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OBJECTIVE: This study explores the intricate relationship between clozapine use, cardiovascular disease (CVD) risk, and cognitive function in patients with schizophrenia (SCZ). METHODS: A cohort comprising 765 patients was stratified based on clozapine usage. Data on demographics, clinical characteristics, and glycolipid metabolism were collected. The Framingham Risk Score and vascular age were calculated using gender-specific Cox regression calculators. Cognitive function was assessed with the Repeatable Battery for Assessment of Neuropsychological Status. RESULTS: Among the patients, 34.6 % were clozapine users. Clozapine users exhibited lower systolic blood pressure, high-density lipoprotein cholesterol and total cholesterol (all ps < 0.05). Furthermore, clozapine users exhibited higher PANSS scores, along with lower scores in RBANS scores (all ps < 0.05). Correlation analysis revealed positive correlation between CVD risk in non-clozapine users and negative symptom scores (r = 0.074, p = 0.043), and negative correlation with positive symptom scores and RBANS scores (r = -0.121, p = 0.001; r = -0.091, p = 0.028). Multivariate stepwise regression analysis indicated that attention scores as predictive factors for increased CVD risk in clozapine users (B = -0.08, 95 %CI = -0.11 to -0.03, p = 0.003). CONCLUSIONS: Patients with SCZ using clozapine exhibit more severe clinical symptoms and cognitive impairments. Attention emerges as a predictor for increased CVD risk in clozapine users.
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Objective: This study assesses the effectiveness and safety of single-port laparoscopic myomectomy (SPLM) versus conventional laparoscopic myomectomy (CLM). Methods: We conducted a retrospective case-control study at a university tertiary hospital, involving 262 patients treated from July 2020 to December 2022. Participants were divided into two groups: 132 underwent SPLM and 130 underwent CLM. Results: The two groups were comparable in terms of age, body mass index, parity, delivery history, preoperative anemia, number of myomas, and size of the largest myoma. The SPLM group showed a significant reduction in operation time (average 93 min) and estimated blood loss (average 50 ml) compared to the CLM group (average 118.5 min and 100 ml, respectively). Subgroup analysis based on the size, location, and number of myomas further highlighted the advantages of SPLM, particularly for patients with large (diameter ≥8 cm) or multiple myomas (number ≥4). Patient satisfaction was also notably higher in the SPLM group. Conclusions: Single-port laparoscopic myomectomy offers a highly effective, safer, and patient-preferred option for the surgical management of fibroids, especially in cases of large or multiple myomas. These findings suggest that SPLM could become the preferred surgical approach for complex fibroid cases, promising less trauma and quicker recovery for patients.
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PURPOSE: To explore the application possibility of macrocephalic sperm from a patient with 100% macrocephalic sperm and AURKC gene variations. METHODS: We diagnosed a case of macrozoospermia with 100% macrocephalic sperm and 39.5% multi-tailed spermatozoa by morphological analysis. Whole-exome sequencing (WES) was used for the patient and his wife. Sanger sequencing technique was used to verify the AURKC mutations in the patient's parents and his offspring. Sperm's ploidy was tested by flow cytometry. The couple asked for intra-couple ART therapy. RESULTS: The patient presented novel compound heterozygous AURKC mutations (c.434C > T, c.497A > T) by WES. Sanger sequencing validation showed that variant of c.434C > T was observed in his father and c.497A > T was observed in his mother. Flow cytometry revealed that there existed a certain proportion of haploid sperm. Macrocephalic spermatozoa whose heads were smaller than the diameter of injection needle were selected for microinjection. A singleton pregnancy was achieved after embryo transfer. Prenatal diagnosis revealed that the fetus had normal chromosomal karyotype. Sanger sequencing technique showed that the fetus carried a c.434C > T mutation in one AURKC allele. A 3730 g healthy male fetus was delivered at term. CONCLUSION: Our study reported a successful live birth from a patient with definite AURKC gene variants and may provide insights for such patients to choose donor sperm or their own sperm.
