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☐ ☆ ✇ BMJ Open

Neoadjuvant/adjuvant relugolix and enzalutamide for the treatment of high-risk locally advanced prostate cancer: study protocol of the RENAPCA phase Ib trial

Por: Loper · M. · Qadar · A. · Vesely · S. K. · Gunter · T. · Ayanambakkam · A. · Wen · Y. · Cookson · M. · Stratton · K. — Abril 24th 2026 at 17:42
Introduction

Treatment for high-risk locally advanced prostate cancer typically includes radiation or radical prostatectomy plus androgen deprivation therapy (ADT), but the optimal use of neoadjuvant and adjuvant ADT in practice remains unclear. Relugolix and enzalutamide have demonstrated strong efficacy independently in the setting of advanced disease, but their combined use in neoadjuvant/adjuvant therapy has not been studied. This trial investigates their safety and efficacy as neoadjuvant/adjuvant therapy in patients undergoing definitive local treatment.

Methods and analysis

Relugolix and Enzalutamide as Neoadjuvant/Adjuvant to Local-regional treatment in Patients with High-risk, Locally Advanced Prostate Cancer (RENAPCA) is a prospective, single-arm, open-label phase Ib trial with blinded outcome assessment. The study is conducted across four tertiary oncology centres within the United States. Eligible participants are adult men with pathologically confirmed locally advanced high-risk prostate cancer who are candidates for definitive local therapy. Patients with significant comorbidities or a life expectancy of less than 6 months are excluded. The trial includes a 3+3 dose-escalation safety lead-in cohort (up to 12 patients) to determine dose-limiting toxicities and recommended phase 2 dose, followed by a dose expansion cohort (up to 46 patients). Interventions consist of 6 months of neoadjuvant therapy with relugolix plus enzalutamide, definitive local therapy (radical prostatectomy or radiation therapy), and 18 months of adjuvant therapy with relugolix plus enzalutamide. Primary outcomes include pathologic CR rate and minimal residual disease rate. Secondary outcomes include prostate-specific antigen response, progression-free survival, objective response rate, frequency and severity of adverse events, and positive margin/pathologic downgrade rate. Exploratory objectives include patient-reported outcomes and quality of life measures. RENAPCA will assess the safety and efficacy of neoadjuvant/adjuvant relugolix+enzalutamide in high-risk, locally advanced prostate cancer to support future larger-scale studies and potentially improve treatment outcomes.

Ethics and dissemination

This research protocol has been approved by the Institutional Review Board of the University of Oklahoma Health Sciences Center (7 March 2024). The study is based on voluntary participation with informed written consent.

Trial registration number

NCT06130995.

☐ ☆ ✇ BMJ Open

Methodologies and methods for the development, evaluation and implementation of psychosocial interventions for dementia: protocol for a scoping review

Por: DAndrea · F. · Bartels · S. L. · Markaryan · M. · Masterson-Algar · P. · Bernal · A. N. · De Bruin · S. R. · Chirico · I. · Flynn · A. · Garcia · L. · Gebhard · D. · Handley · M. · Janssen · N. · Roes · M. · Stephens · N. · Teesing · G. · Van den Block · L. · Windle · K. · Moniz-Cook · E. — Abril 24th 2026 at 17:42
Introduction

Research on psychosocial interventions for dementia demonstrates increased rigour and robustness. However, if we are to influence practice, beyond results from randomised controlled trials, a variety of types and sources of evidence is needed. The Medical Research Council (MRC) framework offers a valuable guide for developing, evaluating and implementing complex interventions, to facilitate integration of research into practice. There is limited knowledge of how researchers design, evaluate and implement psychosocial intervention studies in dementia, using the MRC framework. This scoping review aims to: (1) identify the methodological and methods trends, use and gaps in the development, evaluation and implementation of psychosocial interventions for dementia, and (2) determine if and how the MRC six core elements were considered and applied in studies.

Methods and analysis

Six databases (Ovid MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, Cochrane Library) will be searched for studies published from 2015 (when MRC process guidance was published) to 2025. Identified deduplicated citations will be imported into Covidence software, where up to 40% of title/abstracts will be double screened by independent reviewers. ASReview will be used to rank articles by relevance, with a stopping criterion of 250 consecutive irrelevant articles. Full texts will be reviewed by a single reviewer and those excluded will be checked by a second reviewer. Data extraction will include study aim/objective (ie, to develop/adapt; test feasibility/pilot; evaluate; implement); methodology and methods applied; information on which MRC six core elements were considered (yes/no), and if so, how they were addressed (ie, qualitative details). A narrative synthesis, alongside graphical representations (eg, table/bar charts/histograms), will be used to synthesise findings on methodologies and methods mapped onto the MRC framework.

Ethics and dissemination

This secondary analysis scoping review does not require ethics approval. Results will be disseminated through peer-reviewed publication(s), seminars, webinars, conferences, postgraduate dementia programmes, blogs, commissioner briefings and social media. The findings will provide a state-of-the-art overview of current practices; advance methods/methodology such as informing a Delphi consensus study on appropriate research approaches; and guide researchers in application of the MRC framework to widen the scope of dementia care evidence for practice improvements.

Registration

Submitted to Open Science Framework https://doi.org/10.17605/OSF.IO/S56NQ.

☐ ☆ ✇ BMJ Open

Real-world changes in lipid-lowering therapy use and LDL-C goal attainment in high and very high cardiovascular risk patients in the UK: a secondary analysis of the European SANTORINI study 1-year follow-up

Por: Connolly · D. · Fuat · A. · McCormack · T. · Mcnally · D. · Garstang · J. · Ryan · J. · Reed · A. · Robinson · D. · Catapano · A. L. · Ray · K. K. — Abril 24th 2026 at 17:42
Objectives

This real-world study investigated the changes of lipid lowering therapy (LLT) usage in patients with high or very high cardiovascular (CV) risk in the UK and the group of all other European countries in the SANTORINI study up to 1 year from baseline and the impact this treatment had on the attainment of low-density lipoprotein cholesterol (LDL-C) risk-adjusted goals set by the National Institute for Health and Care Excellence (NICE) and those in the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) dyslipidaemia guidelines.

