Exosomes, small extracellular vesicles secreted by cells, have gained attention as potential therapeutic agents due to their natural ability to deliver biomolecules and traverse biological barriers. However, their limited targeting specificity and payload capacity necessitate modifications for improved therapeutic efficacy. Click chemistry, known for its high specificity, efficiency, and mild reaction conditions, offers an innovative solution for modifying exosomal surfaces. This technique enables precise attachment of targeting ligands, imaging agents, and therapeutic molecules, enhancing the targeting, delivery, and overall effectiveness of exosome-based therapies. By addressing cancer heterogeneity, click chemistry-modified exosomes can target diverse cancer cell populations within tumors, improving treatment specificity and reducing drug resistance. The development of copper-free click chemistry, such as strain-promoted azide-alkyne cycloaddition (SPAAC), minimizes toxicity, ensuring biocompatibility and safety. As research progresses, this approach holds great promise for personalized and effective cancer treatment, paving the way for next-generation therapeutics and diagnostics.

Combination therapy has emerged as an efficacy strategy for treating complex diseases. Its potential to overcome drug resistance and minimize toxicity makes it highly desirable. However, the vast number of potential drug pairs presents a significant challenge, rendering exhaustive clinical testing impractical. In recent years, deep learning-based methods have emerged as promising tools for predicting synergistic drug combinations. This review aims to provide a comprehensive overview of applying diverse deep-learning architectures for drug combination prediction. This review commences by elucidating the quantitative measures employed to assess drug combination synergy. Subsequently, we delve into the various deep-learning methods currently employed for drug combination prediction. Finally, the review concludes by outlining the key challenges facing deep learning approaches and proposes potential challenges for future research.

Intervertebral disc (IVD) degeneration is a common phenomenon that affects patients with increasing prevalence with increasing age. Both conservative treatments, such as the use of pain medication or physical therapy, and surgical treatments, such as fusion or disc replacement therapies, are offered to patients. Both non-invasive and invasive treatments have been shown to improve pain and quality of life for patients. This review explores the role of regenerative medicine techniques as a promising therapeutic intervention that can be used before or in combination with conservative therapy and surgery to enhance the treatment process in patients with IVD degeneration or disc pathology. Currently, there are four major modules of regenerative medicine: genetic therapy, platelet-rich plasma therapy, stem cell transplantation and tissue engineering. Several research studies have shown promising outcomes of stem cell transplantation and tissue engineering when combined with either surgical or conservative treatment, resulting in improved pain outcomes. The additional benefit of regenerative medicine techniques, specifically stem cell transplantation, is the potential for treating the root pathology of degeneration. Regenerative medicine techniques also have the potential to either halt or reverse degeneration as opposed to current standards of care for managing symptoms. There is a plethora of current research highlighting the benefits of regenerative medicine techniques; however, there remains clinical concerns and ethical concerns regarding the use of regenerative therapy techniques such as stem cell transplantation in the context of IVD degeneration.

Genome-wide association studies (GWAS) have been instrumental in elucidating the genetic architecture of various traits and diseases. Despite the success of GWAS, inherent limitations such as identifying rare and ultra-rare variants, the potential for spurious associations and pinpointing causative agents can undermine diagnostic capabilities. This review provides an overview of GWAS and highlights recent advances in genetics that employ a range of methodologies, including whole-genome sequencing (WGS), Mendelian randomisation (MR), the Pangenome's high-quality Telomere-to-Telomere (T2T)-CHM13 panel and the Human BioMolecular Atlas Program (HuBMAP), as potential enablers of current and future GWAS research. The state of the literature demonstrates the capabilities of these techniques to enhance the statistical power of GWAS. WGS, with its comprehensive approach, captures the entire genome, surpassing the capabilities of the traditional GWAS technique focused on predefined single nucleotide polymorphism sites. The Pangenome's T2T-CHM13 panel, with its holistic approach, aids in the analysis of regions with high sequence identity, such as segmental duplications. MR has advanced causative inference, improving clinical diagnostics and facilitating definitive conclusions. Furthermore, spatial biology techniques such as HuBMAP enable 3D molecular mapping of tissues at single-cell resolution, offering insights into pathology of complex traits. This study aimed to elucidate and advocate for the increased application of these technologies, highlighting their potential to shape the future of GWAS research.

