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Objective: Our objective was to investigate the efficacy of letrozole co-treatment in an antagonist protocol for infertile women with polycystic ovary syndrome (PCOS). Patients and Methods: This retrospective cohort study included infertile women with PCOS undergoing IVF/ICSI with and without letrozole co-treatment in an antagonist protocol from 2007-2021 at Shanghai Ninth People's Hospital (Shanghai, China). A total of 1559 participants were enrolled, with 1227 women in the antagonist group and 332 women in the letrozole co-treatment group. Propensity score-based patient-matching model was conducted to balance covariates between the groups. The primary outcome was the number of retrieved oocytes, with secondary outcomes including endocrine parameters, ovarian stimulation outcomes, pregnancy outcomes, and obstetrical and neonatal complications. Results: Letrozole co-treatment induced significant changes in hormonal regulation, increased the percentage of large follicles, and resulted in fewer retrieved oocytes (P < 0.05). However, there was no negative impact on the number of usable embryos or good-quality embryos (P > 0.05). The live birth rates following fresh embryo transfer were comparable between the letrozole and control groups (single embryo transfer: 28.9% vs 29.7%, P > 0.05; double embryo transfer: 37.3% vs 45.6%, P > 0.05). Additionally, there were no significant differences between the two groups in the live birth rate per patient after frozen embryo transfer and the cumulative live birth rate (P > 0.05). No significant differences in obstetrical and neonatal complications were observed between the groups (P > 0.05). Conclusion: The addition of letrozole to the antagonist protocol for women with PCOS undergoing IVF induces a higher percentage of large follicles during oocyte retrieval, while reducing the overall number of retrieved oocytes. Moreover, the use of letrozole demonstrates comparable clinical outcomes following embryo transfers. These findings highlight the potential application of letrozole in an antagonist protocol for women with PCOS.
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Fertilización In Vitro , Letrozol , Síndrome del Ovario Poliquístico , Letrozol/administración & dosificación , Humanos , Femenino , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Estudios Retrospectivos , Adulto , Embarazo , Infertilidad Femenina/tratamiento farmacológico , Inducción de la OvulaciónRESUMEN
Electroencephalography (EEG) has demonstrated significant value in diagnosing brain diseases. In particular, brain networks have gained prominence as they offer additional valuable insights by establishing connections between EEG signal channels. While brain connections are typically delineated by channel signal similarity, there lacks a consistent and reliable strategy for ascertaining node characteristics. Conventional node features such as temporal and frequency domain properties of EEG signals prove inadequate for capturing the extensive EEG information. In our investigation, we introduce a novel adaptive method for extracting node features from EEG signals utilizing a distinctive task-induced self-supervised learning technique. By amalgamating these extracted node features with fundamental edge features constructed using Pearson correlation coefficients, we showed that the proposed approach can function as a plug-in module that can be integrated to many common GNN networks (e.g., GCN, GraphSAGE, GAT) as a replacement of node feature selections module. Comprehensive experiments are then conducted to demonstrate the consistently superior performance and high generality of the proposed method over other feature selection methods in various of brain disorder prediction tasks, such as depression, schizophrenia, and Parkinson's disease. Furthermore, compared to other node features, our approach unveils profound spatial patterns through graph pooling and structural learning, shedding light on pivotal brain regions influencing various brain disorder prediction based on derived features.
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Encefalopatías , Electroencefalografía , Redes Neurales de la Computación , Aprendizaje Automático Supervisado , Humanos , Electroencefalografía/métodos , Encefalopatías/diagnóstico por imagen , Encefalopatías/fisiopatología , Procesamiento de Señales Asistido por Computador , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Masculino , FemeninoRESUMEN
Exploiting a convenient and highly bioavailable ocular drug delivery approach is currently one of the hotspots in the pharmaceutical industry. Eyelid topical application is seen to be a valuable strategy in the treatment of chronic ocular diseases. To further elucidate the feasibility of eyelid topical administration as an alternative route for ocular drug delivery, pharmacokinetic and pharmacodynamic studies of pilocarpine were conducted in rabbits. Besides, a novel physiologically based pharmacokinetic (PBPK) model describing eyelid transdermal absorption and ocular disposition was developed in rabbits. The PBPK model of rabbits was extrapolated to human by integrating the drug-specific permeability parameters and human physiological parameters to predict ocular pharmacokinetic in human. After eyelid topical application of pilocarpine, the concentration of pilocarpine in iris peaked at 2 h with the value of 18,724 ng/g and the concentration in aqueous humor peaked at 1 h with the value of 1,363 ng/mL. Significant miotic effect were observed from 0.5 h to 4.5 h after eyelid topical application of pilocarpine in rabbits, while that were observed from 0.5 h to 3.5 h after eyedrop instillation. The proposed eyelid PBPK model was capable of reasonably predicting ocular exposure of pilocarpine after application on the eyelid skin and based on the PBPK model, the human ocular concentration was predicted to be 10-fold lower than that in rabbits. And it was suggested that drugs applied on the eyelid skin could transfer into the eyeball through corneal pathway and scleral pathway. This work could provide pharmacokinetic and pharmacodynamic data for the development of eyelid drug delivery, as well as the reference for clinical applications.
