RESUMEN
BACKGROUND AND PURPOSE: Colorectal cancer (CRC) is a widespread malignancy with a complex and not entirely elucidated pathogenesis. This study aims to explore the role of Bifidobacterium in the urea cycle (UC) and its influence on the progression of CRC, a topic not extensively studied previously. EXPERIMENTAL APPROACH: Utilizing both bioinformatics and experimental methodologies, this research involved analyzing bacterial abundance in CRC patients in comparison to healthy individuals. The study particularly focused on the abundance of BA. Additionally, transcriptomic data analysis and cellular experiments were conducted to investigate the impact of Bifidobacterium on ammonia metabolism and mitochondrial function, specifically examining its regulation of the key UC gene, ALB. KEY RESULTS: The analysis revealed a significant decrease in Bifidobacterium abundance in CRC patients. Furthermore, Bifidobacterium was found to suppress ammonia metabolism and induce mitochondrial dysfunction through the regulation of the ALB gene, which is essential in the context of UC. These impacts contributed to the suppression of CRC cell proliferation, a finding corroborated by animal experimental results. CONCLUSIONS AND IMPLICATIONS: This study elucidates the molecular mechanism by which Bifidobacterium impacts CRC progression, highlighting its role in regulating key metabolic pathways. These findings provide potential targets for novel therapeutic strategies in CRC treatment, emphasizing the importance of microbiota in cancer progression.
Asunto(s)
Bifidobacterium , Neoplasias Colorrectales , Urea , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/microbiología , Neoplasias Colorrectales/patología , Bifidobacterium/metabolismo , Humanos , Urea/metabolismo , Animales , Proliferación Celular , Amoníaco/metabolismo , Ratones , Mitocondrias/metabolismo , Línea Celular Tumoral , Masculino , Microbioma Gastrointestinal/fisiología , FemeninoRESUMEN
Therapeutics for eradicating hepatitis B virus (HBV) infection are still limited and current nucleos(t)ide analogs (NAs) and interferon are effective in controlling viral replication and improving liver health, but they cannot completely eradicate the hepatitis B virus and only a very small number of patients are cured of it. The TCR-like antibodies recognizing viral peptides presented on human leukocyte antigens (HLA) provide possible tools for targeting and eliminating HBV-infected hepatocytes. Here, we generated three TCR-like antibodies targeting three different HLA-A2.1-presented peptides derived from HBV core and surface proteins. Bispecific antibodies (BsAbs) were developed by fuzing variable fragments of these TCR-like mAbs with an anti-CD3ϵ antibody. Our data demonstrate that the BsAbs could act as T cell engagers, effectively redirecting and activating T cells to target HBV-infected hepatocytes in vitro and in vivo. In HBV-persistent mice expressing human HLA-A2.1, two infusions of BsAbs induced marked and sustained suppression in serum HBsAg levels and also reduced the numbers of HBV-positive hepatocytes. These findings highlighted the therapeutic potential of TCR-like BsAbs as a new strategy to cure hepatitis B.
Asunto(s)
Anticuerpos Biespecíficos , Modelos Animales de Enfermedad , Virus de la Hepatitis B , Hepatitis B , Hepatocitos , Animales , Anticuerpos Biespecíficos/inmunología , Anticuerpos Biespecíficos/farmacología , Hepatocitos/virología , Hepatocitos/inmunología , Ratones , Humanos , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/genética , Hepatitis B/inmunología , Hepatitis B/virología , Antígeno HLA-A2/inmunología , Antígenos de Superficie de la Hepatitis B/inmunología , Receptores de Antígenos de Linfocitos T/inmunología , Linfocitos T/inmunologíaRESUMEN
OBJECTIVE: Colorectal cancer progression involves complex cellular mechanisms. This study examines the effects of Lactobacillus plantarum-derived extracellular vesicles (LEVs) on the SIRT5/p53 axis, focusing on glycolytic metabolic reprogramming and abnormal proliferation in intestinal epithelial cells. METHODS: LEVs were isolated from Lactobacillus plantarum and incubated with Caco-2 cells. Differential gene expression was analyzed through RNA sequencing and compared with TCGA-COAD data. Key target genes and pathways were identified using PPI network and pathway enrichment analysis. Various assays, including RT-qPCR, EdU staining, colony formation, flow cytometry, and Western blotting, were used to assess gene expression, cell proliferation, and metabolic changes. Co-immunoprecipitation confirmed the interaction between SIRT5 and p53, and animal models were employed to validate in vivo effects. RESULTS: Bioinformatics analysis indicated the SIRT5/p53 axis as a critical pathway in LEVs' modulation of colorectal cancer. LEVs were found to inhibit colorectal cancer cell proliferation and glycolytic metabolism by downregulating SIRT5, influencing p53 desuccinylation. In vivo, LEVs regulated this axis, reducing tumor formation in mice. Clinical sample analysis showed that SIRT5 and p53 succinylation levels correlated with patient prognosis. CONCLUSION: Lactobacillus-derived extracellular vesicles play a pivotal role in suppressing colonic tumor formation by modulating the SIRT5/p53 axis. This results in decreased glycolytic metabolic reprogramming and reduced proliferation in intestinal epithelial cells.
