To evaluate the diagnostic yield and clinical implications of so-called 'borderline' ECG findings and ectopic beats in elite football players, in accordance with the 2017 International Criteria (IC17) for ECG interpretation in athletes. A total of 17 685 professional footballers (84.7% males) underwent cardiac screening including a 12-lead ECG and echocardiography between 2017 and 2024. Borderline ECG changes were classified according to the IC17. Supraventricular and ventricular ectopic beats were also analysed. Prevalence of cardiac pathology (major and minor) among athletes with borderline changes was compared with those athletes with normal ECGs. Borderline ECG findings were present in 1389 (7.9%) athletes (8.8% males, 2.6% females; p<0.001), with right atrial enlargement being the most frequently observed pattern (5.5%). Major cardiac pathology was incidentally identified in 2 (1.43%) athletes with isolated left atrial enlargement, compared with 9 (0.06%) athletes with normal ECGs (p=0.004), including 1 case of an anomalous coronary origin and another case with significant aortic root dilatation-both unrelated to the ECG findings. All other borderline patterns as well as ectopy did not reveal any major pathology. No major conditions were identified in 42 athletes with isolated ≥2 borderline ECG findings. Minor cardiac pathology was identified in 18 (1.41%) athletes with isolated borderline findings and in 3 (2.07%) athletes with isolated ectopy. When ≥2 borderline findings were present, 2.38% athletes revealed minor pathology (p=0.463). Minor cardiac pathology was found in 212 (1.34%) of athletes with normal ECGs (p=0.836). Borderline ECG criteria in the IC17 and ventricular ectopy are poor discriminators for major and minor cardiac pathology in athletes. Borderline changes including ≥2 findings do not warrant further evaluation and could be considered normal findings in future iterations of ECG interpretation criteria in athletes.
Photon-counting CT offers higher spatial resolution, improved contrast-to-noise efficiency, and spectral imaging, but its performance against heterogeneous EID-CT systems in routine use remains incompletely characterized. We compared image quality, pathology conspicuity, and radiation dose between clinical PCCT and EID-CT in paired routine neuroradiological examinations, accounting for differences in scanner generation, protocol, and reconstruction. We hypothesized higher image-quality and pathology-conspicuity scores and dose efficiency, while treating the comparison as pragmatic rather than detector-isolating. This retrospective study included consecutive adults undergoing routine clinical PCCT from December 2023 through February 2024 who had a corresponding same-region EID-CT within three months; when several EID-CT scans were eligible, the closest in time was selected. Examinations were grouped by protocol: non-contrast brain CT was the primary cohort; contrast-enhanced brain CT and arterial and venous CTA were exploratory. Four blinded readers assessed image quality and pathology conspicuity, with paired scans assigned to separate sessions at least four weeks apart. CNR, dose-normalized CNR (CNRD), and radiation dose were compared within subjects using the Wilcoxon signed-rank test. The 194 patients (mean age, 65±15 years; 100 males) contributed to 270 pairs: 225 non-contrast brain CTs, 14 contrast-enhanced brain CTs, 26 arterial CTAs, and 5 venous CTAs. In the primary cohort, PCCT was associated with higher overall image-quality scores (median 4 versus 3; p<.001), higher time-independent pathology conspicuity in 224/225 pairs (median 4 versus 3; p<.001), 102%-152% higher GM/WM CNR, 128%-180% higher CNRD, and 22% lower median dose (38.4 versus 49.2 mGy; all p<.001). All three primary endpoints remained significant in the ≤1-day subset (n=60). Artifact scores did not differ significantly. Exploratory contrast-enhanced and angiographic analyses favored PCCT for selected parenchymal and small-vessel metrics, including perforator visualization (median 3 versus 2; p<.001), but these small subgroups were preliminary and did not strengthen the primary conclusions. PCCT was associated with higher image quality, pathology conspicuity, GM/WM CNR and CNRD, and lower dose in routine non-contrast brain CT. Smaller protocol groups were exploratory. Because scanner generations, vendors, protocols, and reconstructions were unmatched, the differences cannot be attributed solely to detector technology.
Although digital breast tomosynthesis (DBT) improves screening performance relative to digital mammography (DM), it remains uncertain whether DBT changes the pathologic profile of detected cancers. We compared tumor grade, nodal status, tumor size, receptor markers, and related pathology features across comparative screening studies. We searched PubMed, Embase, and the Cochrane Library through February 2026. Thirteen comparative screening studies were summarized in the protocol/context table, and six comparative screening studies contributed extractable data to at least one quantitative pathology endpoint. The primary grade analysis included 809 invasive cancers (261 DBT-detected and 548 DM-detected), and the nodal-status analysis included 818 invasive cancers (263 DBT-detected and 555 DM-detected). We used mixed-effects logistic regression with a study-level random intercept and random-effects risk-difference meta-analysis as a sensitivity analysis. Mixed-effects models showed insufficient evidence of major between-modality differences for grade 3 tumors (DM 35.7% [95% CI, 23.8%-49.7%] vs DBT 29.7% [18.8%-43.5%]; P=.15), node-positive disease (36.8% [31.6%-42.4%] vs 32.8% [27.2%-39.0%]; P=.16), tumor size >10 mm (78.0% [63.7%-87.7%] vs 75.0% [59.4%-86.0%]; P=.44), triple-negative phenotype, HER2 positivity, ER/PR positivity, or Ki67 positivity. Receptor and Ki67 analyses were limited by sparse reporting and heterogeneous source definitions. Current comparative evidence suggests that DBT increases detection of breast cancers without demonstrating a consistent shift in pathologic profile relative to DM. These findings should be interpreted cautiously because study protocols, pathology reporting, and endpoint availability varied across studies.
