OBJECTIVE To screen inhibitors that targeting sterol O-acyltransferase 1(SOAT1) protein, and to investigate the effects of the potential inhibitors in vivo. METHODS Hepatoma cells with high SOAT1 expression were screened through CCLE database and used as experimental cell models. Molecular docking between 61 742 compounds from Interbioscreen database and SOAT1 protein was performed using the Autodock Vina software, and the binding energies were calculated. Eight compounds with relative high binding energy were selected, and their effects on the viability of hepatoma cells were detected using CCK8 assays. The two most active compounds in cell models were selected for further study, and their IC50 were determined. Wound healing and crystal violet staining assays were employed to detect the effects of the two compounds on the migration and proliferation of hepatoma cells. Western blotting was used to study the effects of the compounds on SOAT1 protein in hepatoma cells. siRNA were transfected into hepatoma cells to construct a SOAT1-silenced cell model, and effects of the compounds on cell viability were tested. RESULTS Hep3B and PLC/PRF/5 human hepatoma cell lines with high expression of SOAT1 protein selected from the CCLE database as model cells were screened and used as cell models. Among the 8 compounds with relative high binding affinity screened by molecular docking, Compounds 1 and 7 had the most significant inhibitory effects on the viability of the two types of liver cancer cells mentioned above. Moreover, the two compounds inhibited cell migration and cell colony formation, as well as decreased SOAT1 protein expression in hepatoma cells. In SOAT1-silenced hepatoma cells, the inhibitory effects of the two compounds on cell viability were significantly attenuated. CONCLUSION Compound 1 and compound 7 exert anti-hepatoma effects at the cellular level by inhibiting the expression of SOAT1 protein, suggesting that these two compounds have the potential to be developed into SOAT1 inhibitors for the treatment of liver cancer.

OBJECTIVE To evaluate the cost-effectiveness of the first-line treatment using the combination therapy of sugemalimab and chemotherapy （hereinafter referred to as the “combination therapy”） for advanced esophageal squamous cell carcinoma （ESCC） with high programmed death-ligand 1 （PD-L1） expression from the perspective of the Chinese healthcare system. METHODS A partitioned survival model was constructed based on data from the GEMSTONE-304 study. The model cycle was set at 3 weeks， with a study duration of 10 years and a discount rate of 5%. The primary output parameters of the model included total costs， quality-adjusted life year （QALY）， incremental costs， and incremental cost-effectiveness ratio （ICER）. Cost- utility analysis was employed to assess the economic feasibility of the combination therapy compared to chemotherapy alone. The robustness of the base case analysis results was evaluated through univariate sensitivity analysis， probabilistic sensitivity analysis， and scenario analysis. RESULTS The ICER of the combination therapy compared to chemotherapy alone was 288 430.35 yuan/QALY， significantly exceeding the willingness-to-pay （WTP） threshold of 173 354.52 yuan/QALY which was set at 1.94 times the per capita gross domestic product （GDP） in 2023. The price of sugemalimab was the primary factor influencing the ICER. When the WTP threshold was set at 1.94 times the per capita GDP （173 354.52 yuan/QALY）， the probability of the combination therapy being cost-effective compared to chemotherapy alone was 0. The combination therapy only became cost-effective compared to chemotherapy alone when the price of the drug dropped to 6 107.41 yuan per box （600 mg）. CONCLUSIONS From the perspective of the Chinese healthcare system， the combination therapy for first-line treatment of advanced ESCC with high PD-L1 expression is not cost-effective； the combination therapy is cost-effective when the price of sugemalimab decreas by 50.65%.

