Cognitive impairment is a common consequence after stroke. Intermittent theta burst stimulation (iTBS) has emerged as a promising cognitive therapy. However, traditional iTBS typically employs lower doses and one-size-fits-all stimulation targets, which may not fully capitalise on the potential of this therapy and warrants further evaluation for both efficacy and safety. This study aims to evaluate the efficacy and safety of high-dose iTBS targeting the individualised frontoparietal cognitive network (FCN) identified by precision functional neuroimaging for post-stroke cognitive impairment (PSCI).

This is a prospective, double-blind, sham-controlled, parallel-group randomised controlled trial. 60 eligible participants with PSCI will be randomly assigned (1:1) to an active iTBS or a sham-controlled group. The active group will receive high-dose iTBS (3600 pulses/day) at 80% resting motor threshold targeting the left individualised FCN, guided by a real-time neuronavigation system. The sham group will follow identical procedures using a sham coil. Both groups will also undergo conventional computerised cognitive training. The intervention will be administered on workdays over a period of 3 weeks, totalling 15 workdays. The primary outcome is the change in Montreal Cognitive Assessment scores from baseline to immediately post-treatment. Secondary outcomes include long-term change in global cognition, activities of daily living and specific cognitive domains (assessed by a comprehensive neuropsychological battery covering memory, attention, executive function and language), as well as mood. Assessments occur at baseline, post-treatment and 3-month follow-up. Safety outcomes, specifically the number of adverse events related to iTBS, will be monitored and recorded throughout the trial.

This study has been approved by the Medical Ethics Committee of the China Rehabilitation Research Center. The results of this study will be published in peer-reviewed scientific journals and disseminated at academic conferences.

NCT05953415.

To analyse the impact of selected neonatal care interventions on regional care capacity.

Design

Discrete event simulation modelling based on clinical data.

Neonatal care in the southwest of the Netherlands, consisting of one tertiary-level neonatal intensive care unit (NICU), four hospitals with high-care neonatal (HCN) wards and six with medium-care neonatal (MCN) wards.

44 461 neonates admitted to at least one hospital within the specified region or admitted outside of the region but with a residential address inside the region between 2016 and 2021.

The impact of three interventions was simulated: (1) home-based phototherapy for hyperbilirubinaemia, (2) oral antibiotic switch for culture-negative early onset infection and (3) changing tertiary-level NICU admission guidelines.

Regional neonatal capacity defined as: (1) occupancy per ward level, (2) required operational beds per ward level to provide care to all inside region patients at maximum 85% occupancy, (3) proportion rejected, defined as outside region transfers due to no capacity to provide local care and (4) the weekly rejections in relation to occupancy to provide a combined analysis.

In the current situation, with many operational beds closed due to nurse shortages, occupancy was extremely high at the NICU and HCNs (respectively 91.7% (95% CI 91.4 to 92.0) and 98.1% (95% CI 98.0 to 98.2)). The number of required beds exceeded available beds, resulting in >20% rejections for both NICU and HCN patients. Although the three interventions individually demonstrated effect on capacity, clinical impact was marginal. In combination, NICU occupancy was reduced below the 85% government recommendation at the cost of an increased burden for HCNs, highlighting the need for redistribution to MCNs.

Our model confirmed the severity of current neonatal capacity strain and demonstrated the potential impact of three interventions on regional capacity. The model showed to be a low-cost and easy-to-use method for regional capacity impact assessment and could provide the basis for making informed decisions for other interventions and future scenarios, supporting data-driven neonatal capacity planning and policy development.

Ischaemic stroke, the most prevalent stroke subtype, imposes a significant long-term disease burden. However, patients with first-ever stroke exhibit substantial individual variability in poststroke health trajectories, manifesting heterogeneous clinical presentations. We therefore started with the overall health of patients in order to delineate heterogeneous clusters characterised by distinct demographic profiles, clinical features and behavioural determinants and elucidate shared longitudinal trajectories in the temporal development of adverse health outcomes.

