Glaucoma, a progressive optic neuropathy characterized by RGC degeneration and irreversible vision loss, currently affects approximately 76 million individuals globally. Despite conventional therapeutic strategies primarily targeting IOP reduction, the ongoing progression of vision loss in normotensive patients highlights an urgent need for alternative neuroprotective interventions. We employed a comprehensive experimental paradigm that integrated both in vivo and in vitro approaches. The in vivo component was utilized by NMDA-induced excitotoxicity involving Sprague-Dawley rats. In vitro analyses were conducted using R28 and BV2 cells. Quantitative assessments encompassed electroretinography, RGC survival, axonal integrity measurements, inflammatory marker profiles, flow cytometry, as well as molecular pathway analyses through immunofluorescence microscopy, Western blot analysis. Administration of PF4 (500 ng/ml) exhibited significant neuroprotective efficacy via multiple cellular mechanisms. Quantitative analyses indicated substantial preservation of RGC density (p < 0.001) alongside maintenance of inner plexiform layer thickness(p < 0.05) within the NMDA-induced model. PF4 treatment markedly attenuated microglial activation (p < 0.01) while modulating the inflammatory response-characterized by reduced expression of pro-inflammatory cytokines coupled with enhanced production of anti-inflammatory mediators. CTB tracing confirmed the preservation of both RGC axons and their projections. Molecular analyses revealed that PF4 may exerted its effects on RGC through different mechanisms: suppression of the Galectin-3/NLRP3-inflammasome/Caspase-1 pathway in microglia and enhancement of the CaMKII/CREB/BDNF neuroprotective cascade within RGCs; these protective effects can attenuate necroptosis independent from IOP modulation in retinal excitotoxicity. Our findings suggest that PF4 can protect RGCs through activate CaMKII/CREB/BDNF pathway induced by excitotoxicity. Moreover, it attenuates NLRP3 inflammasome activation via mediating Galectin-3 and thus decreasing necroptosis of RGCs. This study demonstrates that PF4 may possesses neuroprotective properties through simultaneous modulation across multiple cellular pathways in glaucomatous neurodegeneration, and emphasized the significance of immune-mediated mechanisms.

Choroidal neovascularization (CNV) is a leading cause of vision loss in ocular diseases, including age-related macular degeneration (AMD). Despite extensive research, the underlying mechanisms of CNV remain incompletely understood, with a predominant focus on endothelial dysfunction. CNV, however, is a multi-cellular, multi-stage process involving complex interactions between endothelial cells, monocytes/macrophages, and other immune cells. In this study, we employed a dual-platform metabolomics approach combining liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) to identify key metabolic alterations associated with CNV. Our results revealed significant changes in metabolic pathways during CNV progression. Using a myeloid lineage tracing mouse model, we further explored how Pipecolic acid regulates interactions between monocytes/macrophages and endothelial cells, key players in CNV development. We found that Pipecolic acid modulates monocyte/macrophage-endothelial cell crosstalk, inhibiting pathological angiogenesis. These results provide valuable insights into the molecular mechanisms driving CNV and highlight potential therapeutic targets for treating ocular neovascular diseases.

Stem cell-derived secreted factors could protect neurons in neurodegenerative disease or after injury. The exact neuroprotective components in the secretome remain challenging to discover. Here we developed a cell-to-cell interaction model to identify a retinal ganglion cell (RGC)-protective factor derived from induced pluripotent stem cells (iPSCs). Primary RGCs were co-cultured with iPSCs or treated with iPSC-conditioned media in vitro. Cell viability were assayed using live-cell staining, and culture supernatant were analyzed via multiplexed antibody-based assays and ELISA. In vivo tests were carried out under mouse optic nerve crush model and RGC transplantation study in rats. Paired t-tests were used for data analysis between two groups. RGC viability was significantly enhanced when iPSCs were first stimulated with RGC-derived supernatant before iPSC-conditioned medium was collected and added into RGC culture. A significant increase of stem cell growth factor-beta (SCGF-β) concentration was detected in the latter conditioned medium. SCGF-β enhanced RGC survival in vitro and in vivo, and RGC-derived interleukin-12(p70) (IL-12[p70]) promotes secretion of iPSC-derived SCGF-β. Downstream of this IL-12(p70)-to-SCGF-β axis, ngn2 was significantly upregulated, and was found both necessary and sufficient for RGC survival. This study addresses a longstanding question of how neurons and stem cells interact to promote neuroprotection, and define a novel molecular interaction pathway whereby RGC’s secretion of IL-12(p70) enhances iPSCs’ secretion of SCGF-β, and SCGF-β protects RGCs via upregulating ngn2, suggesting that neurons may call on stem cells for their own protection.