Patients with breast tumours that metastasise to the brain have limited treatment options and a very poor prognosis. More effective therapeutic strategies are desperately needed for this patient population. Recent evidence demonstrates that brain metastases arising from breast tumours display altered energy production that results in enhanced autophagy. Preclinical studies have shown that genetically or pharmacologically disrupting the autophagy pathway significantly decreases the brain metastatic burden, resulting in improved animal survival and increased sensitivity to lapatinib. These findings pave the way for the development of novel strategies targeting autophagy for breast cancer patients with brain metastatic disease.

Understanding the interplay between immune cells and the bone marrow microenvironment is crucial for elucidating age-related musculoskeletal changes. In this commentary manuscript, we summarized that studies have shown that proinflammatory immune cells in the bone marrow, such as macrophages and neutrophils, can inhibit bone formation by secreting grancalcin. Research on skeletal stem cells (SSCs) in aged mice reveals a shift towards pro-inflammatory gene expression, affecting their osteogenic potential, while another study maps age-related changes in cranial SSC niches, emphasizing the role of the CXCL12–CXCR4 axis in stem cell-immune cell communication, Additionally, the immune system influences hematopoietic stem cells (HSCs); Niche ageing and accumulation of mutations with age lead to HSC exhaustion and a bias towards myeloid differentiation, with toll-like receptors playing a key role in maintaining hematopoiesis and bone metabolism balance.

The persistent threat of tuberculosis (TB) on a global scale hasprompted a reevaluation of preventive strategies, with a particular focus onthe Bacille Calmette-Guérin (BCG) vaccine's role in revaccination. Theresurgence underscores an urgent need for enhanced measures, prompting acritical examination of BCG revaccination strategies. Drawing from the researchof Paulo Cesar Pereira dos Santos and a synthesis of randomized controlledtrials (RCTs), this review identifies key considerations for refining BCGrevaccination's efficacy against Mycobacterium tuberculosis (MTB) andTB. The main body of this review integrates four principal domains essentialfor optimizing BCG revaccination: the timing of revaccination, the assessmentof various BCG strains, the evaluation of the vaccine's effectiveness on MTBand non-tuberculous mycobacteria (NTM) strains, and the enhancement of RCTmethodologies. Determining the optimal revaccination timing is paramount forbolstering immunity, especially in regions with high TB prevalence. Theanalysis of different BCG strains provides insights into strain-specificimmunogenicity, informing vaccine deployment strategies. Additionally, understanding the vaccine's impact on a range of mycobacterial infections iscrucial for its broader application in various microbial contexts. The reviewemphasizes the refinement of RCT designs to ensure robust and consistentoutcomes, facilitating the reproducibility of results in diverse settings. Itproposes a strategy that not only suggests modifications to revaccinationpractices to increase global TB prevention effectiveness but also calls forcontinuous research to improve BCG revaccination methodologies. The paperadvocates for a standardized, evidence-driven approach to global TB preventionthat takes into account regional epidemiological differences. In conclusion, this review significantly contributes to the discourse on TB prevention, advocating for evidence-based, standardized approaches that could potentiallytransform the role of BCG revaccination in global TB prevention efforts. Thefindings support current initiatives aimed at developing policies based onsolid evidence, ensuring the scientific integrity and practical relevance ofBCG revaccination strategies.

Background: Molecular diagnostic technology is the foundation of precision medicine, which has the advantages of good specificity, high sensitivity, strong targeting, rapiddiagnosis, etc. It has a wide range of applications in the field of pediatrics. However, molecular diagnostic technology is characterized by complicated experimental operation, high difficulty in data analysis and interpretation, in consistent standards among laboratories, and difficult standardization of technical processes. Enhancing the application value of molecular diagnostic technology in pediatrics and promoting the high-quality development of the discipline requires careful consideration by relevant management and professionals.

Methods: This study firstly outlines the development history of molecular diagnostic technology. Then, it analyzes the application of molecular diagnostic technology in the field of pediatrics. Finally, it explores the countermeasures for the management of molecular diagnostic laboratories.

Results: This study highlights the importance of molecular diagnostic technology in providing information and decision-making basis for disease prevention, prediction, diagnosis, treatment and regression. It has a wide range of applications in the molecular diagnosis of pediatric hereditary diseases, malignant tumors and infectious diseases. In addition, the countermeasures for the management of molecular diagnostic laboratories are proposed from the five aspects of laboratory, personnel team construction, standardized management, multidisciplinary cross-discipline, research and translation, safety managementand ethical supervision, and management upgrading and modernization.