Alcohol Use Disorder (AUD) is a leading risk factor for negative health consequences associated with disruptions in neural functions. While alcohol-induced neuronal adaptations have remained in the spotlight for researchers investigating AUD, growing evidence highlights glial cell populations and their contributions to AUD pathology. This review explores the role of oligodendrocytes (OLs) and their progenitors (OPCs) in alcohol-induced alterations of white matter (WM), myelin structure, composition, and integrity. Human neuroimaging studies reveal reductions in WM volume and microstructural integrity, accompanied by molecular evidence of impaired myelin architecture and lipid composition in postmortem brains. Preclinical models provide causal evidence linking alcohol to dose-, length of exposure-, and brain-region-dependent dysregulation of OLs at transcriptional, structural, and metabolic levels. Investigations of the underlying mechanisms implicate oxidative stress, neuroinflammation, transcriptional changes, epigenetic modifications, and lipid dysregulation as key pathways through which alcohol disrupts OLs. Because OLs are essential for proper myelination, neural function, and brain connectivity, alcohol-induced changes in these processes likely contribute to the cognitive, learning, and emotional deficits associated with AUD. Investigations into prenatal and adolescent alcohol exposure reveal impairments in OL maturation and myelination that produce long-lasting deficits which persist into adulthood. Together, these findings support alcohol-induced OL dysregulation and circuit disruption as drivers in AUD pathology. Understanding how alcohol impacts OLs and OPCs at both molecular and developmental levels is critical for identifying novel therapeutic targets aimed at ameliorating disruptions to WM integrity, diagnosing AUD, and improving outcomes for individuals impacted by AUD.
Amyloid PET is commonly interpreted using binary visual classification. However, quantitative assessment on the Centiloid scale identifies an intermediate range of amyloid burden not always captured by dichotomous interpretation. The biologic and clinical relevance of this intermediate category remain unclear, despite its implications for biomarker interpretation, prognostic stratification, and eligibility for amyloid-targeting therapies. Our aim was to characterize individuals within this intermediate range using multimodal biomarker profiles and longitudinal cognitive outcomes, as well as deriving Centiloid thresholds for early tau PET positivity, advanced tau PET positivity, and cognitive decline. Methods: We retrospectively analyzed participants who underwent amyloid PET between 2016 and 2024 at the Geneva Memory Center, including cognitively unimpaired individuals and patients with mild cognitive impairment or dementia. Global amyloid burden was quantified in Centiloids, and participants were categorized into low (<12), intermediate (12-37), or high (>37) groups. Group comparisons, receiver-operating-characteristic curve analyses, and linear mixed-effects models were used to assess fluid biomarker differences, define Centiloid thresholds for tau positivity and cognitive decline, and evaluate longitudinal change in Mini-Mental State Examination scores. Results: Among the 512 participants, 202 (39%) had low, 63 (12%) had intermediate, and 247 (48%) had high Centiloid values. The intermediate-Centiloid group showed biomarker profiles, including cerebrospinal fluid and plasma markers of amyloid, tau pathology, and neurodegeneration, between those of the low and high groups. Both the intermediate- and high-Centiloid groups exhibited faster cognitive decline than did individuals in the low-Centiloid group, with a moderate rate in the intermediate-Centiloid group. Thresholds of 13 and 14 Centiloids best identified individuals with cognitive decline and tau accumulation in the mesial temporal lobe, respectively, whereas 51 Centiloids best discriminated advanced neocortical tau involvement. Conclusion: Centiloid-based classification delineates biologically and clinically distinct stages along the amyloid continuum. Individuals with intermediate Centiloid values already show tau involvement and increased risk of cognitive decline, whereas higher amyloid levels are associated with advanced tau pathology. These findings support a 3-level interpretation of amyloid PET beyond binary classification and highlight the clinical relevance of the intermediate zone.
A 50-year-old man with severe presumed gallstone pancreatitis, multiorgan failure, and oliguric stage 3 acute kidney injury underwent bedside acute peritoneal dialysis (PD) for haemodynamically tolerated kidney support and intra peritoneal lavage. Catheter insertion drained a large volume of ascites that rapidly became vivid emerald green. Cultures remained sterile, whereas effluent amylase (11,041 U/L) and lipase (50,750 U/L) were markedly elevated, favouring inflammatory pancreatic leakage over infectious peritonitis or biliary perforation. During PD, effluent enzyme concentrations and cell counts declined, acidosis resolved, and kidney function improved. The patient subsequently died of septic shock. Emerald-green peritoneal effluent is rare and warrants urgent evaluation for serious intra-abdominal pathology.
