Background At high magnetic fields, degraded image quality due to dielectric artifacts and elevated specific absorption rate (SAR) are two technical challenges in fetal MRI. Purpose To assess the potential of high dielectric constant (HDC) pad in increasing image quality and decreasing SAR for 3 T fetal MRI. Study Type Prospective. Field Strength/Sequence 3 T. Balanced steady‐state free precession (bSSFP) and single‐shot fast spin‐echo (SSFSE). Population One hundred twenty‐eight participants (maternal‐age 29.0 ± 3.6, range 20–40; gestational‐age 30.3 ± 3.5 weeks, range 22–37 weeks) undertook bSSFP and 40 participants (maternal‐age 29.5 ± 3.8, range 19–40; gestational‐age 30.4 ± 3.5 weeks, range 23–37 weeks) undertook SSFSE. Assessment Patient clinical characteristics were recorded, such as gestational‐age, amniotic‐fluid‐index, abdominal‐circumference, body‐mass‐index, and fetal‐presentation. Quantitative Image‐quality analysis included signal‐to‐noise ratio (SNR) and contrast‐to‐noise ratio (CNR). Qualitative analysis was performed by three radiologists with four‐point scale to evaluate overall image quality, dielectric artifact, and diagnostic confidence. Whole‐body total SAR was obtained from the vendor workstation. Statistical Testing Paired rank sum test was used to analyze the differences in SNR, CNR, overall image quality, dielectric artifact, diagnostic confidence, and SAR with and without HDC pad. Spearman correlation test was used to detect correlations between image quality variable changes and patient clinical characteristics. P values <0.05 were set as statistical significance. Results With HDC pad, SNR and CNR was significantly higher (41.45% increase in SNR, 54.05% increase in CNR on bSSFP; 258.76% increase in SNR, 459.55% increase in CNR on SSFSE). Overall qualitative image quality, dielectric artifact and diagnostic confidence improved significantly. Adding HDC pad significantly reduced Whole‐body total SAR (32.60% on bSSFP; 15.40% on SSFSE). There was no significant correlation between image quality variable changes and participant clinical characteristics ( P ‐values ranging from 0.072 to 0.992). Data Conclusion In the clinical setting, adding a HDC pad might increase image quality while reducing dielectric artifact and SAR. Plan Language Summary Dielectric artifacts and elevated SAR are two technical problems in 3T fetal MRI. In a prospective analysis of 168 pregnant participants undertaking 3.0T fetal MRI scanning, high dielectric constant (HDC) pad increased SNR by 41.45%, CNR by 54.05% on bSSFP, and SNR by 258.76%, CNR by 459.55% on SSFSE. Overall image quality, dielectric artifact reduction, and diagnostic confidence assessed by three radiologists was improved. Whole‐body total SAR decreased by 32.60% on bSSFP and by 15.40% on SSFSE. These findings suggested that the HDC pad can enhance fetal MRI safety and quality, making it a promising tool for clinical practice. Evidence Level 2 Technical Efficacy Stage 5
Gray matter changes are thought to be closely related to cognitive decline in mild cognitive impairment (MCI) patients. The study aimed to explore cortical and subcortical structural alterations in MCI and their association with cognitive assessment. 24 MCI patients and 22 normal controls (NCs) were included. Voxel-based morphometry (VBM), vertex-based shape analysis and surface-based morphometry (SBM) analysis were applied to explore subcortical nuclei volume, shape and cortical morphology. Correlations between structural changes and cognition were explored using spearman correlation analysis. Support vector machine (SVM) classification evaluated MCI identification accuracy. MCI patients showed significant atrophy in the left thalamus, left hippocampus, left amygdala, right pallidum, right hippocampus, along with inward deformation in the left amygdala. SBM analysis revealed that MCI group exhibited shallower sulci depth in the left hemisphere and increased cortical gyrification index (GI) in the right frontal gyrus. Correlation analysis showed the positive correlation between right hippocampus volume and episodic memory, while negative correlation between the altered GI and memory performance in MCI group. SVM analysis demonstrated superior performance of sulci depth and GI derived from SBM in MCI identification. When combined with cortical and subcortical metrics, SVM achieved a peak accuracy of 89 % in distinguishing MCI from NC. The study reveals significant gray matter structural changes in MCI, suggesting their potential role in underlying functional differences and neural mechanisms behind memory impairment in MCI.