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Radical-nonradical co-dominant pathways have become a hot topic in advanced oxidation, but achieving this on transition metal sulfides (TMS) remains challenging because their inherently higher electron and spin densities always induce radicals rather than nonradicals. Herein, a biosurfactant layer (BLR) was introduced to redistribute the electron and spin structure of nanoscale iron sulfide (FeS), which allowed both radical and nonradical to co-dominate the catalytic reaction. The resulting BLR-encased FeS hybrid (BLR@FeS) exhibited satisfactory removal efficiency (98.5 %) for hydrogen peroxide (H2O2) activation, outperforming both the constituent components [FeS (70.9 %) and BLR (86.2 %)]. Advanced characterizations showed that C, O, N-related sites (-CO and -NC) in BLR attracted electrons in FeS due to their strong electronegativity and electron-withdrawing capacity, which not only decreased electron density in FeS, but also resulted in a shift of the Fe/S sites from the high-spin to the medium-spin state. The reaction routes established by the BLR@FeS/H2O2 system maintained desirable stability against environmental interferences such as common inorganic anions, humic acid and changes in pH. Our study provides a state-of-the-art, molecule-level understanding of tunable co-dominant pathways and expands the targeted applications in the field of advanced oxidation.
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Purpose: Variants in the ARR3 gene have been linked to early-onset high myopia (eoHM) with a unique X-linked female-limited inheritance. However, the clinical validity of this gene-disease association has not been systematically evaluated. Methods: We identified two Chinese families with novel ARR3 splicing variants associated with eoHM. Minigene constructs were generated to assess the effects of the variants on splicing. We integrated previous evidence to curate the clinical validity of ARR3 and eoHM using the ClinGen framework. Results: The variants c.39+1G>A and c.100+4A>G were identified in the two families. Minigene analysis showed both variants resulted in abnormal splicing and introduction of premature termination codons. Based on genetic and experimental evidence, the ARR3-eoHM relationship was classified as "definitive." Conclusions: Our study identified two novel splicing variants of the ARR3 gene linked to eoHM and confirmed their functional validity via minigene assay. This research expanded the mutational spectrum of ARR3 and confirmed the minigene assay technique as an effective tool for understanding variant effects on splicing mechanisms.
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Arrestinas , Miopía , Empalme del ARN , Femenino , Humanos , Mutación , Miopía/genética , Empalme del ARN/genética , Arrestinas/genética , Pueblos del Este de Asia/genéticaRESUMEN
Defective decidualization of endometrial stromal cells (ESCs) in endometriosis (EM) patients leads to inadequate endometrial receptivity and EM-associated infertility. Hypoxia is an inevitable pathological process of EM and participates in deficient decidualization of the eutopic secretory endometrium. Enhancer of zeste homology 2 (EZH2) is a methyltransferase which catalyses H3K27Me3, leading to decreased expression levels of target genes. Although EZH2 expression is low under normal decidualization, it is abundantly increased in the eutopic secretory endometrium of EM and is induced by hypoxia. Chromatin immunoprecipitation-PCR results revealed that decidua marker IGFBP1 is a direct target of EZH2, partially explaining the increased levels of histone methylation modification in defected decidualization of EM. To mechanism controlling this, we examined the effects of hypoxia on EZH2 and decidualization. EZH2 mRNA showed decreased m6 A modification and increased expression levels under hypoxia and decidualization combined treatment. Increased EZH2 expression was due to the increased expression of m6 A demethylase ALKBH5 and decreased expression of the m6 A reader protein YTHDF2. YTHDF2 directly bind to the m6 A modification site of EZH2 to promote EZH2 mRNA degradation in ESCs. Moreover, selective Ezh2 depletion in mouse ESCs increased endometrial receptivity and improved mouse fertility by up-regulating decidua marker IGFBP1 expression. This is the first report showing that YTHDF2 can act as a m6 A reader to promote decidualization by decreasing the stability of EZH2 mRNA and further increasing the expression of IGFBP1 in ESCs. Taken together, our findings highlight the critical role of EZH2/H3K27Me3 in decidualization and reveal a novel epigenetic mechanism by which hypoxia can suppress EM decidualization by decreasing the m6 A modification of EZH2 mRNA.