Asunto(s)
Proliferación Celular , Neoplasias Colorrectales , Vesículas Extracelulares , Glucólisis , Sirtuinas , Proteína p53 Supresora de Tumor , Sirtuinas/metabolismo , Sirtuinas/genética , Proteína p53 Supresora de Tumor/metabolismo , Humanos , Vesículas Extracelulares/metabolismo , Animales , Células CACO-2 , Ratones , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Células Epiteliales/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiología , Lactobacillus plantarum/metabolismo , Ratones Desnudos , Ratones Endogámicos BALB CRESUMEN
The etiology of preeclampsia (PE), a complex and multifactorial condition, remains incompletely understood. DNA methylation, which is primarily regulated by three DNA methyltransferases (DNMTs), DNMT1, DNMT3A, and DNMT3B, plays a vital role in early embryonic development and trophectoderm differentiation. Yet, how DNMTs modulate trophoblast fusion and PE development remains unclear. In this study, we found that the DNMTs expression was downregulated during trophoblast cells fusion. Downregulation of DNMTs was observed during the reconstruction of the denuded syncytiotrophoblast (STB) layer of placental explants. Additionally, overexpression of DNMTs inhibited trophoblast fusion. Conversely, treatment with the DNA methylation inhibitor 5-aza-CdR decreased the expression of DNMTs and promoted trophoblast fusion. A combined analysis of DNA methylation data and gene transcriptome data obtained from the primary cytotrophoblasts (CTBs) fusion process identified 104 potential methylation-regulated differentially expressed genes (MeDEGs) with upregulated expression due to DNA demethylation, including CD59, TNFAIP3, SDC1, and CDK6. The transcription regulation region (TRR) of TNFAIP3 showed a hypomethylation with induction of 5-aza-CdR, which facilitated CREB recruitment and thereby participated in regulating trophoblast fusion. More importantly, clinical correlation analysis of PE showed that the abnormal increase in DNMTs may be involved in the development of PE. This study identified placental DNA methylation-regulated genes that may contribute to PE, offering a novel perspective on the role of epigenetics in trophoblast fusion and its implication in PE development.
Asunto(s)
ADN (Citosina-5-)-Metiltransferasas , Metilación de ADN , Preeclampsia , Trofoblastos , Trofoblastos/metabolismo , Femenino , Preeclampsia/genética , Preeclampsia/metabolismo , Preeclampsia/patología , Embarazo , Humanos , ADN (Citosina-5-)-Metiltransferasas/genética , ADN (Citosina-5-)-Metiltransferasas/metabolismo , Fusión Celular , Placenta/metabolismo , ADN (Citosina-5-)-Metiltransferasa 1/metabolismo , ADN (Citosina-5-)-Metiltransferasa 1/genéticaRESUMEN
Purpose: To compare the influences of propofol, ciprofol and remimazolam on dreaming during painless gastrointestinal endoscopy. Methods: This study was a single-center, prospective, parallel-design, double-blind, randomized clinical trial. Between May 2023 and October 2023, patients undergoing elective painless gastrointestinal endoscopy were recruited and randomly allocated into one of the three groups. Demographic data, intraoperative information, incidence of dreaming, insufficient anesthesia and intraoperative awareness, type of dream, patient satisfaction score, adverse events, and improvement of sleep quality were collected. Results: The difference in incidence of dreaming among the three groups was not significant (33.33% vs 48.33% vs 41.67%, p=0.061). The number of patients with intraoperative hypotension in the propofol group was larger than that of the remimazolam group (32 vs 12, p=0.001). However, the cases of intraoperative hypotension between propofol group and ciprofol group or ciprofol group and remimazolam group were comparable (32 vs 22, p=0.122; 22 vs 12, p=0.064). The percentage of insufficient anesthesia between propofol group and remimazolam group was significant (13.33% vs 1.67%, p=0.001), while no statistical difference was detected between propofol group and remimazolam group or ciprofol group and remimazolam group (13.33% vs 5.00%, p=0.025; 5.00% vs 1.67%, p=0.150). The ability of propofol to improve sleep quality at 1st post-examination day was significantly better than that of remimazolam (86.21% vs 72.88%, p=0.015), while it was not significant between propofol group and ciprofol group or ciprofol group and remimazolam group (86.21% vs 80.36%, p=0.236; 72.88% vs. 72.88%, p=0.181). Incidence of intraoperative awareness, intraoperative hypoxia, type of dream, satisfaction score, adverse events during recovery, and sleep improvement on the 7th post-examination day was not significant among the groups. Conclusion: Anesthesia with propofol, ciprofol and remimazolam, respectively, for gastrointestinal endoscopy did not induce statistical difference in the incidence of dreaming, despite that all of them are more likely to induce pleasant dreams.
