OBJECTIVE To explore the main factors influencing the blood concentration of duloxetine， and provide a scientific basis for the individualized use of duloxetine. METHODS Retrospective analysis was conducted on 434 inpatients with depressive disorders at the First Hospital of Hebei Medical University， who were treated with duloxetine and underwent blood concentration monitoring between January 2022 and April 2024. The study examined the impact of various factors， including gender， age， body mass index （BMI）， gene phenotypes， combined medication， drug type （original/generic）， and genotyping results of gene single nucleotide polymorphism loci， on blood concentration and the concentration-to-dose （C/D） after dose adjustment. RESULTS The blood concentration of duloxetine was 76.65 （45.57， 130.31） ng/mL， and C/D was 0.96 （0.63， 1.60） ng·d/（mL·mg）. The blood concentration of duloxetine was positively correlated with the daily dose of administration （R2＝0.253 7， P＜0.001）. Blood concentration of duloxetine in 38.94% of patients exceeded the recommended range specified in the guidelines. Gender， age， BMI， combined use of CYP2D6 enzyme inhibitors， and CYP2D6 and CYP1A2 phenotypes had significant effects on C/D of duloxetine （P＜0.05）. CONCLUSIONS The patient’s age， gender， BMI， combined medication， and genetic phenotypes are closely related to the blood concentration of duloxetine.

Objective:To systematically evaluate the relationship between thiazide diuretics and the risk of hip fracture in the elderly patients.Methods:The relevant databases at home and abroad were searched up to December 31, 2023 and case-control studies and cohort studies on the relationship between thiazide diuretics and the risk of hip fractures in the elderly patients were collected. Quality of the enrolled studies was evaluated by bias risk assessment tool of Newcastle-Ottawa Scale (NOS). RevMan 5.4 software was used for meta-analysis on related outcome indicators, and the effect sizes were odds ratio ( OR) and the 95% confidence interval ( CI). Funnel plots, Egger′s method and Begg′s method were performed using Stata 15.1 software to analyze the inclusion literature for publication bias. Results:A total of 18 studies were enrolled in the study, including 7 case-control studies and 11 cohort studies and involving 175 200 patients in the trial group (thiazide diuretics) and 1 574 989 in the control group (placebo or other medications). All 18 studies scored ≥5 on the NOS (15 articles of high quality and 3 articles of medium quality). The meta-analysis results indicated that the risk of hip fractures in the trial group was lower than that in the control group ( OR=0.82, 95% CI: 0.75-0.89, P<0.001). Subgroup analyses by study type and gender both revealed that thiazide diuretics were associated with a reduced risk of hip fractures in the elderly (adjusted OR in case-control studies was 0.78, 95% CI: 0.72-0.84, P<0.001; adjusted OR in cohort studies was 0.83, 95% CI: 0.74-0.93, P=0.002; adjusted OR in female was 0.78, 95% CI: 0.72-0.85, P<0.001; adjusted OR in male was 0.73, 95% CI: 0.68-0.80, P<0.001). The subgroup analysis of 11 large-sample studies (≥2 000 cases) indicated that thiazide diuretics were associated with a reduced risk of hip fractures in the elderly (adjusted OR=0.79, 95% CI: 0.72-0.87, P<0.001). However, 6 small-sample studies did not find the similar correlation. A combined analysis of studies that rigorously controlled for confounding factors revealed that thiazide diuretics were associated with a lower risk of hip fractures in the elderly ( OR=0.79, 95% CI: 0.74-0.84, P<0.001), and the combined results showed no heterogeneity ( P=0.72, I2=0%). Conclusions:Thiazide diuretics were associated with a reduced risk of hip fractures in the elderly patients. Based on a comprehensive assessment of the risks and benefits of medication for elderly patients, clinicians may prioritize thiazide diuretics as a component of combination therapy for eligible patients, which may be beneficial in reducing their risk of hip fractures.

