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 investigate the efficacy of magnesium-strontium co-doped hydroxyapatite mineralized collagen (MSHA/Col) in improving the bone repair microenvironment and enhancing bone regeneration capacity, providing a strategy to address the insufficient biomimetic composition and limited bioactivity of traditional hydroxyapatite mineralized collagen (HA/Col) scaffolds. Methods: A high-molecular-weight polyacrylic acid-stabilized amorphous calcium magnesium strontium phosphate precursor (HPAA/ACMSP) was prepared. Its morphology and elemental distribution were characterized by high-resolution transmission electron microscopy (TEM) and energy-dispersive spectroscopy. Recombinant collagen sponge blocks were immersed in the HPAA/ACMSP mineralization solution. Magnesium-strontium co-doped hydroxyapatite was induced to deposit within collagen fibers (experimental group: MSHA/Col; control group: HA/Col). The morphological characteristics of MSHA/Col were observed using scanning electron microscopy (SEM). Its crystal structure and chemical composition were analyzed by X-ray diffraction and Fourier transform infrared spectroscopy, respectively. The mineral phase content was evaluated by thermogravimetric analysis. The scaffold's porosity, ion release, and in vitro degradation performance were also determined. For cytological experiments, CCK-8 assay, live/dead cell staining, alkaline phosphatase staining, alizarin red S staining, RT-qPCR, and western blotting were used to evaluate the effects of the MSHA/Col scaffold on the proliferation, viability, early osteogenic differentiation activity, late mineralization capacity, and gene and protein expression levels of key osteogenic markers [runt-related transcription factor 2 (Runx2), collagen type Ⅰ (Col-Ⅰ), osteopontin (Opn), and osteocalcin (Ocn)] in mouse embryonic osteoblast precursor cells (MC3T3-E1). Results: HPAA/ACMSP appeared as amorphous spherical nanoparticles under TEM, with energy spectrum analysis showing uniform distribution of carbon, oxygen, calcium, phosphorus, magnesium, and strontium elements. SEM results of MSHA/Col indicated successful complete intrafibrillar mineralization. Elemental analysis showed the mass fractions of magnesium and strontium were 0.72% (matching the magnesium content in natural bone) and 2.89%, respectively. X-ray diffraction revealed characteristic peaks of hydroxyapatite crystals (25.86°, 31°-34°). Infrared spectroscopy results showed characteristic absorption peaks for both collagen and hydroxyapatite. Thermogravimetric analysis indicated a mineral phase content of 78.29% in the material. The scaffold porosity was 91.6% ± 1.1%, close to the level of natural bone tissue. Ion release curves demonstrated sustained release behavior for both magnesium and strontium ions. The in vitro degradation rate matched the ingrowth rate of new bone tissue. Cytological experiments showed that MSHA/Col significantly promoted MC3T3-E1 cell proliferation (130% increase in activity at 72 h, P < 0.001). MSHA/Col exhibited excellent efficacy in promoting osteogenic differentiation, significantly upregulating the expression of osteogenesis-related genes and proteins (Runx2, Col-Ⅰ, Opn, Ocn) (P < 0.01). Conclusion The MSHA/Col scaffold achieves dual biomimicry of natural bone in both composition and structure, and effectively promotes osteogenic differentiation at the genetic and protein levels, breaking through the functional limitations of pure hydroxyapatite mineralized collagen. This provides a new strategy for the development of functional bone repair materials

Growth arrest DNA damage-inducible protein 45 β (GADD45B) has been reported to be a regulatory factor for active DNA demethylation and is implicated in the modulation of synaptic plasticity and chronic stress-related psychopathological processes. However, its precise role and mechanism of action in stress susceptibility remain elusive. In this study, we found a significant reduction in GADD45B expression specifically in the ventral, but not the dorsal hippocampal CA1 (dCA1) of stress-susceptible mice. Furthermore, we demonstrated that GADD45B negatively regulates susceptibility to social stress and NMDA receptor-dependent long-term potentiation (LTP) in the ventral hippocampal CA1 (vCA1). Importantly, through pharmacological inhibition using the NMDA receptor antagonist MK801, we provided further evidence supporting the hypothesis that GADD45B potentially modulates susceptibility to social stress by influencing NMDA receptor-mediated LTP. Collectively, these results suggested that modulation of NMDA receptor-mediated synaptic plasticity is a pivotal mechanism underlying the regulation of susceptibility to social stress by GADD45B.
Animals ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors* ; CA1 Region, Hippocampal/drug effects* ; Male ; Stress, Psychological/physiopathology* ; Mice ; Neuronal Plasticity/drug effects* ; Long-Term Potentiation/drug effects* ; Mice, Inbred C57BL ; Antigens, Differentiation/metabolism* ; Dizocilpine Maleate/pharmacology* ; Excitatory Amino Acid Antagonists/pharmacology* ; GADD45 Proteins