Piezo1 is a well-established mechanosensitive ion channel that has been implicated in the progression of osteoarthritis (OA). However, the mechanisms by which Piezo1 contributes to chondrocyte injury within the inflammatory microenvironment, its interplay with mitochondrial dysfunction, and its role in interventions based on natural compounds remain poorly understood. This study investigated the modulatory effects of saikosaponin B1 (SSB1) on Piezo1 and its ability to alleviate mitochondrial damage and apoptosis in osteoarthritic chondrocytes. Through systematic screening of a natural compound library, we identified SSB1 as a potent modulator of Piezo1. In an in vitro inflammatory chondrocyte model, Piezo1 was aberrantly upregulated and hyperactivated, resulting in pathological Ca2⁺ influx, cytosolic calcium overload, and profound mitochondrial dysfunction that ultimately led to chondrocyte apoptosis and matrix degradation, which are hallmark events in OA pathogenesis. SSB1 effectively inhibited Piezo1-mediated Ca2⁺ influx, reduced the mRNA expression of proinflammatory mediators and matrix-degrading enzymes, and increased the expression of type II collagen, a key component of the cartilage matrix. Mechanistically, SSB1 reversed mitochondrial fragmentation, restored mitochondrial membrane potential, reduced reactive oxygen species production, and inhibited the aberrant opening of the mitochondrial permeability transition pore, thereby restoring mitochondrial homeostasis. Furthermore, SSB1 significantly attenuated inflammation-induced chondrocyte apoptosis, an effect associated with the transcriptional inhibition of nuclear factor kappa B (NF-κB) signaling. Collectively, our findings not only reveal the regulatory role of Piezo1 in OA pathology but also establish its potential as a druggable target, providing a promising candidate therapeutic agent for OA treatment.
Objective: To evaluate the prostate cancer (PCa) detection rates of targeted biopsy (TB) alone versus TB combined with systematic biopsy (SB) in patients with prostate imaging reporting and data systemv2.1 (PI-RADS v2.1) 4-5 lesions on biparametric magnetic resonance imaging. Methods: Clinical data were retrospectively collected from 1 060 patients who underwent combined prostate TB and SB at the First Affiliated Hospital of Nanjing Medical University between March 2018 and December 2023. All patients had pre-biopsy biparametric magnetic resonance imaging with PI-RADS v2.1 category 4 or 5 lesions. A comparative analysis was performed to evaluate the PCa detection rate and clinically significant prostate cancer (csPCa) detection rate between the two biopsy strategies. Using the postoperative pathological findings from 730 patients who underwent radical prostatectomy as the reference standard, a comparison of the pathological upgrading rates between TB alone and the combined biopsy approach was performed. Results: TB alone yielded detection rates of 79.6% (844/1 060) for PCa and 67.9% (720/1 060) for csPCa. The combined biopsy approach yielded detection rates of 82.2% (871/1 060) for PCa and 69.7% (739/1 060) for csPCa. The two strategies demonstrated no significant difference in detection rates of PCa and csPCa (P=0.136 and P=0.373) and showed substantial agreement (Kappa=0.918 for PCa and 0.958 for csPCa, both P＜0.001). This diagnostic alignment persisted across subgroups: among patients with PI-RADS category 4 lesions, the csPCa detection rates for TB alone and combined biopsy were 59.2% (395/667) and 61.5% (410/667), respectively, demonstrating high concordance (Kappa=0.953, P＜0.001). Among patients with PI-RADS category 5 lesions, the csPCa detection rates for TB alone and combined biopsy were 82.7% (325/393) and 83.7% (329/393), respectively, also demonstrating a high level of agreement (Kappa=0.964, P＜0.001). When compared with postoperative pathology, the overall pathological upgrading rates were 30.5% (223/730) for TB alone and 25.9% (189/730) for combined biopsy. The rates of upgrading specifically from biopsy-negative or ciPCa to csPCa were 12.3% (90/730) and 9.9% (72/730), respectively. Conclusion: For patients with PI-RADS 4-5 lesions, TB may serve as a clinically equivalent alternative to combined biopsy, achieving comparable diagnostic efficacy while reducing procedural burden on both patients and healthcare systems. 