Comprehensive Serum Proteomic and Metabolomic Profiles of Pediatric Patients with Moyamoya Disease Reveal Core Pathways.

Background: Moyamoya disease (MMD) signifies a cerebrovascular disorder with obscure origin and a more rapid and severe progression in children than adults. This investigation aims to uncover age-associated distinctions through proteomic and metabolomic profiling to gain insights into the underlying mechanisms of MMD. Methods: Twelve MMD patients-six children and six adults-along with six healthy controls (HC), participated, each providing a 10 mL blood sample. Serum proteomic and metabolomic analyses were conducted using ultra-performance liquid chromatography and high-resolution mass spectrometry, complemented by bioinformatics to identify differential biomolecules and their interactions. Pathway implications were ascertained using GO and KEGG enrichment analysis. Results: Notable proteomic and metabolomic discrepancies were observed between pediatric and adult MMD subjects. A total of 235 and 216 proteins varied in adult and pediatric cases compared to HCs, with 73 proteins shared. In addition, 129 and 74 anionic, plus 96 and 104 cationic metabolites, were differentially expressed in the pediatric and adult groups, respectively, with 34 anionic and 28 cationic metabolites in common. Age-specific biomolecules further characterized these distinctions. Enrichment analysis pinpointed immunity and inflammation pathways, with vitamin digestion and absorption highlighted as pivotal in pediatric MMD. Conclusion: This study unveils distinct metabolic and proteomic patterns within pediatric and adult MMD patients. The critical role of the vitamin digestion and absorption pathway in the pathogenesis of pediatric MMD offers novel insight into disease mechanisms.

Exploring the transcriptomic landscape of moyamoya disease and systemic lupus erythematosus: insights into crosstalk genes and immune relationships.

Background: Systemic Lupus Erythematosus (SLE) is acknowledged for its significant influence on systemic health. This study sought to explore potential crosstalk genes, pathways, and immune cells in the relationship between SLE and moyamoya disease (MMD). Methods: We obtained data on SLE and MMD from the Gene Expression Omnibus (GEO) database. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were conducted to identify common genes. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on these shared genes. Hub genes were further selected through the least absolute shrinkage and selection operator (LASSO) regression, and a receiver operating characteristic (ROC) curve was generated based on the results of this selection. Finally, single-sample Gene Set Enrichment Analysis (ssGSEA) was utilized to assess the infiltration levels of 28 immune cells in the expression profile and their association with the identified hub genes. Results: By intersecting the important module genes from WGCNA with the DEGs, the study highlighted CAMP, CFD, MYO1F, CTSS, DEFA3, NLRP12, MAN2B1, NMI, QPCT, KCNJ2, JAML, MPZL3, NDC80, FRAT2, THEMIS2, CCL4, FCER1A, EVI2B, CD74, HLA-DRB5, TOR4A, GAPT, CXCR1, LAG3, CD68, NCKAP1L, TMEM33, and S100P as key crosstalk genes linking SLE and MMD. GO analysis indicated that these shared genes were predominantly enriched in immune system process and immune response. LASSO analysis identified MPZL3 as the optimal shared diagnostic biomarkers for both SLE and MMD. Additionally, the analysis of immune cell infiltration revealed the significant involvement of activation of T and monocytes cells in the pathogenesis of SLE and MMD. Conclusion: This study is pioneering in its use of bioinformatics tools to explore the close genetic relationship between MMD and SLE. The genes CAMP, CFD, MYO1F, CTSS, DEFA3, NLRP12, MAN2B1, NMI, QPCT, KCNJ2, JAML, MPZL3, NDC80, FRAT2, THEMIS2, CCL4, FCER1A, EVI2B, CD74, HLA-DRB5, TOR4A, GAPT, CXCR1, LAG3, CD68, NCKAP1L, TMEM33, and S100P have been identified as key crosstalk genes that connect MMD and SLE. Activation of T and monocytes cells-mediated immune responses are proposed to play a significant role in the association between MMD and SLE.

The study on the role of O-GlcNAcylation of SIRT3 in regulating mitochondrial oxidative stress during simulate myocardial ischemia-reperfusion.