Asunto(s)
Sueños , Endoscopía Gastrointestinal , Propofol , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anestesia , Anestésicos Intravenosos/administración & dosificación , Benzodiazepinas/administración & dosificación , Benzodiazepinas/efectos adversos , Método Doble Ciego , Sueños/efectos de los fármacos , Propofol/administración & dosificación , Estudios ProspectivosRESUMEN
STUDY QUESTION: Can exposure to palmitic acid (PA), a common saturated fatty acid, modulate autophagy in both human and mouse trophoblast cells through the regulation of acyl-coenzyme A-binding protein (ACBP)? SUMMARY ANSWER: PA exposure before and during pregnancy impairs placental development through mechanisms involving placental autophagy and ACBP expression. WHAT IS KNOWN ALREADY: High-fat diets, including PA, have been implicated in adverse effects on human placental and fetal development. Despite this recognition, the precise molecular mechanisms underlying these effects are not fully understood. STUDY DESIGN, SIZE, DURATION: Extravillous trophoblast (EVT) cell line HTR-8/SVneo and human trophoblast stem cell (hTSC)-derived EVT (hTSCs-EVT) were exposed to PA or vehicle control for 24 h. Female wild-type C57BL/6 mice were divided into PA and control groups (n = 10 per group) and subjected to a 12-week dietary intervention. Afterward, they were mated with male wild-type C57BL/6 mice and euthanized on Day 14 of gestation. Female ACBPflox/flox mice were also randomly assigned to control and PA-exposed groups (each with 10 mice), undergoing the same dietary intervention and mating with ACBPflox/floxELF5-Cre male mice, followed by euthanasia on Day 14 of gestation. The study assessed the effects of PA on mouse embryonic development and placental autophagy. Additionally, the role of ACBP in the pathogenesis of PA-induced placental toxicity was investigated. PARTICIPANTS/MATERIALS, SETTING, METHODS: The findings were validated using real-time PCR, Western blot, immunofluorescence, transmission electron microscopy, and shRNA knockdown approaches. MAIN RESULTS AND THE ROLE OF CHANCE: Exposure to PA-upregulated ACBP expression in both human HTR-8/SVneo cells and hTSCs-EVT, as well as in mouse placenta. PA exposure also induced autophagic dysfunction in HTR-8/SVneo cells, hTSCs-EVT, and mouse placenta. Through studies on ACBP placental conditional knockout mice and ACBP knockdown human trophoblast cells, it was revealed that reduced ACBP expression led to trophoblast malfunction and affected the expression of autophagy-related proteins LC3B-II and P62, thereby impacting embryonic development. Conversely, ACBP knockdown partially mitigated PA-induced impairment of placental trophoblast autophagy, observed both in vitro in human trophoblast cells and in vivo in mice. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Primary EVT cells from early pregnancy are fragile, limiting research use. Maintaining their viability is tough, affecting data reliability. The study lacks depth to explore PA diet cessation effects after 12 weeks. Without follow-up, understanding postdiet impacts on pregnancy stages is incomplete. Placental abnormalities linked to elevated PA diet in embryos lack confirmation due to absence of control groups. Clarifying if issues stem solely from PA exposure is difficult without proper controls. WIDER IMPLICATIONS OF THE FINDINGS: Consuming a high-fat diet before and during pregnancy may result in complications or challenges in successfully carrying the pregnancy to term. It suggests that such dietary habits can have detrimental effects on the health of both the mother and the developing fetus. STUDY FUNDING/COMPETING INTEREST(S): This work was supported in part by the National Natural Science Foundation of China (82171664, 82301909) and the Natural Science Foundation of Chongqing Municipality of China (CSTB2022NS·CQ-LZX0062, cstc2019jcyj-msxmX0749, and cstc2021jcyj-msxmX0236). The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.
RESUMEN
BACKGROUND: In the realm of assisted reproduction, a subset of infertile patients demonstrates high ovarian response following controlled ovarian stimulation (COS), with approximately 29.7% facing the risk of Ovarian Hyperstimulation Syndrome (OHSS). Management of OHSS risk often necessitates embryo transfer cancellation, leading to delayed prospects of successful pregnancy and significant psychological distress. Regrettably, these patients have received limited research attention, particularly regarding their metabolic profile. In this study, we aim to utilize gas chromatography-mass spectrometry (GC-MS) to reveal these patients' unique serum metabolic profiles and provide insights into the disease's pathogenesis. METHODS: We categorized 145 infertile women into two main groups: the CON infertility group from tubal infertility patients and the Polycystic Ovary Syndrome (PCOS) infertility group. Within these groups, we further subdivided them into four categories: patients with normal ovarian response (CON-NOR group), patients with high ovarian response and at risk for OHSS (CON-HOR group) within the CON group, as well as patients with normal ovarian response (PCOS-NOR group) and patients with high ovarian response and at risk for OHSS (PCOS-HOR group) within the PCOS group. Serum metabolic profiles were analyzed using GC-MS. The risk criteria for OHSS were: the number of developing follicles > 20, peak Estradiol (E2) > 4000pg/mL, and Anti-Müllerian Hormone (AMH) levels > 4.5ng/mL. RESULTS: The serum metabolomics analysis revealed four different metabolites within the CON group and 14 within the PCOS group. Remarkably, 10-pentadecenoic acid emerged as a discernible risk metabolite for the CON-HOR, also found to be a differential metabolite between CON-NOR and PCOS groups. cysteine and 5-methoxytryptamine were also identified as risk metabolites for the PCOS-HOR. Furthermore, KEGG analysis unveiled significant enrichment of the aminoacyl-tRNA biosynthesis pathway among the metabolites differing between PCOS-NOR and PCOS-HOR. CONCLUSION: Our study highlights significant metabolite differences between patients with normal ovarian response and those with high ovarian response and at risk for OHSS within both the tubal infertility control group and PCOS infertility group. Importantly, we observe metabolic similarities between patients with PCOS and those with a high ovarian response but without PCOS, suggesting potential parallels in their underlying causes.