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Endometriosis , Infertilidad , Femenino , Humanos , Animales , Ratones , Endometriosis/genética , Endometriosis/metabolismo , Histonas/genética , Histonas/metabolismo , ARN/metabolismo , Factores de Transcripción/metabolismo , ARN Mensajero/metabolismo , Metilación , Hipoxia/complicaciones , Hipoxia/genéticaRESUMEN
Endometrium is suspectable to severe injury due to recurrent abortion, curettage or intrauterine infection which could lead to pathological conditions and sabotage women's fertility. Promoting endometrium regeneration is the core of the treatments to uterine related infertility. Patients who received traditional treatments can only expect limited effects, thereby novel therapies are badly in need to promote endometrium regeneration. Here we generated a decellularized extracellular matrix (ECM) from porcine dermis, and composited adipose stem cell derived exosomes (ADSC-exos) on it (ECM@ADSC-exos). In vitro experiments proved that ECM@ADSC-exos exhibited good cytocompatibility and could improve cell proliferation, migration and angiogenesis. We also observed that, when implanted in the uterine cavity of a rat model of endometrium injury, ECM@ADSC-exos improved endometrium regeneration, enhanced local angiogenesis, promoted myometrium repair and finally preserved fertility. Our results proved that ECM@ADSC-exos could be a novel option for endometrium regeneration.
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In order to improve the utilization rate of coal gangue and expand the application range of coal gangue concrete (CGC), a certain proportion of steel fiber was added to the concrete, and the freeze-thaw cycles (FTCs) and flexural tests were used to explore the effects of different mass replacement rates of coal gangue (0%, 25%, 50%, 75%, and 100%) and different proportions of the volumetric blending of the steel fiber (0%, 0.8%, 1.0%, and 1.2%) on the frost resistance of steel fiber-reinforced CGC (SCGC). The governing laws of mass loss rate, relative dynamic elastic modulus and load-midspan deflection curve were obtained on the base of the analysis of testing results. The damage mechanisms of the SCGC under the FTCs were analyzed using the results of scanning electron microscopy (SEM). Based on the Lemaitre's strain equivalence principle and Krajcinovic's vector damage theory, a damage evolution model of the SCGC under the FTCs was established by introducing the damage variable of the SCGC satisfying Weibull distribution. The results show an increasing mass loss rate of the SCGC and a decreasing relative dynamic elastic modulus with an increasing mass replacement rate of coal gangue. The proper content of the steel fiber can reduce the mass loss rate of concrete by 10~40% and the relative loss rate of dynamic elastic modulus of concrete by 2~8%, thus significantly improving the ductility and toughness of the concrete. The established damage evolution model is well validated by the experimental results, which further help to improve the modelling accuracy. This study provides key experimental data and a theoretical basis for a wider range of proper utilization of coal gangue in cold regions.
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Severe endometrium damage causes pathological conditions such as thin endometrium and intrauterine adhesion, resulting in uterine factor infertility. Mesenchymal stem cell (MSC) therapy is a promising strategy in endometrial repair; yet, exogenous MSCs still raise concerns for safety and ethical issues. Human adipose-derived mesenchymal stem cells (ADMSCs) residing in adipose tissue have high translational potentials due to their autologous origin. To harness the high translation potentials of ADMSC in clinical endometrium regeneration, here we constructed an ADMSCs composited porous scaffold (CS/ADMSC) and evaluated its effectiveness on endometrial regeneration in a rat endometrium-injury model. We found that CS/ADMSC intrauterine implantation (i) promoted endometrial thickness and gland number, (ii) enhanced tissue angiogenesis, (iii) reduced fibrosis and (iv) restored fertility. We ascertained the pro-proliferation, pro-angiogenesis, immunomodulating and anti-fibrotic effects of CS/ADMSC in vitro and revealed that the CS/ADMSC influenced extracellular matrix composition and organization by a transcriptomic analysis. Our results demonstrated the effectiveness of CS/ADMSC for endometrial regeneration and provided solid proof for our future clinical study.
