The future of cancer vaccines against colorectal cancer.

INTRODUCTION: Colorectal cancer (CRC) is the second most lethal malignancy worldwide. Immune checkpoint inhibitors (ICIs) benefit only 15% of patients with mismatch repair-deficient/microsatellite instability (dMMR/MSI) CRC. The majority of patients are not suitable due to insufficient immune infiltration. Cancer vaccines are a potential approach for inducing tumor-specific immunity within the solid tumor microenvironment. AREA COVERED: In this review, we have provided an overview of the current progress in CRC vaccines over the past three years and briefly depict promising directions for further exploration. EXPERT OPINION: Cancer vaccines are certainly a promising field for the antitumor treatment against CRC. Compared to monotherapy, cancer vaccines are more appropriate as adjuvants to standard treatment, especially in combination with ICI blockade, for microsatellite stable patients. Improved vaccine construction requires neoantigens with sufficient immunogenicity, satisfactory HLA-binding affinity, and an ideal delivery platform with perfect lymph node retention and minimal off-target effects. Prophylactic vaccines that potentially prevent CRC carcinogenesis are also worth investigating. The exploration of appropriate biomarkers for cancer vaccines may benefit prognostic prediction analysis and therapeutic response prediction in patients with CRC. Although many challenges remain, CRC vaccines represent an exciting area of research that may become an effective addition to current guidelines.

COVID-19 Rebound After VV116 vs Nirmatrelvir-Ritonavir Treatment: A Randomized Clinical Trial.

Importance: With the widespread use of anti-SARS-CoV-2 drugs, accumulating data have revealed potential viral load rebound after treatment. Objective: To compare COVID-19 rebound after a standard 5-day course of antiviral treatment with VV116 vs nirmatrelvir-ritonavir. Design, Setting, and Participants: This is a single-center, investigator-blinded, randomized clinical trial conducted in Shanghai, China. Adult patients with mild-to-moderate COVID-19 and within 5 days of SARS-CoV-2 infection were enrolled between December 20, 2022, and January 19, 2023, and randomly allocated to receive either VV116 or nirmatrelvir-ritonavir. Interventions: Participants in the VV116 treatment group received oral 600-mg VV116 tablets every 12 hours on day 1 and 300 mg every 12 hours on days 2 through 5. Participants in the nirmatrelvir-ritonavir treatment group received oral nirmatrelvir-ritonavir tablets with 300 mg of nirmatrelvir plus 100 mg of ritonavir every 12 hours for 5 days. Participants were followed up every other day until day 28 and every week until day 60. Main Outcomes and Measures: The primary outcome was viral load rebound (VLR), defined as a half-log increase in viral RNA copies per milliliter compared with treatment completion. Secondary outcomes included a reduction in the cycle threshold value of 1.5 or more, time until VLR, and symptom rebound, defined as an increase of more than 2 points in symptom score compared with treatment completion. The primary outcome and secondary outcomes were analyzed using the full analysis set. Sensitivity analyses were conducted using the per protocol set. Adverse events were analyzed using the safety analysis set. Results: The full analysis set included 345 participants (mean [SD] age, 53.2 [16.8] years; 175 [50.7%] were men) who received VV116 (n = 165) or nirmatrelvir-ritonavir (n = 180). Viral load rebound occurred in 33 patients (20.0%) in the VV116 group and 39 patients (21.7%) in the nirmatrelvir-ritonavir group (P = .70). Symptom rebound occurred in 41 of 160 patients (25.6%) in the VV116 group and 40 of 163 patients (24.5%) in the nirmatrelvir-ritonavir group (P = .82). Viral whole-genome sequencing of 24 rebound cases revealed the same lineage at baseline and at viral load rebound in each case. Conclusions and Relevance: In this randomized clinical trial of patients with mild-to-moderate COVID-19, viral load rebound and symptom rebound were both common after a standard 5-day course of treatment with either VV116 or nirmatrelvir-ritonavir. Prolongation of treatment duration might be investigated to reduce COVID-19 rebound. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2200066811.

Early detection of myocardial involvement by non-contrast T1ρ mapping of cardiac magnetic resonance in type 2 diabetes mellitus.

