Colorectal cancer (CRC) is the third leading cause of new cancer cases and the second leading cause of cancer-related deaths worldwide. Current therapeutic modalities for CRC include surgical resection, intravenous chemotherapy (IVC), radiotherapy, immunotherapy, targeted therapy and their combinations. As a mainstream systemic treatment for CRC, IVC leads to widespread drug distribution but relatively low intratumoural drug accumulation. Compared with IVC, transarterial infusion chemotherapy (TAIC) involves selective arterial catheterisation to deliver chemotherapeutic agents directly to the tumour feeding vessels. Hepatic tumours receive their blood supply predominantly through branches of the hepatic artery. Hepatic artery infusion chemotherapy (HAIC) yields significantly superior outcomes compared with IVC and is currently widely employed for the treatment of primary and secondary hepatic malignancies. HAIC in combination with IVC can offer long-term durable disease control in the clinical treatment of liver cancer compared with IVC. CRC is also predominantly grown through angiogenesis. Therefore, we raise the question whether sequential IVC administered after intensive TAIC achieves better clinical efficacy than IVC alone for the treatment of unresectable CRC (uCRC). However, no prospective clinical trials have been conducted to compare the efficacy of these two strategies. This prospective study was therefore designed to fill this clinical knowledge gap.

This is a prospective, multicentre, randomised, open-label clinical trial. The uCRC is defined as inability to achieve an R0 resection owing to locally advanced CRC with clinical T4 disease confirmed by MRI or CT and/or synchronous liver metastases. This study only includes microsatellite stable or proficient mismatch repair uCRC. A total of 50 eligible patients will be randomly assigned to either the IVC group or the TAIC group. Patients in the IVC group will receive FOLFOX (fluorouracil, leucovorin, oxaliplatin)-based IVC every 2 weeks for a total duration of 8 weeks. Patients in the TAIC group will receive FOLFOX-based TAIC at week 0 and week 4 and receive FOLFOX-based IVC at week 2 and week 6. For patients with colorectal liver metastases, cetuximab or bevacizumab will be administered according to the RAS and BRAF status and the primary tumour site. The primary endpoint is the objective response rate. This study is scheduled to commence on 10 January 2026, and complete follow-up on 31 December 2027. The first subject was enrolled on 20 March 2026. To date, one subject in the IVC group and six subjects in the TAIC group have been enrolled.

The present study protocol has been approved by the Medical Ethics Committee of Guang’anmen Hospital, China Academy of Chinese Medical Sciences (ethical approval number 2025-268 KY). On completion of the study, data cleaning and analysis will be performed, and the results will be disseminated at academic conferences and in international peer-reviewed journals. This trial has been registered at ClinicalTrials.gov. The statistical analysis plan will be finalised and approved before the database lock. The final version is retained in the study documentation and will be made available to support the transparency and interpretation of the study results.

NCT07333053.

Single-arm trials (SATs) with objective performance criteria (OPCs) or performance goals (PGs) are increasingly used for regulatory approval of medical devices and other interventions. However, the comparability of study design characteristics between SAT and their external comparator sources remains unclear. This scoping review aimed to evaluate the comparability of study design characteristics between SATs and their matched OPC/PG sources.

Scoping review.

PubMed, Embase, the Cochrane Library and four Chinese databases—China National Knowledge Infrastructure, Wanfang Data, CQVIP and SinoMed—were searched from inception to 30 April 2026.

We included SATs that used one or more OPCs or PGs as external comparators to evaluate safety and/or effectiveness endpoints and reported specific numerical values of OPCs or PGs.

Two reviewers independently screened the retrieved records and extracted data using a standardised form. For each included SAT, we retrieved the cited OPC/PG sources and extracted study design characteristics data (age, sex, health conditions, outcome definitions and measurement time points) for comparison. Age and sex were compared using summary t-tests and ² tests; health conditions were assessed by two clinicians based on eligibility criteria and baseline characteristics. Results were stratified by OPC versus PG.

A total of 1243 records were identified, and 133 SATs were included. Most studies used PGs (84, 63.2%); 34 (25.6%) claimed to use OPCs, and 15 (11.3%) could not be classified. Of the 60 age comparisons available from 41 studies, 30 showed statistically significant differences; of the 82 sex comparisons available from 59 studies, 60 showed significant differences. Health conditions, outcome definitions and time points were assessed descriptively in a subset of studies, and discrepancies were also observed.

Suboptimal comparability of study design characteristics was observed between SATs and their OPC/PG sources, which might influence the treatment effect estimates. Greater attention to the comparability of study design characteristics in SATs with OPC/PGs may improve the validity of evidence.

