Diabetic retinopathy(DR)remains the leading cause of vision loss in patients with diabetes. Current anti-vascular endothelial growth factor(VEGF)therapies are limited by inadequate response in some patients and the necessity for repeated intravitreal injections, underscoring the urgent need for novel therapeutic targets. Angiopoietin-like protein 4(ANGPTL4), a multifunctional secreted protein, has emerged as a critical regulator in the pathogenesis and progression of DR, positioning it as a promising interventional target. This review systematically elaborates the biological characteristics of ANGPTL4, with a focus on its expression dynamics, molecular mechanisms, and regulatory networks rolesin the development of DR. Furthermore, the prospects of ANGPTL4-targeted therapeutic strategies are discussed, aiming to offer new insights and directions for understanding DR pathogenesis, advancing multi-target drug development, and improving clinical management.

Keratoconus(KC)is a blinding eye disease caused by a variety of factors, with its pathogenesis still not well understood. In recent years, it has been discovered that sex hormones and prolactin-induced protein(PIP)have a profound impact on the cornea, with more noticeable changes when there are abnormalities in their body content. It has been found that various sex hormone receptors are distributed in the cornea. Based on this, this article reviews a multitude of studies on how sex hormones and PIP affect the cornea, along with relevant clinical research. It has been observed that sex hormones and PIP also play a role in KC patients and influence the occurrence and progression of KC. Additionally, it has been noted that pregnant and lactating women may be more susceptible to KC. Sex hormones and PIP have the potential to become new diagnostic and therapeutic targets. This article not only provides new insights but also offers important references for clinical practice.

Keratoconus(KC)is a blinding eye disease caused by a variety of factors, with its pathogenesis still not well understood. In recent years, it has been discovered that sex hormones and prolactin-induced protein(PIP)have a profound impact on the cornea, with more noticeable changes when there are abnormalities in their body content. It has been found that various sex hormone receptors are distributed in the cornea. Based on this, this article reviews a multitude of studies on how sex hormones and PIP affect the cornea, along with relevant clinical research. It has been observed that sex hormones and PIP also play a role in KC patients and influence the occurrence and progression of KC. Additionally, it has been noted that pregnant and lactating women may be more susceptible to KC. Sex hormones and PIP have the potential to become new diagnostic and therapeutic targets. This article not only provides new insights but also offers important references for clinical practice.

Objective To evaluate the influence of the wearing position of dosimeters outside lead aprons on effective dose estimation for interventional radiology workers, analyze the differences between single and double dosimeter methods in effective dose estimation, and provide a reference for the personal dose monitoring of interventional radiology workers. Methods This study employed a combined approach of on-site monitoring and Monte Carlo simulation to evaluate the impact of the wearing position of dosimeters outside lead aprons on effective dose estimation, as well as the differences between effective doses measured using single and double dosimeters. Interventional radiology workers wore dosimeters at three positions: the neck outside the lead collar, the left chest outside the lead apron, and inside the lead apron. Effective doses were estimated using the single and double dosimeter methods specified in GBZ 128-2019 Specifications for individual monitoring of occupational external exposure, and the impact of different wearing positions on the estimation results was compared. Geant4 Monte Carlo simulations were used to model dose distributions at the neck outside the lead collar and at the left chest outside the lead apron for operators performing cardiovascular interventions under tube voltages of 70, 80, 90, and 100 kVp and exposure angles of posteroanterior (PA), anteroposterior (AP), and left anterior oblique 45° (LAO45°) positions. The study assessed the impact of dosimeter wearing position on effective dose estimation. Results Monte Carlo simulations demonstrated that neck doses consistently exceeded left chest doses across different tube voltages and exposure angles, with neck-to-chest dose ratios of 0.80-0.90. Under identical tube voltage conditions, AP showed the highest doses, followed by LAO45°, and PA demonstrated the lowest doses. The single and double dosimeter methods exhibited consistent patterns in effective dose estimation. Single dosimeter method generally yielded higher effective doses with relative deviations of 9.9% to 83%, though these deviations decreased under high tube voltages. Field monitoring data indicated that most interventional radiology workers maintained relative deviations between single and double dosimeter calculations below 6%, with neck-to-chest dose ratios of 0.95-1.1. The estimation patterns remained consistent across both methods, though single dosimeter method showed slightly higher results. Conclusion Under PA, AP, or LAO45°, the doses at the neck consistently exceeded those at the left chest. Therefore, when wearing lead protective equipment, the dosimeter should be properly positioned at the neck outside the lead collar to accurately reflect the radiation doses of surgeons. Some interventional radiology workers improperly positioned the dosimeter (intended at the neck outside the lead collar) at the left chest outside the lead apron, and this may result in an underestimation of the effective dose.

