Objective To summarize the best evidence for diaphragm rehabilitation in mechanically ven-tilated ICU patients with ventilator-associated diaphragm dysfunction based on evidence-based methods.Meth-ods A systematic search was conducted across guideline websites,professional associations,and Chinese/English databases for evidence regarding diaphragm rehabilitation in mechanically ventilated ICU patients.The search timeframe spanned from database inception to December 31,2024.Two researchers independently per-formed quality assessment and synthesized the evidence.Results Twenty articles were included:2 clinical de-cisions,1 guideline,2 evidence summaries,3 systematic reviews,7 randomized controlled trials(RCT),and 5 expert consensuses/opinions.Twenty-seven pieces of evidence were formed across 6 themes:rehabilitation team,rehabilitation assessment,rehabilitation interventions,outcome evaluation,precautions,and education/training.Conclusion This study summarizes the best evidence for diaphragm rehabilitation in ICU mechani-cally ventilated patients.Healthcare professionals should implement diaphragm rehabilitation by integrating this evidence with specific clinical contexts to improve patient outcomes and enhance nursing quality.

Alzheimer's disease (AD) is a common neurodegenerative disorder among the elderly, and BuChE has emerged as a potential therapeutic target. In this study, we reported the development of compound 8e, a selective reversible BuChE inhibitor (eqBuChE IC₅₀ = 0.049 μmol/L, huBuChE IC₅₀ = 0.066 μmol/L), identified through extensive virtual screening and lead optimization. Compound 8e demonstrated favorable blood-brain barrier permeability, good drug-likeness property and pronounced neuroprotective efficacy. Additionally, 8e exhibited significant therapeutic effects in zebrafish AD models and scopolamine-induced cognitive impairments in mice. Further, 8e significantly improved cognitive function in APP/PS1 transgenic mice. Proteomics analysis demonstrated that 8e markedly elevated the expression levels of very low-density lipoprotein receptor (VLDLR), offering valuable insights into its potential modulation of the Reelin-mediated signaling pathway. Thus, compound 8e emerges as a novel and potent BuChE inhibitor for the treatment of AD, with significant implications for further exploration into its mechanisms of action and therapeutic applications.

Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with ^99mTc, ⁶⁸Ga, and ¹⁸F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.

Objective To investigate the effects and mechanism of β2 adrenergic receptors(ADRB2)in ferroptosis and autophagy induced by erastin(Era)in prostate cancer.Methods PC-3 cells were infected with lentivirus or control and set to sh-NC group(normal culture),sh-NC+Era group(10 μmol/L Era treatment for 24 h),sh-ADRB2 group(normal culture),and sh-ADRB2+Era group(10 μmol/L Era treatment for 24 h).The viability of the cells treated with Era and ferrostatin-1(Fer-1)was measured by CCK-8 assay.The cell morphology was analyzed by transmission electron microscopy.The malondialdehyde(MDA)content was measured by the Lipid Oxidation Detection Kit and the iron level by Iron Colorimetric Assay.Western blotting was used to detect the expressions of cystine-glutamate exchanger(XCT),ferritin heavy chain 1(FTH1),glutathione peroxidase 4(GPX4),p62,LC3,JNK,c-Jun,and p-c-Jun.PC-3 cells with ADRB2 knockdown were injected into nude mice to construct a xenograft model and then treated with Era.The animals were divided into sh-NC group,sh-NC+Era group,sh-ADRB2 group,and sh-ADRB2+Era group,with 4 mice in each group.The tumor volumes were recorded every other day and the final tumor weight was measured at study termination.The expressions of ADRB2,JNK,c-Jun,and p-c-Jun were detected by immunohistochemistry(IHC).Results The viability of PC-3 cells decreased after Era treatment(P<0.01)and recovered after Fer-1 treatment(P<0.01).Morphological changes of ferroptosis and autophagy were observed in Era-treated cells,and MDA and iron ion contents up-regulated(P<0.05 or P<0.01).Knockdown of ADRB2 and Era treatment further inhibited PC-3 cell viability(P<0.05),and MDA and iron ion contents up-regulated(P<0.01).The expressions of ferroptosis-related proteins FTH1,XCT,GPX4,and LC3 down-regulated(P<0.05 or P<0.05),p62 and JNK pathway-related proteins JNK,c-Jun,and p-c-Jun were up-regulated(P<0.01).After JNK inhibitor treatment,the expressions of FTH1,XCT,and LC3 increased,and p62 decreased(P<0.01).In the PC-3 xenograft model,tumor volume in sh-ADRB2+Era group was significantly smaller than those in sh-NC+Era group and sh-ADBR2 group(P<0.05 or P<0.01).IHC showed that compared with sh-NC group,ADRB2 protein expression level was down-regulated in sh-ADRB2 group(P<0.05),while JNK,c-Jun,and p-c-Jun protein expression levels were elevated(P<0.01).Compared with sh-NC+Era group,the ADRB2 protein expression level in sh-ADRB2+Era group was down-regulated,while JNK,c-Jun,and p-c-Jun protein expression levels were up-regulated(P<0.05).Conclusion ADRB2 regulated ferroptosis and autophagy induced by Era via JNK/c-Jun pathway in prostate cancer.

