Background/Aims: Dexamethasone (DEX) is a widely used exogenous therapeutic glucocorticoid in clinical settings. Its long-term use leads to many side effects. However, its effect on metabolic disorders in individuals on a high-fat diet (HFD) remains poorly understood. Methods: In this study, HFD-fed mice were intraperitoneally injected with DEX 2.5 mg/kg/day for 30 days. Lipid metabolism, adipocyte proliferation, and inflammation were assayed using typical approaches. Results: DEX increased the epididymal fat index and epididymal adipocyte size in HFD-fed mice. The number of epididymal adipocytes with diameters > 70 μm accounted for 0.5% of the cells in the control group, 30% of the cells in the DEX group, 19% of the cells in the HFD group, and 38% of all the cells in the D+H group. Adipocyte proliferation in the D+H group was inhibited by DEX treatment. Adipocyte enlargement in the D+H group was associated with increased the lipid accumulation but not the adipocyte proliferation. In contrast, the liver triglyceride and total cholesterol levels and their metabolism were downregulated by the same treatment, indicating the therapeutic potential of DEX for nonalcoholic fatty liver disease. Conclusions DEX synergizes with HFD to promote lipid deposition in adipose tissues. A high risk of obesity development in patients receiving HFD and DEX treatment is suggested.

Objective Against the backdrop of the Medical Humanistic Care Enhancement Action Plan(2024-2027),this study aims to explore the pathways through which medical institutions can promote cultural construction by leveraging Red Cross initiatives.Methods Taking Hospital P in Shanghai as a case study,participatory observation,document analysis,and in-depth interviews were conducted.Based on Schein's three-level model of organizational culture,the hospital's Red Cross prac-tices were analyzed.Results The study summarizes the implementation process,outcomes,and challenges of Red Cross initia-tives at Hospital P.Reflections and recommendations are provided.Conclusion It is recommended to strengthen communication to deepen recognition of Red Cross culture,enhance teamwork to foster the development of Red Cross teams,and promote volun-teer services to implement Red Cross practices,thereby comprehensively elevating the hospital's cultural construction.

Synovium is the target organ of rheumatoid arthritis.The excessive proliferation of synovial cells and insufficient apoptosis lead to synovial hyperplasia,which in turn causes damage to the surrounding tissues of the joint and bone destruction."Yang transforming qi and yin forming elements"is derived from Su Wen and is a highly summarized description of the functions of yin and yang,which runs through the entire course of the disease.This article elucidated the theoretical connotation of"yang transforming qi and yin forming elements"and its connection with synovial hyperplasia,proposing that the insufficiency of"yang transforming qi"is the root of synovial hyperplasia,while the excess of"yin forming elements"is the manifestation of synovial hyperplasia.Based on this,it put forward that"assisting yang qi as the priority,and according to the bias of pathogenic factors of yin,supplementing the method of reducing yin forming elements"is an important principle for treating this disease,which could provide new ideas for the treatment of the disease.

Aim To explore the mechanism of baicalin combined with heat stimulation in treating acute lym-phoblastic leukemia(ALL)based on network pharma-cology and in vitro experiments.Methods The CCK-8 assay was used to screen the suitable conditions for heat stimulation to interfere ALL cell lines Jurkat,CCRF-CEM,Hut-78 and a normal lymphocyte HMy2.CIR,and the effects of baicalin combined with heat stimulation on the proliferation of three ALL cell lines and a normal lymphocyte were tested.The key targets of baicalin combined with fever stimulation for the treatment of ALL were obtained based on network phar-macological analysis,and the potential mechanisms were predicted by gene ontology(GO)annotation and kyoto encyclopedia of genes and genomes(KEGG)en-richment.The expression levels of TNF-α,AKT1,TYMS and CASP3 mRNA in ALL cell lines Jurkat and CCRF-CEM were examined by RT-qPCR with baicalin alone and baicalin combined with heat stimulation.Results The optimal conditions for heat stimulation to intervene ALL cells were 41 ℃ for 24 h,and heat stimulation combined with baicalin synergistically inhibited the growth of ALL cell lines and effectively reduced the cy-totoxicity of baicalin.Based on the network pharmaco-logical analysis,55 intersecting targets of baicalin with ALL diseases and 77 intersecting targets of baicalin with fever were obtained.The results of GO annotation and KEGG enrichment suggested that baicalin com-bined with fever stimulation to intervene ALL might be associated with influencing intracellular reactive oxygen species metabolism,DNA transcription and apoptotic processes involved in cysteine enzymes.Apoptosis,TNF and IL-17 signaling pathways were the key pathways for baicalin combined with heat stimulation in treating ALL.Under heat stimulation at 41 ℃ using SDHA gene as housekeeping gene,in vitro experiments showed that baicalin significantly up-regulated the expression of TNF-α and CASP3,and down-regulated the expression of TYMS in ALL cells.Conclusions Based on net-work pharmacologic analyses and in vitro experiments,baicalin combined with heat stimulation can regulate TNF-α and CASP3 gene levels in ALL cells and de-stroy cellular structure to promote cell apoptosis,thus synergistically treating ALL.

