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 explore the clinical significance of chromosome microarray analysis (CMA) in the prenatal detection of DMD gene variants in fetuses without family history during prenatal diagnosis.Methods:A retrospective analysis was conducted on amniotic fluid samples from 12 629 pregnant women who underwent CMA prenatal diagnosis due to high-risk factors at Women and Children′s Hospital Affiliated to Qingdao University between January 2019 and December 2024. Samples with CMA-indicated DMD gene variants were further verified by multiplex ligation-dependent probe amplification (MLPA).Results:(1) Among 12 629 amniotic fluid samples, CMA detected 11 samples with DMD gene deletions or duplications (6 male and 5 female fetuses), which were confirmed by MLPA. (2) All 11 samples with DMD gene variants had no family history of genetic diseases, including 5 deletions and 6 duplications. All of the 5 DMD gene deletions occurred in male fetuses and were all pathogenic, and the pregnant women chose to terminate the pregnancies. Among the 6 DMD gene duplications cases, 1 male fetus was diagnosed as pathogenic and had pregnancy termination; the other 5 duplication cases were female fetuses, in which 1 were pathogenic and 4 were likely pathogenic. They continued pregnancy until delivery, and follow-up showed no DMD-related symptoms. (3) Pedigree analysis revealed that among the 11 samples with DMD gene variants, 3 were de novo mutations, 7 were inherited from mothers, and 1 had an unknown origin.Conclusions:For fetuses without pseudohypertrophic muscalar dystrophy family history but requiring invasive prenatal diagnosis for other reasons, CMA helps to increase the detection of DMD gene variants in fetuses. Testing pregnant women for DMD pathogenic gene carriers could effectively prevent the birth of pseudohypertrophic muscalar dystrophy children.

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.

Objective To propose a image processing strategy based on salient object detection algorithm for optimizing the presentation of prosthetic visual information at a limited resolution level,aiming to detect and enhance the salient objects in the scene and remove the background information.Methods A salient object detection model combining CNN and Transformer was used to extract salient objects.On this basis,methods such as object magnification,contour enhancement and contrast enhancement were utilized to optimize the image information.Psychophysical experiments were carried out at 5 resolution levels(16×16,24×24,32×32,48×48 and 64×64).Results In the simulated prosthetic vision,this image processing strategy had a remarkable effect on improving the object recognition ability of the subjects.Regardless of the resolutions of 16×16,24×24,32×32,48×48 and 64×64,the proposed strategy achieved the highest recognition accuracies,specifically 34%±6%,56%±9%,72%±9%,89%±4%and 96%±2%.Conclusion Using the salient object detection method and image processing strategy to extract and enhance salient objects can help prosthesis implant recipients effectively improve their object recognition ability.

Objective To investigate the status of hearing impaired children's hearing device independence skills,and to explore the ways to improve their self-use of hearing equipment.Methods This study surveyed 64 re-habilitation teachers and 411 parents of children with hearing impairment aged 0-12 years.Through face-to-face or remote telephone interview,3 good habits(A asking parents for advice before removing the HA,B putting the de-vice into a moisture-proof box after removing it,C bringing batteries to school and knowing where are them)and 3 key abilities[D wearing the device independently,E replacing the battery independently,and F independently handle foreign bodies in the ear mold(Fa)and water vapor(Fb)]was investigated.The age when mastering skills or de-veloping habits difference of hearing impaired children in different groups were compared.Results ① The ratio of ability D in the bilateral CI group and the bilateral HA group of preschool children was 30.97％and 18.57％respec-tively.Among elementary school children,85.29％and 90.70％had this ability respectively.② The ratio of ability E in the bilateral CI group,the bilateral HA group and the bimodel group were 11.50％,15.71％and 16.49％,re-spectively.Among elementary school children,64.71％,53.49％and 68.52％had this ability,respectively.③Among preschool children,there was no statistical difference in age when different equipment groups developed the three good habits and acquired ability D and E(P＞0.05).④ Among primary school children,there was a statisti-cal difference in the age when different equipment groups formed habit A(P＜0.05),and the age when double CI group had this ability was slightly earlier than the double HA group.There was no significant difference in other abilities among age groups(P＞0.05).Conclusion The age at which hearing impaired children develop the three good habits precedes the age at which they master the key skills,which accords with the law of skill acquisition and development of ordinary children.Corresponding teaching process should be based on the age and ability of hearing-impaired children without considering the type of equipment.

