BACKGROUND:Extracellular vesicles mediate intercellular signal transduction through the proteins,nucleic acids,and lipids they carry,thereby influencing the function of target cells.This vesicle-mediated communication mechanism is involved in regulating female reproductive development.OBJECTIVE:To summarize and analyze the regulatory roles of extracellular vesicle-mediated intercellular communication in female reproductive development.METHODS:A search was conducted in the PubMed database using the search terms"extracellular vesicles,exosomes,reproduction,maternal-embryo communication,maternal-fetal crosstalk,embryo implantation,endometrium,oviduct,follicle."The initial screening was carried out by reading the titles and abstracts of the literature,and then the literature with poor relevance to the research purpose,outdated content,and duplication was excluded according to the inclusion and exclusion criteria.Ultimately,69 relevant articles were included for comprehensive analysis.RESULTS AND CONCLUSION:Extracellular vesicles play a crucial role in key processes of female reproductive development,from folliculogenesis to implantation.(1)Extracellular vesicles mediate intercellular communication within the follicle,particularly the interactions between oocytes and follicular cells,which are essential for follicle development and maturation.(2)Extracellular vesicles and their contents facilitate interactions between the embryo and the fallopian tube,influencing the trajectory of embryonic development.(3)Extracellular vesicles and their contents promote implantation by mediating bidirectional communication between the embryo and the endometrium.Uterine-derived extracellular vesicles regulate processes such as embryo adhesion,invasion,and decidualization,while embryo-derived extracellular vesicles modulate endometrial receptivity,convey embryonic signals,and adjust the endometrial microenvironment.Studying the roles of extracellular vesicles in female reproductive development can provide valuable insights into the mechanisms of infertility and support the development of new therapeutic strategies.

BACKGROUND:Extracellular vesicles mediate intercellular signal transduction through the proteins,nucleic acids,and lipids they carry,thereby influencing the function of target cells.This vesicle-mediated communication mechanism is involved in regulating female reproductive development.OBJECTIVE:To summarize and analyze the regulatory roles of extracellular vesicle-mediated intercellular communication in female reproductive development.METHODS:A search was conducted in the PubMed database using the search terms"extracellular vesicles,exosomes,reproduction,maternal-embryo communication,maternal-fetal crosstalk,embryo implantation,endometrium,oviduct,follicle."The initial screening was carried out by reading the titles and abstracts of the literature,and then the literature with poor relevance to the research purpose,outdated content,and duplication was excluded according to the inclusion and exclusion criteria.Ultimately,69 relevant articles were included for comprehensive analysis.RESULTS AND CONCLUSION:Extracellular vesicles play a crucial role in key processes of female reproductive development,from folliculogenesis to implantation.(1)Extracellular vesicles mediate intercellular communication within the follicle,particularly the interactions between oocytes and follicular cells,which are essential for follicle development and maturation.(2)Extracellular vesicles and their contents facilitate interactions between the embryo and the fallopian tube,influencing the trajectory of embryonic development.(3)Extracellular vesicles and their contents promote implantation by mediating bidirectional communication between the embryo and the endometrium.Uterine-derived extracellular vesicles regulate processes such as embryo adhesion,invasion,and decidualization,while embryo-derived extracellular vesicles modulate endometrial receptivity,convey embryonic signals,and adjust the endometrial microenvironment.Studying the roles of extracellular vesicles in female reproductive development can provide valuable insights into the mechanisms of infertility and support the development of new therapeutic strategies.