目的： 评价靶向穿刺和靶向穿刺联合系统穿刺对前列腺影像报告与数据系统（PI-RADS）评分为4～5分患者的前列腺恶性肿瘤检出效能。 方法： 回顾性收集2018年3月至2023年12月在南京医科大学第一附属医院行前列腺靶向穿刺联合系统穿刺的患者1 060例，活检前均行双参数磁共振平扫，PI-RADS评分为4～5分。比较单独靶向穿刺与靶向穿刺联合系统穿刺的前列腺癌（PCa）检出率和临床显著性前列腺癌（csPCa）检出率。以730例行根治性前列腺切除术患者的术后病理结果为金标准，比较单独靶向穿刺与靶向穿刺联合系统穿刺的术后病理升级率。 结果： 单独靶向穿刺的PCa检出率为79.6%（844/1 060），csPCa检出率为67.9%（720/1 060）。靶向穿刺联合系统穿刺的PCa检出率为82.2%（871/1 060），csPCa检出率为69.7%（739/1 060）。单独靶向穿刺与靶向穿刺联合系统穿刺的PCa检出率、csPCa检出率差异均无统计学意义（P值分别为0.136和0.373），PCa、csPCa检出情况均有较好的一致性（Kappa值分别为0.918和0.958，均P＜0.001）。按照PI-RADS评分分层分析显示，在PI-RADS评分为4分的患者中，单独靶向穿刺的csPCa检出率为59.2%（395/667），靶向穿刺联合系统穿刺的csPCa检出率为61.5%（410/667），表现出较好的一致性（Kappa=0.953，P＜0.001）。在PI-RADS评分为5分的患者中，单独靶向穿刺的csPCa检出率为82.7%（325/393），靶向穿刺联合系统穿刺的csPCa检出率为83.7%（329/393），也具有较好的一致性（Kappa=0.964，P＜0.001）。与术后病理结果比较，单独靶向穿刺的术后病理升级率为30.5%（223/730），其中90例（12.3%）患者从单独靶向穿刺病理阴性或临床非显著性前列腺癌（ciPCa）升级为术后病理的csPCa。靶向穿刺联合系统穿刺的术后病理升级率为25.9%（189/730），其中72例（9.9%）患者从靶向穿刺联合系统穿刺病理阴性或ciPCa升级为术后病理的csPCa。 结论： 前列腺PI-RADS评分为4～5分的患者，采用靶向穿刺取代靶向穿刺联合系统穿刺可以获得相近的诊断效果，能够减少患者痛苦，避免医疗资源浪费。.
Growing evidence shows that air pollution exposure plays a critical role in the development and progression of cardiovascular disease. Pollutants such as airborne particles smaller than 2.5 μm (PM2.5) are linked to systemic inflammation, oxidative stress and vascular dysfunction, thereby increasing the risk of hypertension, atherosclerosis, stroke and myocardial infarction. Understanding the pathology and the disease progression is essential for developing targeted interventions to mitigate the global cardiovascular burden associated with polluted air. We aimed to study how different PM2.5 exposure regimes may affect vasomotor response in coronary arteries. Using well-characterized PM2.5 collected in an urban environment, we exposed rats to re-aerosolized PM2.5, mimicking different potential scenarios of air pollution exposures such as acute high-dose exposure compared to chronic exposure at a lower dose. Vascular tone was studied ex vivo from the PM2.5 exposed rats and their corresponding controls, employing a wire myograph. Also, systemic effects were assessed through plasma biomarkers of soluble Sphingosine-1-phosphate (S1P) and Endothelin-1 (ET-1) together with immunohistochemical assessment of coronary arteries. In our translational experimental set-up, we observed that only the accumulative dose from the chronic exposure played a significant role on the studied outcomes in the vasculature and plasma biomarkers. Following chronic exposure, S1P vasomotor response was altered in coronary arteries, as well as plasma total protein levels and ET-1 concentration, which were significantly decreased. This indicates the importance of prolonged PM2.5 exposure effects on cardiovascular health, highlighting medical intervention options alongside the importance of improving air pollution management.
Intraplacental choriocarcinoma (ICC) is a rare gestational trophoblastic tumor that is often difficult to diagnose and is occasionally associated with fetomaternal hemorrhage (FMH). A 28-year-old woman presented with decreased fetal movements at 38 weeks of gestation. Due to a nonreassuring fetal heart rate pattern, an emergency cesarean section was performed. Severe neonatal anemia (3.2 g/dL) and markedly elevated maternal serum alpha-fetoprotein levels suggested FMH, despite normal maternal hemoglobin F levels. Initial placental pathology was unremarkable. Thirteen days postpartum, the patient developed massive vaginal bleeding requiring uterine artery embolization (UAE). Elevated serum β-hCG levels and multiple pulmonary nodules led to a clinical diagnosis of choriocarcinoma. Placental re-evaluation confirmed ICC. Chemotherapy with methotrexate, etoposide, and actinomycin D resulted in complete remission. In conclusion, ICC should be considered in cases of unexplained FMH or postpartum hemorrhage. UAE did not appear to impair the efficacy of subsequent chemotherapy in this case.