Conclusions: Molecular diagnostic technology, as the basis of precision medicine, has become one of the important frontier fields in the development of contemporary pediatric medicine. Enhanced laboratory capacity in molecular diagnostic techniques can improve outcomes in the prevention, prediction, diagnosis, treatment, prognosis and research of pediatricdiseases, and lay the groundwork for child healthcare.

Colorectal cancer (CRC) is a prevalent malignancy with a high mortality rate, necessitating innovative treatment strategies. PROTACs (PROteolysis Targeting Chimeras) represent a promising therapeutic approach by targeting and degrading oncogenic proteins via the ubiquitin-proteasome pathway. This study explores the potential of using exosomes as delivery vehicles for PROTACs to enhance treatment efficacy. Exosomes, due to their biocompatibility and inherent targeting capabilities, offer a precise method for delivering PROTACs to CRC cells, potentially overcoming challenges associated with traditional therapies such as drug resistance and off-target effects. By harnessing the advantages of both exosome-based delivery and PROTAC technology, this approach aims to improve targeted protein degradation and therapeutic outcomes in CRC treatment. Further research is required to optimize exosome engineering, ensure efficient PROTAC loading, and validate the safety and efficacy of this novel therapeutic strategy through preclinical and clinical trials.

Exosomes, small extracellular vesicles secreted by cells, have emerged as pivotal players in cell-to-cell communication. Plant-derived exosomes, in particular, are gaining attention for their potential therapeutic applications in nano-medicine. These vesicles are naturally occurring nanoparticles that carry bioactive molecules such as proteins, lipids, and nucleic acids. Due to their biocompatibility, low toxicity, and ability to traverse biological barriers, plant-derived exosomes present a promising alternative to synthetic nanoparticles for drug delivery, especially in cancer and microbial infection therapy. Exosomes are secreted by almost every cell and are profusely present in all living organisms, making them excellent candidates for a large spectrum of research and applications. This paper describes the highly organized and regulated biosynthesis of exosomes and the prospects of their application in cancer therapy and treatment of microbial infections.

Background: The use of cervical collars in the management of acute cervical spine injuries has been part of standard practice in the trauma setting for decades, aimed at preventing secondary injuries.

Objectives: To review the recent evidence challenging the routine use of cervical collars, addressing the limited scientific support, associated risks, and guidelines for their use.

Methods: A comprehensive literature review was conducted, analyzing recent studies and guidelines from authoritative bodies such as the American Association for Neurological Surgeons and the Congress of Neurological Surgeons. The review focused on the efficacy, risks, and recommendations regarding cervical collar use in acute cervical spine injuries.

Results: Recent evidence questions the routine use of cervical collars, highlighting limited scientific support and several associated risks, including pressure ulcers and decreased venous return. Cervical collars may also be contraindicated in individuals with abnormal spinal structures, such as those with Ankylosing Spondylitis. The efficacy of cervical collars is debated, particularly concerning undiagnosed spinal fractures, where delayed diagnosis can result in permanent injuries. Despite these risks, cervical collars may be beneficial in low-resource areas and when used effectively with early clearance post-injury. Current guidelines recommend immobilizing patients suspected of cervical spine injury but stress the importance of proper evaluation of the need for immobilization. Recent guidelines advocate for spinal motion restriction over traditional immobilization, emphasizing the need for better risk assessment and implementation strategies.

Conclusions/Clinical Importance: Re-evaluating the routine use of cervical collars is crucial due to potential risks and limited supporting evidence, with a focus on individualized assessment and adherence to updated guidelines favoring spinal motion restriction.

Adenocarcinomas of the stomach and gastroesophageal junction remain one of the most common malignant tumours in humans worldwide, often with a poor prognosis. Particularly in countries without upper gastrointestinal tract screening endoscopy, tumours that have been asymptomatic for a long time are only diagnosed at an advanced stage. This limits the therapeutic options. Often only palliative therapy concepts are available. Great progress has been made in the last two decades. The genetic basis of adenocarcinomas of the stomach and gastroesophageal junction has been deciphered and new targeted drugs have been developed. Cell and tissue-based predictive diagnostics are becoming increasingly important in therapy planning. Here, surgical pathology forms an important link between basic research, clinical trials, and translation into clinical application. This review article summarizes the experiences made in translational tumour research, which point to the problems of spatial and temporal intratumoral heterogeneity of adenocarcinomas of the stomach and gastroesophageal, the development and continuous re-assessment of therapeutically relevant cut-off values, resistance mechanisms, tumour microenvironment, sexual dimorphism and the pitfalls molecular tumour boards may face.