We designed a multicentre, cross-sectional and longitudinal study focusing on patients with first-ever ischaemic stroke. We will employ patient self-reported outcomes and objective measurements to comprehensively evaluate patients’ health status from a multidimensional perspective. Following baseline assessments, participants will undergo follow-up evaluations at 1 month, 3 months and 6 months post inclusion. The primary objective is twofold: (1) to identify distinct patient clusters with heterogeneous multidimensional health profiles using the k-prototype clustering algorithm and (2) to characterise synergistic trajectories of core health attributes within the largest cluster through parallel process latent class growth modelling. By combining cross-sectional and longitudinal analyses, this phased study should elucidate static heterogeneity and dynamic recovery patterns following a first-ever ischaemic stroke.

The project conforms to the ethical principles enshrined in the Declaration of Helsinki (2013 amendment) and all local ethical guidelines. The ethics committee at the University of South China approved the study (approval no. 2024 NHHL023). The ethics committee of Gansu Provincial Hospital approved the study (approval no. 2025–023). The ethics committee of the Central Hospital of Shaoyang approved the study (approval no.KY-2025–12). The findings will be published and presented at conferences for widespread dissemination.

Trial registration number: ChiCTR2500098442

Diabetes distress (DD) constitutes a negative emotional experience for patients with diabetic retinopathy (DR), having a detrimental impact on their physical and mental health.

The aim of this study was to understand the current status and influencing factors of DD in patients with DR and to explore the relationship between self-efficacy, coping styles and DD.

A cross-sectional study.

The study was conducted at the Eye Hospital of Wenzhou Medical University, Zhejiang Province, China.

Patients diagnosed with DR.

The Diabetes Distress Scale was used to assess DD.

DD was present in more than half (53.07%) of patients with DR. There were significant differences in DD among patients with DR who reported different employment statuses, modes of residence and body mass index. Coping styles partially mediated the relationship between self-efficacy and DD, with the mediating effect accounting for 71% of the total effect.

Considering the high prevalence of DD among patients with DR, healthcare professionals should pay more attention to the psychological needs of patients with DR. Effective interventions could be used to promote self-efficacy and coping styles of patients with DR, leading to lower levels of DD.

Osteogenesis imperfecta (OI) is the most common inherited cause of bone fragility (approximately 1 in 16 000). People with OI suffer bone fragility causing fractures, pain and deformity; sarcopenia causing fatigue and poor endurance; aortic root dilatation and hearing loss. No drug currently has market authorisation to treat OI in Europe. Current standard-of-care is multidisciplinary, with pharmacological interventions—primarily bisphosphonates—directed at increasing bone mass; however, such interventions are of equivocal efficacy. The structural damage that can accumulate as a result of repeated fractures over time may not be reversible. The lack of a treatment with clearly defined efficacy in terms of reducing fracture frequency or the sarcopenia, that is increasingly recognised in this condition, leads to the consideration of alternatives based on what is known about the molecular pathophysiology of the condition. For reasons that are currently unclear, transforming growth factor beta (TGFβ) pathway signalling is increased in OI, and both studies in mouse models and more recently also in humans suggest that reducing TGFβ pathway signalling could be of benefit in OI. This demonstrator project tests the hypothesis that losartan, an antihypertensive agent known to reduce circulating TGFβ, will reduce bone turnover and bone loss and have a positive effect on muscle function and quality of life in adults and older adolescents with OI.

This is a phase 2/pilot, open-label, dose-escalating study. This study aims to identify the effective dose for losartan in this population to inform the design of a pivotal phase III study. The study aims to recruit 30 adolescents and adults aged 16 years and above with OI across secondary care study sites in the UK and Italy. Participants will be recruited from the patient populations attending for treatment of OI at the participating hospital sites or referred by clinicians at the Participant Identification Centres (PIC sites). Participants will be randomised to one of three ‘final doses’—25, 50 or 75 mg losartan once daily. All participants will start on 25 mg once daily. Those assigned to higher ‘final doses’ will increase in 25 mg once daily increments on day 8 and day 15 following safety assessments. The primary outcome measures are to establish the effective dose of losartan in OI patients, based on maximal reduction in the bone resorption marker carboxy-terminal crosslink of type I collagen telopeptide (CTX) over the 24-week period of the study.