DNA methylation represents one of the most prevalent and significant epigenetic modifications in humans, playing a crucial role in numerous physiological and pathological processes within the human body. It demonstrates considerable potential as a novel disease biomarker. DNA methylation testing involves diverse sample types and complex procedures, with no unified standards currently established for its workflow. Consequently, developing a consensus on sample processing and detection techniques for DNA methylation holds significant value for advancing technological development, clinical translation, and application in this field. This consensus document, jointly authored by the Laboratory Medicine Committee of the Chinese Association of Integrative Medicine, the Molecular Diagnostics Group of the Chinese Society of Laboratory Medicine of Chinese Medical Association, and the Precision Medicine Committee of the Beijing Association of the Integrating of Traditional and Western Medicine, synthesizes the perspectives and expertise of specialists of laboratory medicine and pathology. The present document provides detailed guidance on key aspects such as the definition of DNA methylation, sample collection and pre-processing, nucleic acid extraction and conversion, methylation detection, and reporting of results. Fourteen consensus statements have been distilled from this comprehensive framework. DNA甲基化是人类常见和重要的表观遗传学修饰之一，在人体多种生理与病理过程中发挥着重要作用，作为新型疾病标志物展现出了巨大潜力。DNA甲基化检测涉及的样本类型多样、过程复杂，其检测流程尚缺乏统一标准。因此，建立DNA甲基化样本处理及检测技术共识，对推动该领域技术开发、临床转化和应用具有重要价值。本共识由中国中西医结合学会检验医学专业委员会、中华医学会检验医学分会分子诊断学组、北京中西医结合学会精准医学专业委员会共同编写，汇聚了来自检验医学、病理学等多个相关领域专家的观点和经验，详细阐述了DNA甲基化的定义、样本的采集和前处理、核酸提取和转化、甲基化检测、结果报告等要点，并从中凝练出14条共识意见。.
Epignathus, a teratoma arising from the palate or pharynx, is extremely rare and palatal fetus-in-fetu represents an even rarer anomaly. We report a prenatally diagnosed palatal fetus-in-fetu successfully managed with ex utero intrapartum treatment (EXIT). A 4 cm oral mass detected at 23 weeks caused polyhydramnios and gastric shrinkage, suggesting impaired swallowing and potential airway obstruction. Multidisciplinary evaluation determined the need for EXIT to secure the airway under placental circulation. At 34+5 weeks of gestation, caesarean delivery with EXIT was performed; a 14 cm tumour was delivered and tracheostomy followed by staged resection was undertaken. Histopathology revealed multiple differentiated tissues-including nerve, gastrointestinal tract, adrenal gland, skin, bone and teeth-meeting Spencer's criteria for fetus-in-fetu. The infant recovered well and was discharged 96 days postnatally. EXIT proved invaluable for airway management in high-risk epignathus, and fetus-in-fetu differs from teratoma by its lower malignant potential, emphasising individualised prenatal planning and team collaboration.
Objective: To investigate the anti-colorectal cancer effect of tremella fuciformis polysaccharides (TFP) via the gut microbiota-metabolite axis. Methods: Colorectal cancer was induced in C57BL/6J mice using azoxymethane/dextran sulfate sodium. TFP or distilled water was administered by gavage for 3 weeks. Disease activity index (DAI), colon length, tumor burden, histopathology, gut microbiota (metagenomics), fecal metabolites (untargeted metabolomics), and colonic protein expression (Western blot) were assessed. Pyridoxic acid's effect on HT-29 cells was tested in vitro. Results: TFP significantly