This study aimed to examine whether lifestyle risk factors were associated with reporting any presenteeism and among primary care physicians (PCPs) who reported presenteeism, with the degree of productivity impairment.

Cross-sectional study.

Primary healthcare institutions across all 31 provincial-level administrative regions of mainland China.

PCPs were eligible if they were aged ≥18 years, had worked in a primary healthcare institution for at least 1 year and provided written informed consent. Participants were recruited using multistage sampling with convenience sampling at the area, institution and physician levels. Of the 1500 questionnaires distributed, 1214 were returned, yielding a response rate of 80.9%. Following data quality screening, 338 questionnaires were excluded, leaving 876 physicians for analysis.

Presenteeism was assessed using the Work Productivity and Activity Impairment Questionnaire: General Health version. Lifestyle risk factors (irregular diet, insufficient leisure-time physical activity (LTPA), poor sleep quality, smoking and drinking) were assessed using a structured questionnaire.

Among the 876 PCPs included in the analysis, 417 (47.6%) reported presenteeism. Insufficient LTPA and poor sleep quality were associated with higher odds of reporting presenteeism (adjusted OR (aOR) 1.65, 95% CI 1.20 to 2.28; and aOR 1.59, 95% CI 1.12 to 2.26, respectively). Among PCPs reporting presenteeism, poor sleep quality was associated with a 3.85-percentage-point higher presenteeism score (average marginal effect 3.85, 95% CI 0.32 to 7.38). Smoking was associated overall with the degree of presenteeism (p=0.003), with category-specific estimates differing in direction. No clear associations were observed for irregular diet or drinking.

Poor sleep quality was associated with both the presence and degree of presenteeism, whereas insufficient LTPA was associated primarily with its presence. Sleep quality and LTPA may warrant further investigation as potentially modifiable factors associated with presenteeism among PCPs.

Preoperative anxiety in children is a common problem in paediatric surgical care. In current practice, anxiety is assessed mainly by behavioural rating scales, of which the modified Yale Preoperative Anxiety Scale (mYPAS) is the most widely used. However, behavioural observation may not capture children whose outward behaviour stays calm while their autonomic stress response is still high. This mismatch between visible behaviour and underlying physiology can lead to under-recognition of anxiety and may explain the modest correlations reported between behavioural scores and physiological markers in children. The aim of this scoping review is to map the published evidence on physiological–behavioural discordance during paediatric perioperative anxiety and to identify methodological gaps that future multimodal assessment research will need to address.

The review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for Scoping Reviews reporting guideline and the Joanna Briggs Institute methodology for scoping reviews. We will search PubMed/MEDLINE, Embase, Web of Science Core Collection, CINAHL Complete and PsycINFO from database inception to 31 December 2025. Eligible studies will recruit children aged 0 to 18 years in perioperative or analogous procedural settings, and will report both a behavioural anxiety measure (such as mYPAS, mYPAS-SF, State–Trait Anxiety Inventory for Children (STAI-C)) and at least one concurrent physiological stress indicator (heart rate variability, salivary cortisol, salivary alpha-amylase, electrodermal activity, heart rate or intraoperative nociception indices). The primary analysis will focus on perioperative anaesthesia induction. Procedural sedation, venipuncture and dental contexts will be analysed as a separate secondary stratum because their stress profile is not the same as anaesthesia induction. Two reviewers will screen and extract data independently. Premedication exposure, regular home psychoactive medication use (including cannabinoids) and the time gap between behavioural and physiological sampling will be extracted as prespecified confounders. Findings will be synthesised narratively following the Synthesis Without Meta-analysis reporting guideline.

Ethical approval is not required because the review uses only published literature. Results will be submitted to a peer-reviewed journal and presented at paediatric anaesthesia conferences. A plain-language summary will be co-produced with parent advisors.

Intravenous thrombolysis is the standard early treatment for acute ischaemic stroke (AIS), yet a substantial proportion of patients, particularly those with mild disabling deficits, do not achieve favourable functional recovery. Tenecteplase (TNK), a fibrin-specific thrombolytic agent administered as a single bolus, and butylphthalide (NBP), a multi-mechanism neuroprotective agent, have each shown benefit in AIS. However, whether their combination confers additional benefit in mild disabling AIS remains unknown. This trial aims to determine whether adding NBP to TNK improves functional outcomes in patients with mild disabling ischaemic stroke treated within 4.5 hours of symptom onset.