Plant-derived exosomes (PDEs) are extracellular vesicles (EVs) occurring naturally, which have propitious applications in the development of cost-effective and fruitful cancer therapy with minimum aftereffects and ramifications. Recent advancements in research based on PDEs demonstrate their extraordinary advantages in cancer therapy. The components of PDEs exhibit accomplished cancer prevention activity and having insignificant or negligible toxicity. The conventional methods to deliver drugs to the target have various problems, several of which can be solved by using PDEs for drug delivery. The main constituents of PDEs are proteins, lipids, DNA and RNA. PDEs are believed to revolutionize cancer therapy due to their magnificent attributes, but only a few clinical trials on PDEs are in progress. The mechanisms and regulations by which PDEs execute anticancer properties are yet not completely understood. Hence, research are conducted worldwide to understand the mechanisms of action of cancer antagonist PDEs more comprehensively and perspicuously. Modified PDEs have prospect in evolution of precision medicine which can bring a new dimension in the treatment of cancer.

This study by Okuno et al. successfully identified eight exo-miRNAs through exosome-based discovery and established an exo-miRNA-based liquid biopsy assay for predicting therapeutic response in metastatic gastric cancer (mGC). Exosomes, a subpopulation of extracellular vesicles originating from endosomes, play a crucial role in this context. Liquid biopsy, analyzing blood for circulating tumor cells, extracellular vesicles, or cell-free nucleic acid, has revolutionized cancer diagnosis and monitoring. It significantly contributes to early detection, staging, and relapse detection in various cancers. Numerous studies have highlighted the clinical significance of miRNA and lncRNA within extracellular vesicles. The authors developed a response-prediction model for chemo-responsiveness in mGC patients. This study's model predicts responses robustly, demonstrating its potential efficacy in clinical practice. It offers a non-invasive and accessible method for therapeutic response prediction, crucial for precision medicine in mGC. Successful translation of these findings into clinical applications promises substantial benefits for patient care.

Ultraviolet (UV) radiation, a component of sunlight, holds both advantageous anddetrimental effects on human health. While shorter wavelengths of UV radiationaid in melanin and vitamin D synthesis, longer wavelengths pose risks like skincancer and premature aging due to DNA damage. To combat such stress, cellsemploy various mechanisms, including the heat shock response (HSR). Activation of this response involves a highly regulated transcriptional processorchestrated by heat shock factors (HSFs). While HSF1 has been observed as a keytranscription factor for HSR, other HSFs are also found to be associated withdiverse cellular functions, including stress responses. Here, we discuss arecent study by Feng et al., published in Clinical and Translational Medicine, shedding light on the novel function of HSF4 in regulating inflammation and senescence following UV exposure. The researchers observed acomplex of HSF4 and the cofactor COIL (Coilin) at R-loops–aberrant DNA-RNAhybrid structures arising from UV-induced DNA damage in human skin cells. Inthe study, they proposed the HSF4-COIL complex at R-loops as a potential therapeutic target to mitigate UV-induced skin damage.

Wet age-related macular degeneration (AMD) is a common cause of vision loss in the elderly. It is characterised by choroidal neovascularisation (CNV), caused by overexpression of vascular endothelial growth factor (VEGF), resulting in abnormal vessel proliferation. Current clinical management predominantly relies on anti-VEGF agents, which require frequent and costly injections. Clustered regularly interspaced short palindromic repeats (CRISPR) technology has emerged as a promising strategy for permanently suppressing angiogenesis by targeting the VEGF-related pathway. Increased research suggests that disrupting this pathway holds potential for preventing CNV progression. This review provides an overview of the aetiology, classification and pathophysiology of wet AMD, followed by a concise summary of current gene editing research using the CRISPR/Cas system via viral vector delivery strategies to target ocular pro-angiogenic factors, including Hif-1α, VEGF and VEGFR. The importance of timely targeting of VEGFA is emphasised and the challenges associated with gene editing therapies are also highlighted.