目的:分析新型冠状病毒肺炎(COVID-19)疫情大流行前后个体的焦虑水平变化,以及基线期(COVID-19 大流行前)杏仁核亚区体积与大流行前后个体焦虑水平的关系.方法:采用纵向随访研究,收集 40 名健康青年人疫情大流行期间的状态-特质焦虑问卷(STAI).这些被试均具备基线(大流行前)脑影像数据和日常焦虑评分.采用广义线性混合模型分析基线杏仁核亚区体积与大流行前后焦虑得分及变化率的关系.结果:COVID-19 大流行期间个体的状态焦虑水平较大流行之前明显增高(t=-2.584,P=0.014).基线期杏仁核的左侧中央核(F=6.197,P =0.018)和内侧核(F=6.753,P=0.014)亚区体积越大,大流行前后状态焦虑水平变化率越小,且此相关性在青年女性中更为明显.结论:杏仁核亚区体积与重大压力事件(如当前的全球健康危机)引起的个体焦虑水平变化显著相关.这有助于我们理解焦虑易感性的神经生物学基础,并可能对开发有针对性的心理和临床干预措施提供信息.
During the COVID-19 pandemic, junior students who had recently entered university may have experienced particular difficulties. This study aimed to investigate the incidence of anxiety, depression, and sleep status among junior college students during school closure. Junior college students from 3colleges in Anhui Province participated in this study from 6th to 20th April, 2022. The students' data were collected using a designed online questionnaire developed on the "Wen juan xing" website and submitted via cell phone. Ordinal logistic regression analysis indicated that female sex was an independent risk factor for increased anxiety, depression, and insomnia (anxiety: OR 1.503, 95% CI 1.191-1.897; depression: OR 1.14, 95% CI 1.023-1.270; ISI OR 2.052, 95% CI 1.646-2.559). Notably, medical specialty was an independent risk factor for depression and anxiety (anxiety: OR 1.367, 95% CI 1.078-1.734; depression: OR 1.289, 95% CI 1.148-1.448). Moreover, being a freshman was a risk factor for increased depression and insomnia (depression: OR 1.036,95% CI 0.931-1.153; insomnia: (OR 1.157,95% CI 0.961-1.394). The findings indicate that a considerable portion of junior college students experienced psychological problems due to lockdowns during the COVID-19 pandemic.
Background: Surgical strategies in older adult patients with acute type A aortic dissection (aTAAD) are crucial. We investigated the safety and efficiency of open limited surgery for septuagenarian and octogenarian patients with aTAAD. Methods: Between 2011 and 2019, 1,092 patients diagnosed with aTAAD underwent open surgery in Nanjing Drum Tower Hospital. Patients were divided into two groups based on age: <70 years (n=956) and >_70 years (n=136). Preoperative baseline characteristics, operative data, and postoperative outcomes were compared between the two groups. To investigate the safety and efficiency of the surgical approach for those aged >_70 years, we separated these patients into two groups: (I) those who underwent root-sparing surgery and less-invasive arch surgery (Limited group; n=86); and (II) all others (Extensive group; n=50). Results: Mortality was significantly higher in those aged >_70 years than in those <70 years (20.6% vs. 13.2%; P=0.000), with age being a strong risk factor for postoperative mortality [odds ratio (OR) 1.619; 95% confidence interval (CI): 1.015-2.582; P=0.043]. Patients aged >_70 years tended to receive less invasive surgery, and the rates of root replacement and arch replacement were lower. Patients in the limited surgery group had a higher rate of pericardial tamponade, and the durations of surgery, hypothermic circulation arrest, cardiopulmonary bypass, and aortic clamp were all significantly shorter than in the extensive group. Mortality and postoperative complications were also lower in the limited surgery group. Conclusions: Although older age was a risk factor for open surgery for aTAAD, limited surgical techniques could lower the mortality and morbidity regardless of the need for extensive surgery.
Repair or replacement remains debatable in rheumatic heart disease. To regain optimal mean transvalvular pressure gradients and end-diastolic peak flow velocity, the modified release technique combined peeling in the anterior leaflet and separated the shortened chordal. In the end, the short and mid-term outcomes of the modified release technique were evaluated.We retrospectively analyzed a series of 128 patients with rheumatic mitral stenosis, from January 2018 to July 2021 in our center. All patients undergoing mitral valve repair were using the modified release technique. The effect of mitral valve repair was evaluated by intraoperative transesophageal echocardiography and postoperative transthoracic echocardiography.All the 128 patients successfully repaired the mitral valve. The intraoperative transesophageal echocardiography showed trivial or mild regurgitation. The aortic valve was repaired without obvious regurgitation in 12 cases, 5 cases received an aortic valve replacement, 89 cases underwent tricuspid annuloplasty. There were no blood transfusions in most patients, no deaths nor complications during peri-operation, also, no deaths and adverse events were observed during the follow-up period from 3 to 42 months. During the follow-up, 122 cases had no mitral valve regurgitation and 2 cases of moderate regurgitation, 4 cases of mild to moderate regurgitation. The mean peak flow velocity was 1.2 ± 0.3 m / s, no new-onset stenosis occurred.Modified release technique is safe and feasible. Its durability is acceptable in the short and mid-term, with no new-onset stenosis during the follow-up.