Secondary outcome measures are to determine the changes in proxy efficacy outcomes for bone (turnover, mass, architecture and strength) using blood tests, high-resolution peripheral quantitative CT (HRpQCT), dual-energy X-ray absorptiometry (DXA) and muscle (strength) using the ‘Timed Up and Go’ test. In addition, the changes in quality of life, including pain and fatigue, will be evaluated by using a disease-specific tool (OI-QOL) and a validated generic tool (EQ-5D-5L-VAS).

In the UK, the study protocol and amendments have been approved by the London Bridge Research Ethics Committee (REC reference: 23/LO/015) and by the Medicines and Healthcare products Regulatory Agency (MHRA). In Italy, the study protocol and amendments have been approved by the Italian and European ethics and regulatory authorities (Clinical Trials Information System European Union (CTIS EU) portal according to EU Regulation 536/2014). Final version of study protocol: Version 3.2, 05.03.2025. Final results will be disseminated in peer-reviewed journals through local OI, orthopaedic and other relevant clinical networks and at national and international meetings. Sheffield Children’s National Health Service Foundation Trust (UK) and Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Ortopedico Rizzoli (Italy) are the joint study sponsors.

ISRCTN (ISRCTN13317811).

Perioperative sleep disturbance (PSD) can adversely affect immunological and cognitive functions, can prolong hospital stays and have long-lasting effects on quality of life, ultimately increasing mortality rates. Unfortunately, PSD is common among surgical patients and can manifest at any stage during surgical care with a high incidence. Owing to the high incidence and severe adverse outcomes of PSD, effective management of PSD is imperative in clinical practice. Intranasal administration of dexmedetomidine is a safe and effective strategy for improving perioperative sleep quality. It is characterised by high bioavailability, a low incidence of adverse events and the avoidance of pain from venipuncture and intramuscular injection. However, this clinical evidence is insufficient due to the limited sample size, diverse outcome observation indicators and inconsistent research quality. Consequently, we will conduct a protocol for a systematic review and meta-analysis to offer clinical evidence on whether intranasal dexmedetomidine can be opted as an effective treatment for PSD.

English databases (PubMed, Web of Science, Ovid Medline, Embase and Cochrane Library), Chinese electronic databases (Wanfang database, VIP Database and China National Knowledge Infrastructure) and clinical trial registry platforms will be screened from their inception up to October 2025 to detect randomised controlled trials of intranasal dexmedetomidine for the management of PSD. We will compute the mean differences (MDs) or standardised MDs along with 95% CIs for continuous data, and the risk ratio with 95% CIs for dichotomous data using Review Manager V.5.4. Either the fixed-effects or random-effects model will be employed depending on the heterogeneity assessed by Cochran’s Q test and the I² statistic. Risk of bias will be assessed by Cochrane risk-of-bias tool V.2, while evidence quality will be evaluated by the Grading of Recommendations Assessment, Development and Evaluation approach. The conclusiveness of evidence will be evaluated via trial sequential analysis. Moreover, publication bias will be assessed via funnel plot analysis supplemented with Egger’s regression test.

Ethical approval was not required for this systematic review protocol. The results will be disseminated through peer-reviewed publications.

CRD420251002119.

Colorectal cancer (CRC) incidence is increasing, and treating low rectal cancer poses challenges in balancing oncological control with functional preservation. While preoperative chemoradiotherapy (CRT) improves sphincter preservation, anastomotic leakage (AL) remains a major complication. This trial aims to compare the efficacy of modified pull-through procedure versus coloanal anastomosis (CAA) with temporary stoma in low rectal cancer patients following preoperative CRT.

