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.

Background Exposure to benzo[a]pyrene (BaP) may impair lung function through various mechanisms; however, it remains uncertain whether BaP induces ferroptosis in lung tissue cells, resulting in lung function impairment. Objective To investigate the ferroptosis of lung tissue cells triggered by subchronic BaP exposure in mice and its correlation with lung injury, and to explore the function of ferroptosis in BaP-induced lung tissue damage. Method Seventy-two healthy 3-weeks-old male C57BL/6J mice were acclimatized for 1 week and then randomly divided into six groups: control group (corn oil 10 mL·kg⁻¹), low-dose BaP group (2.5 mg·kg⁻¹), medium-dose BaP group (5 mg·kg⁻¹), high-dose BaP group (10 mg·kg⁻¹), BaP+ferrostatin-1 (Fer-1) group (10 mg·kg⁻¹+1 mg·kg⁻¹), and Fer-1 group (1 mg·kg⁻¹), with 12 mice each group. Corn oil and BaP were administered via gavage every other day, followed by an intraperitoneal injection of Fer-1 the subsequent day, throughout a period of 90 d. Whole-body plethysmography was applied to detect lung function; hematoxylin-eosin staining (HE) and Masson staining were used to observe lung tissue injury and fibrosis; microscopy of alveolar epithelial cells was conducted to reveal mitochondrial morphology; biochemical assays were used to measure the content of tissue iron, malondialdehyde (MDA), and glutathione (GSH), as well as the activity of glutathione peroxidase (GSH-Px); Western blotting and real-time quantitative PCR (RT-qPCR) analyses were performed to reveal the protein and mRNA expression of ferroptosis markers. Results Compared to the control group, the high-dose BaP group showed a significant increase in expiration time (Te) (P<0.01), and a significant decrease in ratio rate of achieving peak expiratory flow (Rpef), tidal volume (TVb), peak inspiratory flow (PIF), minute volume (MVb), and peak expiratory flow (PEF) (P<0.05 or 0.01). Based on the results of HE and Masson staining, partial destruction of alveolar structures, thickening of alveolar walls, infiltration of inflammatory cells, significant thickening of tracheal walls and a large deposition of collagen fibers in lung tissue were observed in the medium- and high-dose BaP groups. By microscopy, the alveolar epithelial cells exposed to low-dose BaP showed condensed chromatin, and the mitochondria exposed to medium and high-dose BaP showed wrinkles, increased mitochondrial membrane density, and diminished mitochondrial cristae. Compared to the control group, in the medium- and high-dose BaP groups, the lung tissue iron content and the expression levels of ACSL4 protein and mRNA significantly elevated (P<0.01 or 0.05), while the mRNA expression level of SLC7A11 significantly decreased (P<0.05); in the high-dose BaP group, the MDA content, COX2 protein, and PTGS2 mRNA expression levels significantly increased (P<0.05 or 0.01), GSH content and GSH-Px activity, GPX4 protein and mRNA expression levels, and the expression level of SLC7A11 protein significantly decreased (P<0.01 or 0.05). The ferroptosis inhibitor Fer-1 markedly reversed respiratory function, morphology, mitochondrial alterations, and the aforementioned ferroptosis-related biochemical indicators. Conclusion Subchronic exposure to BaP can induce ferroptosis in mice lung tissue cells, resulting in compromised lung function.

