Exosomes (EXOs) are a subgroup of extracellular vesicles (EVs) that contain numerous biologically active molecules. They exhibit an essential mode of cell communication, primarily between distinct cell populations, for the maintenance of tissue homeostasis and coordination of adaptive responses to various stresses. These intercellular communications are vital for the complex, multicellular cardiovascular system. In the last ten years, their potential role as effective tissue-to-tissue communicators has received increasing attention in cardiovascular physiology and pathology. There is growing evidence that repair of the heart and regeneration can be promoted by EXOs derived from cardiomyocytes or stem/progenitor cells. However, the underlying mechanisms remain unclear. EVs derived from different stem/progenitor cell populations have been used as cell-free therapies in different preclinical models involving cardiovascular diseases and have shown promising results. In this review, we have summarized the recent developments in EXOs research, the impact of EXOs derived from different cells on the cardiovascular system, their potential therapeutic roles as well as new diagnostic biomarkers, and the possible clinical translational outcomes.

The development of human papillomavirus (HPV) vaccines has made substantive progress, as represented by the approval of five prophylactic vaccines since 2006. Generally, the deployment of prophylactic HPV vaccines is effective in preventing newly acquired infections and incidences of HPV-related malignancies. However, there is still a long way to go regarding the prevention of all HPV infections and the eradication of established HPV infections, as well as the subsequent progression to cancer. Optimizing prophylactic HPV vaccines by incorporating L1 proteins from more HPV subtypes, exploring adjuvants that reinforce cellular immune responses to eradicate HPV-infected cells, and developing therapeutic HPV vaccines used either alone or in combination with other cancer therapeutic modalities might bring about a new era getting closer to the vision to get rid of HPV infection and related diseases. Herein, we summarize strategies for the development of HPV vaccines, both prophylactic and therapeutic, with an emphasis on the selection of antigens and adjuvants, as well as implications for vaccine efficacy based on preclinical studies and clinical trials. Additionally, we outline current cutting-edge insights on formulation strategies, dosing schedules, and age expansion among HPV vaccine recipients, which might play important roles in addressing barriers to vaccine uptake, such as vaccine hesitancy and vaccine availability.

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CT1812 is a novel, brain penetrant small molecule modulator of the sigma-2 receptor (S2R) that is currently in clinical development for the treatment of Alzheimer\'s disease (AD). Preclinical and early clinical data show that, through S2R, CT1812 selectively prevents and displaces binding of amyloid beta (Aβ) oligomers from neuronal synapses and improves cognitive function in animal models of AD. SHINE is an ongoing phase 2 randomized, double-blind, placebo-controlled clinical trial (COG0201) in participants with mild to moderate AD, designed to assess the safety and efficacy of 6 months of CT1812 treatment. To elucidate the mechanism of action in AD patients and pharmacodynamic biomarkers of CT1812, the present study reports exploratory cerebrospinal fluid (CSF) biomarker data from 18 participants in an interim analysis of the first set of patients in SHINE (part A). Untargeted mass spectrometry-based discovery proteomics detects >2000 proteins in patient CSF and has documented utility in accelerating the identification of novel AD biomarkers reflective of diverse pathophysiologies beyond amyloid and tau, and enabling identification of pharmacodynamic biomarkers in longitudinal interventional trials. We leveraged this technique to analyze CSF samples taken at baseline and after 6 months of CT1812 treatment. Proteome-wide protein levels were detected using tandem mass tag-mass spectrometry (TMT-MS), change from baseline was calculated for each participant, and differential abundance analysis by treatment group was performed. This analysis revealed a set of proteins significantly impacted by CT1812, including pathway engagement biomarkers (i.e., biomarkers tied to S2R biology) and disease modification biomarkers (i.e., biomarkers with altered levels in AD vs. healthy control CSF but normalized by CT1812, and biomarkers correlated with favorable trends in ADAS-Cog11 scores). Brain network mapping, Gene Ontology, and pathway analyses revealed an impact of CT1812 on synapses, lipoprotein and amyloid beta biology, and neuroinflammation. Collectively, the findings highlight the utility of this method in pharmacodynamic biomarker identification and providing mechanistic insights for CT1812, which may facilitate the clinical development of CT1812 and enable appropriate pre-specification of biomarkers in upcoming clinical trials of CT1812.