We built up a risk stratification model to divide acute type A aortic dissection (aTAAD) patients into low- and high-risk groups, further, to evaluate the risk factors for postoperative mortality. A total of 1364 patients from 2010 to 2020 in our center were retrospectively analyzed. More than twenty clinical variables were related with postoperative mortality. The postoperative mortality of the high-risk patients was doubled than the low-risk ones (21.8% vs 10.1%). The increased operation time, combined coronary artery bypass graft, cerebral complications, re-intubation, continuous renal replacement therapy and surgical infection were risk factors of postoperative mortality in low-risk patients. In addition, postoperative lower limbs or visceral malperfusion were risk factors, axillary artery cannulation and moderate hypothermia were protective factors in high-risk patients. A scoring system for quick decision-making is needed to select appropriate surgical strategy in aTAAD patients. For low-risk patients, different surgical treatments can be performed with similar clinical prognosis. Limited arch treatment and appropriate cannulation approach are crucial in high-risk aTAAD patients.
Abstract Background Acute type A aortic dissection (aTAAD) is a lethal disease and age is an important risk factor for outcomes. This retrospective study was to analyze the impact of age stratification in aTAAD, and to provide clues for surgeons when they make choices of therapy strategies. Methods From January 2011 to December 2019, 1092 aTAAD patients from Nanjing Drum Tower Hospital received surgical therapy. Patients were divided into 7 groups according to every ten-year interval (20–80 s). The differences between the groups were analyzed in terms of the baseline preoperative conditions, surgical methods and postoperative outcomes of patients of different age groups. During a median follow-up term of 17 months, the survival rates were compared among 7 groups through Kaplan–Meier analysis. Results The median age was 52.0 years old in whole cohort. The multiple comorbidities were more common in old age groups (60 s, 70 s, 80 s), while the 20 s group patients had the highest proportion of Marfan syndrome (28.1%). Preoperative hypotension was highest in 80 s (16.7%, P = 0.038). Young age groups (20–60 s) had a higher rate of root replacement and total arch replacement, which led to a longer duration of operation and hypothermic circulation arrest. The overall mortality was 14.1%, the tendency of mortality was increased with age except 20 s group (33.3% in 80 s, P = 0.016). The postoperative morbidity of gastrointestinal bleeding and bowel ischemia were 16.7% and 11.1% in 80 s group. Conclusions Age is a major impact factor for aTAAD surgery. Old patients presented more comorbidities before surgery, the mortality and complications rate were significantly higher even with less invasive and conservative surgical therapy. But the favorable long-term survival indicated that the simple or less extensive arch repair is the preferred surgery for patients over 70 years old.
Kidney and brain expressed protein (KIBRA) rs17070145 is associated with working memory function and cognitive processes. However, the neural mechanisms underlying these associations are not fully understood. This study aimed to explore the effect of KIBRA polymorphism on brain microstructure and blood oxygenation level dependent (BOLD) fluctuations using diffusion kurtosis imaging (DKI) and resting-state functional magnetic resonance imaging (fMRI) in 163 young adults. We also investigated that whether the imaging alterations mediated the association between KIBRA gene and working memory performance. Voxel-based analysis of DKI data showed that KIBRA C-allele carriers exhibited increased axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) as well as decreased fractional anisotropy (FA), mean kurtosis (MK) and radial kurtosis (RK) compared with KIBRA TT homozygotes, primarily involving the prefrontal lobe, left precuneus and the left superior parietal white matter. Meanwhile, KIBRA C-allele carriers exhibited decreased amplitude of low-frequency fluctuation (ALFF) in the left precuneus compared to KIBRA TT homozygotes. Mediation analysis revealed that the DKI metrics (MK and RK) of the left precuneus mediated the effect of the KIBRA polymorphism on working memory performance. Moreover, the MK and RK in the left precuneus were positively correlated with ALFF in the same brain region. These findings suggest that abnormal DKI parameters may provide a gene-brain-behavior pathway in which KIBRA rs17070145 affects working memory by modulating brain microstructure in the left precuneus. This illustrates that DKI may provide additional biological information and reveal new insights into the neural mechanisms of the KIBRA polymorphism.
