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reading the titles and abstracts of the literature,and then the literature with poor relevance to the research purpose,outdated content,and duplication was excluded according to the inclusion and exclusion criteria.Ultimately,69 relevant articles were included for comprehensive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

The prevention and treatment of chronic obstructive pulmonary disease （COPD） pose a major global challenge， with difficulties in effectively integrating holistic regulation and precise micro-intervention. The traditional Chinese medicine （TCM） theory of state-target pattern differentiation and treatment advocates the combination of state regulation and target intervention， offering a new paradigm for integrated TCM and Western medicine. This article systematically reviews the theoretical connotations of this theory and constructs a dynamic correspondence framework linking TCM pattern states， signaling pathways， and targeted interventions across different stages of COPD. At the acute exacerbation stage， the phlegm-heat obstructing the lung state is characterized by hyperactivation of the nuclear factor （NF）-κB/NOD-like receptor protein 3 （NLRP3） inflammation pathway， and formulas for clearing heat and resolving phlegm suppress the cytokine storm through multi-component synergy. At the stable stage， the lung-spleen Qi deficiency state is characterized by functional decompensation of the nuclear factor erythroid 2-related factor 2 （Nrf2）/Kelch-like ECH-associated protein 1 （Keap1） antioxidative stress pathway， and therapies for tonifying the lung and spleen repair the essence of Qi deficiency through antioxidative defense and energy metabolism. At the severe/very severe stable stage， the lung-kidney deficiency state is pathologically based on dysregulation of the transforming growth factor （TGF）-β/Wnt repair network and depletion of stem/progenitor cells， and therapies for tonifying the kidney and reinforcing Qi absorption achieve simultaneous regulation of deficiency and stasis by inhibiting aberrant fibrosis and guiding ordered regeneration. These three pathways are not isolated but exhibit dynamic shifts in dominance and cross-talk， constituting the molecular network basis of deficiency causing excess and intermingled deficiency and excess. Furthermore， this article points out the current shortcomings in quantitative evidence， objective syndrome standardization， and coverage of syndrome states， and proposes future directions including building multi-omics databases， conducting biomarker-stratified randomized controlled trials， and developing disease-pattern combined animal models， aiming to provide a theoretical perspective that integrates holism and micro-targeting for precision prevention and treatment of COPD.

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.

The prevention and treatment of chronic obstructive pulmonary disease （COPD） pose a major global challenge， with difficulties in effectively integrating holistic regulation and precise micro-intervention. The traditional Chinese medicine （TCM） theory of state-target pattern differentiation and treatment advocates the combination of state regulation and target intervention， offering a new paradigm for integrated TCM and Western medicine. This article systematically reviews the theoretical connotations of this theory and constructs a dynamic correspondence framework linking TCM pattern states， signaling pathways， and targeted interventions across different stages of COPD. At the acute exacerbation stage， the phlegm-heat obstructing the lung state is characterized by hyperactivation of the nuclear factor （NF）-κB/NOD-like receptor protein 3 （NLRP3） inflammation pathway， and formulas for clearing heat and resolving phlegm suppress the cytokine storm through multi-component synergy. At the stable stage， the lung-spleen Qi deficiency state is characterized by functional decompensation of the nuclear factor erythroid 2-related factor 2 （Nrf2）/Kelch-like ECH-associated protein 1 （Keap1） antioxidative stress pathway， and therapies for tonifying the lung and spleen repair the essence of Qi deficiency through antioxidative defense and energy metabolism. At the severe/very severe stable stage， the lung-kidney deficiency state is pathologically based on dysregulation of the transforming growth factor （TGF）-β/Wnt repair network and depletion of stem/progenitor cells， and therapies for tonifying the kidney and reinforcing Qi absorption achieve simultaneous regulation of deficiency and stasis by inhibiting aberrant fibrosis and guiding ordered regeneration. These three pathways are not isolated but exhibit dynamic shifts in dominance and cross-talk， constituting the molecular network basis of deficiency causing excess and intermingled deficiency and excess. Furthermore， this article points out the current shortcomings in quantitative evidence， objective syndrome standardization， and coverage of syndrome states， and proposes future directions including building multi-omics databases， conducting biomarker-stratified randomized controlled trials， and developing disease-pattern combined animal models， aiming to provide a theoretical perspective that integrates holism and micro-targeting for precision prevention and treatment of COPD.

ObjectiveTo explore the efficacy and potential neural mechanisms of individualized precision rehabilitation combining multimodal neuromodulation technologies under the guidance of multidisciplinary team (MDT)-based whole process dynamic assessment in a patient with large-area cerebral infarction who responded poorly to conventional rehabilitation. MethodsA 38-year-old male patient presented with hemiplegia and complete aphasia following large-area cerebral infarction in the left fronto-temporo-parietal lobe and basal ganglia due to arterial dissection. Under the MDT framework, the patient underwent six months of inpatient rehabilitation and one month of outpatient follow-up. Multimodal assessments were performed at multiple time points using diffusion tensor imaging (DTI), functional magnetic resonance imaging (fMRI), three-dimensional gait analysis and 128-channel electroencephalogram (EEG) monitoring, combined with standardized scales, such as Chinese Rehabilitation Research Center Standard Aphasia Examination (CRRCAE), Loewenstein Occupational Therapy Cognitive Assessment (LOTCA), simplified Fugl-Meyer Assessment (FMA) and modified Barthel Index (MBI). The rehabilitation protocol integrated conventional therapies with multimodal interventions, including multi-target transcranial magnetic stimulation, brain-computer interface (BCI)-driven robotic hand training and task-oriented virtual reality upper limb training. ResultsAfter intervention, the patient showed significant improvements: LOTCA score increased by 16 points, CRRCAE subscale scores improved by 60% to 90%, total FMA score increased from 20 to 54, FMA-Balance reached 12, and MBI improved from 40 to 91. DTI revealed an increase in global fiber tract count, elevated fractional anisotropy in the corpus callosum and right corticospinal tract, and significantly increased amplitude of low-frequency fluctuations and regional homogeneity in specific brain regions on fMRI. Event-related desynchronization dynamically decreased during BCI training, and three-dimensional gait parameters showed overall improvement. ConclusionFor patients with large-area stroke who respond inadequately to conventional rehabilitation, an individualized precision rehabilitation system based on MDT whole-process dynamic assessment and integrating multimodal neuromodulation with conventional therapy can effectively enhance cognitive, language, motor functions and activities of daily living. Neuroimaging and electrophysiological findings suggest that the mechanism may involve promoting neural fiber remodeling and modulating regional brain activity.