ObjectiveTo explore the possible mechanisms of Wenyang Huazhuo Formula （温阳化浊方， WHF） in improving reproductive aging from the perspective of the ovarian mechanical microenvironment. MethodsThe experiment included five groups， 3-month group （20 female mice at 3 months of age）， 6-month group （20 female mice at 6 months of age）， 6-month + WHF group （20 female mice at 5 months of age treated with WHF）， 9-month group （20 female mice at 9 months of age）， and 9-month + WHF group （20 female mice at 8 months of age treated with WHF）. The 6-month + WHF group and 9-month + WHF group were orally administered WHF 41.2 g/（kg·d） once daily for 4 consecutive weeks. The other three groups received no intervention. Reproductive hormone levels were measured by ELISA. HE staining was used to count the numbers of various stages of follicles. Ovarian hyaluronic acid （HA） content and collagen fiber content were measured to evaluate the ovarian mechanical microenvironment. Superovulation was performed to observe the number of eggs obtained， as well as the number of offspring and birth weight to assess fertility. The in vitro fertilization and blastocyst culture of oocytes from female offspring in each group were observed to evaluate the effect of WHF on offspring reproductive potential. ResultsCompared with the 3-month group， the 6-month group and 9-month group showed significantly decreased serum levels of gonadotropin-releasing hormone （GnRH）， follicle-stimulating hormone （FSH）， and luteinizing hormone （LH）， decreased ovarian collagen content， and reduced numbers of primordial and secondary follicles. In contrast， the numbers of primary follicles， antral follicles， and atretic follicles increased. The levels of anti-Müllerian hormone （AMH）， ovarian HA content， and the fertilization rate， cleavage rate， and blastocyst formation rate of oocytes from offspring were significantly lower （P＜0.05）. Compared with the 6-month group， the 6-month + WHF group showed significantly reduced serum levels of GnRH， FSH， and LH， with a significant decrease in primary follicles， antral follicles， and atretic follicles as well as increase of AMH levels， ovarian HA content， number of primordial and secondary follicle， egg count， and offspring birth weight （P＜0.05）. Compared with the 9-month group， the 9-month + WHF group exhibited reduced GnRH， FSH， and collagen fiber content， as well as reduced number of primary follicles， antral follicles， and atretic follicles. However， AMH levels， ovarian HA content， number of primordial and secondary follicle， egg count， offspring numbers， birth weight， fertilization rate， cleavage rate， and blastocyst formation rate of oocytes from offspring all significantly increased （P＜0.05）. ConclusionWHF can significantly improve the ovarian reserve， fertility， and reproductive potential in offspring during reproductive mid-life and late-life stages. Its effect may be related to the remodeling of the mechanical microenvironment of aging ovaries. Moreover， the effect on the mechanical microenvironment remodeling of late-stage ovaries and the improvement of the offspring reproductive potential is more significant.

AIM: To explore the efficacy of bilateral lateral rectus recession in the treatment of basic intermittent exotropia. METHODS: A prospective study was conducted on 104 patients with basic intermittent strabismus admitted to our hospital from October 2022 to October 2023, patients were randomly divided into a study group of 52 cases and a control group of 52 cases using a random number ranking method. The control group received unilateral recess-resect, while the study group received bilateral lateral rectus recession, the differences in surgical success rate, postoperative strabismus, and postoperative exotropia drift were compared between two groups.RESULTS: There was no statistically significant difference between the two groups at 1 d, 1, 3, and 6 mo after surgery(all P>0.05). The strabismus in the 6 m and 33 cm eye positions at 1, 3, and 6 mo after surgery were lower than those at 1 d after surgery(all P<0.05). However, there was no statistically significant difference in the strabismus in the 6 m and 33 cm eye positions between the two groups at 1 d, 1, 3, and 6 mo after surgery(all P>0.05), and there was statistical significant difference between the two groups in exotropia drift at different postoperative time points(all P<0.05). The exotropia drift of both groups increased at 3 and 6 mo after surgery compared to 1 mo after surgery, and the exotropia drift at 6 mo after surgery was greater than that at 3 mo after surgery(all P<0.05). However, the exotropia drift of the study group at 3 and 6 mo after surgery was lower than that of the control group(all P<0.001). CONCLUSION: Bilateral lateral rectus recession for the treatment of basic-type intermittent exotropia effectively reduces the amount of postoperative exotropia drift, and it has better long-term stability.

