Self correction of refractive error among young people in rural China: results of cross sectional investigation

Objective To compare outcomes between adjustable spectacles and conventional methods for refraction in young people

The molecular mechanism for inhibiting the growth of nasopharyngeal carcinoma cells using polymethoxyflavonoids purified from pericarp of Citrus reticulata ‘Chachi’ via HSCCC

Polymethoxyflavonoids (PMFs), the main bioactive compounds naturally occurring in the pericarp of Citrus reticulata ‘Chachi’ (CRCP), possess significant antitumor action. However, the action of PMFs in nasopharyngeal carcinoma (NPC) is currently unknown. The present research study was conducted to investigate the inhibitory mechanisms of PMFs from CRCP on NPC growth in vivo and in vitro. In our research, we used high-speed counter-current chromatography (HSCCC) to separate four PMFs (nobiletin (NOB), 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF), tangeretin (TGN), and 5-hydroxy-6,7,8,3′,4′-pentamethoxyflavone (5-HPMF)) from CRCP. CCK-8 assay was used to preliminarily screen cell viability following exposure to the four PMFs. Colony formation, Hoechst-33258 staining, transwell, and wound scratch assays were performed to assess the anti-proliferation, invasion, migration, and apoptosis-inducing effects of HMF on NPC cells. NPC tumors in xenograft tumor transplantation experiments were also established to explore the effect of HMF (100 and 150 mg/kg/day) on NPC. The histopathological changes in the treated rats were observed by H&E staining and Ki-67 detection by immunohistochemical techniques. The expressions of P70S6K, p-P70S6K, S6, p-S6, COX-2, p53, and p-p53 were measured by Western blot. The four PMFs were obtained with high purity (>95.0%). The results of the preliminary screening by CCK-8 assay suggested that HMF had the strongest inhibitory effect on NPC cell growth. The results of the colony formation, Hoechst-33258 staining, transwell, and wound scratch assays indicated that HMF had significant anti-proliferation, invasion, migration, and apoptosis-inducing ability in NPC cells. Moreover, HMF suppressed NPC tumor growth in xenograft tumor transplantation experiments. Further investigation suggested that HMF regulated NPC cells proliferation, apoptosis, migration, and invasion by activating AMPK-dependent signaling pathways. In conclusion, HMF-induced AMPK activation inhibited NPC cell growth, invasion, and metastatic potency by downregulating the activation of the mTOR signaling pathway and COX-2 protein levels, as well as enhancing the p53 phosphorylation level. Our study provides a crucial experimental basis for the clinical treatment of NPC, as well as the development and utilization of PMFs from CRCP

A novel FCTF evaluation and prediction model for food efficacy based on association rule mining

IntroductionFood-components-target-function (FCTF) is an evaluation and prediction model based on association rule mining (ARM) and network interaction analysis, which is an innovative exploration of interdisciplinary integration in the food field.MethodsUsing the components as the basis, the targets and functions are comprehensively explored in various databases and platforms under the guidance of the ARM concept. The focused active components, key targets and preferred efficacy are then analyzed by different interaction calculations. The FCTF model is particularly suitable for preliminary studies of medicinal plants in remote and poor areas.ResultsThe FCTF model of the local medicinal food Laoxianghuang focuses on the efficacy of digestive system cancers and neurological diseases, with key targets ACE, PTGS2, CYP2C19 and corresponding active components citronellal, trans-nerolidol, linalool, geraniol, α-terpineol, cadinene and α-pinene.DiscussionCenturies of traditional experience point to the efficacy of Laoxianghuang in alleviating digestive disorders, and our established FCTF model of Laoxianghuang not only demonstrates this but also extends to its possible adjunctive efficacy in neurological diseases, which deserves later exploration. The FCTF model is based on the main line of components to target and efficacy and optimizes the research level from different dimensions and aspects of interaction analysis, hoping to make some contribution to the future development of the food discipline

Lenalidomide or bortezomib as maintenance treatment remedy the inferior impact of high-risk cytogenetic abnormalities in non-transplant patients with newly diagnosed multiple myeloma: a real-world multi-centered study in China

