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.

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.

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.

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.

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 ; Cardiovascular Diseases/drug therapy* ; Fibrinolytic Agents/therapeutic use* ; Hemorrhage ; Anticoagulants ; Platelet Aggregation Inhibitors

Objective : High performance liquid chromatography⁃mass spectrometry (LC⁃MS/MS) system was used to accurately determine 22 bile acids in serum , liver, amniotic fluid and placenta of pregnant mice , and a LC⁃MS/ MS method was established for efficient detection and analysis of bile acids in serum , liver, amniotic fluid and placenta of mice. Methods : Pregnant mice serum , liver, amniotic fluid and placenta samples were processed , with 0. 1% glacial acetic acid in 4 mmol/L ammonium acetate aqueous solution as mobile phase A and pure methanol as mobile phase B , the flow rate was 0. 4 ml/min , a gradient elution program was used to elute with Phenomenex Gemini 3 μm NX⁃C18 110A ( 100 mm × 2. 0 mm) chromatographic column elution , and mass spectrometry detection system used an electrospray ion source for negative ion multiple reaction monitoring. Results : The linear relationship of 22 bile acids in the quantitative range was good. The RSD of inter⁃day and intra⁃day precision at low , medium and high concentrations was 0. 5% - 7. 4% , the matrix effect was 88% - 110% , and the extraction recovery was 84% - 108% . Conclusion In this experiment , LC⁃MS/MS was established to detect 22 bile acids in serum , liver, amniotic fluid and placenta of pregnant mice. The method not only has high sensitivity and selectivity , but also can stably detect a large number of samples.

OBJECTIVE: To explore whether the ethanol extract of Herpetospermum caudigerum Wall (EHC), a Xizang medicinal plant traditionally used for treating liver diseases, can improve imiquimod-induced psoriasis-like skin inflammation. METHODS: Immunohistochemistry and immunofluorescence staining were used to determine the effects of topical EHC use in vivo on the skin pathology of imiquimod-induced psoriasis in mice. The protein levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin-17A (IL-17A) in mouse skin samples were examined using immunohistochemical staining. In vitro, IFN-γ-induced HaCaT cells with or without EHC treatment were used to evaluate the expression of keratinocyte-derived intercellular cell adhesion molecule-1 (ICAM-1) and chemokine CXC ligand 9 (CXCL9) using Western blotting and reverse transcription-quantitative polymerase chain reaction. The protein synthesis inhibitor cycloheximide and proteasome inhibitor MG132 were utilized to validate the EHC-mediated mechanism underlying degradation of ICAM-1 and CXCL9. RESULTS: EHC improved inflammation in the imiquimod-induced psoriasis mouse model and reduced the levels of IFN-γ, TNF-α, and IL-17A in psoriatic lesions. Treatment with EHC also suppressed ICAM-1 and CXCL9 in epidermal keratinocytes. Further mechanistic studies revealed that EHC suppressed keratinocyte-derived ICAM-1 and CXCL9 by promoting ubiquitin-proteasome-mediated protein degradation rather than transcriptional repression. Seven primary compounds including ehletianol C, dehydrodiconiferyl alcohol, herpetrione, herpetin, herpetotriol, herpetetrone and herpetetrol were identified from the EHC using ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry. CONCLUSION Topical application of EHC ameliorates psoriasis-like skin symptoms and improves the inflammation at the lesion sites. Please cite this article as: Zhong Y, Zhang BW, Li JT, Zeng X, Pei JX, Zhang YM, Yang YX, Li FL, Deng Y, Zhao Q. Ethanol extract of Herpetospermum caudigerum Wall ameliorates psoriasis-like skin inflammation and promotes degradation of keratinocyte-derived ICAM-1 and CXCL9. J Integr Med. 2023; 21(6): 584-592.
Animals ; Mice ; Interleukin-17/metabolism* ; Intercellular Adhesion Molecule-1 ; Imiquimod/adverse effects* ; Tumor Necrosis Factor-alpha/metabolism* ; Ligands ; Psoriasis/chemically induced* ; Keratinocytes ; Inflammation/drug therapy* ; Chemokines/metabolism* ; Interferon-gamma/metabolism* ; Disease Models, Animal ; Mice, Inbred BALB C

Objective: To establish a rapid and specific quantitative real-time PCR (qPCR) method for the detection of SARS-CoV-2 subgenomic nucleocapsid RNA (SgN) in patients with COVID-19 or environmental samples. Methods: The qPCR assay was established by designing specific primers and TaqMan probe based on the SARS-CoV-2 genomic sequence in Global Initiative of Sharing All Influenza Data (GISAID) database. The reaction conditions were optimized by using different annealing temperature, different primers and probe concentrations and the standard curve was established. Further, the specificity, sensitivity and repeatability were also assessed. The established SgN and genomic RNA (gRNA) qPCR assays were both applied to detect 21 environmental samples and 351 clinical samples containing 48 recovered patients. In the specimens with both positive gRNA and positive SgN, 25 specimens were inoculated on cells. Results: The primers and probes of SgN had good specificity for SARS-CoV-2. The minimum detection limit of the preliminarily established qPCR detection method for SgN was 1.5×10² copies/ml, with a coefficient of variation less than 1%. The positive rate of gRNA in 372 samples was 97.04% (361/372). The positive rates of SgN in positive environmental samples and positive clinical samples were 36.84% (7/19) and 49.42% (169/342), respectively. The positive rate and copy number of SgN in Wild strain were lower than those of SARS-CoV-2 Delta strain. Among the 25 SgN positive samples, 12 samples within 5 days of sampling time were all isolated with virus; 13 samples sampled for more than 12 days had no cytopathic effect. Conclusion: A qPCR method for the detection of SARS-CoV-2 SgN has been successfully established. The sensitivity, specificity and repeatability of this method are good.
Humans ; SARS-CoV-2/genetics* ; COVID-19/diagnosis* ; Subgenomic RNA ; Real-Time Polymerase Chain Reaction/methods* ; RNA, Viral/genetics* ; Sensitivity and Specificity ; Nucleocapsid/chemistry* ; COVID-19 Testing