Colonoscopy is an essential procedure for the early diagnosis of colorectal conditions; however, over 60% of patients undergoing non-sedated colonoscopy report moderate to severe pain. This study aims to investigate the central analgesic mechanisms of transcutaneous electrical nerve stimulation based on wrist-ankle acupuncture theory (TENS-WAA). A multimodal approach combining electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) will be employed to assess pain-related brain activity, with artificial intelligence applied to model the relationship between objective neurophysiological signals and subjective pain experience.

This is a single-centre, randomised, double-blind, controlled trial involving 60 patients undergoing colonoscopy without anaesthesia. Participants will be randomly allocated (1:1) to either an electrical stimulation group receiving TENS-WAA or a sham stimulation group. EEG and fNIRS data will be acquired before, during and after the procedure. The primary outcome is the analysis of EEG-fNIRS signals to characterise cerebral responses associated with pain modulation. Secondary outcomes include patient-reported pain using the Visual Analogue Scale (VAS), total colonoscopy duration and the correlation between EEG-fNIRS indicators and VAS scores. A deep learning framework will be used to enhance pain prediction accuracy.

This study has received ethical approval from the Ethics Committee of Changhai Hospital, Shanghai (approval reference CHEC2025-006), and has been registered at ClinicalTrials.gov. Written informed consent will be obtained from all participants. Findings will be disseminated in peer-reviewed academic journals and at relevant scientific conferences, regardless of outcome, contributing to evidence-based, non-pharmacological pain management strategies.

ClinicalTrials.gov, NCT06813703.

Coronary artery bypass grafting (CABG) is a standard treatment for coronary artery disease, particularly in patients with multivessel disease. Connecting the saphenous vein graft (SVG) to the right internal mammary artery (RIMA) instead of the aorta has been proposed as an alternative approach to minimise aortic manipulation and potentially improve graft patency. This study aims to determine whether the RIMA-SVG technique is non-inferior to the conventional Aorta (Ao)-SVG approach in terms of 1-year graft patency, while also comparing perioperative complications and short-term clinical outcomes.

This non-inferiority, single-centre, prospective, double-blind, randomised clinical trial will enrol 300 patients undergoing CABG. Participants will be randomised into two surgical groups (RIMA-SVG vs Ao-SVG). The primary outcome is the 1-year SVG patency rate, assessed using coronary CT angiography. Secondary outcomes include perioperative complications, all-cause mortality, major adverse cardiovascular and cerebrovascular events (MACCE), and surgical site infections occurring during hospitalisation and up to 1 year postoperatively. Randomisation will be computer-generated, and all procedures will be performed by experienced surgeons. Patients will be followed up 12 months post-surgery. Non-inferiority will be established if the upper bound of the one-sided 97.5% CI for the difference in graft occlusion rates is less than the prespecified non-inferiority margin of 10%.

This study has been approved by the Ethics Committee of the Second Hospital of Jilin University (No. 460) and registered at ClinicalTrials.gov (NCT06787651). All participants will provide written informed consent before enrolment. To ensure data integrity and minimise bias, randomisation details will be concealed from researchers until surgery, and data analysts will remain blinded to group assignments. The findings will be disseminated through academic journals and conference presentations to promote knowledge sharing and clinical application in the field of cardiovascular surgery.

NCT06787651.

Systemic therapies for advanced gastric cancer (GC), including chemotherapy, targeted therapy and immunotherapy, have evolved significantly in the past few years. The combination of immune checkpoint inhibitors (ICIs) and chemotherapy has become the standard first-line (1L) treatment for advanced gastric or gastro-oesophageal junction (G/GEJ) cancer, although there remains a need for improvement in efficacy. Fruquintinib, an oral and highly selective vascular endothelial growth factor receptor inhibitor, has shown a synergistic antitumour effect when paired with ICI or chemotherapy. Moreover, it has demonstrated a tolerable safety profile and high potential for synergy with chemotherapy or immunotherapy, suggesting that a combination of fruquintinib, sintilimab and oxaliplatin+capecitabine (CAPEOX) can be a promising treatment for locally advanced G/GEJ cancer. This phase 1b/2 study aims to investigate the safety and efficacy of the combination of fruquintinib, sintilimab and CAPEOX regimen as a 1L combination therapy for unresectable advanced or metastatic G/GEJ cancer.