This is a multicentre, assessor-blinded, randomised controlled trial. A total of 216 patients with low rectal cancer (≤7 cm from the anal verge) after preoperative CRT will be enrolled and randomly assigned (1:1) to undergo either the modified pull-through procedure or CAA with temporary stoma. The primary outcome is the incidence of AL within 1 month. Secondary outcomes include complications (Clavien-Dindo classification), length of hospital stay, anorectal function (LARS score (Low Anterior Resection Syndrome Score)), and quality of life (EQ-5D questionnaire (EuroQol five dimensions questionnaire)). Patients will be followed for 36 months.

The study has obtained ethics approval from the Biomedical Ethics Committee of West China Hospital, Sichuan University (ethics approval ID: 2025-Review-(144)). All centres have obtained local institutional review board approval. Results will be disseminated via academic conferences and peer-reviewed journals to optimise clinical practice for low rectal cancer surgery.

ChiCTR2500100246.

Previous studies have indicated that exposure to anaesthetics has potential neurotoxic effects, particularly in cases of multiple and long-term general anaesthesia. However, there is currently no research exploring the relationship between early anaesthesia and neurological development in children with congenital scoliosis, who may require multiple surgical treatments. Herein, we present our design for a prospective longitudinal observational cohort study, assessing the long-term impact of general anaesthesia for surgery before school age on neurocognitive function and behaviour in children with congenital scoliosis.

A dynamic cohort of children aged 6–16 years diagnosed with congenital scoliosis between July 2020 and December 2025 in the Department of Orthopaedic Surgery at a tertiary hospital will be enrolled, with an aim to include 150 patients. Detailed information about baseline characteristics, previous anaesthesia and surgery will be collected from medical records, parents or guardians. Neurodevelopment will be evaluated using the abbreviated version of the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) for neurocognition, and parent-report Achenbach Child Behaviour Checklist and Strengths and Difficulties Questionnaire for neurobehaviour. Repeated measures will be performed during follow-up, with at least a 1-year interval from the previous assessment, whenever the participants are available. The primary outcome is the full-scale intelligence quotient estimated by the WISC-IV. A linear mixed effects model will be constructed, with exposure group—categorised as none, single or multiple anaesthesia exposures based on all episodes of general anaesthesia for surgery before the age of 7 years—as a fixed effect and subject-specific random effects intercept.

The study was approved by the Institutional Review Board of Peking Union Medical College Hospital (S-K1093). Written informed consents will be obtained from the parents or guardians. The results of this research will be disseminated through peer-reviewed publications and conference presentations, and shared with paediatric surgical patients and their families who are concerned about the potential neurotoxicity of anaesthesia in clinical practice.

NCT06315933.

To systematically summarise and evaluate the existing evidence of the associations between diverse folate exposures and the risk of colorectal cancer (CRC), while identifying evidence quality.

Umbrella review of meta-analyses.

PubMed, Web of Science, Cochrane and Embase were searched from the database inception to March 2024, with an update to 12 October 2025.

We included meta-analyses of randomised controlled trials or observational studies that investigated the associations between folate exposures and CRC or precancerous lesions (ie, adenoma and polyps).

For each association, we recalculated the summary effect size with 95% CI using the DerSimonian and Laird random-effects model, heterogeneity (I² statistic), 95% prediction interval, small-study effect (Egger’s test) and excess significance bias (² test).

This umbrella review included five meta-analyses describing 10 associations between folate exposures and CRC risk. In the general population, moderate-quality evidence supported an inverse association between total folate intake (from foods and supplements) and CRC risk (RR 0.84; 95% CI 0.80 to 0.90), while low-quality evidence suggested inverse associations of dietary folate intake (from foods alone) (RR 0.88; 95% CI 0.81 to 0.96) and folic acid supplement intake (RR 0.83; 95% CI 0.77 to 0.90) with CRC risk. Among patients with inflammatory bowel disease, low-quality evidence suggested an inverse association between folic acid supplement intake and CRC incidence (HR 0.71; 95% CI 0.53 to 0.96). Additionally, elevated circulating folate levels were observed to have a provoking effect on advanced-stage tumours (OR 1.95; 95% CI 1.18 to 3.22; Grading of Recommendations Assessment, Development and Evaluation (GRADE): very low). Sensitivity analysis revealed a potential increased risk of adenoma recurrence associated with folic acid supplement use among patients with a history of adenoma (RR 1.05; 95% CI 0.86 to 1.29; GRADE: high).