Objective To explore the feasibility and corresponding implementation methods of constructing a sample resource bank based on individual-level data of completed clinical trials and using it to construct external controls for drug/device clinical trials.Methods Taking the pre-marketing clinical trial of transcatheter active valve replacement(TAVR)for the treatment of aortic valve stenosis as an example,the individual-level databases of multiple trials were standardized to form a sample bank.The original data of any trial in the sample bank were selected as the experimental group,and the remaining samples were selected as the control group.The potential confounding was handled by using the propensity score matching and stratification methods to clarify the process of constructing external controls based on the sample bank of individual-level data of clinical trials.Results This study included individual-level data of single-group trials of 4 TAVR devices,with a total of 569 subjects(59.2%male).The number of subjects in Trials 1 to 4 was 120,120,163,and 166,respectively.Propensity score matching enabled the matching of 113,117,125,and 147 subjects with comparable or similar characteristics from individual-level data from other trials,respectively,demonstrating a high matching success rate.The PS score distribution plot after stratification showed that the proportions of subjects in the experimental and control groups in strata 1 to 5 in scheme 1 were 4/103,11/103,22/92,32/87,and 51/64,respectively.For all constructed external controlled trials,a certain number of control samples with similar baseline characteristics to the experimental groups were distributed within each propensity score stratum.The results of the simulation test also reflected the potential differences between different devices in the 12-month all-cause mortality rate.Conclusions The sample bank constructed with individual-level data from clinical trials,as a high-quality data source,can serve as a source of external control for single-arm trials in the same field,and as a useful supplement to the external control scenario of real-world evidence to support drug and device development.At the same time,targeted research on research methods and bias control measures in related fields is also needed.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Objective:To explore the relationship between urinary cadmium levels and thyroid hormone levels in people aged 40-89 years old in selected areas of China.Methods:Based on the "Investigation of the Impact of Soil Quality of Agricultural Land on Human Health in Typical Areas" project from October 2019 to August 2020, a multi-stage stratified random sampling method was used to include 6 588 middle-aged and older adults aged 40-89. Demographic characteristics, dietary frequency and disease status were collected through the questionnaire and physical examination. Urinary cadmium and urinary creatinine were detected by random midstream urine. Fasting venous blood was collected for the detection of Triiodothyronine (T3) and Thyroxine (T4). The linear mixed effects model was used to explore the association of urine cadmium levels with thyroid hormone levels. Its dose-response relationship was explored by using the restricted cubic spline.Results:The age of the subjects was (63.48±12.18) years, with males accounting for 51.28%. The M ( Q 1,Q 3) of urinary cadmium level, T3 and T4 was 2.48 (1.36, 4.42) μg/g·creatinine, (1.96±0.51) nmol/L and (113.75±29.11) nmol/L, respectively. The linear mixed effects model showed that the changes of T3 and T4 were 0.027 (0.009, 0.044) nmol/L and 2.019 (1.084, 2.953) nmol/L for each one-unit increase (natural logarithm transformed) of urinary cadmium. The restricted cubic spline showed that there was a positive nonlinear association between urinary cadmium and T3 as well as T4 (all Pnonlinear<0.05). Conclusion:In selected areas of China, the urinary cadmium level of middle-aged and older adults aged 40-89 years is positively associated with T3 and T4.