Objective:To explore the genotype and the clinical phenotype of SCN2A-related developmental delay in children. Methods:A case series study was adopted. Collect clinical data from 10 cases of children with SCN2A gene variants diagnosed with global developmental delay/intellectual disability who were admitted to the Children′s Hospital between July 2019 and March 2023. Summarize the clinical phenotype and genotype based on clinical data such as general information, clinical manifestations, imaging examinations, laboratory tests, genetic testing results, and comprehensive pediatric neuropsychological development assessment. Results:A total of 10 patients were recruited, including 7 males and 3 females, with an age range of 27 days to 5 years and 9 months. 9 patients underwent children′s neuropsychological and behavioral assessments, and the results were consistent with global developmental delay, including 2 mild cases, 4 moderate cases, and 3 severe cases. 3 cases had autism spectrum disorder, and 2 cases had epilepsy. 6 patients underwent complete head MRI examination, and 4 of them showed abnormalities, including delayed myelination, widening of the local extra brain space in the frontal lobe, and abnormal frontal lobe morphology. All 10 cases had point variants. Among them, 9 cases are de novo and 1 case is maternal inheritance. Out of 10 cases, there were 5 cases with copy number variations, but all of them were of unknown significance. Among the 10 variants, 8 have been reported and 2 have not been reported, namely c.4145A>T(p.N1382I) and c.4937T>A(p.I1646N). In this study, 4 out of 10 patients with SCN2A variants had variation sites located in the S4 segment of domain which constitute Nav1.2, the sodium ion channel encoded by SCN2A. The developmental quotient level was lower when the variation sites were located in the S4 segment of domain, and the difference was statistically significant ( t=-3.101, P=0.017), indicating that the severity of developmental delay may be related to the localization of amino acids corresponding to variant sites within the protein domain. Conclusion:SCN2A mutations are strongly associated with diverse neurodevelopmental disorders. In this study, the phenotypic spectrum of SCN2A variants encompassed epilepsy, global developmental delay, and autism spectrum disorder. Affected individuals exhibited early-onset developmental delays, predominantly moderate to severe in severity. Voltage-sensing domain dysfunction in sodium channels may constitute a critical pathomechanism underlying neurodevelopmental impairments. Further electrophysiological characterization and molecular mechanistic studies are warranted todelineate the genotype-phenotype correlations between specific variant loci and clinical severity.

Lipids play an important role in the regulation of cell life processes. Although there are various lipid detection methods, Raman spectroscopy, a non-invasive technique, provides the detailed chemical composition of lipid profiles without a complex sample preparation procedure and possesses greater potential in basic biology, clinical diagnosis and disease therapy. In this review, we summarized the characteristics and advantages of Raman-based techniques and their primary contribution to illustrating cellular lipid metabolism.

Lingguizhugan Decoction (LGZG) demonstrates significant efficacy in treating various cardiovascular diseases clinically, yet its precise mechanism of action remains elusive. This study aimed to elucidate the potential mechanisms and effects of LGZG on isoproterenol (ISO) continuous stimulation-induced chronic heart failure (CHF) in mice, providing direct experimental evidence for further clinical applications. In vivo, continuous ISO infusion was administered to mice, and ventricular myocytes were utilized to explore LGZG?s potential mechanism of action on the ?1-adrenergic receptor (?1-AR)/Gs/G protein-coupled receptor kinases (GRKs)/?-arrestin signaling deflection system in the heart. The findings reveal that LGZG significantly reduced the messenger ribonucleic acid (mRNA) expression of hypertrophy-related biomarkers [atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)] and improved cardiac remodeling and left ventricular diastolic function in mice with ISO-induced CHF. Furthermore, LGZG inhibited the overactivation of Gs/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling and downregulated the downstream transcriptional activity of cAMP-response element binding protein (CREB) and the expression of the coactivator CBP/P300. Notably, LGZG downregulated the expression of ?-arrestin1 and GRK 2/3/5 while upregulating the expression of ?1-AR and ?-arrestin2. These results suggest that LGZG inhibits Gs/cAMP/PKA signaling and ?-arrestin/GRK-mediated desensitization and internalization of ?1-AR, potentially exerting cardioprotective effects through the synergistic regulation of the ?1-AR/Gs/GRKs/?-arrestin signaling deflection system via multiple pathways.
Animals ; Heart Failure/genetics* ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Male ; G-Protein-Coupled Receptor Kinases/genetics* ; Mice, Inbred C57BL ; Humans ; Isoproterenol ; Arrestins/genetics* ; Chronic Disease

Lipids play an important role in the regulation of cell life processes.Although there are various lipid detection methods,Raman spectroscopy,a non-invasive technique,provides the detailed chemical composition of lipid profiles without a complex sample preparation procedure and possesses greater potential in basic biology,clinical diagnosis and disease therapy.In this review,we summarized the characteristics and advantages of Raman-based techniques and their primary contribution to illustrating cellular lipid metabolism.

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.