reduced DAI [2.0(1.8, 3.3) vs. 3.5(2.8, 4.5), P＜0.01], increased colon length [(7.2±1.1) vs. (5.5±0.5) cm, P＜0.05], lowered pathological score [6(3, 8) vs. 9(8, 10), P＜0.05], and decreased tumor number [2(1, 3) vs. 4(3, 4), P＜0.05] and volume [(11.02±7.88) vs. (24.99±3.38), P＜0.01]. Metagenomics revealed that TFP significantly reshaped gut microbiota (R²=0.173, P=0.027), enriching Candidatus Amulumruptor, Helicobacter, and Akkermansia. Metabolomics showed distinct profiles (R²=0.159, P=0.004), with pyridoxic acid elevated 1.20 fold (P＜0.001). Pyridoxic acid suppressed HT-29 cell viability and migration, and correlated positively with several upregulated bacteria, suggesting a microbiota-metabolite axis underlying its anti-tumor effect. TFP downregulated nuclear factor-κB (NF-κB) (P＜0.01) and upregulated phosphorylated AMP-activated protein kinase alpha (p-AMPKα) (P＜0.001), BAX (P＜0.001), and cleaved caspase-3 (P＜0.05). Conclusion: TFP inhibits colorectal cancer progression by modulating gut microbiota, elevating pyridoxic acid, suppressing NF-κB, and activating AMPK-mediated apoptosis. 目的： 从菌群-代谢物的角度探讨银耳多糖对结直肠癌的抑制作用及其机制。 方法： 利用氧化偶氮甲烷联合葡聚糖硫酸钠诱导C57BL/6J小鼠构建结直肠癌模型，银耳多糖组将建模小鼠以银耳多糖灌胃3周，对照组将不建模小鼠以等量蒸馏水灌胃3周。评估各组小鼠的疾病活动指数（DAI）、结肠长度、肿瘤负荷及组织病理学变化，利用宏基因组学技术分析肠道菌群结构，利用非靶向代谢组学技术分析肠道菌群代谢物谱，采用蛋白质免疫印迹法检测结肠组织中核因子κB（NF-κB）、腺苷酸活化蛋白激酶α（AMPKα）及磷酸化AMPKα（p-AMPKα）、Bcl-2相关X蛋白（BAX）、caspase-3及活化型caspase-3的表达。通过细胞实验，验证吡啶甲酸对结直肠癌HT-29细胞活力和迁移能力的影响。 结果： 与模型组比较，银耳多糖组小鼠的DAI评分降低［2.0（1.8，3.3）分比3.5（2.8，4.5）分，P＜0.01］，结肠长度增加［（7.2±1.1）cm比（5.5±0.5）cm，P＜0.05］，病理评分降低［6（3，8）分比9（8，10）分，P＜0.05］，肿瘤的数量减少［2（1，3）个比4（3，4）个，P＜0.05］，肿瘤体积缩小［（11.02±7.88）mm3比（24.99±3.38）mm3，P＜0.01］。宏基因组分析显示，与模型组比较，银耳多糖组小鼠肠道菌种的结构发生了明显改变（R²=0.173，P=0.027），小鼠粪便中暂定淀粉分解菌属、螺杆菌属、阿克曼氏菌属等相对丰度较高，轻型乳杆菌属、理研菌属、乳杆菌属等相对丰度下降。银耳多糖组与模型组小鼠粪便中的差异菌有36种（log10线性判别分析分数＞2.0），模型组显著富集的菌种包括弗雷特邓肯氏菌、鼠轻型乳杆菌和鼠盲肠拟杆菌等，银耳多糖组显著富集的菌种为暂定盲肠淀粉分解菌、鼠杆菌科细菌分离株110 HZI和啮齿类螺杆菌等。代谢组学分析显示，银耳多糖组与模型组小鼠肠道菌群代谢物谱存在差异（R²=0.159，P=0.004），与模型组比较，银耳多糖组小鼠的粪便中有60种肠道菌群代谢物出现显著变化，其中33种上调，27种下调，吡啶甲酸的相对丰度升高到模型组的2.20倍（P＜0.001）。体外实验证实，吡啶甲酸能抑制结直肠癌HT-29细胞活力与迁移能力。与模型组比较，银耳多糖组小鼠结肠组织中NF-κB表达下调（0.65±0.04比1.00±0.06，P＜0.01），p-AMPKα（2.94±0.27比1.00±0.16，P＜0.001）、BAX（6.77±1.21比1.00±0.27，P＜0.001）和活化型caspase-3表达（2.10±0.73比1.00±0.15，P＜0.05）上调。 结论： 银耳多糖可能通过重塑肠道菌群，抑制NF-κB介导的炎症信号，激活AMPK介导的代谢和凋亡信号，并诱导细胞凋亡，从而抑制结直肠癌进展。.
The pathogenesis of Alzheimer's disease (AD) involves multiple pathological processes, including β-amyloid (Aβ) deposition, aberrant tau modification, oxidative stress, and neuroinflammation. The molecular interaction mechanism among them remains to be further clarified. Peroxynitrite (ONOO⁻) is a potent oxidizing and nitrating reactive nitrogen species formed from the rapid reaction between nitric oxide and superoxide. It mediates protein nitration, lipid peroxidation, and mitochondrial damage, thereby contributing to multiple pathological events in AD. This review outlines the physicochemical properties and biological behavior of ONOO⁻, and summarizes recent advances in detection techniques such as fluorescent probes and electrochemical sensors. It focuses on the role of ONOO⁻ within the AD pathological network and its interconnections with Aβ deposition, tau pathology, neuroinflammation, and blood-brain barrier disruption. Additionally, this review discusses the therapeutic potential of ONOO⁻-targeted strategies, aiming to provide novel insights into the crosstalk among multiple pathological pathways in Alzheimer's disease.