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To evaluate the association between the number of oocytes retrieved and cumulative live birth rate (CLBR) in different female age strata. 17,931 women undergoing their first IVF/ICSI-ET cycle in the Sir Run Run Shaw Hospital of Zhejiang University were grouped by age (A: ≤ 35 years; B: ≥ 36 years) as well as the number of oocytes retrieved (a: ≤ 5; b:6-9; c:10-14; d: ≥ 15). Multivariate regression analysis was performed to assess the OR of CLBR for the variable 'age' and 'number of oocytes retrieved'. The group ≥ 36 years exhibited lower cumulative pregnancy rates (CPRs) and cumulative live birth rates (CLBRs), which are proportional to the number of oocytes retrieved but opposite to increasing age. Multivariate logistic regression analysis revealed that the age and number of oocytes retrieved remain significant independent predictive factors (P < 0.001). Age and number of oocytes retrieved are two independent factors affecting the CLBR. The discrepancy of the minimum number of oocytes retrieved for patients with different ages to achieve ideal CLBR is instructive for clinical practice. The practice of controlling the stimulation dose is feasible for patients ≤ 35 years who can achieve over 60% CLBR once the number of oocytes obtained is more than 6. However, additional stimulation cycles and accumulation of embryos are necessary for elderly group especially those ≥ 38 years old who need more than 14 oocytes to obtain higher live birth rate.
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Tasa de Natalidad , Oocitos , Femenino , Embarazo , Humanos , Índice de Embarazo , Hospitales , Análisis MultivarianteRESUMEN
Slow electron migration in iron sulfide nanoparticles (C-FeS NPs) synthesized by co-precipitation severely limits the activation performance of hydrogen peroxide (H2O2). Herein, a biofunctional FeS NPs (P-FeS NPs) derived from Pinus massoniana Lamb biomass, with interface coupling effect, was used for enhanced H2O2 activation and norfloxacin (NOR) degradation. It was discovered that P-FeS NPs exhibited superior catalytic activity (100%) compared to C-FeS NPs (53.1%). Fe atoms of FeS NPs and hydroxyl groups (-OH) of Pinus massoniana Lamb biomass were mutually coupled to produce Fe-OH interfacial sites, which significantly increased the generation of multi-reactive species by accelerating the transfer of electrons across interfaces. Additionally, radical quenching tests elucidated that singlet oxygen (1O2) (66.6%) played a leading role, while hydroxyl radicals (â¢OH) (14.5%) and superoxide radicals (â¢O2-) (18.9%) were secondary oxidants. Finally, P-FeS NPs showed a high tolerance to a wide range of pH conditions and could remove 96.4% NOR from wastewater. Overall, this work generates important insights into understanding how green sustainable interfacial catalysts can accelerate catalytic activity.
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Although carbon-nano zero-valent iron (C@nZVI) composites with unique properties have been used for environmental remediation, the origins of their superior properties and multifunctionalities of C@nZVI still need to be verified. Here, iron precursor nanoparticles (PML-Fe NPs) synthesized by Pinus massoniana Lamb and carbonized C@nZVI were systemically compared to reveal the origins of the structure and performance of C@nZVI composites. Characterizations showed that structure-modulated C@nZVI has favorable properties of good crystallinity, graphite carbon-rich structure but also defects when compared to PML-Fe NPs. The resultant carbon layer fundamentally improved its dispersion and anti-oxidation properties. Further experiments demonstrated that the evolution of material crystallinity, graphitization and defects affected the reaction pathway of hexavalent chromium (Cr(VI)), oxytetracycline hydrochloride (OTC), and 17ß-estradiol (ßE2). The multifunctionalities covered adsorption, reduction and catalytic oxidation. This study explains the origins of multifunctional C@nZVI by understanding the structure-property correlation in the carbonization process.