Objective To investigate the safety of endoscopic inflatable thyroid surgery on elderly patients by comparing the clinical characteristics and incidence of postoperative complications between elderly and non-elderly patients.Methods A retrospective analysis of clinical data was conducted on 204 patients who underwent endoscopic inflatable thyroid surgery at The Second Affiliated Hospital of Xi'an Jiaotong University from May 2021 to August 2024.Based on propensity score matching(PSM),a total of 54 elderly patients(age ≥60 years)and 150 middle-aged and young patients(18-59 years)were selected for comparison of clinical data,surgical-related indicators,and postoperative outcomes between the two groups.Results After matching,baseline data in both groups exhibited no statistically significant differences(P＞0.05).There were no statistically significant variances(P＞0.05)in intraoperative blood loss,surgical time,postoperative drainage volume,Faces Pain Scale-Revised(FPS-R),hoarseness,or hypoparathyroidism between the two groups.Although the two groups differed significantly in the Charlson Comorbidity Index(CCI)and age-adjusted Charlson Comorbidity Index(aCCI)(P＜0.05),there were no significant differences in the postoperative delirium,acute cardiocerebrovascular events,hospitalization costs,or postoperative length of stay(P＞0.05).One patient in the elderly group had postoperative delirium and but recovered 5 days after surgery.Conclusion Although elderly patients have more chronic complications than non-elderly,endoscopic thyroid surgery in elderly patients with thyroid tumors remains safe and effective,which makes it deserve clinical application.

Objective To investigate the clinical characteristics,diagnosis,and treatment of gastric duplication(GD)in children.Methods A retrospective analysis was conducted on the clinical data of 46 pediatric patients with GD treated at our hospital from January 2008 to January 2025.The evaluated parameters included age,gender,symptoms,comorbidities,imaging data,surgical process,postoperative treatment and follow-up situation.Analyze the clinical characteristics of GD.Results Forty-four cases were cystic structures,and 2 cases were sinus tracts or tubular structures respectively.The most common site was the cardia/fundus area(20 cases).Seventeen cases were asymptomatic(7 detected during prenatal screening and 10 identified incidentally).The most common associated anomalies were inguinal hernia(4 cases),pulmonary airway malformation(3 cases),pulmonary sequestration(3 cases),and hiatal hernia(3 cases).All 46 patients underwent ultrasound examination,with an accuracy of 97.8％.Upper gastrointestinal contrast studies were performed in 16 cases and computed tomography(CT)was conducted in 34 patients.Perforation occurred in 7 cases.Surgical approaches included laparoscopy(35 cases,with 5 conversions to open surgery),open surgery(9 cases),robotic surgery(1 case),transthoracic surgery(1 case).Operative time ranged from 50 to 250 minutes(median:105 minutes).Postoperative pathology identified pancreatic heterotopia in 6 cases.Time to resume oral intake ranged from 1 to 17 days(median:4 days),and postoperative hospital stay lasted 3-21 days(median:7 days).During follow-up,one patient was readmitted for adhesive intestinal obstruction and managed conservatively,with no other significant complications reported.Conclusion Pediatric GD is a rare congenital anomaly,typically presenting as non-communicating cystic lesions with nonspecific clinical manifestations.Ultrasonography is the primary diagnostic tool,with upper GI series,CT/MRI,and endoscopy as adjuncts.While prompt surgical intervention is indicated for symptomatic cases,those complicated by perforation/infection should undergo delayed elective resection ≥ 3 months following complete inflammatory resolution.Laparoscopic approach is the treatment of choice,while endoscopic intraoperative localization or endoscopic therapy may be considered for small intraluminal lesions.

Therapeutic cancer vaccines have experienced a resurgence over the past ten years. Cancer vaccines are typically designed to enhance specific stages of the cancer-immunity cycle, primarily by activating the immune system to promote tumor regression and overcome immune resistance. In this review, we summarize the significant recent advancements in cancer immunotherapy based on the cancer-immunity cycle, including the effector cell function, infiltration, initiation, and exhaustion. We summarize the identification of tumor antigens and their delivery through cancer vaccines. We discuss how specific stages of the cancer-immunity cycle have been leveraged to augment anti-tumor immune responses and improve vaccine efficacy. Additionally, the impact of aging and myelosuppression, two prevalent forms of immunological stress, on the effectiveness of therapeutic cancer vaccines is deliberated. Finally, we summarize the current status of various therapeutic cancer vaccines at different clinical trial phases.
Humans ; Cancer Vaccines/therapeutic use* ; Neoplasms/therapy* ; Immunotherapy/methods* ; Antigens, Neoplasm/immunology* ; Animals