Asunto(s)
Fertilización In Vitro , Infertilidad Femenina , Inducción de la Ovulación , Humanos , Femenino , Infertilidad Femenina/metabolismo , Infertilidad Femenina/sangre , Adulto , Síndrome de Hiperestimulación Ovárica/sangre , Síndrome de Hiperestimulación Ovárica/metabolismo , Síndrome del Ovario Poliquístico/metabolismo , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/complicaciones , Cromatografía de Gases y Espectrometría de Masas , Metaboloma , Metabolómica/métodos , Embarazo , Ovario/metabolismoRESUMEN
Purpose: To determine whether perioperative esketamine use decreases the risk of postpartum depression (PPD). Methods: Online search of PubMed, Web of Science, and Embase was conducted to identify relevant studies. Key words for search included, but were not limited to, postpartum depression, esketamine, and clinical trials. The mean and standard deviation of the Edinburgh Postnatal Depression Scale (EPDS) scores were extracted from the studies as primary parameters. Results: The literature search identified 226 articles, of which 5 met the criteria and were enrolled in the study. In total, 886 patients in the studies were taken into analysis. The EPDS scores in the esketamine group were lower than those of the control group at the early stage of puerperium (WMD=-2.05, 95% CI: -3.77, -0.34, p=0.019), whereas there was no significant difference at the middle and later stages (WMD=-1.41, 95% CI: -2.86, 0.04, p=0.056). The sensitivity analyses indicated that the result for the early stage was stable, whereas it was unreliable for the middle and later stages. The results of the Egger's test indicated no publication bias. Conclusion: Perioperative use of esketamine contributes to a lower risk of PPD at the early stage of puerperium but not at the middle and later stages. To further verify this conclusion, more high-quality studies are required.
RESUMEN
OBJECTIVE: The purpose of this study is to investigate the role of high mobility group protein B1 (HMGB1) in placental development and fetal growth. METHODS: We employed the Cre-loxP recombination system to establish a placenta-specific HMGB1 knockout mouse model. Breeding HMGB1flox/flox mice with Elf5-Cre mice facilitated the knockout, leveraging Elf5 expression in extra-embryonic ectoderm, ectoplacental cone, and trophoblast giant cells at 12.5 days of embryonic development. The primary goal of this model was to elucidate the molecular mechanism of HMGB1 in placental development, assessing parameters such as placental weight, fetal weight, and bone development. Additionally, we utilized lentiviral interference and overexpression of HMGB1 in human trophoblast cells to further investigate HMGB1's functional role. RESULTS: Our findings indicate that the HMGB1flox/floxElf5cre/+ mouse displays fetal growth restriction, characterized by decreased placental and fetal weight and impaired bone development. The absence of HMGB1 inhibits autophagosome formation, impairs lysosomal degradation, and disrupts autophagic flux. Depletion of HMGB1 in human trophoblast cells also suppresses cell viability, proliferation, migration, and invasion by inhibiting the ERK signaling pathway. Overexpression of HMGB1 observed the opposite phenotypes. CONCLUSIONS: HMGB1 participates in the regulation of autophagy through the ERK signaling pathway and affects placental development.
