OBJECTIVE To analyze the distribution characteristics of mirtazapine steady-state trough concentration and concentration-to-dose ratio （ C / D ）， and to investigate the influence of clinical and genetic factors on C / D . METHODS A retrospective study was conducted on hospitalized patients with depression who received mirtazapine treatment and underwent therapeutic drug monitoring at the First Hospital of Hebei Medical University from May 2022 to May 2025. The collected data included patients’ gender， age， body mass index， daily dose， steady-state trough concentration， smoking status， history of liver disease， drug type， concomitant medications， and CYP2D6 metabolic phenotype. The C / D was calculated. Spearman rank correlation was used to analyze the relationship between mirtazapine steady-state trough concentration and daily dose. Univariate analysis and multiple linear regression model were employed to screen the factors potentially influencing the C / D of mirtazapine. RESULTS A total of 226 patients were included. The daily dose of mirtazapine was 25.00 （24.82， 30.00） mg/d， the steady-state trough concentration was 44.46 （20.00， 70.00） ng/mL， and the C / D was 1.83 （1.00， 2.00） （ng·d）/（mL·mg）. Steady-state trough concentrations were within the reference range （30-80 ng/mL） in 121 patients （53.54%）， below the lower limit in 80 patients （35.40%）， and above the upper limit in 25 patients （11.06%）. A positive correlation was observed between mirtazapine steady-state trough concentration and daily dose （coefficient of determination was 0.320 8， P ＜0.001）. Gender， smoking status， and CYP2D6 metabolic phenotype were significantly associated with the mirtazapine C / D （ P ＜0.05）. CONCLUSIONS Significant interindividual variability exists in mirtazapine steady-state trough concentrations. Gender， smoking status， and CYP2D6 metabolic phenotype are identified as independent influencing factors for the mirtazapine C / D ， with higher C / D ratios observed in females， non-smokers， and intermediate metabolizers.

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.

Irritable bowel syndrome (IBS) is an extremely common chronic intestinal disorder characterized by recurrent abdominal pain and altered bowel habits, significantly impacting patients' quality of life. The etiology of IBS remains incompletely understood. Research has identified low-grade intestinal inflammation and immune activation, primarily manifested as an imbalance between pro-inflammatory and anti-inflammatory cytokines, as key pathogenic mechanisms in IBS. Among these, interleukin-6 (IL-6), a core pro-inflammatory cytokine, is significantly elevated in IBS patients. IL-6 contributes to the pathogenesis of IBS through various mechanisms, including altering individual susceptibility to IBS, promoting gastrointestinal motility and secretion, activating the hypothalamic-pituitary-adrenal axis, inducing visceral hypersensitivity, and impairing intestinal mucosal barrier function. Furthermore, IL-6 levels are closely associated with the severity of IBS symptoms. This review summarizes the role and mechanisms of IL-6 in IBS, aiming to provide insights and references for clinicians and researchers investigating the etiology of IBS.

Objective To investigate the predictive value of serum lipoprotein-associated phospholipase A2(Lp-PLA2)and homocysteine(Hcy)combined with white matter hyperintensities(WMH)for cognitive impairment in patients with cerebral small vessel disease(CSVD).Methods A total of 240 patients with CSVD were selected.According to the Montreal Cognitive Assessment(MoCA)scale,all subjects were divided into the non-cognitive impairment group(MoCA≥26 points,120 cases)and the cognitive impairment group(MoCA＜26 points,120 cases).Paraventricular white matter high signal(PWMHs)and deep white matter high signal(DWMHs)were scored by Fazekas scale.The sum of the two parts was the total score,and the severity of DWMHs was graded by the score.The basic information,serum Lp-PLA2,Hcy level and severity of WMH were compared between the two groups.Logistic regression was applied to analyze influencing factors of cognitive impairment in CSVD patients.The predictive value of serum level of Lp-PLA2 and Hcy and WMH for cognitive impairment in CSVD patients was analyzed by receiver operating characteristic(ROC)curve.Results Compared with the non-cognitive impairment group,patients of the cognitive impairment group were older,had higher serum levels of Lp-PLA2 and Hcy,and had more severe of WMH(P＜0.05).Results of Logistic regression analysis showed that serum Lp-PLA2,Hcy levels and severity of WMH were influencing factors for cognitive impairment of patients with CSVD(P＜0.05).The results of ROC curve analysis showed that the area under the curve of serum Lp-PLA2,Hcy level combined with severity of WMH predicting cognitive impairment in patents with CSVD was 0.812,the sensitivity was 81.7%and the specificity was 71.7%(P＜0.05).Conclusion Patients with cognitive impairment caused by CSVD have higher serum levels of Lp-PLA2 and Hcy,and more severe WMH.The combination of the three has a relatively high predictive value for cognitive impairment in patents with CSVD.

