Objective·To develop physiologically based pharmacokinetic(PBPK)models specifically designed for the Chinese population by utilizing the combination of clozapine and fluvoxamine as a case,and predict the drug-drug interaction(DDI)associated with the combination medication of clozapine,ultimately optimizing the dosage of clozapine.Methods·By obtaining the physicochemical parameters,absorption,distribution,metabolism,excretion(ADME)-related parameters,and physiologically relevant parameters of the Chinese population through literature and pharmacology-related databases,PBPK models for the clozapine and fluvoxamine were constructed by using PK-Sim? software.The models' accuracy was evaluated by comparing predicted values of the area under the curve(AUC)and peak concentration(Cmax)to observed data,using the mean percentage error(MPE)and mean absolute percentage error(MAPE)as evaluation indicators.The models were validated against real-world plasma drug concentration data.Additionally,combining the inhibitory effect of fluvoxamine on clozapine,models for the combination therapy of clozapine and fluvoxamine were developed to predict the pharmacokinetic changes of clozapine.The presence of clinically significant DDI was determined by using the 90%confidence interval of the AUC ratio(AUCR)or Cmax ratio(CmaxR)as evaluation metrics,with a non-effect boundary set at 80%?125%.The pharmacokinetic changes of clozapine upon co-administration with fluvoxamine based on PBPK models were quantified,and a dosage optimization for clozapine was developed.Results·The constructed model of clozapine and fluvoxamine was considered accurate if the absolute value of the MPE was≤10%and the MAPE was<25%during validation,indicating that the predicted concentration-time curves were accurate.The PBPK model for the co-administration of clozapine and fluvoxamine was able to accurately predict pharmacokinetic parameters if the ratio of predicted AUC to observed AUC was within 1.25.The prediction of PBPK model for the co-administration showed that the 90%confidence intervals for AUCR and CmaxR of the combination therapy of clozapine and fluvoxamine were not entirely within the ineffective effect boundary,indicating a clinically significant DDI when these two drugs were used concomitantly.Moreover,the dose optimization according to the PBPK models indicated that when subjects were co-administered with clozapine and fluvoxamine,reducing the dose of clozapine to 50%of the original dose could maintain the exposure levels of clozapine consistent with monotherapy.Conclusion·The established PBPK model can effectively simulate the impact of combination therapy on pharmacokinetic changes of clozapine,providing valuable insights for predicting potential DDI and optimizing dosage regimens.If clozapine needs to be co-administered with fluvoxamine during the treatment,clinicians should remain vigilant for clinically significant DDI and contemplate optimizing the dosage of clozapine accordingly.

Purpose::Internal iliac artery ligation (IIAL) has been used as a damage control procedure to treat hemodynamically unstable pelvic fracture for many years. However, there is ongoing debate regarding the effectiveness and safety of this hemostatic method. Therefore, we performed a systematic literature review to assess the efficacy and safety of IIAL for pelvic fracture hemostasis.Methods::Three major databases, PubMed, Embase, and Google Scholar, were searched to screen eligible original studies published in English journals. Two reviewers independently read the titles, abstracts, and full texts of all literature. Articles were included if they reported the use and effects of IIAL.Results::A total of 171 articles were initially identified, with 22 fully meeting the inclusion criteria. Among the analyzed cases, up to 66.7% of patients had associated abdominal and pelvic organ injuries, with the urethra being the most frequently injured organ, followed by the bowel. The outcomes of IIAL for achieving hemostasis in pelvic fractures were found to be satisfactory, with an effective rate of 80%. Hemorrhagic shock was the leading cause of death, followed by craniocerebral injury. Notably, no reports of ischemic complications involving the pelvic organs due to IIAL were found.Conclusion::IIAL has a good effect in treating hemodynamically unstable pelvic fracture without the risk of pelvic organ ischemia. This procedure should be considered a priority for hemodynamically unstable pelvic fracture patients with abdominal organ injuries.