BENEFIT-2 is a prospective, multicentre, randomised, double-blind, active-controlled trial. Eligible patients will be randomised 1:1 to receive either TNK plus NBP (combination group) or TNK plus placebo (control group) via block randomisation. The intervention comprises intravenous NBP 25 mg/100 mL two times per day for 7 days, followed by oral NBP 0.2 g three times per day up to day 14, with matching placebos for the control group. Key eligibility criteria include age 18–80 years, symptom onset within 4.5 hours, baseline National Institutes of Health Stroke Scale (NIHSS) score 2–5 with persistent unilateral weakness or speech impairment, and prestroke modified Rankin Scale (mRS) score 0 or 1. The primary outcome is the proportion of patients achieving mRS 0–1 at 90 days (allowable window ±7 days). Secondary endpoints include change in NIHSS, stroke recurrence, major vascular events, quality of life measured by EQ-5D and penumbral salvage on imaging. Safety endpoints comprise symptomatic intracranial haemorrhage, vascular death, all-cause mortality and other adverse events within 90 days. The primary analysis will follow the intention-to-treat principle.

Ethics approval has been obtained from the Independent Ethics Committee of Xiangya Hospital (No. 2026020399), Central South University. Results will be published in peer-reviewed journals and presented at academic conferences.

NCT07369999

Dietary modification is an important strategy for the prevention of type 2 diabetes, with fibre intake recognised as a key factor in promoting metabolic health. Resistant starch (RS), a type of fermentable dietary fibre, has emerged as a promising therapeutic approach due to its association with weight loss, enhanced insulin sensitivity and improved glucose metabolism. As nutritional research progresses, the focus has shifted from individual nutrients to overall dietary patterns. Based on this concept, this study aims to investigate the metabolic effects of a dietary pattern that optimises carbohydrate structure by increasing RS intake and reducing rapidly digestible carbohydrate in adults with pre-diabetes.

This is a multicentre, randomised, parallel-controlled clinical trial, which will enrol 250 adults diagnosed with pre-diabetes. Eligible participants will undergo randomisation to receive either a guideline-based conventional diet or an optimised carbohydrate diet (OCD). In the OCD intervention, daily RS intake will be increased to approximately 40 g, with fibre intake rising to 20–40 g per 1000 kcal. At the same time, the intake of rapidly digestible starch and free sugars will be reduced. The intervention will last for 6 months, followed by a 3-month post-intervention follow-up period. The primary outcome is the change in postprandial glycaemic response, assessed using the incremental area under the curve (iAUC) for plasma glucose during the oral glucose tolerance test (OGTT). Secondary outcomes include the proportion of participants achieving remission to normoglycaemia or progressing to type 2 diabetes, changes in other glucose- and lipid-related metabolic parameters and changes in lifestyle-related behavioural factors. Exploratory outcomes will include changes in appetite-related hormones, circulating cytokines, immune function and multi-omics profiles.

This study was approved by the Ethics Committee of Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (Approval No. 2025-122; Protocol V.1.0, 20250811) and the Ethics Committee of Shenzhen Center for Chronic Disease Control (Approval No. SZCCC-2024-011-01-PJ) and registered in the Chinese Clinical Trial Registry. Findings from this study will be disseminated in peer-reviewed journal publications.

ChiCTR2500113583.

To examine the association between sleep quality and psychological resilience in a Chinese community-based cohort and assess the consistency of this association across two sleep measures.

Cross-sectional analysis of baseline data.

Community-based cohort in Hangzhou, China (2016–2019).

10 268 adults aged 18–80 years enrolled via quota sampling stratified by sex and age group. After excluding participants with missing data, analytic samples were 9781 (single-item measure) and 9780 (Pittsburgh Sleep Quality Index (PSQI)), owing to one additional missing response.

Low psychological resilience, defined by a median split on a 9-item scale adapted from the Brief Resilience Scale and Connor–Davidson Resilience Scale.

Poor sleep quality was associated with higher odds of low resilience across both measures (single-item measure, adjusted OR=1.5, 95% CI 1.3 to 1.6; PSQI, adjusted OR=1.5, 95% CI 1.4 to 1.7), after adjustment for demographic factors, socio-economic factors, mental health indicators and health behaviours. Interaction tests showed no evidence of effect modification by sex, age group, loneliness or depression history for the single-item measure (p>0.05). For the PSQI, the association differed by loneliness (p<0.05), with a larger magnitude of association among lonely participants (adjusted OR=2.1, 95% CI 1.6 to 2.7) than non-lonely participants (adjusted OR=1.5, 95% CI 1.3 to 1.6).

Poor sleep quality was consistently associated with low resilience across both measures. Because the design was cross-sectional, temporal direction cannot be established. Longitudinal and interventional studies are needed to establish temporal ordering, and intervention studies are needed to determine whether improving sleep increases resilience.