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BACKGROUND: Although nontuberculous mycobacterial (NTM) infection is a common cause of pulmonary disease worldwide, few studies have focused on epidemiological and therapeutic factors related to NTM cases in Anhui Province, China. This retrospective study aimed to identify aetiological and clinical factors, and treatment outcomes of patients with NTM pulmonary disease (NTMPD) in Anhui.
METHODS: Retrospective clinical data obtained from medical records of NTMPD patients seeking care at Anhui Chest Hospital from July 2019 to June 2022 were analyzed. Treatment outcomes were compared between two patient groups: one receiving a standardised NTM treatment regimen and the other receiving precision treatment regimens.
RESULTS: Genotypic analysis of 672 clinical NTMPD-associated isolates revealed that most were Mycobacterium intracellulare, while drug-susceptibility test results demonstrated diverse antibiotic resistance profiles for these isolates. Cough was the most common symptom for 101 NTMPD patients. After patients of both groups received treatment, symptoms improved, sputum culture conversion was observed for some patients, imaging findings stabilised; however, no statistically significant intergroup differences in treatment outcomes were found.
CONCLUSIONS: In this study, M. intracellulare was the predominant NTM species identified in isolates obtained from NTMPD patients. Drug resistance profiles of our patient isolates were complex, highlighting the need for administration of timely, more effective, standardised treatments for patients with NTMPD in Anhui Province, China.

Melatonin, a versatile hormone produced by the pineal gland, has garnered considerable scientific interest due to its diverse functions. In the eye, melatonin regulates a variety of key processes like inhibiting angiogenesis by reducing vascular endothelial growth factor levels and protecting the blood-retinal barrier (BRB) integrity by enhancing tight junction proteins and pericyte coverage. Melatonin also maintains cell health by modulating autophagy via the Sirt1/mTOR pathways, reduces inflammation, promotes antioxidant enzyme activity, and regulates intraocular pressure fluctuations. Additionally, melatonin protects retinal ganglion cells by modulating aging and inflammatory pathways. Understanding melatonin\'s multifaceted functions in ocular health could expand the knowledge of ocular pathogenesis, and shed new light on therapeutic approaches in ocular diseases. In this review, we summarize the current evidence of ocular functions and therapeutic potential of melatonin and describe its roles in angiogenesis, BRB integrity maintenance, and modulation of various eye diseases, which leads to a conclusion that melatonin holds promising treatment potential for a wide range of ocular health conditions.

Primary liver cancer is one of the most common malignant tumors. A liver tumor is defined as a large cancer when its diameter is ≥5 cm. Resection surgical therapy can be performed only on a small portion of large cancers because of its own features. As a result, non-resection surgical therapy has become a hot and difficult issue of widespread concern. In recent years, with the development of ablation technology, research on the use of ablation alone and ablation combined with other modalities for the treatment of large liver cancer has continued to deepen, and good clinical results have been achieved. Although there are many reports on ablation treatment for large liver cancer, there are currently no standardized treatment guidelines, and there are still controversies about treatment strategies. This article reviews the development of ablation therapy, the current status of single and combined ablation therapy, the prevention of related complications, and other aspects of large liver cancer.
原发性肝癌是常见的恶性肿瘤之一，当肿瘤直径≥5 cm时被定义为大肝癌，大肝癌因其自身特点，只有少部分能接受切除手术治疗，因而其非切除手术治疗成为广为关注的热点和难点问题。近年随着消融技术的发展，单独应用消融和消融联合其他方式治疗大肝癌的研究不断深入，取得了较好的临床效果。虽然消融治疗大肝癌的报道很多，但目前并没有规范的治疗指南，在治疗策略方面仍存在争议，现就消融治疗大肝癌的发展、单独及联合消融治疗大肝癌的现状及其相关并发症的防范等方面进行综述。.