Accelerated senescence is triggered by key mediators of arrhythmogenic substrates and contributes to atrial fibrillation (AF). We sought to understand senescence in AF and the extent to which it aggravates the AF process. Twenty-six AF patients undergoing open-heart surgery were included, and 12 patients with sinus rhythm served as controls. Another cohort included 120 consecutive persistent AF patients with valvular heart diseases. HL-1 atrial myocytes were tachypaced (TP) to simulate experimental AF. Compared with sinus rhythm, left atrial appendages (LAAs) with AF presented a significantly increased positive area of cellular senescence, with upregulated expression of p16, p21 and p53. Next, p21 mRNA was increased in patients with AF recurrence compared with that in patients without recurrence. In multivariate analysis, p21 (OR: 2.97; 95% CI: 1.65-5.34; P<0.001) was a significant independent predictor of AF early recurrence. Interestingly, TP induced HL-1 atrial myocyte senescence in vitro, accompanied by a marked increase in the senescence-associated secretory phenotype (SASP) and altered the expression of sarcoplasmic reticulum (SR)-related proteins. Suppression of p21 by siRNA reduced TP induced cell senescence and IL-1β, IL-6 elevation, and partly changed SR-related proteins expression. Moreover, we show that the level of γH2AX, a marker of DNA damage, was higher in AF patients than in sinus rhythm controls. Similarly, an increase in γH2AX levels was observed following TP. AF underlies cardiomyocyte senescence and contributes to deleterious atrial remodeling during disease progression. This finding may help facilitate the search for new therapeutic approaches for antiaging therapy for AF.
Decidualization is a prerequisite for successful embryo implantation, in which elongated fibroblast-like endometrial stromal cells differentiate into more rounded decidual cells. Accumulating evidence has stressed the important role of the defective eutopic endometrium in infertility in endometriosis patients. However, the role of arginine methylation in the process of physiological decidualization and pathological decidualization defects is not clear. Here, we observed that the expression level of PRMT5, the main type II PRMT, was decreased in the endometrium of endometriosis patients, predominantly in stromal cells. Compared with the undecidualized state, PRMT5 was increased in the stromal cells of normal secretory endometrium in humans and in the decidua of normal pregnant mice or mice with artificially induced decidualization. The inhibition of PRMT5 resulted in a significant decrease in uterine weight and decidualization-related regulator expression, including FOXO1, HOXA10 and WNT4, in mice and IGFBP1 and prolactin levels in human endometrial stromal cells. Transcriptome analysis showed that decreased PRMT5 activity led to NF-κB signaling activation by inducing p65 translocation to the nucleus, which was also observed in endometriosis patients. Finally, overexpression of PRMT5 rescued the defective expression of IGFBP1 and prolactin in primary endometrial stromal cells from endometriosis patients. Our results indicate that promotion of PRMT5 may provide novel therapeutic strategies for the treatment of decidualization defects in infertile women, such as those with endometriosis.
Research question: What are the potential clinical benefits of embryo culture and assessment in a time-lapse incubator compared with a standard incubator using static assessment? Design: This large multicentre, single-blinded, randomized controlled study included 1224 participants randomly assigned (1:1) to the time-lapse or standard incubator group. In all patients one or two embryos were transferred on day 3. The primary outcome was the implantation rate in the first embryo transfer cycle. Secondary outcomes included the cumulative implantation rate, live birth rate in the first embryo transfer cycle and cumulative live birth rate. Results: Among 1224 participants recruited, 1182 underwent embryo transfer. The number of successfully implanted embryos in the first transfer cycle was significantly higher in the time-lapse incubator group (time-lapse group: 52.35%, standard incubator group: 47.11%, P = 0.014). The implantation rate in the first embryo transfer cycle was still significantly higher in the time-lapse group than the standard incubator group after adjusting for age, body mass
The present study aimed to evaluate the clinical outcomes of magnetic-activated cell sorting (MACS) in sperm preparation for male subjects with a sperm DNA fragmentation index (DFI) ≥30%. A total of 86 patients who had undergone their first long-term long protocol were selected. The protocol involved in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles, and the patients were divided into the MACS or control groups. The MACS group included sperm samples analyzed with MACS that were combined with density gradient centrifugation (DGC) and the swim-up (SU) technique (n = 39), and the control group included sperm samples prepared using standard techniques (DGC and SU; n = 41). No differences were noted with regard to basic clinical characteristics, number of oocytes retrieved, normal fertilization rate, cleavage rate, or transplantable embryo rate between the two groups in IVF/ICSI. In addition, the clinical pregnancy and implantation rates of the first embryo transfer cycles indicated no significant differences between the two groups. However, there was a tendency to improve the live birth rate (LBR) of the first embryo transfer cycle (63.2% vs 53.9%) and the cumulative LBR (79.5% vs 70.7%) in the MACS group compared with the control group. Moreover, the number of transferred embryos (mean ± standard deviation [s.d.]: 1.7 ± 0.7 vs 2.3 ± 1.6) and the transfer number of each retrieved cycle (mean ± s.d.: 1.2 ± 0.5 vs 1.6 ± 0.8) were significantly lower in the MACS group than those in the control group. Thus, the selection of nonapoptotic spermatozoa by MACS for higher sperm DFI could improve assisted reproductive clinical outcomes.