Myocardial ischemia-reperfusion injury (MIRI) is a significant complication following reperfusion therapy after myocardial infarction. Mitochondrial oxidative stress is a critical factor in MIRI, and Sirtuin 3 (SIRT3), as a major mitochondrial deacetylase, plays a key protective role, with its activity potentially regulated by O-GlcNAcylation. This study used the H9C2 cell line to establish a simulated ischemia/reperfusion (SI/R) model, we utilized co-immunoprecipitated to validate the relationship between O-GlcNAc transferase (OGT) and SIRT3, demonstrated SIRT3 O-GlcNAcylation sites through LC-MS/MS, and performed site mutations using CRISPR/Cas9 technology. The results were validated using immunoblotting. SIRT3 and superoxide dismutase 2 (SOD2) activities were detected using a fluorometric assay, while mitochondrial reactive oxygen species (MROS) levels and cellular apoptosis were assessed using immunofluorescence. We have identified an interaction between SIRT3 and OGT, where SIRT3 undergoes dynamic O-GlcNAcylation at the S190 site, facilitating SIRT3 deacetylase activity. During SI/R, elevated levels of O-GlcNAcylation activate SOD2 by promoting SIRT3 enzyme activity, thereby inhibiting excessive MROS production. This significantly mitigates the occurrence of malignant autophagy in myocardial cells during reperfusion, promoting their survival. Conversely, blocking SIRT3 O-GlcNAcylation at the S190 site exacerbates SI/R injury. We demonstrate that O-GlcNAcylation is a crucial post-translational modification (PTM) of SIRT3 during SI/R, shedding light on a promising mechanism for future therapeutic approaches.

Association of N-terminal pro-B natriuretic peptide with all-cause mortality and cardiovascular mortality in obese and non-obese populations and the development of a machine learning prediction model: National Health and Nutrition Examination Survey (NHANES) 1999-2004.

AIMS: To explore the potential of N-terminal pro-B natriuretic peptide (NTproBNP) in identifying adverse outcomes, particularly cardiovascular adverse outcomes, in a population with obesity, and to establish a risk prediction model. METHODS: The data for this study were obtained from the National Health and Nutrition Examination Survey (NHANES) for 6772 participants without heart failure, for the years 1999 to 2004. Multivariable Cox regression models, cubic spline restricted models and Kaplan-Meier curves were used to evaluate the relationship between NTproBNP and both all-cause mortality and cardiovascular mortality. Predictive models were established using seven machine learning methods, and evaluation was conducted using precision, recall, F1 score, accuracy, and area under the curve (AUC) values. RESULTS: During the population follow-up, out of 6772 participants, 1554 died, with 365 deaths attributed to cardiovascular disease. After adjusting for relevant covariates, NTproBNP levels ≥300 pg/mL were positively associated with both all-cause mortality (hazard ratio [HR] 3.00, 95% confidence interval [CI] 2.48, 3.67) and cardiovascular mortality (HR 6.05, 95% CI 3.67, 9.97), and remained significant across different body mass index (BMI) strata. However, in participants without abdominal obesity, the correlation between NTproBNP and cardiovascular mortality was significantly reduced. Among the seven machine learning methods, logistic regression demonstrated better predictive performance for both all-cause mortality (AUC 0.86925) and cardiovascular mortality (AUC 0.85115). However, establishing accurate cardiovascular mortality prediction models for non-abdominal obese individuals proved challenging. CONCLUSION: The study showed that NTproBNP can serve as a predictive factor for all-cause mortality and cardiovascular mortality in individuals with different BMIs, including obese individuals. However, significant cardiovascular mortality correlation was observed only for NTproBNP levels ≥300 pg/mL, and only among participants with abdominal obesity.

Encoding of 2D Self-Centered Plans and World-Centered Positions in the Rat Frontal Orienting Field.

The neural mechanisms of motor planning have been extensively studied in rodents. Preparatory activity in the frontal cortex predicts upcoming choice, but limitations of typical tasks have made it challenging to determine whether the spatial information is in a self-centered direction reference frame or a world-centered position reference frame. Here, we trained male rats to make delayed visually guided orienting movements to six different directions, with four different target positions for each direction, which allowed us to disentangle direction versus position tuning in neural activity. We recorded single unit activity from the rat frontal orienting field (FOF) in the secondary motor cortex, a region involved in planning orienting movements. Population analyses revealed that the FOF encodes two separate 2D maps of space. First, a 2D map of the planned and ongoing movement in a self-centered direction reference frame. Second, a 2D map of the animal's current position on the port wall in a world-centered reference frame. Thus, preparatory activity in the FOF represents self-centered upcoming movement directions, but FOF neurons multiplex both self- and world-reference frame variables at the level of single neurons. Neural network model comparison supports the view that despite the presence of world-centered representations, the FOF receives the target information as self-centered input and generates self-centered planning signals.