The FUNCTION trial (NCT06329973) is a single-arm, prospective, multicentre, phase Ib/II clinical trial that will consist of a dose escalation phase and an expansion phase. The study is planned to be conducted at 16 public hospitals. A total of 70 participants will be enrolled, comprising nine in the dose escalation phase and 61 in the expansion phase. The dosing regimen during the dose escalation phase will include three different doses of fruquintinib (3 mg, 4 mg and 5 mg, per oral, once per day days 1–14) + sintilimab, 200 mg, intravenous, day 1 +oxaliplatin 130 mg/m², day 1, intravenous, + capecitabine 800 mg/m², per oral, twice daily, days 1–14, every 21 days. The recommended phase 2 dose (RP2D) and maximum tolerated dose will be determined in the escalation phase, and the RP2D will be used in the expansion phase. The primary endpoints will be the maximum tolerated dose and objective response rate; the secondary endpoints will include OS, progression-free survival, disease control rate, duration of response, surgical conversion rate and adverse events and identification of molecular biomarkers for efficacy. The results from this study will provide evidence for expanding the clinical applications of fruquintinib plus sintilimab and CAPEOX as a 1L combination therapy in metastatic or non-resectable, locally advanced G/GEJ cancer and lay the foundation for future large-scale clinical investigations.

This study will be conducted in full compliance with the ICH (The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, ICH) GCP (Good Clinical Practice, GCP) guidelines, the rules of the Declaration of Helsinki and ICH E2A (Clinical Safety Data Management: Definitions and Standards for Expedited Reporting) Guidelines . The study protocol has received approval from the Henan Cancer Hospital ethical committee (Approval No. 2023-237-002). Written informed consent will be obtained from all patients prior to enrolment. For patients who have the mental capacity for informed consent, their consent for participation will be sought and will not be overridden by their family members. For patients who have impaired cognition, informed consent will be sought from their legally acceptable representative. On completion of the analyses, the study findings will be disseminated locally and internationally through manuscript publications in peer-reviewed journals and conference presentations.

NCT06329973.

This study aims to describe the knowledge, attitude and practice (KAP) regarding surgical scars among patients who had postorthopaedic surgery, and to explore correlations between these factors.

A multicentre, cross-sectional, observational study.

Conducted across multiple secondary/tertiary care hospitals between July and September 2024.

Of 816 enrolled participants undergoing orthopaedic surgery, 54.5% were male, 43.6% were aged 31–45 years, 73.9% were urban dwellers, 31.2% had a bachelor’s degree and 65.4% were married.

None (questionnaire-based assessment).

Primary outcomes were KAP scores (knowledge: 0–22; attitude: 9–45 and practice: 7–35), analysed via correlation and regression.

Mean scores: knowledge (12.5±6.9), attitude (27.6±3.3) and practice (28.2±6.5). Knowledge was negatively correlated with attitude (r=–0.24, p

Patients who had postorthopaedic surgery demonstrated poor scar-related knowledge and negative attitudes but proactive practices. Greater knowledge correlated with better practice, suggesting targeted education could optimise scar management. Further research should explore causal relationships and the efficacy of interventions.

We will recruit 478 paediatric patients with newly diagnosed IgAV across multiple centres. Participants will undergo prospective longitudinal assessment at disease onset and at 1, 3, 6 and 12 months postdiagnosis. Standardised evaluations will include clinical manifestations, physical examinations, laboratory parameters and patient-reported outcomes. The data will be analysed statistically with SPSS software (V.27.0), adopting a significance threshold of p

This study has been approved by the Medical Ethics Committee of the First Affiliated Hospital of Guangxi Medical University (2024-K0480), the Ethics Committee of the First People’s Hospital of Yulin (YLSY-IRB-SR-2025060), the Medical Research Ethics Committee of the Liuzhou Workers’ Hospital (KY2024356) and the Ethics Committee of the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region (No. (2025–1)003) and written informed consent was obtained from all the parents or guardians of the patients involved. It will be disseminated by publication of peer-reviewed manuscripts and presentation in abstract form at national and international scientific meetings.