Objective: This study aims to determine the effectiveness of T1ρ in detecting myocardial fibrosis in type 2 diabetes mellitus (T2DM) patients by comparing with native T1 and extracellular volume (ECV) fraction. Methods: T2DM patients (n = 35) and healthy controls (n = 30) underwent cardiac magnetic resonance. ECV, T1ρ, native T1, and global longitudinal strain (GLS) values were assessed. Diagnostic performance was analyzed using receiver operating curves. Results: The global ECV and T1ρ of T2DM group (ECV = 32.1 ± 3.2%, T1ρ = 51.6 ± 3.8 msec) were significantly higher than those of controls (ECV = 26.2 ± 1.6%, T1ρ = 46.8 ± 2.0 msec) (all P < 0.001), whether there was no significant difference in native T1 between T2DM and controls (P = 0.264). The GLS decreased significantly in T2DM patients compared with controls (-16.5 ± 2.4% vs. -18.3 ± 2.6%, P = 0.015). The T1ρ and native T1 were associated with ECV (Pearson's r = 0.50 and 0.25, respectively, both P < 0.001); the native T1, T1ρ, and ECV were associated with hemoglobin A1c (Pearson's r = 0.41, 0.52, and 0.61, respectively, all P < 0.05); and the ECV was associated with diabetes duration (Pearson's r = 0.41, P = 0.016). The AUC of ECV, T1ρ, GLS, and native T1 were 0.869, 0.810, 0.659, and 0.524, respectively. Conclusion: In T2DM patients, T1ρ may be a new non-contrast cardiac magnetic resonance technique for identifying myocardial diffuse fibrosis, and T1ρ may be more sensitive than native T1 in the detection of myocardial diffuse fibrosis.

Changes in subclinical cardiac abnormalities 1 Year after recovering from COVID-19 in patients without clinical cardiac findings.

Aim: To evaluate the subclinical cardiac involvement in COVID-19 patients without clinical cardiac evidence using cardiac MR imaging. Material and methods: Participants recovered from COVID-19 without cardiac symptoms and no cardiovascular medical history were enrolled in a prospective cohort study. They underwent baseline cardiac MR and follow-up cardiac MR > 300 days after discharge (n = 20). The study also included healthy controls (n = 20). Extracellular volume fraction (ECV), native T1, and 2D strain data were assessed and compared. Results: The ECV values of participants at baseline [30.0% (28.3%-32.5%)] and at follow-up [31.0% (28.0%-32.8%)] were increased compared to the healthy control group [27.0% (25.3%-28.0%)] (both p < 0.001). However, the ECV increase from baseline cardiac MR to follow-up cardiac MR was not significant (p = 0.378). There was a statistically significant difference in global native T1 between baseline [1140 (1108.3-1192.0) ms] and follow-up [1176.0 (1113.0-1206.3) ms] (p = 0.016). However, no native T1 difference was found between the healthy controls [1160.7 (1119.6-1195.4) ms] and the baseline (p = 0.394) or follow-up group (p = 0.168). The global T2 was 41(40-42) ms at follow-up which was within the normal range. In addition, We found a recovery in 2D GLS among COVID-19 participants between baseline and follow-up [-12.4(-11.7 to -14.3)% vs. -17.2(-16.2 to -18.3)%; p＜0.001]. Conclusion: Using cardiac MR myocardial tissue and strain imaging parameters, 35% of people without cardiac symptoms or clinical evidence of myocardial injury still had subclinical myocardial tissue characteristic abnormalities at 300 days, but 2D GLS had recovered.

CircHAS2 activates CCNE2 to promote cell proliferation and sensitizes the response of colorectal cancer to anlotinib.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) are crucial in the targeted treatment of advanced colorectal cancer (CRC). Anlotinib, a multi-target TKI, has previously been demonstrated to offer therapeutic benefits in previous studies. Circular RNAs (circRNAs) have been implicated in CRC progression and their unique structural stability serves as promising biomarkers. The detailed molecular mechanisms and specific biomarkers related to circRNAs in the era of targeted therapies, however, remain obscure. METHODS: The whole transcriptome RNA sequencing and function experiments were conducted to identify candidate anlotinib-regulated circRNAs, whose mechanism was confirmed by molecular biology experiments. CircHAS2 was profiled in a library of patient-derived CRC organoids (n = 22) and patient-derived CRC tumors in mice. Furthermore, a prospective phase II clinical study of 14 advanced CRC patients with anlotinib-based therapy was commenced to verify drug sensitivity (ClinicalTrials.gov identifier: NCT05262335). RESULTS: Anlotinib inhibits tumor growth in vitro and in vivo by downregulating circHAS2. CircHAS2 modulates CCNE2 activation by acting as a sponge for miR-1244, and binding to USP10 to facilitate p53 nuclear export as well as degradation. In parallel, circHAS2 serves as a potent biomarker predictive of anlotinib sensitivity, both in patient-derived organoids and xenograft models. Moreover, the efficacy of anlotinib inclusion into the treatment regimen yields meaningful clinical responses in patients with high levels of circHAS2. Our findings offer a promising targeted strategy for approximately 52.9% of advanced CRC patients who have high circHAS2 levels. CONCLUSIONS: CircHAS2 promotes cell proliferation via the miR-1244/CCNE2 and USP10/p53/CCNE2 bidirectional axes. Patient-derived organoids and xenograft models are employed to validate the sensitivity to anlotinib. Furthermore, our preliminary Phase II clinical study, involving advanced CRC patients treated with anlotinib, confirmed circHAS2 as a potential sensitivity marker.