A retrospective analysis was made on the clinical data and gene mutation characteristics of 2 children admitted to the Children′s Hospital of Zhejiang University School of Medicine for epilepsy without periventricular nodules caused by the ARF1 gene mutation from August 2023 to February 2024, and relevant literature was reviewed.Both patients presented with seizures and psychomotor retardation, and 1 of them was diagnosed with West syndrome.Whole exome sequencing confirmed that the 2 patients carried a missense mutation in the ARF1 gene (c.55C>A, p.R19S).Brain magnetic resonance imaging (MRI) of 2 patients revealed no obvious abnormalities.A summary analysis of 5 cases of ARF1 gene mutations reported in three foreign literatures showed that patients with ARF1 gene mutations usually presented with seizures, developmental delay, hypotonia, mental retardation, and motor stereotypies.MRI showed periventricular nodular heterotopia, corpus callosum dysplasia, subcortical white matter abnormalities, and delayed myelination.This study found for the first time that ARF1-related disorders can occur without significant brain structural malformations, indicating that there are inconsistencies in neuroimaging findings, adding valuable phenotypic information to this gene.The differences in imaging findings may be the result of genetic background or variation in ARF1-interacting proteins, or may be caused by altered regulatory mechanisms of protein activity.

Evidence indicates that metabolic reprogramming characterized by the changes in cellular metabolic patterns contributes to the pathogenesis of pulmonary fibrosis(PF).It is considered as a promising ther-apeutic target anti-PF.The well-documented against PF properties of Tanshinone ⅡA(Tan ⅡA)have been primarily attributed to its antioxidant and anti-inflammatory potency.Emerging evidence suggests that TanⅡA may target energy metabolism pathways,including glycolysis and tricarboxylic acid(TCA)cycle.However,the detailed and advanced mechanisms underlying the anti-PF activities remain obscure.In this study,we applied[U-13C]-glucose metabolic flux analysis(MFA)to examine metabolism flux disruption and modulation nodes of Tan ⅡA in PF.We identified that Tan ⅡA inhibited the glycolysis and TCA flux,thereby suppressing the production of transforming growth factor-β1(TGF-β1)-dependent extracellular matrix and the differentiation and proliferation of myofibroblasts in vitro.We further revealed that Tan ⅡA inhibited the expression of key metabolic enzyme hexokinase 2(HK2)by inhibiting phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/hypoxia-inducible factor 1α(HIF-1α)pathway activities,which decreased the accumulation of abnormal metabolites.Notably,we demonstrated that Tan ⅡA inhibited ATP citrate lyase(ACLY)activity,which reduced the collagen synthesis pathway caused by cytosol citrate consumption.Further,these results were validated in a mouse model of bleomycin-induced PF.This study was novel in exploring the mechanism of the occurrence and develop-ment of Tan ⅡA in treating PF using 13C-MFA technology.It provided a novel understanding of the mechanism of Tan ⅡA against PF from the perspective of metabolic reprogramming.

Objective:To explore the clinical effectiveness of hemostatic bandage on wound safety and comfort after transradial coronary angiography and/or interventional therapy.Methods:This was a experimental study. A total of 400 consecutive patients who underwent transradial coronary angiography and/or interventional therapy in the Department of Cardiology, Peking University Third Hospital from July to October 2022 were enrolled and randomly divided into the hemostatic bandage group and the hemostatic balloon compressor group by the envelope method with 200 cases in each group. The hemostatic bandage group and the hemostatic balloon compressor group were treated with hemostatic bandage and hemostatic balloon compressor as transradial artery hemostatic device, respectively, to observe and compare postoperative hemostatic effect, hemostat use time, complication rate, postoperative pain, the degree of numbness in the finger on the operated side and wristband comfort between the two groups.Results:The hemostatic success rate was 98.5% (197/200) and 99.0% (198/200) in the hemostatic bandage and the hemostatic balloon compressor group, respectively, with no statistical difference ( χ2=0.20, P>0.05). The hemostat use time in the hemostatic bandage group and the hemostatic balloon compressor group was (6.23 ± 0.47) h and (17.01 ± 7.74) h, respectively, and the difference was statistically significant ( t=-19.66, P<0.01). The incidence of complications in the hemostatic bandage group and the hemostatic balloon compressor group was 13.5%(27/200) and 29.5%(59/200), respectively, and the difference was statistically significant ( χ2=8.01, P<0.05). Among the complications, swelling occurred in 21 individuals of the hemostatic bandage group and 54 individuals of the hemostatic balloon compressor group with statistically significant differences ( U=16 689.50, P<0.01). Besides, the hemostatic bandage group was significantly better than the hemostatic balloon compressor group with statistically significant differences in wound pain at immediate postoperative ( U=13 669.50, P<0.01), in finger numbness at immediate postoperative and 1-hour postoperative (immediate postoperative: U=17 838.00, P<0.05; 1-hour postoperative: U=13 342.50, P<0.01), in comfort at immediate postoperative, 4-hours, 8-hours and 12-hour postoperative(immediate postoperative: U=9 966.50, P<0.01; 4-hour postoperative: U=12 851, P<0.01; 8-hour postoperative: U=14 900, P<0.01; 12-hour postoperative: U=15 920, P<0.01). Conclusions:The hemostatic bandage shows better hemostatic effect, shorter compression time, lower complication rate, less wound pain, less numbness of the finger on the operation side, and higher comfort of the wrist band compared to hemostatic balloon compressor after transradial coronary angiography and/or interventional therapy, which is worthy of clinical promotion.