Objective: To explore the development history trends and research hotspots in children and adolescent overweight and obesity studies, so as to provide a basis for conducting scientific research in related fields. Methods: Relevant literature were retrieved from CNKI, WanFang Data Knowledge Service Platform, VIP Chinese Journal Service Platform, China Biomedical Literature Service System, Web of Science Core Collection and PubMed database from January 1980 to September 2024, and knowledge graph was constructed by using CiteSpace visualization software to explore and analyze. Results: A total of 9 108 articles were retrieved (5 197 in Chinese and 3 911 in English). From 1980 to 2024, the number of publications in the field of overweight and obesity research in children and adolescents showed an upward trend. Keyword cooccurrence analysis showed that body fat percentage (intermediary centrality:0.69), body mass index (intermediary centrality:0.50) and physical activity (intermediary centrality:0.13) were the bridge keywords connecting the research field. The keyword clustering results showed that coexistence outcomes of multiple diseases such as cardiovascular metabolic diseases and psychological disorders, as well as intervention plans based on family, school and community became research hotspots. The evaluation of the effects of highintensity interval training and emerging weight loss interventions such as electronic games gradually became a new trend in research. Conclusion Influencing factors, coexistence outcomes of multiple diseases, and the application and evaluation of intervention remain key research focuses in children and adolescent overweight/obesity studies.

Tissue-resident memory T cells （T_RM cells） are a subset of memory T cells that reside in tissues， exhibit tissue specificity， and do not recirculate. When potential hazards threaten the liver， such as pathogen invasion （bacteria， viruses， etc.） and excessive autoimmune responses， T_RM cells are essential as the first line of immune defense， playing an important role in viral hepatitis， autoimmune liver disease， metabolic dysfunction-associated fatty liver disease， liver cirrhosis， and liver transplantation. Here， we present the immunophenotypes of T_RM cells in the liver and their surface markers and transcriptional profiles， aiming to clarify the role of T_RM cells in chronic liver diseases and explore their potential function as therapeutic targets in immunotherapy.

Objective To investigate the effects of hyaluronic acid and proteoglycan-linked protein 1 (HAPLN1) secreted by synovial fibroblasts (FLS) on the polarization of macrophages (Mϕ) in rheumatoid arthritis (RA). Methods Human monocytic leukemia cells (THP-1) were differentiated into Mϕ, which were subsequently exposed to recombinant HAPLN1 (rHAPLN1). RA-FLS were transfected separately with HAPLN1 overexpression plasmid (HAPLN1^OE) or small interfering RNA targeting HAPLN1 (si-HAPLN1), and then co-cultured with Mϕ to establish a co-culture model. The viability of Mϕ was assessed using the CCK-8 assay, and the proportions of pro-inflammatory M1-type and anti-inflammatory M2-type Mϕ were analyzed by flow cytometry. Additionally, the expression levels of inflammatory markers, including interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), and inducible nitric oxide synthase (iNOS), were quantified using quantitative real-time PCR and Western blot analysis. Results The viability of Mϕ was increased in the rHAPLN1 group compared to the control group. Furthermore, both the M1/Mϕ ratio and inflammatory factor levels were elevated in the rHAPLN1 and HAPLN1^OE groups. In contrast, the si-HAPLN1 group exhibited a decrease in the M1/Mϕ ratio and inflammatory factor expression. Notably, the introduction of rHAPLN1 in rescue experiments further promoted Mϕ polarization towards the M1 phenotype. Conclusion HAPLN1, secreted by RA fibroblast-like synoviocytes (RA-FLS), enhances Mϕ polarization towards the M1 phenotype.
Humans ; Arthritis, Rheumatoid/genetics* ; Macrophages/immunology* ; Fibroblasts/metabolism* ; Phenotype ; Extracellular Matrix Proteins/genetics* ; Proteoglycans/genetics* ; Synovial Membrane/cytology* ; Tumor Necrosis Factor-alpha/genetics* ; Interleukin-1beta/genetics* ; Nitric Oxide Synthase Type II/genetics* ; Cell Differentiation ; Coculture Techniques ; THP-1 Cells

