Establishment of iPS cell line (KLRMMEi003-A) from a patient with Usher syndrome due to USH2A mutation.

We generated an induced pluripotent stem (iPS) cell line by reprogramming peripheral blood mononuclear cells of a patient with Usher syndrome type II carrying USH2A gene mutation (c.8559-2A > G). The iPS cell line with confirmed patient-specific point mutation exhibited typical iPS cell characteristics and maintained a normal karyotype. It can be used as 2D and 3D models to investigate the underlying pathogenic mechanism and lay a solid foundation for future personalized therapy.

Retinal organoids and microfluidic chip-based approaches to explore the retinitis pigmentosa with USH2A mutations.

Retinitis pigmentosa (RP) is a leading cause of vision impairment and blindness worldwide, with limited medical treatment options. USH2A mutations are one of the most common causes of non-syndromic RP. In this study, we developed retinal organoids (ROs) and retinal pigment epithelium (RPE) cells from induced pluripotent stem cells (iPSCs) of RP patient to establish a sustainable in vitro RP disease model. RT-qPCR, western blot, and immunofluorescent staining assessments showed that USH2A mutations induced apoptosis of iPSCs and ROs, and deficiency of the extracellular matrix (ECM) components. Transcriptomics and proteomics findings suggested that abnormal ECM-receptor interactions could result in apoptosis of ROs with USH2A mutations via the PI3K-Akt pathway. To optimize the culture conditions of ROs, we fabricated a microfluidic chip to co-culture the ROs with RPE cells. Our results showed that this perfusion system could efficiently improve the survival rate of ROs. Further, ECM components such as laminin and collagen IV of ROs in the RP group were upregulated compared with those maintained in static culture. These findings illustrate the potential of microfluidic chip combined with ROs technology in disease modelling for RP.

Predictive value of baseline metabolic tumor volume for non-small-cell lung cancer patients treated with immune checkpoint inhibitors: A meta-analysis.

Background: Immune checkpoint inhibitors (ICIs) have emerged as a promising treatment option for advanced non-small-cell lung cancer (NSCLC) patients, highlighting the need for biomarkers to identify responders and predict the outcome of ICIs. The purpose of this study was to evaluate the predictive value of baseline standardized uptake value (SUV), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) derived from 18F-FDG-PET/CT in advanced NSCLC patients receiving ICIs. Methods: PubMed and Web of Science databases were searched from January 1st, 2011 to July 18th, 2022, utilizing the search terms "non-small-cell lung cancer", "PET/CT", "standardized uptake value", "metabolic tumor volume", " total lesion glycolysis", and "immune checkpoint inhibitors". Studies that analyzed the association between PET/CT parameters and objective response, immune-related adverse events (irAEs) and prognosis of NSCLC patients treated with ICIs were included. We extracted the hazard ratio (HR) with a 95% confidence interval (CI) for progression-free survival (PFS) and overall survival (OS). We performed a meta-analysis of HR using Review Manager v.5.4.1. Results: Sixteen studies were included for review and thirteen for meta-analysis covering 770 patients. As for objective response and irAEs after ICIs, more studies with consistent assessment methods are needed to determine their relationship with MTV. In the meta-analysis, low SUVmax corresponded to poor PFS with a pooled HR of 0.74 (95% CI, 0.57-0.96, P=0.02). And a high level of baseline MTV level was related to shorter PFS (HR=1.45, 95% CI, 1.11-1.89, P<0.01) and OS (HR, 2.72; 95% CI, 1.97-3.73, P<0.01) especially when the cut-off value was set between 50-100 cm3. SUVmean and TLG were not associated with the prognosis of NSCLC patients receiving ICIs. Conclusions: High level of baseline MTV corresponded to shorter PFS and OS, especially when the cut-off value was set between 50-100 cm3. MTV is a potential predictive value for the outcome of ICIs in NSCLC patients.

Establishment of iPS cell line (KLRMMEi002-A) by reprogramming peripheral blood mononuclear cells from a patient with USH2A-associated Usher syndrome.

USH type 2 (USH2) is an autosomal recessive disorder that is characterized by inherited retinopathies and sensorineural hearing loss. USH type 2 (USH2) is frequently caused by USH2A mutations, which account for 74-90% of USH2 cases. We used peripheral blood mononuclear cells (PBMCs) from a USH2 patient with a USH2A gene mutation (c.8559-2A > G) to create an induced pluripotent stem (iPS) cell line. The patient-specific iPS cell line with the specific point mutation exhibited typical iPS cell characteristics, and it can be used as a model to investigate the pathogenic mechanisms underlying USH2A-associated retinal degeneration and sensorineural hearing loss.