Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

Objective To establish an expert consensus on the management of low anterior resection syndrome(LARS)in patients with rectal cancer post-surgery(hereinafter referred to as"consensus"),aiming to standardize the related work of medical institutions in the context of post-operative LARS.Methods A comprehensive search of domestic and international databases was conducted to collect guidelines,expert consensuses,systematic reviews,evidence summaries,and original research related to post-operative LARS in rectal cancer published from the establishment of the databases until August 2024.Based on clinical practice experience,a preliminary draft of the"consensus"was formed.From September to November 2024,22 experts were invited to participate in 2 rounds of expert consultations,during which the draft content was revised and improved,and the final version of the"consensus"was determined through expert validation.Results A total of 22 experts responded,achieving a response rate of 100％.The effective recovery rate of the consultation questionnaires in both rounds was 100％,with an expert authority coefficient of 0.89,a judgment coefficient of 0.97,and a familiarity degree of 0.84.The Kendall harmony coefficients for the 2 rounds of expert consultations were 0.122 and 0.136,respectively(P＜0.001).This consensus covers 5 main aspects:definition,assessment,prevention,treatment,and follow-up management of LARS.Conclusion This consensus demonstrates a high level of scientific rigor and can provide a strong reference for clinical nursing personnel in the specialized care of rectal cancer patients with post-operative LARS.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

Objective:To retrieve, appraise and synthesize evidence regarding the prevention and management of high-output ileostomy in post-enterostomy patients, thereby providing a scientific reference for clinical practice.Methods:A computerized search was conducted, systematically exploring national and international databases, as well as the websites of pertinent associations, to gather evidence relevant to the topic. The literature types included clinical decision-making, evidence summaries, guidelines, expert consensus, and systematic reviews. The search timeframe was established from the date of database construction until 23 August 2024. The methodological quality assessment of the literature, along with the extraction and synthesis of the evidence, was performed by two independent researchers utilizing established criteria and adhering to rigorous standards.Results:A total of 13 papers were included in the review, comprising one clinical decision, four guidelines, and eight systematic reviews. Eighteen pieces of best evidence were distilled and summarized across six key areas: diagnosis and risk identification, fluid/diet/nutrition management, medication administration, skin management, monitoring and health education, and follow-up care.Conclusions:The clinical practice rationale for the prevention and management of high-output ileostomy in post-enterostomy patients, when summarized, would offer scientific and effective evidence-based support for practice changes by clinical care staff. The practical application and translation of this evidence should thoroughly consider the nuances of clinical practice in China, as well as individual patient differences, to ensure the effective implementation of the best evidence for maximizing patient benefit.

Objective:To summarize the best evidence regarding early maternal-neonatal skin-to-skin contact during cesarean section, with the aim of providing an evidence-based foundation for clinical nursing practice.Methods:Developing a literature search strategy to systematically retrieve relevant literature on early maternal-neonatal skin-to-skin contact during cesarean sections from UpToDate, BMJ Best Practice, PubMed, Cochrane Library, CINAHL, Web of Science, Embase, China National Knowledge Infrastructure, VIP, China Biology Medicine disc, and Wanfang Database. The search focus on clinical decision-making, guidelines, expert consensus, evidence summaries, and systematic reviews. The search timeframe should cover from the inception of each database to June 2024. Literature was subjected to quality appraisal, and only high-quality sources were included for evidence extraction and synthesis.Results:A total of eight documents were included, consisting of one clinical decision-making, five guidelines, one expert consensus, and one systematic review. A total of 23 best practice recommendations were extracted and categorized into six domains: team composition and training, indications and contraindications, pre-implementation preparation, implementation protocols, implementation recommendations, and precautions.Conclusions:This study provides a comprehensive summary of current evidence related to early maternal-neonatal skin-to-skin contact during cesarean section. The findings offer evidence-based guidance for clinical nursing practice and contribute to improving the safety of maternal-neonatal skin-to-skin contact implementation during cesarean section.

Objective To establish an expert consensus on the management of low anterior resection syndrome(LARS)in patients with rectal cancer post-surgery(hereinafter referred to as"consensus"),aiming to standardize the related work of medical institutions in the context of post-operative LARS.Methods A comprehensive search of domestic and international databases was conducted to collect guidelines,expert consensuses,systematic reviews,evidence summaries,and original research related to post-operative LARS in rectal cancer published from the establishment of the databases until August 2024.Based on clinical practice experience,a preliminary draft of the"consensus"was formed.From September to November 2024,22 experts were invited to participate in 2 rounds of expert consultations,during which the draft content was revised and improved,and the final version of the"consensus"was determined through expert validation.Results A total of 22 experts responded,achieving a response rate of 100％.The effective recovery rate of the consultation questionnaires in both rounds was 100％,with an expert authority coefficient of 0.89,a judgment coefficient of 0.97,and a familiarity degree of 0.84.The Kendall harmony coefficients for the 2 rounds of expert consultations were 0.122 and 0.136,respectively(P＜0.001).This consensus covers 5 main aspects:definition,assessment,prevention,treatment,and follow-up management of LARS.Conclusion This consensus demonstrates a high level of scientific rigor and can provide a strong reference for clinical nursing personnel in the specialized care of rectal cancer patients with post-operative LARS.

Objective:To retrieve, appraise and synthesize evidence regarding the prevention and management of high-output ileostomy in post-enterostomy patients, thereby providing a scientific reference for clinical practice.Methods:A computerized search was conducted, systematically exploring national and international databases, as well as the websites of pertinent associations, to gather evidence relevant to the topic. The literature types included clinical decision-making, evidence summaries, guidelines, expert consensus, and systematic reviews. The search timeframe was established from the date of database construction until 23 August 2024. The methodological quality assessment of the literature, along with the extraction and synthesis of the evidence, was performed by two independent researchers utilizing established criteria and adhering to rigorous standards.Results:A total of 13 papers were included in the review, comprising one clinical decision, four guidelines, and eight systematic reviews. Eighteen pieces of best evidence were distilled and summarized across six key areas: diagnosis and risk identification, fluid/diet/nutrition management, medication administration, skin management, monitoring and health education, and follow-up care.Conclusions:The clinical practice rationale for the prevention and management of high-output ileostomy in post-enterostomy patients, when summarized, would offer scientific and effective evidence-based support for practice changes by clinical care staff. The practical application and translation of this evidence should thoroughly consider the nuances of clinical practice in China, as well as individual patient differences, to ensure the effective implementation of the best evidence for maximizing patient benefit.