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Restauración y Remediación Ambiental , Contaminantes Químicos del Agua , Carbono , Hierro/química , Pirólisis , Contaminantes Químicos del Agua/química , Cromo/química , AdsorciónRESUMEN
Despite the oxidation mechanism of antimonite (Sb(â ¢)) by biosynthesized iron nanoparticles (Fe NPs) has been reported, the impact of coexisting components in acid mine drainage (AMD) on the Sb(III) oxidation by Fe NPs is unknown. Herein, how the coexisting components in AMD affect Sb(â ¢) oxidation by Fe NPs was investigated. Firstly, Fe NPs achieved complete oxidation of Sb(â ¢) (100%), while only 65.0% of Sb(â ¢) was oxidized when As(â ¢) was added, due to competitive oxidation between As(â ¢) and Sb(â ¢), which was verified by characterization analysis. Secondly, the decline in solution pH improved Sb(â ¢) oxidation from 69.5% (pH 4) to 100% (pH 2), which could be attributed to the rise of Fe3+ in solution promoting the electron transfer between Sb(â ¢) and Fe NPs. Thirdly, the oxidation efficiencies of Sb(â ¢) fell by 14.9 and 44.2% following the addition of oxalic and citric acid, respectively, resulting from the fact that these two acids reduced the redox potential of Fe NPs, thereby inhibiting Sb(â ¢) oxidation by Fe NPs. Finally, the interference effect of coexisting ions was studied, where PO43- significantly reduced Sb(â ¢) oxidation efficiency due to the occupation of the surface-active sites on Fe NPs. Overall, this study has significant implications for the prevention of Sb contamination in AMD.
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Hierro , Minería , Hierro/química , Oxidación-ReducciónRESUMEN
Over the last 40 years, a burrowing mammal eradication policy has been prevalent on the Qinghai-Tibetan Plateau (QTP). This policy is based on similar burrowing mammal eradication programs in other areas and is justified on the assumptions that burrowing mammals compete with livestock for forage and contribute to grassland degradation. However, there is no clear theoretical or experimental evidence supporting these assumptions. This paper synthesizes the ecological functioning of small burrowing mammals in natural grasslands and discusses the irrationality and consequences of burrowing mammal eradication for sustainable livestock grazing and grassland degradation. Past burrowing mammal eradication efforts have failed because increased food availability for the remaining rodents and reduced predator populations led to rapid population rebounds. Herbivores differ in diet, and there is clear evidence that burrowing mammals, especially plateau zokors Myospalax baileyi, have a different diet than livestock. In QTP meadows, burrowing mammal eradication induces a shift towards plant communities with fewer species preferred by livestock and more species preferred by burrowing mammals. Thus, eradicating burrowing mammals has the opposite effect, a reduction in livestock preferred vegetation. We suggest that the policy of poisoning burrowing mammals needs to be reconsidered and revoked as soon as possible. We argue that incorporating density-dependent factors such as predation and food availability are essential for maintaining a low burrowing mammal density. For degraded grasslands, we suggest that the optimal sustainable approach is to decrease the intensity of livestock grazing. Lower grazing induces changes in vegetation structure and plant species composition that increases predation on burrowing mammals and decreases the abundance of plants preferred by burrowing mammals. Such a nature-based grassland management system maintains the density of burrowing mammals at a low stable density while minimizing human management and interventions.