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Párpados , Modelos Biológicos , Pilocarpina , Pilocarpina/farmacocinética , Pilocarpina/administración & dosificación , Animales , Conejos , Humanos , Párpados/metabolismo , Párpados/efectos de los fármacos , Administración Tópica , Masculino , Mióticos/farmacocinética , Mióticos/administración & dosificación , Agonistas Muscarínicos/farmacocinética , Agonistas Muscarínicos/administración & dosificación , Humor Acuoso/metabolismo , Humor Acuoso/efectos de los fármacos , Administración Oftálmica , Absorción Cutánea/efectos de los fármacos , Soluciones Oftálmicas/farmacocinética , Soluciones Oftálmicas/administración & dosificación , Sistemas de Liberación de Medicamentos/métodosRESUMEN
Histone acetylation modifications in filamentous fungi play a crucial role in epigenetic gene regulation and are closely linked to the transcription of secondary metabolite (SM) biosynthetic gene clusters (BGCs). Histone deacetylases (HDACs) play a pivotal role in determining the extent of histone acetylation modifications and act as triggers for the expression activity of target BGCs. The genus Chaetomium is widely recognized as a rich source of novel and bioactive SMs. Deletion of a class I HDAC gene of Chaetomium olivaceum SD-80A, g7489, induces a substantial pleiotropic effect on the expression of SM BGCs. The C. olivaceum SD-80A ∆g7489 strain exhibited significant changes in morphology, sporulation ability, and secondary metabolic profile, resulting in the emergence of new compound peaks. Notably, three polyketides (A1-A3) and one asterriquinone (A4) were isolated from this mutant strain. Furthermore, our study explored the BGCs of A1-A4, confirming the function of two polyketide synthases (PKSs). Collectively, our findings highlight the promising potential of molecular epigenetic approaches for the elucidation of novel active compounds and their biosynthetic elements in Chaetomium species. This finding holds great significance for the exploration and utilization of Chaetomium resources. KEY POINTS: ⢠Deletion of a class I histone deacetylase activated secondary metabolite gene clusters. ⢠Three polyketides and one asterriquinone were isolated from HDAC deleted strain. ⢠Two different PKSs were reported in C. olivaceum SD-80A.
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Chaetomium , Histona Desacetilasas , Familia de Multigenes , Policétidos , Metabolismo Secundario , Chaetomium/genética , Chaetomium/enzimología , Chaetomium/metabolismo , Metabolismo Secundario/genética , Histona Desacetilasas/genética , Histona Desacetilasas/metabolismo , Policétidos/metabolismo , Eliminación de Gen , Regulación Fúngica de la Expresión Génica , Sintasas Poliquetidas/genética , Sintasas Poliquetidas/metabolismo , Vías Biosintéticas/genética , Epigénesis GenéticaRESUMEN
In pursuit of cultivating automated models for magnetic resonance imaging (MRI) to aid in diagnostics, an escalating demand for extensive, multisite, and heterogeneous brain imaging datasets has emerged. This potentially introduces biased outcomes when directly applied for subsequent analysis. Researchers have endeavored to address this issue by pursuing the harmonization of MRIs. However, most existing image-based harmonization methods for MRI are tailored for 2D slices, which may introduce inter-slice variations when they are combined into a 3D volume. In this study, we aim to resolve inconsistencies between slices by introducing a pseudo-warping field. This field is created randomly and utilized to transform a slice into an artificially warped subsequent slice. The objective of this pseudo-warping field is to ensure that generators can consistently harmonize adjacent slices to another domain, without being affected by the varying content present in different slices. Furthermore, we construct unsupervised spatial and recycle loss to enhance the spatial accuracy and slice-wise consistency across the 3D images. The results demonstrate that our model effectively mitigates inter-slice variations and successfully preserves the anatomical details of the images during the harmonization process. Compared to generative harmonization models that employ 3D operators, our model exhibits greater computational efficiency and flexibility.
