Ferroptosis has been shown to mediate the development of fibrosis. Polyphyllin VII (PP7), a bioactive component of Paris polyphylla, exhibits potent anti-inflammatory activity and can significantly alleviate liver fibrosis. In this study, treatment with PP7 significantly inhibited the proliferation and activation of hepatic stellate cells (HSCs), which could be suppressed by a ferroptosis inhibitor. In addition, it promoted HSC ferroptosis by suppressing glutathione (GSH) peroxidase 4 (GPX4) and enhanced the expression of CX3C chemokine ligand 1 (CX3CL1). Depletion of CX3CL1 attenuated the effects of PP7 on the activation and ferroptosis of HSCs and the expression of GPX4. Notably, CX3CL1 directly interacted with GPX4, triggering HSC ferroptosis. The transcription factor hypermethylated in cancer 1 (Hic1), which binds to the Cx3cl1 promoter, increased the expression of CX3CL1. Its absence resulted in downregulation of CX3CL1, suppressing the GPX4-dependent ferroptosis of PP7-treated HSCs and promoting their activation. HIC1 was found to directly interact with PP7 at the GLY164 site. Co-culture experiments showed that PP7-induced HSC ferroptosis attenuated macrophage recruitment by regulating inflammation-related genes. HSC-specific inhibition of HIC1 counteracted PP7-induced collagen depletion and HSC ferroptosis in vivo. These findings suggest that PP7 induces HSC ferroptosis through the HIC1/CX3CL1/GPX4 axis.

Leber's hereditary optic neuropathy (LHON) is an ocular mitochondrial disease that involves the impairment of mitochondrial complex I, which is an important contributor to blindness among young adults across the globe. However, the disorder has no available cures, since the approved drug idebenone for LHON in Europe relies on bypassing complex I defects rather than fixing them. Herein, PARKIN mRNA-loaded nanoparticle (mNP)-engineered mitochondria (mNP-Mito) were designed to replace dysfunctional mitochondria with the delivery of exogenous mitochondria, normalizing the function of complex I for treating LHON. The mNP-Mito facilitated the supplementation of healthy mitochondria containing functional complex I via mitochondrial transfer, along with the elimination of dysfunctional mitochondria with impaired complex I via an enhanced PARKIN-mediated mitophagy process. In a mouse model induced with a complex I inhibitor (rotenone, Rot), mNP-Mito enhanced the presence of healthy mitochondria and exhibited a sharp increase in complex I activity (76.5%) compared to the group exposed to Rot damage (29.5%), which greatly promoted the restoration of ATP generation and mitigation of ocular mitochondrial disease-related phenotypes. This study highlights the significance of nanoengineered mitochondria as a promising and feasible tool for the replacement of dysfunctional mitochondria and the repair of mitochondrial function in mitochondrial disease therapies.

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Under the leadership of the Beijing Winter Olympic Organizing Committee and the Beijing Municipal Health Commission, the Beijing Emergency Center, as the designated medical institution for the 2022 Beijing Winter Olympic Games, has completed the first aid support task of this Winter Olympic Games with other medical institutions. The author systematically analyzed the development of each link in the pre-hospital emergency support for the 2022 Beijing Winter Olympic Games, summarizes the key links of the entire Winter Olympics cycle, such as the construction of the organizational system, the formulation of support plans, and the training of support personnel, and analyzed the results of related work, so as to provide reference for the pre-hospital emergency support for China to host large-scale international events in the future.

To explore predictive value of fragmented QRS wave (fQRS) for prognosis in patients with a‐cute no ST elevation myocardial infarction (NSTEMI).Methods : According to ECG measure result , 120 NSTEMI patients treated in our hospital from Jan 2015 to Feb 2017 were divided into fQRS group (n＝73) and no fQRS group (n＝47).Both groups received same treatment .General information and incidence of MACE during one‐year fol‐low‐up were compared between two groups .Results : There were no significant difference in heart rate ,percentage of dyslipidemia ,hypertension and diabetes mellitus between two groups ( P＞ 0. 05 all).Compared with no fQRS group ,there were significant reduction in left ventricular ejection fraction [(63. 81 ± 5.67)% vs.(52. 18 ± 5. 81)%, P＝0. 001] , and significant rise in percentage of previous myocardial infarction (21.28% vs.39. 73%, P＝0.035) and more than three coronary stenosis greater than or equal to 50%(36.17% vs.54.79%, P＝ 0.046) in fQRS group .Compared with no fQRS group ,incidence of MACE of fQRS group was higher (25. 53% vs.45.21%, P＝0.030).Conclusion :Cardiac function of NSTEMI patients with fQRS is significantly poorer than that of patients without fQRS ,so patients with fQRS predicts their state of an illness is serious and prognosis is poor .

Objective To study the changes of tissue plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), and soluble thrombomodulin (sTM) induced by dengue 2 virus (D 2V) infection of vascular endothelial cells. Methods The effects of D 2V infection on the production of t-PA, PAI-1, and sTM of human umbilical cord vein cells were studied. Results D 2V infection significantly induced the secretion of sTM and t-PA but showed no such effects on PAI-1 of human endothelial cells. Antibody against IL-6 inhibited D 2V-induced t-PA production of endothelial cells. A close correlation between serum levels of IL-6 and t-PA was found in dengue hemorrhagic fever (DHF) but not in dengue fever (DF) patients. Conclusion IL-6 can regulate D 2V-induced t-PA production of endothelial cells, suggesting that endothelial cells can be the target for D 2V infection and that D 2V-induced t-PA, TM, and IL-6 production of endothelial cells may contribute to the pathogenic development of dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS).