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Background: Previous epidemiological studies have reported associations between vitamin D and postpartum depression (PPD); however, the findings are inconsistent. This study employs bidirectional Mendelian Randomization (MR) to investigate the causal link between serum 25-hydroxyvitamin D [25(OH)D] levels and PPD. By utilizing genetic data from cohorts, this research aims to provide a more robust understanding of the potential relationship between vitamin D and PPD, addressing a critical gap in the current literature. Methods: A bidirectional MR analysis was conducted to investigate the genetic association between serum 25(OH)D and PPD using summary statistics extracted from GWAS datasets. The study included data from 15,668 patients with PPD and 376,755 healthy controls of European ancestry. The GWAS data for 25(OH)D were obtained from two studies within the UK Biobank, encompassing 496,946 and 79,366 participants. The primary analysis employed the inverse-variance weighted (IVW) method, while supplementary MR estimates were derived through the MR-Egger and weighted median (WME) methods. Furthermore, sensitivity analyses were implemented to ensure robustness and reliability, including Cochran's Q test, MR-PRESSO, MR-Egger intercept test, and the leave-one-out test. Results: The MR study revealed no substantial genetic correlation between serum 25(OH)D levels and PPD (OR = 1.065, 95%CI = 0.878-1.293, P = 0.522 for set A; OR = 0.978, 95 % CI = 0.669-1.430, P = 0.910 for set B). Additionally, in the reverse analysis, we did not observe a significant causal impact of PPD on serum 25(OH)D (OR = 1.001, 95%CI = 0.974-1.028, P = 0.951 for set A; OR = 1.011, 95%CI = 0.992-1.031, P = 0.261 for set B). The results obtained from MR-Egger and WME analyses concord with those derived from the IVW method. Conducting leave-one-out tests did not identify any single nucleotide polymorphism that might have influenced the MR results, confirming the robustness and reliability of the findings. Conclusions: The results suggest the absence of a causal link between vitamin D concentrations and PPD. Inconsistent observations in previous observational studies may be attributed to residual confounding.
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Objective and Impact Statement: High-intensity focused ultrasound (HIFU) therapy is a promising noninvasive method that induces coagulative necrosis in diseased tissues through thermal and cavitation effects, while avoiding surrounding damage to surrounding normal tissues. Introduction: Accurate and real-time acquisition of the focal region temperature field during HIFU treatment marked enhances therapeutic efficacy, holding paramount scientific and practical value in clinical cancer therapy. Methods: In this paper, we initially designed and assembled an integrated HIFU system incorporating diagnostic, therapeutic, and temperature measurement functionalities to collect ultrasound echo signals and temperature variations during HIFU therapy. Furthermore, we introduced a novel multimodal teacher-student model approach, which utilizes the shared self-expressive coefficients and the deep canonical correlation analysis layer to aggregate each modality data, then through knowledge distillation strategies, transfers the knowledge from the teacher model to the student model. Results: By investigating the relationship between the phantoms, in vitro, and in vivo ultrasound echo signals and temperatures, we successfully achieved real-time reconstruction of the HIFU focal 2D temperature field region with a maximum temperature error of less than 2.5 °C. Conclusion: Our method effectively monitored the distribution of the HIFU temperature field in real time, providing scientifically precise predictive schemes for HIFU therapy, laying a theoretical foundation for subsequent personalized treatment dose planning, and providing efficient guidance for noninvasive, nonionizing cancer treatment.
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The mechanism involved in the pathogenesis of endometriosis is poorly understood. The purpose of this study is to identify key deubiquitinating enzymes (DUBs) for endometriosis diagnosis and elucidate the possible mechanism, offering novel insights for noninvasive early diagnosis and treatment. Four gene expression datasets were employed from the Gene Expression Omnibus to identify differentially expressed genes (DEGs) between endometriosis and normal controls. GO and KEGG pathways were performed for enrichment analysis. Calibration curves, ROC, DCA, and clinical impact curves verified the clinical usefulness of the nomogram model. In addition, the ssGSEA method was conducted to estimate 23 types of immune cells. A specific DUB gene signature was constructed with Lasso regression, univariate logistic regression, and SVM analysis. RT-qPCR validated the expression of biomarkers. A total of 85 endometriosis-related DUBs were identified in the eutopic endometrium. Among them, 20 DUBs were found to be correlated with the severity of endometriosis. A diagnostic risk model based on five DUB-related genes (USP21, USP48, ZRANB1, COPS5, and EIF3F) was developed using lasso-cox regression analysis. The nomogram model exhibited a strong predictive ability to diagnose endometriosis. KEGG analysis revealed that ubiquitin-mediated proteolysis was activated in patients suffering from severe symptoms. Analysis of immune cell infiltration revealed a positive correlation between USP21 and multiple immune cells in the eutopic endometrium. However, EIF3F showed an opposite relationship. Dysregulation of DUBs was related to the immune microenvironment in endometriosis. Results from RT-qPCR confirmed the expression of DEGs in clinical samples. In summary, the diagnostic model for endometriosis constructed using five differentially expressed DUB genes demonstrates strong diagnostic capability, suggesting that these genes could serve as potential candidate biomarkers and therapeutic targets.
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Dermatomiositis , Inhibidores de las Cinasas Janus , Neoplasias , Humanos , Análisis de Mediación , AutoanticuerposRESUMEN
BACKGROUND: Down syndrome (DS), which is characterized by various malfunctions, is the most common chromosomal disorder. As the DS population continues to grow and most of those with DS live beyond puberty, early-onset health problems have become apparent. However, the cellular landscape and molecular alterations have not been thoroughly studied. METHODS: This study utilized single-cell resolution techniques to examine DS in humans and mice, spanning seven distinct organs. A total of 71 934 mouse and 98 207 human cells were analyzed to uncover the molecular alterations occurring in different cell types and organs related to DS, specifically starting from the fetal stage. Additionally, SA-ß-Gal staining, western blot, and histological study were employed to verify the alterations. RESULTS: In this study, we firstly established the transcriptomic profile of the mammalian DS, deciphering the cellular map and molecular mechanism. Our analysis indicated that DS cells across various types and organs experienced senescence stresses from as early as the fetal stage. This was marked by elevated SA-ß-Gal activity, overexpression of cell cycle inhibitors, augmented inflammatory responses, and a loss of cellular identity. Furthermore, we found evidence of mitochondrial disturbance, an increase in ribosomal protein transcription, and heightened apoptosis in fetal DS cells. This investigation also unearthed a regulatory network driven by an HSA21 gene, which leads to genome-wide expression changes. CONCLUSION: The findings from this study offer significant insights into the molecular alterations that occur in DS, shedding light on the pathological processes underlying this disorder. These results can potentially guide future research and treatment development for DS.