Objective:To systematically evaluate the relationship between thiazide diuretics and the risk of hip fracture in the elderly patients.Methods:The relevant databases at home and abroad were searched up to December 31, 2023 and case-control studies and cohort studies on the relationship between thiazide diuretics and the risk of hip fractures in the elderly patients were collected. Quality of the enrolled studies was evaluated by bias risk assessment tool of Newcastle-Ottawa Scale (NOS). RevMan 5.4 software was used for meta-analysis on related outcome indicators, and the effect sizes were odds ratio ( OR) and the 95% confidence interval ( CI). Funnel plots, Egger′s method and Begg′s method were performed using Stata 15.1 software to analyze the inclusion literature for publication bias. Results:A total of 18 studies were enrolled in the study, including 7 case-control studies and 11 cohort studies and involving 175 200 patients in the trial group (thiazide diuretics) and 1 574 989 in the control group (placebo or other medications). All 18 studies scored ≥5 on the NOS (15 articles of high quality and 3 articles of medium quality). The meta-analysis results indicated that the risk of hip fractures in the trial group was lower than that in the control group ( OR=0.82, 95% CI: 0.75-0.89, P<0.001). Subgroup analyses by study type and gender both revealed that thiazide diuretics were associated with a reduced risk of hip fractures in the elderly (adjusted OR in case-control studies was 0.78, 95% CI: 0.72-0.84, P<0.001; adjusted OR in cohort studies was 0.83, 95% CI: 0.74-0.93, P=0.002; adjusted OR in female was 0.78, 95% CI: 0.72-0.85, P<0.001; adjusted OR in male was 0.73, 95% CI: 0.68-0.80, P<0.001). The subgroup analysis of 11 large-sample studies (≥2 000 cases) indicated that thiazide diuretics were associated with a reduced risk of hip fractures in the elderly (adjusted OR=0.79, 95% CI: 0.72-0.87, P<0.001). However, 6 small-sample studies did not find the similar correlation. A combined analysis of studies that rigorously controlled for confounding factors revealed that thiazide diuretics were associated with a lower risk of hip fractures in the elderly ( OR=0.79, 95% CI: 0.74-0.84, P<0.001), and the combined results showed no heterogeneity ( P=0.72, I2=0%). Conclusions:Thiazide diuretics were associated with a reduced risk of hip fractures in the elderly patients. Based on a comprehensive assessment of the risks and benefits of medication for elderly patients, clinicians may prioritize thiazide diuretics as a component of combination therapy for eligible patients, which may be beneficial in reducing their risk of hip fractures.

OBJECTIVETo investigate the inhibitory effect of resveratrol on interleukin-1β (IL-1β) production in mesenchymal stem cells (MSCs) exposed to radiation and the action mechanism of resveratrol.

METHODSMSCs were divided into blank control group, radiation group, shRNA interference group, and resveratrol groups. The resveratrol groups were given different doses of resveratrol (50, 100, and 200 µmol/L) before radiation. The secretion and expression of IL-1β was measured by enzyme-linked immunosorbent assay, Western blot, and RT-PCR.

RESULTSCompared with the radiation group, the resveratrol groups had significantly decreased extracellular secretion of IL-1β (t = 83.34, 24.48, and 12.52, P < 0.05 for all) and significantly decreased intracellular expression of IL-1β protein and mRNA (t = 8.695, 14.77, and 13.9, P < 0.05 for all). Compared with those given 200 µmol/L resveratrol alone before radiation, the MSCs treated by SIRT1 silencing and given 200 µmol/L resveratrol before radiation had significantly increased extracellular secretion of IL-1β (t = 18.57, P < 0.05) and significantly increased intracellular expression of IL-1β protein and mRNA (t = 10.24, P < 0.05).

CONCLUSIONResveratrol can significantly inhibit the production of IL-1β in MSCs exposed to radiation, and SIRT1 may play a key regulatory role in the process of inflammation induced by radiation.

Cells, Cultured ; Humans ; Interleukin-1beta ; metabolism ; Mesenchymal Stromal Cells ; drug effects ; metabolism ; radiation effects ; Radiation ; Radiation Dosage ; Stilbenes ; pharmacology