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Background Acquired resistance of 5-fluorouracil (5-FU) remains a clinical challenge in colorectal cancer (CRC), and efforts to develop targeted agents to reduce resistance have not yielded success. Metabolic reprogramming is a key cancer hallmark and confers several tumor phenotypes including chemoresistance. Glucose metabolic reprogramming events of 5-FU resistance in CRC has not been evaluated, and whether abnormal glucose metabolism could impart 5-FU resistance in CRC is also poorly defined. Methods Three separate acquired 5-FU resistance CRC cell line models were generated, and glucose metabolism was assessed by measuring glucose and lactate utilization, RNA and protein expressions of glucose metabolism-related enzymes and changes of intermediate metabolites of glucose metabolite pool. The protein levels of hypoxia inducible factor 1α (HIF-1α) in primary tumors and circulating tumor cells of CRC patients were detected by immunohistochemistry and immunofluorescence. Stable HIF1A knockdown in cell models was established with a lentiviral system. The influence of both HIF1A gene knockdown and pharmacological inhibition on 5-FU resistance in CRC was evaluated in cell models in vivo and in vitro. Results The abnormality of glucose metabolism in 5-FU-resistant CRC were described in detail. The enhanced glycolysis and pentose phosphate pathway in CRC were associated with increased HIF-1α expression. HIF-1α-induced glucose metabolic reprogramming imparted 5-FU resistance in CRC. HIF-1α showed enhanced expression in 5-FU-resistant CRC cell lines and clinical specimens, and increased HIF-1α levels were associated with failure of fluorouracil analog-based chemotherapy in CRC patients and poor survival. Upregulation of HIF-1α in 5-FU-resistant CRC occurred through non-oxygen-dependent mechanisms of reactive oxygen species-mediated activation of PI3K/Akt signaling and aberrant activation of β-catenin in the nucleus. Both HIF-1α gene knock-down and pharmacological inhibition restored the sensitivity of CRC to 5-FU. Conclusions HIF-1α is a potential biomarker for 5-FU-resistant CRC, and targeting HIF-1a in combination with 5-FU may represent an effective therapeutic strategy in 5-FU-resistant CRC.

Glucose lowering agents that reduce the risk of major adverse cardiovascular events (MACE) would be considered a major advance. The reduction of cardiovascular risk by sodium-glucose cotransporter 2 inhibitors (SGLT-2i) has been confirmed by some large-scale randomized controlled studies (RCTs) and systematic reviews of RCTs, but exact indicators of cardiovascular risk remained controversial. Whether consistent results can be obtained in clinical practice is unclear. Therefore, in this meta-analysis, we analyzed the real-world effect of SGLT-2i on cardiovascular outcome in patients with type 2 diabetes mellitus (T2DM). We did a real-world systematic review and meta-analysis of cardiovascular outcome of SGLT-2i in patients with T2DM. We searched PubMed and Embase for trials published up to October 23, 2019. Data search and extraction were completed with a standardized data form and any discrepancies were resolved by consensus. The primary outcome was MACE and all-cause mortality (ACM). Secondary outcomes were hospitalization for heart failure (HHF), atrial fibrillation (AF), myocardial infarction (MI), stroke, cardiovascular mortality (CVM), unstable angina (UA), heart failure (HF). Odds ratio (OR) with 95% CIs were pooled across trials, and cardiovascular outcomes were stratified by baseline incidence of cardiovascular disease (CVD), usage rate of cardiovascular benefit drug, follow-up period and region. Fourteen trials enrolling 3,157,259 patients were included. SGLT-2i reduced MACE (OR, 0.71; 95% CI 0.67,0.75, P<0.001) and ACM (OR, 0.53; 95% CI 0.49,0.57, P<0.001) compared to other glucose lowering drugs (oGLD). Compared with oGLD, SGLT-2i had significantly lowered the risk of HHF (OR, 0.56; 95% CI 0.46,0.68, P<0.001), MI (OR, 0.77; 95% CI 0.73,0.81, P<0.001), stroke (OR, 0.75; 95% CI 0.72,0.78, P<0.001), CVM (OR, 0.58; 95% CI 0.49,0.69, P<0.001) and HF (OR, 0.56; 95% CI 0.48,0.67, P<0.001), but there was no benefit from UA or AF. SGLT-2i significantly reduced the risk of severe hypoglycemia (OR, 0.78; 95% CI 0.69,0.90, P<0.001) and lower limb amputation (OR, 0.83; 95% CI 0.71,0.98, P<0.001), but it may increase the risk of diabetic ketoacidosis. Subgroup analysis showed SGLT-2i reduced the risk of MACE, ACM, HHF, MI, stroke, CVM and HF with a similar benefit regardless of the incidence of CVD was (20-30)% or < 15%, (15-30)% or <15% have been treated with GLP-1 receptor agonists (GLP-1RA), >80% or <70% have been treated with statins or both GLP-1RA and statins. SGLT-2i reduced the risk of ACM in low-risk population (P<0.001). No inconsistencies were found when stratification was performed at 1 or (3-4) years of follow-up except for BKA followed up for 1 year. SGLT-2i showed similar cardiovascular benefits in the Nordic countries, Asia and the United States. The predominant impact of SGLT-2i is on cardiovascular outcome driven predominantly by reduction in MACE, ACM, HHF, MI, stroke, CVM, HF, but not UA or AF. SGLT-2i has robust benefits on reducing MACE, ACM, HHF, MI, stroke, CVM and HF regardless of a history of usage rate of GLP-1RA and/or statins and /or metformin. SGLT-2i does not increase the risk of severe hypoglycemia and lower limb amputation.

