Yishu Fan

Introduction Anterior cruciate ligament (ACL) rupture can be treated surgically or non-surgically, with several surgical interventions available at present. However, the comparatively effective surgical intervention with relatively fewer side effects remains unknown. This study aims to fill in this gap by conducting a Bayesian network meta-analysis (NMA) and provide a theoretical basis for the clinical application. Method and analysis We will perform a Bayesian NMA and will include randomised controlled trials (RCTs) published in English or Chinese that compare surgical intervention (ie, standard ACL reconstruction, ACL remnant-preserving reconstruction and ACL repair with suture augmentation to conservative therapy or studies that compare one surgical intervention to another for the symptom relief and function recovery of patients with ACL rupture. Primary outcome will be the proportion of patients with symptomatic and functional improvement measured by the Knee Injury and Osteoarthritis Outcome Score before and 6 months after treatment, with scores ranging from 0 (worst) to 100 (best). Secondary outcomes will be knee-specific quality of life (ACL QoL), return to activity and level of sport participation (Tegner or modified Tegner score), health-related QoL (EuroQol Group 5-Dimension 5-Level, EQ-5D-5L), resource use, intervention-related complications and patient satisfaction. We have developed search strategies for PubMed, Embase, the Cochrane Library and Web of Science, retrieving RCTs that meet the inclusion criteria from database inception to 1 December 2023. The methodological quality of the included RCTs will be assessed based on the Cochrane risk of bias table. The relative ranking probability of the best intervention will be estimated using the surface under the cumulative ranking curve. The Bayesian NMA will be conducted by using WinBUGS V.1.4.3. The Grading of Recommendations Assessment, Development and Evaluation approach will be applied to determine our confidence in an overall treatment ranking from the NMA. Ethics and dissemination Ethical approval for this study is not required because no private or confidential patient data will be used in this study. Findings of this study would be disseminated through the publication in a peer-reviewed medical journal. PROSPERO registration number CRD42023437115.

Vascular cognitive impairment (VCI) encompasses a wide range of cognitive disorders stemming from cerebrovascular issues, such as strokes or small vessel disease. These conditions often pose challenges to traditional diagnostic approaches due to their multifactorial nature and varied clinical presentations. Recently, next-generation sequencing (NGS) technologies have provided detailed analyses of long non-coding RNAs (lncRNAs) in the molecular pathobiology of VCI. These new findings help with molecular-based diagnostics and treatments of VCI. Within this realm, the concept of immune modulation, especially through specific vaccinations, emerges as a promising therapeutic strategy in VCI mitigation. In this review, we comprehensively elucidate the function of lncRNAs in VCI, emphasizing the advanced understanding of VCI’s molecular underpinnings made possible through NGS technologies. Significant focus is placed on the immune system’s role in VCI, particularly the neuroinflammatory processes which are consequential to cerebrovascular abnormalities. We believe that lncRNAs participate in regulating these immunological pathways, potentially guiding the development of vaccines targeting VCI. In this context, we propose a novel perspective: using knowledge about lncRNA profiles and functions to guide vaccine development, we can potentially exploit the body’s immune response to mitigate or prevent VCI. This approach has the potential to revolutionize VCI management by introducing targeted immunization strategies informed by molecular signatures, a concept that remains largely unexplored in current research endeavors. In addition, we summarize current progress and propose future directions, advocating for robust, interdisciplinary studies to validate the potential intersections between lncRNA landscapes, VCI pathology, and immunology. This review aims to spur innovative research and promote the development of lncRNA-informed vaccine strategies as proactive interventions against the cognitive consequences of VCI.

Currently, adipose-derived mesenchymal stromal/stem cells (ADMSCs) are recognized as a highly promising material for stem cell therapy due to their accessibility and safety. Given the frequently irreversible damage to neural cells associated with CNS disorders, ADMSC-related therapy, which primarily encompasses ADMSC transplantation and injection with exosomes derived from ADMSCs or secretome, has the capability to inhibit inflammatory response and neuronal apoptosis, promote neural regeneration, as well as modulate immune responses, holding potential as a comprehensive approach to treat CNS disorders and improve prognosis. Empirical evidence from both experiments and clinical trials convincingly demonstrates the satisfactory safety and efficacy of ADMSC-related therapies. This review provides a systematic summary of the role of ADMSCs in the treatment of central nervous system (CNS) disorders and explores their therapeutic potential for clinical application. ADMSC-related therapy offers a promising avenue to mitigate damage and enhance neurological function in central nervous system (CNS) disorders. However, further research is necessary to establish the safety and efficacy of clinical ADMSC-based therapy, optimize targeting accuracy, and refine delivery approaches for practical applications.

Osteoarthritis (OA) is a prevalent and debilitating age-related joint disease characterized by articular cartilage degeneration, synovial membrane inflammation, osteophyte formation, as well as subchondral bone sclerosis. OA drugs at present are mainly palliative and do not halt or reverse disease progression. Currently, no disease-modifying OA drugs (DMOADs) are available and total joint arthroplasty remains a last resort. Therefore, there is an urgent need for the development of efficacious treatments for OA management. Among all novel pharmaco-therapeutical options, exosome-based therapeutic strategies are highly promising. Exosome cargoes, which include proteins, lipids, cytokines, and various RNA subtypes, are potentially capable of regulating intercellular communications and gene expression in target cells and tissues involved in OA development. With extensive research in recent years, exosomes in OA studies are no longer limited to classic, mesenchymal stem cell (MSC)-derived vesicles. New origins, structures, and functions of exosomes are constantly being discovered and investigated. This review systematically summarizes the non-classic origins, biosynthesis, and extraction of exosomes, describes modification and delivery techniques, explores their role in OA pathogenesis and progression, and discusses their therapeutic potential and hurdles to overcome in OA treatment.