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reading the titles and abstracts of the literature,and then the literature with poor relevance to the research purpose,outdated content,and duplication was excluded according to the inclusion and exclusion criteria.Ultimately,69 relevant articles were included for comprehensive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.

Objective:To study the clinical outcome of palmar approach to on-top plasty in the treatment of unequal radial polydactyly.Methods:A retrospective analysis was conducted on patients with unequal radial polydactyly in which neither thumb duplicates possess both well-developed proximal and distal components. All the patients underwent palmar approach to on-top plasty between September 2013 and September 2023 at Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine and Shanxi Children’s Hospital. At the final follow-up, the active flexion-extension range of motion of the first metacarpophalangeal and interphalangeal joints was measured, along with grip and pinch strength. The Vancouver scar scale was used to assess scar formation (total score 0-15, with higher scores indicating more severe scarring). Additionally, the pediatric quality of life inventory (total score 0-100, with higher scores indicating better quality of life, evaluated by the children themselves or by their parents/guardians on their behalf) and the satisfaction questionnaire (total score ranges from 1 to 5, with higher scores indicating greater satisfaction) were used to assess the patients’ daily quality of life and parents’satisfaction.Results:A total of 28 pediatric patients were included, comprising 15 males and 13 females, with an average age of 15 months (range: 10-36 months). All cases presented unilateral radial polydactyly, including 18 right hands and 10 left hands. The mean follow-up duration was 4.2 years (range: 1.5-6.0 years). All incisions healed in one stage, and the skin flaps survived well without infection. Joint stability was maintained without any deviation. All reconstructed thumbs demonstrated satisfactory aesthetic appearance. The reconstructed thumbs demonstrated mean active flexion-extension arcs of 76° (range 61°-85°) at the first metacarpophalangeal joint, and 42° (range 21°-65°) at the interphalangeal joint. The grip strength of the hand was 82% (63%-90%) of the normal opposite hand. The key, tip and tripod pinch strength were 76%(66%-83%), 77%(66%-85%) and 79%(68%-87%) of the normal opposite hand, respectively. No scar hyperplasia was found in all cases, and the Vancouver scar scale score was 1.2(0-3) points. The self-assessment score of the children on the pediatric quality of life inventory was 86 points, and the score of the parents/guardians was 91 points. In terms of family satisfaction, 23 patients scored 5, and 5 patients scored 4.Conclusion:The use of palmar approach to on-top plasty to treat unequal radial polydactyly can achieve functional and aesthetic results.

Tissue-resident memory T cells(TRM 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,TRM 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 TRM cells in the liver and their surface markers and transcriptional profiles,aiming to clarify the role of TRM cells in chronic liver diseases and explore their potential function as therapeutic targets in immunotherapy.

Endothelial dysfunction is a key factor linking obstructive sleep apnea hypopnea syndrome(OSAHS)with cardiovascular diseases.In this study,we used advanced proteomics and metabolomics approaches to investigate the impact of extracellular vesicles(EVs)derived from the serum of OSAHS patients on endothelial function.Our multi-omics analysis identified dysregulated pathways related to fatty acid metabolism,apoptosis regulation,and inflammatory responses,highlighting fatty acid synthase(FASN)as a crucial player in OSAHS-induced endothelial dysfunction.Both in vitro and in vivo experiments demonstrated that FASN-enriched EVs impair endothelial cell viability and disrupt metabolic homeo-stasis,offering new insights for the development of targeted therapies for cardiovascular complications associated with OSAHS.

Objective:To study the clinical outcome of palmar approach to on-top plasty in the treatment of unequal radial polydactyly.Methods:A retrospective analysis was conducted on patients with unequal radial polydactyly in which neither thumb duplicates possess both well-developed proximal and distal components. All the patients underwent palmar approach to on-top plasty between September 2013 and September 2023 at Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine and Shanxi Children’s Hospital. At the final follow-up, the active flexion-extension range of motion of the first metacarpophalangeal and interphalangeal joints was measured, along with grip and pinch strength. The Vancouver scar scale was used to assess scar formation (total score 0-15, with higher scores indicating more severe scarring). Additionally, the pediatric quality of life inventory (total score 0-100, with higher scores indicating better quality of life, evaluated by the children themselves or by their parents/guardians on their behalf) and the satisfaction questionnaire (total score ranges from 1 to 5, with higher scores indicating greater satisfaction) were used to assess the patients’ daily quality of life and parents’satisfaction.Results:A total of 28 pediatric patients were included, comprising 15 males and 13 females, with an average age of 15 months (range: 10-36 months). All cases presented unilateral radial polydactyly, including 18 right hands and 10 left hands. The mean follow-up duration was 4.2 years (range: 1.5-6.0 years). All incisions healed in one stage, and the skin flaps survived well without infection. Joint stability was maintained without any deviation. All reconstructed thumbs demonstrated satisfactory aesthetic appearance. The reconstructed thumbs demonstrated mean active flexion-extension arcs of 76° (range 61°-85°) at the first metacarpophalangeal joint, and 42° (range 21°-65°) at the interphalangeal joint. The grip strength of the hand was 82% (63%-90%) of the normal opposite hand. The key, tip and tripod pinch strength were 76%(66%-83%), 77%(66%-85%) and 79%(68%-87%) of the normal opposite hand, respectively. No scar hyperplasia was found in all cases, and the Vancouver scar scale score was 1.2(0-3) points. The self-assessment score of the children on the pediatric quality of life inventory was 86 points, and the score of the parents/guardians was 91 points. In terms of family satisfaction, 23 patients scored 5, and 5 patients scored 4.Conclusion:The use of palmar approach to on-top plasty to treat unequal radial polydactyly can achieve functional and aesthetic results.