Stargardt disease (STGD), predominantly caused by mutations in the ABCA4 gene, is a leading cause of inherited retinal degeneration. Although several lines of mice expressing disease-causing variants have been produced, mice due to the lack of macular may not be the perfect model to mimic the characteristics of STGD. To address this knowledge gap, we generated retinal organoids from patient-derived induced pluripotent stem cells (iPSCs) harboring ABCA4 mutations and performed biological validation. The generated retinal organoids were subjected to single-cell RNA sequencing (scRNA-seq) at major developmental stages (40, 90, 150, 200, and 260 days), and we additionally compared the transcriptomics with our recently published control retinal organoids to further confirm the reliability of the dataset. By using iPSCs carrying most common variant in Chinese STGD patients, the dataset not only provides a powerful resource for studying STGD, but also offers novels insight into the developmental mechanisms underlying ABCA4-associated pathological changes in the retinal organoid system.

Objective:Preoperative exercise prehabilitation in lung cancer patients can improve preoperative functional reserve, reduce postoperative complications, accelerate postoperative recovery compared with postoperative rehabilitation. To integrate and evaluate the evidence related to preoperative exercise prehabilitation in patients with lung cancer. Methods:Conducted utilizing the "6S" model of evidence resources, according to the search strategy searching for relevant guidelines, evidence summaries, best practices, systematic reviews, and expert consensuses on preoperative exercise prehabilitation for lung cancer patients. Based on the evidence inclusion and exclusion criteria, filter out relevant literature published between the beginning of each database and December 2024. Evaluated the quality of the selected literature, and then synthesis the evidence from the literature and made the recommendation level formulation. Results:There were 16 pieces of literature in total, including two guidelines, three evidence summaries, one expert consensus, and ten systematic reviews. Twenty-two pieces of evidence were summarized from seven aspects: patient selection and assessment, exercise implementation and supervision, type of the exercise program, exercise prescription, safety of the exercise program, adherence to exercise program and exercise outcome evaluation. Conclusion:The evidence presented in this study is scientific, comprehensive and of good clinical applicability, which can provide an evidence-based basis for medical staff to carry out preoperative exercise prehabilitation of lung cancer patients.

BackgroundOver-proliferation of mesangial cells (MCs) is one of the main pathological changes in the early stages of diabetic kidney disease (DKD). Roxadustat, an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor, is widely studied in different models of kidney disease. Whether roxadustat has beneficial effect on the proliferation of MCs and DKD remains unknown.MethodsThe optimal concentration of roxadustat for inhibiting MC proliferation was determined using CCK-8 and colony formation assays. Changes in the cell cycle were detected using flow cytometry, and changes in cell cycle-related proteins were screened using quantitative reverse transcription polymerase chain reaction. Reverse experiments were applied using Trp53-/- cell line. Co-immunoprecipitation was used to verify the interaction between HIF-1α and p53 and predict sites of interaction. Finally, a corresponding in vivo verification was performed.ResultsOptimal concentrations of high glucose (30 mM) and roxadustat (100 μM) were established. Roxadustat showed anti-proliferation effect on MCs through S-phase arrest. HIF-1α/p53/p21 and downstream cyclins (cyclin A1, cyclin A2, and cyclin E1) showed corresponding changes. A reverse experiment confirmed that HIF-1α affected cell cycle and proliferation through p53, and co-immunoprecipitation results showed a interaction between HIF-1α and p53. Molecular docking predicted the possible interaction between Lys328, Pro332, Arg245, and Lys251 of HIF-1α and Ala222, Tyr226, Glu225, and Asp265 of p53, respectively. Finally, animal experiments demonstrated similar effect of roxadustat in db/db mice.ConclusionRoxadustat regulates and inhibits cell proliferation of MCs via the HIF-1α/p53/p21 pathway. This may be a potential therapeutic target in the early stages of diabetic kidney disease.

