Pheochromocytomas (PCCs) and paragangliomas (PGLs) are the most heritable endocrine tumors. Genetic testing for 12 driver susceptibility genes is recommended in all PCC and PGL cases. However, detection of somatic mutations in PCC and PGL remains unrealizable for genetic diagnosis and preoperative assessment. We compared the serum exosomal DNA and tumor tissue DNA from patients or mice with PCC or PGL and found double-stranded DNA (dsDNA) fragments in the circulating exosomes of patients with PCC or PGL. Exosomal dsDNA shared the same mutations in the susceptibility genes with that of the parent tumor cells. Moreover, our research showed that serum-derived exosomal dsDNA in PCC and PGL was highly consistent with the paired tumor genome. Our findings provide the first definitive evidence of the presence of exosomal dsDNA that can be used as a noninvasive genetic marker in one of the most effective somatic mutation screens for the diagnosis and preoperative assessment of PCCs and PGLs.

Redox homeostasis refers to the dynamic equilibrium between oxidant and reducing agent in the body which plays a crucial role in maintaining normal physiological activities of the body. The imbalance of redox homeostasis can lead to the development of various human diseases. Lysosomes regulate the degradation of cellular proteins and play an important role in influencing cell function and fate, and lysosomal dysfunction is closely associated with the development of various diseases. In addition, several studies have shown that redox homeostasis plays a direct or indirect role in regulating lysosomes. Therefore, this paper systematically reviews the role and mechanisms of redox homeostasis in the regulation of lysosomal function. Therapeutic strategies based on the regulation of redox exerted to disrupt or restore lysosomal function are further discussed. Uncovering the role of redox in the regulation of lysosomes helps to point new directions for the treatment of many human diseases.

The global annual incidence of brain tumors is approximately seven out of 100,000, accounting for 2% of all tumors. The mortality rate ranks first among children under 12 and 10th among adults. Therefore, the localization and segmentation of brain tumor images constitute an active field of medical research. The traditional manual segmentation method is time-consuming, laborious, and subjective. In addition, the information provided by a single-image modality is often limited and cannot meet the needs of clinical application. Therefore, in this study, we developed a multimodality feature fusion network, MM-UNet, for brain tumor segmentation by adopting a multi-encoder and single-decoder structure. In the proposed network, each encoder independently extracts low-level features from the corresponding imaging modality, and the hybrid attention block strengthens the features. After fusion with the high-level semantic of the decoder path through skip connection, the decoder restores the pixel-level segmentation results. We evaluated the performance of the proposed model on the BraTS 2020 dataset. MM-UNet achieved the mean Dice score of 79.2% and mean Hausdorff distance of 8.466, which is a consistent performance improvement over the U-Net, Attention U-Net, and ResUNet baseline models and demonstrates the effectiveness of the proposed model.

Inducing immunogenic cell death (ICD) can tackle the issue of low immune response levels in tumor immunotherapy. Photodynamic therapy (PDT) uses photosensitizers to generate reactive oxygen species that kill tumor cells, while photothermal therapy (PTT) directly uses heat from photothermal converters to destroy tumor cells. However, these single treatments have their limitations. The development of optical therapy nanodelivery systems, along with the combination of PTT/PDT with chemotherapy and immunotherapy, offers new strategies for tumor immunotherapy. This article explores the application of PDT and PTT mediated by nanodelivery systems in promoting immunogenic cell death in tumor cells. This article explores nano-delivery systems that precisely release photosensitizers to boost efficacy and reduce toxicity. It also discusses their potential for combination therapy through co-delivery, utilizing multimodal strategies to enhance both phototherapy and chemotherapy, thus improving anticancer effectiveness.

High density lipoprotein cholesterol (HDL-C) has been reported as a significant indicator of systemic inflammation. The association underlying HDL-C and persistent organ failure (POF), pancreatic necrosis (PNec) and mortality in acute pancreatitis (AP) has not been evaluated. From 2007 to 2016, consecutive AP patients with admission lipid profiles assessment were included in this study. The association of HDL-C value and other lipids with outcomes was explored with Cox proportional regression models, which were adjusted for confounding factors. 1131 consecutive AP patients were clinically eligible. Overall, 17.9% of the patients developed with POF, 27.1% experienced PNec, and 6.7% died during hospitalization. Lower HDL-C median (<1.06 mmol/L) was identified as an independent prognostic factor of the outcomes. Moreover, there was a positive trend for the association across increasing HDL-C quartiles and POF, PNec and mortality after multivariable analysis (p values were <0.001, <0.001 and 0.043, respectively). The AUC of HDL-C for the outcomes were comparable to that of Ranson score for diagnosing POF (0.778 vs. 0.678; P < 0.001), PNec (0.734 vs. 0.701; P = 0.143) and mortality (0.768 vs. 0.745; P = 0.516). Decreased HDL-C value is an independent risk factor for the incidence of POF, PNec and in-hospital mortality in AP.

Kabuki syndrome (KS) is a rare pediatric congenital disorder with multiple congenital anomalies and intellectual disabilities, which is inherited in an autosomal dominant manner. Mutations in KMT2D and KDM6A have been proven to be the primary cause in most cases of KS. Here we report two Chinese boys with clinical features of KS referred to our hospital for clinical diagnosis. Next-generation sequencing was performed on MiSeq to analyze the genetic mutations in both patients. In both, two novel de novo mutations in KMT2D gene (c.5235delA, p.(A1746Lfs*39) and c.7048G > A, p.(Q2350*)) were detected, both of which were subsequently confirmed by the two-generation pedigree analysis based on Sanger sequencing. A systematic literature review of previously reported mutational spectrum of KMT2D was also conducted. Two novel de novo mutations in KMT2D gene were identified and considered to be pathogenic in both of KS patients. Our data adds information to the growing knowledge on the mutational spectrum of KS.