Asunto(s)
Autofagia , Proteína HMGB1 , Sistema de Señalización de MAP Quinasas , Placenta , Trofoblastos , Animales , Femenino , Trofoblastos/metabolismo , Trofoblastos/fisiología , Autofagia/fisiología , Proteína HMGB1/metabolismo , Proteína HMGB1/genética , Embarazo , Ratones , Sistema de Señalización de MAP Quinasas/fisiología , Placenta/metabolismo , Humanos , Ratones Noqueados , Placentación/fisiologíaRESUMEN
In this retrospective study conducted at Sichuan Jinxin Xinan Women and Children's Hospital spanning January 2015 to December 2021, our objective was to investigate the impact of embryo cryopreservation duration on outcomes in frozen embryo transfer. Participants, totaling 47,006 cycles, were classified into 3 groups based on cryopreservation duration: ≤1 year (Group 1), 1 to 6 years (Group 2), andâ ≥6 years (Group 3). Employing various statistical analyses, including 1-way ANOVA, Kruskal-Wallis test, chi-square test, and a generalized estimating equation model, we rigorously adjusted for confounding factors. Primary outcomes encompassed clinical pregnancy rate and Live Birth Rate (LBR), while secondary outcomes included biochemical pregnancy rate, multiple pregnancy rate, ectopic pregnancy rate, early and late miscarriage rates, preterm birth rate, neonatal birth weight, weeks at birth, and newborn sex. Patient distribution across cryopreservation duration groups was as follows: Group 1 (40,461 cycles), Group 2 (6337 cycles), and Group 3 (208 cycles). Postcontrolling for confounding factors, Group 1 exhibited a decreased likelihood of achieving biochemical pregnancy rate, clinical pregnancy rate, and LBR (ORâ <â 1, aORâ <â 1, Pâ <â .05). Furthermore, an elevated incidence of ectopic pregnancy was observed (ORâ >â 1, aORâ >â 1), notably significant after 6 years of freezing time [aORâ =â 4.141, 95% confidence intervals (1.013-16.921), Pâ =â .05]. Cryopreservation exceeding 1 year was associated with an increased risk of early miscarriage and preterm birth (ORâ >â 1, aORâ >â 1). No statistically significant differences were observed in birth weight or sex between groups. However, male infant birth rates were consistently higher than those of female infants across all groups. In conclusion, favorable pregnancy outcomes align with embryo cryopreservation durations within 1 year, while freezing for more than 1 year may diminish clinical pregnancy and LBRs, concurrently elevating the risk of ectopic pregnancy and preterm birth.
Asunto(s)
Aborto Espontáneo , Embarazo Ectópico , Nacimiento Prematuro , Niño , Embarazo , Femenino , Masculino , Recién Nacido , Humanos , Resultado del Embarazo/epidemiología , Estudios Retrospectivos , Aborto Espontáneo/epidemiología , Aborto Espontáneo/etiología , Peso al Nacer , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/etiología , Nacimiento Vivo , Transferencia de Embrión/efectos adversos , Índice de Embarazo , Criopreservación , Embarazo Ectópico/epidemiología , Embarazo Ectópico/etiologíaRESUMEN
Human trophoblastic lineage development is intertwined with placental development and pregnancy outcomes, but the regulatory mechanisms underpinning this process remain inadequately understood. In this study, based on single-nuclei RNA sequencing (snRNA-seq) analysis of the human early maternal-fetal interface, we compared the gene expression pattern of trophoblast at different developmental stages. Our findings reveal a predominant upregulation of TBX3 during the transition from villous cytotrophoblast (VCT) to syncytiotrophoblast (SCT), but downregulation of TBX3 as VCT progresses into extravillous trophoblast cells (EVT). Immunofluorescence analysis verified the primary expression of TBX3 in SCT, partial expression in MKi67-positive VCT, and absence in HLA-G-positive EVT, consistent with our snRNA-seq results. Using immortalized trophoblastic cell lines (BeWo and HTR8/SVneo) and human primary trophoblast stem cells (hTSCs), we observed that TBX3 knockdown impedes SCT formation through RAS-MAPK signaling, while TBX3 overexpression disrupts the cytoskeleton structure of EVT and hinders EVT differentiation by suppressing FAK signaling. In conclusion, our study suggests that the spatiotemporal expression of TBX3 plays a critical role in regulating trophoblastic lineage development via distinct signaling pathways. This underscores TBX3 as a key determinant during hemochorial placental development.
Asunto(s)
Placenta , Placentación , Humanos , Embarazo , Femenino , Placenta/metabolismo , Placentación/genética , Primer Trimestre del Embarazo , Trofoblastos/metabolismo , ARN Nuclear Pequeño/metabolismo , Movimiento Celular , Proteínas de Dominio T Box/genética , Proteínas de Dominio T Box/metabolismoRESUMEN
STATEMENT OF PROBLEM: Information regarding the effect of tooth color under different light conditions on the accuracy of intraoral complete arch scanning is limited. PURPOSE: The purpose of this in vitro study was to evaluate the effect of color and ambient light conditions on the accuracy of mandibular complete arch scanning with an intraoral scanner (IOS) using a zirconia restoration model with different shades. MATERIAL AND METHODS: Five mandible dentition models with zirconia restorations of different shades were fabricated by computer-aided design and computer-aided manufacturing (CAD-CAM). The spectral reflectance and transmittance curves were collected with a spectrophotometer to determine color parameters (Rb, T, S+A, L*, a*, b*, C*, and h). Under 4 different lighting conditions: no light (ZL), natural light (NL), room light (RL), and chair light (CL), each model was scanned 10 times by using an IOS (TRIOS 3). Three-dimensional (3D) deviation analysis and a linear deviation analysis were performed for an accurate quantitative measurement of intraoral scanning. The multivariate test was used to determine significant differences in 3D deviation and linear deviation among groups. The multiple linear regression test was conducted to investigate the relevant independent factors of mean absolute 3D deviation. RESULTS: The 3D deviation analysis showed that the mean absolute 3D deviation of 3M2 model scanning was the lowest (P<.001). Moreover, under CL and RL, the accuracy results from the 3M2 model scan were demonstrated as significantly better than the tested scans under other light conditions (P=.021). The result of the linear deviation analysis indicated that the variation in distance was only significant between the bilateral canines (P=.032). Ambient light conditions, C*, and h were factors influencing mean absolute 3D deviation (R2=0.593, P<.001). CONCLUSIONS: Color change influenced the accuracy of intraoral mandibular complete arch scanning under different light conditions. This effect may be attributable to the interaction between the ambient light condition and color parameters such as C* and h.