Understanding the barriers and facilitators of prehabilitation in elderly patients with early-stage lung cancer is of significant importance. This study aimed to elucidate these barriers and facilitators from the perspectives of different clinical professionals. A qualitative descriptive study was undertaken. Semi-structured interviews with clinical professionals, using purposive sampling and content analysis were conducted in March to May 2023 to summarize and refine the key themes. From the perspective of clinical professionals, the facilitators of prehabilitation have been categorized into five major themes. These include the recognized importance of prehabilitation, the positive attitude of clinical professionals, the support of leadership, the willingness of the majority of patients to accept prehabilitation, and the initial implementation of an enhanced recovery after surgery - multidisciplinary team (ERAS-MDT) approach. Conversely, clinical professionals identify several barriers to prehabilitation, which are grouped into seven themes. These impediments encompass a lack of knowledge regarding clinical practice, insufficient preoperative preparation time, the absence of an aging-friendly clinical practice scheme, an immature multidisciplinary cooperation mechanism, a lack of explicit regulations, inadequate emergency safeguards, and a shortage of specialized professionals. Practice strategies for promoting prehabilitation in elderly patients with early lung cancer include development of evidence summaries, develop healthcare training materials, develop patient health education brochures, clarify the division of labor of ERAS-MDT, improve patient safety and monitoring measures, optimize practice flow and obtain funding support. To enhance the feasibility and clinical relevance of prehabilitation, clinical professionals should consider establishing a multidisciplinary information consulting team, developing a comprehensive prehabilitation program, and reinforcing the support system prior to surgery.

BACKGROUND:Various programmes and models for post-intensive care unit (ICU) follow-up services have been developed worldwide. In China, post-ICU follow-up remains in the exploratory stage and little is known regarding the appropriate form and challenges of implementation, which need to be further explored. AIM:This study aimed to explore and describe the barriers to and facilitators of post-ICU follow-up services from the perspective of critical care professionals. DESIGN:This was a descriptive qualitative study. Semi-structured interviews were conducted with 21 health care workers whose units had offered ICU survivors different forms of follow-up services; the data were analysed by qualitative content analysis during August 2022 and December 2022. SETTING:The study was conducted at 14 ICUs in 11 tertiary hospitals in Shanghai, China. FINDINGS:Seventeen subthemes were extracted as barriers and facilitators in the follow-up of ICU survivors. In the initiating process, the barriers included the restriction of decision-making rights and scope of practice, indifferent attitude towards survivors and repeated work. The facilitators included admitted significance, the needs of ICU survivors, the conscientiousness of professionals and the pioneers and leadership support. In the implementation process, lack of confidence, lack of cooperation in medical consortium, distrusted relationships, restrictions of medical insurance, ageing problems and insufficient human resources acted as barriers, whereas lessons learned, positive feedback and digital support served as facilitators. Furthermore, recommendations and tips were identified for offering follow-up services. CONCLUSION:Medical personnel can better utilize available resources and develop strategies to overcome constraints by gaining insights into the abovementioned barriers and facilitators. The findings of this study can provide a useful reference for structured and systematic follow-ups to ameliorate post-intensive care syndrome in low- and middle-income countries. RELEVANCE TO CLINICAL PRACTICE:Publicity and educational measures play a crucial role in enhancing the awareness of survivors and the consensus of health care professionals from medical consortium regarding impairments after critical care. Leadership and policy support can address numerous obstacles to guiding follow-up services.