ChiCTR2500099716.

Evidence suggests a 38% risk reduction in breast and bowel cancer-specific mortality with higher levels of exercise, however, most of this evidence is observational. More clinical trials are needed to build strong evidence for exercise’s impact on recurrence and survival. This study aims to assess the feasibility, acceptability and potential efficacy of a remote, tailored exercise programme on disease-free survival in patients recently completing curative treatment for early-stage, high-risk lung, breast or bowel cancer.

This UK-based, multicentre randomised controlled basket feasibility trial compares a personalised, remote-delivered exercise programme supported by exercise professionals against usual care. Potential participants are approached if they are: aged 18 or over, diagnosed with high-risk, early-stage breast, bowel or lung cancer, and within 24 weeks of completing primary curative treatments. Participants complete objective measures of physical function (submaximal cardiovascular fitness, endurance, muscle strength and balance), body composition (bioelectrical impedance) and self-reported outcomes (total physical activity, sleep quality, general quality of life (QoL), cancer-related QoL and exercise confidence/motivation). Clinical case note review provides disease-free survival outcomes at 6, 12 and 24 months. The 12-week programme is delivered remotely (via phone, email and/or video conference) with trainer contact tapering off over the subsequent 12 weeks (24 weeks total). Recruitment is ongoing with a 660-participant goal. Descriptive measures (quantitative and qualitative) will be reported for feasibility outcomes: recruitment, adherence, retention rates, data collection quality, adverse events, intervention acceptability and fidelity. A process evaluation is being conducted concurrently and is reported separately. Kaplan-Meier curves will be plotted and median disease-free survival calculated for each arm. To determine intervention impact, a log-rank test (unadjusted) will compare 2-year disease-free survival between groups within and among cancer types. Secondary outcomes (physical function status, general/cancer-specific QoL and determinants of meeting activity guidelines) will be reported at each time point.

Ethical approvals were obtained through Hull York Medical School (ID: 23/SS/0060) and UK NHS Health Research Authority (ID: 327663). Findings will be submitted for publication in high-impact journals, presentation at national and international conferences, press releases where appropriate, and dissemination activities to be decided on with the Patient Advisory Group.

ISRCTN97662203.

Eye injury poses a significant challenge to the global burden of blindness. Using the Global Burden of Disease (GBD) database, this study aims to comprehensively assess the latest global burden of eye injury and examine its relationship with the Socio-Demographic Index (SDI).

Observational study.

Population-based data on eye injury from the GBD 2021 database, covering the period 1990–2021.

Primary outcomes included incidence, prevalence and years lived with disability (YLDs) due to eye injury. Secondary outcomes included temporal trends analysed using joinpoint regression, age-period-cohort effects, health inequality indices (Slope Index of Inequality (SII) and Concentration Index) and decomposition analysis of contributing factors.

From 1990 to 2021, global eye injury incidence (in thousands) increased from 33 702.80 (95% uncertainty interval (UI): 27 271.41 to 44 086.12) to 39 996.91 cases (95% UI: 32 341.74 to 52 215.74), while age-standardised incidence rates (ASIR) declined from 622.73 to 503.26 per 100 000 population (average annual percent change (AAPC): –0.63, 95% confidence interval (CI) –0.81 to –0.46, p75 years). Health inequality between SDI regions narrowed (SII decreased from 3.10 to 2.21 per 100 000), with population growth contributing 207.93% to increased incidence.

The burden of eye injury exhibits distinct patterns across development levels, requiring tailored interventions: occupational safety for young adults in developing regions and fall prevention for the elderly in developed areas. Prevention strategies should align with regional economic development stages, emphasising workplace safety in industrialising regions while maintaining robust healthcare accessibility.

To investigate the causal relationship between serotonin levels, adenosine deaminase (ADA) activity and multiple sclerosis (MS) progression using an integrative multi-omics approach.