OBJECTIVE To investigate the implementation effects of the national centralized drug volume-based procurement policy （abbreviated as “national centralized procurement policy”） in Guangxi Zhuang Autonomous Region prefecture， and to provide a reference for the future centralized drug procurement work of the medical institution. METHODS Drug procurement data before and after policy implementation were included in the study. The six secondary indicators （such as availability， affordability， and drug safety） and eighteen third-level indicators （such as completion rate of agreed purchase volume， affordability level， drug revenue proportion） were introduced， guided by the policy objectives and issues of concern to policy beneficiaries. Descriptive statistics was adopted to analyze the data before and after policy implementation （in 2019 and 2020） in terms of differences and change trends. RESULTS In terms of accessibility， the participation rate of medical institutions in Guangxi Zhuang Autonomous Region was 92.55%， the proportion of diseases involved and median completed procurement rate were 40.16%， and 287.82% respectively， and the total centralized delivery rate was 97.20%. In terms of affordability， the total reduction amplitude in drug price was 74.80% from 2019 to 2022； the charge for medicine per capita in hospitalization， the proportion of medicine used for outpatient service and hospitalization， decreased by 17.61%， 10.22%， and 20.10% in order； the burden levels on medical fares for patients were all below 1 in addition to chronic diseases， and anti-tumor drugs. In terms of the impact on medicine， the ratio of adverse drug reaction event cases in 2022 was 66.00%， an increase of 1.29% compared to the previous； since the implementation of the policy， 12 drugs from local pharmaceutical enterprises from Guangxi Zhuang Autonomous Region had passed the consistency evaluation， and the market concentration rate of the top 8 pharmaceutical companies was less than 20.00%. In terms of the impact on healthcare and medical insurance， the public medical institutions achieved generic substitution for originator drugs mostly until 2022； about 9.12% of drugs that were non- centrally purchased in the same category were used； 63.39% of people under investigation did not show a need for a second dressing change； drug expenditure decreased by 2.459 billion yuan. CONCLUSIONS The national centralized procurement policy achieves a significant effect in Guangxi Zhuang Autonomous Region. On the other hand， attention should be paid to these suggestions as follows: expanding the category of drugs used in clinic， conducting clinically comprehensive evaluation of selected drugs， and improving reasonable allocation strategy， etc.

Objective:To understand the clinical application status of the best evidence for airway clearance in Intensive Care Unit (ICU) patients, analyze the barriers and enablers in the process of evidence application, so as to provide reference for formulating transformation strategies.Methods:The literature on airway clearance in ICU patients was systematically searched in domestic and foreign databases and association websites. The best evidences were summarized based on the included literature, and corresponding review indicators were constructed based on the best evidence for clinical baseline review. From July to August 2022, convenience sampling was used to select 30 nurses and 30 patients from ICU of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. We conducted barriers and transformation strategy analysis based on the review results.Results:A total of 33 review indicators were formulated. The clinical execution rate of the review indicators was 0 to 100%, with 60.6% (20/33) of the review indicators having a clinical execution rate of <60%. The main barriers were that the specialized team for airway clearance involved great personnel and was difficult to organize, nurses had insufficient awareness and importance of airway clearance knowledge, the department lacked corresponding evaluation tools and equipment, the implementation standards for airway clearance treatment within the department were not sound, and the health education materials for airway clearance were incomplete. The transformation strategy mainly included strengthening leadership support, conducting knowledge training on airway clearance, introducing tools and equipment related to airway clearance, improving the implementation standards of airway clearance and health education materials for airway clearance.Conclusions:There is a significant gap between the best evidence for airway clearance in ICU patients and clinical practice. Timely improvement should be made on relevant barriers to promote the conversion of best evidence into clinical practice and improve patient clinical outcomes.