Design

Secondary analysis of the SANTORINI dataset (an international, prospective, observational, non-interventional study (NCT04271280)).

Setting

Primary and secondary care centres in the UK and the group of other European countries (Austria, Belgium, Denmark, Finland, France, Germany, Ireland, Italy, the Netherlands, Portugal, Spain, Sweden and Switzerland).

Participants

663 UK patients with high and very high CV risk were included in this analysis and 8502 from the group of other European countries. Of these, 380 UK patients and 6830 from the group of other European countries had LDL-C information available at baseline and 1-year follow-up.

Primary outcome measures

The primary objectives were to describe patients’ lipid management, LDL-C levels at 1-year follow-up and their attainment of 2023 NICE (≤2.0 mmol/L) and 2019 ESC/EAS LDL-C 2019 guideline-recommended LDL-C goals (

Results

Over the course of 1-year follow-up, the overall proportion of UK patients on no LLT reduced from 20.4% at baseline to 7.1%, similar to that observed in the group of other European countries (baseline–20.9%, 1 year–3.0%). The proportion of UK patients receiving LLT monotherapy increased from 74.8% at baseline to 84.9%, higher at both time points than that observed for the group of other European countries (baseline: 52.0%, 1 year: 55.0%). The use of any combination therapy increased slightly from baseline to 1 year in the UK overall cohort (4.9% vs 7.1%) and overall in the group of all other European countries, the cohort increased from baseline (27.1%) to 1 year (40.2%). Overall, mean (SD) LDL-C levels in the UK were 2.5 (1.2) mmol/L at baseline and 2.1 (1.0) mmol/L at 1 year and for the group of other European countries were 2.4 (1.2) mmol/L at baseline and 2.0 (0.9) mmol/L at 1 year. The overall proportions of UK patients achieving the UK NICE treatment goal and ESC/EAS 2019 guidelines at baseline versus 1-year follow-up were 40.3% vs 52.6% and 22.9% vs 32.9%, respectively; 21.1% and 30.9% of patients in the group of other European countries achieved the ESC/EAS 2019 guidelines at baseline and 1-year follow-up, respectively.

Conclusions

In this UK-focused analysis of the SANTORINI study, use of LLT increased modestly over 1 year, accompanied by a reduction in average LDL-C levels. However, mean LDL-C remained above the NICE goal, and attainment of both NICE and ESC/EAS LDL-C thresholds remained suboptimal. The findings highlight continued opportunities to optimise lipid management in UK clinical practice, including the potential for broader use of combination therapies.

☐ ☆ ✇ PLOS ONE Medicine&Health

A secondary head-to-head comparison of low-intensity focused ultrasound and repetitive transcranial magnetic stimulation for motor recovery after stroke

Por: Shuhong Zheng · Renxiu Bian · Haixin Song · Zhiping Liao · Ting Gao · Min Yan · Heqing Huang · Zuodong Lou · Fangchao Wu · Jianhua Li — Abril 24th 2026 at 16:00

by Shuhong Zheng, Renxiu Bian, Haixin Song, Zhiping Liao, Ting Gao, Min Yan, Heqing Huang, Zuodong Lou, Fangchao Wu, Jianhua Li

Background

Low-intensity focused ultrasound (LIFU) is a non-invasive neuromodulation technique with high spatial precision and the ability to reach deeper brain regions, offering potential advantages for post-stroke rehabilitation. Repetitive transcranial magnetic stimulation (rTMS) is a widely adopted non-invasive brain stimulation technique that modulates cortical excitability to promote neuroplasticity. However, direct head-to-head comparisons between these two modalities for post-stroke motor recovery remain limited.

Objective

To perform a secondary head-to-head comparison of LIFU and repetitive transcranial magnetic stimulation (rTMS) for motor recovery after stroke, based on a prospectively registered randomized controlled trial.

Methods

This secondary analysis included patients with subacute stroke who received two weeks of standard rehabilitation combined with either LIFU (n = 25) or rTMS (n = 25) targeting the ipsilesional primary motor cortex. LIFU parameters: 0.5 MHz, spatial-peak pulse-average intensity (ISPPA) 10.2 W/cm² (free-field), pulse duration 0.2 ms, duty cycle 20%, 20 minutes per session, five days per week for two weeks (10 sessions total). rTMS parameters: 10 Hz, 80% resting motor threshold, 1,000 pulses per session (20 trains of 5 seconds), 20 minutes per session, five days per week for two weeks (10 sessions total). Motor outcomes were assessed using the Fugl–Meyer Assessment (FMA; upper and lower extremities), Modified Barthel Index (MBI), and Brunnstrom stages. Resting-state functional near-infrared spectroscopy (fNIRS) was used to evaluate cortical activity and functional connectivity before and after the intervention. Primary analyses were conducted in the intention-to-treat (ITT) population (n = 50), with completer analyses (n = 43) performed as sensitivity analyses.

Results

Both groups showed significant within-group improvements in FMA and MBI after the intervention (all p  0.05), and completer analyses yielded consistent between-group conclusions. In contrast, change-from-baseline analyses demonstrated greater improvements in FMA scores in the LIFU group compared with the rTMS group (ΔFMA upper limb: median 7 [IQR 3–10.5] vs. 2 [1–3], p = 0.001; lower limb: 3 [1–4.5] vs. 1 [0–1.5], p  Conclusion

LIFU and rTMS were associated with comparable short-term motor outcomes in subacute stroke. Differences observed in change-from-baseline motor improvements and exploratory neuroimaging measures suggest potential divergence in recovery dynamics and cortical modulation, warranting further investigation in larger, longitudinal studies.