Lactate modulates RNA splicing to promote CTLA-4 expression in tumor-infiltrating regulatory T cells.

RNA splicing is involved in cancer initiation and progression, but how it influences host antitumor immunity in the metabolically abnormal tumor microenvironment (TME) remains unclear. Here, we demonstrate that lactate modulates Foxp3-dependent RNA splicing to maintain the phenotypic and functional status of tumor-infiltrating regulatory T (Treg) cells via CTLA-4. RNA splicing in Treg cells was correlated with the Treg cell signatures in the TME. Ubiquitin-specific peptidase 39 (USP39), a component of the RNA splicing machinery, maintained RNA-splicing-mediated CTLA-4 expression to control Treg cell function. Mechanistically, lactate promoted USP39-mediated RNA splicing to facilitate CTLA-4 expression in a Foxp3-dependent manner. Moreover, the efficiency of CTLA-4 RNA splicing was increased in tumor-infiltrating Treg cells from patients with colorectal cancer. These findings highlight the immunological relevance of RNA splicing in Treg cells and provide important insights into the environmental mechanism governing CTLA-4 expression in Treg cells.

Comparing Strain Assessment in Compressed Sensing and Conventional Cine MRI.

The aim of this study is to assess the feasibility of compressed sensing (CS) acceleration methods compared to conventional segmented cine (Seg) cardiac magnetic resonance (CMR) for evaluating left ventricular (LV) function and strain by feature tracking (FT). In this prospective study, 45 healthy volunteers underwent CMR imaging used Seg, threefold (CS3), fourfold (CS4), and eightfold (CS8) CS acceleration. Cine images were scored for quality (1-5 scale). LV volumetric and functional parameters and global longitudinal (GLS), circumferential (GCS), and radial strains (GRS) were quantified. LV volumetric and functional parameters exhibited no differences between Seg and all CS cines (all P > 0.05). The strains were similar for Seg, CS3, and CS4 (all P > 0.05). Similarly, no significant differences were observed in GRS and GCS between Seg and CS8 (all P > 0.05), but the global longitudinal strain was significantly lower for CS8 versus Seg (P < 0.001). Image quality declined with CS acceleration, especially in long-axis views with CS8. CS cine MRI at acceleration factor 4 maintained good image quality and accurate measurements of LV function and strain, although there was a slight reduction in the quality of long-axis images and GLS with CS8. CS acceleration up to a factor of 4 enabled fast CMR evaluations, making it suitable for clinical use.

Circular RNAs: Potential biomarkers and therapeutic targets for autoimmune diseases.

The outcomes and prognosis of autoimmune diseases depend on early diagnosis and effective treatments. However, symptoms of early autoimmune diseases are often remarkably similar to many inflammatory diseases, leading to difficulty in precise diagnosis. Circular RNAs (circRNAs) belong to a novel class of endogenous RNAs, functioning as microRNA (miRNA) sponges or participating in protein coding. It has been shown in many studies that patients with autoimmune diseases have aberrant circRNA expression in liquid biopsy samples (such as plasma, saliva, and urine). Thus, circRNAs are potential biomarkers for the diagnosis and prognosis of autoimmune diseases. Moreover, overexpression and depletion of target circRNAs can be utilized as possible therapeutic approaches for treating autoimmune diseases. In this review, we summarized recent progress in the roles of circRNAs in the pathogenesis of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and type 1 diabetes. We also discussed their potential as biomarkers and therapeutic targets.