Objective To investigate the clinical characteristics of patients with chronic abacterial pros-tafitis(CAP),the CAP related factors were analyzed,and a risk prediction model for CAP were constructed and validated.Methods The clinical dataes of 252 suspected CAP patients admitted to the hospital from June 2022 to December 2024 were collected,the patients were divided into modeling set(ni=177)and validation set(n=75)by 7∶3 ratio.Based on the modeling set dataes,the Lasso was used to screen CAP related predictive factors,a logistic multiple factor model was used to analyze the independent influence factors of CAP and a risk prediction model was constructed.The validation set patient dataes were used to plot ROC and DCA and validate the predic-tion model.Results There were 86 cases of CAP in the modeling set,accounting for 48.59％;32 cases of CAP in the validation set,accounting for 42.67％.The Logistic multiple regression analysis showed that BMI,waist to hip ratio,abnormal elevation of IL-8,COX-2,and PGE2 in prostate fluid were independent influence factors of CAP(P＜0.05),a Nomogram column chart based on this was established.The ROC analysis showed that the sensitivity of the model for detecting CAP in the modeling and validation sets were 0.814 and 0.802,respectively,and the specificity were 0.673 and 0.703,respectively.The DCA analysis showed that the net benefit thresholds for model-ing and validation sets by column charts are 0.1～0.9 and 0.2～1.0,respectively.Conclusions The occurrence of CAP is related to the patient's BMI,waist to hip ratio,the levels of IL-8,COX-2,and PGE2 in prostate fluid.The predictive model established based on this is highly accurate and it can help for CAP screening.

Objective:To explore the association between the metabolic score for insulin resistance (METS-IR) and metabolic dysfunction-associated fatty liver disease (MAFLD), and to compare the diagnostic ability of METS-IR with the fatty liver index (FLI) and hepatic steatosis index (HSI) for MAFLD.Methods:This cross-sectional study enrolled 551 individuals participating in community health screenings in Suzhou between September and November 2022. Data collected included basic demographics, clinical indicators, and iLivTouch? (FibroTouch FT5000, Wuxi Hisky Medical Technologies, China) transient elastography results. Participants were categorized into non-MAFLD ( n=218) and MAFLD ( n=333) groups based on an ultrasound attenuation parameter (UAP) cutoff of 244 dB/m measured by iLivTouch. Logistic regression and restricted cubic spline (RCS) analyses were employed to assess the relationship between METS-IR and MAFLD. The diagnostic value of METS-IR was evaluated using receiver operating characteristic (ROC) curves. DeLong′s test was used to compare the diagnostic performance of the different indices. Results:Among the 551 participants, the prevalence of MAFLD diagnosed by transient elastography was 60.4% (333/552). Compared to the non-MAFLD group, the MAFLD group had significantly higher levels of BMI, SBP, DBP, HbA1c, FPG, 2hPG, TC, TG, LDL-C, ALT, AST, GGT, SUA, liver stiffness measurement (LSM), METS-IR, FLI, and HSI, while HDL-C levels were lower (all P<0.05). The MAFLD group also had a higher prevalence of males, overweight/obesity, smoking, hypertension, pre-diabetes, dyslipidemia, hyperuricemia, metabolic syndrome, and antihypertensive medication use (all P<0.05). Multivariate logistic regression analysis, after adjusting for gender, age, smoking, alcohol consumption, hypertension, diabetes, dyslipidemia, hyperuricemia, ALT, AST, and GGT, demonstrated that METS-IR, FLI, and HSI remained significantly associated with an increased risk of MAFLD ( OR=1.148, 1.042, 1.270, respectively; all P<0.001). The areas under the ROC curve for METS-IR, FLI, and HSI in diagnosing MAFLD were 0.733 (95% CI: 0.691-0.774), 0.727 (95% CI: 0.685-0.770), and 0.677 (95% CI: 0.632-0.722), respectively. The sensitivities were 57.40%, 62.20%, and 48.30%; specificities were 78.00%, 72.90%, and 78.40%; and optimal cutoff values were 38.526, 35.225, and 35.386, respectively. DeLong′s test indicated no significant difference in diagnostic performance between METS-IR and FLI ( P=0.722). However, both METS-IR and FLI demonstrated significantly better diagnostic performance than HSI ( P=0.008 and P=0.018, respectively). Conclusion:METS-IR is significantly associated with MAFLD and effectively identifies MAFLD in community settings. Its diagnostic performance is comparable to FLI and superior to HSI.