A two-sample Mendelian randomisation (MR) analysis was performed using inverse variance weighted (IVW) estimation to assess causality between serotonin, ADA and MS risk. Single-cell transcriptomic data from the Gene Expression Omnibus (GSE194078) were analysed to identify ADA-expressing immune cell subpopulations. Moreover, machine learning algorithms (Support Vector Machine-Recursive Feature Elimination, Least Absolute Shrinkage and Selection Operator and random forest) were applied to identify diagnostic biomarkers, following which a nomogram was constructed and validated.

MR analysis revealed that serotonin levels were positively correlated with MS progression (IVW β=0.350, p=3.63E-05), whereas genetically predicted ADA levels were inversely associated with MS risk (IVW β=–0.395, p=2.73E-04). Additionally, serotonin levels exhibited an inverse causal relationship with ADA activity (IVW β=–0.089, p=8.70E-03), with no evidence of reverse causation. Single-cell analysis identified 18 cellular subpopulations and six major immune cell types, with ADA highly expressed in T-NK cells and expressed at lower levels in platelets. Meanwhile, ADA expression was higher in the low immune receptor signalling group. Enrichment analysis indicated that differentially expressed genes were enriched in biological processes such as cytoplasmic translation and RNA splicing, as well as Kyoto Encyclopedia of Genes and Genome pathways such as Ribosome and Neurodegeneration-Multiple Diseases. Three key feature genes (IK, UBA52 and CCDC25) were identified, and the nomogram based on these genes demonstrated high diagnostic accuracy, with an AUC of 1.000 in the training dataset and 0.976 in the validation dataset.

Serotonin promotes MS progression by inhibiting ADA activity, positioning the serotonin-ADA axis as a potential therapeutic target. The identified biomarkers (IK, UBA52 and CCDC25) and the constructed nomogram may enhance diagnostic precision for MS, providing valuable insights for MS management and laying a theoretical reference for future studies.

Although a number of preclinical studies have demonstrated the therapeutic potential of puerarin for metabolic-associated fatty liver disease (MAFLD), there is a lack of high-quality clinical evidence. This study aims to evaluate the safety and efficacy of puerarin in patients with MAFLD in a randomised, controlled, crossover trial.

This study will use the randomised, double-blind, placebo-controlled crossover trial design. We plan to enrol 50 patients diagnosed with MAFLD, and they will be randomly assigned in a 1:1 ratio to receive either puerarin or placebo (maltodextrin) after a 2-week adaptation period. Participants in the two groups will receive the daily intervention of puerarin (180 mg/day) and placebo (180 mg/day) for 12 weeks, respectively. After a 4-week washout period, puerarin-treated and placebo-treated participants will cross over to receive the daily intervention of placebo and puerarin for 12 more weeks. The primary outcome measure will be defined as the changes in liver fat content, which will be assessed using MRI-proton density fat fraction before and after 12 weeks of puerarin or placebo supplement in patients with MAFLD. The secondary outcome measures include liver and kidney function changes, lipid metabolism indicators, blood glucose levels, iron metabolism parameters, blood routine, serum high-sensitivity C-reactive protein and anthropometric measurements. Additionally, alterations in gut microbiota composition and metabolic activity will be evaluated using 16S ribosomal RNA gene sequencing and liquid chromatography-mass spectrometry.

The study protocol has been approved by the ethics committee of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (Approval Number 2024-1625-208-01). The findings will be published in international peer-reviewed journals and presented at relevant academic conferences.

The trial has been registered with the Chinese Clinical Trial Registry (ChiCTR2400094017).

Ultrasound-guided serratus anterior plane block (SAPB) is commonly used for postoperative pain management in video-assisted thoracoscopic surgery (VATS). However, the choice of local anaesthetics for SAPB remains controversial. This study aims to compare the efficacy and safety of liposomal bupivacaine versus ropivacaine combined with two local anaesthetic adjuncts (dexamethasone and dexmedetomidine) for postoperative pain relief in VATS patients.

This is a single-centre, double-blinded, randomised controlled trial conducted at the Hangzhou First People’s Hospital Affiliated to Westlake University School of Medicine in Hangzhou, China. A total of 120 adult patients scheduled for VATS will be randomly assigned in a 1:1:1 ratio to one of the following three groups: liposomal bupivacaine (group L), ropivacaine combined with dexamethasone (group D) and ropivacaine combined with dexmedetomidine (group R). The primary outcome is the Numeric Rating Scale pain score at rest at 24, 48 and 72 hours postoperatively. Secondary outcomes include opioid consumption, adverse events, Quality of Recovery-15 scores, patient satisfaction and length of hospital stay.