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Resistance to ferroptosis, a form of regulated cell death caused by disruptions in iron ion and intracellular redox homeostasis, is closely related to tumorigenesis and tumor drug resistance; therefore, targeting ferroptosis-related pathways has garnered attention as a potential antitumor therapeutic strategy. However, the molecular mechanisms underlying ferroptosis resistance in tumor cells remain unknown. Zinc-finger estrogen receptor interaction clone 6 (ZER6) consists of two isoforms with distinct N-termini, p52-ZER6 and p71-ZER6. ZER6 is upregulated in tumors and promotes tumorigenic potential; however, whether ZER6 is involved in tumor cell ferroptosis resistance remains unknown. Herein, we identified p52-ZER6 as a novel regulator of tumor cell ferroptosis resistance. p52-ZER6 promotes the transcriptional activity of DAZAP1, an RNA-binding protein. DAZAP1, in turn, enhances the stability of SLC7A11 mRNA by binding to its 3'-UTR region, thereby increasing SLC7A11 expression and cellular glutathione levels. This subsequently reduces lipid peroxide accumulation and enhances tumor cell ferroptosis resistance, eventually promoting tumorigenic potential. These findings reveal a new function of p52-ZER6 in regulating SLC7A11 mRNA stability via DAZAP1, ultimately leading to ferroptosis resistance and tumorigenic potential. Additionally, we also suggest targeting p52-ZER6 as a potential strategy to promote the efficacy of ferroptosis-based antitumor therapies.

Sepsis is an organ dysfunction caused by a dysregulated host response to infection,often characterized by immune dysfunction.This condition typically manifests as an excessive inflammatory response at early stages,followed by immunosuppression at later stages.Due to this immunosuppressive state,patients with sepsis are susceptible to new infections,termed secondary infections,even after the primary infection has been controlled or resolved.In recent years,secondary infections in sepsis have garnered increasing clinical attention due to their risks to exacerbate the disease course,prolong hospital stay,and increase mortality risk.The sepsis-induced immunosuppression is central to the development of secondary infections,especially at the later stage of sepsis.Specifically,T cell function becomes impaired,natural killer cell activity decreases,and macrophage phagocytic ability weakens,all contributing to diminished immune surveillance.Additionally,the immune evasion mechanisms employed by pathogens responsible for secondary infections further complicate treatment.This review aims to elucidate the mechanisms of immunosuppression and its clinical significance in sepsis-related secondary infections,providing a guidance for optimizing treatment strategies.

Ferroptosis is a unique and new mode of cell death, which is driven by iron-dependent lipid peroxidation and mainly characterized by the accumulation of reactive oxygen species in cytoplasm and lipids. Ferroptosis plays an important role in the pathogenesis of many ocular fundus diseases, such as retinitis pigmentosa, age-related macular degeneration, diabetic retinopathy, retinal detachment, retinoblastoma and so on. The use of ferroptosis-related inhibitors or activators can regulate the course of the disease and provide new ideas for the research, prevention and treatment of ophthalmic diseases.