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Síndrome de Down , Humanos , Ratones , Animales , Síndrome de Down/genética , Síndrome de Down/metabolismo , Síndrome de Down/patología , MamíferosRESUMEN
RATIONALE: Mayer-Rokitansky-Küster-Hauser syndrome (MRKH syndrome) present with genital inguinal hernia was rare and probably under reported, on account of lack in typical gynecological symptom. It should be regarded with care.Here 3 cases diagnosed at our institution with detailed clinical information were present, and the literature was reviewed to paint a comprehensive profile of hernia uterine inguinale associated with MRKH syndrome. PATIENT CONCERNS: Case no. 1 was a 36-year-old female with recurrent dragalgia for 5 years. Left rudimentary uterus at the left groin area was revealed by sonography scan and confirmed by diagnostic laparoscopy.Case no. 2 was a 27-year-old woman diagnosed with MRKH syndrome and her MRI examination suggested a suspicious swelling measuring 2.0cm×2.0cm in left groin. The left nonfunctionally rudimentary uterus and adnexa were incarcerated in the left inguinal hernial sac, which was revealed by laparoscopy.Case no. 3 was a 29-year-old woman, admitted with right abdominal pain with a provisional diagnosis of appendicitis. After appendicectomy, pelvic exploration showed a part of left rudimentary uterus and elongated oviduct herniated through the left internal inguinal ring. DIAGNOSES: Hernia uterine inguinale associated with MRKH syndrome. INTERVENTIONS AND OUTCOMES: Case no.1: When the rudimentary uterus was pulled out from the hernia sac, it appearance dark ocher. Then the left rudimentary uterus was removed and the indirect defect of inguinal duct was closed.The patient was followed up for 18 months with no recurrence of abdominal pain.Case no.2 and 3:The left rudimentary uterus were replaced from the hernia sac, and the indirect defect was fixed with sutures.The patients recovered smoothly without complications for 12-month follow-up. LESSONS: Left involvement of rudimentary uterus was frequently observed in patients with MRKH syndrome, along with ipsilateral ovary and/or fallopian tube horned in the hernia. Abdominal pain or inguinale mass could be the chief complaints while some individuals were asymptomatic. Either surgical removal or replacement of rudimentary uterus was an effectively optional treatment strategy for hernia uterine inguinale.When a patient with MRKH syndrome presented with abdominal pain of unknown cause or inguinal mass, rudimentary uterine inguinal hernia should be suspected.
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Anomalías Múltiples , Anomalías Congénitas , Hernia Inguinal , Humanos , Femenino , Adulto , Anomalías Múltiples/diagnóstico , Hernia Inguinal/etiología , Útero/cirugía , Conductos Paramesonéfricos , Dolor Abdominal , Anomalías Congénitas/diagnósticoRESUMEN
BACKGROUND: Antenatal depression might cause adverse pregnancy outcomes. However, previous study results were inconsistent, especially in the low- and middle- income countries. We aimed to study the association between antenatal depression and adverse perinatal outcomes in a Chinese population. METHODS: We performed a prospective cohort study and enrolled pregnant women from January 2020 to January 2021. Antenatal depressive symptoms in the third trimester of pregnancy were evaluated by the Edinburgh Postpartum Depression Scale (EPDS). Baseline characteristics and pregnancy outcomes were recorded. After adjusting for confounding factors (age, occupation, education level, and annual income), multivariate logistic regression analysis was applied to evaluate the associations between antenatal depression and pregnancy outcomes. RESULTS: Among the 5209 participants, 1448 (27.7 %) pregnant women were positive for depression. After adjusting for potential confounders, women with antenatal depressive symptoms were significantly more likely to deliver prematurely [Odds ratio (OR) = 1.404, 95 % confidence interval (CI) = 1.020-1.933, P = 0.037] and receive cesarean section (OR = 1.154, 95 % CI = 1.002-1.331, P = 0.048). LIMITATIONS: EPDS, not a structured diagnostic interview, was used for psychological assessment. In addition, we only screened the women in their third trimester in a single research center. The association between the duration of antenatal depression and perinatal outcomes was not evaluated. CONCLUSIONS: Depressive symptoms were common among Chinese women in their third trimester of pregnancy. Women with antenatal depressive symptoms had increased cesarean section and preterm delivery risks. Screening and treatment for antenatal depression are needed during the prenatal care.
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Depresión Posparto , Complicaciones del Embarazo , Recién Nacido , Embarazo , Femenino , Humanos , Depresión/epidemiología , Depresión/diagnóstico , Depresión Posparto/diagnóstico , Depresión Posparto/epidemiología , Depresión Posparto/psicología , Estudios Prospectivos , Cesárea , Complicaciones del Embarazo/psicología , PartoRESUMEN
BACKGROUND: Placement of a levonorgestrel-releasing intrauterine system (LNG-IUS) is an effective treatment for adenomyosis, especially for patients who have severe dysmenorrhea symptoms but a strong desire to preserve fertility. Nonetheless, for patients with adenomyosis accompanied by an enlarged uterus, expulsion of the ring is a troublesome problem. In this study, we sewed and fixed the LNG-IUS in the uterus, which provides a good solution to this problem. METHODS: In this prospective case series approved by the Ethics Committee of Hangzhou Women's Hospital, 12 patients with adenomyosis were successfully enrolled after providing informed consent, and all patients underwent long-term postoperative follow-up. RESULTS: Twelve patients with adenomyosis underwent suture fixation with an LNG-IUS, and during the long-term postoperative follow-up, every patient experienced complete remission of their symptoms: a significant decrease in menstrual flow, relief of dysmenorrhea, and improvement in quality of life. Only one person reported expulsion a year later. CONCLUSION: In patients with adenomyosis suffering from dysmenorrhea or excessive menstrual blood loss, suture fixation of an LNG-IUS using the hysteroscopic cold knife surgery system is a minimally invasive and effective alternative treatment for adenomyosis and decreases the risk of LNG-IUS expulsion.
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Adenomiosis , Dispositivos Intrauterinos Medicados , Humanos , Femenino , Adenomiosis/complicaciones , Adenomiosis/tratamiento farmacológico , Adenomiosis/cirugía , Levonorgestrel/uso terapéutico , Dismenorrea/etiología , Dismenorrea/complicaciones , Calidad de Vida , SuturasRESUMEN
Background: Ovarian cancer (OC) is the leading cause of gynecologic malignant tumors. The role of necroptosis-related lncRNAs (NRLs) in OC remains unclear. This study aims to explore the association between NRLs and prognosis in OC patients. Methods: The Cancer Genome Atlas (TCGA) and GTEx datasets were used to obtain OC's data. A NRLs signature associated with overall survival (OS) was constructed by Cox-LASSO regression analysis in training cohort for calculating risk score and then validated in testing cohort. Subsequently, the area under the curve (AUC) and Kaplan-Meier survival analysis were used to evaluate the predictive accuracy of the risk score. Finally, the immune infiltration and functional enrichment were compared between different risk groups. Results: A 8-NRLs signature including AC245128.3, AL355488.1, AC092794.1, AC068888.2, AL590652.1, AC008982.2, FOXP4-AS1, and Z94721.1 was identified to assess the OS of OC. Kaplan-Meier survival analysis, AUC value, and Cox regression analysis confirmed its predictive value and showed that the clinical outcomes were worse for high-risk patients. There were also differences in immunological functioning and immune pathways between the high-risk and low-risk groups. Conclusions: The signature based on eight NRLs has significant values in predicting prognostic prediction in OC, as well as providing a new sight for targeted therapies.
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AIMS: To introduce and compare the modified laparoscopic Vecchietti and Davydov techniques for vaginoplasty in patients with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. Moreover, the long-term treatment of vaginal agenesis was followed-up. METHODS: This comparative retrospective cohort study enrolled a total of 53 women with MRKH syndrome. The patients underwent surgical creation of a neovagina including 32 patients who underwent the modified laparoscopic Vecchietti technique, and 21 patients who underwent the modified laparoscopic Davydov technique from January 2009 to February 2019. The perioperative parameters, complications, anatomical, and functional outcomes of the two groups were compared. Patients' sexual functions were evaluated over a long-term follow-up using the female sexual function index (FSFI) and the revised female sexual distress scale (FSDS-R). RESULTS: The medians (25th-75th) of the surgery duration for modified Vecchietti procedures was 50.0 (40.0-59.0) minutes, comparing to 135.0 (117.5-162.5) min for Davydov procedures (p < 0.001). The intraoperative blood loss was 20 (7.5-20.0) mL versus 50.0 (50.0-100.0) mL using the modified Vecchietti and Davydov approaches (p < 0.001), respectively. In the 39 follow-up cases, the lengths of the neovagina of the patients for Vecchietti group versus Davydov group were 7.9 ± 1.0 cm versus 8.6 ± 1.2 cm at 6 months after the vaginoplasty and 8.3 ± 0.7 cm versus 8.5 ± 0.9 cm after 2 years. There was no statistical difference in the FSFI and FSDS-R scores between the two groups. CONCLUSIONS: Both the modified Davydov and Vecchietti laparoscopic procedures successfully achieved optimal anatomic and functional outcomes in treatments of vaginal agenesis. The modified Vecchietti technique is relatively simpler than the modified Davydov technique.
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Trastornos del Desarrollo Sexual 46, XX , Anomalías Congénitas , Laparoscopía , Procedimientos de Cirugía Plástica , Trastornos del Desarrollo Sexual 46, XX/cirugía , Anomalías Congénitas/cirugía , Femenino , Estudios de Seguimiento , Humanos , Laparoscopía/métodos , Conductos Paramesonéfricos/anomalías , Conductos Paramesonéfricos/cirugía , Procedimientos de Cirugía Plástica/métodos , Estudios Retrospectivos , Resultado del Tratamiento , Vagina/anomalías , Vagina/cirugíaRESUMEN
One type of age-related macular degeneration (AMD), neovascular (nAMD), characterized by choroidal neovascularization (CNV), accounts for the majority of the severe central vision impairment associated with AMD. Endothelial cells (ECs) in direct contact with retinal pigment epithelial (RPE) cells are more prone to the pathological angiogenesis involved in CNV. Herein, we investigated the effect of crosstalk between RPE cells and choroidal endothelial cells (CECs) via the ANXA1/FPR2/NLRP3 inflammasome/pyroptosis axis on the development of choroidal neovascularization (CNV) in vitro and in vivo. ANXA1 expression and secretion from ARPE-19 cells were upregulated by hypoxia. FPR2 expression, especially on the plasma membrane, in HCECs was upregulated under hypoxic conditions. ANXA1 secreted from ARPE-19 cells inhibited NLRP3 inflammasome activation and NLRP3 inflammasome-mediated pyroptosis in HCECs by activating the FPR2/SHP2 axis. Moreover, ANXA1 secreted by ARPE-19 cells promoted behaviors of HCECs, including proliferation, migration, and tube formation, by activating the FPR2/SHP2 axis and inhibiting NLRP3 inflammasome-mediated pyroptosis. Inhibiting the upregulated ANXA1/FPR2/SHP2/NLRP3 inflammasome/pyroptosis axis decreased the volume of CNV. Our data suggest that the crosstalk between RPE cells and CECs via the ANXA1/FPR2/NLRP3 inflammasome/pyroptosis axis promotes CNV. This finding could identify a potential target for the prevention and treatment of CNV.
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Coroides/metabolismo , Neovascularización Coroidal/metabolismo , Células Endoteliales/metabolismo , Inflamasomas/metabolismo , Piroptosis , Epitelio Pigmentado de la Retina/metabolismo , Anexina A1/metabolismo , Biomarcadores/metabolismo , Línea Celular , Humanos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína Tirosina Fosfatasa no Receptora Tipo 11/metabolismo , Receptores de Formil Péptido/metabolismo , Receptores de Lipoxina/metabolismoRESUMEN
AIM: To introduce the novel use of lauromacrogol for cesarean scar pregnancy (CSP), and to compare the clinical efficacy and safety of curettage combined with ultrasound-guided sclerosant injection (USI) and curettage following uterine artery embolization (UAE) in the treatment of CSP. METHODS: CSP patients undergoing curettage combined with USI (n = 72) from December 2014 to May 2020 were compared to patient with curettage following UAE (n = 72).The basic clinical findings and clinical outcomes were reviewed between the two groups. RESULTS: For USI group, 69 patients underwent successful treatment (95.8% success rate), while the number of cured patients for the UAE group was 70 (97.2% success rate). Differences between USI group and UAE group in intraoperative blood loss (10.0 [10.0-20.0] vs. 10.0 [10.0-20.0] mL) and time for serum ß human chorionic gonadotropin (ß-hCG) to reduce to normal (28.0 [21.0-40.0] vs. 28.0 [21.0-35.0] days) were not statistically significant. The hospital stay for USI group was significantly shorter than that for UAE group (4.0 [4.0-6.0] vs. 6.0 [5.0-7.0] days, respectively). Statistically significant decreases were noted in hospitalization expenses and adverse events in USI group, compared to UAE group. There was no difference in live birth rate between the two groups with fertility intentions during the follow-up. CONCLUSION: For treatment of CSP, curettage combined with USI yielded clinical results comparable to those of curettage following UAE. Curettage combined with USI was associated with lower hospitalization expenses, shorter hospital stay and less complications, and it merited an effective and safe treatment for CSP.
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Soluciones Esclerosantes , Embolización de la Arteria Uterina , Cesárea/efectos adversos , Cicatriz/terapia , Femenino , Humanos , Metotrexato , Polidocanol , Embarazo , Estudios Retrospectivos , Resultado del Tratamiento , Ultrasonografía IntervencionalRESUMEN
Geniposide (GEN) is a natural antioxidant and anti-inflammatory product and plays an important role in the treatment of diabetes and diabetic complications. To explore the biological functions and mechanism of GEN in diabetic retinopathy (DR), we constructed the in vitro and in vivo model of DR by using primary cultured mouse retinal Müller cells and C57BL/6 mice, respectively. We found that GEN inhibited ROS accumulation, NF-κB activation, Müller cell activation, and inflammatory cytokine secretion both in vitro and in vivo, which is probably mediated through the Nrf2 pathway. Exendin (9-39) (EX-9), an antagonist of glucagon-like peptide-1 receptor (GLP-1R), abolished the protective effect of GEN on high glucose- (HG-) induced Müller cells. Additionally, GEN decreased hyperglycemia-induced damage to Müller cells and blood-retinal barrier in the retinas of mice with DR. We demonstrated that GEN was capable of protecting Müller cells and mice from HG-induced oxidative stress and inflammation, which is mostly dependent on the Nrf2 signaling pathway through GLP-1R. GEN may be an effective approach for the treatment of DR.
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Diabetes Mellitus Experimental/complicaciones , Retinopatía Diabética/prevención & control , Hiperglucemia/complicaciones , Inflamación/prevención & control , Iridoides/farmacología , Factor 2 Relacionado con NF-E2/agonistas , Estrés Oxidativo , Animales , Retinopatía Diabética/etiología , Retinopatía Diabética/metabolismo , Retinopatía Diabética/patología , Células Ependimogliales/efectos de los fármacos , Células Ependimogliales/metabolismo , Células Ependimogliales/patología , Inflamación/etiología , Inflamación/metabolismo , Inflamación/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Choroidal neovascularization (CNV), a feature of neovasular age-related macular degeneration (AMD), acts as a leading cause of vision loss in the elderly. Shikonin (SHI), a natural bioactive compound extracted from Chinese herb radix arnebiae, exerts anti-inflammatory and anti-angiogenic roles and also acts as a potential pyruvate kinase M2 (PKM2) inhibitor in macrophages. The major immune cells macrophages infiltrate the CNV lesions, where the production of pro-angiognic cytokines from macrophage facilitates the development of CNV. PKM2 contributes to the neovascular diseases. In this study, we found that SHI oral gavage alleviated the leakage, area and volume of mouse laser-induced CNV lesion and inhibited macrophage infiltration without ocular cytotoxicity. Moreover, SHI inhibited the secretion of pro-angiogenic cytokine, including basic fibroblast growth factor (FGF2), insulin-like growth factor-1 (IGF1), chemokine (C-C motif) ligand 2 (CCL2), placental growth factor and vascular endothelial growth factor (VEGF), from primary human macrophages by down-regulating PKM2/STAT3/CD163 pathway, indicating a novel potential therapy strategy for CNV.
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Inhibidores de la Angiogénesis/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Neovascularización Coroidal/tratamiento farmacológico , Macrófagos/efectos de los fármacos , Naftoquinonas/uso terapéutico , Piruvato Quinasa/antagonistas & inhibidores , Inductores de la Angiogénesis/metabolismo , Animales , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Western Blotting , Células Cultivadas , Neovascularización Coroidal/enzimología , Cromatografía Líquida de Alta Presión , Colorantes/administración & dosificación , Citocinas/metabolismo , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/uso terapéutico , Ensayo de Inmunoadsorción Enzimática , Angiografía con Fluoresceína , Humanos , Etiquetado Corte-Fin in Situ , Verde de Indocianina/administración & dosificación , Macrófagos/enzimología , Masculino , Ratones , Ratones Endogámicos C57BL , Fosforilación , Piruvato Quinasa/metabolismo , Receptores de Superficie Celular/antagonistas & inhibidores , Receptores de Superficie Celular/metabolismo , Factor de Transcripción STAT3/antagonistas & inhibidores , Factor de Transcripción STAT3/metabolismoRESUMEN
BACKGROUND: Not only glycolysis but also lncRNAs play a significant role in the growth, proliferation, invasion and metastasis of of ovarian cancer (OC). However, researches about glycolysis -related lncRNAs (GRLs) remain unclear in OC. Herein, we first constructed a GRL-based risk model for patients with OC. METHODS: The processed RNA sequencing (RNA-seq) profiles with clinicopathological data were downloaded from TCGA and glycolysis-related genes (GRGs) were obtained from MSigDB. Pearson correlation coefficient between glycolysis-related genes (GRGs) and annotated lncRNAs (|r| > 0.4 and p < 0.05) were calculated to identify GRLs. After screening prognostic GRLs, a risk model based on five GRLs was constructed using Univariate and Cox regression. The identified risk model was validated by two validation sets. Further, the differences in clinicopathology, biological function, hypoxia score, immune microenvironment, immune checkpoint, immune checkpoint blockade, chemotherapy drug sensitivity, N6-methyladenosine (m6A) regulators, and ferroptosis-related genes between risk groups were explored by abundant algorithms. Finally, we established networks based on co-expression, ceRNA, cis and trans interaction. RESULTS: A total of 535 GRLs were gained and 35 GRLs with significant prognostic value were identified. The prognostic signature containing five GRLs was constructed and validated and can predict prognosis. The nomogram proved the accuracy of the model for predicting prognosis. After computing hypoxia score of each sample by ssGSEA, we found patients with higher risk scores exhibited higher hypoxia score and high hypoxia score was a risk factor. It was revealed that a total of 21 microenvironment cells (such as Central memory CD4 T cell, Neutrophil, Regulatory T cell and so on) and Stromal score had significant differences between the two groups. Four immune checkpoint genes (CD274, LAG3, VTCN1, and CD47) showed disparate expression levels in the two groups. Besides, 16 m6A regulators and 126 ferroptosis-related genes were expressed higher in the low-risk group. GSEA revealed that the risk groups were associated with tumor-related pathways. The two risk groups were confirmed to be sensitive to several chemotherapeutic agents and patients in the low-risk group were more sensitive to ICB therapy. The networks based on co-expression, ceRNA, cis and trans interaction provided insights into the regulatory mechanisms of GRLs. CONCLUSIONS: Our identified and validated risk model based on five GRLs is an independent prognostic factor for OC patients. Through comprehensive analyses, findings of our study uncovered potential biomarker and therapeutic target for the risk model based on the GRLs.