Spatiotemporal trends and coordination of agricultural carbon efficiency in the Yangtze River Economic Belt and Yellow River Basin, China: An analysis of influencing factors and green finance integration.

As China's second-largest source of greenhouse gas emissions, agriculture is essential to achieving the goal of "carbon peak" and "carbon neutrality." Based on the measurement of agricultural carbon emissions (ACE) and agricultural carbon intensity (ACI) in 19 regions along the Yangtze River Economic Belt (YEB) and Yellow River Basin (YRB) in China from 2001 to 2020, this paper first uses the super-efficiency SBM model to measure ACE efficiency from static and dynamic perspectives. Then, the coupling coordination degree (CCD) between ACE efficiency and green finance in each region of the two basins is explored. Finally, Grey Relation Analysis (GRA) is used to obtain the influencing factors of CCD. The following conclusions are drawn: (1) The ACE in the YEB is almost twice that of the YRB. The ACE of the two basins generally experienced a trend of first growth and then declined, but the peak time was different. The ACI of the two basins showed a trend of continuous decline, and the decline rate of the YRB was faster. (2) The ACE efficiency of the two basins showed an overall upward trend, and the growth degree of different regions was vastly different. From the factor decomposition, the technological progress (TP) of the two basins significantly impacts the total factor productivity (TFP). (3) The CCD of ACE efficiency and green finance in the two basins increased from near imbalance to barely coordination level, and the CCD of the YEB increased slightly faster. The CCD of the two basins has a spatial difference of "downstream > midstream > upstream." (4) Among the influencing factors of the CCD of the two systems, the influencing degree of the factors is as follows from large to small: quality of human capital, level of economic development, government regulation, scientific and technological innovation ability.

Eurycomanone inhibits osteosarcoma growth and metastasis by suppressing GRP78 expression.

ETHNOPHARMACOLOGICAL RELEVANCE: Osteosarcoma (OS) is characterized by rapid growth and frequent pulmonary metastasis. Eurycoma longifolia Jack, a flowering plant primarily found in Southeast Asian countries, is commonly used in traditional herbal medicine. Its root extract is mainly used for against cancer, malaria, parasites and other conditions. The active compound in its root extract, eurycomanone (EUR), has been proven to inhibit lung and liver cancer proliferation. AIM OF THE STUDY: Our research aimed to investigate the inhibitory effect and underlying molecular mechanism of EUR on OS growth and metastasis. MATERIALS AND METHODS: In vitro experiments: western blotting (WB) screened 41 compounds that inhibited GRP78 expression and evaluated the protein levels of GRP78, PARP, cleaved-PARP, MMP2, and MMP9. Cell proliferation was evaluated using CCK-8, EdU, colony formation assay, and cell apoptosis was assessed by flow cytometry. Transwell, wound healing, and tube formation assays were performed to determine the effect of EUR on tumor invasion, migration, and angiogenesis, respectively. Quantitative real-time polymerase chain (qRT-PCR) and dual-luciferase activity assays detected GRP78 mRNA stability and transcription levels post-EUR and thapsigargin treatment. RNA-Seq identified signaling pathways inhibited by EUR. In vivo experiments: effects of EUR in mice were evaluated by H&E staining to detect lung metastasis and potential toxic effects in tissues. Immunohistochemical (IHC) staining detected the expression of Ki-67, CD31, and cleaved caspase-3 in tumors. RESULTS: GRP78 is highly expressed in OS and correlated with poor prognosis. In vitro, eurycomanone (EUR) significantly downregulated GRP78 expression, inhibited cell proliferation, migration, invasion, tube formation, and induced apoptosis. Moreover, it enhanced trichostatin A (TSA) sensitivity and exhibited inhibitory effects on other cancer types. Mechanistically, EUR decreased GRP78 mRNA stability and transcription. In vivo, EUR inhibited proliferation and invasion in tibial and PDX models. CONCLUSIONS: Our study demonstrated that EUR inhibits the growth and metastasis of OS by reducing GRP78 mRNA stability and inhibiting its transcription, which offers a novel approach for clinical treatment of OS.