The purpose of this study was to analyze the effects of shading intensity on the growth, yield, and quality of Artemisia stolonifera so as to provide references for the artificial cultivation of A. stolonifera. The seedlings of A. stolonifera with consistent growth underwent shading treatment at four shading intensity levels(0, 55%, 85%, and 95%) with different layers of black shading nets. The agronomic indexes, yield, moxa yield, total ash, quality characteristics of moxa during combustion and pyrolysis, main volatile components, flavonoids, and phenolic acids were measured. The results showed that under shading conditions, the stem diameter, leaf width, 5-leaf spacing, branch number, and yield of A. stolonifera decreased significantly, while the plant height, leaf length, leaf number, chlorophyll content, and moxa yield increased first and then decreased with the increase in shading intensity. The burning performance of moxa under natural light was better than that under moderate and severe shading conditions. The content of eucalyptol first increased and then decreased with the increase in shading intensity. The humulene content was negatively correlated with shading intensity. Other major volatile components showed no significant difference under various shading conditions. The content of neochlorogenic acid, cryptochlorogenic acid, isoschaftoside, and isochlorogenic acid B was positively correlated with shading intensity, while the content of chlorogenic acid, isochlorogenic acid A, and isochlorogenic acid C decreased first and then increased with the increase in shading intensity. To sum up, A. stolonifera is a light-loving plant, and shading can greatly reduce the yield, the content of internal components, and the burning performance of moxa. It is the main reason why A. stolonifera is mainly distributed in the forest edge, open forest, roadside, and wasteland grass in the middle and high mountains in the wild. For artificial domestication and cultivation of A. stolonifera, it is better to select plots with sufficient light.

Objective:To summarize the best evidence of thirst management in ICU patients and provide evidence-based basis for dinical practice.Method:According to the "6S" evidence pyramid model, the literature on thirst management of ICU patients was systematically retrieved from relevant guidelines websites, evidence-based databases, association websites and original literature databases at home and abroad. The retrieval time was from the establishment of the database to June 31, 2022. Two researchers with evidence-based nursing training independently completed literature quality evaluation. To extract and summarize the evidence of the literature that meets the quality standard.Results:A total of 17 articles were included, including 8 randomized controlled trials, 5 quasi-experimental studies and 4 cross-sectional studies. The 18 pieces of best evidence were formed, including 5 aspects: basic requirements of thirst management, intervention evaluation, intervention methods, matters needing attention and health education.Conclusions:This study summarized the best evidence of thirst management in ICU patients. Nurses should translate and apply the best evidence in combination with the clinical situation and specific policies of the department to relieve the thirst symptoms of ICU patients.

The effect of vitamin D supplementation on individuals with autism spectrum disorder (ASD) is inconclusive. We aimed to conduct a meta-analysis of the available randomized controlled trials (RCTs) to explore whether vitamin D supplementation can improve core symptoms and coexisting conditions in children with ASD. Data were obtained by searching the PubMed, Embase, Web of Science, CINAHL and Cochrane Library databases up to February 2022 following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Using a random-effects model, mean differences with 95% confidence intervals (CIs) were calculated through a meta-analysis. There were eight RCTs with 266 children with ASD in the present review, among which six RCTs were included in the meta-analysis.Children who received vitamin D supplementation showed a significant improvement in stereotypical behavior scores (pooled mean difference (MD): −1.39; 95% CI: −2.7, −0.07; p = 0.04) with low heterogeneity (I2 = 34%), and there was a trend toward decreased total scores on the Social Responsiveness Scale (SRS) and Childhood Autism Rating Scale (CARS, p = 0.05); however, there were no other significant differences in the core symptoms of ASD and coexisting conditions between groups as measured by the Aberrant Behavior Checklist (ABC). Vitamin D supplementation appears to improve stereotypical behaviors but does not improve other core symptoms and coexisting conditions. Further randomized controlled trials with large sample sizes and individualized doses are needed.