X-linked retinitis pigmentosa (XLRP) is a severe hereditary retinal disorder marked by progressive vision loss due to photoreceptor dysfunction. The retinitis pigmentosa GTPase regulator (RPGR) gene, responsible for most XLRP cases, encodes a protein crucial for the transport of visual signal proteins between the photoreceptor inner and outer segments. However, the mechanism of RPGR mutation causing photoreceptor disorder is not clear and effective treatments remain elusive. This study utilized retinal organoids (ROs) derived from normal and RPGR-mutant human induced pluripotent stem cells (hiPSC) at four developmental stages (40, 90, 150, and 200 days). Single-cell RNA sequencing (scRNA-seq) was conducted on 71,096 cells, including 33,839 cells from the control group and 37,257 cells from the RPGR group. Key retinal cell types were identified and the obtained scRNAseq dataset was validated reliable and high -quality. This study has provided data resources and references for exploring the mechanism of RPGR-related retinal degeneration and support the development of targeted therapies.

Backgrounds: With the advent of the big data era, hospital information systems and mobile care systems, among others, generate massive amounts of medical data. Data mining, as a powerful information processing technology, can discover non-obvious information by processing large-scale data and analyzing them in multiple dimensions. How to find the effective information hidden in the database and apply it to nursing clinical practice has received more and more attention from nursing researchers. Aim: To look over the articles on data mining in nursing, compiled research status, identified hotspots, highlighted research trends, and offer recommendations for how data mining technology might be used in the nursing area going forward. Methods: Data mining in nursing publications published between 2002 and 2023 were taken from the Web of Science Core Collection. CiteSpace was utilized for reviewing the number of articles, countries/regions, institutions, journals, authors, and keywords. Results: According to the findings, the pace of data mining in nursing progress is not encouraging. Nursing data mining research is dominated by the United States and China. However, no consistent core group of writers or organizations has emerged in the field of nursing data mining. Studies on data mining in nursing have been increasingly gradually conducted in the 21st century, but the overall number is not large. Institution of Columbia University, journal of Cin-computers Informatics Nursing, author Diana J Wilkie, Muhammad Kamran Lodhi, Yingwei Yao are most influential in nursing data mining research. Nursing data mining researchers are currently focusing on electronic health records, text mining, machine learning, and natural language processing. Future research themes in data mining in nursing most include nursing informatics and clinical care quality enhancement. Conclusion: Research data shows that data mining gives more perspectives for the growth of the nursing discipline and encourages the discipline's development, but it also introduces a slew of new issues that need researchers to address.

Purpose: It is unknown whether febuxostat can delay the progression of kidney dysfunction and reduce kidney endpoint events. The aim was to evaluate the renoprotective effect of febuxostat in patients with hyperuricemia or gout by performing a meta-analysis of randomized controlled trials (RCTs). Methods: MEDLINE, Web of science, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register for Randomized Controlled Trials were searched. The main outcomes included kidney events (serum creatinine doubling or progression to end-stage kidney disease or dialysis). The secondary outcomes were the rate of change in the estimated glomerular filtration rate (eGFR) and changes in the urine protein or urine albumin to creatinine ratio from baseline to the end of follow-up. We used random-effects models to calculate the pooled risk estimates and 95% CIs. Results: A total of 16 RCTs were included in the meta-analysis. In comparison with the control group, the patients who received febuxostat showed a reduced risk of kidney events (RR = 0.56, 95% CI 0.37-0.84, p = 0.006) and a slower decline in eGFR (WMD = 0.90 mL/min/1.73 m(2), 95% CI 0.31-1.48, p = 0.003). The pooled results also revealed that febuxostat use reduced the urine albumin to creatinine ratio (SMD = -0.21, 95% CI -0.41 to -0.01, p = 0.042). Conclusion: Febuxostat use is associated with a reduced risk of kidney events and a slow decline in eGFR. In addition, the urine albumin to creatinine ratio decreased in febuxostat users. Accordingly, it is an effective drug for delaying the progression of kidney function deterioration in patients with gout. [GRAPHICS]