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Encéfalo , Imagenología Tridimensional , Imagen por Resonancia Magnética , Imagen por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/normas , Humanos , Imagenología Tridimensional/métodos , Encéfalo/diagnóstico por imagen , Algoritmos , Neuroimagen/métodos , Neuroimagen/normasRESUMEN
Background: There is a significant imbalance of mitochondrial activity and oxidative stress (OS) status in patients with atopic dermatitis (AD). This study aims to screen skin and peripheral mitochondria-related biomarkers, providing insights into the underlying mechanisms of mitochondrial dysfunction in AD. Methods: Public data were obtained from MitoCarta 3.0 and GEO database. We screened mitochondria-related differentially expressed genes (MitoDEGs) using R language and then performed GO and KEGG pathway analysis on MitoDEGs. PPI and machine learning algorithms were also used to select hub MitoDEGs. Meanwhile, the expression of hub MitoDEGs in clinical samples were verified. Using ROC curve analysis, the diagnostic performance of risk model constructed from these hub MitoDEGs was evaluated in the training and validation sets. Further computer-aided algorithm analyses included gene set enrichment analysis (GSEA), immune infiltration and mitochondrial metabolism, centered on these hub MitoDEGs. We also used real-time PCR and Spearman method to evaluate the relationship between plasma circulating cell-free mitochondrial DNA (ccf-mtDNA) levels and disease severity in AD patients. Results: MitoDEGs in AD were significantly enriched in pathways involved in mitochondrial respiration, mitochondrial metabolism, and mitochondrial membrane transport. Four hub genes (BAX, IDH3A, MRPS6, and GPT2) were selected to take part in the creation of a novel mitochondrial-based risk model for AD prediction. The risk score demonstrated excellent diagnostic performance in both the training cohort (AUC = 1.000) and the validation cohort (AUC = 0.810). Four hub MitoDEGs were also clearly associated with the innate immune cells' infiltration and the molecular modifications of mitochondrial hypermetabolism in AD. We further discovered that AD patients had considerably greater plasma ccf-mtDNA levels than controls (U = 92.0, p< 0.001). Besides, there was a significant relationship between the up-regulation of plasma mtDNA and the severity of AD symptoms. Conclusions: The study highlights BAX, IDH3A, MRPS6 and GPT2 as crucial MitoDEGs and demonstrates their efficiency in identifying AD. Moderate to severe AD is associated with increased markers of mitochondrial damage and cellular stress (ccf=mtDNA). Our study provides data support for the variation in mitochondria-related functional characteristics of AD patients.
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Biomarcadores , Biología Computacional , Dermatitis Atópica , Aprendizaje Automático , Mitocondrias , Piel , Humanos , Dermatitis Atópica/genética , Dermatitis Atópica/sangre , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/inmunología , Biomarcadores/sangre , Mitocondrias/metabolismo , Mitocondrias/genética , Biología Computacional/métodos , Piel/metabolismo , Piel/inmunología , Masculino , ADN Mitocondrial/genética , Femenino , Perfilación de la Expresión GénicaRESUMEN
The escalating spread of drug-resistant bacteria and viruses is a grave concern for global health. Nucleic acids dominate the drug-resistance and transmission of pathogenic microbes. Here, imidazolium-type poly(ionic liquid)/porphyrin (PIL-P) based electrospun nanofibrous membrane and its cerium (IV) ion complex (PIL-P-Ce) are developed. The obtained PIL-P-Ce membrane exhibits high and stable efficiency in eradicating various microorganisms (bacteria, fungi, and viruses) and decomposing microbial antibiotic resistance genes and viral nucleic acids under light. The nuclease-mimetic and photocatalytic mechanisms of the PIL-P-Ce are elucidated. Co-infection wound models in mice with methicillin-resistant S. aureus and hepatitis B virus demonstrate that PIL-P-Ce integrate the triple effects of cationic polymer, photocatalysis, and nuclease-mimetic activities. As revealed by proteomic analysis, PIL-P-Ce shows minimal phototoxicity to normal tissues. Hence, PIL-P-Ce has potential as a "green" wound dressing to curb the spread of drug-resistant bacteria and viruses in clinical settings.
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Antiinfecciosos , Antivirales , Coinfección , Modelos Animales de Enfermedad , Nanofibras , Animales , Ratones , Antivirales/farmacología , Nanofibras/química , Antiinfecciosos/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Catálisis , Porfirinas/farmacología , Porfirinas/química , Líquidos Iónicos/farmacología , Líquidos Iónicos/químicaRESUMEN
BACKGROUND: The present study aimed to explore the maternal and perinatal risks in cases of monozygotic twins (MZT) following frozen-thawed embryo transfer (FET). METHODS: All twin births that were conceived following FET from 2007 to 2021 at Shanghai Ninth People's Hospital in Shanghai, China were retrospectively reviewed. The exposure variable was twin type (monozygotic and dizygotic). The primary outcome was the incidence of neonatal death while secondary outcomes included hypertensive disorders of pregnancy, gestational diabetes, intrahepatic cholestasis of pregnancy, placenta previa, placental abruption, preterm premature rupture of the membranes, Cesarean delivery, gestational age, birth weight, weight discordance, stillbirth, birth defects, pneumonia, respiratory distress syndrome, necrotizing enterocolitis, and neonatal jaundice. Analysis of the outcomes was performed using logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). The causal mediation analysis was conducted. A doubly robust estimation model was used to validate the results. Kaplan-Meier method was used to calculate survival probability. The sensitivity analysis was performed with a propensity score-based patient-matching model. RESULTS: Of 6101 dizygotic twin (DZT) and 164 MZT births conceived by FET, MZT showed an increased risk of neonatal death based on the multivariate logistic regression models (partially adjusted OR: 4.19; 95% CI, 1.23-10.8; fully adjusted OR: 4.95; 95% CI, 1.41-13.2). Similar results were obtained with the doubly robust estimation. Comparing MZT with DZT, the neonatal survival probability was lower for MZT (P < 0.05). The results were robust in the sensitivity analysis. Females with MZT pregnancies exhibited an elevated risk of preterm premature rupture of the membranes (adjusted OR: 2.42; 95% CI, 1.54-3.70). MZT were also associated with higher odds of preterm birth (prior to 37 weeks) (adjusted OR: 2.31; 95% CI, 1.48-3.67), low birth weight (adjusted OR: 1.92; 95% CI, 1.27-2.93), and small for gestational age (adjusted OR: 2.18; 95% CI, 1.21-3.69) in the fully adjusted analyses. The effect of MZT on neonatal death was partially mediated by preterm birth and low birth weight (P < 0.05). CONCLUSIONS: This study indicates that MZT conceived by FET are related to an increased risk of neonatal death, emphasizing a potential need for comprehensive antenatal surveillance in these at-risk pregnancies.