Clinical reasoning is an essential competency for all physicians, and fostering this skill in medical students is a primary objective of medical education. Currently, clinical reasoning is predominantly cultivated through experiences in clinical settings; however, this approach presents certain limitations. The emergence of innovative medical simulation teaching methods has led to the increasing utilisation of standardised patient (SP) simulations in medical education. However, the specific contribution of the SP teaching method to the development of clinical reasoning skills in medical students remains unclear. Therefore, we propose a systematic review to summarise the impact of the SP teaching method on the clinical reasoning competence of medical students.

This systematic review protocol adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines for reporting results. A comprehensive literature search will be conducted across five major online databases: PubMed, Embase, Web of Science, Education Research Complete and the Cochrane Library. The screening process comprises an initial review of titles and abstracts to identify relevant studies efficiently, followed by a full-text assessment of the selected articles. Two reviewers will independently conduct study selection, data extraction and risk of bias assessment. Data extraction will be performed using a standardised form. The primary outcome is clinical reasoning competence, and secondary outcomes are communication skills and student satisfaction. The risk of bias in included studies will be evaluated using the Cochrane Risk of Bias tool 2. Depending on the literature search results and the characteristics of the selected studies, a meta-analysis will be conducted where feasible. Otherwise, a narrative synthesis will be performed.

This study presents a protocol for a systematic review and does not involve human subjects. The findings will be disseminated through publication as a manuscript submitted to a peer-reviewed journal.

CRD420251163882.

To evaluate the association between cataract surgery and the incidence and progression of diabetic retinopathy (DR) in a population-based cohort of patients with diabetes.

A nationwide population-based retrospective cohort study.

A nationwide administrative claims database in Taiwan covering more than 99% of the population, with longitudinal follow-up from 2010 to 2021.

Adult patients (≥20 years) with diabetes mellitus and cataract were identified. Patients with prior cataract surgery before the first recorded cataract diagnosis were excluded. A total of 15 360 patients who underwent first-time cataract surgery and 15 846 patients without surgery were included. After two-stage matching (1:2 age-matching and sex-matching followed by 1:1 propensity score matching), 7837 matched pairs were analysed.

Not applicable.

The primary outcomes were (1) incident DR and (2) DR progression within 6 months and 1 year after the index date. Incident DR was defined as new-onset non-proliferative DR (NPDR) or proliferative DR (PDR). DR progression was defined as transition from no DR to NPDR/PDR or from NPDR to PDR. Outcomes were identified using diagnostic codes recorded at least twice in outpatient visits or once during hospitalisation.

Cataract surgery was associated with higher risks of both incident DR and DR progression within 1 year. In the 1:2 matched cohort, the adjusted ORs were 3.40 (95% CI 2.65 to 4.36) for incident DR and 3.11 (95% CI 2.47 to 3.92) for DR progression. Similar findings were observed in the 1:1 propensity score-matched analysis. Absolute event rates at 1 year showed DR progression in approximately 3.1% of patients undergoing surgery compared with 1% in the non-surgical group. Increased risk was also associated with more intensive antidiabetic treatment.

Cataract surgery in patients with diabetes was associated with an increased risk of incident DR and disease progression, particularly within the first postoperative year. These findings support the consideration of cataract surgery as a clinically relevant risk window for enhanced retinal monitoring. Incorporating surgical history into DR risk stratification and screening strategies may improve early detection and inform postoperative care pathways.

Children with autism spectrum disorder (ASD) often experience challenges in social interaction, emotional regulation and parent–child bonding, which can negatively impact overall well-being and happiness. Music therapy, particularly when integrated with movement-based interventions, such as piano training, is increasingly recognised as a promising non-pharmacological approach to enhance social engagement and improve psychological outcomes in this population. Although multiple primary studies and pilot trials have been conducted, the evidence remains fragmented and inconsistent. To date, no comprehensive systematic review has synthesised the effects of music-based interventions on (1) social withdrawal, (2) parent–child relationship quality and (3) subjective happiness in children with ASD.

This protocol adheres to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. A systematic search will be conducted across PubMed, Web of Science, Scopus, China National Knowledge Infrastructure and Wanfang Data from inception to May 2026. Eligible studies will include randomised controlled trials and quasi-experimental studies evaluating music or music–movement interventions for children with ASD. The primary outcome is social withdrawal, whereas the secondary outcomes are the parent–child relationship and overall happiness assessed using validated measures. Data extraction and risk-of-bias assessments will be conducted independently by two reviewers. Where feasible, quantitative synthesis will be performed using random-effects meta-analysis. Subgroup analyses will explore the influence of age, intervention type and intervention duration. The certainty of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach.

Ethical approval is not required as this review involves published data only. Findings will be disseminated through peer-reviewed publications, conference presentations and community reports targeting clinicians, therapists and parents.

CRD420251132116.