Objective:To explore the evaluation of nursing undergraduates on the effect of ideological and political teaching in nursing research courses.Methods:Using the purposive sampling method, a total of 19 undergraduate students from School of Nursing at Peking University who participated in nursing research ideological and political education courses were selected for face-to-face semi-structured interviews from March to June 2022. The interview data was analyzed using the Colaizzi phenomenological data analysis method.Results:A total of 19 students were interviewed, and the interviewees stated that through the study of nursing research ideological and political teaching courses, they had mastered scientific research methods, cultivated scientific thinking, strengthened innovation consciousness, expanded international vision and enhanced professional identity.Conclusions:This study is a beneficial attempt at ideological and political education in nursing research courses, providing a basis for the design, implementation and evaluation of ideological and political teaching of similar courses in the future.

The clinical data of a case with late-onset isolated sulfite oxidase deficiency(ISOD)admitted in the Department of Neurology, Children′s Hospital, Zhejiang University School of Medicine in July 2021 were retrospectively analyzed.Fifteen previously published cases of late-onset ISOD were also reviewed.The patient was a girl, who was hospitalized because of " motor regression with mental retardation for 5 days" at 1 year old.The manifestations of the patient were extrapyramidal symptoms, regression of motor development and seizures.The level of urinary sulfites in the patient was increased.Magnetic resonance imaging (MRI) features were bilateral pallidus and substantia nigra.Gene sequencing suggested a pure missense mutation of the sulfite oxidase( SUOX) gene c. 650(exon5)G>A(p.Arg217Gln). In 16 cases of late-onset ISOD, the median age at onset and diagnosis was 10.5 months and 34.0 months, respectively.The common clinical manifestations were hypotonia (13 cases), seizures (10 cases), movement disorders (9 cases), and ectopia lentis (6 cases). The most common brain MRI feature was pallidus changes (11 cases), followed by lesions of substantia nigra (5 cases), and cerebral atrophy (4 cases). Fourteen cases of late-onset ISOD showed a positive urinary sulfite test.The missense mutation of the SUOX gene was found in 9 cases.It suggested that brain MRI involvement of bilateral pallidus, high excretion of urine sulfites and the missense mutation of the SUOX gene were important diagnostic clues for late-onset ISOD.