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Rotura Prematura de Membranas Fetales , Gemelos Monocigóticos , Femenino , Humanos , Recién Nacido , Embarazo , China , Transferencia de Embrión/efectos adversos , Transferencia de Embrión/métodos , Muerte Perinatal , Placenta , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/etiología , Estudios RetrospectivosRESUMEN
In traditional textile manufacturing, downstream manufacturers use raw materials, such as Nylon and cotton yarns, to produce textile products. The manufacturing process involves warping, sizing, beaming, weaving, and inspection. Staff members typically use a trial-and-error approach to adjust the appropriate production parameters in the manufacturing process, which can be time consuming and a waste of resources. To enhance the efficiency and effectiveness of textile manufacturing economically, this study proposes a query-based learning method in regression analytics using existing manufacturing data. Query-based learning allows the model training to evolve its decision-making process through dynamic interactions with its solution space. In this study, predefined target parameters of quality factors were first used to validate the training results and create new training patterns. These new patterns were then imported into the solution space of the training model. In predicting product quality, the results show that the proposed query-based regression algorithm has a mean squared error of 0.0153, which is better than those of the original regression-related methods (Avg. mean squared error = 0.020). The trained model was deployed as an application programing interface (API) for cloud-based analytics and an extensive auto-notification service.
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Thrombolytic therapy or percutaneous coronary intervention for myocardial infarction often cause myocardial ischemia/reperfusion injury (MIRI) and poor prognosis of patients. This study aimed to explore the protective effect and potential mechanism of hydromorphone hydrochloride (HH) on MIRI. Fifty Sprague-Dawley male rats were randomly divided into Sham group, I/R group, HH-pre group, HH-post group, and HH-pre + post group. Except Sham group, MIRI models were established by ligating and relaxing the left anterior descending coronary artery, followed by tail vein injection of HH (0.3 µmol/L) 10 min before ligation (HH-pre group), 10 min after reperfusion (HH-post group), and twice at the above two time points (HH-pre + post group). After intervention, the cardiac function of rats was evaluated by echocardiography, and the levels of myocardial injury markers, oxidative stress indicators, and mitochondrial function indicators were detected. Next, the myocardial infarction area was evaluated by 2,3,5-triphenyltetrazolium chloride staining, mitochondrial biogenesis, and phosphoinositide 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway by western blot. Compared with the I/R group, HH intervention improved cardiac function, decreased myocardial infarction area, reduced serum myocardial injury markers, alleviated oxidative stress, improved mitochondrial function, up-regulated mitochondrial biogenesis, and activated PI3K/Akt signaling pathway. Moreover, the HH-pre + post group was superior to the HH-pre and HH-post groups in the above aspects. Collectively, HH had protective effect on MIRI rats, and HH preconditioning combined with postconditioning showed optimal efficacy. Such efficacy may be achieved by promoting mitochondrial biogenesis to improve mitochondrial function and reduce oxidative stress, and activating the PI3K/Akt signaling pathway.