Trial registration

This study was derived from a prospectively registered, three-arm randomized controlled trial in the Chinese Clinical Trial Registry (ChiCTR2500114687). The present manuscript reports a secondary head-to-head comparison between the two neuromodulation intervention arms.

☐ ☆ ✇ PLOS ONE Medicine&Health

The impact of COVID-19 vaccination on long-term risk of new-onset atrial fibrillation/flutter after COVID-19 infection: A retrospective cohort study

Por: Ching-Chung Ko · Jheng-Yan Wu · Kuo-Chuan Hung · Shu-Wei Liao · Ya-Wen Tsai · Tsung Yu · Chien-Ming Lin · I-Wen Chen — Abril 24th 2026 at 16:00

by Ching-Chung Ko, Jheng-Yan Wu, Kuo-Chuan Hung, Shu-Wei Liao, Ya-Wen Tsai, Tsung Yu, Chien-Ming Lin, I-Wen Chen

Purpose

COVID-19 infection has been associated with cardiovascular complications, including new-onset atrial fibrillation/flutter (NOAF). However, the potential protective effect of COVID-19 vaccination against long-term NOAF risk following COVID-19 infection remains unclear.

Methods

This retrospective cohort study used the TriNetX Research Network to identify adults diagnosed with COVID-19. Patients were divided into a vaccine group and control group (unvaccinated). After propensity score matching (238,750 patients per group), we assessed the primary outcome of 24-month NOAF incidence, with secondary outcomes at 1, 6 and 12 months. Subgroup analyses examined effects across patient characteristics and comorbidities. Sensitivity analysis was performed by excluding patients with severe COVID-19 illness.

Results

The 24-month NOAF incidence was significantly lower in the vaccine group compared to the control group (1.91% vs 2.18%; HR: 0.82, 95% CI: 0.78–0.85). This protective effect was also observed at 1 month (HR: 0.73, p  Conclusion

COVID-19 vaccination was associated with a significantly reduced 24-month risk of NOAF after COVID-19 infection. These findings suggest vaccination may mitigate long-term cardiovascular sequelae of COVID-19. Future research should elucidate underlying protective mechanisms and optimize vaccination strategies for cardiovascular protection, particularly in high-risk populations.

☐ ☆ ✇ PLOS ONE Medicine&Health

Gut microbiome alterations among Ghanaian children with asymptomatic malaria infections

by Amma Aboagyewa Larbi, Moses Etsey, Obed Brew, Bismark Koduah, Rosemond Enam Mawuenyega, Emmanuel Kobla Atsu Amewu, Nehemiah Kweku Essilfie, Solomon Wireko, Alexander Kwarteng, Ben Adu Gyan

The human gut microbiome, consisting of bacteria, archaea, fungi, and viruses, influences various physiological processes of the body. The gut microbiome composition is shaped by factors such as diet, geography, and antibiotic use. Malaria has been a global health challenge over the years, especially in low- and middle-income countries. This study investigated how asymptomatic malaria infection altered gut microbial communities in Ghanaian children, offering insights for novel malaria control strategies. Standard aseptic phlebotomy procedures were employed to collect venous blood samples for Plasmodium species detection. The gut microbial community was profiled by sequencing the 16S rRNA V4 region, and sequence data were processed using the DADA2 pipeline in R. Asymptomatic malaria infections were predominantly mixed with P. falciparum and P. malariae. Microbiome analysis revealed that Firmicutes and Bacteroidetes comprised nearly 70% of the total microbial population. Asymptomatic individuals showed a decrease in Firmicutes abundance from 52.5% to 44.0% and an increase in Bacteroidetes from 34.7% to 45.6%. There was also a slight increase in the abundance of Proteobacteria from 3.0% to 4.8%. At the genus level, Prevotella_9 was the most abundant and exhibited the highest variability in the infected groups. The Alloprevotella and Streptococcus genera increased in both infected groups, but Escherichia-Shigella was significantly elevated in only those with mixed infections. Faecalibacterium significantly declined in asymptomatic malaria-infected individuals compared to healthy controls, with variability further reduced in mixed infections. Beta-diversity analysis indicated a significant effect of malaria status on microbial composition (PERMANOVA, p 
☐ ☆ ✇ PLOS ONE Medicine&Health

Machine learning identifies pupil size and corneal thickness as key predictors of axial elongation rate

Por: Peng Zhou · Sitong Chen · Yingli Li · Yan Li — Abril 24th 2026 at 16:00

by Peng Zhou, Sitong Chen, Yingli Li, Yan Li

Purpose

This study aimed to develop a machine learning-based prediction model for myopia progression using ocular biometric parameters to provide an objective assessment tool for clinical practice.

Methods

A retrospective analysis was conducted on patients treated at Shanghai Parkway Health Ophthalmology Department as the training set, and myopic individuals from the Optometry Center of Peking University People’s Hospital as the validation set. Demographic and biometric data were collected, including central corneal thickness (CCT), axial length (AL), corneal curvature (K-value), anterior chamber depth (ACD), corneal diameter (WTW), and pupil size (PS). Seven machine learning models (e.g., XGBoost, random forest, support vector machine) were employed for modeling, with performance optimized via 5-fold cross-validation. Model accuracy was evaluated using mean squared error (MSE) and the coefficient of determination (R²), and variable importance was analyzed.

Results

No statistically significant differences were observed in baseline characteristics between the training and validation sets (all P > 0.05). The XGBoost model demonstrated the best performance, achieving R² = 0.913 (MSE = 0.005) on the training set and R² = 0.766 (MSE = 0.016) on the test set. Variable importance analysis revealed pupil size (score 100) and corneal thickness (40.88) as the key predictors of axial elongation rate, followed by age of onset (17.96).