Objective:To analyze the clinical features and prognosis of acute B lymphoblastic leukemia (B-ALL) children carrying a TCF3: : PBX1 fusion gene and to evaluate the prognostic value of this gene.Methods:Retrospective cohort study.A total of 2 164 B-ALL children aged 0-18 years diagnosed and treated at 19 pediatric centers from October 2016 to June 2022 were enrolled.They were divided into the positive group and the negative group according to whether they carried a TCF3: : PBX1 fusion gene.The clinical characteristics, treatment response, adverse reactions, and prognosis of the 2 groups of patients were analyzed.The rank sum and Kruskal-Wallis tests were used to compare two and more than two groups of numerical variables, respectively.Fisher′s exact test was used to compare categorical variables.Results:Among the 2 164 patients, 116 (5.4%) were TCF3: : PBX1 positive, of which 70 patients were female, accounting for 60.3%.There were 840 female patients in the TCF3: : PBX1-negative group, accounting for 41.0%.There was a significant difference in the ratio of females between the TCF3: : PBX1-positive and TCF3: : PBX1-negative groups ( P<0.001).No significant difference was observed in age of onset between the two groups( P>0.05).The proportion of bone marrow naive cells [54.00 (14.00, 76.50)% vs.29.00 (3.00, 68.00)%], white blood cell counts [25.30 (10.46, 60.94)×10 9/L vs.9.03 (4.38, 30.73)×10 9/L] and hemoglobin counts [82.00(63.00, 101.00) g/L vs.74.00(60.00, 90.00) g/L] in the TCF3: : PBX1-positive group were significantly higher than those in the negative group at the onset (all P<0.05).In terms of treatment response, the proportion of peripheral blood naive cells on Day 8 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group [2.00 (0, 9.00)% vs.0 (0, 2.00)%, P<0.001].The proportion of minimal residual disease <0.1% on Day 15 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group ( P=0.038).There were no significant differences in cumulative recurrence rate, treatment-related mortality (TRM), and overall survival (OS) between the TCF3: : PBX1-positive group and TCF3: : PBX1-negative group (all P>0.05).The cumulative recurrence risk of TCF3: : PBX1-positive patients was 9.646 times higher than that of ETV6: : RUNX1-positive patients with better prognosis( HR=9.646, 95% CI: 1.026-90.700, P=0.047).There were no significant differences in TRM and OS between TCF3: : PBX1-positive and ETV6: : RUNX1-positive patients (all P>0.05).A significant enrichment of PAX5 mutations was detected in TCF3: : PBX1-positive patients.Among the 7 high-risk TCF3: : PBX1-positive patients in a single center, 4 patients had PAX5 mutations, and this proportion was significantly higher than that in other patients ( P<0.001). Conclusions:B-ALL children carrying a TCF3: : PBX1 fusion gene have a high remission rate and good long-term prognosis after intensive chemotherapy.It is suggesting that TCF3: : PBX1-positive B-ALL patients should be rated at intermediate risk to receive intensive chemotherapy.

During decidualization, lactic acid is produced and accumulated in large amounts, becoming a prominent feature of the decidual microenvironment. Lactic acid not only serves as a key product in metabolic pathways, participating in rapid energy generation and conversion, but also influences cellular functional states by regulating the acid-base balance of the microenvironment. Furthermore, as a signaling molecule, lactic acid plays a central role in regulating decidual immune metabolism, promoting decidual angiogenesis, and facilitating trophoblast invasion, all of which are crucial for embryo implantation. In recent years, the role of lactic acid in epigenetics has also gradually emerged, with lactylation modifications involved in regulating gene expression and maintaining the homeostasis of the decidual microenvironment. This article will delve into the specific roles of lactic acid in the decidual microenvironment, aiming to provide new perspectives and theoretical foundations for the study of pregnancy-related diseases.

Decreased endometrial receptivity is a critical factor contributing to the decline in fertility among women of advanced age. With the increase of age, the endometrium exhibits diminished hormonal responsiveness, a phenomenon known as inflammaging, and an imbalance in immune cell populations. These changes impede the processes of endometrial epithelial-mesenchymal transition and decidualization, thereby negatively impacting embryo implantation and reducing overall fertility potential. Furthermore, adverse lifestyle choices, exposure to environmental factors, inflammatory conditions, and repeated interventions within the uterine cavity can result in pathological aging of the endometrium that does not align with its chronological age. This misalignment may be associated with the emergence of various reproductive disorders, even in younger women. This paper seeks to investigate the relationship between pathological aging of the endometrium and reproductive disorders, particularly in the context of embryo implantation, with the aim of providing new insights into the pathogenesis, clinical diagnosis, and treatment of reproductive disorders.