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Infarto del Miocardio , Daño por Reperfusión Miocárdica , Humanos , Ratas , Masculino , Animales , Fosfatidilinositol 3-Quinasa/metabolismo , Fosfatidilinositol 3-Quinasa/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Ratas Sprague-Dawley , Hidromorfona/uso terapéutico , Hidromorfona/farmacología , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/metabolismo , Transducción de Señal , Infarto del Miocardio/tratamiento farmacológico , Mitocondrias/metabolismoRESUMEN
The clinical effect of Coronavirus disease 2019 (COVID-19) on endometrial receptivity and embryo implantation remains unclear. Herein, we aim to investigate whether a COVID-19 history adversely affect female pregnancy outcomes after frozen-thawed embryo transfer (FET). This prospective cohort study enrolled 230 women who underwent FET cycles from December 2022 to April 2023 in an academic fertility center. Based on the history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection before FET, women were divided into the infected group (n = 136) and the control group (n = 94). The primary outcome was the clinical pregnancy rate per cycle. Multivariate logistic regression analysis was conducted to adjust for potential confounders, while subgroup analysis and restricted cubic splines were used to depict the effect of postinfection time interval on FET. The results showed that the clinical pregnancy rate was 59.6% in the infected group and 63.9% in the control group (p = 0.513). Similarly, the two groups were comparable in the rates of biochemical pregnancy (69.1% vs. 76.6%; p = 0.214) and embryo implantation (51.7% vs. 54.5%; p = 0.628). After adjustment, the nonsignificant association remained between prior infection and clinical pregnancy (OR = 0.78, 95% CI: 0.42-1.46). However, the odds for clinical pregnancy were significantly lower in the ≤30 days subgroup (OR = 0.15, 95% CI: 0.03-0.77), while no statistical significance was detected for 31-60 days and >60 days subgroups compared with the uninfected women. In conclusion, our findings suggested that SARS-CoV-2 infection in women had no significant effect on subsequent FET treatment overall, but pregnancy rates tended to be decreased if vitrified-thawed embryos were transferred within 30 days after infection. A 1-month postponement should be rationally recommended, while further studies with larger sample groups and longer follow-up periods are warranted for confirmation.
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COVID-19 , Resultado del Embarazo , Embarazo , Femenino , Humanos , Estudios Prospectivos , Criopreservación/métodos , Estudios Retrospectivos , COVID-19/terapia , SARS-CoV-2 , Transferencia de Embrión/métodosRESUMEN
Background: Primary biliary cholangitis (PBC) is a rare autoimmune liver disease with few effective treatments and a poor prognosis, and its incidence is on the rise. There is an urgent need for more targeted treatment strategies to accurately identify high-risk patients. The use of stochastic survival forest models in machine learning is an innovative approach to constructing a prognostic model for PBC that can improve the prognosis by identifying high-risk patients for targeted treatment. Method: Based on the inclusion and exclusion criteria, the clinical data and follow-up data of patients diagnosed with PBC-associated cirrhosis between January 2011 and December 2021 at Taizhou Hospital of Zhejiang Province were retrospectively collected and analyzed. Data analyses and random survival forest model construction were based on the R language. Result: Through a Cox univariate regression analysis of 90 included samples and 46 variables, 17 variables with p-values <0.1 were selected for initial model construction. The out-of-bag (OOB) performance error was 0.2094, and K-fold cross-validation yielded an internal validation C-index of 0.8182. Through model selection, cholinesterase, bile acid, the white blood cell count, total bilirubin, and albumin were chosen for the final predictive model, with a final OOB performance error of 0.2002 and C-index of 0.7805. Using the final model, patients were stratified into high- and low-risk groups, which showed significant differences with a P value <0.0001. The area under the curve was used to evaluate the predictive ability for patients in the first, third, and fifth years, with respective results of 0.9595, 0.8898, and 0.9088. Conclusion: The present study constructed a prognostic model for PBC-associated cirrhosis patients using a random survival forest model, which accurately stratified patients into low- and high-risk groups. Treatment strategies can thus be more targeted, leading to improved outcomes for high-risk patients.
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Cirrosis Hepática Biliar , Humanos , Pronóstico , Cirrosis Hepática Biliar/diagnóstico , Cirrosis Hepática Biliar/tratamiento farmacológico , Ácido Ursodesoxicólico/uso terapéutico , Estudios Retrospectivos , Cirrosis Hepática/tratamiento farmacológicoRESUMEN
The severity evaluation of Parkinson's disease (PD) is of great significance for the treatment of PD. However, existing methods either have limitations based on prior knowledge or are invasive methods. To propose a more generalized severity evaluation model, this paper proposes an explainable 3D multi-head attention residual convolution network. First, we introduce the 3D attention-based convolution layer to extract video features. Second, features will be fed into LSTM and residual backbone networks, which can be used to capture the contextual information of the video. Finally, we design a feature compression module to condense the learned contextual features. We develop some interpretable experiments to better explain this black-box model so that it can be better generalized. Experiments show that our model can achieve state-of-the-art diagnosis performance. The proposed lightweight but effective model is expected to serve as a suitable end-to-end deep learning baseline in future research on PD video-based severity evaluation and has the potential for large-scale application in PD telemedicine. The source code is available at https://github.com/JackAILab/MARNet.