Cardiac T1ρ Mapping Values Affected by Age and Sex in a Healthy Chinese Cohort.

BACKGROUND: To facilitate the clinical use of cardiac T1ρ, it is important to understand the impact of age and sex on T1ρ values of the myocardium. PURPOSE: To investigate the impact of age and gender on myocardial T1ρ values. STUDY TYPE: Cross-sectional. POPULATION: Two hundred ten healthy Han Chinese volunteers without cardiovascular risk factors (85 males, mean age 34.4 ± 12.5 years; 125 females, mean age 37.9 ± 14.8 years). FIELD STRENGTH/SEQUENCE: 1.5 T; T1ρ-prepared steady-state free precession (T1ρ mapping) sequence. ASSESSMENT: Basal, mid, and apical short-axis left ventricular T1ρ maps were acquired. T1ρ maps acquired with spin-lock frequencies of 5 and 400 Hz were subtracted to create a myocardial fibrosis index (mFI) map. T1ρ and mFI values across different age decades, sex, and slice locations were compared. STATISTICAL TESTS: Shapiro-Wilk test, Student's t test, Mann-Whitney U test, linear regression analysis, one-way analysis of variance and intraclass correlation coefficient. SIGNIFICANCE: P value <0.05. RESULTS: Women had significantly higher T1ρ and mFI values than men (50.3 ± 2.0 msec vs. 47.7 ± 2.4 msec and 4.7 ± 1.0 msec vs. 4.3 ± 1.1 msec, respectively). Additionally, in males and females combined, there was a significant positive but weak correlation between T1ρ values and age (r = 0.27), while no correlation was observed between the mFI values and age (P = 0.969). DATA CONCLUSION: We report potential reference values for cardiac T1ρ by sex, age distribution, and slice location in a Chinese population. T1ρ was significantly correlated with age and sex, while mFI was only associated with sex. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

Myocardial involvement characteristics by cardiac MR imaging in neurological and non-neurological Wilson disease patients.

OBJECTIVES: To explore the characteristics of myocardial involvement in Wilson Disease (WD) patients by cardiac magnetic resonance (CMR). METHODS: We prospectively included WD patients and age- and sex-matched healthy population. We applied CMR to analyze cardiac function, strain, T1 maps, T2 maps, extracellular volume fraction (ECV) maps, and LGE images. Subgroup analyzes were performed for patients with WD with predominantly neurologic manifestations (WD-neuro +) or only hepatic manifestations (WD-neuro -). RESULTS: Forty-one WD patients (age 27.9 ± 8.0 years) and 40 healthy controls (age 25.4 ± 2.9 years) were included in this study. Compared to controls, the T1, T2, and ECV values were significantly increased in the WD group (T1 1085.1 ± 39.1 vs. 1046.5 ± 33.1 ms, T2 54.2 ± 3.3 ms vs. 51.5 ± 2.6 ms, ECV 31.8 ± 3.6% vs. 24.3 ± 3.7%) (all p < 0.001). LGE analysis revealed that LGE in WD patients was predominantly localized to the right ventricular insertion point and interventricular septum. Furthermore, the WD-neuro + group showed more severe myocardial damage compared to WD-neuro - group. The Unified Wilson Disease Rating Scale score was significantly correlated with ECV (Pearson's r = 0.64, p < 0.001). CONCLUSIONS: CMR could detect early myocardial involvement in WD patients without overt cardiac function dysfunction. Furthermore, characteristics of myocardial involvement were different between WD-neuro + and WD-neuro - , and myocardial involvement might be more severe in WD-neuro + patients. CRITICAL RELEVANCE STATEMENT: Cardiac magnetic resonance enables early detection of myocardial involvement in Wilson disease patients, contributing to the understanding of distinct myocardial characteristics in different subgroups and potentially aiding in the assessment of disease severity. KEY POINTS: • CMR detects WD myocardial involvement with increased T1, T2, ECV. • WD-neuro + patients show more severe myocardial damage and correlation with ECV. • Differences of myocardial characteristics exist between WD-neuro + and WD-neuro - patients.

A copper-platinum nanoplatform for synergistic photothermal and chemodynamic tumor therapy via ROS outburst and GSH exhaustion.

