Decoding and reconstructing disease relations between dry eye and depression: a multimodal investigation comprising meta-analysis, genetic pathways and Mendelian randomization.

INTRODUCTION: The clinical presentations of dry eye disease (DED) and depression (DEP) often comanifest. However, the robustness and the mechanisms underlying this association were undetermined. OBJECTIVES: To this end, we set up a three-segment study that employed multimodality results (meta-analysis, genome-wide association study [GWAS] and Mendelian randomization [MR]) to elucidate the association, common pathways and causality between DED and DEP. METHODS: A meta-analysis comprising 26 case-control studies was first conducted to confirm the DED-DEP association. Next, we performed a linkage disequilibrium (LD)-adjusted GWAS and targeted phenotype association study (PheWAS) in East Asian TW Biobank (TWB) and European UK Biobank (UKB) populations. Single-nucleotide polymorphisms (SNPs) were further screened for molecular interactions and common pathways at the functional gene level. To further elucidate the activated pathways in DED and DEP, a systemic transcriptome review was conducted on RNA sequencing samples from the Gene Expression Omnibus. Finally, 48 MR experiments were implemented to examine the bidirectional causation between DED and DEP. RESULTS: Our meta-analysis showed that DED patients are associated with an increased DEP prevalence (OR = 1.83), while DEP patients have a concurrent higher risk of DED (OR = 2.34). Notably, cross-disease GWAS analysis revealed that similar genetic architecture (rG = 0.19) and pleiotropic functional genes contributed to phenotypes in both diseases. Through protein-protein interaction and ontology convergence, we summarized the pleiotropic functional genes under the ontology of immune activation, which was further validated by a transcriptome systemic review. Importantly, the inverse variance-weighted (IVW)-MR experiments in both TWB and UKB populations (p value <0.001) supported the bidirectional exposure-outcome causation for DED-to-DEP and DEP-to-DED. Despite stringent LD-corrected instrumental variable re-selection, the bidirectional causation between DED and DEP remained. CONCLUSION: With the multi-modal evidence combined, we consolidated the association and causation between DED and DEP.

Antipsychotic drug trifluoperazine as a potential therapeutic agent against nasopharyngeal carcinoma.

BACKGROUND: Trifluoperazine (TFP) is a typical antipsychotic primarily used to treat schizophrenia. In this study, we aimed to evaluate whether TFP can be used as a therapeutic agent against nasopharyngeal carcinoma (NPC) and identify its underlying molecular mechanisms. METHODS: We used NPC-TW01, TW03, TW04, and BM to assess the anticancer effects of TFP by using cytotoxicity, wound healing, colony formation, and cell invasion assays. An in vivo animal study was conducted. RNA sequencing combined with Ingenuity Pathways Analysis was performed to identify the mechanism by which TFP influences NPC cells. RESULTS: Our data revealed that TFP decreased NPC cell viability in a dose-dependent manner. The invasion and migration of NPC tumor cells were inhibited by TFP. An in vivo study also demonstrated the anticancer effects of TFP. RNA sequencing revealed several anticancer molecular mechanisms following TFP administration. CONCLUSIONS: The antipsychotic drug TFP could be a potential therapeutic regimen for NPC treatment.

Epidemiological distribution characteristics of peripheral blood mosaic chromosomal alteration in adults from 10 regions of China / 中华流行病学杂志

Objective: To describe the epidemiological distribution characteristics of peripheral blood mosaic chromosomal alteration (mCA) in community adults aged 30-79 years in 10 regions of China. Methods: A total of 100 297 participants with complete baseline information (demographic characteristics, lifestyle, physical examination, etc.) and genotyping data of blood-derived DNA in ten regions of the China Kadoorie Biobank study were included. The mCAs were detected with the Mosaic Chromosomal Alterations pipeline, and logistic regression models were used to compare the differences in the detection rate of mCAs in different regions and populations. Results: A total of 5 810 mCA carriers were detected, with the detection rate of 5.8%. The standardized detection rate was 5.1%. The baseline detection rate of mCA increased with age, which were 3.4%, 5.0%, and 9.4% in those aged 30-, 51-, and >60 years, respectively (trend test P<0.001). A more significant proportion of mCAs were found in men (8.0%) than women (4.0%), as well as in urban areas (6.4%) than in rural areas (5.3%), the difference was significant (P<0.001). After adjusting for age and gender, the detection rate of mCA was higher in current smokers or people quitting smoking due to illness and people with low physical activity level, and the mCA detection rate was lower in obesy people (5.3%) than that in people with normal body weight (5.9%) (P=0.006). Conclusions: The detection rate of mCAs varied with region and population in community adults aged 30-79 years in 10 regions of China. The study results might contribute to the molecular identification of aging populations and guide precision prevention of age-related diseases such as cancers.

Effects of different feeding methods on the iodine status of the infants during the weaning period / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the iodine levels of urine from 1 month old breast-fed infants and the ones of milk and urine from the lactating women, and to observe the effects of different feeding methods (breast-feeding, mixed-feeding, bottle-feeding) on the iodine status of the infants during the weaning period in Beijing.</p><p><b>METHODS</b>From March, 2001 to March, 2002, the iodine levels of urine from 97 breast-fed infants 1 month of age and the ones in milk and urine from lactating women were measured and compared. The infants followed up were divided into 3 groups (breast-fed, mixed and bottle-fed) until 6 months old. Their iodine levels of urine were measured and compared with the ones of 1 month of age.</p><p><b>RESULTS</b>The median value of urine iodine from breast-fed 1 month old infants was 183 micro g/L, suggesting that the infants with breast-fed had good iodine nutritional status. The median value of urine iodine from lactating women was 122 micro g/L, significantly lower than the value of milk iodine, 201 micro g/L (P < 0.001). which suggests that the lactating women were iodine deficient but could provide infants iodine adequately through breast feeding. Compared with 1 month af age, the urine iodine levels of 6 months old infants with breast-feeding increased (P < 0.001), the ones with bottle-feeding decreased significantly (P < 0.001) and the mixed-feeding group did not change (P > 0.05). The differences among 3 groups were significant (P < 0.005), the urine iodine levels of infants of both breast-feeding and mixed-feeding groups were higher than the ones of bottle-feeding. The breast-feeding group was the highest one among three groups.</p><p><b>CONCLUSION</b>The breast-fed infants were nourished with iodine, but the lactating women were iodine deficient. Accompanied the decrease of the amount of breast milk, the iodine levels of infants urine decreased during the weaning period, some bottle-feeding infants were iodine deficient.</p>