Meningitis, which is defined by inflammation of the meninges, is a major cause of death and morbidity worldwide. Traditional diagnostic approaches, such as imaging procedures and the study of cerebrospinal fluid, are intrusive, time consuming and sometimes non-specific. The suggested approach entails creating a biosensor based on microneedles that can detect in real time without the requirement for labels. The biosensor uses highly sensitive detection techniques to detect changes in ionic current and modulation of impedance in response to biomolecules that are of interest, such as proteins and nucleic acids, which are linked to meningitis infections. Initial studies have shown that the microneedle-based biosensor for meningitis diagnosis is both feasible and effective. When it comes to identifying bacterial and aseptic meningitis biomarkers from blood and cerebrospinal fluid (CSF) samples, the biosensor showed excellent sensitivity and specificity. This novel technique has the potential to enhance patient outcomes by facilitating prompt intervention and tailored therapy by offering a quick, safe and accurate way to distinguish between bacterial and aseptic meningitis. To maximise the biosensor's performance and confirm its therapeutic usefulness in various contexts, more investigations and advancements are necessary.

Cancer therapeutic development is the most challenging domain in cancer. Cell-based cancer therapeutics come up with promising effectiveness. This approach was also cell-modified for better targeting efficiency development. Cell engineering-based cancer therapeutic is a cutting-edge method in cancer therapy. Due to complications of this process, cost and post-treatment side effects, this phenomenon came into the question mark. In this scenario, extracellular vesicle (EVs) research introduces a cell-free cancer therapeutic approach. In the therapeutic aspect most used EVs, come from stem cells, plants, and engineered cells. Among several EVs populations, Exosomes are the most used worldwide cell-free therapeutic tool for ageing cancer. The most interesting facts about exosomes are the biocompatible, non-immunoreactive, cross-biological barrier, and non-toxic (depending on the parental cell's nature). In this article, we are exploring modified exosomes (biological or chemical) that create a remarkable outcome in cancer therapeutic development compared to engineered cell-based therapeutics. Hope, in the future, modified exosomes become an effective, affordable, and specific cancer-targeting precision medicine.

Extracellular vesicles (EVs), including exosomes, ectosomes, and apoptotic bodies, play crucial roles in cellular communication and disease processes. Among these, exosomes are particularly significant for diagnosing, and cancer (which remains a leading cause of death worldwide). Exosomes offer cutting-edge approaches in cancer nanomedicine, cancer biomarkers investigation (diagnosis and prognosis), and therapeutic. Exosomes are found in several body fluids (Blood, plasma, serum, urine, saliva, sweat, CSF, tear). It transforms the liquid biopsy method with more specificity. Exosome-based sensor (electrochemical and aptamer-based) developers were more effective and sensitive for cancer scanning. Therapeutic prospect stem cell-derived exosomes, and plant-derived exosomes become more promising. Due to its non-toxicity (depending on the source), non-immunogenic, biocompatibility and ability to cross biological membranes. Exosomes are an exciting nano-drug transporter with specificity. Current time-modified exosomes support to development of effective, efficient, and cost-effective nanomedicine against cancer. Advanced nanotechnology and exosome combining (single exosome profiling, exosome barcoding)transform cancer theranostics approaches. Exosomes introduce a new horizon of cancer nanomedicine.

Telocytes (TCs) are a new type of interstitial cell identified in multiple tissues of mammals, including the human lung, and mediate homocellular or heterocellular cell-cell communication. Acute respiratory distress syndrome (ARDS) is characterized by acute hypoxemia respiratory failure and combined with direct and indirect lung injury, which is induced by pneumonia, sepsis, burns, etc. Pulmonary fibrosis is a progressive lung disease that occurs due to increased fibrosis of lung tissue in response to chronic injury of the epithelium and gets more and more attention as a well-recognized sequela of ARDS or mechanical ventilation. However, the existing intervention measures could not prevent the progression of pulmonary fibrosis. Although the protective effect of TCs in acute lung injury had been demonstrated in both cellular and animal models in previous studies by our or other researchers, the roles of TCs mediated cell-cell communication in fibroproliferative ARDS is unclear. This review is aimed at integrating our understanding of TC-mediated cell–cell communication in lung diseases with pulmonary fibrosis after ARDS.

