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 explore the effect of scutellarin on lipopolysaccharide(LPS)induced neuroinflammation in BV-2 microglia cells.Methods BV-2 microglia were cultured and randomly divided into 6 groups:control group(Ctrl),cyclic GMP-AMP synthetase(cGAS)inhibitor RU320521 group(RU.521 group),LPS group,LPS+RU.521 group,LPS+scutellarin pretreatment group(LPS+S)and LPS+S+RU.521 group.The expressions of cGAS,stimulator of interferon gene(STING),nuclear factor kappa B(NF-κB),phosphorylated NF-κB(p-NF-κB),neuroinflammatory factors PYD domains-containing protein 3(NLRP3)and tumor necrosis factor α(TNF-α)in BV-2 microglia were detected by Western blotting and immunofluorescent double staining(n= 3).Results Western blotting and immunofluorescent double staining showed that compared with the control group,the expression of cGAS,STING,p-NF-κB,NLRP3 and TNF-α in BV-2 microglia increased significantly after LPS induction(P<0.05),while the expression of cGAS,STING,p-NF-κB,NLRP3 and TNF-α in LPS+S group were significantly lower than those in LPS group(P<0.05).Treatment with cGAS pathway inhibitor RU.521 showed similar effects as the pre-treatment group with scutellarin.In addition,the change of NF-κB in each group was not statistically significant(P>0.05).Conclusion Scutellarin inhibits the neuroinflammation mediated by BV-2 microglia cells,which may be related to cGAS-STING signaling pathway.

Objective To investigate the effect of miR-217 on gefitinib resistance in non-small cell lung cancer(NSCLC),and to explore the downstream target genes and related pathways.Methods qRT-PCR was used to detect the expression of miR-217 in human lung normal epithelial cell lines BEAS-2B,NSCLC cell lines A549,HCC827,PC9,NCI-H1975 and gefitinib resistant strain PC9/GR.PC9/GR cells were selected and the cells of control group,NC-mimic group,miR-217 mimic group,miR-217 mimic+si-NC group,and miR-217 mimic+si-FOXO3 group were constructed using liposome transfection technique.CCK8 and clonal formation assay were used to detect changes in cell proliferation capacity,flow cytometry was used to detect changes in cell apoptosis capacity,and western blot was used to detect protein expression related to PI3K/AKT signaling pathway.The Targetscan bioinformatics website predicted the downstream target genes of miR-217,and the correlation between miR-217 and the target gene FOXO3 was detected by dual luciferase assay.Results Compared with BEAS-2B cells,the expression of miR-217 in A549,HCC827,PC9 and NCI-H1975 cells was significantly decreased(P＜0.05).With the increase of gefitinib concentration,the expression of miR-217 gene in PC9 cells was gradually decreased(P＜0.05),and the expression of miR-217 in PC9/GR cells was lower than that in PC9(P＜0.05).Compared with the control group and NC-mimic group,the cell proliferation capacity of miR-217 mimic group was significantly decreased(P＜0.05),the number of apoptosis was increased(P＜0.05),and the expression levels of p-PI3K and p-AKT were decreased(P＜0.05).Dual luciferase reporter gene assay proved that FOXO3 is the target of miR-217.Compared with miR-217 mimic group and miR-217 mimic+si-NC group,the cell drug resistance of miR-217 mimic+si-FOXO3 group was increased(P＜0.05),the proliferation ability was significantly increased(P＜0.05),and the number of apoptosis was decreased(P＜0.05).The expression levels of P-PI3K and P-AKT were increased(P＜0.05).Conclusion Overexpression of miR-217 reversed the resistance of PC9/GR to gefitinib in NSCLC cells and inhibited the proliferation and accelerated apoptosis of PC9/GR cells,which may be related to the regulation of PI3K/AKT signaling pathway by targeting FOXO3.

Electrical impedance tomography(EIT)is a non-invasive imaging technique that generates cross-sec-tional images of chest by measuring changes in impedance as electric currents passing through human body.In peri-operative respiratory management,EIT provides a real-time,consecutive monitoring of lung ventilation and perfusion status,guiding respiratory management of perioperative patients including medication for COPD and asth-ma,personalized PEEP settings for specific patient populations,lung protection for pediatric perioperative cases,and predicting postoperative pulmonary complications.Application of EIT in the perioperative period helps clinicians to manage patient respiratory status more accurately,reduces complications and improves outcomes.Through real-time monitoring and individualized treatment guidance,EIT enhances the safety and effectiveness of perioperative respiratory management,becoming an essential part of the operating room.This review summarises the application of EIT in the perioperative period,aiming to provide reference for the clinical application of EIT.