Conclusion

The machine learning-based prediction model effectively utilizes ocular biometric data to assess myopia progression risk, with pupil size and corneal thickness identified as core predictive factors. This model provides a quantitative tool for early clinical intervention. Future studies should expand the sample size and incorporate additional biomarkers to optimize performance.

☐ ☆ ✇ BMJ Open

Protocol for a multicentre survey of sexual and reproductive health and fertility among unmarried women living in Chinas megacities

Por: Yang · F. · Hu · J. · Liu · H. · Liu · T. · Wu · D. · Stewart · T. · Chen · G. — Abril 21st 2026 at 12:58
Introduction

Despite the rapid increase in the proportion of unmarried women in the Chinese population, little is known about their sexual and reproductive health (SRH) and well-being. The aim of this survey is to collect data on SRH knowledge and needs, past care-seeking experiences, fertility goals and attitudes towards fertility technology among unmarried women in four megacities in China where singlehood is prominent among women of reproductive age.

Methods and analysis

This multi-centre cross-sectional survey, Survey of Unmarried women on Reproductive health and Fertility (SURF), aims to recruit 6000 eligible women, with 1500 from each study site. Eligibility criteria include: (1) women; (2) aged 25–40 years; (3) currently unmarried (never married, divorced or widowed); and (4) reside in Beijing, Shanghai, Shenzhen or Guangzhou metropolitan areas. Quota sampling is used to ensure the age strata in the final sample correspond to the age distribution from the latest Chinese census. Data are currently being collected through referral recruitment and a self-administered questionnaire available on the mobile devices and computers of participants.

Ethics and dissemination

SURF has been approved by the Biomedical Ethics Committee of Peking University (institutional review board (IRB) number: IRB00001052-24040). Each participant receives comprehensive information about the objectives, procedure and data handling of the survey before proceeding to the questionnaire. Participants are also provided with the contact information of the principal investigator in case they have questions regarding the survey. Written informed consent is obtained before data collection starts. Participation is anonymous and no personal identifiers are collected. Findings from this survey will be disseminated through peer-reviewed journals and at scientific conferences.

☐ ☆ ✇ BMJ Open

Intranasal dexmedetomidine in reducing postoperative delirium among cardiac surgery patients by improving sleep quality in China (DREAMS): study protocol for a single-centre, double-blind, randomised controlled trial

Por: Zhang · Z. · Yang · X. · Qin · Y. · Gao · B. · Wang · Y. · Ji · J. · Gao · J. · Huang · M. · Wang · L. · Zheng · Z. · Lei · C. — Abril 21st 2026 at 12:58
Introduction

Postoperative delirium (POD) is a common complication following cardiac surgery and is closely associated with adverse clinical outcomes. The effect of perioperative dexmedetomidine on reducing POD remains controversial in the existing literature. In our previous meta-analysis, we obtained preliminary evidence suggesting that dexmedetomidine may reduce the incidence of POD by improving sleep quality, which may partly explain the heterogeneity reported in previous studies. Based on these findings, the present randomised controlled trial aims to test the hypothesis that preoperative intranasal administration of dexmedetomidine reduces the incidence of POD in patients undergoing cardiopulmonary bypass assisted cardiac surgery by enhancing preoperative sleep quality.

Methods and analysis

This trial is a single-centre, investigator-initiated, parallel, double-blind, randomised, placebo-controlled trial. Individuals aged 18 years or older who are scheduled for elective cardiopulmonary bypass—assisted cardiac surgery will be enrolled in the study. The planned sample size is 686. Participants will be randomly assigned to either the dexmedetomidine group receiving two doses of dexmedetomidine (1.5 µg/kg according to ideal body weight) administered between 21:00 and 21:30 on the night before surgery and 15 min before anaesthesia induction, or the placebo group, receiving an equivalent volume of normal saline at the same time points. The primary outcome is the incidence of delirium within 7 days after surgery. Secondary outcomes include the severity, subtypes and duration of delirium, length of postoperative hospital stay, in-hospital all-cause mortality, postoperative sleep assessed by the Numerical Rating Scale score, pain intensity, postoperative anxiety and depression scores. Mediation analyses will be conducted using the preoperative Sleep Quality Index to assess whether dexmedetomidine reduces POD by improving preoperative sleep quality. The Baron and Kenny causal steps framework in conjunction with bootstrap resampling will be employed to estimate the direct, indirect and total effects.

Ethics and dissemination

The study is approved by the Institutional Review Board of Xijing Hospital (KY20242259). Written informed consent will be obtained from all participants. The results will be submitted for publication in peer-reviewed journals.

Trial registration number

NCT06619912.

☐ ☆ ✇ PLOS ONE Medicine&Health

Analyzing the collaborative development needs of grassroots centers for disease control and prevention using the Kano model: A case study of China’s Chengdu–Chongqing Economic Circle

Por: Yang Tong · Huang Qianzhen · Tan Bo · Hu Bin · Zhang Min — Abril 20th 2026 at 16:00

by Yang Tong, Huang Qianzhen, Tan Bo, Hu Bin, Zhang Min

Background

Advancing the development of centers for disease control and prevention (CDCs) has become a priority within global public health governance. However, public health governance capacity varies significantly among CDCs across different countries and regions, grassroots CDCs face particular disadvantages. Establishing stable, efficient collaborative development mechanisms among CDCs across diverse regions to maximize overall effectiveness and ensure sustainable development represents a critical public health science issue.

Objective

This study aims to provide scientific references and a theoretical foundation for the coordinated development of grassroots CDCs within the Chengdu–Chongqing Economic Circle (CCEC) and the construction of public health systems.