Objective:To evaluate the efficacy of botulinum toxin A injection therapy with ultrasound-guided for benign masseter hypertrophy.Methods:Twenty cases (40 sides) of masseter hypertrophy were injected with botulinum toxin A, among which 10 cases were taken as experimental group and the other 10 cases as control group. The experimental group had preoperative ultrasound examination to measure the thickness of masseter, and use ultrasound-guided precise injection during the operation, and then ultrasound recheck to measure the postoperative masseter thickness; The other 10 cases of control group adopt traditional 3-point injection method.Results:The masseter thickness of the two groups at different period of times after treatment was decreased ( P<0.001), the most obviously decrease happened 4-12 weeks after injection. The mean reduction was 26.8% at 4 weeks and 28.4% at 12 weeks after injection. Masseter muscle thickness recovered by 22% at 24 weeks and by 20% at 36 weeks. The average follow-up was 6.0±2.4 months with no serious complications occurred. In the control group, there was a partial masseter bulge in one case. The satisfactory rate of the patients in the experimental group was higher than that of the control group. Conclusions:Botulinum toxin A injection therapy with ultrasound-guided for benign masseter hypertrophy is an effective treatment, which is more accurate and effective than the traditional injection method.

Objective:To establish a risk prediction model for hospital acute heart failure in elderly patients with chronic heart failure (CHF) .Methods:From January 2018 to December 2020, 619 elderly CHF patients admitted to the Cardiovascular Department of Peking University Third Hospital were selected as the research object by convenience sampling. The patients were divided into the occurrence group ( n=55) and the non-occurrence group ( n=564) according to whether the patients had acute heart failure in hospital. Binomial Logistic regression was used to explore the independent risk factors of acute heart failure in elderly CHF patients. The nomogram model was constructed by R software, and its prediction effect was verified. Results:Binomial Logistic regression showed that high heart rate at admission [ OR=1.021, 95% CI (1.003, 1.039) ], history of cerebrovascular disease [ OR=2.253, 95% CI (1.197, 4.240) ], constipation [ OR=10.382, 95% CI (1.376, 78.308) ], arrhythmia [ OR=2.051, 95% CI (1.079, 3.898) , taking aspirin [ OR=2.741, 95% CI (1.447, 5.193) ], intravenous diuretics [ OR=6.326, 95% CI (2.629, 15.220) ]and high level of N-terminal forebrain natriuretic peptide [ OR=3.511, 95% CI (1.890, 6.521) ]were independent risk factors for hospital onset of acute heart failure in elderly patients with CHF, and the use of vasodilator was a protective factor. The nomogram model was validated. The area under the receiver operating characteristic curve ( AUC) of the subject was 0.808 [95% CI (0.753, 0.864) ], the AUC of internal validation was 0.821 [95% CI (0.764, 0.871) ], and the calibration curve was a straight line with a slope close to 1. Conclusions:There are many risk factors of hospital acute heart failure in elderly CHF patients. The prediction model based on risk factors has good discrimination and calibration, and can predict the risk of acute heart failure in elderly CHF patients in hospital.

Epithelial ovarian cancer (EOC) is one of the leading causes of death from gynecologic cancers and peritoneal dissemination is the major cause of death in patients with EOC. Although the loss of 4.1N is associated with increased risk of malignancy, its association with EOC remains unclear. To explore the underlying mechanism of the loss of 4.1N in constitutive activation of epithelial-mesenchymal transition (EMT) and matrix-detached cell death resistance, we investigated samples from 268 formalin-fixed EOC tissues and performed various in vitro and in vivo assays. We report that the loss of 4.1N correlated with progress in clinical stage, as well as poor survival in EOC patients. The loss of 4.1N induces EMT in adherent EOC cells and its expression inhibits anoikis resistance and EMT by directly binding and accelerating the degradation of 14-3-3 in suspension EOC cells. Furthermore, the loss of 4.1N could increase the rate of entosis, which aggravates cell death resistance in suspension EOC cells. Moreover, xenograft tumors in nude mice also show that the loss of 4.1N can aggravate peritoneal dissemination of EOC cells. Single-agent and combination therapy with a ROCK inhibitor and a 14-3-3 antagonist can reduce tumor spread to varying degrees. Our results not only define the vital role of 4.1N loss in inducing EMT, anoikis resistance, and entosis-induced cell death resistance in EOC, but also suggest that individual or combined application of 4.1N, 14-3-3 antagonists, and entosis inhibitors may be a promising therapeutic approach for the treatment of EOC.