Objective To discuss the effect of multidisciplinary family empowerment mode in home care for patients after receiving percutaneous endoscopic gastrostomy(PEG).Methods A total of 86 patients,who received initial PEG at the Jilin Provincial Cancer Hospital of China from January 2021 to July 2023,were selected for this study.The patients were randomly divided into observation group.The patients of the control group received routine nursing guidance for gastrostomy,while the patients of the observation group received multidisciplinary family empowerment nursing mode.The self-care ability[using self-care ability scale of the elderly(SASE)score],health behavior ability[using self-rating scale of health behavior ability(SRAHP)score],incidence of complications,and healing time of complications were compared between the two groups.Results In the observation group the SASE[(129.48±5.48)points vs.(73.05±12.04)points]and the SRAHP[(80.14±1.00)points vs.(70.25±7.92)points]were significantly higher than those in the control group(all P＜0.05),the incidence of complications was lower than that in the control group,and the healing time of complications was shorter than that in the control group.Conclusion The implementation of multidisciplinary family empowerment nursing mode can improve the self-care ability and health behavior ability of patients after receiving PEG,reduce postoperative complications,as well as shorten the healing time of complications,therefore,this nursing mode is suitable for home patients after receiving PEG.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To evaluate the effect of low-dose recombinant interleukin-2(rIL-2)therapy on immunocyte subsets and its side effects in children with solid tumor.Methods:A total of 22 children(11 males and 11 females)with solid tumor in our department from December 2012 to November 2017 were selected,with a median age of 9(3-16)years old when starting IL-2 therapy.ALL surgeries and chemotherapy of children had been completed before low-dose rIL-2 therapy,and 17 cases achieved complete remission(CR)and 5 cases achieved partial remission(PR).A low-dose rIL-2 therapy was given 1 month after chemotherapy for 1 year:4 × 105 IU/(m2·d),s.c.for every other day,3 times per week.The immunocyte subsets were detected every 3 months until the end of treatment,meanwhile,disease condition and therapy-related side effects were followed up.Results:After low-dose rIL-2 therapy in 22 children,the absolute values of CD3+T cells,CD3-CD56+natural killer cells,CD3+CD4+helper T cells(Th)and CD3+CD8+cytotoxic T cells were up-regulated remarkably,as well as Th/suppressor T cells(all P＜0.05).While,there were no significant differences in absolute value and proportion of CD4+CD25+CD127-Treg cells during therapy.Among the 17 children who achieved CR before rIL-2 therapy,14 cases continued to maintain CR after therapy,while 3 cases relapsed,and with 2 died after treatment abandonment.The 5 children who achieved PR before low-dose rIL-2 therapy were evaluated CR by PET/CT scan after treatment.In the early stage of low-dose rIL-2 therapy,1 child developed skin rashes at the injection sites,and 2 children ran a slight to mild transient fever.Their symptoms disappeared without any organ damage after symptomatic treatment.Conclusion:Low-dose rIL-2 therapy has good drug tolerance,and changes the distribution of anti-tumor immune-cell subgroup in peripheral blood of children with solid tumor remarkably without up-regulation of absolute value and ratio of Treg cells.

Lung cancer,a malignant tumor with high incidence and mortality rate,is characterized by multiple types,high malignancy and poor prognosis.Immunotherapy is to stimulate and enhance immune system of the host to achieve the purpose of controlling and killing tumor cells,and has been proven to have good therapeutic effects on many types of cancer.Immunogenic cell death(ICD)is a programmed cell death characterized by the release of large amounts of damage-associated molecular pat-terns(DAMPs).After treatment of certain chemotherapy drugs,physical therapy,biological therapy or combination therapy,lung cancer cells will undergo ICD,altering from non-immunogenic to immunogenic.Immune cells will then be recruited and ac-tivated,and finally activate and enhance anti-tumor immune response in the body.This article reviews the mechanism of ICD and the application of ICD inducers in the treatment of lung cancer.

ObjectiveTo examine the current status of preschoolers' eating behaviors and investigate its correlation with family cohesion and adaptability. MethodsA cross-sectional study was conducted involving 21，954 preschoolers and their families from Pingshan District， Shenzhen， between September 2021 and December 2021. A general demographic questionnaire， the Chinese version of Family Adaptability and Cohesion Evaluation Scale Ⅱ （FACESⅡ-CV） and Chinese Preschoolers’ Eating Behavior Questionnaire （CPEBQ） were used to collect the relevant information. Multiple linear regression was used to analyze the association of family cohesion and adaptability with eating behaviors of preschoolers. ResultsTypes of family cohesion and adaptability were significantly correlated with all the 7 dimensions of preschoolers' eating behaviors， including food fussiness （R²=0.252， F=114.457， P<0.001）， food responsiveness （R² = 0.111， F =24.973， P<0.001）， eating habit （R²= 0.304， F =139.658， P<0.001）， satiety responsiveness （R² = 0.259， F =105.332， P<0.001）， external eating （R² = 0.182， F =50.150， P<0.001）， emotional eating （R² = 0.234， F =91.084， P<0.001） and initiative eating （R² = 0.349， F =168.608， P<0.001）. After adjusting for confounding factors， our study showed that types of family cohesion and adaptability were independent predictors of preschoolers' eating behaviors （P<0.05）. ConclusionsTypes of family cohesion and adaptability have a significant predictive effect on the 7 dimensions of preschoolers' eating behaviors. Higher scores of family cohesion and adaptability imply stronger initiative eating ability and less poor dietary behaviors in preschoolers.