The study was approved by the Ethics Committee of the Hangzhou First People’s Hospital Affiliated to Westlake University School of Medicine (approval number IIT-2024405-01) on 6 November 2024. The protocol was registered in the Chinese Clinical Trial Registry on 9 January 2025. The planned study period is from 1 January 2025 to 31 December 2027, with participant recruitment scheduled from 1 March 2025 to 31 December 2026. Recruitment has not yet started. All participants will provide written informed consent. The results will be disseminated through peer-reviewed journals and academic conferences.

ChiCTR2500095609.

Urolithiasis represents a significant global health burden. Comparing incidence trends between countries with distinct socioeconomic profiles, such as the United States and China, is crucial for tailoring public health strategies. This study aimed to characterise and compare the temporal trends of urolithiasis incidence in the United States and China from 1992 to 2021, thereby providing insights for global disease management.

Data on urolithiasis incidence in the United States and China from 1992 to 2021 were extracted from the Global Burden of Disease (GBD) 2021 study. First, we utilised joinpoint regression analysis to quantify the magnitude and identify significant turning points in age-standardised incidence rate trends over the study period. Second, an age-period-cohort model (APC model) was applied to assess the independent influence of age, period and cohort effects on incidence. Finally, the Nordpred model was employed to project the incidence trends for the next decade.

From 1992 to 2021, the overall incidence of urolithiasis in the United States decreased, but has recently shown an increase; in China, there was a significant reduction. According to the APC model, the highest risk was observed among middle-aged and elderly individuals in these countries. The period and cohort effects in China showed a decline. In the United States, the period effect initially declined but has recently shown an increase; cohort effect peaked around 1930, then declined and also increased in recent years. Over the next decade, the incidence of urolithiasis in both countries was expected to increase.

This study analysed the temporal trends in urolithiasis incidence over the past 30 years in the United States and China. Both countries experienced notable advancements in the burden of urolithiasis; however, the risk of an increased incidence remained higher in the United States.

Millions of patients receive general anaesthesia every year with either propofol total intravenous anaesthesia (TIVA) or inhaled volatile anaesthesia (INVA). It is currently unknown which of these techniques is superior in relation to patient experience, safety and clinical outcomes. The primary aims of this trial are to determine (1) whether patients undergoing (a) major inpatient surgery, (b) minor inpatient surgery or (c) outpatient surgery have a superior quality of recovery after INVA or TIVA and (2) whether TIVA confers no more than a small (0.2%) increased risk of definite intraoperative awareness than INVA.

This protocol was co-created by a diverse team, including patient partners with personal experience of TIVA or INVA. The design is a 13 000-patient, multicentre, patient-blinded, randomised, comparative effectiveness trial. Patients 18 years of age or older, undergoing elective non-cardiac surgery requiring general anaesthesia with a tracheal tube or laryngeal mask airway will be eligible. Patients will be randomised 1:1 to one of two anaesthetic approaches, TIVA or INVA, using minimisation. The primary effectiveness endpoints are Quality of Recovery-15 (QOR-15) score on postoperative day (POD) 1 in patients undergoing (1) major inpatient surgery, (2) minor inpatient surgery or (3) outpatient surgery, and the primary safety endpoint is the incidence of unintended definite intraoperative awareness with recall in all patients, assessed on POD1 or POD30. Secondary endpoints include QOR-15 score on POD0, POD2 and POD7; incidence of delirium on POD0 and POD1; functional status on POD30 and POD90; health-related quality of life on POD30, POD90, POD180 and POD365; days alive and at home at POD30; patient satisfaction with anaesthesia at POD2; respiratory failure on POD0; kidney injury on POD7; all-cause mortality at POD30 and POD90; intraoperative hypotension; moderate-to-severe intraoperative movement; unplanned hospital admission after outpatient surgery in a free-standing ambulatory surgery centre setting; propofol-related infusion syndrome and malignant hyperthermia.