Objective:To identify latent classes of preoperative physical dysfunction in elderly patients with early lung cancer. To analyze the differences in demographic characteristics between different classes.Methods:We invited elderly patients with early lung cancer who were scheduled for surgery at Shanghai Elderly Characteristic Hospital to participate in the study using a convenience sampling method. We took latent class analysis to divide elderly patients with early lung cancer into latent classes based on preoperative physical dysfunction features. Furthermore, we used single-factor analysis and multinomial logistic regression to investigate the influence variables of each latent class.Results:The characteristics of preoperative physical dysfunction in elderly patients with early lung cancer can be divided into "Anxiety/depression emotion-poor sleep group" "Frailty of physical function group" "Pulmonary hypofunction-low activity tolerance group". The distribution of age, chronic disease history, COPD history, smoking history and perceived social support level of elderly patients with early lung cancer in different potential categories were not the same, and the differences were statistically significant (P<0.05). The elderly lung cancer patients with chronic disease history and age ≥75 years were more likely to be classified as "frailty of physical function group". The elderly lung cancer patients with COPD and smoking history were more likely to be classified into "pulmonary hypofunction-low activity tolerance group". Elderly lung cancer patients with moderate or low degree of perceived social support were more prone to be grouped into "anxiety/depression emotion-poor sleep group".Conclusion:The variety of preoperative physical dysfunction seen in elderly patients with early lung cancer can be categorized into three latent classes. Medical professionals should create strategies for intervention for multiple patient populations with the goal of further enhancing their general state of life.

在老龄化、失能化愈发严峻的形势下,我国提出医养结合并引入长期护理保险(长护险).本文通过综述长护险的政策实践、研究进展以及现存问题与建议,希望促进形成完备的中国特色长期护理保险体系.结论医养结合背景下,长护险在筹资与支付体系上仍存在独立性与公平性的问题,失能资格审查分级流程尚待完善,服务递送与质量评价应由专门的部门统筹并予以监督,长护险服务的人才储备及人员队伍建设还需整合各领域资源,从教育教学和人员待遇为切入,助力长护险稳健、长久发展.

目的 实施降低经桡动脉冠状动脉介入术(PCI)后并发症的循证实践,并观察其对桡动脉闭塞、出血、血肿、瘀斑和肿胀等并发症的影响.方法 应用循证护理的方法获取最佳证据,并基于证据的持续质量改进模式为理论框架,于2019年12月1日-2020年10月31日,按照证据获取、现状审查、证据引入和效果评价4个阶段将循证实践应用于经桡动脉PCI术后患者,比较循证实践应用前后经桡动脉PCI术后患者术肢并发症发生率的变化.结果 经过12条最佳证据的循证实践后,经桡动脉PCI术后患者的桡动脉闭塞、血肿和瘀斑发生率均减少(P＜0.05).结论 循证护理规范了经桡动脉PCI术后的术肢护理,降低术肢并发症的发生,并为PCI围手术期护理提供参考.

目的 护理人员在临床中应用了解《成人患者经鼻胃管喂养临床实践指南》的情况以及应用该指南的促进因素和障碍因素.方法 2022年9-10月采用质性研究的方法对上海市3家三级甲等医院根据鼻饲指南进行鼻胃管喂养的16名护理人员进行半结构式访谈,数据逐字转录并按主题分析.结果 整理分析出3个主题,(1)指南应用下的鼻饲护理实践内容.(2)鼻饲指南应用中的促进因素和阻碍因素.(3)鼻饲指南的更新建议.结论 根据实践内容的促进及障碍因素得出更新掼的建议,建议在更新鼻饲指南时考虑特殊患者群体,将恶心、呕吐、堵管等鼻饲并发症内容纳入更新目录.

目的 了解护士在临床中应用《住院患者跌倒预防临床实践指南》的促进因素和阻碍因素.方法 采用描述性质性研究,于 2022 年 9-11 月选取上海市应用该跌倒指南的 3 所综合性医院即复旦大学附属华东医院、华山医院和中山医院的心内科、神经内科、骨科的 13 名临床护理管理者和一线护士进行半结构式访谈,使用内容分析法进行整理分析访谈资料.结果 归纳出 3 个主题.分别为指南应用下预防跌倒的实践内容、指南应用的促进因素和阻碍因素以及指南更新的建议.结论 护士应用指南的促进因素和阻碍因素包括指南层面、护士层面、患者层面以及医疗系统层面.建议在指南更新时关注到特殊人群的个性化跌倒策略以及延续性护理内容.

