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 construction of heart preservation model of empty beating donor based on extracorporeal membrane oxygenation (ECMO). Methods From January 2022 to August 2023, 20 Guangxi Bama miniature pigs weighing 25-30 kg were selected, half male and half female. Under general anesthesia and heparinization, a midline thoracotomy was performed. The pericardium was cut after freeing the anterior and posterior vena cavae, and a perfusion needle was inserted near the brachiocephalic artery in the ascending aorta, connected to a blood collection bag to collect 500-600 mL of blood. The anterior and posterior vena cavae were ligated, the aorta was blocked and perfused with HTK solution to stop the heart beating. The superior and inferior vena cavae were cut off, the right pulmonary vein was decompressed, the aorta and left and right pulmonary arteries and veins were cut off, and the whole heart was removed. An ECMO device was used to continuously perfuse a cardioprotective solution mainly composed of oxygenated warm blood, maintaining the isolated pig heart beating for 8 hours, monitoring (once/hour) ECMO perfusion parameters, blood gas indicators, perfusate electrolytes, inflammatory factors, myocardial enzymes, myoglobin, and troponin levels. Myocardial tissue was taken for hematoxylin-eosin (HE) staining to observe myocardial cell damage and evaluate the quality of heart preservation. Results Among the 20 isolated beating pig hearts, 17 successfully resumed beating, 3 experienced ventricular fibrillation, resuscitated after intracardiac electrical defibrillation, and all 20 pig hearts successfully beat for 8 hours. There was no statistical difference in ECMO perfusion parameters, blood gas indicators, perfusate electrolytes, and inflammatory factors at each time point (P>0.05). There were statistical increases in myocardial enzymes, myoglobin, and troponin levels (P<0.05). HE staining results suggested that there was no severe myocardial damage. Conclusion ECMO technology can be used for pig heart preservation with good results, and this study provides experimental evidence for improving heart preservation research in clinical heart transplantation.

Objective To study influencing factors of hypoproteinemia in maintenance hemodialysis pa-tients.Methods A multicenter study was conducted.We selected 397 maintenance hemodialysis patients hos-pitalized at five hospitals of Wenzhou Kangning Hospital Group from April to June 2024 as study subjects.Pa-tients'general data and laboratory test results were collected.Logistic regression combined with the CHAID decision tree model was used to analyze indicators of hypoproteinemia in patients.Results Among 397 main-tenance hemodialysis patients,92 had hypoproteinemia(hypoproteinemia group),with a prevalence of 23.17%;others were assigned to the normal protein group.Statistically significant differences existed between groups in gender,age,occupation,education level,diabetes,vascular access type,insurance type,weight,Hb,blood calcium,blood phosphorus,blood potassium,blood glucose,parathyroid hormone,creatinine,blood urea,and cholesterol(P<0.05).Logistic regression showed occupation,insurance type,diabetes,Hb,and creatinine were independent influencing factors(P<0.05).The CHAID decision tree model identified age as the root node.Conclusion Occupation,insurance type,diabetes,Hb,age,and creatinine are important influencing fac-tors for hypoproteinemia in maintenance hemodialysis patients.Logistic regression combined with decision tree analysis can play complementary roles.

Objective To investigate the impact of catheter-associated urinary tract infection(CAUTI)on the prognosis of neurosurgical inpatients with indwelling catheters.Methods Neurosurgical inpatients with indwelling catheters and hospital stays＞2 days from January 2018 to December 2023 were selected as the study subjects.CAUTI during hospitalization was used as the exposure factor.A 1∶2 propensity score matc-hing method was applied to control for confounding factors,subsequently,63 patients were included in the CAUTI group and 121 in the non-CAUTI group.The impact of CAUTI on prognostic indicators in these pa-tients was analyzed.Results A total of 554 neurosurgical inpatients with indwelling catheters were included,among whom 70 developed CAUTI,yielding an infection rate of 12.64％.After propensity score matching,compared with the non-CAUTI group,the CAUTI group showed significantly longer hospital stays and in-dwelling catheter durations,higher total hospitalization costs,and higher out-of-pocket expenses,the differ-ences were statistically significant(P＜0.05).However,there was no significant difference in mortality be-tween the two groups(P＞0.05).Among the various medical cost items,significant differences were observed in medical service fees,diagnostic fees,other treatment fees,Western medicine fees,antibacterial drug fees,traditional Chinese medicine fees,consumable costs,and other expenses(P＜0.05),while no significant differ-ence was found in surgical treatment fees(P＞0.05).Conclusion CAUTI prolongs hospital stays and in-dwelling catheter durations,and increases medical costs.Effective measures should be taken to prevent and control CAUTI,thereby improving patient prognosis,reducing patients' direct financial burden,and enhancing the utilization of medical resources.