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Compresión de Datos , Enfermedad de Parkinson , Telemedicina , Humanos , Enfermedad de Parkinson/diagnóstico , Programas InformáticosRESUMEN
BACKGROUND: Dual transcranial direct current stimulation (tDCS) over the bilateral primary somatosensory cortex (PSC) has potential benefits in stroke. In addition, compared with traditional rehabilitation training, sensorimotor training can significantly improve the sensorimotor function of patients. However, the efficacy of dual-tDCS combined with sensorimotor training in patients with subacute stroke is unknown. OBJECTIVE: To assess whether dual-tDCS may enhance the efficacy of sensorimotor training on the upper limb functions in patients with subacute stroke. In addition, this study aims to explore the potential clinical mechanism of this combination therapy. METHODS: We randomized 52 individuals with first-ever, unilateral subcortical stroke into the experimental group (n = 26) and the control group (n = 26). Patients in the experimental group received 20 min of dual-tDCS over the PSC and 40 min of sensorimotor training each session, while patients in the control group received sham dual-tDCS. The treatment cycle was a 1-h session of therapy each day, 5 days per week for 4 weeks. The Fugl-Meyer Assessment of Upper Extremity (FMA-UE) subscale, Action Research Arm Test (ARAT), Box and Block test (BBT), Erasmus MC revised Nottingham sensory assessment scale (Em-NSA), Neurometer sensory nerve quantitative detector (CPT), the Barthel index (BI), and Hospital Anxiety and Depression Scale (HADS) were used to assess upper limb function, activities of daily living (ADL), and mental health before and after the 4-week treatment period. In addition, functional near-infrared spectroscopy (fNIRS) was used to explore potential clinical brain mechanisms. RESULTS: Both groups showed significant improvement in all clinical scales (All p < 0.05) after treatment. Compared with sham-tDCS plus sensorimotor training, active dual-tDCS coupled with sensorimotor training can significantly improve the FMA-UE, ARAT, Em-NSA-Stereognosis, and CPT-2K Hz. In addition, dual-tDCS combined with sensorimotor training can significantly activate the left pre-Motor and supplementary motor cortex (PM-SMC) and enhance the functional connection between the left somatosensory association cortex (SAC) and RPM-SMC. Furthermore, the difference of FMA-UE in the experimental group was positively correlated with the functional connectivity of RPM-SMC-LSAC (r = 0.815, p < 0.001). CONCLUSION: Dual-tDCS over the PSC combined with sensorimotor training can improve upper limb sensory and motor dysfunction, enhance ADL, and alleviate depression and anxiety for subacute stroke patients. Our results indicated that RPM-SMC-LSAC may be potential therapeutic targets for dual-tDCS in upper limb rehabilitation on stroke.
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Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Estimulación Transcraneal de Corriente Directa , Humanos , Estimulación Transcraneal de Corriente Directa/métodos , Actividades Cotidianas , Rehabilitación de Accidente Cerebrovascular/métodos , Recuperación de la Función/fisiología , Extremidad Superior , Resultado del TratamientoRESUMEN
Objective: The present study aimed to compare the effectiveness of two different doses of letrozole (2.5 mg and 5 mg daily) in an antagonist protocol for infertile women with normal ovarian reserve. Methods: This retrospective cohort study included infertile women who underwent in vitro fertilization treatment with letrozole co-treatment at doses of 2.5 mg and 5 mg from 2007 - 2021 at Shanghai Ninth People's Hospital (Shanghai, China). The control group comprised infertile women who received gonadotropin-releasing hormone antagonist alone. The primary outcome was the cumulative live birth rate, while secondary outcomes included follicular phase endocrine parameters, ovarian stimulation outcomes, pregnancy outcomes, and the incidences of maternal and neonatal complications. Baseline and follow-up data were compared between the groups using ANOVA for normally distributed variables, the Kruskal-Wallis test for non-normally distributed variables, and the Chi-square test for categorical variables. Results: A total of 422 participants were enrolled in the study, with 211 women in the antagonist group, 109 women in the 2.5 mg letrozole co-treatment group, and 102 women in the 5 mg letrozole co-treatment group. Letrozole co-treatment significantly suppressed oestradiol and follicle-stimulating hormone concentrations from stimulation day 5 and onwards, while increasing luteinizing hormone levels on stimulation day 5 and trigger day. The effect was more pronounced with a 5 mg dose of letrozole compared to a 2.5 mg dose (P < 0.05). Administration of 5 mg letrozole reduced the gonadotropin dose (P < 0.05) without negatively affecting the number of oocytes retrieved and subsequent embryo parameters (P > 0.05). The analysis of cumulative live birth rates showed rates of 29.4% in the letrozole 5 mg group, 27.5% in the letrozole 2.5 mg group, and 33.6% in the control group, with no statistically significant difference (P > 0.05). There were no reported pregnancy complications in the two letrozole groups. Additionally, there were no significant differences among the three groups in terms of gestational age and birth weight for both singleton and twin births. Conclusion: This study indicates that the administration of letrozole in an antagonist protocol, at both 2.5 mg and 5 mg dosages, results in comparable clinical outcomes.