Incidence, clinical classification and risk factors of cyclosporin A-induced liver injury in allogeneic haematopoietic stem cell transplant recipients.

AIMS: There is limited real-world data on cyclosporin A (CsA)-induced liver injury (CILI). This study aims to investigate the incidence, clinical classification and risk factors of CILI, thereby providing evidence to inform the treatment of CILI. METHODS: Inpatients receiving haematopoietic stem cell transplantation (HSCT) and treated with CsA were included. Patient information was collected to assess suspicious CILI by the Roussel Uclaf causality assessment method (RUCAM) scale. We evaluated the pattern and severity of CILI. The independent risk factors of CILI were identified by multivariable logistic regression. RESULTS: A total of 216 allogeneic HSCT (allo-HSCT) recipients were included in this study. The incidence of CILI was 15.3% (95% confidence interval [CI]: 10.4%-20.1%). Among these cases, 84.8% displayed a hepatocellular pattern, and 90.9% of CILI was of mild severity. Baseline alanine aminotransferase (ALT) level (OR = 1.030, 95% CI: 1.008-1.053, P = .008) and trough concentration level of CsA (OR = 1.007, 95% CI: 1.002-1.012, P = .009) were identified as independent risk factors for CILI. CONCLUSIONS: The incidence of CILI in allo-HSCT recipients is notably high. Recipients with elevated baseline ALT levels and higher exposure to CsA are more susceptible to developing CILI.

Encephaloduroarteriosynangiosis for Symptomatic Intracranial Atherosclerotic Arterial Steno-Occlusive Disease: Clinical and Radiological Outcomes.

BACKGROUND: This study investigated the long-term clinical and angiographic outcomes of encephaloduroarteriosynangiosis treatment for symptomatic intracranial atherosclerotic arterial steno-occlusive disease to further evaluate the potential therapeutic role of encephaloduroarteriosynangiosis in this population. METHODS AND RESULTS: A total of 152 adult patients with symptomatic intracranial atherosclerotic arterial steno-occlusive disease who were treated with encephaloduroarteriosynangiosis and intensive medical management across 3 tertiary centers in China between January 2011 and September 2019 were retrospectively included. The primary outcomes were defined as postoperative cerebrovascular events, including ischemic and hemorrhagic stroke. The postoperative neovascularization was analyzed qualitatively and quantitatively by using angiography. Clinical, radiological, and long-term follow-up data were analyzed using Cox regression, logistic regression, and linear regression analyses. Primary outcome rates were 3.2% (5/152) within 30 days, 6.6% (10/152) within 2 years, 9.2% (14/152) within 5 years, and 11.1% (17/152) during a median 9.13 years follow-up. Initial infarction symptoms were positively associated with recurrent ischemic stroke. Additionally, posterior circulation involvement and coexisting cardiac disease indicated poorer neurological status, whereas encephaloduroarteriosynangiosis neovascularization efficacy was negatively associated with older age and vascular risk factors but positively associated with posterior circulation involvement. CONCLUSIONS: Encephaloduroarteriosynangiosis plus intensive medical management appears efficacious and safe for symptomatic intracranial atherosclerotic arterial steno-occlusive disease, with low perioperative risk and favorable long-term results. Further prospective trials are needed to verify its efficacy and determine the optimal patient selection criteria.

Research on financing and technological innovation efficiency of China's energy-saving and environmental protection enterprises.