Objective To explore the related factors of postoperative nutritional risk in elderly patients with proximal femoral nail anti rotation(PFNA)internal fixation and establish a prediction model of malnutrition.Methods A total of 574 elderly patients who underwent PFNA internal fixation in the First Medical Center of Chinese PLA General Hospital from January 2021 to June 2024 were included and divided into malnutrition group(n=389)and good nutrition group(n=185).The differences in 39 indicators in aspects of physiological,psychological,social,economic,environmental and medical fields were compared between the 2 groups.Logistic analysis was used to screen the nutritional risk factors,and then a nomogram model was constructed based on these factors.Results Advanced age,lower BMI,higher postoperative Self-Rating Anxiety Scale(SAS)score,less exercise before fracture,being farmers,higher economic pressure,lower preoperative albumin,preprotein and hemoglobin,and lower Barthel index before fracture were independent risk factors for nutritional risk in patients undergoing PFNA internal fixation(P＜0.05).The nomogram prediction model based on the above factors had an AUC value of 0.995(95％CI:0.987～1.000)in predicting the risk of malnutrition in these patients.When the threshold probability＞0.02,this model could be clinically beneficial in predicting the risk of postoperative malnutrition in patients after PFNA internal fixation.Conclusion Our nutritional risk prediction model based on age,BMI,economic pressure,pre-fracture exercise and preoperative albumin and other indicators is constructed for the elderly patients after PFNA internal fixation,and the model has high accuracy and clinical application value.

OBJECTIVE To investigate the improved anesthesia method of arytenoid cartilage reduction under general anesthesia in the treatment of arytenoid dislocation.METHODS The clinical data of 12 patients who underwent modified arytenoid cartilage reduction under general anesthesia in Beijing Tongren Hospital from July 2020 to March 2024 were retrospectively analyzed.To evaluate and analyze the modified anesthesia method of maintaining low degree of neuromuscular block during operation,the recovery of arytenoid cartilage movement and sound after operation.RESULTS All the 12 patients successfully completed arytenoid cartilage reduction.The articulation,arytenoid movement and glottis closure were improved significantly.Compared with the total voice handicap index(VHI),physical scores,functional scores and emotional scores before reduction,the scores at 1 month after surgery were significantly lower[83.5(75-91)vs.13(7-19),30.5(26.5-33)vs.5.5(3-7),25.5(22.5-29)vs.4(2-6),26(23.5-30)vs.4(1.5-6),P<0.001].No complications such as laryngeal spasm and laryngeal edema occurred during perioperative period.CONCLUSION Arytenoid cartilage reduction under modified general anesthesia has high safety,good patient cooperation and high reduction success rate.It provides a new option for the treatment of arytenoid dislocation.

Objective To explore the relationship between serum long non-coding RNA X-inactive specific transcript(LncRNA XIST)and microRNA-122-5p(miR-122-5p)expression and the severity of brain injury and prognosis in patients with sepsis-associated encephalopathy(SAE).Methods A total of 108 SAE patients(SAE group)and 52 patients with sepsis only(non-SAE group)admitted to the Ankang Hospital of Tradi-tional Chinese Medicine from January 2019 to December 2023 were selected as the study subjects.According to the degree of brain injury,the SAE patients were categorized into mild brain injury group[Glasgow Coma Scale(GCS)score 13-14,27 cases],moderate brain injury group(GCS score 9-12,36 cases),and severe brain injury group(GCS score 3-8,45 cases).Based on the 28-day prognosis,they were divided into death group(51 cases)and survival group(57 cases).Serum LncRNA XIST and miR-122-5p expression levels were measured using real-time quantitative PCR.The binding site of LncRNA XIST and miR-122-5p was predicted using the StarBase database,and Pearson correlation analysis was performed to evaluate the relationship be-tween serum LncRNA XIST and miR-122-5p expression in SAE patients.Multivariate unconditional Logistic regression was used to determine the association between serum LncRNA XIST,miR-122-5p expression,and prognosis in SAE patients.Receiver operating characteristic curves were used to assess the predictive efficacy of LncRNA XIST and miR-122-5p expression for SAE prognosis.Results Compared with non-SAE group,se-rum LncRNA XIST expression was increased and miR-122-5p expression was decreased in SAE group,with statistical significance(P＜0.05).There were binding sites between LncRNA XIST and miR-122-5p,and the expression of LncRNA XIST in serum of SAE patients was negatively correlated with that of miR-122-5p(P＜0.05).Serum LncRNA XIST expression in mild brain injury group,middle brain injury group and severe brain injury group was increased successively,while miR-122-5p expression was decreased successively,with statistical significance(P＜0.05).The 28-day mortality rate of SAE patients after admission was 47.22％(51/108).Compared with the survival group,the expression of serum LncRNA XIST was higher in the death group,and the expression of miR-122-5p was lower,with statistical significance(P＜0.05).High sequential organ failure assessment(SOFA)score and high expression of LncRNA XIST were independent risk factors for death in SAE patients,while high GCS scores and high miR-122-5p expression of were independent protec-tive factors(P＜0.05).The combined expression of serum LncRNA XIST and miR-122-5p predicted the death of SAE patients with greater area under the curve than that of serum LncRNA XIST and miR-122-5p a-lone(P＜0.05).Conclusion Elevated serum LncRNA XIST and decreased miR-122-5p expression levels are associated with the severity of brain injury and poor prognosis in SAE patients.The combined detection of Ln-cRNA XIST and miR-122-5p has a high predictive value for SAE prognosis.