Asunto(s)
Diseño Asistido por Computadora , Circonio , Iluminación , Imagenología Tridimensional , Técnica de Impresión Dental , Arco DentalRESUMEN
Delirium is a common postoperative complication in children with congenital heart disease, which affects their postoperative recovery. The purpose of this study is to explore the risk factors of delirium and construct a nomogram model to provide novel references for the prevention and management of postoperative delirium in children with congenital heart disease. 470 children after congenital heart surgery treated in the cardiac intensive care unit (CICU) of Shanghai Children's Medical Center were divided into a model and a validation cohort according to the principle of 7:3 distribution temporally. Then, the delirium-related influencing factors of 330 children in the training cohort were analyzed, and the nomogram model was established by a combination of Lasso regression and logistic regression. The data of 140 children in the validation cohort were used to verify the effectiveness of the model. Multivariable logistic regression analysis showed that age, disease severity, non-invasive ventilation after extubation, delayed chest closure, phenobarbital dosage, promethazine dosage, mannitol usage, and elevated temperature were independent risk factors for postoperative delirium. The area under the receiver operating characteristic curve (AUC) of the nomogram model was 0.864 and the Brier value was 0.121. Regarding the validation of the model's effect, our results showed that 51 cases were predicted by the model and 34 cases actually occurred, including 4 cases of false negative and 21 cases of false positive. The positive predictive value of the model was 58.8%, and its negative predictive value was 95.5%. The nomogram model established in this study showed acceptable performance in predicting postoperative delirium in children with congenital heart disease.
Asunto(s)
Delirio del Despertar , Cardiopatías Congénitas , Niño , Humanos , Estudios Prospectivos , Nomogramas , China/epidemiología , Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/cirugía , Factores de Riesgo , Estudios RetrospectivosRESUMEN
BACKGROUND: The influence of SARS-CoV-2 infection after embryo transfer on early pregnancy outcomes in in vitro fertilization or intracytoplasmic sperm injection-embryo transfer treatment remains inadequately understood. This knowledge gap endures despite an abundance of studies investigating the repercussions of preceding SARS-CoV-2 infection on early pregnancy outcomes in spontaneous pregnancies. OBJECTIVE: This study aimed to investigate the association between SARS-CoV-2 infection within 10 weeks after embryo transfer and early pregnancy outcomes in patients undergoing in vitro fertilization/intracytoplasmic sperm injection treatment. STUDY DESIGN: This prospective cohort study was conducted at a single public in vitro fertilization center in China. Female patients aged 20 to 39 years, with a body mass index ranging from 18 to 30 kg/m2, undergoing in vitro fertilization/intracytoplasmic sperm injection treatment, were enrolled between September 2022 and December 2022, with follow-up extended until March 2023. The study tracked SARS-CoV-2 infection time (≤14 days, ≤28 days, and ≤10 weeks after embryo transfer), symptoms, vaccination status, the interval between vaccination and embryo transfer, and early pregnancy outcomes, encompassing biochemical pregnancy rate, implantation rate, clinical pregnancy rate, and early miscarriage rate. The study used single-factor analysis and multivariate logistic regression to examine the association between SARS-CoV-2 infection status, along with other relevant factors, and the early pregnancy outcomes. RESULTS: A total of 857 female patients undergoing in vitro fertilization/intracytoplasmic sperm injection treatment were analyzed. In the first stage, SARS-CoV-2 infection within 14 days after embryo transfer did not have a significant negative association with the biochemical pregnancy rate (adjusted odds ratio, 0.74; 95% confidence interval, 0.51-1.09). In the second stage, SARS-CoV-2 infection within 28 days after embryo transfer had no significant association with the implantation rate (36.6% in infected vs 44.0% in uninfected group; P=.181). No statistically significant association was found with the clinical pregnancy rate after adjusting for confounding factors (adjusted odds ratio, 0.69; 95% confidence interval, 0.56-1.09). In the third stage, SARS-CoV-2 infection within 10 weeks after embryo transfer had no significant association with the early miscarriage rate (adjusted odds ratio, 0.77; 95% confidence interval, 0.35-1.71). CONCLUSION: Our study suggests that SARS-CoV-2 infection within 10 weeks after embryo transfer may not be negatively associated with the biochemical pregnancy rate, implantation rate, clinical pregnancy rate, and early miscarriage rate in patients undergoing in vitro fertilization/intracytoplasmic sperm injection treatment. It is important to note that these findings are specific to the target population of in vitro fertilization/intracytoplasmic sperm injection patients aged 20 to 39 years, without previous SARS-CoV-2 infection, and with a body mass index of 18 to 30 kg/m2. This information offers valuable insights, addressing current concerns and providing a clearer understanding of the actual risk associated with SARS-CoV-2 infection after embryo transfer.