Green, low-carbon circular economy and the development model of energy-saving and environmental protection are emerging worldwide, and the world's economies have taken the energy-saving and environmental protection industry as a strategic emerging industry to cultivate and develop. Coordinating finance and technological innovation is crucial to promoting the healthy development of Energy-Saving and Environmental Protection Enterprises (ESEPEs). According to industry classification, this paper divides 121 ESEPEs into 12 categories as research objects. Firstly, the DEA-SBM model is used to calculate financing efficiency (FE) and technological innovation efficiency (TIE). Subsequently, the changes in the two efficiencies are analyzed from the perspectives of time series, industry, and annual mean value, and the changes of the two efficiencies are analyzed from the perspectives of time series, industry, and annual average values. Secondly, through the coupling coordination degree (CCD) model, the development status of the coupling coordination between the two efficiencies is innovated expounded. Finally, the Tobit regression model is used to discuss the factors influencing CCD from the whole and industry perspectives. The results show that: (1) TIE is generally lower than FE, and FE shows a downward trend while TIE shows an upward trend. (2) CCD between the two efficiencies is Near dysfunction, and TIE restricts the development of CCD between the two efficiencies to a certain extent. (3) R&D intensity, enterprise size, and government subsidy intensity have a significant positive impact on CCD between FE and TIE of ESEPEs, while the impact of other factors is not significant.

Design of Fluxgate Current Sensor Based on Magnetization Residence Times and Neural Networks.

This study introduces a novel fluxgate current sensor with a compact, ring-shaped configuration that exhibits improved performance through the integration of magnetization residence times and neural networks. The sensor distinguishes itself with a unique magnetization profile, denoted as M waves, which emerge from the interaction between the target signal and ambient magnetic interference, effectively enhancing interference suppression. These M waves highlight the non-linear coupling between the magnetic field and magnetization residence times. Detection of these residence times is accomplished using full-wave rectification circuits and a Schmitt trigger, with a digital output provided by timing sequence detection. A dual-layer feedforward neural network deciphers the target signal, exploiting this non-linear relationship. The sensor achieves a linearity error of 0.054% within a measurement range of 15 A. When juxtaposed with conventional sensors utilizing the residence-time difference strategy, our sensor reduces linearity error by more than 40-fold and extends the effective measurement range by 150%. Furthermore, it demonstrates a significant decrease in ambient magnetic interference.

Oxidative stress in hair follicle development and hair growth: Signalling pathways, intervening mechanisms and potential of natural antioxidants.

Hair follicle development and hair growth are regulated by multiple factors and multiple signalling pathways. The hair follicle, as an important skin appendage, is the basis for hair growth, and it has the functions of safeguarding the body, perceiving the environment and regulating body temperature. Hair growth undergoes a regular hair cycle, including anagen, catagen and telogen. A small amount of physiological shedding of hair occurs under normal conditions, always in a dynamic equilibrium. Hair loss occurs when the skin or hair follicles are stimulated by oxidative stress, inflammation or hormonal disorders that disrupt the homeostasis of the hair follicles. Numerous researches have indicated that oxidative stress is an important factor causing hair loss. Here, we summarize the signalling pathways and intervention mechanisms by which oxidative stress affects hair follicle development and hair growth, discuss existing treatments for hair loss via the antioxidant pathway and provide our own insights. In addition, we collate antioxidant natural products promoting hair growth in recent years and discuss the limitations and perspectives of current hair loss prevention and treatment.

Discovery of petroleum ether extract of eclipta targeting p53/Fas pathway for the treatment of chemotherapy-induced alopecia: Network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Ecliptea herba, a traditional Chinese herbal medicine for hair loss, was first recorded in the Tang Dynasty's 'Qian Jin Yue Ling', of which the active ingredients and mechanisms of action in the treatment of chemotherapy-induced hair loss remain poorly investigated. AIM OF THE STUDY: To investigate the effects of the petroleum ether extract of Eclipta (PEE) on alopecia and follicle damage and elucidate its potential therapeutic mechanisms using the integration of network pharmacology, bioinformatics, and experimental validation. MATERIALS AND METHODS: UPLC-MS was used to analyse the chemical composition of PEE. A network pharmacology approach was employed to establish the 'components-targets-pathways' network of PEE to explore potential therapeutic pathways and targets. Molecular docking was used for validation, and the mechanism of PEE in treating chemotherapy-induced alopecia (CIA) was elucidated using in vitro and in vivo on CIA models. RESULTS: UPLC-MS analysis of PEE revealed 185 components, while network pharmacology and molecular docking analyses revealed potential active compounds and their target molecules, suggesting the involvement of core genes, such as TP53, ESR1, AKT1, IL6, TNF, and EGFR. The key components included wedelolactone, dimethyl-wedelolactone, luteoloside, linarin, and hispidulin. In vivo, PEE promoted hair growth, restored the number of hair follicles, and reduced follicle apoptosis. Conversely, in vitro, PEE enhanced cell viability, reduced apoptosis, and protected HaCaT cells from damage induced by 4-hydroperoxycyclophosphamide (4-HC). CONCLUSIONS: PEE alleviated hair follicle damage in CIA mice by inhibiting the P53/Fas pathway, which may be associated with inhibiting hair follicle cell apoptosis. This study provides a novel therapeutic strategy for treating cyclophosphamide-induced hair loss.

