Metformin in elderly type 2 diabetes mellitus: dose-dependent dementia risk reduction.

This study aimed to investigate the controversial association between metformin use and diabetes-associated dementia in elderly patients with type 2 diabetes mellitus (T2DM) and evaluate the potential protective effects of metformin, as well as its intensity of use and dose-dependency, against dementia in this population. The study used a time-dependent Cox hazards model to evaluate the effect of metformin use on the incidence of dementia. The case group included elderly patients with T2DM (≥60 years old) who received metformin, while the control group consisted of elderly patients with T2DM who did not receive metformin during the follow-up period. Our analysis revealed a significant reduction in the risk of dementia among elderly individuals using metformin, with an adjusted hazard ratio of 0.34 (95% confidence interval: 0.33 to 0.36). Notably, metformin users with a daily intensity of 1 defined daily dose (DDD) or higher had a lower risk of dementia, with an adjusted hazard ratio (95% confidence interval) of 0.46 (0.22 to 0.6), compared to those with a daily intensity of <1 DDD. Additionally, the analysis of cumulative DDDs of metformin showed a dose-response relationship, with progressively lower adjusted hazard ratio across quartiles (0.15, 0.21, 0.28, and 0.53 for quartiles 4, 3, 2 and 1, respectively), compared to never metformin users (P for trend < 0.0001). Metformin use in elderly patients with T2DM is significantly associated with a substantial reduction in the risk of dementia. Notably, the protective effect of metformin demonstrates a dose-dependent relationship, with higher daily and cumulative dosages of metformin showing a greater risk reduction.

Prognostic factors for survival in unresectable stage III EGFR mutation-positive lung adenocarcinoma: impact of pre-CCRT PET-CT.

PURPOSE: To assess the survival impact of pre-concurrent chemoradiotherapy (CCRT) staging with positron emission tomography-CT (PET-CT) in patients with unresectable epidermal growth factor receptor (EGFR) mutation-positive adenocarcinoma. METHODS: Patients with unresectable stage IIIA-IIIC EGFR mutation-positive adenocarcinoma undergoing definitive CCRT were divided into two groups: those who received PET-CT staging prior to CCRT and those with other staging methods. Survival outcomes were compared after propensity score matching. RESULTS: Analysis of 11 856 patients (5928 in each group) showed that PET-CT staging was associated with improved survival (adjusted HR of all-cause mortality: 0.74, 95% CI 0.71 to 0.79). Other prognostic factors included male sex, age group, clinical stage, adjuvant treatment, smoking status, Charlson Comorbidity Index score and treatment setting. CONCLUSION: Pre-CCRT staging with PET-CT in patients with unresectable EGFR mutation-positive adenocarcinoma of clinical stage IIIA-IIIC was associated with enhanced survival. Independent prognostic factors were also identified.

1,25(OH)2 D3 inhibits Lewis lung cancer cell migration via NHE1-sensitive metabolic reprograming.

High prevalence and metastasis rates are characteristics of lung cancer. Glycolysis provides energy for the development and metastasis of cancer cells. The 1,25-dihydroxy vitamin D3 (1,25(OH)2 D3 ) has been linked to reducing cancer risk and regulates various physiological functions. We hypothesized that 1,25(OH)2 D3 could be associated with the expression and activity of Na+ /H+ exchanger isoform 1 (NHE1) of Lewis lung cancer cells, thus regulating glycolysis as well as migration by actin reorganization. Followed by online public data analysis, Vitamin D3 receptor, the receptor of 1,25(OH)2 D3 has been proved to be abundant in lung cancers. We demonstrated that 1,25(OH)2 D3 treatment suppressed transcript levels, protein levels, and activity of NHE1 in LLC cells. Furthermore, 1,25(OH)2 D3 treatment resets the metabolic balance between glycolysis and OXPHOS, mainly including reducing glycolytic enzymes expression and lactate production. In vivo experiments showed the inhibition effects on tumor growth as well. Therefore, we concluded that 1,25(OH)2 D3 could amend the NHE1 function, which leads to metabolic reprogramming and cytoskeleton reconstruction, finally inhibits the cell migration.

Allelic Variation of BnaFTA2 and BnaFTC6 Is Associated With Flowering Time and Seasonal Crop Type in Rapeseed (Brassica napus L.).

Different ecological types of rapeseed (Brassica napus L.), including winter, spring, and semi-winter cultivars, exhibit varying flowering times and cannot be planted in the same cultivation areas. FLOWERING LOCUS T (FT) plays a key role in regulating flowering. In allotetraploid B. napus six copies of FT (BnaFT) have been reported. However, there is uncertainty about how the translated products of each paralog, as well as cis-allelic variations at each locus, contribute functionally to flowering time and define specific crop types. In this study, we confirm that BnaFT exhibit distinct expression patterns in different crop types of rapeseed. Using the CRISPR/Cas9 gene editing system, we provide functional evidence that the mutants between Bnaft paralogues affects the regulation of flowering time. Furthermore, we identify a new haplotype of BnaFT.A2 that is associated with early flowering time, although this appears necessary but not sufficient to confer a spring type phenotype. Three haplotypes of BnaFT.C6 were further identified and associated with both flowering time and crop types. We speculate that variations in both BnaFT.A2 and BnaFT.C6 may have undergone diversifying selection during the divergence of seasonal crop types in rapeseed.

