Conectar
by Xiuxin Liu, Yuhui Han, Ruixue Kuang, Wenjiong Sheng, Yan Zhang, Xinyu Jia, Xiaoxiao Gao, Yanchao Ma
DNA damage-induced by radiotherapy is a critical factor in promoting the death of colorectal cancer cells (CRC). Although high mobility group box 1 (HMGB1) reportedly plays a vital role in tumor radioresistance by modulating DNA damage repair, the precise mechanisms remain unclear. In this study, HMGB1 knockdown markedly enhanced cell apoptosis after radiation. HMGB1 downregulation significantly inhibited DNA damage repair and reactive oxygen species (ROS)-mediated redox homeostasis after irradiation in CRC cells. Mechanistically, HMGB1 interacts with KU70 via its region spanning residues 95–163. This interaction subsequently activates the non-homologous end joining (NHEJ) pathway to facilitate DNA damage repair, ultimately leading to reduced radiation-induced cell apoptosis. KU70 silencing showed the same effect as HMGB1 depletion mediated cell apoptosis and DNA damage response both in vitro and in vivo. Additionally, HMGB1 and KU70 were overexpressed in CRC tissues. Analysis of the GEPIA database indicated that elevated levels of both genes showed a trend toward association with poor patient prognosis, although this did not reach statistical significance. The current study revealed that HMGB1 may promote DNA damage repair through KU70 and its mediated NHEJ pathway to affect apoptosis in CRC cells after irradiation. Thus, targeting the HMGB1/KU70/NHEJ axis may be a potential therapeutic target to promote the response of CRC to radiotherapy and in-depth study of the specific mechanism of this axis in CRC radioresistance will help to the develop more effective treatment strategies.The prolonged survival of lung cancer patients is accompanied by an increasing incidence of leptomeningeal metastases (LM). Patients with LM have a poor prognosis, significantly impacting their quality of life and overall survival. Recent studies have shown that while intrathecal pemetrexed (IP) can improve symptoms and confer a survival benefit in non-small cell lung cancer (NSCLC) patients with LM, drug resistance remains a significant challenge. As for systemic therapy, intravenous bevacizumab combined with chemotherapy has demonstrated clinical benefits in NSCLC patients. However, clinical data on intrathecal bevacizumab remain scarce. Therefore, this study aims to preliminarily explore the efficacy and safety of intrathecal pemetrexed and bevacizumab in the treatment of NSCLC patients with LM.
This is a single-centre, single-arm, prospective, investigator-initiated phase Ia clinical trial sponsored by Shanghai Chest Hospital, involving patients with advanced NSCLC and LM. Participants will be enrolled and allocated into two predefined cohorts. Cohort A: six participants will receive IP monotherapy for safety exploration. Cohort B: participants will receive intrathecal pemetrexed and bevacizumab. Pemetrexed will be administered at a fixed dose, while the dosage exploration for bevacizumab will employ a combination of a 3+3 design and an accelerated titration design (ATD). The primary endpoint is the safety and the secondary endpoint is the overall survival (OS).
This study protocol (Version 1.1, dated 8 October 2024) was approved by the Ethics Commission of Shanghai Chest Hospital (IS24103) on 23 October 2024. Trial results will be published in a peer-reviewed journal.
NCT06663306, ClinicalTrials.gov.
Stroke is a major global health issue with rising incidence in China. Current estimates often focus on specific deaths, underestimating their impact. This study aimed to quantify and predict the all-cause and cause-specific burden of stroke using real-world data.
Population-based study.
Residents in Shanghai Pudong, which covers an area of 1210.41 km² (467.34 mi²) and has a population of 3.17 million, spanning from 2005 to 2021.
Stroke-related deaths in Pudong (2005–2021) were analysed by gender, age and subtype. Metrics included crude mortality rates (CMR), age-standardised mortality rates (ASMRW) and years of life lost (YLL). The Joinpoint Regression Programme determined average annual per cent change (AAPC), while the decomposition method assessed ageing’s impact. The AutoRegressive Integrated Moving-Average (ARIMA) model projected trends from 2022 to 2035.
Among the 92 779 stroke-related deaths, the top three causes were stroke, heart disease and diabetes mellitus. From 2005 to 2021, the CMR for stroke-related deaths (AAPC=1.65%), stroke-specific deaths (AAPC=0.60%) and YLL rates (AAPC=0.36%) increased significantly (all p
Stroke’s real-world burden is substantial, with ageing exacerbating mortality. Urgent action is needed to manage risk factors and prevent stroke.