Background Recurrence of intrahepatic cholangiocarcinoma (ICC) after curative resection is common. Objective The aim of this study was to investigate the patterns, timing and risk factors of disease recurrence after curative-intent resection for ICC. Methods Patients undergoing curative resection for ICC were identified from a multi-institutional database. Data on clinicopathological and initial operation information, timing and first sites of recurrence, recurrence management, and long-term outcomes were analyzed. Results A total of 920 patients were included. With a median follow-up of 38 months, 607 patients (66.0%) experienced ICC recurrence. In the cohort, 145 patients (23.9%) recurred at the surgical margin, 178 (29.3%) recurred within the liver away from the surgical margin, 90 (14.8%) recurred at extraheptatic sites, and 194 (32.0%) developed both intrahepatic and extrahepatic recurrence. Intrahepatic margin recurrence (median 6.0 m) and extrahepatic-only recurrence (median 8.0 m) tended to occur early, while intrahepatic recurrence at non-margin sites occurred later (median 14.0 m; p  < 0.05). On multivariate analysis, surgical margin < 10 mm was associated with increased margin recurrence (hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.11–2.60; p  = 0.014), whereas female sex (HR 2.12, 95% CI 1.40–3.22; p  < 0.001) and liver cirrhosis (HR 2.36, 95% CI 1.31–4.25; p  = 0.004) were both associated with an increased risk of intrahepatic recurrence at other sites. Median survival after recurrence was better among patients who underwent repeat curative-intent surgery (48.7 months) versus other treatments (9.7 months) [ p  < 0.001]. Conclusions Different recurrence patterns and timing of recurrence suggest biological heterogeneity of ICC tumor recurrence. Understanding timing and risk factors associated with different types of recurrence can hopefully inform discussions around adjuvant therapy, surveillance, and treatment of recurrent disease.

Anomalous left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital anomaly with exceptional survival into adulthood. We present a 66-year-old woman with chest and back pain in whom ALCAPA was diagnosed using coronary computed tomography angiography (CCTA) with curved planar reformation and cinematic volume rendering technique (cVRT). Photorealistic three-dimensional reconstruction provided complementary three-dimensional visualization that may facilitate anatomic understanding and communication of the anomalous origin. Conservative management was adopted given the patient's age and well-developed collateral circulation. This case underscores the value of advanced CCTA visualization in diagnosing rare coronary anomalies in elderly patients.

