The aggressive nature and poor prognosis of lung cancer led us to explore the mechanisms driving disease progression. Utilizing our invasive cell-based model, we identified methylthioadenosine phosphorylase (MTAP) and confirmed its suppressive effects on tumorigenesis and metastasis. Patients with low MTAP expression display worse overall and progression-free survival. Mechanistically, accumulation of methylthioadenosine substrate in MTAP-deficient cells reduce the level of protein arginine methyltransferase 5 (PRMT5)-mediated symmetric dimethylarginine (sDMA) modification on proteins. We identify vimentin as a dimethyl-protein whose dimethylation levels drop in response to MTAP deficiency. The sDMA modification on vimentin reduces its protein abundance but trivially affects its filamentous structure. In MTAP-deficient cells, lower sDMA modification prevents ubiquitination-mediated vimentin degradation, thereby stabilizing vimentin and contributing to cell invasion. MTAP and PRMT5 negatively correlate with vimentin in lung cancer samples. Taken together, we propose a mechanism for metastasis involving vimentin post-translational regulation.

The identification of early distant metastases (DM) in patients with newly diagnosed, previously untreated nasopharyngeal carcinoma (NPC) plays an important role in selecting the most appropriate treatment approach. Here, we sought to investigate the predictive value of distinct MRI parameters for the detection of early DM.Between November 2010 and June 2011, a total of 51 newly diagnosed NPC patients were included. All of the study participants were followed until December 2014 at a single institution after completion of therapy. DM was defined as early when they were detected on pretreatment FDG-PET scans or within 6 months after initial diagnosis. The following parameters were tested for their ability to predict early DM: pretreatment FDG-PET standardized uptake value (SUV), MRI-derived AJCC tumor staging, tumor volume, and dynamic contrast-enhanced (DCE) values. The DCE-derived ve was defined as the volume fraction of the extravascular, extracellular space.Compared with patients without early DM, patients with early DM had higher SUV, tumor volume, DCE mean (median) ve, ve skewness, ve kurtosis, and the largest mean ve selected among sequential slices (P < 0.05). No differences were identified when early DM were defined only according to the results of pretreatment FDG-PET. Among different quantitative DCE parameters, the mean ve had the highest area under curve (AUC, 0.765). However, the AUCs of SUV, tumor volume, mean ve, ve skewness, ve kurtosis, or the largest mean ve selected among the sequential slices did not differ significantly from one another (P = 0.82).Taken together, our results suggest that DCE-derived ve may be a useful parameter in combination with SUV and tumor volume for predicting early DM. Dynamic contrast-enhanced MRI may be complementary to FDG-PET for selecting the most appropriate treatment approach in NPC patients.

This article - Recommendations and Guidelines of Integrative Medicine (IM) for COVID-19 Care - was one of the outcomes from an Asia-Pacific Economic Cooperation (APEC) Project (Integrative Medicine (IM) and COVID -19 Care) during the time between May 2022 and March 2023. With the efforts from care providers, researchers, health policy makers and healthcare administrative leaders among APEC economies, the purpose of this file was to provide comprehensive IM systems for COVID-19 care as recommendations and suggestive guidelines including care methods, tools, procedures, symptom conditions and targets selections, and points need to be considered during care applications. All cited COVID-19 care practices have confirmed their efficacy and usefulness either used alone or combined with conventional medicine. This article provides current useful medical information on IM for COVID-19 care which could benefit APEC economies and world health communities on their healthcare system.

PURPOSE: To describe the clinical, electrophysiological and genetic spectrum of inherited retinal diseases associated with variants in the PRPH2 gene. METHODS: A total of 241 patients from 168 families across 15 sites in 9 countries with pathogenic or likely pathogenic variants in PRPH2 were included. Records were reviewed for age at symptom onset, visual acuity, full-field ERG, fundus colour photography, fundus autofluorescence (FAF), and SD-OCT. Images were graded into six phenotypes. Statistical analyses were performed to determine genotype-phenotype correlations. RESULTS: The median age at symptom onset was 40 years (range, 4-78 years). FAF phenotypes included normal (5%), butterfly pattern dystrophy, or vitelliform macular dystrophy (11%), central areolar choroidal dystrophy (28%), pseudo-Stargardt pattern dystrophy (41%), and retinitis pigmentosa (25%). Symptom onset was earlier in retinitis pigmentosa as compared with pseudo-Stargardt pattern dystrophy (34 vs 44 years; P = 0.004). The median visual acuity was 0.18 logMAR (interquartile range, 0-0.54 logMAR) and 0.18 logMAR (interquartile range 0-0.42 logMAR) in the right and left eyes, respectively. ERG showed a significantly reduced amplitude across all components (P < 0.001) and a peak time delay in the light-adapted 30-Hz flicker and single-flash b-wave (P < 0.001). Twenty-two variants were novel. The central areolar choroidal dystrophy phenotype was associated with 13 missense variants. The remaining variants showed marked phenotypic variability. CONCLUSIONS: We described six distinct FAF phenotypes associated with variants in the PRPH2 gene. One FAF phenotype may have multiple ERG phenotypes, demonstrating a discordance between structure and function. Given the vast spectrum of PRPH2 disease our findings are useful for future clinical trials.