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Pradera , Mamíferos , Humanos , Animales , Mamíferos/fisiología , Roedores , Herbivoria , Plantas , Ganado/fisiología , EcosistemaRESUMEN
BACKGROUND: Nuclear Yes1-associated transcriptional regulator (YAP1) promotes tumor progression. However, the function of cytoplasmic YAP1 in breast cancer cells and its impact on the survival of breast cancer patients remain unclear. Our research aimed to explore the biological function of cytoplasmic YAP1 in breast cancer cells and the possibility of cytoplasmic YAP1 as a predictive marker of breast cancer survival. METHODS: We constructed cell mutant models, including NLS-YAP15SA (nuclear localized), YAP1S94A (incapable of binding to the TEA domain transcription factor family) and YAP1S127D (cytoplasmic localized), and used Cell Counting Kit-8 (CCK-8) assays, 5-ethynyl-2'-deoxyuridine (EdU) incorporation assays, and Western blotting (WB) analysis to detect cell proliferation and apoptosis. The specific mechanism of cytoplasmic YAP1-mediated endosomal sorting complexes required for transport III (ESCRT-III) assembly was studied by co-immunoprecipitation, immunofluorescence staining, and WB analysis. Epigallocatechin gallate (EGCG) was used to simulate YAP1 retention in the cytoplasm in in vitro and in vivo experiments to study the function of cytoplasmic YAP1. YAP1 binding to NEDD4-like E3 ubiquitin protein ligase (NEDD4L) was identified using mass spectrometry and was verified in vitro. Breast tissue microarrays were used to analyze the relationship between cytoplasmic YAP1 expression and the survival of breast cancer patients. RESULTS: YAP1 was mainly expressed in the cytoplasm in breast cancer cells. Cytoplasmic YAP1 promoted autophagic death of breast cancer cells. Cytoplasmic YAP1 bound to the ESCRT-III complex subunits charged multivesicular body protein 2B (CHMP2B) and vacuolar protein sorting 4 homolog B (VPS4B), promoting assembly of CHMP2B-VPS4B and activating autophagosome formation. EGCG retained YAP1 in the cytoplasm, promoting the assembly of CHMP2B-VPS4B to promote autophagic death of breast cancer cells. YAP1 bound to NEDD4L, and NEDD4L mediated ubiquitination and degradation of YAP1. Breast tissue microarrays revealed that high levels of cytoplasmic YAP1 were beneficial to the survival of breast cancer patients. CONCLUSIONS: Cytoplasmic YAP1 mediated autophagic death of breast cancer cells by promoting assembly of the ESCRT-III complex; furthermore, we established a new breast cancer survival prediction model based on cytoplasmic YAP1 expression.
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Muerte Celular Autofágica , Neoplasias de la Mama , Femenino , Humanos , Citoplasma/metabolismo , Complejos de Clasificación Endosomal Requeridos para el Transporte/genética , Complejos de Clasificación Endosomal Requeridos para el Transporte/metabolismo , Factores de Transcripción/genéticaRESUMEN
RATIONALE: Placental mesenchymal dysplasia (PMD) is a rare placental disease frequently associated with severe maternal and/or fetal complications. Its sonographic appearance is very similar to that of a hydatidiform mole. Hence, PMD is easily misdiagnosed as a hydatidiform mole. In this study, we reported the clinical features of PMD and analyzed its relationship to other severe maternal and/or fetal complications. PATIENT CONCERNS: A 28-year-old female, gravida 2, para 1, was referred to our maternal and child health hospital at 15 weeksâ +â 2 days due to an ultrasonic diagnosis of partial hydatidiform mole. Analysis of chromosome karyotypeâ +â mononucleotide-based gene microarray by amniocentesis at the 19th week of gestation showed that fetal amniocentesis chromosome 46, XN, high-resolution chromosome microarray analysis of Affymetrix CytoScan 750K Array revealed a 210 kb fragment deletion in chromosome 2p16.3 containing NRXN1, an OMIM gene, the deleted fragment was derived from a mother with a normal phenotype. The pregnant woman delivered a healthy baby girl at 36 weeksâ +â 5 days. DIAGNOSES: Based on the clinical characteristics, imaging, and genetic test findings, the postoperative diagnosis was PMD. INTERVENTION: Because of "Scar uterus" and "Pregnancy with hydatidiform mole," a 2490 g female infant was delivered by cesarean section at 36 weeksâ +â 5 days of gestation with an Apgar score of 9/9. OUTCOMES: The maternal human chorionic gonadotropin level decreased to the normal range after 10 days of delivery, and the infant was not found abnormal after 3 months of follow-up. LESSONS: From our cases and 19 other cases obtained from the PMD literature review are associated with unique clinical, laboratory, and imaging features compared with a hydatidiform mole, such as stained glass sign, normal serum levels of serum human chorionic gonadotropin, elevated alpha-fetoprotein levels and female fetus.