Objective To explore the regulation of Chaihuang Qingyi Huoxue Granule on intestinal microecological changes in rats with severe acute pancreatitis (SAP) and the potential mechanism for its treatment of SAP. Methods Forty-eight rats were randomly divided into sham operation group (SHAM),SAP model group (SAP),and Chaihuang Qingyi Huoxue Granule (CH)group,with 16 rats in each group. Each group was further divided into 12 h and 24 h subgroups. The SAP model was induced by retrograde injection of 5％ sodium taurocholate into the pancreaticobiliary duct through duodenal wall. The SHAM and SAP groups received normal saline by gavage,while the CH group received 1.2 g·kg-1 Chaihuang Qingyi Huoxue Granule solution by gavage every six hours. At 12 h and 24 h after operation,eight rats from each group were sacrificed to collect abdominal aortic blood,pancreatic and ileal tissues for analysis. Ascites,pancreatic and ileal tissues were observed. Serum amylase(AMY) and lipase (LPS) levels were measured biochemically. Pathological changes in pancreatic and ileal tissues were investigated by HE staining. Claudin-1 protein expression in ileal tissue was detected by Western Blot. Changes in the intestinal flora of ileocecal contents were analyzed by 16S rDNA high-throughput sequencing. Results Compared to the SHAM group at the same time points,the SAP group exhibited extensive pancreatic edema and necrosis. Serum AMY and LPS levels,pancreatic and ileal histopathological scores increased,and Claudin-1 protein expression in ileal tissue markedly decreased (all P<0.05). The differences in abundance of microbial community increased,while the evenness of community composition reduced. The microbial richness showed no significant change (P>0.05),but the microbial diversity decreased(P<0.05). Proteobacteria were dominant intestinal bacteria. Relative abundances of Oscillospira,Ruminococcus,Bifidobacterium,and Bacteroides S24-7 decreased,whereas relative abundances of Shigella and Allobaculum increased. The differences in abundance of microbial community reduced,and the evenness of community composition increased. The microbial richness showed no significant change(P>0.05),but the microbial diversity increased (P<0.05). Firmicutes and Bacteroidetes were the dominant intestinal bacteria. Relative abundances of Oscillospira,Ruminococcus,Bifidobacterium,and Bacteroides S24-7 increased,whereas relative abundances of Shigella and Allobaculum decreased. After the intervention of CH,pathological damage in ileal tissue was improved. The expression of Claudin-1 protein in the intestinal mucosal barrier increased compared to the model group(P<0.05). The differences in abundance of microbial community reduced,and the evenness of community composition increased. CH group showed an increase in some beneficial bacteria and decrease in pathogenic bacteria compared to model group. Conclusion Chaihuang Qingyi Huoxue Granule may reduce pancreas injury in rats with SAP,which may be involved in modulating the intestinal microecology and improving intestinal mucosal barrier function.

Objective To investigate the protective effect and mechanism of Chaihuang Qingyi Huoxue Granules on pancreatic tissue of rats with severe acute pancreatitis,and to observe its regulation on NLRP3 inflammasome activation.Methods Sixty-four SD rats were randomly divided into sham-surgery(SO)group,severe acute pancreatitis model(SAP)group,Chaihuang Qingyi Huoxue Granules(CH)group,and MCC950(NLRP3 inhibitor)group.Each group was further divided into 12-hour and 24-hour subgroups,with rats in each group.The SAP group,CH group,and MCC950 group were retrogradely injected with 3.5%sodium taurocholate(2 mL·kg-1)into the pancreatic ducts to establish SAP model.The MCC950 group was immediately intraperitoneally injected with MCC950(1 mg·mL-1)after model preparation.After awakening from anesthesia,the CH group was administrated by gavage with Chaihuang Qingyi Huoxue Granules solution(0.35 g·mL-1)once every 6 hours.Ascites,abdominal aortic blood,and pancreatic tissue were collected at 12 hours and 24 hours after SAP model construction.The serum amylase and lipase activities were detected using an automated biochemical analyzer.HE staining was used to observe pancreatic injury.Serum levels of IL-18 and IL-1β were detected by ELISA.The expressions of gene and proteins related to the activation of NLRP3 inflammasome were analyzed by IHC,qRT-PCR and Western Blot.Results Compared with the SAP group,the pathological damage of pancreatic tissues in the CH and MCC950 groups was significantly reduced,and the pathological score was significantly reduced(P＜0.05).The levels of serum lipase,amylase,IL-18,and IL-1β were also significantly decreased(P＜0.05).After treatment with Chaihuang Qingyi Huoxue Granules or intraperitoneal injection of NLRP3 inhibitor,the positive expressions of NLRP3,ASC and Caspase-1 in pancreatic tissues,as well as the mRNA levels of NLRP3,ASC and Caspase-1,the protein levels of NLRP3,ASC,Pro-Caspase-1 and Caspase-1 were significantly reduced compared to the SAP group(P＜0.05).Conclusion Chaihuang Qingyi Huoxue Granules can inhibit the activation of NLRP3 inflammasome,reduce the mRNA and protein expressions of NLRP3,ASC and Caspase-1 in pancreatic tissues,and suppress the release of the downstream inflammatory factors IL-18 and IL-1β and alleviate pancreatitis damage in SAP model rats.

Objective:To construct a risk prediction model for unplanned extubation (UEX) in postoperative patients, and to verify the predictive performance of the model.Methods:From January 2019 to April 2020, 314 patients who underwent surgy in Wuxi People's Hospital Affiliated to Nanjing Medical University and had postoperative indwelling catheters were selected by convenience sampling as the research object. The patients were divided into UEX group ( n=25) and non-UEX group ( n=289) according to whether UEX occurred postoperatively. The gender, age, admission to ICU, tracheal intubation, physical restraint, catheter number, analgesia, sedation, taking sleeping pills and postoperative fever of the two groups of patients were counted. Binomial Logistic regression was used to analyze the risk factors of postoperative UEX, and a risk prediction model was established. The area under the curve ( AUC) of receiver operating characteristic curve was used to test the predictive performance of the model. According to the same standard, the clinical data of 134 patients who underwent surgy from May to December 2020 were selected to validate the model. Results:The risk prediction model for UEX in postoperative patients finally included 3 risk factors, physical restraint, tracheal intubation, and age, and assigned 0-2, 0-4, and 0-5 respectively. The scores of the 3 indicators were summed up as a total score, with a total score of 0 to 11. The AUC was 0.887 [95% CI (0.807, 0.967) ] , the maximum Youden index was 0.591, the sensitivity was 0.640, the specificity was 0.951, and the predictive critical value was 5.5. The model validation showed that the sensitivity was 66.7%, the specificity was 92.6%, and the correct rate was 90.3%. Conclusions:The risk prediction model for UEX in postoperative patients has a good predictive performance, which can help clinical medical and nursing staff to quickly identify patients with high risk of UEX after surgery, and provide a reference for formulating targeted interventions.