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Infertilidad Femenina , Embarazo , Recién Nacido , Femenino , Humanos , Letrozol , Estudios Retrospectivos , Infertilidad Femenina/tratamiento farmacológico , Infertilidad Femenina/etiología , Hormona Liberadora de Gonadotropina , China/epidemiología , Fertilización In Vitro/métodosRESUMEN
Objectives: Acute respiratory failure (ARF) is a common complication of bronchial asthma (BA). ARF onset increases the risk of patient death. This study aims to develop a predictive model for ARF in BA patients during hospitalization. Methods: This was a retrospective cohort study carried out at two large tertiary hospitals. Three models were developed using three different ways: (1) the statistics-driven model, (2) the clinical knowledge-driven model, and (3) the decision tree model. The simplest and most efficient model was obtained by comparing their predictive power, stability, and practicability. Results: This study included 398 patients, with 298 constituting the modeling group and 100 constituting the validation group. Models A, B, and C yielded seven, seven, and eleven predictors, respectively. Finally, we chose the clinical knowledge-driven model, whose C-statistics and Brier scores were 0.862 (0.820-0.904) and 0.1320, respectively. The Hosmer-Lemeshow test revealed that this model had good calibration. The clinical knowledge-driven model demonstrated satisfactory C-statistics during external and internal validation, with values of 0.890 (0.815-0.965) and 0.854 (0.820-0.900), respectively. A risk score for ARF incidence was created: The A2-BEST2 Risk Score (A2 (area of pulmonary infection, albumin), BMI, Economic condition, Smoking, and T2(hormone initiation Time and long-term regular medication Treatment)). ARF incidence increased gradually from 1.37% (The A2-BEST2 Risk Score ≤ 4) to 90.32% (A2-BEST2 Risk Score ≥ 11.5). Conclusion: We constructed a predictive model of seven predictors to predict ARF in BA patients. This predictor's model is simple, practical, and supported by existing clinical knowledge.
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Pacientes , Insuficiencia Respiratoria , Humanos , Estudios Retrospectivos , Pronóstico , Factores de Riesgo , Insuficiencia Respiratoria/epidemiologíaRESUMEN
Mutations in mitochondrial DNA (mtDNA) contribute to a variety of serious multi-organ human diseases, which are strictly inherited from the maternal germline. However, there is currently no curative treatment. Attention has been focused on preventing the transmission of mitochondrial diseases through mitochondrial replacement (MR) therapy, but levels of mutant mtDNA can often unexpectedly undergo significant changes known as mitochondrial genetic drift. Here, we proposed a novel strategy to perform spindle-chromosomal complex transfer (SCCT) with maximal residue removal (MRR) in metaphase II (MII) oocytes, thus hopefully eliminated the transmission of mtDNA diseases. With the MRR procedure, we initially investigated the proportions of mtDNA copy numbers in isolated karyoplasts to those of individual oocytes. Spindle-chromosomal morphology and copy number variation (CNV) analysis also confirmed the safety of this method. Then, we reconstructed oocytes by MRR-SCCT, which well developed to blastocysts with minimal mtDNA residue and normal chromosomal copy numbers. Meanwhile, we optimized the manipulation order between intracytoplasmic sperm injection (ICSI) and SCC transfer and concluded that ICSI-then-transfer was conducive to avoid premature activation of reconstructed oocytes in favor of normal fertilization. Offspring of mice generated by embryos transplantation in vivo and embryonic stem cells derivation further presented evidences for competitive development competence and stable mtDNA carryover without genetic drift. Importantly, we also successfully accomplished SCCT in human MII oocytes resulting in tiny mtDNA residue and excellent embryo development through MRR manipulation. Taken together, our preclinical mouse and human models of the MRR-SCCT strategy not only demonstrated efficient residue removal but also high compatibility with normal embryo development, thus could potentially be served as a feasible clinical treatment to prevent the transmission of inherited mtDNA diseases.
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Variaciones en el Número de Copia de ADN , Enfermedades Mitocondriales , Masculino , Humanos , Animales , Ratones , Variaciones en el Número de Copia de ADN/genética , Semen , Mitocondrias/genética , ADN Mitocondrial/genética , ADN Mitocondrial/análisis , Enfermedades Mitocondriales/genética , Enfermedades Mitocondriales/prevención & control , OocitosRESUMEN
Background: Suicide is a worldwide public health problem. Evidence from previous studies has confirmed the relationship among anxiety, depression and suicidal ideation. However, the complex psychopathological pathways between anxiety and suicidal ideation and between depression and suicidal ideation require further study. Methods: A total of 505 college students from Shanghai during COVID-19 pandemic were investigated in an online study. Anxiety, depression and suicidal ideation of the participants were investigated. R software was used to construct the anxiety-suicidal ideation and depression-suicidal ideation networks and to evaluate the bridge expected influences. Results: The anxiety-suicidal ideation network had 28 cross-community edges, the strongest one was A7 "Afraid something will happen"-S7 "Unable to solve personal problem"; A5 "Restlessness" and S3 "Hopelessness and suicide thoughts" had the highest bridge expected influences. The depression-suicidal ideation network had 36 cross-community edges, and the strongest one was D9 "Thoughts of death"-S5 "Unable to accomplish something important"; D9 "Thoughts of death" and S3 "Hopelessness and suicide thoughts" had the highest bridge expected influences. Conclusion: Intricate psychopathological pathways exist between anxiety and suicidal ideation and between depression and suicidal ideation. "Restlessness", "Thoughts of death" and "Hopelessness and suicide thoughts" are considered targets for suicidal ideation interventions. The present study enriches the theory of symptoms and mental disorders and provides a reliable reference for the intervention practice of suicidal ideation.