Evaluating the quality of home care in community health service centres: A machine learning approach.

AIMS: The aim of the study is to develop a model using a machine learning approach that can effectively identify the quality of home care in communities. DESIGN: A cross-sectional design. METHODS: In this study, we evaluated the quality of home care in 170 community health service centres between October 2022 and February 2023. The Home Care Service Quality Questionnaire was used to collect information on home care structure, process and outcome quality. Then, an intelligent and comprehensive evaluation model was developed using a convolutional neural network, and its performance was compared with random forest and logistic regression models through various performance indicators. RESULTS: The convolutional neural network model was built upon seven variables, which encompassed the qualification of home nursing staff, developing and practicing emergency plan to cope with different emergency rescues in home environment, being equipped with medication and supplies for first aid according to specific situations, assessing nutrition condition of home patients, allocation of the number of home nursing staff, cases of new pressure ulcers and patient satisfaction rate. Remarkably, the convolutional neural network model demonstrated superior performance, outperforming both the random forest and regression models. CONCLUSION: The successful development and application of the convolutional neural network model highlight its ability to leverage data from community health service centres for rapid and accurate grading of home care quality. This research points the way to home care quality improvement. IMPACT: The model proposed in this study, coupled with the aforementioned factors, is expected to enhance the accuracy and efficiency of a comprehensive evaluation of home care quality. It will also help managers to take purposeful measures to improve the quality of home care. REPORTING METHOD: The reporting of this study (Observational, cross-sectional study) conforms to the STROBE statement. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: The application of this model has the potential to contribute to the advancement of high-quality home care, particularly in lower-middle-income communities.

Development and validation of a novel nomogram for predicting long-term rebleeding risk among patients with hemorrhagic moyamoya disease: a 10-year multicenter retrospective cohort study.

OBJECTIVE: The aim of this study was to develop and validate a predictive nomogram model for long-term rebleeding events in patients with hemorrhagic moyamoya disease (HMMD). METHODS: In total, 554 patients with HMMD from the Fifth Medical Center of the Chinese PLA General Hospital (5-PLAGH cohort) were included and randomly divided into training (390 patients) and internal validation (164 patients) sets. An independent cohort from the First Medical Center and Eighth Medical Center of Chinese PLA General Hospital (the 1-PLAGH and 8-PLAGH cohort) was used for external validation (133 patients). Univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression algorithm were used to identify significant factors associated with rebleeding, which were used to develop a nomogram for predicting 5- and 10-year rebleeding. RESULTS: Intraventricular hemorrhage was the most common type of cerebral hemorrhage (39.0% of patients in the 5-PLAGH cohort and 42.9% of the 1-PLAGH and 8-PLAGH cohort). During the mean ± SD follow-up period of 10.4 ± 2.9 years, 91 (16.4%) patients had rebleeding events in the 5-PLAGH cohort. The rebleeding rates were 12.3% (68 patients) at 5 years and 14.8% (82 patients) at 10 years. Rebleeding events were observed in 72 patients (14.3%) in the encephaloduroarteriosynangiosis (EDAS) surgery group, whereas 19 patients (37.3%) experienced rebleeding events in the conservative treatment group. This difference was statistically significant (p < 0.001). We selected 4 predictors (age at onset, number of episodes of bleeding, posterior circulation involvement, and EDAS surgery) for nomogram development. The concordance index (C-index) values of the nomograms of the training cohort, internal validation cohort, and the external validation cohort were 0.767 (95% CI 0.704-0.830), 0.814 (95% CI 0.694-0.934), and 0.718 (95% CI 0.661-0.775), respectively. The nomogram at 5 years exhibited a sensitivity of 48.1% and specificity of 87.5%. The positive and negative predictive values were 38.2% and 91.3%, respectively. The nomogram at 10 years exhibited a sensitivity of 47.1% and specificity of 89.1%. The positive and negative predictive values were 48.5% and 88.5%, respectively. CONCLUSIONS: EDAS may prevent rebleeding events and improve long-term clinical outcomes in patients with HMMD. The nomogram accurately predicted rebleeding events and assisted clinicians in identifying high-risk patients and devising individual treatments. Simultaneously, comprehensive and ongoing monitoring should be implemented for specific patients with HMMD throughout their entire lifespan.