Fibrolamellar hepatocellular carcinoma (FLC) and combined hepatocellular-cholangiocarcinoma (cHCC-CCA) are rare primary liver cancers for which limited evidence is available to guide clinical management. cHCC-CCA could arises in the context of chronic liver disease and shares epidemiological and molecular features with both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), reflecting its intermediate biological and clinical position between these two entities. Its diagnosis remains challenging particularly when based on tumor biopsy specimens. Surgical resection remains the standard of care when feasible. Liver transplantation, trans-arterial chemoembolization, ablation, or selective internal radiation therapy have been used in selected cases. For advanced disease, systemic treatments commonly used for HCC or CCA have been applied in real-world practice, including platinum-based chemotherapy, tyrosine kinase inhibitors, and more recently immunotherapy. In addition, molecularly guided therapies have been explored, as targetable genetic alterations can be identified in a subset of cHCC-CCA. In contrast, FLC typically arises in non-cirrhotic livers of young patients and is frequently associated with metastatic disease, including lymph node involvement. At the molecular level, FLC is characterized by the presence of the DNAJB1-PRKACA fusion and by elevated serum procalcitonin secreted by the tumor. Surgical resection remains the cornerstone of treatment when feasible, but data guiding systemic therapy in unresectable cases are limited. Several regimens, including gemcitabine-oxaliplatin, lenvatinib, and immunotherapy, have been evaluated. More recently, clinical trials have reported antitumor activity with combinations of immunotherapy and vaccines targeting the DNAJB1-PRKACA fusion. To improve patient care, since cHCC-CCA and FLC are rare subtypes of liver cancer, we need to compile prospective samples and clinical data from the patients, including their response to any type of treatment at the national and international levels.
Perturbation of macropinocytosis triggers methuosis, a non-apoptotic cell death characterized by cytoplasmic vacuolization. However, the regulatory mechanisms of methuosis remain poorly defined. Lipid metabolism dysregulation is implicated in various cell death pathways, while its role in methuosis has remained elusive. Herein, LXX-8250, an isopropanolamine derivative of β-elemene, induced a vacuolization-associated cell death in breast and liver cancer cell lines. This process was accompanied by massive macropinocytosis, thereby confirming the occurrence of methuosis. Mechanistically, hypoxia-inducible lipid droplet-associated protein (HILPDA), a key regulator that promotes intracellular triacylglycerol (TAG) accumulation, was identified as the direct target of LXX-8250. By suppressing HILPDA, LXX-8250 inhibited diacylglycerol O-acyltransferase 1 (DGAT1) and activated adipose triglyceride lipase (ATGL). Consequently, lipid droplets and cellular TAG levels were reduced, while the subsequent increased diacylglycerol (DAG) stimulated macropinosome formation, leading to methuosis in these cells. In this study, we discover a novel methuosis agonist LXX-8250, and elucidate the critical role of HILPDA repression-dysregulated lipid metabolism in methuosis. Our study highlighted the potential of targeting this pathway as a therapeutic strategy to trigger cancer cell death.
The urethral caruncle is the most common lesion arising from the posterior lip of the urethral meatus in women; however, various benign and malignant tumours may mimic this condition. We report a case of a solitary fibrous tumour (SFT) presenting as a urethral caruncle. A woman in her late 60s presented with a progressively enlarging urethral mass that was accompanied by urinary spraying. Physical examination revealed a smooth spherical mass measuring 1.2 cm at the posterior urethral meatus. The lesion was completely excised under local anaesthesia. Histologically, the tumour consisted of spindle cells within collagenous stroma. Immunohistochemically, the tumour cells showed nuclear expression of STAT6 with focal CD34 positivity, supporting the diagnosis of SFT. No recurrence was observed during the 9-month follow-up period. This case highlights that lesions clinically resembling urethral caruncle may include mesenchymal tumours such as SFT, underscoring the importance of histopathological evaluation.