Asunto(s)
Aborto Espontáneo , COVID-19 , Embarazo , Humanos , Masculino , Femenino , Resultado del Embarazo , Aborto Espontáneo/epidemiología , Aborto Espontáneo/etiología , Estudios Prospectivos , COVID-19/terapia , COVID-19/etiología , SARS-CoV-2 , Semen , Fertilización In Vitro/efectos adversos , Transferencia de Embrión , Índice de Embarazo , Estudios RetrospectivosRESUMEN
BACKGROUND: Children and adolescents may experience a variety of subjective adverse events (AEs) caused by cancer treatment. The identification of distinct groups of patients is crucial for guiding symptomatic AE management interventions to prevent AEs from worsening. OBJECTIVE: The aim of this study was to identify subgroups of children with cancer experiencing similar patterns of subjective toxicities and evaluate differences among these subgroups in demographic and clinical characteristics. METHODS: A cross-sectional survey was conducted of 356 children in China with malignancies who received chemotherapy within the past 7 days using the pediatric Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events. A latent class analysis (LCA) was conducted to identify subgroups of patients with distinct profiles of symptomatic AE occurrence. RESULTS: Nausea (54.5%), anorexia (53.4%), and headache (39.3%) were the top 3 AEs children experienced. Nearly all participants (97.8%) experienced ≥1 core AEs, and 30.3% experienced ≥5 AEs. The LCA results identified 3 subgroups ("high gastrotoxicity and low neurotoxicity" [53.2%], "moderate gastrotoxicity and high neurotoxicity" [23.6%], and "high gastrotoxicity and high neurotoxicity" [22.8%]). The subgroups were differentiated by monthly family per-capita income, time since diagnosis, and Karnofsky Performance Status score. CONCLUSIONS: Children experienced multiple subjective toxicities during chemotherapy, especially gastrotoxicity and neurotoxicity. Heterogeneity was found in the LCA in the patients' toxicities. The prevalence of toxicities could be distinguished by the children's characteristics. IMPLICATIONS FOR PRACTICE: The results showing different subgroups in our study may assist clinical staff in focusing on patients with higher toxicities to provide effective interventions.
Asunto(s)
Neoplasias , Adolescente , Humanos , Niño , Estudios Transversales , Análisis de Clases Latentes , Neoplasias/tratamiento farmacológico , Medición de Resultados Informados por el Paciente , Náusea/inducido químicamenteRESUMEN
Background & Aims: HBV infection is a global health burden. Covalently closed circular DNA (cccDNA) transcriptional regulation is a major cause of poor cure rates of chronic hepatitis B (CHB) infection. Herein, we evaluated whether targeting host factors to achieve functional silencing of cccDNA may represent a novel strategy for the treatment of HBV infection. Methods: To evaluate the effects of Jumonji C domain-containing (JMJD2) protein subfamily JMJD2A-2D proteins on HBV replication, we used lentivirus-based RNA interference to suppress the expression of isoforms JMJD2A-2D in HBV-infected cells. JMJD2D-knockout mice were generated to obtain an HBV-injected model for in vivo experiments. Co-immunoprecipitation and ubiquitylation assays were used to detect JMJD2D-HBx interactions and HBx stability modulated by JMJD2D. Chromatin immunoprecipitation assays were performed to investigate JMJD2D-cccDNA and HBx-cccDNA interactions. Results: Among the JMJD2 family members, JMJD2D was significantly upregulated in mouse livers and human hepatoma cells. Downregulation of JMJD2D inhibited cccDNA transcription and HBV replication. Molecularly, JMJD2D sustained HBx stability by suppressing the TRIM14-mediated ubiquitin-proteasome degradation pathway and acted as a key co-activator of HBx to augment HBV replication. The JMJD2D-targeting inhibitor, 5C-8-HQ, suppressed cccDNA transcription and HBV replication. Conclusion: Our study clarified the mechanism by which JMJD2D regulates HBV transcription and replication and identified JMJD2D as a potential diagnostic biomarker and promising drug target against CHB, and HBV-associated hepatocarcinoma. Impact and implications: HBV cccDNA is central to persistent infection and is a major obstacle to healing CHB. In this study, using cellular and animal HBV models, JMJD2D was found to stabilise and cooperate with HBx to augment HBV transcription and replication. This study reveals a potential novel translational target for intervention in the treatment of chronic hepatitis B infection.