Methods

A questionnaire for collaborative development needs indicators in grassroots CDCs, comprising 4 primary needs and 13 secondary needs, was developed through literature review, the Delphi expert consultation method, and the Kano model. Analysis focused on questionnaires collected from eight grassroots CDCs within the CCEC. The importance of needs was ranked using the better–worse coefficient and satisfaction sensitivity analysis.

Results

Analysis of the 110 valid questionnaires showed that for the must-be attribute, satisfaction sensitivity ranked as follows: performance compensation (0.883)> talent exchange and scientific research and innovation cooperation (0.824)> public health emergency rescue mechanism (emergency material reserve and cross-regional material mobilization; 0.817)> cross-regional case monitoring, investigation, and tracking (0.775). Regarding the one-dimensional attribute, the satisfaction sensitivity ranking was joint risk assessment and emergency command (0.937)> business archive co-construction and sharing mechanism (emergency response plan, and technical scheme) (0.909)> regional co-construction and sharing between the university and the local area (0.832). For the attractive attribute, the satisfaction sensitivity ranking was regional monitoring and early-warning information management system (0.922)> community chronic disease prevention and service (0.804)> coordinated transfer and diversion diagnosis and treatment of patient with infectious diseases within the region (0.734). However, the collaborative release and interaction mechanism of social integrated media information, public health collaborative governance entities, and the construction of a cross-regional expert database constitute indifferent attributes.

Conclusions

This study provides preliminary scientific evidence for the precise allocation of public health resources and the establishment of localized collaborative development mechanisms. Simultaneously, the research methodology and analytical framework offer new theoretical references for similar studies in other regions globally.

☐ ☆ ✇ PLOS ONE Medicine&Health

Ectopic expression of <i>Aspergillus flavus</i> uricase and URAT1 in therapeutic cells promotes intracellular degradation of uric acid in hyperuricemic mice

Por: Yuzhong Feng · Jiazhen Cui · Xuan Huang · Yupeng Li · Haolong Dong · Xianghua Xiong · Gang Liu · Qingyang Wang · Huipeng Chen — Abril 20th 2026 at 16:00

by Yuzhong Feng, Jiazhen Cui, Xuan Huang, Yupeng Li, Haolong Dong, Xianghua Xiong, Gang Liu, Qingyang Wang, Huipeng Chen

Uricase-based drugs excel at treating refractory hyperuricemia and tumor lysis syndrome by directly degrading uric acid but are limited by immunogenicity. Here, we engineered RAW264.7 macrophages with ectopic co-expression of Aspergillus flavus uricase and murine urate anion transporter 1 (URAT1), forming a “transport-degradation” system: URAT1 actively transports uric acid into cells for intracellular degradation. Recombinant lentiviral vectors carrying target genes were transfected into RAW264.7 cells, followed by puromycin screening. In vitro assays showed that the engineered macrophages nearly completely degraded uric acid (from 556.0 ± 37.0 μmol/L to 0.7 ± 0.6 μmol/L) at 72 h. URAT1 inhibition with benzbromarone abolished uric acid degradation in URAT1-expressing cells. In both acute dietary-induced and chronic genetic hyperuricemic mouse models, RAW-afUri-URAT1 exerted robust and sustained uric acid-lowering activity, maintaining serum uric acid at 77.14 ± 37.48 μmol/L on day 16 in yeast extract gavaged mice and normalizing serum uric acid to 76.2 ± 15.9 μmol/L in liver uricase conditional knockout mice, both significantly superior to the rebound levels observed in mice treated with Rasburicase (143.19 ± 38.21 μmol/L and 142.4 ± 17.4 μmol/L, respectively; P
☐ ☆ ✇ PLOS ONE Medicine&Health

Identification and clinical implications of immune-related hub genes in psoriasis

Por: Yuzhen Sun · Ziguang Zhou · Yu Mao · Niu Liu · Yanfeng Li · Weiyuan Fang — Abril 20th 2026 at 16:00

by Yuzhen Sun, Ziguang Zhou, Yu Mao, Niu Liu, Yanfeng Li, Weiyuan Fang

Background

Psoriasis, a chronic inflammatory skin disease affecting 2–3% of the global population, is driven by dysregulated immune responses. Despite advancements in biologic therapies, treatment challenges persist due to high recurrence rates. This study aimed to identify immune-related hub genes and elucidate their clinical implications in psoriasis pathogenesis and therapy.

Methods

Multiple microarray datasets from psoriasis patients (GSE30999, GSE106992, GSE14905, GSE78097, and GSE117468) were obtained to identify immune-key genes by differential gene analysis and Weighted Gene Co-expression Network Analysis (WGCNA). Subsequently, immune-related hub genes were identified using the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and Protein-Protein Interaction (PPI) networks, with further validation through Gene Set Enrichment Analysis (GSEA) and Receiver Operating Characteristic (ROC) curves to assess exploratory within-sample discrimination. Pearson correlation analysis evaluated the relationship between hub genes, skin lesion severity, and treatment outcomes. The study also conducted immune infiltration by using the Cell-type Identification by Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) algorithm and identified potential therapeutic targets by the Drug-Gene Interaction Database (DGIdb).

Results

Thirty-one immune-related key genes were identified, and six hub genes (CLEC7A, CXCL1, IRF1, S100A12, S100A8, S100A9) were validated as central players in immune signaling pathways. These genes exhibited within-sample discrimination (AUC > 0.9) and correlated with disease severity and biological therapy efficacy. Immune infiltration analysis revealed increased activated memory CD4+ T cells and M1 macrophages in lesional skin, which was strongly associated with hub gene expression. Additionally, drug-gene interaction analysis identified potential therapeutic agents targeting these genes.