methyltransferase gene (DNA) methylation is a key process in epigenetic modification. This transformation leads to genomic instability that creates an impact on gene expression. DNA methylation is also involved in several mutations of tumour suppressor genes (TSGs) or proto-oncogenes, resulting in cancer (hypermethylation and hypomethylation). Hypermethylation of promoter segments in TSGs causes transcriptional silencing, whereas hypomethylation of regulatory sequence activates proto-oncogenes and retrotransposons. DNA methylation regulated by DNA methyltransferases is one of the essential epigenetic mechanisms that controls the cell cycle, cell proliferation, differentiation, apoptosis and transformation in eukaryotes, leading to genetic instability of tumour cells. Recent scientific research has highlighted that DNA methylation is a vital cancer biomarker source of several parts of body fluids that allow primary-stage cancer cell detection during clinical screening. Nowadays, epigenetic biomarkers have been introduced as a decision maker with the potential to improve cancer prognosis. DNA methylation profiling helps to determine cancer at the deep genetic level, and create high impactful cancer screening approach in the future.

Background: The brain is a central key organ of the body containing the second highest lipid content only after adipose tissue. Lipids as the main structural components of biological membranes play important roles in a vast number of biological processes within the brain such as energy homeostasis, material transport, signal transduction, neurogenesis and synaptogenesis, providing a balanced cellular environment required for proper functioning of brain cells. Lipids and their metabolism are of great physiological importance in view of the crucial roles of lipids in brain development and function. Astrocytes are the most abundant glial cells in the brain and involved in various processes including metabolic homeostasis, blood brain barrier maintenance, neuronal support and crosstalk.

Results: Disturbances in lipid metabolism and astrocytic functions may lead to pathological alterations associated with numerous neurological diseases like Alzheimer's disease (AD) recognised as the most frequent cause of dementia leading to major progressive memory and cognitive deficits as well as glioblastoma (GBM) known as the most aggressive malignant brain tumour with a poor prognosis.

Conclusions: Herein, we not only review the level and role of altered lipid metabolism in correlation with astrocytic function and astrocyte-neuron crosstalk in AD and GBM, but also discuss important lipid-related metabolites and proteins participating in possible mechanisms of pathologically dysregulated lipid metabolism, offering potential therapeutic targets in targeted molecular therapies for AD and GBM.

Background: Telocyte (TC) is a recently defined renewed cell and its dominant intercommunication with other cells displays multiple functions in tissue homeostasis and diseases. Alveolar epithelial cells and immune cells were in the lung cancer heterogeneity, progression, and metastasis, and further associated with antitumor therapeutic strategies. However, few studies focus on the roles of TCs in lung cancer.

Methods: In this article, we used the public scRNA-Seq data (including healthy control, chronic obstructive pulmonary disease, non–small cell lung cancer, lymph node metastases from non–small cell lung cancer, and systemic sclerosis–associated interstitial lung disease patients) to analyze the cellular dynamics in human lung and distinct types of TCs and their communication networks with the variety of cell types.

Results: Six subclusters of TCs were identified by expression of specific biological function markers, which demonstrated the diversity of TCs subsets in lung tissue. Further results showed TCs had communication with epithelial cells or immune cells subsets by the ligand–receptor interaction, including TIMP metallopeptidase inhibitor 1CD63, fibulin 1integrin subunit beta 1, vimentinCD44, macrophage migration inhibitory factorCD74, and amyloid beta precursor proteinCD74. Ligand–receptor interaction heterogeneity was revealed in lung tissue of healthy or diseases. Enhanced specific signals in ligandreceptor interaction were revealed, including integrin beta 1 and CD44 were appraised in the communication of TCs with epithelial cells, NK cells, NKT cells, CD4⁺ exhausted T cells, CD4⁺ memory/effector T cells, CD4⁺ naïve T cells, CD8⁺ exhausted T cells, CD8⁺ memory/effector T cells, and CD8⁺ naïve T cells. CD63, a marker identified in TCs exosomes was emphasized in our current analysis which is closely related to communication of TCs with other cell types.

Conclusion: These results will provide us with new insight into the mechanisms of TCs-dominated communication and promise therapy of TC exosomes in lung diseases.

