OBJECTIVE To evaluate the effect and safety of ciprofol combined with local anesthesia on elderly patients undergoing hemorrhoidectomy. METHODS A total of 108 elderly patients who underwent hemorrhoidectomy at the Department of Proctology， Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine from February 2023 to June 2024， were included. The patients were randomly divided into the etomidate group （54 cases） and the ciprofol group （54 cases） based on a computer-generated random sequence. One patient with intraoperative bleeding and one who refused postoperative examination were excluded， resulting in a final total of 106 patients completing this trial （52 in the etomidate group and 54 in the ciprofol group）. The two groups of patients underwent hemorrhoidectomy under local anesthesia with sedative assistance， receiving either etomidate at 0.2 mg/kg or ciprofol at 0.3 mg/kg combined with sufentanil at 0.1 μg/kg. The sedation success rate， induction time， recovery time， operation time and hemodynamic parameters [heart rate （HR）， mean arterial pressure （MAP）， pulse oxygen saturation （SpO2） and respiratory rate （RR）] were observed at baseline （T0）， after successful induction of anesthesia （T1）， 10 minutes after the start of surgery （T2）， and awakening （T3）. Additionally， the levels of oxidative stress markers [malondialdehyde （MDA） and superoxide dismutase （SOD）] were measured at T0， T2 and T3. The occurrence of adverse reactions was also recorded. RESULTS The induction time of the ciprofol group was significantly shorter than that of the etomidate group （P＜0.05）， while the recovery time was significantly longer in the ciprofol group compared to the etomidate group （P＜0.05）. AtT1 and T2， HR， MAP and RR of two groups were significantly lower compared to the same group at T0 （P＜0.05）. However， no significant differences were observed in the hemodynamic parameters at each time point between the two groups （P＞0.05）. At T2 and T3， the MDA levels in both groups were significantly higher than at T0， while the SOD levels were significantly lower than the same group at T0； the ciprofol group showed significantly better outcomes than the etomidate group at the same time points （P＜0.05）. The proportion of patients with intraoperative somatic movements was significantly lower in the ciprofol group compared to the etomidate group （P＜0.05）. CONCLUSIONS When ciprofol is used in elderly patients undergoing hemorrhoidectomy， it demonstrates certain advantages over etomidate in maintaining hemodynamic stability and reducing oxidative stress. Additionally， ciprofol has higher safety.

BACKGROUND: Retinal ganglion cell (RGC) death caused by acute ocular hypertension is an important characteristic of acute glaucoma. Receptor-interacting protein kinase 3 (RIPK3) that mediates necroptosis is a potential therapeutic target for RGC death. However, the current understanding of the targeting agents and mechanisms of RIPK3 in the treatment of glaucoma remains limited. Notably, artificial intelligence (AI) technologies have significantly advanced drug discovery. This study aimed to discover RIPK3 inhibitor with AI assistance. METHODS: An acute ocular hypertension model was used to simulate pathological ocular hypertension in vivo . We employed a series of AI methods, including large language and graph neural network models, to identify the target compounds of RIPK3. Subsequently, these target candidates were validated using molecular simulations (molecular docking, absorption, distribution, metabolism, excretion, and toxicity [ADMET] prediction, and molecular dynamics simulations) and biological experiments (Western blotting and fluorescence staining) in vitro and in vivo . RESULTS: AI-driven drug screening techniques have the potential to greatly accelerate drug development. A compound called HG9-91-01, identified using AI methods, exerted neuroprotective effects in acute glaucoma. Our research indicates that all five candidates recommended by AI were able to protect the morphological integrity of RGC cells when exposed to hypoxia and glucose deficiency, and HG9-91-01 showed a higher cell survival rate compared to the other candidates. Furthermore, HG9-91-01 was found to protect the retinal structure and reduce the loss of retinal layers in an acute glaucoma model. It was also observed that the neuroprotective effects of HG9-91-01 were highly correlated with the inhibition of PANoptosis (apoptosis, pyroptosis, and necroptosis). Finally, we found that HG9-91-01 can regulate key proteins related to PANoptosis, indicating that this compound exerts neuroprotective effects in the retina by inhibiting the expression of proteins related to apoptosis, pyroptosis, and necroptosis. CONCLUSION AI-enabled drug discovery revealed that HG9-91-01 could serve as a potential treatment for acute glaucoma.
Animals ; Glaucoma/metabolism* ; Neuroprotective Agents/pharmacology* ; Mice ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism* ; Artificial Intelligence ; Retinal Ganglion Cells/metabolism* ; Disease Models, Animal ; Molecular Docking Simulation ; Mice, Inbred C57BL ; Male

Endothelial dysfunction is one of the early triggers of vascular remodeling during pulmonary hypertension (PH) with complex predisposing mechanisms, mainly via an unbalanced generation of vasoactive factors, increased expression of growth factors, prothrombotic elements, and inflammatory markers. Conventional treatment regimens are restricted to a single therapeutic pathway, which usually leads to limited clinical outcomes. Combination therapies targeting multiple cells and several signaling pathways are increasingly adopted in PH treatment. Herein, inspired by the cocrystal pleomorphism theory, we prepared rod-shaped nanococrystals of the endothelin-1 (ET-1) receptor antagonist (bosentan, BST) and the anti-inflammatory drug (andrographolide, AG) for targeting the pulmonary endothelium and alleviating PH. The 525 nm-sized co-delivery system displayed a rod-like morphology, preferentially accumulated in the pulmonary endothelium and alleviated pulmonary artery (PA) remodeling. A three-week treatment with the preparation significantly alleviated the monocrotaline (MCT)- or Sugen 5416/hypoxia (SuHx)-induced PH by reducing the pulmonary artery pressure, increasing the survival rate, improving the hemodynamics, and inhibiting vascular remodeling. Mechanistically, the nanococrystals collaboratively repaired endothelial dysfunction by suppressing the pathways of ET-1/NF-κB/ICAM-1/TNF-α/IL-6. In conclusion, the cocrystal-based strategy offers a promising approach for constructing co-delivery systems. The developed rod-shaped nanococrystals effectively target the pulmonary endothelium and relieve experimental PH.

