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Genome-wide significant loci for metformin response in type 2 diabetes reported elsewhere have not been replicated in the Diabetes Prevention Program (DPP). To assess pharmacogenetic interactions in prediabetes, we conducted a genome-wide association study (GWAS) in the DPP. Cox proportional hazards models tested associations with diabetes incidence in the metformin (MET; n = 876) and placebo (PBO; n = 887) arms. Multiple linear regression assessed association with 1-year change in metformin-related quantitative traits, adjusted for baseline trait, age, sex, and 10 ancestry principal components. We tested for gene-by-treatment interaction. No significant associations emerged for diabetes incidence. We identified four genome-wide significant variants after correcting for correlated traits (P < 9 × 10-9). In the MET arm, rs144322333 near ENOSF1 (minor allele frequency [MAF]AFR = 0.07; MAFEUR = 0.002) was associated with an increase in percentage of glycated hemoglobin (per minor allele, β = 0.39 [95% CI 0.28, 0.50]; P = 2.8 × 10-12). rs145591055 near OMSR (MAF = 0.10 in American Indians) was associated with weight loss (kilograms) (per G allele, β = -7.55 [95% CI -9.88, -5.22]; P = 3.2 × 10-10) in the MET arm. Neither variant was significant in PBO; gene-by-treatment interaction was significant for both variants [P(G×T) < 1.0 × 10-4]. Replication in individuals with diabetes did not yield significant findings. A GWAS for metformin response in prediabetes revealed novel ethnic-specific associations that require further investigation but may have implications for tailored therapy.

With the increasing prevalence of tumors, effective symptom management has emerged as a cornerstone of patient care. While surgical interventions remain pivotal, non-surgical nursing methods have gained prominence in providing relief from pain, discomfort, and other tumor-related symptoms. This review delves into the various non-surgical approaches employed, emphasizing tumor sedation and analgesia. We discuss the array of non-pharmacological and pharmacological strategies, shedding light on their indications, contraindications, and potential side effects. Furthermore, the importance of addressing individual differences in pain perception and the ethical considerations in symptom management are highlighted. We conclude by providing insights into the recent innovations in the field, emphasizing the need for personalized and comprehensive care to enhance patients’ quality of life. Tumor sedation, Tumor analgesia, Non-surgical nursing care, Pain management, Non-pharmacological interventions, Palliative care, Recent innovations, Symptom management.

OBJECTIVE: To determine glycemic and nonglycemic risk factors that contribute to the presence of diabetic retinopathy (DR) before and after the onset of type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: During the Diabetes Prevention Program (DPP) and DPP Outcome Study (DPPOS), we performed fundus photography over time in adults at high risk for developing T2D, including after they developed diabetes. Fundus photographs were graded using the Early Treatment Diabetic Retinopathy Study (ETDRS) grading system, with DR defined as typical lesions of DR (microaneurysms, exudates, hemorrhage, or worse) in either eye. RESULTS: By DPPOS year 16 (∼20 years after random assignment into DPP), 24% of 1,614 participants who had developed T2D and 14% of 885 who remained without diabetes had DR. In univariate analyses, using results from across the entire duration of follow-up, American Indian race was associated with less frequent DR compared with non-Hispanic White (NHW) race, and higher HbA1c, fasting and 2-h plasma glucose levels during an oral glucose tolerance test, weight, and history of hypertension, dyslipidemia, and smoking, but not treatment group assignment, were associated with more frequent DR. On multivariate analysis, American Indian race was associated with less DR compared with NHW (odds ratio [OR] 0.36, 95% CI 0.20-0.66), and average HbA1c was associated with more DR (OR 1.92, 95% CI 1.46-1.74 per SD [0.7%] increase in HbA1c). CONCLUSIONS: DR may occur in adults with prediabetes and early in the course of T2D. HbA1c was an important risk factor for the development of DR across the entire glycemic range from prediabetes to T2D.

Graphitic carbon nitride(g-C3N4) loaded by metal atom has been applied as an effective single atom catalyst. In the work, the complexation behaviors of g-C3N4(CN) with metal ions have been examined by relativistic density functional theory. The formed ［M(CN)］z+(M=Sc, Y, La, Ac and U; z=2 and 3) have been explored for their structures, metal-ligand interactions and redox properties. It is found that the metal ion has been rendered by six M-N dative bonds, each of which has the bonding strength ranging from -0.79 to -0.47 eV. Regarding Sc complexes, one-electron reduction mainly occurs around the metal center, while La and U complexes have metal-modified ligand reduction mechanism; both metal and ligand in Y complex are approximately equally reduced; in contrast, the ligand of Ac complex gets the reducing electron, and the metal is redox-innocent. This agrees with the fact that there are no experimental reports on Ac(Ⅱ) complexes. Electronic-structure analyses indicate that ［U(CN)］3+ bears three high-lying single U(5f) occupied orbitals, suggesting the trivalent uranium center. However, despite having four single U(5f) occupied orbitals, ［U(CN)］2+ still possesses considerable ligand contribution, leading to the uranium oxidation state mediating between Ⅱ and Ⅲ.