RESUMEN
Background: ICSI (intracytoplasmic sperm injection) leads to a reduced male-to-female ratio at birth, whereas blastocyst transfer results in an increased male-to-female ratio. However, limited knowledge exists regarding the impact of these factors on the live birth rate for each gender. This study aimed to investigate the influence of patient characteristics and treatment parameters on the live birth rate for each gender, as well as the ultimate male-to-female ratio at birth in frozen-thawed embryo transfer (FET) cycles. Method: This retrospective cohort study involved a total of 28,376 FET cycles and 9,217 subsequent deliveries, spanning from January 2003 to December 2015. The study consisted of two parts. First, logistic regression models were constructed to determine the factors influencing the male-to-female ratio among babies born after FET. Second, we aimed to investigate the mechanisms underlying this sex ratio imbalance by analyzing data from all transfer cycles. Generalized estimated equations were employed to assess the impact of risk factors on rates of male and female live births separately. Results: ICSI resulted in a lower proportion of male offspring compared to in vitro fertilization (IVF) (50.1% vs. 53.7%, aOR: 0.87, 95% CI: 0.80-0.96). Conversely, blastocyst transfer yielded a higher proportion of male offspring than cleavage-stage embryo transfer (58.7% vs. 51.6%, aOR: 1.32, 95% CI: 1.17-1.48). Analysis of all cycles indicated that ICSI resulted in a reduced likelihood of male live birth in comparison to IVF (19.8% vs. 21.6%, aOR: 0.90, 95% CI: 0.83-0.97). However, the transfer of blastocysts rather than cleavage-stage embryos not only increased the chance of male live birth (26.9% vs. 20.2%, aOR: 1.70, 95% CI:1.56-1.85) but also facilitated female live birth (20.3% vs. 19.3%, aOR: 1.26, 95% CI: 1.15-1.39). Conclusion: ICSI was associated with a reduction in the male-to-female sex ratio and a lower rate of male live births, while blastocyst transfer was associated with an increased male-to-female sex ratio at birth and a higher rate of male live births.
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Transferencia de Embrión , Semen , Recién Nacido , Lactante , Humanos , Masculino , Femenino , Estudios Retrospectivos , Transferencia de Embrión/métodos , Fertilización In Vitro/efectos adversos , Inyecciones de Esperma IntracitoplasmáticasRESUMEN
Patients preparing for their renewal fertility treatments with embryos frozen before coronavirus disease 2019 (COVID-19) infection do not need to be concerned about the potential impact of COVID-19 infection on oocyte quality and embryonic development. However, many women are still hesitant to undergo frozen embryo transfer (FET) due to fear of the detrimental effect of COVID-19 infection on endometrial receptivity and embryo implantation. The objective was to explore whether COVID-19 infection after oocyte retrieval is related to an increased risk of adverse pregnancy outcomes in a cohort of Chinese women undergoing FET. A retrospective cohort study was conducted among 300 infertile women undergoing FET with embryos frozen before COVID-19 infection. Women were categorized into noninfection, infection before FET, or infection after FET groups. Multivariable logistic regression was performed to assess the association of COVID-19 infection with clinical pregnancy outcomes, including biochemical pregnancy, clinical pregnancy, and early miscarriage. The implantation rates for patients in the group with infection before FET (29.14%) and the group with infection after FET (30.38%) were not significantly lower than those in the noninfection group (31.03%). The rate of biochemical pregnancy (54.55% vs. 52.27%, p = 0.750; 43.14% vs. 52.27%, p = 0.209) was not significantly different among the three groups. Although the clinical pregnancy rate showed a declining trend from 45.45% in the noninfection group to 38.27% in the group with infection after FET, this result was not statistically significant. The early miscarriage rate was similar in the group with infection before FET and the group with infection after FET compared with that in the noninfection group (3.64% vs. 5.68%, p = 0.496; 6.86% vs. 5.68%, p = 0.739). After adjusting for potential confounders, the biochemical pregnancy rate, clinical pregnancy rate, and early miscarriage rate were not significantly different for patients with infection before or after FET compared with patients without infection. This research indicated that COVID-19 infection after oocyte retrieval with embryos frozen before infection did not cause any detrimental effect on endometrial receptivity for embryo implantation.