RESUMEN
BACKGROUND: To propose and validate a modified noninvasive method for the diagnosis of chronic syndesmotic injuries. METHODS: This study included 16 patients with chronic ankle instability. Herein, we propose the Modified Stabilization Test, a new measurement for use in the diagnosis of chronic syndesmotic injury, as determined by wearing a 60-kPa pneumatic brace. The test combines the center of pressure and sensory organization test to measure postural control. For comparison, we also measured the tibiofibular clear space, tibiofibular overlap, and medial clear space using anteroposterior radiograph; a line marked horizontally above the tibial plaque using computed tomography (CT) to measure the syndesmotic gap and fibular rotation angle; and magnetic resonance imaging (MRI) scans to determine the presence of the λ sign. The distance of syndesmosis was confirmed in 16 individuals through arthroscopy, and the results of the examination were used to determine the diagnostic efficacy of each index. RESULTS: Receiver operating characteristic curve analysis revealed that the optimal cut-off value, sensitivity, and specificity of the Modified Stabilization Test for the diagnosis of chronic syndesmotic injuries were 0.80, 100%, and 87.5%, respectively. The area under the curve (AUC) of the Modified Stabilization Test was 0.906 (95% CI 0.656, 0.993; P < .001), which was superior to imaging indices such as radiography, CT, and MRI (AUC = 0.516-0.891). CONCLUSION: We developed the Modified Stabilization Test-a noninvasive diagnostic tool for the screening of chronic syndesmotic injuries. The test showed high sensitivity and specificity for the identification of chronic syndesmotic injuries and is helpful in the identification of chronic syndesmotic injuries. LEVEL OF EVIDENCE: Level II, diagnostic-investigating a diagnostic test.
Asunto(s)
Traumatismos del Tobillo , Humanos , Traumatismos del Tobillo/diagnóstico por imagen , Radiografía , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada por Rayos X , Equilibrio Postural , Articulación del TobilloRESUMEN
Triple-negative breast cancer (TNBC) is always the most challenging breast cancer subtype. Herein, brucine, encapsulated in peptide-modified liposomes, was proposed for treating TNBC by transdermal delivery. For the TD peptide-modified brucine-loaded liposome (Bru-TD-Lip) we developed, it presents high encapsulation efficiency of brucine and stability. In vitro, Bru-TD-Lip shows the enhanced percutaneous permeability of brucine, is able to readily enter TNBC cells, and significantly inhibits the proliferation, migration, and invasion of these cells. In vivo, through transdermal delivery, Bru-TD-Lip presents good biosafety and anti-tumor efficacy. The transdermal delivery of Bru-TD-Lip effectively targets and inhibits subcutaneous mammary carcinogenesis in female nude mice. Compared with oral administration, the transdermal delivery significantly reduces the damage of brucine to major organs and enhances the antitumor outcomes of brucine in treating TNBC. This study provides a new therapeutic strategy for treating triple-negative breast cancer by brucine.
Asunto(s)
Liposomas , Neoplasias de la Mama Triple Negativas , Humanos , Ratones , Animales , Femenino , Liposomas/uso terapéutico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Ratones Desnudos , Péptidos/uso terapéuticoRESUMEN
PURPOSE: Fetal growth restriction (FGR) is a common complication characterized by impaired placental function and unfavorable pregnancy outcomes. This study aims to elucidate the expression pattern of miR-181d-5p in FGR placentas and explore its effects on trophoblast fusion. METHODS: The expression pattern of miR-181d-5p in human FGR placentas were evaluated using qRT-PCR. Western blot, qRT-PCR, and Immunofluorescence analysis were performed in a Forskolin (FSK)-induced BeWo cell fusion model following the transfection of miR-181d-5p mimic or inhibitor. Potential target genes for miR-181d-5p were identified by screening miRNA databases. The interaction between miR-181d-5p and Luman/CREB3 Recruitment Factor (CREBRF) was determined through a luciferase assay. Moreover, the effect of CREBRF on BeWo cell fusion was examined under hypoxic conditions. RESULTS: Aberrant up-regulation of miR-181d-5p and altered expression of trophoblast fusion makers, including glial cell missing 1 (GCM1), Syncytin1 (Syn1), and E-cadherin (ECAD), were found in human FGR placentas. A down-regulation of miR-181d-5p expression was observed in the FSK-induced BeWo cell fusion model. Transfection of the miR-181d-5p mimic resulted in the inhibition of BeWo cell fusion, characterized by a down-regulation of GCM1 and Syn1, accompanied by an up-regulation of ECAD. Conversely, the miR-181d-5p inhibitor promoted BeWo cell fusion. Furthermore, miR-181d-5p exhibited negative regulation of CREBRF, which was significantly down-regulated in the hypoxia-induced BeWo cell model. The overexpression of CREBRF was effectively ameliorated the impaired BeWo cell fusion induced by hypoxia. CONCLUSIONS: Our study demonstrated that miR-181d-5p, which is elevated in FGR placenta, inhibited the BeWo cell fusion through negatively regulating the expression of CREBRF.