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Mola Hidatiforme , Enfermedades Placentarias , Neoplasias Uterinas , Niño , Femenino , Embarazo , Humanos , Adulto , Placenta/patología , Neoplasias Uterinas/patología , Cesárea , Mola Hidatiforme/diagnóstico , Mola Hidatiforme/patología , Enfermedades Placentarias/diagnóstico , Enfermedades Placentarias/patología , Gonadotropina Coriónica , Hiperplasia/patología , Errores DiagnósticosRESUMEN
Background Previous studies found an association between self-reported sleep duration and mortality. This study aimed to compare the effects of objective and self-reported sleep duration on all-cause and cardiovascular disease (CVD) mortality. Methods and Results A total of 2341 men and 2686 women (aged 63.9±11.1 years) were selected from the SHHS (Sleep Heart Health Study). Objective sleep duration was acquired using in-home polysomnography records, and self-reported sleep duration on weekdays and weekends was based on a sleep habits questionnaire. The sleep duration was categorized as ≤4 hours, 4 to 5 hours, 5 to 6 hours, 6 to 7 hours, 7 to 8 hours, and >8 hours. Multivariable Cox regression analysis was used to investigate the association of objective and self-reported sleep duration with all-cause and CVD mortality. During a mean follow-up period of 11 years, 1172 (23.3%) participants died, including 359 (7.1%) deaths from CVD. All-cause and CVD mortality rates decreased gradually with increasing objective sleep duration. In multivariable Cox regression analysis, the greatest association for all-cause and CVD mortality was with an objective sleep duration of 5 hours or shorter. In addition, we found a J-shaped association of self-reported sleep duration on both weekdays and weekends with all-cause and CVD mortality. Self-reported short (≤4 hours) and long (>8 hours) sleep duration on weekdays and weekends were associated with an increased risk of all-cause and CVD mortality compared with 7 to 8 hours sleep duration. Furthermore, a weak correlation was observed between objective and self-reported sleep duration. Conclusions This study showed that both objective and self-reported sleep duration were associated with all-cause and CVD mortality, but with different characteristics. Registration URL: https://clinicaltrials.gov/ct2/show/NCT00005275; Unique identifier: NCT00005275.
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Enfermedades Cardiovasculares , Femenino , Humanos , Masculino , Factores de Riesgo , Autoinforme , Sueño , Duración del Sueño , Encuestas y Cuestionarios , Persona de Mediana Edad , AncianoRESUMEN
The mechanism by which endometriosis, a common gynecological disease characterized by chronic pelvic pain and infertility, causes infertility remains elusive. Luteinized unruptured follicle syndrome, the most common type of ovulatory dysfunction, is a cause of endometriosis-associated infertility involving reduced numbers of retrieved and mature oocytes. Ovulation is controlled by luteinizing hormone and paracrine signals produced within the follicle microenvironment. Generally, interleukin (IL)-1ß is elevated in endometriosis follicular fluid, whereby it amplifies ovulation signals by activating extracellular-regulated kinase 1/2 and CCAAT/enhancer binding protein ß pathways. However, this amplification of ovulation by IL-1ß does not occur in patients with endometriosis. To illuminate the mechanism of ovulatory dysfunction in endometriosis, we analyzed the effect of oxidative stress and IL-1ß expression on endometriosis follicles. We found that oxidative stress decreased EZH2 expression and reduced H3K27Me3 levels in endometriosis ovarian granulosa cells (GCs). Selective Ezh2 depletion in mice ovarian GCs reduced fertility by disturbing cumulus-oocyte complex expansion and reducing epidermal growth factor-like factor expression. Gene expression and H3K27Me3 ChIP-sequencing (ChIP-Seq) of GCs revealed IL-1 receptor 2 (IL-1R2), a high-affinity IL-1ß-receptor that suppresses IL-1ß-mediated inflammatory cascades during ovulation, as a crucial target gene of the EZH2-H3K27Me3 axis. Moreover, IL-1ß addition did not restore ovulation upon Ezh2 knockdown, indicating a vital function of IL-1R2 in endometriosis. Thus, our findings show that reducing EZH2 and H3K27Me3 in GCs suppressed ovulatory signals by increasing IL-1R2 expression, which may ultimately contribute to endometriosis-associated infertility.