IntroductionIt is necessary to explore the evidence-based practice of perioperative management of elderly patients undergoing ambulatory surgery, to optimize the clinical workflow and improve the quality of nursing care.MethodsBased on the best evidence obtained from the previous study, the perioperative management model and examination index of elderly patients undergoing day surgery were established, and the evidence of best practice was obtained by using the evidence-based methodology. Then, we integrated evidence into clinical practice and improved the process. We made a comparative analysis of the effect before and after the implementation of the evidence.ResultsThis study summarized 26 pieces of evidence of perioperative management of elderly patients undergoing day surgery and transformed the evidence into 7 items and 11 items of examination index. After the application of the best evidence, knowledge, belief, and practice of perioperative management of nurses for elderly patients in the day operation ward reached 100%, and the rate of reaching the standard of most indicators increased after the application of evidence. The length of waiting for admission and waiting for operation and returning to the ward to discharge of elderly patients decreased significantly, and the difference was statistically significant (All p < 0.05).ConclusionEvidence-based perioperative management of elderly patients undergoing day surgery improves the nursing practice of clinical nurses and shortens the waiting time and hospitalization time of elderly patients undergoing day surgery, which should be promoted in clinical nursing care.

目的:了解老年脑卒中病人对跌倒及院内防跌倒措施的看法.方法:采用现象学质性研究方法,以目的性抽样方法选取上海市某三级甲等医院神经内科老年脑卒中病人16例进行半结构式访谈,使用内容分析法整理分析访谈资料.结果:访谈结果可归纳为3个主题:对跌倒感知(跌倒原因的感知、负向情绪体验、角色行为冲突、预防跌倒意识增强、盲目 自信);对院内跌倒预防措施态度(感到安全、身体形象紊乱、重视独立性、住院负性体验、防跌倒意识减退因素);院内防跌倒措施引起行为改变(积极应对行为、依从障碍行为).结论:医院跌倒预防系统应促进多角色人员共同参与,加强病人跌倒宣教的同时关注干预措施对病人造成的影响,加强心理护理,医院、家庭和社会共建防跌倒文化.

Uveal melanoma (UM) is the most common intraocular malignant tumor in adults, with a lack of effective treatment for metastasis and a poor prognosis. Stimulator of interferon genes (STING, also known as TMEM173) plays an important role in tumor development by regulating cell proliferation, metastasis and other cellular processes. However, the function of STING in UM remains unclear and requires further investigation. The present study analyzed the expression status of STING to elucidate the mechanisms underlying UM. The correlation between STING and the prognosis of UM was evaluated based on UM RNA‑seq data and clinical information extracted from The Cancer Genome Atlas database. Quantification of STING in UM cell lines and tissues was performed using the Wes Separation protein immunoassay. The effects of STING on the proliferation, migration and invasion of UM cells were investigated using Cell Counting Kit‑8, Transwell and wound healing experiments. Survival analysis demonstrated that high levels of STING in UM tissues indicated a poor prognosis. The expression of STING in UM tissues was higher than that in the choroid membranes. Furthermore, it was found that downregulation of STING expression in UM cells suppressed migration and invasion, whereas overexpression of STING significantly promoted migration and invasion. Notably, STING had no significant effect on UM cell proliferation. It was also identified that STING positively upregulated the phosphorylation of p38 mitogen‑activated protein kinase (p38‑MAPK) in UM cells, enhancing cell migration and invasion, which the p38‑MAPK inhibitor SB203580 reversed. Finally, the results of the present study demonstrated that high STING expression in UM indicates a poor prognosis. STING was revealed to promote the migration and invasion of UM cells through p38‑MAPK signaling.