误诊为小儿急性呼吸衰竭的肺外疾病分析

小儿肺外疾病常有呼吸道症状，有时急性呼吸衰竭为其重要表现。1995年以来，我院抢救12例首诊均被误诊为肺炎并呼吸衰竭的患儿，现报告如下。     

Visfatin研究进展

Visfatin是新发现的由内脏脂肪细胞分泌的一种脂肪细胞因子,可结合并激活胰岛素受体的非胰岛素结合部位,激活胰岛素受体信号通路,从而模拟胰岛素作用,降低机体血糖。这一因子还能够促进脂肪组织的分化、合成及积累。Visfatin cDNA序列与前B细胞克隆增强因子(PBEF)相同,Visfatin在细胞内尚发挥尼克酰胺磷酸核糖转移酶(Nampt)的作用,通过调节氧化型辅酶Ⅰ(NAD)的生成从而调控Sirt1的活性,参与细胞的增殖、分化及调亡等过程。     

Qiangli Wuhu mixture alleviates LPS-induced pneumonia by inhibiting the TLR4/NF-κB/NLRP3 pathway: a study based on network pharmacology

ContextQiangli Wuhu (QLWH) mixture is a concoction approved and registered by Ningxia Medical Products Administration. It has therapeutic effects on various types of pneumonia.ObjectiveTo clarify the mechanisms of QLWH in treating pneumonia.Materials and methodsThe potential targets of QLWH in the treatment of pneumonia were predicted by network pharmacology. Male, Institute of Cancer Research (ICR) mice were randomly divided into five groups of 12 mice, control, vehicle, QLWH (10 and 20 mg/kg) and dexamethasone (DXM), and orally treated twice daily with normal saline, QLWH or DXM. The pneumonia model was established by tracheal instillation of lipopolysaccharide (LPS). After treatment five days, ELISA, H&E staining and Western blot were used to investigate protective effects of QLWH.ResultsNine hundred and ninety-four active ingredients were found through network pharmacology, corresponding to 135 targets for the treatment of pneumonia; compared to the vehicle group, QLWH (10 and 20 mg/kg) significantly decreased the levels of TNF-α (14.3% and 28.8%), IL-1β (23.9% and 42.8%) and IL-6 (13.2% and 16.1%), increased the levels of IL-10 (134.3% and 172.9%); in terms of mechanism, QLWH down-regulated TLR4/NF-κB/NLRP3 axis related proteins in lung tissue of pneumonia model mice (p < 0.05).Discussion and conclusionsThis study combined network pharmacology and animal experiments, providing effective evidence for the clinical promotion of QLWH. Meanwhile, it is of significance for further development.     

Healthy Taiwanese Eating Approach (TEA) toward Total Wellbeing and Healthy Longevity

A healthy dietary pattern review for Asian countries is scarce, which is crucial for guiding healthy eating. We reviewed Taiwanese dietary pattern discovery studies. Included were 19 studies, the majority of which employed dimension reduction methods to find dietary patterns associated with various health conditions. To show what is a high or low intake of foods in Taiwan, we also report the average dietary content and the 25th and 75th percentile values of the adult population for six food groups gathered by the Nutrition and Health Survey in Taiwan, 2017–2020. The healthy Taiwanese dietary approach is cohesive across multiple health outcomes occurring at different ages. It is featured with higher intakes of plant-based foods, aquatic foods, and some beneficial ethnic foods (soy products), drinks (tea), and cooking methods (boiling and steaming); lower intakes of fast foods, fatty and processed meats, sugar, salt rich foods/drinks, and fried foods; but with mixed findings for dairy and egg. Yet, the average Taiwanese person consumed many refined staple foods and livestock, but not sufficient vegetables, fruits, whole grains and roots, beans, and nuts. Dairy consumption remains low. In conclusion, Taiwanese discovery studies point to a mortality-lowering total wellbeing dietary pattern consistent with the current knowledge, which discloses potential benefits of soy product, tea, and boiling and steaming.     

先天性巨结肠中miR-939靶向调控SOX4表达抑制肠神经嵴前体细胞功能表型的实验研究

目的 检测MicroRNA-939(miR-939)和性别决定区相关HMG族盒蛋白4(Sry-related HMG box 4,SOX4)在先天性巨结肠(Hirschsprung's disease,HSCR)中的表达水平,评估miR-939在SOX4调控肠神经嵴前体细胞(enteric neural crest c...     

IL‐27 improves adoptive CD8+ T cells’ antitumor activity via enhancing cell survival and memory T cell differentiation

IL‐27 is an anti‐inflammatory cytokine that triggers enhanced antitumor immunity, particularly cytotoxic T lymphocyte responses. In the present study, we sought to develop IL‐27 into a therapeutic adjutant for adoptive T cell therapy using our well‐established models. We have found that IL‐27 directly improved the survival status and cytotoxicity of adoptive OT‐1 CD8⁺ T cells in vitro and in vivo. Meanwhile, IL‐27 treatment programs memory T cell differentiation in CD8⁺ T cells, characterized by upregulation of genes associated with T cell memory differentiation (T‐bet, Eomes, Blimp1, and Ly6C). Additionally, we engineered the adoptive OT‐1 CD8⁺ T cells to deliver IL‐27. In mice, the established tumors treated with OT‐1 CD8⁺ T‐IL‐27 were completely rejected, which demonstrated that IL‐27 delivered via tumor antigen–specific T cells enhances adoptive T cells’ cancer immunity. To our knowledge, this is the first application of CD8⁺ T cells as a vehicle to deliver IL‐27 to treat tumors. Thus, this study demonstrates IL‐27 is a feasible approach for enhancing CD8⁺ T cells’ antitumor immunity and can be used as a therapeutic adjutant for T cell adoptive transfer to treat cancer.     

“Pincer movement”: Reversing cisplatin resistance based on simultaneous glutathione depletion and glutathione S-transferases inhibition by redox-responsive degradable organosilica hybrid nanoparticles

The therapeutic efficacy of cisplatin has been restricted by drug resistance of cancers. Intracellular glutathione (GSH) detoxification of cisplatin under the catalysis of glutathione S-transferases (GST) plays important roles in the development of cisplatin resistance. Herein, a strategy of “pincer movement” based on simultaneous GSH depletion and GST inhibition is proposed to enhance cisplatin-based chemotherapy. Specifically, a redox-responsive nanomedicine based on disulfide-bridged degradable organosilica hybrid nanoparticles is developed and loaded with cisplatin and ethacrynic acid (EA), a GST inhibitor. Responding to high level of intracellular GSH, the hybrid nanoparticles can be gradually degraded due to the break of disulfide bonds, which further promotes drug release. Meanwhile, the disulfide-mediated GSH depletion and EA-induced GST inhibition cooperatively prevent cellular detoxification of cisplatin and reverse drug resistance. Moreover, the nanomedicine is integrated into microneedles for intralesional drug delivery against cisplatin-resistant melanoma. The in vivo results show that the nanomedicine-loaded microneedles can achieve significant GSH depletion, GST inhibition, and consequent tumor growth suppression. Overall, this research provides a promising strategy for the construction of new-type nanomedicines to overcome cisplatin resistance, which extends the biomedical application of organosilica hybrid nanomaterials and enables more efficient chemotherapy against drug-resistant cancers.KEY WORDS: Cancer therapy, Cisplatin, Drug resistance, Glutathione depletion, Glutathione S-transferases, Disulfide bonds, Organosilica hybrid nanoparticles, Ethacrynic acid