Influenza A virus (IAV) infection is a significant risk factor for invasive pulmonary aspergillosis, particularly in severe influenza patients, where the incidence and mortality of influenza‐associated pulmonary aspergillosis (IAPA) are markedly elevated. IAPA creates a state of acute acquired immunodeficiency in patients who were previously healthy, challenging the traditional view of fungal disease as a condition restricted to the classically immunocompromised. Drawing on emerging evidence, this review maps out the pathogenesis of IAPA as a specific, sequential cascade of host failure. The process begins with barrier disruption, where the virus induces Type III interferons and interleukin‐1β (IL‐1β) signalling to arrest epithelial repair and compromise tissue integrity. This is followed by recognition failure, characterized by the specific depletion of innate B1a lymphocytes and natural IgG antibodies, rendering fungal spores undetectable to phagocytes. The final stage is effector paralysis, where a cytokine storm drives neutrophil oxidative shutdown and transcriptional suppression. Ultimately, IAPA is a disorder of functional dissociation: The body is hyper‐inflamed, yet its antimicrobial metabolism is paralysed. Understanding this framework reveals precise therapeutic windows for host‐directed interventions, such as timed IL‐1 receptor blockade or nebulized immunostimulants, which can restore immune competence and improve clinical outcomes. From barrier dysfunction to metabolic paralysis: IAPA progression is characterized by a functional dissociation: the host experiences hyper‐inflammatory cytokine storms (IL‐1β, IFN‐λ) while simultaneously suffering from antimicrobial metabolic paralysis (loss of ROS and recognition). This creates a specific window for host‐directed therapies, including IL‐1 receptor blockade to restore neutrophil function and immunostimulants to re‐engage host defences.

IntroductionEffective compression haemostasis is essential after transradial coronary procedures. However, evidence directly comparing different haemostatic materials remains limited. This study aims to compare and rank the efficacy and safety of different haemostatic materials used as adjuncts to compression after transradial coronary angiography and/or percutaneous coronary intervention, and to explore whether compression modality modifies their relative effects.Methods and analysisWe will systematically search nine databases (Cochrane Library, Embase, PubMed, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Wanfang Data, VIP Database and Cumulative Index to Nursing and Allied Health Literature) for randomized controlled trials on post-transradial access (TRA) compression haemostasis with different haemostatic materials, from database inception to December 2025. Supplementary searches will be conducted in ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, academic search engines and reference lists of included studies. Two reviewers will independently perform study selection, data extraction and risk of bias assessment using the Cochrane Risk of Bias V.2 tool. A network meta-analysis will be conducted within a frequentist framework using Stata V.16.0. Heterogeneity, inconsistency, small-study effects, evidence quality, sensitivity and the assumption of transitivity will be assessed. Subgroup analyses will be performed according to compression modality (manual vs mechanical) and, where data permit, other prespecified study-level characteristics that may modify treatment effects.Ethics and disseminationAs this study is a systematic review and network meta-analysis based on published data, ethical approval is not required. The results will be disseminated through publication in a peer-reviewed journal and presentation at academic conferences.PROSPERO registration numberCRD420251250499.

Systemic air embolism (SAE) is a rare but potentially catastrophic complication of computed tomography (CT)-guided percutaneous lung procedures, with reported incidence ranging from 0.02% to 0.4%. Despite its low frequency, SAE can result in severe neurological impairment or death, yet the factors that determine divergent clinical outcomes remain poorly characterized. We present two cases with contrasting neurological sequelae to elucidate the imaging spectrum and potential prognostic determinants of SAE. In Case 1, a 60-year-old man developed SAE after CT-guided fiducial marker placement for a 7-mm pure ground-glass nodule and achieved full clinical recovery. In Case 2, a 68-year-old man developed SAE following CT-guided percutaneous transthoracic needle biopsy of a 16-mm solid nodule and progressed to persistent semi-comatose status with cortical laminar necrosis. These cases illustrate the heterogeneous neurological outcomes of SAE and underscore the critical role of early post-procedure CT in detecting intravascular gas. Several factors may contribute to divergent outcomes, including procedural technique, nodule characteristics, and the extent and distribution of intracardiac and intracranial air. The absence of hyperbaric oxygen therapy in both patients further highlights the importance of prompt recognition and supportive management. Radiologists and interventionalists must maintain vigilant post-procedural surveillance to facilitate timely diagnosis and optimize patient outcomes.