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This study aims to explore the clinicopathological and immunological characteristics of Talaromyces marneffei (TM) infection in patients with acquired immunodeficiency syndrome-related diffuse large B-cell lymphoma (AIDS-DLBCL), and to analyze the risk factors and prognostic impact. This study was designed as a retrospective cohort study, clinical data of 73 patients with AIDS-DLBCL admitted to the First Hospital of Changsha from January 2020 to December 2021 were collected and analyzed, and the patients aged 26 to 84 years, including 63 males and 10 females.Patients were divided into a TM infection group (n=17) and a non-TM infection group(n=56) based on the presence or absence of TM infection.The clinical and pathological characteristics as well as therapeutic effects of the two groups of patients were compared using the χ2 test and Fisher's exact test. Survival curves were plotted using the Kaplan-Meier method, and the association between AIDS-DLBCL specific variables and TM infection was analyzed using the binary logistic regression model. The results showed that a total of 73 patients with AIDS-DLBCL were included. Among them, 23.3% had TM infection(17/73). The histopathological examination of biopsy tissues showed that TM appeared as yeast-like round or oval spores under special staining, some of which were sausage-shaped or joint-like, with a septum in the middle, and existed within or outside macrophages. Comparative analysis between the two groups showed that the proportions of patients with HIV-RNA>200 copies/ml [88.24% (15/17) vs. 58.93% (33/56), χ2=4.260, P=0.039], CD4⁺ T cell count<50 cells/μl [41.18% (7/17) vs. 8.93% (5/56), χ2=9.553, P=0.004], occult blood (OB) positivity [47.06% (8/17) vs. 17.86% (10/56), χ²=5.173, P=0.023], and Mycobacterium tuberculosis (MTB) positivity [29.41% (5/17) vs. 3.57% (2/56), Fisher's exact test, P=0.006] were significantly higher in the TM infection group than in the non-TM infection group, with statistically significant differences between the groups (all P<0.05). Survival curve analysis showed that the 2-year overall survival rate of the TM infection group was significantly lower than that of the non-TM infection group [52.94% (9/17) vs. 92.85% (52/56), χ²=17.670, P<0.001]. The binary logistic regression model analysis showed that CD4+T cell count<50 cells/μl (OR=8.29, 95%CI:1.47-46.81), positive tuberculosis (OR=17.70, 95%CI:2.21-148.01), and positive occult blood (OR=5.19, 95%CI:1.14-23.57) were risk factors affecting the occurrence of TM infection in AIDS-DLBCL. In conclusion, CD4⁺ T cell count<50 cells/μl, occult blood positivity, and tuberculosis positivity may be risk factors for TM infection in patients with AIDS-DLBCL. 本研究探讨获得性免疫缺陷综合征（AIDS）相关弥漫性大B细胞淋巴瘤（DLBCL）患者中合并马尔尼菲篮状菌（TM）感染的临床病理及免疫学特征，并分析其危险因素及预后影响。本研究采用回顾性队列研究设计，分析2020年1月至2021年12月长沙市第一医院收治的73例AIDS-DLBCL患者的临床资料，年龄范围26~84岁，其中男性63例、女性10例。根据是否合并TM感染分为TM感染组（17例）和非TM感染组（56例）。采用χ2检验和Fisher精确检验比较两组患者的临床与病理学特征及疗效差异，通过生存分析Kaplan-Meier法绘制生存曲线、采用二元logistic回归模型分析AIDS-DLBCL特异性变量与马尔尼菲篮状菌感染之间的关联。结果显示，共纳入73例AIDS-DLBCL患者，合并马尔尼菲篮状菌感染患者占23.3%（17/73）；活检组织病理学检查显示马尔尼菲篮状菌在特殊染色下表现为酵母相的圆形或椭圆形孢子，部分呈腊肠形或关节状，孢子中间有横隔，存在于巨噬细胞内或细胞外。组间比较分析显示，AIDS-DLBCL合并TM感染患者HIV-RNA>200 copies/ml［88.24%（15/17）比 58.93%（33/56），χ²=4.260，P=0.039］、CD4+T细胞计数<50个/μl［41.18%（7/17）比 8.93%（5/56），χ²=9.553，P=0.004］、隐血阳性［47.06%（8/17）比 17.86%（10/56），χ²=5.173，P=0.023］、结核阳性［29.41%（5/17）比 3.57%（2/56），Fisher确切概率法，P=0.006］的比例显著高于非TM感染组，组间差异均有统计学意义（均P<0.05）；生存曲线分析显示，TM感染组2年总生存率显著低于非TM感染组［52.94%（9/17）比 92.85%（52/56），χ²=17.6700，P<0.001］。二元logistic回归模型分析显示，CD4+T细胞计数<50个/μl（OR=8.29，95%CI：1.47~46.81）、结核阳性（OR=17.70，95%CI：2.21~148.01）、隐血阳性（OR=5.19，95%CI：1.14~23.57）是影响AIDS-DLBCL发生TM感染的危险因素。综上，CD4+T细胞计数<50个/μl、隐血阳性、结核阳性可能是影响AIDS-DLBCL发生TM感染的危险因素。.
Oral mucosal melanoma (OMM) is a rare, aggressive malignancy biologically distinct from cutaneous melanoma. Given complex anatomy and limited chemotherapy efficacy, immune checkpoint inhibitors (ICIs) are increasingly used. This systematic review evaluated the clinical outcomes and safety of ICIs in primary OMM. A comprehensive literature search was conducted in accordance with PRISMA guidelines via Ovid MEDLINE, Web of Science, and Scopus for English-language human studies from January 1, 1990, to May 13, 2026, focusing on OMM and ICIs (PD-1/PD-L1, CTLA-4). Study screening and data extraction were independently performed by two reviewers, and case-report bias was assessed via the JBI Checklist. Fourteen case reports and two cohorts (n=124) met the inclusion criteria. The mean age in case reports was 65 years, with the maxilla as the predominant site. The majority of patients had advanced disease (IVa 57.1%). RECIST assessments indicated one complete response with pembrolizumab and topical imiquimod and partial responses in 9 of 14 patients (64.3%). Survival ranged from 3 to >96 months (mean ∼25). Immune-related adverse events (irAEs) occurred in 57.1% of the patients. In the cohort studies, the mean age ranged from 53 to 57 years, with a male predominance (54%), and most patients had advanced OMM. The two-year overall survival (OS) and progression-free survival (PFS) rates were 71% and 53.6%, respectively, with adjuvant PD-1-based therapy. With pembrolizumab-anlotinib, the objective response rate was 41.5%, the median PFS was 7.7 months, and the median OS was 10.8 months; toxicity was frequent but mostly manageable. Findings derived from case reports and two cohort studies suggest clinically meaningful responses and survival benefits of ICIs in a subset of patients with advanced OMM.