This study is approved by the ethics board at Washington University, serving as the single Institutional Review Board for all participating sites. Recruitment began in September 2023. Dissemination plans include presentations at scientific conferences, scientific publications, internet-based educational materials and mass media.

NCT05991453.

Immunotherapy combined with chemotherapy has shown potential in improving the pathological complete response (pCR) rate in luminal-type breast cancer. This study explores whether the addition of stereotactic body radiotherapy (SBRT) and the bispecific antibody AK112 (Ivonescimab) further enhances treatment efficacy.

This is a single-centre, prospective, phase II trial using Simon’s two-stage design to evaluate the efficacy and safety of neoadjuvant SBRT combined with Ivonescimab and chemotherapy. A total of 50 patients will be enrolled. The primary endpoint is pCR. Secondary endpoints include objective response rate, disease control rate, Residual Cancer Burden Index, 12-month event-free survival, safety and quality of life. Exploratory endpoints include six-point minimal residual disease (MRD) assessment. Data will be analysed using the Kaplan-Meier method and one-sided exact binomial test (alpha=0.05).

This study has been approved by the ethics committee of Hubei Cancer Hospital (Approval No.: LCKY2024011). Results will be disseminated through peer-reviewed journals and conference presentations.

NCT06402435.

To identify risk factors and develop a predictive model for postdischarge all-cause mortality in patients with heart failure with preserved ejection fraction (HFpEF).

Retrospective cohort study.

Tertiary care, Xiangtan Central Hospital, Hunan, China.

9419 patients with HFpEF, diagnosed between May 2014 and January 2023 according to 2021 European Society of Cardiology criteria (N-terminal pro-B-type natriuretic peptide (NT-proBNP) ≥125 pg/mL, left ventricular ejection fraction ≥50%, New York Heart Association (NYHA) class II-IV). Exclusions were age

All-cause mortality within 3 years of hospital discharge.

10 independent predictors were identified: NT-proBNP, albumin, age, NYHA class III-IV, C reactive protein, right atrial end-systolic diameter, haemoglobin, chronic obstructive pulmonary disease, hyponatraemia and prior percutaneous coronary intervention. The prediction model demonstrated good discrimination, an area under the receiver operating characteristic curve of 0.756 (95% CI 0.743 to 0.769) in the training cohort and 0.764 in the validation cohort. Based on calculated risk scores, patients were classified into low-risk (≤200.36), medium-risk (200.37–232.24) and high-risk (≥232.25) groups, corresponding to 3-year mortality rates of 12.6%, 40.8% and 68.0%, respectively.

A simple clinical model using routinely available parameters enables effective 3-year mortality risk stratification in HFpEF patients after discharge. External validation is needed to confirm its generalisability.

NCT06487468.

Diabetic retinopathy (DR) is a common microvascular complication of diabetes that has the potential to progress to vision-threatening DR (VTDR) even in the absence of symptoms. Plasma proteins in response to physiological and pathological conditions in the body may be intricately connected to the initiation of VTDR.

To determine the causality between 4489 plasma proteins and the risk of VTDR to explore potential therapeutic targets for VTDR.

A Mendelian randomisation (MR) study.

A two-sample MR study was performed to investigate the causality between plasma proteins and VTDR.

Genetic information on plasma proteins and VTDR in European populations from IEU OpenGWAS.

Mediation analysis was performed to evaluate the indirect impacts of plasma proteins on VTDR via related risk variables. Furthermore, the druggability and potential role of the target proteins in VTDR were explored.

According to the MR study, 92 proteins out of 4489 plasma proteins had causal relationships with VTDR. Five potential proteins (MMP8, BST1, ARL1, MRPL33 and SDF2L1) were causally related to both VTDR and risk factors. Mediation analysis revealed that the protein-mediating effects on VTDR outcomes were achieved through risk factors (body mass index; glycated haemoglobin). Seven drugs that interacted with MMP8 were potential target drugs for VTDR.

Our investigation elucidated the causal connections between plasma proteins, risk factors and VTDR, identified MMP8 protein as a potential drug target and highlighted seven candidate drugs. These results provide a translational framework for developing novel therapies for VTDR.