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Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Femenino , Glucólisis , Humanos , PronósticoRESUMEN
OBJECTIVE: To introduce an effective approach using the hysteroscopic cold-knife surgery system (HCSS) for suture fixation of the levonorgestrel-releasing intrauterine device (LNG-IUD) in patients with adenomyosis. DESIGN: Video description of the surgical procedures to demonstrate the detailed technique. The study was reviewed and approved by the institutional review board of Hangzhou Women's Hospital. SETTING: Maternity hospital. PATIENT(S): A 39-year-old woman diagnosed with adenomyosis had endured 7 years of severe dysmenorrhea and 4 years of heavy menstrual bleeding. She had a past medical history that was significant for expulsion of an LNG-IUD. Transvaginal ultrasonography revealed that her uterus was enlarged by adenomyosis. She insisted on preserving fertility potential. INTERVENTION(S): We proceeded with the HCSS and the uterine cavity was found enlarged significantly. In consideration of the patient's strong desire for maintaining fertility options, the fixation of the LNG-IUD on the intrauterine posterior wall with an Ethibond suture was performed successfully through an endoscopic needle driver and a knot-pushing device. Proficient endoscopic suturing is the key to the technique. Informed consent was obtained from the patient. MAIN OUTCOME MEASURE(S): Feasibility and value of using the HCSS to fix an LNG-IUD for treatment of adenomyosis. RESULT(S): The LNG-IUD was fixed successfully by the HCSS with an Ethibond suture on the posterior wall of the uterus within 30 minutes, and the intraoperative blood loss was 2 mL. The patient was discharged 24 hours postoperatively without any adverse perioperative complications. At the one-year follow-up, the patient reported obvious relief of her dysmenorrhea and menorrhagia and no more experience with expulsion. Ultrasound demonstrated normal position of the IUD at 1, 3, 6, and 12 months postoperatively. CONCLUSION(S): Hysteroscopy presents a clear visual field to locate and fix the IUD. In patients with adenomyosis suffering from dysmenorrhea or excessive menstrual blood loss, suture fixation of the LNG-IUD using the HCSS can be a minimally invasive and effective alternative for treating adenomyosis, especially in patients who have previously expelled an LNG-IUD, preventing the risk of expulsion.
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Adenomiosis/terapia , Agentes Anticonceptivos Hormonales/administración & dosificación , Criocirugía , Histeroscopía , Dispositivos Intrauterinos Medicados , Levonorgestrel/administración & dosificación , Técnicas de Sutura , Adenomiosis/diagnóstico por imagen , Adulto , Femenino , Humanos , Resultado del TratamientoRESUMEN
Diabetic retinopathy (DR) is a vision-loss complication caused by diabetes with high prevalence. During DR, the retinal microvascular injury and neurodegeneration derived from chronic hyperglycemia have attracted global attention to retinal Müller cells (RMCs), the major macroglia in the retina contributes to neuroprotection. Protein Phosphatase 1 Catalytic Subunit Alpha (PPP1CA) dephosphorylates the transcriptional coactivator Yes-associated protein (YAP) to promote the transcription of glutamine synthetase (GS). GS catalyzes the transformation of neurotoxic glutamate (Glu) into nontoxic glutamine (Gln) to activate the mammalian target of rapamycin complex 1 (mTORC1), which promotes the activation of RMCs. In this study, in vitro MIO-M1 cell and in vivo mouse high-fat diet and streptozotocin (STZ)-induced diabetic model to explore the role of the PPP1CA/YAP/GS/Gln/mTORC1 pathway on the activation of MRCs during DR. Results showed that PPP1CA promoted the dephosphorylation and nuclear translocation of YAP in high glucose (HG)-exposed MIO-M1 cells. YAP transcribed GS in HG-exposed MIO-M1 cells in a TEAD1-dependent and PPP1CA-dependent way. GS promoted the biosynthesis of Gln in HG-exposed MIO-M1 cells. Gln activated mTORC1 instead of mTORC2 in HG-exposed MIO-M1 cells. The proliferation and activation of HG-exposed MIO-M1 cells were PPP1CA/YAP/GS/Gln/mTORC1-dependent. Finally, RMC proliferation and activation during DR were inhibited by the PPP1CA/YAP/GS/Gln/mTORC1 blockade. The findings supplied a potential idea to protect RMCs and alleviate the development of DR.