OBJECTIVES: To evaluate the inhibitory effect of Macrothele raveni crude venom against proliferation of different cancer cells and identify the active components in the venom. METHODS: Different cancer cell lines were treated with different concentrations of Macrothele raveni venom for 48 h, and cell proliferation and the half-maximal inhibitory concentrations (IC₅₀) of the venom were assessed with CCK-8 assay. The apoptosis rate of breast cancer MCF7 cells following the treatment was analyzed with flow cytometry, and the changes in cellular caspase-8 and caspase-9 expressions were detected. The crude venom was separated into protein, peptide, and small-molecule compound fractions using gel filtration chromatography and high-performance liquid chromatography (HPLC). The protein and peptide components were identified using proteomics analysis, and small-molecule compounds were structurally characterized using nuclear magnetic resonance (NMR), mass spectrometry (MS), and HPLC. RESULTS The crude venom exhibited strong concentration-dependent inhibitory effects on proliferation of MCF7 cells and nasopharyngeal carcinoma SUNE1 and HONE1 cells (IC₅₀ of 2.14±0.29, 1.57±0.14, and 2.85±0.15 µg/mL, respectively), with less potent inhibitory effects in gastric cancer HGC27 cells and colorectal cancer SW620 cells (IC₅₀ of 3.02±0.27 and 3.02±0.28 µg/mL, respectively). The crude venom significantly promoted MCF7 cell apoptosis likely via the caspase 8 signaling pathway. The protein fraction from the crude venom showed a weak inhibitory effect in MCF7 cells, whereas the peptide fraction exhibited a much stronger inhibitory effect (IC₅₀ of 6.41±0.31 µg/mL). The peptides in the peptide fraction, with relative molecular mass around 10 000, were homologous to those found in Macrothele gigas venom. The small-molecule fraction consisted mainly of nucleotide metabolites without obvious inhibitory effects in MCF7 cells, but its combination with the peptide fraction showed significantly enhanced inhibitory activity. Conclusion The inhibitory effects of Macrothele raveni venom, which vary significantly across different cancer cell lines, are attributed primarily to its peptide components, which may act synergistically with the nucleotide metabolites.
Humans ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Animals ; Cell Line, Tumor ; MCF-7 Cells ; Caspase 8/metabolism* ; Peptides/pharmacology* ; Caspase 9/metabolism*

Natural antimicrobial peptides (AMPs) are promising candidates for the development of a new generation of antimicrobials to combat antibiotic-resistant pathogens. They have found extensive applications in the fields of medicine, food, and agriculture. However, efficiently screening AMPs from natural sources poses several challenges, including low efficiency and high antibiotic resistance. This review focuses on the action mechanisms of AMPs, both through membrane and non-membrane routes. We thoroughly examine various highly efficient AMP screening methods, including whole-bacterial adsorption binding, cell membrane chromatography (CMC), phospholipid membrane chromatography binding, membrane-mediated capillary electrophoresis (CE), colorimetric assays, thin layer chromatography (TLC), fluorescence-based screening, genetic sequencing-based analysis, computational mining of AMP databases, and virtual screening methods. Additionally, we discuss potential developmental applications for enhancing the efficiency of AMP discovery. This review provides a comprehensive framework for identifying AMPs within complex natural product systems.

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