Objective To evaluate the association of different obesity phenotypes and their components with the risk of cognitive impairment in older Chinese adults,and to assess the association between obesity and cognitive impairment in different cognition-related genetic backgrounds.Methods A cross-sectional study based on the West China Health and Aging Cohort was conducted.Logistic regression was applied to estimate the association of obesity phenotypes and components with cognitive impairment in older Chinese adults stratified by APOE gene and polygenic risk scores.Results A total of 7 316 participants were enrolled,of whom 1 820 had cognitive impairment.Weight gains were associated with a reduced risk of cognitive impairment(odds ratio[OR]=0.96,95%CI,0.95-0.97).Being overweight with a normal waist-to-hip ratio was a protective factor for cognition(OR=0.74,95%CI,0.61-0.90),whereas the coexistence of elevated waist-to-hip ratio and overweight did not increase the risk of cognitive impairment.Sarcopenia was associated with an elevated risk of cognitive impairment.This association was found in both overweight(OR=2.03,95%CI,1.71-2.41)and non-overweight older adults(OR=1.86,95%CI,1.58-2.20),and was significant across all polygenic risk score strata.Conclusion Increasing body mass may serve as a key protective factor against cognitive decline in older adults.Having sarcopenia and obesity is associated with an elevated risk of cognitive impairment,independent of genetic susceptibility.

Objective:To explore the clinical significance of chromosome microarray analysis (CMA) in the prenatal detection of DMD gene variants in fetuses without family history during prenatal diagnosis.Methods:A retrospective analysis was conducted on amniotic fluid samples from 12 629 pregnant women who underwent CMA prenatal diagnosis due to high-risk factors at Women and Children′s Hospital Affiliated to Qingdao University between January 2019 and December 2024. Samples with CMA-indicated DMD gene variants were further verified by multiplex ligation-dependent probe amplification (MLPA).Results:(1) Among 12 629 amniotic fluid samples, CMA detected 11 samples with DMD gene deletions or duplications (6 male and 5 female fetuses), which were confirmed by MLPA. (2) All 11 samples with DMD gene variants had no family history of genetic diseases, including 5 deletions and 6 duplications. All of the 5 DMD gene deletions occurred in male fetuses and were all pathogenic, and the pregnant women chose to terminate the pregnancies. Among the 6 DMD gene duplications cases, 1 male fetus was diagnosed as pathogenic and had pregnancy termination; the other 5 duplication cases were female fetuses, in which 1 were pathogenic and 4 were likely pathogenic. They continued pregnancy until delivery, and follow-up showed no DMD-related symptoms. (3) Pedigree analysis revealed that among the 11 samples with DMD gene variants, 3 were de novo mutations, 7 were inherited from mothers, and 1 had an unknown origin.Conclusions:For fetuses without pseudohypertrophic muscalar dystrophy family history but requiring invasive prenatal diagnosis for other reasons, CMA helps to increase the detection of DMD gene variants in fetuses. Testing pregnant women for DMD pathogenic gene carriers could effectively prevent the birth of pseudohypertrophic muscalar dystrophy children.