These findings suggest that consuming dietary folate and total folate intake may be beneficial in CRC primary prevention. Specifically, folic acid supplements may inhibit colorectal carcinogenesis in normal tissues while promoting cancer in the established neoplastic foci.

CRD42024537550.

Microvascular obstruction (MVO) is a common complication following primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI) and is strongly associated with adverse clinical outcomes. MVO is a dynamic, multifactorial process shaped by factors spanning the myocardial infarction–reperfusion continuum and by PPCI-related microcirculatory injury, which leaves current early risk stratification—often a static snapshot—with limited power to anticipate its evolution. Renalase, a cardioprotective enzyme, exhibits a post-reperfusion surge that parallels MVO development; periprocedural renalase release may likewise be driven by overlapping mechanisms along the ischaemia–reperfusion pathway. This hypothesis-generating observation supports evaluating the delta-Renalase (periprocedural change in serum renalase) as a candidate association-based biomarker. Accordingly, this study aims to assess whether delta-Renalase is independently associated with MVO in patients with STEMI after PPCI and to evaluate its incremental predictive value, without causal inference.

The Renalase and MicroVascular Obstruction Study (ReMVOS) is a prospective, single-centre, observational cohort study conducted at a nationally accredited chest pain centre in China. We will enrol 266 patients with consecutive STEMI with symptom onset within 12 hours who undergo PPCI. The exposure variable is delta-Renalase, calculated as the increase in serum renalase levels at 24 hours post-PPCI relative to the preprocedural baseline. The primary outcome is the presence of MVO, assessed by cardiovascular magnetic resonance (CMR) performed 2–5 days post-PPCI. Secondary outcomes include infarct size and peak global longitudinal strain quantified by CMR, major adverse cardiovascular events within 90 days and peak oxygen pulse from cardiopulmonary exercise testing (CPET) at the 90-day visit. The independent association and predictive value of delta-Renalase will be evaluated using a prespecified multivariable logistic regression model.

This protocol has been approved by the Ethics Committee of the Third Xiangya Hospital of Central South University (approval No. K24655). All patients will provide written informed consent prior to enrolment. The findings of this study will be disseminated through publications in peer-reviewed international medical journals and presentations at relevant academic conferences.

NCT06669520.

The development of myopia is subject to individual genetic predisposition and environmental risk exposures. This study aims to investigate the trajectories and predictors of spherical equivalent (SE) among multiethnic school-aged children in Southwest China.

The school-based cohort study was conducted from October 2020 to March 2023 in Yunnan province, Southwest China. Ocular examinations and questionnaire surveys were administered at each visit. A total of 679 students with complete records from all three visits were included in the final analyses. Group-based trajectory modelling was used to identify SE trajectories. Associations between the trajectory groups and baseline predictors were assessed using multinomial logistic regression.

We identified two distinct trajectory groups of SE in grades 2–3: slow progressive (84.4% of students) and rapid progressive (15.6%). Multivariate analysis indicated that children with myopic parents and those who often stayed in the classrooms during recess were more likely to belong to the rapid progressive group. By contrast, three trajectory groups of SE were identified in grade 7: slow progressive (52.3% of students), moderate initial and rapid progressive (33%) and low initial and rapid progressive (14.7%). In multivariate models, being a girl, having myopic parents, using mobile screens for more than 0.5 hours per day and often staying in the classrooms during recess were predictors of the progressive groups. Moreover, there were no significant differences in SE trajectories between Han and ethnic groups.

There is heterogeneity in the developmental trajectories of SE, for both primary and secondary school students. Tailored intervention strategies based on the predictors of the SE trajectories should be under special consideration.