In black tea,theaflavins (TFs) are one important class of substances that determine sensory quality and have significant medicinal activities. In addition to the four kinds of common TFs,there may be many other theaflavin analogues (TFAs) with similar chemical structures in tea,but the study on them is very limited. Based on the characteristic sub-structure,mass spectrometry (MS) and MS/MS information,a method for screening and annotation of TFAs from the complex ultra high performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS) data was proposed in this work. By analyzing the oxidation and polymerization process of a few TFs,the theoretical reaction model of TFs were summarized,which was used to calculate the precursor ion values of potential TFAs. Meanwhile,the diagnostic fragmentation ions and neutral loss of TFAs according to the fragmentation pathways obtained from chemical standards or documented in literatures were summarized. As a result,36 kinds of compounds were successfully annotated based on the calculated precursor ion values and the MS fragmentation patterns,among which 6 kinds of compounds were reported for the first time in tea. In vitro synthesis experiments were carried out to verified the annotation results. Based on the results of quantitation of 36 kinds of TFAs,a partial least squares-discriminant analysis model was used to investigate the changes of these components during black tea manufacturing. The results indicated that these novel TFAs could be used to effectively distinguish the black tea samples before and after fermentation.

Objective:To investigate the efficacy and safety of a treatment regimen based on daratumumab in patients with high-risk relapsed refractory multiple myeloma(MM)with mSMART 3.0 score.Methods:Clinical data were collected from 16 patients with mSMART3.0 score high-risk relapsed refractory MM treated at the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from May 2020 to May 2023,all of whom received daltezumab-based regimen(regimen drugs including dexamethasone,isazomib,bortezomib,lenalidomide).The efficacy and safety of the treatment were retrospectively analyzed.Results:The median age of 16 patients was 63.5(47-70)years old,including 10 cases of IgG type,2 cases of IgA type,and 4 cases of light chain type.The curative efficacy was judged in all 16 patients,with an overall response rate of 93.75％(15/16),including 4 cases of strict complete remission(sCR),1 case of complete remission(CR),2 case of very good partial remission(VGPR),partial remission(PR)in 5 cases,and minor remission(MR)in 3 cases.The median follow-up time was 11(2-30)months,and the median progression-free survival and median overall survival were not achieved in 16 patients at the median follow-up period.The hematologic adverse effects of the treatment regimen using daratumumab-based were mainly neutropenia,and the non-hematologic adverse effects were mainly infusion-related adverse reactions and infections.Conclusion:Daratumumab-based regimen for the treatment of relapsed refractory MM patients with high risk of mSMART3.0 score has better efficacy and safety.

Humans ; Stroke, Lacunar ; Mendelian Randomization Analysis ; Leukocytes ; Telomere/genetics* ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide

OBJECTIVES: To study the protective effect of melatonin (Mel) against oxygen-induced retinopathy (OIR) in neonatal mice and the role of the HMGB1/NF-κB/NLRP3 axis. METHODS: Neonatal C57BL/6J mice, aged 7 days, were randomly divided into a control group, a model group (OIR group), and a Mel treatment group (OIR+Mel group), with 9 mice in each group. The hyperoxia induction method was used to establish a model of OIR. Hematoxylin and eosin staining and retinal flat-mount preparation were used to observe retinal structure and neovascularization. Immunofluorescent staining was used to measure the expression of proteins and inflammatory factors associated with the HMGB1/NF-κB/NLRP3 axis and lymphocyte antigen 6G. Colorimetry was used to measure the activity of myeloperoxidase. RESULTS: The OIR group had destruction of retinal structure with a large perfusion-free area and neovascularization, while the OIR+Mel group had improvement in destruction of retinal structure with reductions in neovascularization and perfusion-free area. Compared with the control group, the OIR group had significant increases in the expression of proteins and inflammatory factors associated with the HMGB1/NF-κB/NLRP3 axis, the expression of lymphocyte antigen 6G, and the activity of myeloperoxidase (P<0.05). Compared with the OIR group, the OIR+Mel group had significant reductions in the above indices (P<0.05). Compared with the control group, the OIR group had significant reductions in the expression of melatonin receptors in the retina (P<0.05). Compared with the OIR group, the OIR+Mel group had significant increases in the expression of melatonin receptors (P<0.05). CONCLUSIONS Mel can alleviate OIR-induced retinal damage in neonatal mice by inhibiting the HMGB1/NF-κB/NLRP3 axis and may exert an effect through the melatonin receptor pathway.
Animals ; Mice ; HMGB1 Protein ; Melatonin/therapeutic use* ; Mice, Inbred C57BL ; NF-kappa B ; NLR Family, Pyrin Domain-Containing 3 Protein ; Oxygen/adverse effects* ; Peroxidase ; Receptors, Melatonin ; Retinal Diseases/drug therapy*