Objective To explore the effects of cerium-doped mesoporous bioactive glass nanoparticles(Ce-MBGNs)as reactive oxy-gen species(ROS)-responsive nanocarriers on inflammation in pulp and their potential to promote odontogenic differentiation of dental pulp stem cells(DPSCs).Methods The cytotoxicity of Ce-MBGNs was assessed by CCK-8.The expression of mRNA of osteogenic/odontogenic differentiation in DPSCs and that of inflammatory factor in RAW264.7 cells were detected by RT-qPCR.Alkaline phospha-tase and Alizarin Red S staining were utilized to investigate their ability to promote dentin mineralization.The ability of Ce-MBGNs to scavenge ROS was evaluated by immunofluorescence and JC-1 staining was used to assess the membrane potential(MMP)of mitochon-drial.Results Ce-MBGNs exhibited good biocompatibility and significantly increased the expression of osteogenic/odontogenic-related genes in DPSCs,promoting mineralization.Additionally,Ce-MBGNs effectively scavenged intracellular ROS,maintained MMP,inhib-ited the expression of pro-inflammatory factors,and promoted the expression of anti-inflammatory factors.Conclusion Ce-MBGNs can protect DPSCs from oxidative damage by maintaining the MMP of mitochondrial and controlling inflammation,and promote their odonto-blastic differentiation,providing a theoretical basis for the development of novel therapeutic agents for oral treatment.

Objective:To construct a rat model of non-alcoholic fatty liver disease(NAFLD)by choline-deficient high fat diet(CDHFD),and to observe the association between feeding cycle and antioxidant pathway.Methods:The study lasted 16 weeks and was divided into 4 cycles.Detection of pathological changes and expression of antioxidant enzymes in rats liver in different cycles.Results:The early stage of liver steatosis and inflammation in model rats was 2～4 weeks,non-alcoholic steatohepatitis(NASH)stage was 4～8 weeks,and liver fibrosis progression was 8～16 weeks.Mechanistic studies had shown that the expressions of antioxidant enzymes Nrf2,SOD and GSH-Px in the liver of NAFLD rats gradually decreased with the extension of the feeding cycle.Conclusion:Different modeling cycles can successfully induce the pathological changes of steatosis,inflammation and liver fibrosis in rat liver,and the pathological changes are time-dependent with the expressions of antioxidant enzymes.

Objective To explore the effects of cerium-doped mesoporous bioactive glass nanoparticles(Ce-MBGNs)as reactive oxy-gen species(ROS)-responsive nanocarriers on inflammation in pulp and their potential to promote odontogenic differentiation of dental pulp stem cells(DPSCs).Methods The cytotoxicity of Ce-MBGNs was assessed by CCK-8.The expression of mRNA of osteogenic/odontogenic differentiation in DPSCs and that of inflammatory factor in RAW264.7 cells were detected by RT-qPCR.Alkaline phospha-tase and Alizarin Red S staining were utilized to investigate their ability to promote dentin mineralization.The ability of Ce-MBGNs to scavenge ROS was evaluated by immunofluorescence and JC-1 staining was used to assess the membrane potential(MMP)of mitochon-drial.Results Ce-MBGNs exhibited good biocompatibility and significantly increased the expression of osteogenic/odontogenic-related genes in DPSCs,promoting mineralization.Additionally,Ce-MBGNs effectively scavenged intracellular ROS,maintained MMP,inhib-ited the expression of pro-inflammatory factors,and promoted the expression of anti-inflammatory factors.Conclusion Ce-MBGNs can protect DPSCs from oxidative damage by maintaining the MMP of mitochondrial and controlling inflammation,and promote their odonto-blastic differentiation,providing a theoretical basis for the development of novel therapeutic agents for oral treatment.

Objective To investigate the safety of endoscopic inflatable thyroid surgery on elderly patients by comparing the clinical characteristics and incidence of postoperative complications between elderly and non-elderly patients.Methods A retrospective analysis of clinical data was conducted on 204 patients who underwent endoscopic inflatable thyroid surgery at The Second Affiliated Hospital of Xi'an Jiaotong University from May 2021 to August 2024.Based on propensity score matching(PSM),a total of 54 elderly patients(age ≥60 years)and 150 middle-aged and young patients(18-59 years)were selected for comparison of clinical data,surgical-related indicators,and postoperative outcomes between the two groups.Results After matching,baseline data in both groups exhibited no statistically significant differences(P＞0.05).There were no statistically significant variances(P＞0.05)in intraoperative blood loss,surgical time,postoperative drainage volume,Faces Pain Scale-Revised(FPS-R),hoarseness,or hypoparathyroidism between the two groups.Although the two groups differed significantly in the Charlson Comorbidity Index(CCI)and age-adjusted Charlson Comorbidity Index(aCCI)(P＜0.05),there were no significant differences in the postoperative delirium,acute cardiocerebrovascular events,hospitalization costs,or postoperative length of stay(P＞0.05).One patient in the elderly group had postoperative delirium and but recovered 5 days after surgery.Conclusion Although elderly patients have more chronic complications than non-elderly,endoscopic thyroid surgery in elderly patients with thyroid tumors remains safe and effective,which makes it deserve clinical application.