The effect of deep and awake extubation on emergence agitation after nasal surgery: a randomized controlled trial.

BACKGROUND: Post-anesthetic emergence agitation is common after general anesthesia and may cause adverse consequences, such as injury as well as respiratory and circulatory complications. Emergence agitation after general anesthesia occurs more frequently in nasal surgery than in other surgical procedures. This study aimed to assess the occurrence of emergence agitation in patients undergoing nasal surgery who were extubated under deep anesthesia or when fully awake. METHODS: A total of 202 patients (18-60 years, American Society of Anesthesiologists classification: I-II) undergoing nasal surgery under general anesthesia were randomized 1:1 into two groups: a deep extubation group (group D) and an awake extubation group (group A). The primary outcome was the incidence of emergence agitation. The secondary outcomes included number of emergence agitations, sedation score, vital signs, and incidence of adverse events. RESULTS: The incidence of emergence agitation was lower in group D than in group A (34.7% vs. 72.8%; p < 0.001). Compared to group A, patients in group D had lower Richmond Agitation-Sedation Scale scores, higher Ramsay sedation scores, fewer agitation episodes, and lower mean arterial pressure when extubated and 30 min after surgery, whereas these indicators did not differ 90 min after surgery. There was no difference in the incidence of adverse events between the two groups. CONCLUSIONS: Extubation under deep anesthesia can significantly reduce emergence agitation after nasal surgery under general anesthesia without increasing the incidence of adverse events. TRIAL REGISTRATION: Registered in Clinicaltrials.gov (NCT04844333) on 14/04/2021.

Development and validation of a novel nomogram for predicting good neoangiogenesis after encephaloduroarteriosynangiosis in patients with moyamoya disease and type 2 diabetes mellitus: a case-control study.

OBJECTIVE: Diabetes is often linked to poorer outcomes in patients with moyamoya disease (MMD). However, experience has shown that certain individuals with diabetes have favorable outcomes after encephaloduroarteriosynangiosis (EDAS). The authors aimed to develop a nomogram to predict good neoangiogenesis in patients with MMD and type 2 diabetes mellitus (T2DM) to aid neurosurgeons in the identification of suitable candidates for EDAS. METHODS: Adults with MMD and T2DM who underwent EDAS between June 2004 and December 2018 were included in the analysis. In total, 126 patients (213 hemispheres) with MMD and T2DM from the Fifth Medical Centre of the Chinese PLA General Hospital were included and randomly divided into training (152 hemispheres) and internal validation (61 hemispheres) cohorts at a ratio of 7:3. Univariate logistic and least absolute shrinkage and selection operator regression analyses were used to identify the significant factors associated with good neoangiogenesis, which were used to develop a nomogram. The discrimination, calibration, and clinical utility were assessed. RESULTS: A total of 213 hemispheres in 126 patients were reviewed, including 152 (71.36%) hemispheres with good postoperative collateral formation and 61 (28.64%) with poor postoperative collateral formation. The authors selected 4 predictors (FGD5 rs11128722, VEGFA rs9472135, Suzuki stage, and internal carotid artery [ICA] moyamoya vessels) for nomogram development. The C-indices of the nomogram in the training and internal validation cohorts were 0.873 and 0.841, respectively. The nomogram exhibited a sensitivity of 84.5% and specificity of 81.0%. The positive and negative predictive values were 92.1% and 66.7%, respectively. The calibration curves indicated high predictive accuracy, and receiver operating characteristic curve analysis showed the superiority of the nomogram. The decision-making analysis validated the fitness and clinical application value of this nomogram. Then a web-based calculator to facilitate clinical application was generated. CONCLUSIONS: The nomogram developed in this study accurately predicted neoangiogenesis in patients with MMD and T2DM after EDAS and may assist neurosurgeons in identifying suitable candidates for indirect revascularization surgery.