Investigating the Structure-property Relationships of Two Cd-based Hybrid Multifunctional Compounds with High Tc, Bright Fluorescence and Wide Band-gap.

Organic-inorganic hybrid multifunctional materials have shown significant application in lighting and sensor fields, owing to their prominent performance and diversity structures. Herein, we synthesized two multifunctional compounds: (propyl-quinuclidone)2 CdBr4 (1) and (F-butyl-quinuclidone)2 CdBr4 (2). By introducing light-emitting organic cation with flexible long chain, 1 and 2 exhibit excellent transition properties and bright blue-white fluorescence. Then, combine fluorescence lifetime and first-principal calculation, providing evidence for the electron transfer emission. Subsequently, investigated the impact of substituent carbon chain length (methyl to butyl), structural rigidity (C-C to C-F) and halide framework (Cl to I) on the fluorescence properties. Results indicate that Cd⋅⋅⋅Cd distance and structural rigidity play an important role in fluorescence. Overall, our research provides valuable insight and example for chemical modifications enhance compound performance.

Early childhood general anesthesia and risk of Attention Deficit Hyperactivity Disorder.

BACKGROUND: The relationship between early childhood exposure to general anesthesia (GA) and the risk of developing Attention Deficit Hyperactivity Disorder (ADHD) is still uncertain and previous studies have presented conflicting results. This population-based cohort study aimed to investigate the potential relationship between GA exposure and ADHD risk using propensity score matching (PSM) in a large sample size. METHODS: The study included 15,072 children aged 0-3 years who received GA and were hospitalized for more than 1 day in Taiwan from 2004 to 2014. The nonexposed group was randomly selected through 1:1 PSM from the Taiwan Maternal and Child Health Database (TMCHD). The primary objectives of this study were to determine the incidence rates (IR) and incidence rate ratios (IRR) of ADHD in the two cohorts, employing Poisson regression models. RESULTS: The GA group and non-GA group each comprised 7,536 patients. The IR of ADHD was higher in the GA group (122.45 per 10,000 person-years) than in the non-GA group (64.15 per 10,000 person-years), and the IRR of ADHD in the GA group was 1.39 (95% CI: 1.26, 1.55). The study found that the number of times of exposure to GA, duration of exposure, male gender, and central nervous system surgery were significant risk factors for ADHD in the future. CONCLUSIONS: This study's findings suggest that there is a significant correlation between early childhood exposure to GA and the risk of developing ADHD, and GA may be an important risk factor for ADHD in children undergoing surgery. The study also identified several risk factors for ADHD, including the number of times of exposure to GA, duration of exposure, male gender, and central nervous system surgery.

Metformin monotherapy versus predominantly older non-metformin antidiabetic medications for cerebrovascular risk in early type 2 diabetes management.

AIM: Choosing the initial treatment for type 2 diabetes (T2D) is pivotal, requiring consideration of solid clinical evidence and patient characteristics. Despite metformin's historical preference, its efficacy in preventing cerebrovascular events lacked empirical validation. This study aimed to evaluate the associations between first-line monotherapy (metformin or non-metformin antidiabetic medications) and cerebrovascular complications in patients with T2D without diabetic complications. METHODS: We analysed 9090 patients with T2D without complications who were prescribed either metformin or non-metformin medications as initial therapy. Propensity score matching ensured group comparability. Cox regression analyses, stratified by initial metformin use, assessed cerebrovascular disease risk, adjusting for multiple covariates and using competing risk analysis. Metformin exposure was measured using cumulative defined daily doses. RESULTS: Metformin users had a significantly lower crude incidence of cerebrovascular diseases compared with non-users (p < .0001). Adjusted hazard ratios (aHRs) consistently showed an association between metformin use and a lower risk of overall cerebrovascular diseases (aHRs: 0.67-0.69) and severe events (aHRs: 0.67-0.69). The association with reduced risk of mild cerebrovascular diseases was significant across all models (aHRs: 0.73-0.74). Higher cumulative defined daily doses of metformin correlated with reduced cerebrovascular risk (incidence rate ratio: 0.62-0.94, p < .0001), indicating a dose-dependent effect. CONCLUSION: Metformin monotherapy is associated with a reduced risk of cerebrovascular diseases in early-stage T2D, highlighting its dose-dependent efficacy. However, the observed benefits might also be influenced by baseline differences and the increased risks associated with other medications, such as sulphonylureas. These findings emphasize the need for personalized diabetes management, particularly in mitigating cerebrovascular risk in early T2D stages.

