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.

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 investigate the application of cardiovascular magnetic resonance feature tracking(CMR-FT)in assessing myocardial strain in dilated cardiomyopathy(DCM)patients residing at high altitudes.Methods We retrospectively enrolled 29 DCM patients living at high altitudes(DCM-H),27 DCM patients living in a low-altitude plain environment(DCM-P),23 healthy volunteers living at a high altitude(HV-H),and 24 healthy volunteers living in a low-altitude plain environment(HV-P).All subjects underwent cine MRI scanning using a 3.0T rapid steady-state free precession sequence.The CMR images thus acquired were analyzed using cvi42,a post-processing software,to obtain left ventricular function and myocardial strain parameters.Results Compared with the HV-H group,the DCM-H group showed higher left ventricle end-diastolic volume(LVEDV)and left ventricle end-systolic volume(LVESV),and lower left ventricular ejection fraction(LVEF)and stroke volume(LVSV)(all P＜0.01).No significant difference was observed in cardiac function between the DCM-H and DCM-P groups(all P＞0.05).The absolute values of global radial strain(GRS),global circumferential strain(GCS),and global longitudinal strain(GLS)in the DCM-H group were lower than those in the HV-P group([14.5±6.5]％vs.[34.2±10.7]％,[-11.1±4.4]％vs.[-19.9±2.8]％,and[-7.7±3.2]％vs.[-13.6±4.1]％,respectively),with the differences being statistically significant(all P＜0.001).The DCM-H group had higher absolute GRS,GCS,and GCS values than the DCM-P group did([14.5±6.5]％vs.[7.0±2.7]％,[-11.1±4.4]％vs.[—5.4±2.2]％,and[—7.7±3.2]％vs.[—4.3±1.7]％,respectivley,all P＜0.01).Conclusion Myocardial strain in DCM patients living at a high altitude is lower than that in healthy volunteers living at a high altitude,but higher than that in DCM patients living in a low-altitude plain environment.CMR-FT can be used to quantitatively assess myocardial contractility in DCM patients living at a high altitude,showing promise for clinical application.

Objective To establish primary breast cancer cell lines from patient tissues and offer a new cancer cell model for basic research.Methods Breast cancer biopsy tissues were digested with typeⅡcollagenase and cultured in BCMI medium.When the cells proliferated rapidly,the medium was switched to DMEM.STR genotyping was per-formed to identify specific genetic markers of the four primary breast cancer cell lines.Colony expansion assays and sphere formation assays were conducted to analyze its tumorigenicity.Real-time PCR and Western blot experiments were used to analyze the expression of the epithelial-mesenchymal transition(EMT)molecule markers.Migration and invasion assays were performed to assess the metastatic potential of the primary breast cancer cells.Results We es?tablished four primary breast cancer cell lines:BC25#,BC51#,BC56#,and BC57#.These cell lines were cultured in DMEM medium,passaged multiple times and tagged with details about their clinical past.STR genotyping identified specific genetic markers for each of the four primary breast cancer cell lines.Clonogenic and sphere formation assays revealed that the four lines have a stronger tumor?forming capability compared to the classic breast cancer cell line T?47D.Real?time PCR and Western blot experiments showed that,compared to T?47D,the four primary breast cancer cell lines have decreased E?cadherin expression and increased vimentin expression.Migration and invasion assays indicated that BC25#had a higher metastatic potential than the traditional breast cancer cell line T?47D.Conclusions Four primary breast cancer cell lines,BC25#,BC51#,BC56#and BC57#are successfully estab?lished,which may act as new cancer cell model for laboratory research of breast cancer.

Objective To investigate the role of a novel human-specific long noncoding RNA(lncRNA),MEK6-AS1,and its potential molecular mechanism in improving the osteogenic differentiation of senescent mesenchymal stem cells(MSCs).Methods An in vitro human MSCs replicative senescence model was established by sequen-tial passaging,and then senescence was identified by β staining and senescence-related gene expression.RT-qPCR was used to detect the expression of MEK6-AS1 during senescence and osteogenic differentiation of human MSCs(hMSCs);Lentiviral knockdown technology was used to regulate the expression of MEK6-AS1 in the MSCs replicative senescence model.Transcriptome sequencing technology was utilized to analyze the effects of MEK6-AS1 on the transcriptome of hMSCs especially on genes and pathways related to osteogenic differentiation.The effect of MEK6-AS1 as an intervention target at osteogenic differentiation of human senescent hMSCs was evaluated with alkaline phosphatase staining microscopy.PCR technology was used to detect osteogenic gene expression levels in cells.Results With aging process,the osteogenic differentiation ability of hMSCs decreased significantly while the expression level of MEK6-AS1 was enhanced(P＜0.000 1).Knockdown of MEK6-AS1 significantly enhanced the osteogenic differentiation of MSCs by the up-regulating expression of osteogenic markers and increasing minerali-zation capacity(P＜0.001).Conclusions Knockdown of human-specific lncRNA MEK6-AS1 improves osteogenic differentiation of senescent MSCs,providing a new target and theoretical basis for the treatment of senescence-asso-ciated osteoporosis.

Natural killer cells(NK)are important innate immune cells that do not require prior antigen exposure and can directly recognize and attack virus-infected cells and tumor cells.The activation and effector functions of NK cells are regulated by a balance of signals delivered through their surface activating receptors and inhibitory re-ceptors,which bind to ligands on target cells to achieve cytotoxicity via"induced self"and"missing self"recogni-tion models.The killing mechanisms of NK cells primarily include release of cytotoxic granules such as perforin and granzymes to induce target cell lysis,death receptor-mediated apoptosis,secretion of various cytokines,chemokines and growth factors to coordinate with other immune cells in killing tumor cells,thereby generating secondary im-mune responses and antibody-dependent cellular cytotoxicity(ADCC).

This article focuses on the clinical need for curative interventions in chronic diseases.It proposes an inte-grated medical framework that combines"quantum prediction,prevention and control through Traditional Chinese and Western Medicine,and stem cell repair"and details its path to clinical application.To address the complex,multi-target pathology of diseases like diabetes,this research integrates multiple disciplines:stem cell technology,the holistic philosophy of Traditional Chinese Medicine(TCM),the evidence-based rigor of Western Medicine,and the cutting-edge concepts of quantum biology.The goal is to create a new diagnostic and therapeutic model that syn-thesizes disease and syndrome classification while bridging macro and micro perspectives,ultimately driving break-throughs in chronic disease management.Theoretically,the study proposes a strategy to rejuvenate cells and remodel the microenvironment using pluripotent stem cells combined with synergistic TCM-Western Medicine approaches.Practically,it establishes a seamless system—from molecular early-warning and dynamic prevention to tissue re-pair—supported by standardized protocols,preclinical validation,multi-center clinical trials,and an intelligent health management platform.