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Endometriosis , Infertilidad Femenina , Animales , Femenino , Ratones , Endometriosis/complicaciones , Endometriosis/genética , Endometriosis/metabolismo , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Células de la Granulosa/metabolismo , Histonas/metabolismo , Infertilidad Femenina/genética , Infertilidad Femenina/metabolismo , Receptores Tipo II de Interleucina-1/genética , Receptores Tipo II de Interleucina-1/metabolismo , HumanosRESUMEN
Herein, we introduced a novel individual sperm freezing device named SpermCD, which consists of a right angular cryopiece (RA-Cryopiece, or "C") and a grooved petri dish ("D"). SpermCD allows embryologists to transfer sperm and perform ICSI on the same focal plane. Thirty-five patients underwent single sperm cryopreservation using SpermCD, including four patients with non-obstructive azoospermia (NOA), 14 patients with virtual azoospermia and 17 patients with cryptozoospermia. One hundred and twenty-five cryopreserved spermatozoa from nine patients were thawed on the day of the oocyte retrieval and 121 spermatozoa were found, with a sperm recovery rate of 97.1 ± 4.6%. Sixty-five MII oocytes from their spouse were injected with thawed sperm. Normal fertilization and high-quality embryo rates were 68.0% ± 33.2% and 24.4% ± 22.2%. Nineteen transplantable embryos were formed after fertilization with frozen sperm, eight of which were transplanted in five couples, resulting in four successful deliveries. SpermCD is a simple and practical individual sperm freezing device.
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Azoospermia , Humanos , Masculino , Azoospermia/terapia , Inyecciones de Esperma Intracitoplasmáticas/métodos , Congelación , Transferencia de Embrión , Espermatozoides , Criopreservación/métodos , TestículoRESUMEN
Recurrent pregnancy loss (RPL) is a severe complication of pregnancy that is caused by genetic abnormalities, immune dysfunction, aberrant cell biology, and tissue structure destruction. Among which, placental dysfunction is crucial in the pathogenetic progression of RPL. Although some regulatory factors associated with RPL have been reported, the placental changes correlated with RPL still need to be elucidated. Here, we found that a portion of RPL patients presented with low serum and placental S100P expression. Using a human trophoblast stem cell model, we demonstrated that S100P was exclusively expressed in syncytiotrophoblast (ST)-like syncytia (ST(2D)-TSCT) and that loss of S100P expression in ST(2D)-TSCT cells impaired ß-hCG secretion, leading to syncytialization failure during early placental development. Moreover, we found that S100P is involved in regulating trophoblast syncytialization by downregulating the protein level of Yes-associated protein 1 (YAP1), which plays a pivotal role in maintaining trophoblast stemness. Together, our findings suggest that S100P plays an essential role in regulating trophoblast syncytialization during early placental development in humans via YAP1. Additionally, lower serum S100P levels may predict poor pregnancy outcomes and represent a potentially useful marker for evaluating placental biological function during early pregnancy.