Silver/Antimony-Base Multifunctional Double Perovskite with H/F Substitution Enhance Properties.

Two-dimensional double perovskites have experienced rapid development due to their outstanding optoelectronic properties and diverse structural characteristics. However, the synthesis of high-performance multifunctional compounds and the regulation of their properties still lack relevant examples. Herein, we synthesized two multifunctional compounds, (C6H14N)4AgSbBr8 (1) and (F2-C6H12N)4AgSbBr8 (2), which exhibit high solid-state phase transition temperature, bistable dielectric constant switching, second harmonic generation (SHG), and bright emission. Through H/F substitution, the transition temperature increases and achieves a smaller band gap attributed to reduced interlayer spacing. Furthermore, we investigated the broad emission mechanism of the compounds through first-principles calculation and variable-temperature fluorescence, confirming the presence of the STE1 emission. Our work provides insight into the further development of multifunctional compounds and chemical modification that enhances compound properties.

Improved postoperative outcomes in pediatric major surgery: evidence from hospital volume analysis.

This study aimed to examine the association between hospital volume and postoperative outcomes in pediatric major surgery using a nationwide database. The study included pediatric patients who underwent first major elective inpatient surgery and hospitalization for more than 1 day. The results showed no significant difference in the risk of 30-day postoperative mortality based on hospital volume. However, patients in the middle- and high-volume groups had significantly lower rates of 30-day major complications, particularly deep wound infection. In terms of 90-day postoperative outcomes, patients in the high-volume group had a significantly lower risk of mortality and lower rates of major complications, particularly deep wound infection, pneumonia, and septicemia.  Conclusions: The study suggests that pediatric patients undergoing major surgery in high and middle-volume groups have better outcomes in terms of major complications compared to the low-volume group. What is Known: • Limited evidence exists on the connection between hospital volume and pediatric surgery outcomes. What is New: • A Taiwan-based study, using national data, found that high and middle hospital-volume groups experienced significantly lower rates of major complications within 30 and 90 days after surgery. • High-volume hospitals demonstrated a substantial decrease in the risk of 90-day postoperative mortality. • The study underscores the importance of specialized pediatric surgical centers and advocates for clear guidelines for hospital selection, potentially improving outcomes and informing future health policies.

Adverse postoperative outcomes in elderly patients with sarcopenia.

PURPOSE: No study has compared 30-day and 90-day adverse postoperative outcomes between old-age patients with and those without sarcopenia. PATIENTS AND METHODS: We categorize elderly patients receiving major surgery into two groups according to the presence or absence of preoperative sarcopenia that were matched at a 1:4 ratio through propensity score matching (PSM). We analyzed 30-day or 90-day adverse postoperative outcomes and mortality in patients with and without sarcopenia receiving major surgery. RESULTS: Multivariate logistic regression analyses revealed that the patients with preoperative sarcopenia were at significantly higher risk of 30-day postoperative mortality (adjusted odds ratio [aOR]. = 1.25; 95% confidence interval [CI]. = 1.03-1.52) and 30-day major complications such as postoperative pneumonia (aOR = 1.15; 95% CI = 1.00-1.40), postoperative bleeding (aOR = 2.18; 95% CI = 1.04-4.57), septicemia (aOR = 1.31; 95% CI = 1.03-1.66), and overall complications (aOR = 1.13; 95% CI = 1.00-1.46). In addition, surgical patients with sarcopenia were at significantly higher risk of 90-day postoperative mortality (aOR = 1.50; 95% CI = 1.29-1.74) and 90-day major complications such as pneumonia (aOR = 1.27; 95% CI = 1.10-1.47), postoperative bleeding (aOR = 1.90; 95% CI = 1.04-3.48), septicemia (aOR = 1.52; 95% CI = 1.28-1.82), and overall complications (aOR = 1.24; 95% CI = 1.08-1.42). CONCLUSIONS: Sarcopenia is an independent risk factor for 30-day and 90-day adverse postoperative outcomes such as pneumonia, postoperative bleeding, and septicemia and increases 30-day and 90-day postoperative mortality among patients receiving major surgery. No study has compared 30-day and 90-day adverse postoperative outcomes between patients with and those without sarcopenia. We conducted a propensity score?matched (PSM) population-based cohort study to investigate the adverse postoperative outcomes and mortality in patients undergoing major elective surgery with preoperative sarcopenia versus those without preoperative sarcopenia. We demonstrated that sarcopenia is an independent risk factor for 30-day and 90-day adverse postoperative outcomes, such as postoperative pneumonia, bleeding, septicemia, and mortality after major surgery. Therefore, surgeons and anesthesiologists should attempt to correct preoperative sarcopenia, swallowing function, and respiratory muscle training before elective surgery to reduce postoperative complications that contribute to the decrease in surgical mortality.