Maintenance treatment is a pivotal part in the whole process management of multiple myeloma (MM), which further deepens response and improves survival. However, evidence of maintenance in non-transplant MM patients is inadequate in real-world practice. Here, we retrospectively analyzed the efficacy and survival of 375 non-transplant MM patients from 11 centers between 2010 and 2021 in north China. After a median of seven cycles of front-line regimens, there were 141, 79, and 155 patients receiving lenalidomide maintenance (L-MT), bortezomib maintenance (B-MT), or thalidomide maintenance (T-MT), respectively. Patients on L-MT and B-MT had significantly greater proportions of high-risk cytogenetic abnormalities (HRCAs) detected by fluorescence in situ hybridization (FISH), which was defined as 1q21 gain, 17p deletion, adverse immunoglobulin heavy chain (IgH) translocations. Although the progression-free survival (PFS) and overall survival (OS) were comparable among the three groups, L-MT and B-MT remedied the negative impact of HRCAs on survival (PFS of patients with HRCAs vs. patients without HRCAs: L-MT, 26.9 vs. 39.2 months, p=0.19; B-MT, 20.0 vs. 29.7 months, p=0.36; OS not reached in all groups). Patients with HRCAs in the T-MT group presented inferior clinical outcomes compared to standard-risk patients (PFS, 12.1 vs. 22.8 months, p=0.02, HR=1.8, 95% CI 1.0–3.4; OS, 54.9 months vs. NR, p<0.001, HR=3.2, 95% CI 1.5–7.0). Achieving complete response (CR) after induction therapy led to superior PFS compared to other degrees of response, regardless of maintenance medication. Furthermore, maintenance duration over 24 months correlated with favorable survival. Due to the large gap of transplant eligibility in China, optimizing maintenance therapy is important for non-transplant MM patients. In this real-world multi-centered study, our findings suggest that clinicians prefer to prescribe lenalidomide or bortezomib as maintenance therapy in high-risk settings, which are superior to thalidomide in non-transplant MM patients. Achievement of CR and maintenance duration over 2 years are positive factors that influence survival

Meta-analysis Followed by Replication Identifies Loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as Associated with Systemic Lupus Erythematosus in Asians

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic involvement and ethnic differences. Susceptibility genes identified so far only explain a small portion of the genetic heritability of SLE, suggesting that many more loci are yet to be uncovered for this disease. In this study, we performed a meta-analysis of genome-wide association studies on SLE in Chinese Han populations and followed up the findings by replication in four additional Asian cohorts with a total of 5,365 cases and 10,054 corresponding controls. We identified genetic variants in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with the disease. These findings point to potential roles of cell-cycle regulation, autophagy, and DNA demethylation in SLE pathogenesis. For the region involving TET3 and that involving CDKN1B, multiple independent SNPs were identified, highlighting a phenomenon that might partially explain the missing heritability of complex diseases

Human germline heterozygous gain-of-function STAT6 variants cause severe allergic disease

STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. We have identified 16 patients from 10 families spanning three continents with a profound phenotype of early-life onset allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, and anaphylaxis. The cases were either sporadic (seven kindreds) or followed an autosomal dominant inheritance pattern (three kindreds). All patients carried monoallelic rare variants in STAT6 and functional studies established their gain-of-function (GOF) phenotype with sustained STAT6 phosphorylation, increased STAT6 target gene expression, and TH2 skewing. Precision treatment with the anti-IL-4Rα antibody, dupilumab, was highly effective improving both clinical manifestations and immunological biomarkers. This study identifies heterozygous GOF variants in STAT6 as a novel autosomal dominant allergic disorder. We anticipate that our discovery of multiple kindreds with germline STAT6 GOF variants will facilitate the recognition of more affected individuals and the full definition of this new primary atopic disorder

Phenomic analysis of chronic granulomatous disease reveals more severe integumentary infections in X-Linked compared with autosomal recessive chronic granulomatous disease

BACKGROUND : Chronic granulomatous disease (CGD) is an inborn error of immunity (IEI), characterised by recurrent bacterial and fungal infections. It is inherited either in an Xlinked (XL) or autosomal recessive (AR) mode. Phenome refers to the entire set of phenotypes expressed, and its study allows us to generate new knowledge of the disease. The objective of the study is to reveal the phenomic differences between XL and AR-CGD by using Human Phenotype Ontology (HPO) terms. METHODS : We collected data on 117 patients with genetically diagnosed CGD from Asia and Africa referred to the Asian Primary Immunodeficiency Network (APID network). Only 90 patients with sufficient clinical information were included for phenomic analysis. We used HPO terms to describe all phenotypes manifested in the patients. RESULTS : XL-CGD patients had a lower age of onset, referral, clinical diagnosis, and genetic diagnosis compared with AR-CGD patients. The integument and central nervous system were more frequently affected in XL-CGD patients. Regarding HPO terms, perianal abscess, cutaneous abscess, and elevated hepatic transaminase were correlated with XL-CGD. A higher percentage of XL-CGD patients presented with BCGitis/BCGosis as their first manifestation. Among our CGD patients, lung was the most frequently infected organ, with gastrointestinal system and skin ranking second and third, respectively. Aspergillus species, Mycobacterium bovis, and Mycobacteirum tuberculosis were the most frequent pathogens to be found. CONCLUSION : Phenomic analysis confirmed that XL-CGD patients have more recurrent and aggressive infections compared with AR-CGD patients. Various phenotypic differences listed out can be used as clinical handles to distinguish XL or AR-CGD based on clinical features.The Society for Relief of Disabled Children and Jeffrey Modell Foundation.https://www.frontiersin.org/journals/immunologydm2022Paediatrics and Child Healt