A multifunctional nanoplatform is obtained by modifying copper hexacyanoferrate (Cu-HCF) nanozyme with hyaluronic acid (HA) and further loading platinum (Pt) nanoparticles. This Cu-HCF-HA@Pt platform shows peroxidase-like and glutathione oxidase-like dual-enzyme catalytic activities and photothermal properties, enabling synergistic chemodynamic and photothermal tumor therapy. HA binds to the CD44 receptor, which is highly expressed on the exterior surface of tumor cells, endowing the nanoplatform with tumor specificity. Cu-HCF-HA@Pt catalyzes the decomposition of H2O2 to produce abundant hydroxyl radicals within tumor cells, increasing intracellular oxidative stress levels and inducing tumor cell apoptosis. Meanwhile, Cu-HCF-HA@Pt catalyzes the conversion of intracellular reduced glutathione (GSH) to oxidized glutathione, resulting in GSH exhaustion. The conversion of CuII to CuI in Cu-HCF via a Fenton-like reaction can improve the peroxidase-like property of Cu-HCF-HA@Pt. After the probe is targeted to the tumor site, irradiation by an 808 nm near-infrared laser causes local heating and brings about photothermal tumor apoptosis when reaching 45 °C. The prepared Cu-HCF-HA@Pt combines nanozyme-catalyzed therapy with photothermal therapy to induce apoptosis in tumor cells.

Vaccarin alleviates cisplatin-induced acute kidney injury via decreasing NOX4-derived ROS.

Cisplatin is a chemotherapeutant widely used in treating solid tumors, with the common side effect of acute kidney injury (AKI). Developing effective useful agent for preventing or treating cisplatin-induced AKI is of great importance. In this study, we investigate the protective effect of vaccarin, a chemical entity of flavonoid glycoside, against cisplatin-induced AKI. Cisplatin-treated C57BL/6J mice and human kidney-2 (HK-2) cells were used as the model of cisplatin-induced AKI. The levels of blood urea nitrogen (BUN) and creatine (Cr) levels and periodic acid-Schiff staining (PAS) scores decreased when vaccarin was administrated. Vaccarin had no impact on renal platinum accumulation, which was detected by the ICP-MS 6 h after cisplatin injection. Moreover, vaccarin can significantly alleviate the product of reactive oxygen species and the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) in cisplatin-induced AKI, both in vivo and in vitro. In addition, vaccarin decreased the receptor-interacting protein kinase 1 (RIPK1) related programmed necrosis (necroptosis), cell apoptosis (shown by the protein levels of cleaved-caspase3 and flow cytometry) and inflammation (shown by the decreased levels of NLRP3, p-P65 and the mRNA of several inflammatory factors). NOX4 inhibitor GLX351322 (GLX) and NOX4 kowndown by siRNA have equivalent protective effect of vaccarin in vitro. When vaccarin was administered together with GLX or NOX4 siRNA, this protective effect of vaccarin did not further increase, as indicating by the index of oxidative stress, cell viability, necroptosis and apoptosis. In conclusion, vaccarin can alleviate cisplatin-induced AKI via inhibiting NOX4.

Clinical status and future prospects of single-incision robotic-assisted surgery: a review.

Since the advent of conventional multiport laparoscopic surgery, the prosperity of minimally invasive surgery has been thriving on the advancement of endoscopic techniques. Cosmetic superiority, recovery benefits, and noninferior surgical outcomes weigh single-incision laparoscopic surgery as a promising modality. Although there are surgical challenges posed by steep learning curve and technological difficulties, such as instruments collision, triangulation loss and limited retraction, the establishment of robotic surgical platform as a solution to all is inspiring. Furthermore, with enhanced instrument maneuverability and stability, robotic ergonomic innovations adopt the advantages of single-incision laparoscopic surgery and surmount its recognized barriers by introducing a novel combination, single-incision robotic-assisted surgery. As was gradually diffused in general surgery and other specialties, single-incision robotic-assisted surgery manifests privileges in noninferior clinical outcomes an satisfactory cosmetic effect among strictly selected patients, and has the potential of a preferable surgical option for minimally invasive surgery.

Licochalcone A Induces Ferroptosis in Hepatocellular Carcinoma via Reactive Oxygen Species Activated by the SLC7A11/GPX4 Pathway.