Phosphorylation of IDH1 Facilitates Progestin Resistance in Endometrial Cancer.

The progestin regimen is one of the main therapeutic strategies for women with endometrial cancer who undergo conservative management. Although many patients respond well to initial therapy, progestin-refractory disease inevitably emerges, and the molecular basis underlying progestin resistance has not been comprehensively elucidated. Herein, they demonstrated progestin results in p38-dependent IDH1 Thr 77 phosphorylation (pT77-IDH1). pT77-IDH1 translocates into the nucleus and is recruited to chromatin through its interaction with OCT6. IDH1-produced α-ketoglutarate (αKG) then facilitates the activity of OCT6 to promote focal adhesion related target gene transcription to confer progestin resistance. Pharmacological inhibition of p38 or focal adhesion signaling sensitizes endometrial cancer cells to progestin in vivo. The study reveals p38-dependent pT77-IDH1 as a key mediator of progestin resistance and a promising target for improving the efficacy of progestin therapy.

Association between polymorphism in the MTHFR gene and encephaloduroarteriosynangiosis-induced collateral circulation formation.

OBJECTIVE: This study aimed to investigate whether high homocysteine (Hcy) levels associated with the MTHFR gene influence the formation of the collateral vascular network in patients with moyamoya disease (MMD) after encephaloduroarteriosynangiosis (EDAS) by influencing the number of endothelial progenitor cells (EPCs) in peripheral blood. METHODS: A total of 118 Chinese patients with bilateral primary MMD were prospectively included. Blood samples were collected from the anterior cubital vein before surgery, and MTHFR rs9651118 was genotyped using high-throughput mass spectrometry to determine the genotype of the test specimen. Serum Hcy and EPC levels were measured, the latter with flow cytometry. Digital subtraction angiography was performed 6 months after EDAS, and the formation of collateral circulation was evaluated using the Matsushima grade system. The correlations between MTHFR rs9651118 genotype, Hcy and EPC levels, and Matsushima grade were compared. RESULTS: Among the 118 patients, 53 had the TT genotype (wild type) of MTHFR rs9651118, 33 TC genotype (heterozygous mutation), and 32 CC genotype (homozygous mutation). The mean ± SD Hcy level was 13.4 ± 9.5 µmol/L in TT patients, 9.8 ± 3.2 µmol/L in TC patients, and 8.9 ± 2.9 µmol/L in CC patients (p < 0.001). The level of EPCs in the venous blood of TT patients was 0.039% ± 0.016%, that of TC patients 0.088% ± 0.061%, and that of CC patients 0.103% ± 0.062% (p < 0.001). When the rs9651118 gene locus was mutated, Matsushima grade was better (p < 0.001) but there was no difference between heterozygous and homozygous mutations. CONCLUSIONS: The results suggest that the MTHFR rs9651118 polymorphism is a good biomarker for collateral vascular network formation after EDAS in MMD patients.

Effects of Ninjurin 2 polymorphisms on susceptibility to coronary heart disease.

OBJECTIVE: The aim of this study was to explore the effects of Ninjurin 2 (NINJ2) polymorphisms on susceptibility to coronary heart disease (CHD). METHODS: We conducted a case-control study with 499 CHD cases and 505 age and gender-matched controls. Five single nucleotide polymorphisms (SNPs) in NINJ2 (rs118050317, rs75750647, rs7307242, rs10849390, and rs11610368) were genotyped by the Agena MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression analysis to assess the association of NINJ2 polymorphisms and CHD risk-adjusted for age and gender. What's more, risk genes and molecular functions were screened via protein-protein interaction (PPI) network and functional enrichment analysis. RESULTS: Rs118050317 in NINJ2 significantly increased CHD risk in people aged more than 60 years and women. Rs118050317 and rs7307242 had strong relationships with hypertension risk in CHD patients. Additionally, rs75750647 exceedingly raised diabetes risk in cases under multiple models, whereas rs10849390 could protect CHD patients from diabetes in allele, homozygote, and additive models. We also observed two blocks in NINJ2. Further interaction network and enrichment analysis showed that NINJ2 played a greater role in the pathogenesis and progression of CHD. CONCLUSION: Our results suggest that NINJ2 polymorphisms are associated with CHD risk.