KMT2C promotes proliferation and invasion in NF2-wild-type meningioma cells. Mechanistically, KMT2C deficiency suppresses NF2 transcription and inactivates Hippo signaling, leading to enhanced oncogenic activity and increased sensitivity to ferroptosis. Loss of KMT2C impairs the acetyltransferase activity of CBP/EP300, resulting in a global reduction of H3K27ac and transcriptional silencing of NF2. Pharmacological restoration of histone acetylation with the HDAC inhibitor Trichostatin A (TSA) effectively suppressed tumor growth. Collectively, our findings identify KMT2C as a key epigenetic regulator linking promoter histone acetylation, NF2-Hippo pathway activity, and ferroptosis susceptibility. These results provide mechanistic insights into high-grade meningioma progression and highlight ferroptosis induction and epigenetic modulation as promising therapeutic strategies for NF2-wild-type, KMT2C-deficient meningiomas.

ABSTRACT Primary liver cancer remains a significant global public health challenge, characterized by persistently high incidence and mortality. This review synthesizes current epidemiological data to analyze trends and etiological shifts, with particular emphasis on China, which bears over 40% of the global burden. Findings highlight a transition in dominant risk factors from viral hepatitis to metabolic dysfunction‐associated steatotic liver disease (MASLD), alongside persistent threats from aflatoxin exposure and lifestyle behaviors. Evidence‐based prevention strategies, including universal hepatitis B virus (HBV) vaccination, antiviral therapy expansion, aflatoxin control, and early metabolic intervention, are critical to reducing disease burden. The integration of artificial intelligence into screening and management represents a promising advancement. A multi‐faceted approach combining vaccination, surveillance, lifestyle modification, and technological innovation is essential for effective global liver cancer control.

Dysregulation of the CARD11-BCL10-MALT1 (CBM) complex is associated with a group of inborn errors of immunity termed “CBM-opathies,” which encompass a spectrum of clinical manifestations including combined immunodeficiency, autoimmune inflammation, atopic disorders, and lymphoproliferation. In this study, we identified novel compound heterozygous variants in the CBM complex in a patient with a family history of immune dysfunction. The patient inherited the variants CARD11 p.K215N and MALT1 p.K543R/p.M732T from asymptomatic carrier parents. Phenotypically, the patient exhibited a developmental arrest of B lymphocytes at the transitional/naïve B cell stage, accompanied by activation of virus-response pathways. Impaired development of T follicular helper cells was linked to defective germinal center formation and agammaglobulinemia. Furthermore, the patient showed expansion of T peripheral helper cells and a deficiency in regulatory T cells, both associated with autoimmunity and colitis. In vitro studies confirmed an imbalance in Tph/Tfh cell differentiation. Single-cell RNA sequencing further revealed a deficiency in B cell development and an enriched population of pro-inflammatory CD3dimCD4−CD8−CD247+ T cells, functionally enriched in the MAPK signaling pathway. Mechanistically, the MALT1 K543R and M732T variants attenuated MALT1’s enzymatic activity and compromised its protein stability, while the CARD11K215N variant disrupted CARD11-mediated promotion of BCL10 filament formation. We demonstrated that these three variants act synergistically to impair NF-κB activation. Specifically, CARD11K215N cooperates with the co-pathogenic MALT1M732T and the modifier variant MALT1K543R to destabilize the functional integrity of the CBM complex, thereby driving the patient’s phenotype. In summary, our study provides new insights into the pathogenesis of autoimmune inflammatory disorders within the spectrum of CBM-opathies and reveals a potential role for the CBM complex in regulating the balance between T peripheral helper and T follicular helper cells. Identified three novel variants in the CBM complex in a patient with a family history of immune dysfunction. CARD11K215N/MALT1K543R/M732T variants impaired B cell development and CD4+T cell differentiation, especially T peripheral helper and T follicular helper cells, by destabilizing the functional integrity of CBM complex.

ObjectiveTo investigate the correlation between vaginal microbiota indicators and HPV infection, providing a reference for clinical prevention and treatment of HPV-related diseases.MethodsClinical data of 5,362 female patients who underwent vaginal microbiota testing and HPV detection were retrospectively analyzed. The distribution of vaginal microbiota indicators and their association with HPV infection were statistically analyzed using the chi-square test. Three hundred fifty-five patients infected with HPV 16/18 were enrolled, followed up their HPV re-detection results at 12 months, and performed univariate analysis and logistic regression analysis to identify the risk factors for persistent HPV infection.ResultsAmong the 5,362 subjects, the positive rates of hydrogen peroxide, sialidase, leukocyte esterase, Trichomonas vaginalis, mold, and clue cells were 96.38%, 16.51%, 59.29%, 0.93%, 16.09%, and 8.65% respectively. 63.19% of the subjects had vaginal cleanliness of III-IV, and 71.73% had a vaginal pH value >4.5. Statistical analysis showed that sialidase (χ2 = 4.13, P = 0.04), and vaginal cleanliness (χ2 = 8.32, P = 0.00) were significantly associated with HPV infection; Vaginal Cleanliness(χ2 = 8.32, P = 0.04) and pH(χ2 = 14.63, P = 0.00) were significantly associated with HPV Genotypes. Vaginal pH value (OR = 2.65, 95% CI: 1.55–4.52, P < 0.001), N-acetylglucosaminidase positive (OR = 2.14, 95% CI: 1.12–4.08, P = 0.021), and fungus detected (OR = 1.88, 95% CI: 1.06–3.35, P = 0.032) were identified as independent risk factors for persistent HPV infection.ConclusionVaginal microbiota imbalance, as indicated by abnormal sialidase, poor vaginal cleanliness, and elevated pH value, may be related to HPV infection. Vaginal pH value, N-acetylglucosaminidase positive and fungus detected were identified as independent risk factors for persistent HPV infection.

Pancreatic ductal adenocarcinoma (PDAC), the deadliest epithelial malignancy, is increasingly prevalent and contributes significantly to cancer-related mortality. Research over the past decade has demonstrated that microbiota may play a pivotal role in both PDAC oncogenesis and its resistance to chemotherapy. Emerging preclinical and clinical data highlight the impact of microbiota on therapeutic outcomes in PDAC patients. This review systematically explores the role and underlying mechanisms of microbiota in PDAC, with a particular focus on their clinical implications and translational potential in disease progression and therapeutic responses. Finally, this review addresses the potential of microbiome-based therapies to enhance the efficacy of PDAC treatments.

We read with great interest a recent study investigating the role of nuclear receptor coactivator 7 (NCOA7) as a critical regulator of lysosomal function, oxysterol, and bile acid metabolism, and its link to endothelial cells (ECs) inflammation and immune activation in pulmonary artery hypertension (PAH). The study demonstrated that NCOA7 deficiency exacerbated lysosomal dysfunction, leading to inflammatory sterol accumulation and immune activation, which subsequently triggers endothelial immune responses. Translationally, NCOA7 activation emerges as a promising therapeutic strategy, while plasma oxysterol and bile acid levels offer potential prognostic biomarkers for PAH severity and mortality.