Liver cancer is a common malignant tumor, and its incidence is increasing yearly. Millions of people suffer from liver cancer annually, which has a serious impact on global public health security. Licochalcone A (Lico A), an important component of the traditional Chinese herb licorice, is a natural small molecule drug with multiple pharmacological activities. In this study, we evaluated the inhibitory effects of Lico A on hepatocellular carcinoma cell lines (HepG2 and Huh-7), and explored the inhibitory mechanism of Lico A on hepatocellular carcinoma. First, we evaluated the inhibitory effects of Lico A on hepatocellular carcinoma, and showed that Lico A significantly inhibited and killed HepG2 and Huh-7 cells in vivo and in vitro. Transcriptomic analysis showed that Lico A inhibited the expression of solute carrier family 7 member 11 (SLC7A11), which induced ferroptosis. We confirmed through in vivo and in vitro experiments that Lico A promoted ferroptosis in hepatocellular carcinoma cells by downregulating SLC7A11 expression, thereby inhibiting the glutathione (GSH)-glutathione peroxidase 4 (GPX4) pathway and inducing activation of reactive oxygen species (ROS). In this study, we suggest that Lico A is a potential SLC7A11 inhibitor that induces ferroptotic death in hepatocellular carcinoma cells, thereby providing a theoretical basis for the development of natural small molecule drugs against hepatocellular carcinoma.

USP47 inhibits m6A-dependent c-Myc translation to maintain regulatory T cell metabolic and functional homeostasis.

The functional integrity of Tregs is interwoven with cellular metabolism; however, the mechanisms governing Treg metabolic programs remain elusive. Here, we identified that the deubiquitinase USP47 inhibited c-Myc translation mediated by the RNA N6-methyladenosine (m6A) reader YTHDF1 to maintain Treg metabolic and functional homeostasis. USP47 positively correlated with the tumor-infiltrating Treg signature in samples from patients with colorectal cancer and gastric cancer. USP47 ablation compromised Treg homeostasis and function in vivo, resulting in the development of inflammatory disorders, and boosted antitumor immune responses. USP47 deficiency in Tregs triggered the accumulation of the c-Myc protein and in turn exacerbated hyperglycolysis. Mechanistically, USP47 prevented YTHDF1 ubiquitination to attenuate the association of YTHDF1 with translation initiation machinery, thereby decreasing m6A-based c-Myc translation efficiency. Our findings reveal that USP47 directs m6A-dependent metabolic programs to orchestrate Treg homeostasis and suggest novel approaches for selective immune modulation in cancer and autoimmune diseases by targeting of USP47.

Dietary fructose-mediated adipocyte metabolism drives antitumor CD8+ T cell responses.

Fructose consumption is associated with tumor growth and metastasis in mice, yet its impact on antitumor immune responses remains unclear. Here, we show that dietary fructose modulates adipocyte metabolism to enhance antitumor CD8+ T cell immune responses and control tumor growth. Transcriptional profiling of tumor-infiltrating CD8+ T cells reveals that dietary fructose mediates attenuated transition of CD8+ T cells to terminal exhaustion, leading to a superior antitumor efficacy. High-fructose feeding initiates adipocyte-derived leptin production in an mTORC1-dependent manner, thereby triggering leptin-boosted antitumor CD8+ T cell responses. Importantly, high plasma leptin levels are correlated with elevated plasma fructose concentrations and improved antitumor CD8+ T cell responses in patients with lung cancer. Our study characterizes a critical role for dietary fructose in shaping adipocyte metabolism to prime antitumor CD8+ T cell responses and highlights that the fructose-leptin axis may be harnessed for cancer immunotherapy.

Clinical manifestations and MRI features of Danon disease: a case series.

BACKGROUND: Danon disease (DD) is an exceptionally uncommon X-linked dominant lysosomal glycogen storage disorder characterized by pronounced ventricular hypertrophy and cardiac insufficiency. The timely identification of cardiac impairment in individuals with DD holds significant clinical importance. CASE PRESENTATION: We present a case of Danon Disease in a three-generation pedigree from Anhui Province, China. Clinical features and laboratory data were collected and analyzed for a 16-year-old male proband (III-1) and two affected female family members (II-2 and II-3). The proband exhibited Wolf-Parkinson-White syndrome, hypertrophic cardiomyopathy, abnormal cognitive function, and muscle weakness. Gene sequencing confirmed a mutation (c.963G > A) in the LAMP-2 gene. CONCLUSION: Patients with DD may present both dilated and hypertrophic cardiomyopathy. Comprehensive myocardial tissue characterization by MRI plays a key role in the diagnosis of the disease.