The World Health Organization (WHO) released the Global Health Sector Strategy 2016, which explicitly proposes a 90% reduction in the new hepatitis B virus (HBV) infection rate and a 65% reduction in HBV-related mortality by 2030. However, at present, there are still 296 million chronic hepatitis B virus-infected patients worldwide, and nearly 900,000 patients die every year from cirrhosis and liver cancer caused by HBV infection. Antiviral treatment for chronic hepatitis B virus infection can effectively inhibit HBV replication, reduce liver inflammation and necrosis, effectively block and reverse liver fibrosis, and even early cirrhosis, thereby lowering cirrhosis-related complications, liver cancer, and liver disease-related mortality. Although the domestic and foreign guidelines have gradually eased antiviral treatment indications for chronic hepatitis B, there are still a considerable number of chronic hepatitis B patients with nonconformity who cannot receive antiviral treatment because they do not meet the existing standards, resulting in the progression of more severe diseases. This study analyzed the prevalence of hepatitis B, the therapeutic effect of antiviral drugs, domestic and international guideline treatment standards, the assessment of key indicators changes in the guidelines, comprehensively considered the coverage rate and treatment standards for antiviral treatment, and explored the changes in disease burden and cost-effectiveness following increasing the coverage rate and reducing treatment thresholds in order to achieve the global strategic goal of eliminating hepatitis B as soon as possible as a public health threat.
世界卫生组织于2016年发布《全球卫生部门战略》，明确提出在2030年实现降低90%的HBV新发感染率和降低65%的HBV相关死亡率。而目前全球的慢性HBV感染者仍有2.96亿，每年有近90万人死于HBV感染所致肝硬化及肝癌等。慢性HBV感染者抗病毒治疗可以有效抑制HBV复制，减轻肝脏炎症坏死、有效阻断和逆转肝纤维化甚至早期肝硬化，从而减少肝硬化相关并发症、降低肝癌和肝病相关死亡率。尽管国内外指南对于慢性乙型肝炎抗病毒治疗的适应证均已逐步放宽，但仍有相当数量的慢性乙型肝炎患者因不符合现有标准而未能接受抗病毒治疗，因而导致进展为更严重的疾病。通过对乙型肝炎流行病学、抗病毒药物治疗效果及国内外的指南治疗标准进行分析，判断指南中关键指标变化，综合考虑抗病毒治疗的覆盖率及治疗标准，探索提高覆盖率及治疗阈值降低后疾病负担变化和成本效果，以期尽早实现消除乙型肝炎作为公共卫生危害的全球战略目标。.

Hepatitis B is a major infectious disease that seriously endangers the health of the people of China. Patients with hepatitis B have a large base in our country, and the core indicators such as detection and antiviral treatment ratio are far from the real goal of eliminating the public health threat of uiral hepatitis.Notably, the chronic hepatitis B prevention and control system lacks a wide targeted strategies. This paper systematically analyzes our country\'s main successful experience with AIDS prevention and control and, on that basis, proposes the ideas and strategic paths for the construction of a chronic hepatitis B prevention and control system, analyzes and discusses the current difficulties and problems in prevention and control, and looks forward to future prevention and control efforts.
乙型肝炎是严重危害我国人民群众健康的重大传染性疾病，我国乙型肝炎患者基数大，检测发现和抗病毒治疗比例等核心指标距离实现消除病毒性肝炎作为公共卫生危害目标差距较大，缺乏针对性的慢性乙型肝炎防控体系和防控策略、措施。该文系统分析了我国艾滋病防控的主要成功经验，在此基础上提出了我国慢性乙型肝炎防控体系建设和防控策略的思路和路径，对目前存在的防控难点及问题进行了分析和探讨，并对未来防控工作进行了展望。.