Objective To investigate the effects of fibrin-derived peptide Bβ15-42(FgBβ15-42)on mitophagy in acute kidney injury(AKI)with ischemia-reperfusion at the cellular level.Methods Human kidney-2(HK2)cells were cultured in vitro and ran-domly divided into five groups:normal control group(Control group),hypoxia/reoxygenation(H/R)model group(H/R group),H/R+9μmol/L FgBβ15-42 peptide group(Fg group),H/R+20μmol/L chloroquine group(CQ group),and H/R+9μmol/L FgBβ15-42 peptide+20μmol/L chloroquine group(Fg+CQ group).Control group:cells were homogenized and replaced with complete medium and incubated in an aerobic incubator(5％CO2,21％O2)for 28hours.H/R group:cells were added to sugar-free and serum-free DMEM/F12medium and then placed in a hypoxic incubator(5％CO2,1％O2 and 94％N2)for 24hours,washed with PBS and added to DMEM/F12medium containing serum and then placed in a reoxygenated environment(5％CO2,21％O2)for 4hours.Fg group:mod-eled according to the above method,intervention was performed by adding FgBβ15-42 peptide 9μmol/L to the complete medium when reoxygenation was performed after the completion of hypoxia.CQ group:pre-treatment with chloroquine(20μmol/L)in serum-free medium at the time of homogenization,with the same post-procedural steps as in the H/R group.Fg+CQ group:the intervention was performed according to the dosing sequence of the CQ group and FgBβ15-42 group at different time periods as mentioned above,and the modeling time of the H/R group.After the intervention,CCK-8 was used to detect the cell viability of HK2.The mitochondrial morphol-ogy,mitophagosome structure and number were observed by electron microscope.The expression levels of autophagy related proteins p62 and LC3 were detected by Western blot.Results Compared with the control group,the survival rate of H/R group was decreased(P＜0.01);the mitochondrial damage was obvious,such as swelling and spinous rupture,and the number of mitophagosomes increased.The expression of autophagy protein LC-3 Ⅱ/Ⅰ was up-regulated(P＜0.05),and the expression of autophagy substrate protein p62 was down-regulated(P＜0.01).Compared with H/R group,the survival rate of Fg,CQ and Fg+CQ groups increased(P＜0.01),mito-phagosome was decreased.the expression of LC-3 Ⅱ/Ⅰ was down-regulated(P＜0.01),the expression of p62 was up-regulated(P＜0.05),and autophagy was inhibited.Conclusion The intervention of FgBβ15-42 peptide can reduce the level of autophagy and mitophagy in H/R-AKI cells,and has a protective effect on H/R injury in HK2 cells.

Objective:To retrieve, summarize, evaluate and integrate the best evidence for the prevention and management of center venous catheter dysfunction in hemodialysis patients.Methods:The relevant literature on prevention of center venous catheter dysfunction in hemodialysis patients was systematically searched in UpToDate, BMJ Best Practice, Cochrane Library, National Guideline Clearinghouse, Guidelines International Network, National Kidney Foundation, PubMed, CNKI and other databases, including guidelines, clinical decision-making, evidence summary, systematic evaluation and expert consensus. The search period was from January 1st, 2013 to March 1st, 2023. Two researchers independently evaluated the quality of the literature, evaluated the quality of the included literature and extracted evidence.Results:A total of 15 articles were included, including three guidelines, three clinical decision-making, five expert consensus, two systematic evaluations, one evidence summary and one government document. Ultimately, seven themes and 32 best evidence were formed, including personnel training and management, evaluation and monitoring, catheter insertion, catheter maintenance, drug prevention, catheter dysfunction management and health education.Conclusions:This study summarizes the best evidence for the prevention and management of center venous catheter dysfunction in hemodialysis patients. Medical staff can choose and apply this evidence-based basis based on clinical situations and patient preferences, thereby reducing the incidence of catheter dysfunction.