Background and purpose:Human papilloma virus(HPV)infection status is crucial for diagnosing cervical precancerous lesions and classifying cervical cancer.High-risk(HR)HPV is often linked to P16 protein overexpression,so P16 detection via immunohistochemistry(IHC)is commonly used to assess HPV infection.However,the differences between HPV status and P16 expression remains unclear.An in-depth study of the correlation between HPV and P16 is essential for clinical guidance.Methods:We retrospectively collected clinical and pathological data of cervical lesions from 618 patients diagnosed at the Department of Pathology,Fudan University Shanghai Cancer Center from January 2020 to December 2023(Ethical number:050432-4-2307E).Polymerase chain reaction(PCR)reverse dot hybridization was used to detect HPV including HR and low-risk(LR)subtypes,and immunohistochemistry was used to detect P16 for comparative analysis.Based on different clinical and pathological diagnoses,the sensitivity and specificity of P16 expression in evaluating HPV infection were evaluated.Among the 618 cases of cervical lesions,there were 92 cases of cervical squamous cell carcinoma,257 cases of cervical adenocarcinoma,79 cases of high-grade squamous intraepithelial lesions(HSIL),105 cases of low-grade squamous intraepithelial lesions(LSIL),and 85 cases of chronic cervical inflammation.Results:According to clinical diagnosis,the HR-HPV positive rate in cervical squamous cell carcinoma was 88.0%(81/92),the P16 positive rate was 91.3%(84/92),and the overall consistency rate between P16 and HPV detection was 90.2%(88/92);for HR-HPV infection,the sensitivity and specificity of P16 were 96.3%and 45.5%.The positive rate of HR-HPV in adenocarcinoma was 54.5%(140/257),the positive rate of P16 was 58.8%(151/257),and the overall consistency rate between P16 and HPV detection was 82.5%(212/257);for HR-HPV infection,the sensitivity and specificity of P16 were 87.9%and 76.1%.In HSIL,the HR-HPV positive rate was 75.9%(60/79),the positive rate of P16 was 70.9%(56/79),and the overall consistency rate between P16 and HR-HPV detection was 82.2%(65/79);for HR-HPV infection,the sensitivity and specificity of P16 were 85.0%and 73.7%.In LSIL,the HR-HPV positive rate was 73.3%(77/105),the positive rate of P16 was 8.5%(9/105),and the overall consistency rate between P16 and HR-HPV detection was 33.3%(35/105);for HR-HPV infection,the sensitivity and specificity of P16 were 10.4%and 96.4%.In chronic cervical inflammation,the HR-HPV positive rate was 20%(17/85),the positive rate of P16 was 0.0%(0/85);for HR-HPV infection,the sensitivity and specificity of P16 were 0.0%and 100.0%.There was a significant positive correlation between P16 positivity and HPV16/18 in cervical squamous cell carcinoma,adenocarcinoma,and HSIL(P=0.000),while there was no significant correlation in LSIL and chronic cervical inflammation(P＞0.05).Conclusion:In cervical squamous cell carcinoma and adenocarcinoma,the consistency of P16 expression and HPV DNA positivity are high,especially in HPV16/18 subtype.There is a good concordance between HR-HPV positivity and P16 protein overexpression.The positive expression of P16 in HSIL may initially reflect HPV infection status.However,in LSIL and chronic cervicitis,P16 expression may not accurately correlate with HPV infection.The inconsistency between P16 and HPV DNA testing could be influenced by multiple factors,including HPV subtypes,histopathological categories,specimen quality,and technical limitations.In clinical practice,it is recommended to conduct comprehensive analysis or employ multiple diagnostic methods to confirm HPV infection status for precise evaluation.

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.