Conclusion

This study identified six immune-related hub genes that were closely linked to the severity of psoriasis, the effectiveness of biological treatments, and infiltrated activated memory CD4+ T cells and M1 macrophages. Our findings elucidate a novel immune-related hub gene network in psoriasis and provide potential targets for the development and application of biologics.

☐ ☆ ✇ Journal of Clinical Nursing

Development and Psychometric Validation of the Palliative Care Experience Scale (PCES): An Experience‐Oriented Assessment Instrument

Por: Yisui Su · Mei Liu · Ye Chen · Meiliyang Wu · Xi Zhang · Ping Ni · Xiaoli Wei · Chenxi Zhou · Haifeng Gu · Huiping Chen · Ke Zhang · Tieying Zeng — Abril 20th 2026 at 06:31

ABSTRACT

Aims

Accelerated population aging has driven substantial growth in demand for palliative care services. Such services can effectively enhance the living quality for end-of-life patients through multidimensional interventions. Currently, China lacks a localised experience-oriented quality assessment scale for palliative care, resulting in gaps in service quality supervision. To develop a self-reported measurement for palliative care services, with the foundation in the Senses Framework.

Design

This study developed a scale by extracting core contributors of palliative care experiences through 14 patients and 16 families' narratives. To refine and improve the scale, a total of 19 experts were invited to participate in a two-round Delphi expert consultation. Additionally, an empirical research was conducted, with 380 valid samples from two independent cohorts collected to complete the full psychometric testing of the scale.

Results

The final Palliative Care Experience Scale (PCES) comprises two dimensions: sense of security and belonging, and sense of purpose and significance, with a total of 13 items. The total variance includes 79.26% that is explained by these two factors. Confirmatory factor analysis confirmed a stable factor structure for the PCES. The scale exhibited good reliability, with a total Cronbach' α of 0.937, McDonald' ω of 0.952, and Spearman-Brown corrected split-half reliability of 0.897. Cronbach's α for both dimensions exceeded 0.88. The scale's SEM was 1.50 and MDC95 was 4.16, offering a validated threshold to identify real changes in patients' palliative care experience.

Conclusion

This study developed an assessment scale of palliative care quality based on the Senses Framework, uniquely centred on patient experiences. Validated through robust methodologies, this scale fills a gap in the evaluation of experiential dimensions of palliative care in China, providing a scientific and feasible measurement tool for the continuous improvement of services.

Impact

This study addresses the critical gap of a culturally adapted, patient experience-centred tool for evaluating palliative care service quality in China. Its core finding is the successful development and full psychometric validation of the 13-item Palliative Care Experience Scale (PCES). This research provides a reliable tool for palliative care clinical practice and academic research to capture patients' care experience, offers clinicians and administrators a practical instrument to identify service gaps and guide quality improvement, and delivers foundational reference data for policymakers to advance patient-centred palliative care development in China.

Reporting Method

We adhered to the relevant EQUATOR reporting guidelines. The development and validation process followed the COSMIN framework for patient-reported outcome measures.

Patient or Public Contribution

Patients receiving palliative care and familes played an integral role in designing and conducting this study. In Phase I, qualitative data from semi-structured interviews with 14 patients and 16 families helped define core thematic constructs and develop the initial item pool, which ensured the scale's content validity were based on their real-life experiences. In Phase III, we recruited a new, independent cohort of participants to complete the psychometric testing of the scale, providing key data for its validation.

☐ ☆ ✇ PLOS ONE Medicine&Health

A systematic review protocol: Efficacy and safety of nitrous oxide in analgesia in burn patients with dressing change

Por: Weifeng Wang · Xianli Meng · Yan Zhao · Wei Gong · Xiaochen Jiang · Wenjuan Cao · Xueling Qiu · Chenxi Sun · Fan Sun · Yuchen Wang · Lu Tang — Abril 17th 2026 at 16:00

by Weifeng Wang, Xianli Meng, Yan Zhao, Wei Gong, Xiaochen Jiang, Wenjuan Cao, Xueling Qiu, Chenxi Sun, Fan Sun, Yuchen Wang, Lu Tang

Background

To alleviate pain in burn patients during dressing changes, it is necessary to identify an effective analgesic method. Conventional opioid analgesics have many limitations. Nitrous oxide is a fast-acting, safe and reversible inhaled analgesic gas. This systematic review will evaluate the effectiveness and safety of nitrous oxide in the treatment of pain during dressing changes in burn patients.

Method

The protocol was developed according to the PRISMA-P checklist and registered on PROSPERO (CRD42024550197). A systematic search will be performed in the following databases: PubMed, EMBASE, Web of Science, Cochrane Library to identify clinical trials comparing nitrous oxide inhalation with standard care in pain management during dressing changes in burn wounds. The search of all databases will be conducted on October 15, 2025.Our search scope will include studies published between each database creation and search date.Two researchers will independently screen studies, extract data, and evaluate study quality using the Risk of Bias2 tool. Primary outcomes will include pain, anxiety, side effects, among others.R statistical software (version 4.3.1) and R studio will be used to perform meta-analyses.Effect size will be expressed by 95% confidence interval (Cl) of weighted mean difference (MD) and risk ratio (RR). Subgroup analyses and sensitivity analyses will be performed to explore sources of heterogeneity and assess the robustness of the results.Publication bias will be assessed using funnel plot and Egger test. We will use the Grading of Recommendation, Evaluation, Development and Evaluation (GRADE) to assess the quality of the evidence.

Discussion

Operative pain has always been a difficult problem for burn patients. This study will evaluate the analgesic effect of nitrous oxide on dressing change in burn patients through comprehensive search and rigorous methods, and provide evidence support for clinical decision-making.