Objective To explore and identify the nutritional/inflammatory indicator with the highest predictive potential for overall survival(OS)in postoperative tumor patients so as to provide guidance for postoperative rehabilitation of tumor patients.Methods Data from 3 191 surgical patients were collected,including 15 nutritional/inflammatory indicators.The maximum selection rank statistic method was used to calculate the optimal cut-off values for continuous indicators.The Kaplan-Meier method was used to assess OS,and Cox proportional hazards models were used to analyze the association between the aforementioned 15 indicators and survival.The predictive value of these 15 indicators was evaluated with receiver operating characteristic(ROC)curves and C-index.Results Multivariate analysis showed that all 15 indicators were significantly associated with poorer OS in surgical patients(P＜0.05 for all).Time-dependent area under the curve(AUC)and C-index analysis indicated that 3 indicators with the highest predictive potential in OS in postoperative tumor patients were the nutritional risk index(NRI)(C-index:0.597),C-reactive protein-to-albumin ratio(CAR)(C-index:0.587),and C-reactive protein-to-lymphocyte ratio(CLR)(C-index:0.587).The optimal cut-off value for NRI was determined to be 104.31(i.e.,NRI＜104.31 suggests malnutrition)with the maximum selection rank statistic method,the optimal cut-off value for CAR to be 0.05(i.e.,CAR≥0.05 suggests a strong inflammatory response,often accompanied by malnutrition),and the optimal cut-off value for CLR to be 1.18(i.e.,CLR≥1.18 suggests a strong inflammatory response).Subgroup analysis indicated that NRI,CAR,and CLR had good correlation with tumor staging,and there were significant differences between tumor node metastasis(TNM)Ⅲ/Ⅳ stage patients and TNM Ⅰ/Ⅱ stage patients when there was a strong inflammatory response or malnutrition.Conclusion In postoperative tumor patients,NRI,CLR,and CAR have high prognostic value.Combining these with the patient's clinical stage,it enables more precise guidance for clinical diagnosis and treatment strategies.

Amoenucles A-F (1-6), six previously undescribed nucleoside derivatives, and two known analogs (7 and 8) were isolated from the culture of Aspergillus amoenus TJ507. Their structures were elucidated through spectroscopic analysis, single-crystal X-ray crystallography, and chemical reactions. Notably, 3 and 4 represent the first reported instances of nucleosides with an attached pyrrole moiety. Of particular significance, the absolute configuration of the sugar moiety of 1-4 was determined using nuclear magnetic resonance (NMR), electric circular dichroism (ECD) calculations, and a hydrolysis reaction, presenting a potentially valuable method for confirming nucleoside structures. Furthermore, 1, 2, and 5-8 exhibited potential tumor necrosis factor α (TNF-α) inhibitory activities, which may provide a novel chemical template for the development of agents targeting autoimmune and inflammatory diseases.
Aspergillus/chemistry* ; Tumor Necrosis Factor-alpha/antagonists & inhibitors* ; Molecular Structure ; Nucleosides/isolation & purification* ; Crystallography, X-Ray ; Animals ; Humans ; Mice ; Magnetic Resonance Spectroscopy

Objective : To verify the role of vascular endothelial growth factor B(VEGFB) in maintenance of skeletal muscle mass under chow-fed and high-fat diet, and to investigate the role of crosstalk between VEGFB and fibroblast growth factor(FGF) signaling pathways in the process. Methods : Four experimental groups were designed: VEGFB+/+chow-fed diet group, VEGFB-/-chow-fed diet group, VEGFB+/+high-fat diet group, VEGFB-/-high-fat diet group. Skeletal muscles from 24 weeks mice were isolated and weighed. Gene expression association analysis and qPCR experiments were conducted to assess FGFs expression levels. Results : Under both dietary conditions, VEGFB ablation resulted in reduced muscle mass. Under chow-fed diet condition, 8 FGFs level reduced including 6 paracrine FGFs in the skeletal muscle from VEGFB-/-mice. Under high-fat diet condition, 11 FGFs level decreased including 8 paracrine FGFs in VEGFB-/-mice. Conclusion VEGFB may participate in regulating skeletal muscle mass through FGF networks in the skeletal muscles.