Objective:To evaluate the levels and source of cadmium exposure by dietary pathway among middle-aged and elderly people ≥40 in cadmium-contaminated areas of China.Methods:A total of 7 193 people aged 40-89 years from four typical cadmium-contaminated areas in China were selected as the study subjects. Food Frequency Questionnaire (FFQ), Total Diet Study (TDS) and a 3-day-24-hour dietary recall survey were conducted. Dietary cadmium intake and food sources through dietary pathways were assessed based on cadmium content in foods, consumption amounts and intake frequencies.Results:The mean age of the participants was 63.39±12.21 years, with 50.05% being males. The average monthly dietary cadmium intake was 7.39 μg/(kg·BW). Staple foods and vegetables were the primary sources of dietary cadmium intake, accounting for 57.51% and 32.48%, respectively. The monthly dietary cadmium intake in all surveyed regions did not exceed the Provisional Tolerable Monthly Intake (PTMI) recommended by the Joint FAO/WHO Expert Committee on Food Additives (JECFA).Conclusion:The monthly dietary cadmium intake among middle-aged and elderly people in cadmium-contaminated areas of China is relatively low, with the risk remaining at an acceptable level. Staple foods and vegetables are the most significant contributors to dietary cadmium intake.

Objective To investigate the practical effects of pediatric rapid sequence intubation(RSI)nursing coordination training based on the LSPPDM(learn,see,practice,prove,do,maintain)framework in order to provide evidence for optimizing pediatric RSI nursing training programs.Methods Nurses from the intensive care unit(ICU)of Children's Hospital,Fudan University during Feb 2023 and Jan 2024 were divided into the experimental group(n=35)and the control group(n=35)by block randomization.The experimental group received LSPPDM framework-based training,while the control group underwent conventional training with theoretical lectures and procedural demonstrations.Outcomes included training satisfaction,theoretical knowledge and procedural skill assessment scores,team collaboration compliance and RSI procedure time were compared between the two groups.Results The experimental group demonstrated significantly higher training satisfaction(123.80±2.04 vs.117.26±9.82,P<0.05),superior post-training theoretical knowledge and procedural skills(P<0.05),enhanced team collaboration compliance(P<0.05),and shorter RSI completion time(P<0.05)compared with the control group.Conclusion Pediatric RSI nursing coordination training based on the LSPPDM framework can effectively increase training satisfaction,promote theoretical and procedural skills and reduce completion time in nurses.

Objective To study the efficacy of hemoperfusion(HP)in series with continuous renal replace-ment therapy(CRRT)integrated combined blood purification under extracorporeal citrate anticoagulation in the treatment of severe hypertriglyceridemic acute pancreatitis(HTG-AP).Methods A total of 62 patients with severe HTG-AP admitted to the Affiliated Hospital of Xuzhou Medical University from June 2022 to May 2024 were selected and randomly divided into control group and observation group,with 31 cases in each group.The control group was treated with conventional medical treatment+HP combined with CRRT staged combined blood purifica-tion treatment,and the observation group was treated with conventional medical treatment+HP in series with CRRT integrated combined blood purification treatment under extracorporeal citrate anticoagulation.The indexes and clinical efficacy before and 7 days after treatment were compared between the two groups.Results The single CRRT time of the observation group was longer than that of the control group,and the frequency of CRRT was less than that of the control group(P<0.05).There were no significant differences in the total CRRT time,single HP time,HP frequency and total HP time between the two groups(P>0.05).The blood routine,inflammatory factors,blood biochemistry and clinical scores of the two groups after treatment were improved compared with those before treatment(P<0.05).After treatment,the hemoglobin(Hb)and platelet count(Plt)of the observation group were higher than those of the control group(P<0.05),and there were no significant differences in other indexes of blood routine,inflammatory factors,blood biochemistry and clinical scores between the two groups(P>0.05).There were no significant differences in clinical indexes,prognosis and complications between the two groups(P>0.05).Conclusions Without affecting the efficacy,HP in series with CRRT integrated combined blood purification under extracorporeal citrate anticoagulation in the treatment of severe HTG-AP can prolong the use time of CRRT blood filter and pipeline,reduce the use of consumables,reduce the risk of bleeding,and avoid multiple catheter removal of HP and CRRT operation separately,and reduce the risk of related infection.It is worthy of clinical application.