Primary pulmonary artery sarcoma (PPAS) is a mesenchymal tumor originating from the pulmonary artery, accounting for approximately 0.001-0.003% of all sarcomas. The early clinical symptoms are atypical, and diagnosis is often delayed, making the management of this disease challenging. The widespread availability of multidetector computed tomography (MDCT), F-fluorodeoxyglucose positron emission tomography/computed tomography ( F-FDG PET/CT), and high-resolution echocardiography has significantly improved the diagnostic capability for PPAS. We herein report a 74-year-old female patient who presented with a 3-week history of exertional dyspnea without an apparent trigger. She had received anti-inflammatory therapy at another hospital for one week. Five days before admission, she experienced right-sided chest pain without apparent cause, which was respiratory-related. On the day of admission, laboratory tests revealed a slight elevation in D-dimer levels. Echocardiography showed an irregular, moderately echogenic mass at the origin of the right pulmonary artery. Enhanced computed tomography (CT) of the chest revealed a filling defect in the right pulmonary artery accompanied by bilateral pleural effusion. The patient was given heparin anticoagulation therapy. To confirm the nature of these lesions, a PET/CT scan was conducted five days after admission, which indicated hypermetabolism in the right pulmonary artery, suggesting primary pulmonary artery sarcoma. Due to the poor efficacy of anticoagulation therapy, the patient continued to experience breath-holding after physical activity. Subsequently, catheter-guided interventional angiography was carried out for pulmonary artery thrombectomy and biopsy, and histopathological examination revealed pulmonary artery sarcoma. Given the patient's respiratory failure and heart failure, as well as the uncertain efficacy of radiotherapy and chemotherapy, interventional pulmonary artery thrombectomy alleviated the chest pain. Currently, the patient's overall condition is stable.

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease driven by immune dysregulation and epidermal barrier dysfunction. Current therapeutic options are often limited by safety concerns or suboptimal tolerability. In this study, we isolated and structurally characterized GRB-H—a λ-carrageenan-enriched sulfated hybrid galactan from the marine red alga Gigartina radula—as a complex polysaccharide containing κ-, ι-, μ-, ν-, and λ-carrageenan structural units, and systematically evaluated its anti-AD potential using both in vitro and in vivo models. In vitro, GRB-H significantly suppressed lipopolysaccharide (LPS)-induced nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in RAW 264.7 macrophages, and reduced 2,4-dinitrochlorobenzene (DNCB)-evoked TNF-α and IL-1β expression in HaCaT keratinocytes. In a DNCB-induced murine model of AD, topical application of GRB-H markedly ameliorated skin inflammation, epidermal hyperplasia, and dermal immune cell infiltration. GRB-H treatment lowered total serum immunoglobulin E (IgE) levels, restored the imbalanced Th1/Th2 cell ratio in the spleen, and downregulated the mRNA expression of key inflammatory cytokines—including TNF-α, IL-4, IL-5, IL-31, and interferon-γ (IFN-γ)—in lesional skin. Collectively, these findings demonstrate that GRB-H alleviates AD symptoms through coordinated local anti-inflammatory and systemic immunomodulatory actions, highlighting its promise as a marine-derived candidate for the topical management of AD.

We present a 33‐year‐old diver who developed decompression sickness after a 26‐m dive. Initially improving with hyperbaric oxygen therapy, his lower abdomen rash unexpectedly progressed to diffuse cutis marmorata. He required multiple additional recompression sessions for complete resolution, highlighting the need for close monitoring. A 33‐year‐old diver who developed decompression sickness with an initial rash that improved after hyperbaric oxygen therapy but shortly after relapsed into diffuse cutis marmorata. The patient required multiple additional recompression sessions to achieve complete recovery. This case illustrates that the clinical progression of cutis marmorata following initial treatment can signal incomplete disease resolution.