Aim To study the therapeutic effect of Balanophora polysaccharide(BPS)on gastric ulcer(GU)induced by acetic acid in rats and to investigateits mechanisms. Methods Sixty male SD rats were randomly divided into sham-operated group, GU model group, omeprazole positive group(3.6 mg·kg-1), and low, medium and high dose of BPS treatment groups(100, 200 and 400 mg·kg-1). The GU model group was prepared by acetic acid cautery method, and the morphology and pathological changes of ulcers were observed by visual observation combined with HE staining, and the ulcer area and inhibition rate were measured and calculated; superoxide dismutase(SOD)activity, malondialdehyde(MDA)content and glutathione peroxidase(GSH-PX)activity were measured by enzymatic assay; tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)content were detected by ELISA. The expression levels of epidermal growth factor(EGF)and epidermal growth factor receptor(EGFR)were measured by immunohistochemistry staining and Western blot. Results Compared with the sham-operated group, obvious ulcer damage was seen in the model group. Compared with the model group, the BPS-treated group showed a significant reduction in ulcer area, an increase in SOD and GSH-PX activity and EGF and EGFR expression levels, and a significant decrease in MDA, TNF-α and IL-6 content. Conclusions BPS has a therapeutic effect on GU in rats, and its mechanism may be related to the inhibition of oxidative stress, suppression of inflammatory stimuli and promotion of regenerative repair of gastric mucosa.

Pulmonary fibrosis is a severe lung interstitial disease characterized by the destruction of lung tissue structure, excessive activation and proliferation of fibroblasts, secretion and accumulation of a large amount of extracellular matrix (ECM), and impaired lung function. Due to the complexity of the disease, a suitable animal model to mimic human pulmonary fibrosis has not yet been established. Precision-cut lung slice (PCLS) has been a widely used in vitro method to study lung physiology and pathogenesis in recent years. This method is an in vitro culture technology at the level between organs and cells, because it can preserve the lung tissue structure and various types of airway cells in the lung tissue, simulate the in vivo lung environment, and conduct the observation of various interactions between cells and ECM. Therefore, PCLS can compensate for the limitations of other models such as cell culture. In order to explore the role of discoidin domain receptor 2 (DDR2) in pulmonary fibrosis, Ddr2^flox/flox mice were successfully constructed. The Cre-LoxP system and PCLS technology were used to verify the deletion or knockdown of DDR2 in mouse PCLS. Transforming growth factor β1 (TGF-β1) can induce fibrosis of mouse PCLS in vitro, which can simulate the in vivo environment of pulmonary fibrosis. In the DDR2 knock down-PCLS in vitro model, the expression of various fibrosis-related factors induced by TGF-β1 was significantly reduced, suggesting that knocking down DDR2 can inhibit the formation of pulmonary fibrosis. The results provide a new perspective for the clinical study of DDR2 as a therapeutic target in pulmonary fibrosis.
Animals ; Humans ; Mice ; Discoidin Domain Receptor 2/metabolism* ; Fibroblasts/pathology* ; Fibrosis ; Lung/pathology* ; Pulmonary Fibrosis/metabolism* ; Transforming Growth Factor beta1/metabolism*

The main components and working principle of the fluid infusion and blood transfusion warmer were introduced,and the causes for the adverse events of the warmer were summarized based on National Medical Device Adverse Event Monitoring Information System and related literature in the world.The potential risks of the warmer were analyzed during operation,and the quality concerns and corresponding evaluation methods were proposed for the warmer from the aspects of device marking and documentation,structure,and temperature.References were provided for standard preparation,pre-market technical review and system verification of the fluid infusion and blood transfusion warmer.[Chinese Medical Equipment Journal,2023,44(10):76-80]