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 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 develop a clinical prediction model based on ⁶⁸Ga-prostate-specific membrane antigen-11 (⁶⁸Ga-PSMA-11), positron emission tomography/computed tomography (PET/CT) and multiparametric magnetic resonance imaging (mpMRI) parameters to stratify prostate cancer patients undergoing targeted biopsy, so as to avoid unnecessary systematic biopsy. 【Methods】 A total of 96 clinically significant prostate cancer (csPCa) patients who underwent ⁶⁸Ga-PSMA-11 PET/CT and mpMRI prior to prostate targeted biopsy with systematic biopsy during Jan.2020 and Feb.2023 in Nanjing Drum Tower Hospital were retrospectively analyzed.By univariate and multivariate logistic regression analyses, maximum standard uptake value (SUVmax) in ⁶⁸Ga-PSMA-11 PET/CT and minimum apparent diffusion coefficien (ADCmin) in mpMRI, as well as clinical parameters were evaluated to identify the independent predictors correlative with the effective diagnosis of targeted biopsy, and a clinical prediction model was constructed. 【Results】 Multivariate logistic regression analysis showed that SUVmax (OR=0.878, 95%CI: 0.804-0.959, P=0.004) and ADCmin (OR=1.005, 95%CI:1.001-1.010, P=0.027) were independent predictors of the effective diagnosis of targeted biopsy alone.The sensitivity, specificity, accuracy and area under the receiver operator characteristic curve (AUC) of the model were 0.80, 0.80, 0.83 and 0.84, respectively. 【Conclusion】 The clinical prediction model based on ⁶⁸Ga-PSMA-11 PET/CT and mpMRI parameters is helpful to improve the effective diagnosis of targeted biopsy alone, and has practical value to stratify patients with csPCa so as to safely avoid systematic biopsy and effectively balance the benefits and risks.

Objective To understand the recognition and coping strategies of ICU nurses on post-ICU syndrome in family members of patients during hospitalisation so as to provide a reference for handling post-ICU syndrome of the family members of patients.Methods A phenomenological approach within qualitative research was adopted.Semi-structured in-depth interviews were conducted with 15 ICU nurses from 3 wards of the Second Affiliated Hospital of South China University.Colaizzi 7-step method was applied to analyse and refine the interview data themes.Results Three main themes and nine sub-themes were identified and they were insufficient cognition of post-ICU syndrome of the family members(limited understanding of post-ICU syndrome in family members,difficulty in recognising or ignoring symptoms,uncertainty about the impact of post-ICU syndrome),active coping with post-ICU syndrome of the family members(coping mainly through listening and explaining,coping mainly through verbal and physical actions,diligent patient care)and various factors hindering nurses'coping with post-ICU syndrome of the family members(compassion fatigue,high ICU work intensity,limited contact time with family members).Conclusion ICU nurses have insufficient understanding of post-ICU syndrome with the family members of patients during hospitalisation.It requires to enhance a comprehensive understanding in ICU nurses about post-ICU syndrome of the family members of patients and to optimise coping strategies to alleviate negative emotions of the family members.Additionally,efforts should be made to overcome factors that hinder nurses'coping with post-ICU syndrome of the family members of patients and to promote a harmonious relationship between medical staff and patients.

Objective:To evaluate the safety and necessity of vasopressor infusion through midline catheter.Methods:A convenient sampling method was used for a controlled study. A total of 88 adult patients who used vasopressors admitted to respiratory intensive care unit (RICU) of Fenyang Hospital in Shanxi Province from June 2022 to June 2023 were enrolled as the research subjects. A total of 44 patients who were infused with vasopressors through peripherally inserted central venous catheter (PICC) from June to December 2022 were enrolled as the PICC group, and 44 patients who were infused with vasopressors through midline catheter from January to June 2023 were enrolled as the midline catheter group. Both groups of patients used the modified Sedinger technique under the guidance of B-ultrasound for puncture and catheter placement. The middle 1/3 site between the cubital fossa and the axilla was selected. The catheters were 5 Fr double lumen. After catheter placement, the patients were followed until catheter removal, death, or 30 days (whichever came first). Based on the Infusion therapy standards of practice revised by American Infusion Nurses Society (INS), and combined with the results of previous preliminary tests, the safety evaluation was conducted on incomplete catheter obstruction, catheter-related bloodstream infection (CRBSI), phlebitis, thrombus within the catheter during extubation, redness of the puncture site (but no infection), and exudation of the puncture site in the two groups of patients.Results:There were no statistical differences in gender, age, catheter indwelling time, and primary disease between the two groups, indicating that the baseline data of the two groups were balanced and comparable. No CRBSI or phlebitis occurred in both groups during the observation period after catheterization. One patient in both groups had exudation at the puncture site [both were 2.27% (1/44)]. Compared with the PICC group, the incidence of incomplete catheter obstruction, thrombus within the catheter during extubation, redness of the puncture site (but no infection) in the midline catheter group were lowered [incomplete catheter obstruction: 4.55% (2/44) vs. 6.82% (3/44), thrombus within the catheter during extubation: 0% (0/44) vs. 2.27% (1/44), redness of the puncture site (but no infection): 0% (0/44) vs. 4.55% (2/44)], the overall incidence was significantly decreased [6.82% (3/44) vs. 15.91% (7/44), P < 0.01]. Conclusion:Administering vasopressor through a midline catheter can reduce the incidence of catheter-related complications, decrease the rate of central venous catheterization, and reduce the financial burden on patients.