☐ ☆ ✇ PLOS ONE Medicine&Health

Identification and detection of genetic markers associated with antimicrobial susceptibility and evaluation of efflux pump mechanisms in <i>Mycoplasma iowae</i>

by Dominika Buni, Áron Botond Kovács, Enikő Wehmann, Dénes Grózner, Krisztián Bányai, Eszter Zsófia Nagy, Janet Bradbury, Marco Bottinelli, Elisabetta Stefani, Salvatore Catania, Inna Lysnyansky, László Kovács, Miklós Gyuranecz, Zsuzsa Kreizinger

Mycoplasma iowae is an economically significant pathogen that causes reduced hatchability, late embryo mortality and leg deformities, chondrodystrophy and skeletal lesions in poults. While prevention is essential in the control of infection, the appropriate administration of antibiotics may reduce economic losses during outbreaks. As a first step in the exploration of antimicrobial resistance mechanisms in M. iowae, target modification and efflux pump activity were examined in the present study. Point mutations were analyzed in previously described antibiotic binding sites in the whole genome sequences of 99 M. iowae strains. Mismatch amplification mutation assays (MAMAs) were designed and validated for the differentiation of mutations corresponding to elevated minimum inhibitory concentration (MIC) values for fluoroquinolones. Broth microdilution assays were performed to evaluate the effect of efflux pump inhibitors. In the presence of orthovanadate (OV), MIC values were significantly lower than in the absence of OV for spiramycin, tilmicosin, tylosin and oxytetracycline, which may indicate the presence of an active efflux system in M. iowae. Putative promoter regions of efflux-related genes were predicted and characterized. Genetic mutations, previously described in other bacteria, were described to be associated with elevated fluoroquinolone, macrolide and lincomycin MICs in M. iowae, although certain resistant phenotypes remained unexplained, promoting future examinations for deeper insights. The developed MAMAs may support rapid identification of M. iowae strains with elevated MIC values for fluoroquinolones. The better understanding of the efflux pump mechanisms enables the development of alternative methods for the support of therapy against this pathogen.
☐ ☆ ✇ PLOS ONE Medicine&Health

The clinical characteristics and risk factors of steroid-induced ocular hypertension following pars plana vitrectomy

Por: Shuanghong Jiang · Hongxia Yang · Ting Chen · Zhenyu Ji · Xixi Yan — Abril 17th 2026 at 16:00

by Shuanghong Jiang, Hongxia Yang, Ting Chen, Zhenyu Ji, Xixi Yan

Objective

This study aimed to assess the incidence and risk factors for the development of steroid-induced ocular hypertension (SIOH) following 23-gauge (23G) pars plana vitrectomy.

Methods

The clinical data of patients treated with 23G vitrectomy from January 2019 to March 2022 were reviewed retrospectively. The incidence and characteristics of SIOH post-operatively and treatment provided were recorded. The clinical risk factors for developing SIOH were analyzed using logistic regression analysis.

Results

Among the 540 eligible patients, 111 (20.56%) cases developed SIOH. The majority (83.78%) of the SIOH cases developed between the third and seventh day postoperatively. Among these cases, 65 (58.56%) patients had an intraoperative pressure (IOP) of 30 mmHg or higher, and 31 (27.9%) had an IOP of 40 mmHg or higher. The IOP of all SIOH patients returned to normal within 1 month following the discontinuation of steroid and IOP-lowering medicine treatment. The independent risk factors for SIOH (IOP ≥ 23 mmHg) were myopia (odds ratio (OR) 5.22) and silicone oil filling (OR 8.20). For severe SIOH (IOP ≥ 30 mmHg) myopia and silicone oil filling were also identified as risk factors with an OR of 3.23 and 12.86, respectively. After adjusting the steroid administration pattern, the incidence of all SIOH and severe SIOH decreased to 17.11% and 9.14%, respectively.

Conclusions

Myopia and silicone oil filling were identified as potential independent risk factors for the development of SIOH after vitrectomy. A shorter topical steroid therapy was associated with a lower incidence of SIOH particularly in high-risk patients.

☐ ☆ ✇ BMJ Open

Preventive interventions for preschool children at risk for emotional and behavioural problems: a scoping review protocol

Por: Anggeriyane · E. · Fitri · S. Y. R. · Dhamayanti · M. · Rakhmawati · W. · Mardya · B. — Abril 16th 2026 at 16:54
Introduction

Emotional and behavioural problems (EBPs) are receiving increasing attention at the global level, and preschool children are no exception. These issues have a significant impact on future development. Preventive interventions in preschool age are effective in preventing more serious disorders by improving social skills, emotional regulation and resilience in children. Although various preventive interventions have been developed and their effectiveness demonstrated, the evidence remains fragmented. At present, there has been no comprehensive study mapping EBPs prevention interventions at the preschool age level using the Neuman Systems Model approach.

Methods and analysis

This scoping review will be conducted in accordance with the Joanna Briggs Institute (JBI) methodology for scoping reviews.The completed scoping review will be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR). A systematic search will be conducted in four major databases, namely Scopus, PubMed, Web of Science, Cochrane Library, and online searches using Google Scholar, without language and publication year restrictions. Two reviewers will independently screen the literature according to the inclusion criteria and then extract the data. Any differences between the two reviewers will be resolved through discussion with a third reviewer. We will compile, summarise and analyse the extracted data and present the results in figures, tables and descriptive narratives to ensure clarity and facilitate comparison across studies.

Ethics and dissemination

Ethical approval is not required, as the review will use only published literature. Findings will be disseminated through publication in a peer-reviewed international journal and may inform policy and practice in early childhood preventive interventions.

Registration

Open Science Framework (https://osf.io/zg6ty).

