In this comprehensive review, we delve into the evolution of drug delivery systems in reproductive medicine with a focus on the emerging role of exosomes, a class of extracellular vesicles. Exosomes offer unique advantages in overcoming these challenges due to their inherent biocompatibility, stability, and ability to facilitate targeted delivery. This review provides a detailed examination of exosome biogenesis and their function in cellular communication, setting the stage for understanding their potential as drug delivery vehicles. We explore the mechanisms through which exosomes can be loaded with small molecule drugs and the benefits they offer over synthetic nanoparticles. The review highlights groundbreaking case studies that illustrate the successful application of exosome-mediated drug delivery in reproductive health, including enhancing fertility treatments, supporting gamete and embryo development, and facilitating maternal-fetal communication. This study aims to provide a precise understanding of how exosomal drug delivery can revolutionize treatments for reproductive health disorders, paving the way for future therapeutic applications. Lastly, we touch upon the promising therapeutic implications of exosomal delivery for proteins and genes, offering a window into future treatments for reproductive health disorders.

Objective To establish the reference intervals of neutrophil to lymphocyte ratio(NLR),mono-cyte to lymphocyte ratio(MLR)and platelet to lymphocyte ratio(PLR)in different genders and age groups in northern Chinese adults.Methods The data were analyzed according to the Clinical and Laboratory Stand-ards Institute C28-A3.Outliers were checked and judged according to the Dixon method.Subgroups were di-vided according to gender or age factors,and reference intervals were established for different subgroups.Ref-erence intervals were expressed as two-sided 95％percentiles.Results The reference intervals of NLR,MLR and PLR were 0.90-3.82,0.09-0.33 and 71.20-246.87,respectively.The results showed that NLR and PLR in men were lower than those in women(P＜0.001),while MLR in men was significantly higher than that in women(P＜0.001).Linear trend plots showed that NLR,MLR and PLR changed significantly in dif-ferent genders and age groups.In men,NLR and MLR increased with age,while PLR gradually increased and reached the peak before 50 years old,and gradually decreased after 50 years old.In women,NLR and MLR showed the lowest values at 50-＜60 years old,while PLR reached the peak at about 50 years old.The refer-ence intervals established by the model set were verified,and the percentages beyond the reference intervals were less than 10％in different genders and age groups.Conclusion The reference intervals of NLR,MLR and PLR in different genders and age groups of healthy adults in northern China are established in the study.

This paper introduced the Quality Assessment of Diagnostic Accuracy Studies-Comparative (QUADAS-C), illustrated the comparison with the QUADAS-2, and using QUADAS-C together with QUADAS-2 to present QUADAS-C results through systematic reviews. Like the domain for QUADAS-2, QUADAS-C retained four domains, including patient selection, index test, reference standard, flow, and timing, and comprised additional questions for each QUADAS-2 part. Unlike the QUADAS-2 tool, the starting question of each domain for QUADAS-C was designed to summarize the risk of biased information captured by QUADAS-2. QUADAS-C only dealt with the risk of bias but did not include the part of concerns regarding applicability. The answers to signaling questions for each domain of QUADAS-C would lead to a 'low''high' or 'unclear' risk of biased judgment for the original study.

Wake up ischemic stroke (WUIS),also known as awakening stroke,refers to patients with no new stroke symptoms during sleep,but after waking up,the patients or witness who found the acute cerebral infarction with stroke performance.The key to the treatment of acute ischernic stroke is to effectively restore reperfusion within the time window.The original intravenous recombinant tissue-type plasminogen activator (rt-PA) thrombolytic therapy,is widely recognized as an effective treatment method of choice for 4.5h onset of acute ischemic stroke reperfusion.Because the exact onset time of WUIS is unclear and limited by current scientific and technical levels,intravenous thrombolysis may lead to an increased risk of intracranial hemorrhage.Therefore,the American Heart Association and the American Stroke Association (AHA/ASA) were included in the "Intravenous Thrombolysis".Intravenous thrombolysis is not recommended in the Standard Scientific Statement.Patients who may be suitable for thrombolytic therapy are not able to obtain thrombolytic therapy,resulting in poor clinical prognosis.In recent years,with the further development of relevant clinical research and the rapid development of imaging technology,the latest research found that multi-mode imaging examination is safe and effective for intravenous thrombolytic therapy in patients with poststroke stroke.Multi-mode imaging studies help screening patients with acute reperfusion therapy,so that part of WUIS patients will benefit from the acute reperfusion therapy.This article reviews and summarizes the literature findings of WUIS in recent years.The pathophysiological changes,clinical features and imaging changes of patients with WUIS and non-WUIS are almost unanimously.Early CT and MRI examinations can help to extend acute stroke treatment to patients with WUIS.At present,for this type of patients,there are great research progress in the formulation and implementation of clinical treatment strategies.This article will briefly summarize the research progress and treatment status of WUIS.

The induced pluripotent stem cells (iPSCs), derived by ectopic expression of reprogramming factors in somatic cells, can potentially provide unlimited autologous cells for regenerative medicine. In theory, the autologous cells derived from patient iPSCs should be immune tolerant by the host without any immune rejections. However, our recent studies have found that even syngeneic iPSC-derived cells can be immunogenic in syngeneic hosts by using a teratoma transplantation model (Nature 474:212-215, 2011). Recently two research groups differentiated the iPSCs into different germ layers or cells, transplanted those cells to the syngeneic hosts, and evaluated the immunogenicity of those cells. Both of the two studies support our conclusions that some certain but not all tissues derived from iPSCs can be immunogenic, although they claimed either "negligible" or "lack of" immunogenicity in iPSC derivatives (Nature 494:100-104, 2013; Cell Stem Cell 12:407-412, 2013). To test the immunogenicity of clinically valuable cells differentiated from human iPSCs are emergently required for translation of iPSC technology to clinics.
Animals ; Cell Cycle Proteins ; metabolism ; Cell Transplantation ; methods ; Graft Rejection ; immunology ; Induced Pluripotent Stem Cells ; immunology ; transplantation ; Membrane Proteins ; metabolism ; Mice, Knockout ; Teratoma ; immunology ; metabolism