Objective To explore clinical effect of Jiawei Sangju decoction combined with oseltamivir in the treatment of influenza B complicated with benign acute childhood myositis(BACM).Methods Sixty children with influenza B complicated with BACM hospitalized in the Department of Pediatrics,Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine from January 2021 to January 2024 were selected and divided into control group and study group according to random number table method,with 30 cases in each group.The control group was treated with oseltamivir,and the study group was treated with Jiawei Sangju decoction combined with oseltamivir.The clinical efficacy,symptom improvement time and aspartate transaminase(AST),alanine transaminase(ALT),creatine kinase(CK),creatine kinase isozyme(CK-MB),lactate dehydrogenase(LDH)and myoglobin(Mb)before and after treatment were compared between two groups.Results After treatment,the total effective rate of study group was significantly higher than that of control group(χ2=5.455,P=0.020).The duration of fever and leg pain relief in study group were significantly shorter than those in control group(P<0.05).After 5 days of treatment,the levels of AST,CK,CK-MB,LDH and Mb in two groups were significantly lower than before treatment(P<0.05),and the levels of AST,CK,CK-MB,LDH and Mb in study group were significantly lower than those in control group(P<0.05).Conclusion Jiawei Sangju decoction combined with oseltamivir can improve the symptoms of influenza B with BACM,reduce the levels of muscle enzyme and Mb,and have a positive effect on the prognosis of children.

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.

BACKGROUND: Venous thromboembolism (VTE) as the most common cancer-associated complication has become the second death-causing reason among cancer patients. The management of VTE in patients with lung adenocarcinoma should focus on early and timely detection of risk factors. The aim of the study is to investigate the current situation of VTE in patients with lung adenocarcinoma treated with anti-tumor therapy and then explore the risk factors associated with the occurrence of VTE during anti-tumor therapy for early detection and screening of VTE. METHODS: The present study included patients diagnosed as lung adenocarcinoma undergoing anti-tumor therapy in First Affiliated Hospital of Nanjing Medical University between December 2019 and May 2021. The risk factors were identified via univariate and multivariate Cox analysis. The incidence of independent risk factors were investigated through Kaplan-Meier curves combined with Log-rank test. RESULTS: The results of univariate and multivariate Cox regression showed that history of VTE, targeted therapy and radiotherapy were risk factors for VTE in patients with lung adenocarcinoma treated with anti-tumor therapy (P<0.05). Furthermore, the results of Kaplan-Meier curves and Log-rank tests indicated the incidences of VTE in patients with history of VTE, targeted therapy and radiotherapy were higher (P<0.05). CONCLUSIONS History of VTE, radiotherapy and targeted therapy are found as independent risk factors for the occurrence of VTE, which should be identified and monitored for reduction of VTE incidence.
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Humans ; Venous Thromboembolism ; Incidence ; Lung Neoplasms ; Adenocarcinoma of Lung ; Risk Factors

Objective:To compare the clinical effect of transpedicular impaction and grafting of allogeneic bone containing enriched bone marrow combined with posterior internal fixation and posterior subtotal vertebrectomy combined with posterior internal fixation in the treatment of stage III Kümmell′s disease.Methods:A retrospective cohort study was made on clinical data of 40 patients with stage III Kümmell′s disease admitted to Zhengzhou Orthopedic Hospital from June 2015 to December 2018. There were 10 males and 30 females, at age range of 57-79 years［(67.7±6.1)years］. A total of 19 patients were treated by transpedicular impaction and grafting of allogeneic bone containing enriched bone marrow combined with posterior internal fixation (impaction bone graft group), and 21 patients by posterior subtotal vertebrectomy combined with posterior internal fixation (subtotal vertebrectomy group). Operation time and intraoperative blood loss were compared between the two groups. Degree of pain, lumbar dysfunction and degree of kyphosis were evaluated by visual analogue scale (VAS), Japanese Orthopedic Association (JOA) score and kyphotic Cobb angle before operation, at 1 week after operation and at the last follow-up. Bone healing time was compared between the two groups. The complications of the two groups were observed.Results:All patients were followed up for 25-64 months［(40.6±10.4)months］. Operation time and intraoperative blood loss were (130.0±10.1)minutes and (284.5±43.5)ml in impaction bone graft group, lower than those in subtotal vertebrectomy group［(253.8±33.2)minutes, (889.1±95.7)ml］(both P<0.01). There were no significant differences in VAS, JOA score or kyphotic Cobb angle between the two groups before operation, at 1 week after operation and at the last follow-up (all P>0.05). Both VAS and JOA score showed significant differences within each group at any time point (all P<0.01). In both groups, the kyphotic Cobb angle reduced significantly at 1 week after operation when compared with that before operation (all P<0.01), and the angle showed a slight increase at the last follow-up, but remained significantly lower than that before operation (all P<0.01). There were no relapse of pain or aggravation of kyphosis. Bone healing time in impaction bone graft group［4.4(4.0, 5.0)months］was significantly shorter than that in subtotal vertebrectomy group［6.4(5.2, 8.1)months］( P<0.01). There were 2 patients with delayed healing of surgical incision in impaction bone graft group, with the complication rate of 11%. There were 2 patients with dural tear and 3 patients with delayed healing of surgical incision in subtotal vertebrectomy group, with the complication rate of 24%. The complication rate was not statistically significant between the two groups ( P>0.05). No loosening or breakage of internal fixation was observed during the follow-up. Conclusions:Transpedicular impaction and grafting of allogeneic bone containing enriched bone marrow combined with posterior internal fixation and posterior subtotal vertebrectomy combined with posterior internal fixation are effective in the treatment of stage III Kümmell disease. However, the former can shorten the operation time, reduce the intraoperative blood loss and accelerate the healing of injured vertebral bone, suggesting a relatively minimally invasive surgical method for reconstruction and maintenance of spinal biomechanical stability.