by Junjie Kuang, Jie Ju, Xin Xu
Aerobic and resistance exercises are the two most common modes of physical activity. They may cause some functional changes such as elevation of VO2max and muscle mass. However, descriptions of changes in complex molecular network induced by exercise are often insufficiently comprehensive, limiting the exploration of some new indicators. We utilized a metabolomics analysis method based on Liquid chromatography-mass spectrometry (LC-MS) to investigate the metabolic characteristics of 10 healthy male college students at two time points before and after a single session of aerobic and resistance exercise. The analysis was conducted at both the metabolite and metabolic pathway levels. Notably, the concentrations of several amino acids including aspartic acid, glutamic acid, histidine and tryptophan exhibited significant changes following both modes of exercise. These findings offer a more comprehensive understanding of the molecular effects of acute exercise on the human body, contributing to evaluating post-exercise physiological states and screening for relevant metabolite indicators. Future research could employ multi-omics approaches to validate these results and explore the long-term impact of exercise on human metabolic profiles, linking specific metabolic pathways to functional outcomes.Intracranial atherosclerotic disease (ICAD), prevalent in over 65% of Asian populations, is a major cause of global cerebrovascular morbidity and mortality through cerebral hypoperfusion. Despite guideline-directed medical therapy, recurrent ischaemic events remain common due to inadequate collateral circulation. Previous randomised controlled trials (ie, International Extracranial-Intracranial Bypass Study, carotid occlusion surgery study, carotid and middle cerebral artery occlusion surgery study) demonstrated high perioperative risks of extracranial-to-intracranial bypass surgery, while recent single-arm studies suggest that indirect cerebral revascularisation may improve cerebral perfusion with enhanced safety.
This is a multicentre, randomised, open-label trial designed to enrol 378 participants (189 per group) with symptomatic ICAD (≥70% stenosis/occlusion, American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology Collateral Score 0–2). Participants will be allocated using minimisation randomisation via an interactive web response system to receive multimodal indirect revascularisation plus intensive medical therapy or intensive medical therapy alone. The primary endpoints are the composite of stroke or death within 30 days and ipsilateral ischaemic stroke within 24 months. Secondary outcomes include transient ischaemic attack reduction, neurological function preservation (modified Rankin Scale), and cerebral perfusion improvements assessed by CT perfusion and MRI.
The study protocol has been approved by the Biomedical Research Ethics Committee of West China Hospital, Sichuan University (approval number: 2024 Review (2588)). Written informed consent will be obtained from all participants prior to enrolment. The study results will be disseminated through peer-reviewed publications and presentations at national and international conferences.
Chinese Clinical Trial Registry (ChiCTR2500099882).
Postoperative pulmonary complications are a common and significant concern following head and neck surgeries. Patients with oral and maxillofacial cancer are particularly susceptible to reduced pulmonary function, impaired exercise capacity and diminished quality of life. Pulmonary rehabilitation (PR) has been widely validated as an effective intervention for managing respiratory diseases, improving functional capacity and enhancing health-related quality of life. However, a critical gap persists in developing PR programmes specifically tailored to the distinct physiological and functional challenges faced by patients with oral and maxillofacial cancer. This protocol introduces an innovative PR intervention uniquely designed to address these challenges, bridging the gap in current rehabilitation practices and offering a comprehensive approach to improve recovery outcomes.
This single-blind, two-arm, randomised controlled trial will enrol 144 patients with oral and maxillofacial malignancies from a tertiary hospital in China. Participants will be randomly assigned to either the intervention group (n=72), receiving routine care alongside a tailored PR programme designed by the research team, or the control group (n=72), receiving routine care alone. The primary outcome is pulmonary function, which is assessed using pulmonary function tests. Secondary outcomes include exercise capacity, quality of life and cancer-related fatigue. Outcomes will be assessed at three time points: baseline (T0), before discharge and 2 months postdischarge (T1), allowing for evaluation of both immediate and sustained intervention effects.
The trial has received ethical approval from the Ethics Committee of West China Hospital of Stomatology, Sichuan University (WCHSIRB-D-2025–025). Study findings will be disseminated through peer-reviewed journals and conference presentations.
ChiCTR2500099236.
Depression is characterised by disruptions in brain circuitry, and interventions like intermittent theta burst stimulation (iTBS) offer the potential for normalising these circuits and improving clinical symptoms. However, personalised treatment targets for depression remain underexplored. This trial aims to evaluate the clinical efficacy of iTBS as an additional treatment to a stable antidepressant regimen in patients with treatment-resistant depression (TRD) by modulating brain circuits identified through personalized brain functional sectors compared with sham treatment. This work is a part of the China Study to Predict Optimised Treatment bioMarkers of Individualised Neuromodulation in Depression project.
This is a multi-centre, double-blind, sham-controlled randomised trial, with a 2:1 allocation ratio to 21 days of active or sham iTBS. A total of 360 eligible participants, diagnosed with current treatment-resistant unipolar major depressive disorder, who have been on a stable antidepressant regimen for at least 4 weeks and are experiencing moderate-to-severe depressive episodes, will be recruited from seven clinical centres in China. The primary outcome is the change in the Montgomery–Asberg Depression Rating Scale immediately following 21-day treatment. Secondary outcomes include response rate and remission rate, change in the Hamilton Rating Scale for Depression, efficacy sustainability and recurrence within 6 months post-treatment. Additionally, safety, blinding, dropout and potential moderators of response will be examined.
The study has been approved by each centre’s ethics committee, with the first ethical approval granted by the Ethics Committee of Beijing Anding Hospital on 30 December 2022 (approval 2022206FS-2). Written informed consent will be obtained from all participants prior to enrolment. The study results will be published in relevant peer-reviewed journals.
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