Objective To explore the patterns of motor and linguistic activation in cortical and its correlations with abnormal gray matter in patients with malformations of cortical development(MCD)and epilepsy.Methods Seven MCD patients with epilepsy(2 patients with focal cortical dysplasia,2 heterotopia,2 schizencephaly,and 1 polymicrogyria)underwent blood-oxygen-level-dependent(BOLD)functional MRI(fMRI)in a 3 T MR scanner when practicing bilateral fingers tapping,toes twisting,verb generation,and picture naming.Functional images were post-processed by using SPM 5 software based on a general linear model(GLM)to generate activations above a uniform threshold with the cluster size (≥30 voxels,P ＜0.001 corrected).The activations were recognized and classified by two experienced neuroradiologists,and then compared with that in abnormal gray matter.Results The clusters and intensities of motor activations were mainly located in the sensormotor cortex(SMC)and premotor area (PMA).In linguistic tasks,activations produced by verb generation were found in language-associated cortical regions and PMA with higher activation in Wemicke area,picture naming significantly in the visual cortex,and language in Broca area.Combination of the two linguistic tasks produced significant clusters and intensities in language cortex.For MCD patients with abnormal cortical abnormalities,motor and language task could produce neuronal activities within normal as well as abnormal cortex regions.In 6 patients who underwent resective surgery,epileptic seizures decreased significantly,and the follow-up images demonstrated no new neurological dysfunctions and cognitive impairments.Conclusions fMRI can visualize neuronal activities in patients with MCD and epilepsy and demonstrate the motor and linguistic activations occurring in normal and abnormal gray matter.It should be cautious for surgery in patient with MCD and epilepsy.

Objective To investigate the development of the digital wireless network billing system of oxygen flow in clinical application. Methods By random 220 cases of patients who need to absorb oxygen were divided into the observation group(108 cases)and the control group(112 cases), the observation group used the digital wireless network billing system of oxygen flow, and the control group adopted the traditional buoy type oxygen gauge instrument. The following items were compared between the two groups: dispute rates between nurses and patients for different amount of absorbed oxygen, the average time cost for nurses in measuring the duration of oxygen absorbing, total income per barrel for recycling oxygen. Results For the dispute rates between nurses and patients for different amount of absorbed oxygen were 0.93% in the observation group, and 75.89% in the control group. The average time cost for nurses in measuring the duration of oxygen absorbing was 2.03 minutes for the observation group, and 12.54 minutes for the control group; total income per barrel for recycling oxygen was 42.68 yuan per barrel of the observation group, and 28.23 yuan in the control group. The statistical analysis between the two groups was supported by 95% confidential level. Conclusions Using the digital wireless network billing system of oxygen flow in clinical can reduce the dispute rates between the nurses and patients, improve patients' satisfaction degree, reduce the total time cost for nurses in measuring the duration of oxygen absorbing, raise efficiency, build a clear scientific charge system of oxygen flow, and restore economic loss.

Objective To explore the diagnostic value of CT cerebral perfusion imaging on the brain injury of the high +Gx in Rhesus. Methods Seven healthy male adult Rhesus were randomly divided into control group and +15 Gx group. The +15 Gx group underwent parabolic G curve in animal centrifuge. The animals were all examined by CT cerebral perfusion before +Gx exposure, 2 h, 24 h, and 1 week after ~+Gx exposure. The results were compared with pathologic examination. Results 2 h and 24 h after +15 Gx exposure, brain ischemia was showed on CT cerebral perfusion imaging. After 1 week, the brain ischemia was almost recovered to normal. Mild ischemic atrophy was observed in pyramidal neurons in cerebral cortex by light microscopy. Electron microscopic observation showed chromatin marginating and mitochondria cristae blurring in pyramidal cells after +Gx overload. Conclusion High G from simulating spaceship emergency return can cause ischemic injuries of the brain in Rhesus, and CT brain perfusion imaging can provide valuable diagnostic information.