Exosomes can be defined as extracellular vesicles, of size ranging from 30 to 150 nm, secreted from almost all kinds of cells and can also be obtained from the body fluids. Exosomes have different components depending on the type of cell from which they originate. Exosomes are capable of transporting various molecules such as proteins, nucleic acids, chemical compounds and metabolites. Experiments show that exosomes can perform important functions in cell growth, migration, differentiation, neuronal signalling, immune cell modulation. Exosomes can also be used in cancer therapy, as they can be key players in intercellular communication and signalling. Experiments have also demonstrated that exosomes are chief players in viral persistence and dissemination. The reasons why application of exosomes in targeted therapy is gaining significance are their ability to initiate cellular responses, high tolerance levels in host cells and high efficiency in penetrating other cells. Exosomes can be used both as therapeutic agents and escorts of drugs. Even though numerous studies have been performed in search of better anticancer therapies, most of them have come to a halt due to the failure in achieving a therapy best in all parameters. However, both in vitro and in vivo application of exosomes in diagnosis and therapy of tumours are prospective and has a future.

Objective: Screening and early diagnosis of gastric cancer (GC) are crucial for improved prognosis. However, gastroscopic screening is not feasible in large populations due to its high cost and invasive nature. The detection of circulating cell-free DNA (cfDNA) provides an attractive minimally-invasive alternative for screening of GC. In this systematic review and meta-analysis, we evaluate the diagnostic value of cfDNA-based markers for GC, including the detection of total concentration, mutations, and methylation alterations.

Methods: We performed a systematic search of four literature databases (PubMed, Embase, Web of Science, and Cochrane Library) for articles published before November 2022. The revised tool for the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used to evaluate the quality of included studies. PROSPERO registration number: CRD42021210830.

Results: A total of 15 original articles involving 2849 individuals were included in this meta-analysis, comprising five studies on concentration, nine studies on methylation alterations, and one study on mutation biomarkers of cfDNA. Among these studies, seven selected early-stage GC subjects. For the diagnoses of overall stages and early-stage GC, the pooled sensitivities with 95% confidence interval were 0.74 (0.66–0.82) and 0.64 (0.51–0.76), and the pooled specificities were 0.92 (0.84–0.96) and 0.94 (0.87–0.98) with summary areas under the curve (SAUCs) of 0.89 (0.86–0.91) and 0.86 (0.83–0.89), respectively.

Conclusions: This meta-analysis suggests that cfDNA-based biomarkers show diagnostic value for GC early detection.

Background: Chronic back pain affected 619 million people globally in 2020 which accounts for a heavy disease burden causing tremendous productivity losses. Current therapies including ibuprofen, duloxetine, and opioids might cause side effects and even severe drug use disorders. Therefore, a non-pharmacologic therapy with better or equivalent efficacy and fewer side effects is needed.

Methods: We did a multi-center, single-blinded, randomized, positive drug controlled, clinical trial. Patients with chronic back pain in moderate severity were randomized into receiving hot stone massage or flurbiprofen plaster group. Both interventions were 2 weeks with a follow-up of 4 weeks. The primary outcome was the change in the score of the Global Pain Scale (GPS) from baseline to week 2. Secondary outcomes included Numerical Rating Scale (NRS), Chronic Pain Acceptance Questionnaire (CPAQ), Pain Self-Efficacy Questionnaire (PSEQ), Hospital Anxiety and Depression Scale (HADS), and Short Form-36 (SF36) from baseline to week 2 and week 6. Exploratory outcome assessment included the muscle thickness measured by ultrasound. Any adverse event was monitored throughout the study period.

Results: A total of 120 patients were enrolled in this trial. At 2 weeks GPS decreased significantly in the hot stone massage group compared to the flurbiprofen group (difference between groups = -8.1 points, 95% confidence interval [CI] -15.8 to -0.3, p = 0.047). Moreover, hot stone massage also showed more improvement at 2 weeks compared to flurbiprofen, including NRS (-0.5 points, 95% CI -1.0 to -0.1, p = 0.029), PSEQ (5.4 points, 95% CI 0.5 to 10.2, p = 0.030), and mental component of Short Form-36 (SF-36) (1.7 points, 95% CI 0.4 to 2.9, p = 0.010), but not in CPAQ (p = 0.131), HADS (p = 0.303 for depression, p = 0.399 for anxiety), or SF-36 (p = 0.129 for physical component, p = 0.246 for social component, p = 0.076 for fatigue component). A total of two participants in the hot stone massage group reported mild pain on skin surface when receiving the procedure at the first intervention session.