☐ ☆ ✇ BMJ Open

Prefilled versus infused regional citrate anticoagulation during continuous renal replacement therapy on circuit lifespan: protocol for a randomised controlled trial

Por: Zou · H. · Wang · F. · Mali · N. · Yang · Y. · Zhang · L. — Abril 16th 2026 at 16:54
Introduction

For critically ill patients requiring continuous renal replacement therapy, regional citrate anticoagulation is the preferred strategy to maintain extracorporeal circuit patency. Current clinical practice relies on two citrate-based protocols, with the widely used but complex 4% trisodium citrate solution posing a hypernatraemia risk and haemofiltration replacement fluid of sodium citrate offering procedural simplification and a more physiological electrolyte profile. Direct prospective comparison of their circuit lifespan efficacy is currently unavailable.

Methods and analysis

This single-centre, prospective, open-label, parallel-group randomised controlled trial will be conducted in China. 90 patients will be enrolled and randomly assigned (1:1) to receive anticoagulation with either citrate-based haemofiltration replacement fluid or 4% trisodium citrate solution, with all patients undergoing a standardised continuous venovenous haemofiltration protocol. The primary outcome is circuit lifespan, with a non-inferiority margin set at 2.43 hours. Secondary outcomes include the 72-hour circuit survival probability, duration of hospitalisation, and all-cause mortality rates at 28 and 90 days. The primary analysis will follow the intention-to-treat principle.

Ethics and dissemination

The study protocol has been approved by the Biomedical Research Ethics Committee of West China Hospital, Sichuan University (Approval No. (2025)1157). Any subsequent amendments must be submitted to the same ethics committee for further review and approval prior to implementation. Furthermore, the findings of this trial will be disseminated through presentations at relevant national and international conferences and via publication in peer-reviewed scientific journals.

Trial registration number

Chinese Clinical Trial Registry ChiCTR2500106991.

☐ ☆ ✇ BMJ Open

Comparison of the effects of eHealth-delivered sedentary breaks versus physical activity promotion interventions on sedentary time: protocol for a systematic review and meta-analysis

Por: Chen · S. · Nie · X. · Giovannucci · E. · Yang · L. — Abril 16th 2026 at 16:54
Introduction

Prolonged sedentary behaviour (SB) is an independent risk factor for adverse health outcomes, with current WHO guidelines emphasising both increased physical activity (PA) and reduced sitting time. While electronic health (eHealth) interventions offer scalable solutions, the comparative effectiveness of two dominant strategies: sedentary break interventions (frequent interruptions of sitting) versus PA promotion (structured activity sessions) remains unclear. This systematic review and meta-analysis protocol aims to compare the effectiveness of interventions targeting breaks in SB versus increased PA in reducing sedentary time through meta-analysis of randomised controlled trials (RCTs) comparing either intervention to a control condition, while exploring key moderating factors including participant characteristics, intervention type, duration, eHealth delivery mode, theoretical basis, use of behaviour change techniques (BCTs), PA intensity and SB frequency.

Methods and analysis

This protocol follows the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines. A comprehensive search will be conducted in PubMed, Embase, Web of Science and the Cochrane Library from inception to 31 July 2025, with language restrictions limited to English and Chinese publications. RCTs comparing eHealth-delivered interventions promoting sedentary breaks with those increasing PA in adults will be included. The primary outcome is sedentary time (objectively measured or self-reported), and secondary outcomes include health outcomes such as cardiometabolic markers, fatigue and well-being. Two reviewers (SC and XN) will independently screen studies, extract data and assess risk of bias using validated tools. Meta-analyses will be performed if sufficient homogeneous data are available, comparing changes in sedentary time. Subgroup analyses will explore effects by participant characteristics including gender (male vs female), age groups (3 to

Ethics and dissemination

Ethical approval is not required as this study involves secondary analysis of published data. Findings will be disseminated through peer-reviewed publication and conference presentations.

PROSPERO registration number

CRD420251042994.

☐ ☆ ✇ BMJ Open

Patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs) used in ambulatory palliative care for adult patients with cancer in low-income and middle-income countries: a systematic review protocol

Por: Mathew · M. · Ghoshal · A. · Kabukye · J. K. · Shetty · N. · Dhyani · V. S. · Chakraborty · S. · Shetty · D. K. · B · B. · Salins · N. — Abril 16th 2026 at 16:54
Introduction

The global burden of cancer is increasingly concentrated in low-income and middle-income countries (LMICs), where health systems face significant challenges such as late-stage diagnosis, limited resources and restricted access to specialised care. Palliative care plays a vital role in improving symptom control and quality of life for patients with cancer, particularly as care delivery shifts toward ambulatory and community-based settings. In this context, patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs) are crucial for capturing patients’ perspectives on the quality of care. However, the use and characteristics of these instruments in ambulatory palliative care settings within LMICs remain poorly understood. This systematic review aims to identify and map PROMs and PREMs used among adult patients with cancer receiving ambulatory palliative care in LMICs, and to examine their content, psychometric properties and alignment with key domains of quality palliative care.

Methods and analysis

This systematic review protocol was developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA) guidelines. The search will be conducted across seven databases from the database inception to December 2025. Two independent reviewers will screen titles, abstracts and full-text articles using Rayyan software to identify studies involving adults (≥18 years) with cancer in ambulatory palliative care settings. Data extraction will capture study characteristics, instrument content and psychometric properties. The final review will be reported in accordance with the PRISMA-COSMIN for Outcome Measurement Instruments. A narrative synthesis will be conducted, mapping the identified instruments against the eight domains of the National Consensus Project Clinical Practice Guidelines for Quality Palliative Care to identify measurement gaps and inform future instrument development. A meta-analysis will be conducted if sufficient homogeneity exists.

Ethics and dissemination

This review will include only published data; therefore, no approval is required. The findings of this review will be presented at conferences and published in an open-access peer-reviewed journal.

PROSPERO registration number

CRD420251273579.

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