Objective:To conduct the visual analysis of emergency palliative care based on the Web of Science database.Methods:The literature on emergency palliative care collected from 2012 to 2022 was systematically searched in the Web of Science core collection. CiteSpace software was used for visual analysis.Results:A total of 630 articles were included, and the number of publications was on the rise. The country with the highest number of publications was the United States, with 8 out of the top 10 institutions in terms of publication volume coming from the United States. The author with the highest number of publications was Grudzen. The top 10 journals in terms of citation frequency were mostly specialized journals on palliative care and first aid. The results of keyword analysis showed that a total of 15 clustering labels and 20 emergent words were output, reflecting the changes of key research objects, main research types and areas of concern.Conclusions:At present, nursing research in this field is in the development stage in China. We can draw on the practical experience of foreign countries to further explore the emergency palliative care model and service system based on China's national conditions.

"Toxicity Testing in the 21st Century—A Vision and Strategy"proposed by the National Research Council of US has brought innovative directives and objectives for toxicity evaluation and risk assessment,pushing forward the next generation of toxicity testing and risk assessment.In this initiative,the concept of adverse outcome pathways(AOPs)has emerged as a prominent methodology,capturing the attention of toxicologists and researchers due to its promising applications in recent years.The quantitative AOP(qAOP)is an extension of the adverse outcome pathway,which is built upon the foundational qualitative adverse outcome pathway model and leverages mathematical frame-works to depict dose-response and/or response-response relationships.This article reviews the princi-ples and advancement surrounding qAOP,introduceds two prevalent methodologies for constructing qAOP,Bayesian network models and regression models,and demonstrates diverse applications of qAOP.Actual cases are used to underscore the transformative role of qAOP in contemporary toxicology and risk assessment practices.

The timely use of screening tools to assess the palliative care needs of emergency patients can provide decision-making basis for patient referral and help patients receive palliative care in a timely manner.This paper reviews the palliative care needs screening tools for emergency patients at home and abroad,describes their development methods,scoring criteria and application status,compares and analyzes their characteristics and shortcomings.It aims to provide references for the localized development and application of palliative care needs screening tools in emergency patients.

Objective To analyze the publication profile and research hotspots of studies at home and abroad on postoperative cognitive dysfunction by bibliometric methods. Methods Literatures related to postoperative cognitive dysfunction published in the China National Knowledge Infrastructure (CNKI) and Web of Science databases from 2013 to 2023 were included, and statistical analysis was conducted by CiteSpace software. Results A total of 2 705 Chinese literatures and 2 412 English core literatures were included. The number of literatures on postoperative cognitive dysfunction showed an annual increase from 2013 to 2023; China was the country with the highest number of publications internationally, with Capital Medical University ranking the top among Chinese institutions; domestically, postoperative cognitive dysfunction researches predominantly focused on clinical studies, while overseas researches emphasized pathological mechanisms and basic investigations. Research hotspot analysis revealed an enhanced interest in the inflammatory mechanisms and anesthetic aspects of postoperative cognitive dysfunction. Conclusion From 2013 to 2023, the overall research at home and abroad interest in postoperative cognitive dysfunction has shown an upward trend, yet its pathophysiological mechanisms need further exploration. The risk factors for postoperative cognitive impairment and their correlations with anesthesia and mortality are being actively explored, and new methods for prevention and treatment such as percutaneous electrical stimulation are gradually emerging.

In recent years, there has been an increasing emphasis on exploring innovative drug delivery approaches due to the limitations of conventional therapeutic strategies, such as inadequate drug targeting, insufficient therapeutic efficacy, and significant adverse effects. Nanomedicines have emerged as a promising solution with notable advantages, including extended drug circulation, targeted delivery, and improved bioavailability, potentially enhancing the clinical treatment of various diseases. Natural products/materials-derived nanomedicines, characterized by their natural therapeutic efficacy, superior biocompatibility, and safety profile, play a crucial role in nanomedicine-based treatments. This review provides a comprehensive overview of currently approved natural products-derived nanomedicines, emphasizing the essential properties of natural products-derived drug carriers, their applications in clinical diagnosis and treatment, and the current therapeutic potential and challenges. The aim is to offer guidance for the application and further development of these innovative therapeutic approaches.
Animals ; Humans ; Biological Products/chemistry* ; Drug Carriers/chemistry* ; Drug Delivery Systems ; Nanomedicine/methods*

Owing to the inherent shortcomings of traditional therapeutic drugs in terms of inadequate therapeutic efficacy and toxicity in clinical treatment, nanomedicine designs have received widespread attention with significantly improved efficacy and reduced non-target side effects. Nanomedicines hold tremendous theranostic potential for treating, monitoring, diagnosing, and controlling various diseases and are attracting an unfathomable amount of input of research resources. Against the backdrop of an exponentially growing number of publications, it is imperative to help the audience get a panorama image of the research activities in the field of nanomedicines. Herein, this review elaborates on the development trends of nanomedicines, emerging nanocarriers, in vivo fate and safety of nanomedicines, and their extensive applications. Moreover, the potential challenges and the obstacles hindering the clinical translation of nanomedicines are also discussed. The elaboration on various aspects of the research trends of nanomedicines may help enlighten the readers and set the route for future endeavors.