OBJECTIVE: To derive the Chinese medicine (CM) syndrome classification and subgroup syndrome characteristics of ischemic stroke patients. METHODS: By extracting the CM clinical electronic medical records (EMRs) of 7,170 hospitalized patients with ischemic stroke from 2016 to 2018 at Weifang Hospital of Traditional Chinese Medicine, Shandong Province, China, a patient similarity network (PSN) was constructed based on the symptomatic phenotype of the patients. Thereafter the efficient community detection method BGLL was used to identify subgroups of patients. Finally, subgroups with a large number of cases were selected to analyze the specific manifestations of clinical symptoms and CM syndromes in each subgroup. RESULTS: Seven main subgroups of patients with specific symptom characteristics were identified, including M3, M2, M1, M5, M0, M29 and M4. M3 and M0 subgroups had prominent posterior circulatory symptoms, while M3 was associated with autonomic disorders, and M4 manifested as anxiety; M2 and M4 had motor and motor coordination disorders; M1 had sensory disorders; M5 had more obvious lung infections; M29 had a disorder of consciousness. The specificity of CM syndromes of each subgroup was as follows. M3, M2, M1, M0, M29 and M4 all had the same syndrome as wind phlegm pattern; M3 and M0 both showed hyperactivity of Gan (Liver) yang pattern; M2 and M29 had similar syndromes, which corresponded to intertwined phlegm and blood stasis pattern and phlegm-stasis obstructing meridians pattern, respectively. The manifestations of CM syndromes often appeared in a combination of 2 or more syndrome elements. The most common combination of these 7 subgroups was wind-phlegm. The 7 subgroups of CM syndrome elements were specifically manifested as pathogenic wind, pathogenic phlegm, and deficiency pathogens. CONCLUSIONS There were 7 main symptom similarity-based subgroups in ischemic stroke patients, and their specific characteristics were obvious. The main syndromes were wind phlegm pattern and hyperactivity of Gan yang pattern.
Humans ; Syndrome ; Ischemic Stroke ; Medicine, Chinese Traditional ; Liver ; Phenotype

Objective: To observe the present situation, efficacy and safety of immunotherapy in patients with malignant pleural mesothelioma (MPM). Methods: The data of 39 patients with MPM in two centers from 2016 to 2021 were collected and the efficacy and safety were evaluated. According to the application of immune checkpoint inhibitors (ICIs), these patients, whose median clinical follow-up amounting to 18.97 months, were divided into immunotherapy group (19 cases) and control group (20 cases). Kaplan-Meier method and Log-rank test were used for the survival analysis. Results: The objective response rate (ORR) and the disease control rate (DCR) in the immunotherapy group is 21.05% and 79.0% respectively, compared with 10.0% and 55.0% in the control group; and the difference was not statistically significant (P>0.05). The median overall survival (OS) in the immunotherapy group was significantly longer than that in the control group (14.53 months vs 7.07 months, P=0.015), but there was no significant difference in the median progression free survival (PFS) between two groups (4.80 months vs 2.03 months, P=0.062). Single factor survival analysis showed that the nature of pleural effusion, pathological subtype and the efficacy of immunotherapy were related to both PFS and OS of the patients with MPM (P<0.05). The incidence of adverse reactions in immunotherapy group was 89.5% (17 out of 19 cases), and the most common adverse event was hematological toxicity (9 cases), followed by nausea and vomiting (7 cases), fatigue (6 cases) and skin damage (6 cases). Five patients had immune checkpoint inhibitors (ICIs) related adverse reactions with grade 1-2. Conclusions: Patients with MPM have begun to receive immunotherapy in more than 2-line mainly combined chemotherapy in the real world, and the median treatment line is 2-line. Either combined with chemotherapy or anti-angiogenesis therapy, ICI inhibitors have significant efficacy, controllable adverse events and good clinical value.
Humans ; Mesothelioma, Malignant/drug therapy* ; Mesothelioma/drug therapy* ; Lung Neoplasms/drug therapy* ; Immune Checkpoint Inhibitors/therapeutic use* ; Immunotherapy/adverse effects*