Neuropathic pain, often featuring allodynia, imposes significant physical and psychological burdens on patients, with limited treatments due to unclear central mechanisms. Addressing this challenge remains a crucial unsolved issue in pain medicine. Our previous study, using protein kinase C gamma (PKCγ)-tdTomato mice, highlights the spinal feedforward inhibitory circuit involving PKCγ neurons in gating neuropathic allodynia. However, the regulatory mechanisms governing this circuit necessitate further elucidation. We used diverse transgenic mice and advanced techniques to uncover the regulatory role of the descending serotonin (5-HT) facilitation system on spinal PKCγ neurons. Our findings revealed that 5-HT neurons from the rostral ventromedial medulla hyperpolarize spinal inhibitory interneurons via 5-HT_2C receptors, disinhibiting the feedforward inhibitory circuit involving PKCγ neurons and exacerbating allodynia. Inhibiting spinal 5-HT_2C receptors restored the feedforward inhibitory circuit, effectively preventing neuropathic allodynia. These insights offer promising therapeutic targets for neuropathic allodynia management, emphasizing the potential of spinal 5-HT_2C receptors as a novel avenue for intervention.
Animals ; Neuralgia/physiopathology* ; Protein Kinase C/metabolism* ; Receptor, Serotonin, 5-HT2C/metabolism* ; Hyperalgesia/physiopathology* ; Mice, Transgenic ; Mice ; Spinal Cord/metabolism* ; Serotonin/metabolism* ; Male ; Neurons/metabolism* ; Mice, Inbred C57BL

OBJECTIVE: To explore the genetic etiology of fetal skeletal dysplasia using whole exome sequencing (WES) and copy number variation sequencing (CNV-seq) techniques, and the feasibility of using WES as the first-tier method for such fetuses. METHODS: Seventy four fetuses with skeletal dysplasia detected by prenatal ultrasound at the Genetic Testing Center of the Women and Children's Hospital Affiliated to Qingdao University from January 2020 to August 2024 were selected as the study subjects. Fetal muscle and peripheral blood samples of the pregnant women and their spouses were collected and subjected to WES analysis. CNV-seq was carried out on all fetal muscle tissue samples. And the results were compared with the CNVs indicated by WES. Genetic etiologies were analyzed across different subtypes of skeletal dysplasia. And the feasibility of using WES as the first-tier genetic test for similar fetuses was assessed, in addition with a systematic cost-effectiveness analysis. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: QFELL-YJ-2024-201). RESULTS: A total of 50 fetuses were diagnosed, which yielded a diagnostic rate of 67.57%. These included 6 chromosomal aneuploidies, 4 chromosomal CNVs and 40 monogenic disorders. The monogenic diseases had involved 46 variant sites in 23 pathogenic genes, among which 12 were unreported previously, including MYH3: c.735T>C, ALPL: c.1324C>T, NEK9: c.1973G>A, MAGEL2: c.2024_2025del, LMBR1: c.423+4914A>C, NEB: c.21273_21276del, COL1A1: c.2651G>C and c.2758G>C, ASPM: c.2473delinsGA, TBX5: c.704G>A, DYNC2H1: c.10893del, and DYNC2I2: c.1270C>T. Substantial concordance was reached between WES-derived CNV calls and CNV-seq findings. No clinically significant CNV was exclusively detected by CNV-seq. Cost-effectiveness modeling demonstrated that implementing WES as the first-tier genetic testing method could reduce the total expenditure when WES unit cost remained below 6.4 folds that of the CNV-seq. CONCLUSION Genetic variants including single nucleotide variations (SNV) of monogenic disorders, chromosomal aneuploidies and genomic CNVs are important causes for fetal skeletal dysplasia. WES is an accurate and efficient method for analyzing the etiology of fetal skeletal dysplasia, particularly in those with a family history of similar phenotype or maternal history of adverse pregnancies.
Humans ; Exome Sequencing/methods* ; Female ; Pregnancy ; DNA Copy Number Variations/genetics* ; Genetic Testing/methods* ; Prenatal Diagnosis/methods* ; Adult ; Male ; Fetus ; Bone Diseases, Developmental/diagnosis* ; Ultrasonography, Prenatal