Stanford type A aortic dissection (TA-AD) is a life-threatening disease. Most cases of aortic dissection (AD) are sporadic rather than inherited. Unlike that of inherited AD, the pathogenesis of sporadic AD is still unclear. In the current study, we aimed to explore the pathogenesis of sporadic AD through transcriptome sequencing data analyses. We downloaded sporadic TA-AD transcriptome profiles from Gene Expression Omnibus (GEO) and found response to DNA damage stimulus was activated in AD. Furthermore, by conducting mouse AD tissue single cell RNA sequencing and immunostaining, we found that DNA damage mainly occurred in smooth muscle cells (SMCs) and fibroblasts. Next, we examined the repair patterns in response to DNA damage and found the linker molecules RBBP8/NOTCH1 between DNA damage/repair and extracellular matrix (ECM) organization through protein-protein interaction analysis. Thus, we proposed that DNA damage could contribute to AD by regulating ECM changes. To explore the underlying mechanism, we knocked down the DNA repair-related gene RBBP8 in aortic SMCs, which could exacerbate DNA damage, and observed decreased expression level of NOTCH1. Inhibition of NOTCH1 with crenigacestat in vivo accelerated β-aminopropionitrile-induced formation of AD and increased mortality. Meanwhile, phenotype switching of SMCs was induced by Notch1 knockdown or inhibition; this switching occurred via a pathway involving downregulation of contractile marker gene expression and upregulation of MMP2 expression, which might aggravate ECM degradation. In conclusion, excessive DNA damage is a characteristic pathological change of sporadic aortic dissection, which might contribute to ECM changes and AD development via action on the NOTCH1 pathway.
Endometrial receptivity damage caused by impaired decidualization may be one of the mechanisms of infertility in endometriosis (EMs). Our previous study demonstrated that Calpain-7 (CAPN7) is abnormally overexpressed in EMs. Whether CAPN7 affects the regulation of decidualization and by what mechanism CAPN7 regulates decidualization remains to be determined. In this study, we found CAPN7 expression decreased during human endometrial stromal cell (HESC) decidualization in vitro. CAPN7 negatively regulated decidualization in vitro and in vivo. We also identified one conserved potential PEST sequence in the AKT1 protein and found that CAPN7 was able to hydrolyse AKT1 and enhance AKT1’s phosphorylation. Correspondingly, CAPN7 notably promoted the phosphorylation of Forkhead Box O1 (FoxO1), the downstream of AKT1 protein, at Ser319, leading to increased FoxO1 exclusion from nuclei and attenuated FoxO1 transcriptional activity in decidualized HESC. In addition, we detected endometrium CAPN7, p-AKT1, and p-FoxO1 expressions were increased in EMs. These data demonstrate that CAPN7 negatively regulates HESC decidualization in EMs probably by promoting FoxO1’s phosphorylation and FoxO1 nuclear exclusion via hydrolyzing AKT1. The dysregulation of CAPN7 may be a novel cause of EMs.
BACKGROUND:Epicardial adipose tissue (EAT) accumulation is associated with the progression of atrial fibrillation. However, the histological features of EATs are poorly defined and their correlation with atrial fibrosis is unclear.OBJECTIVE:The purpose of this study was to identify and characterize EAT subgroups in the persistent atrial fibrillation (PeAF) cohorts.METHODS:EATs and the corresponding left atrial appendage samples were obtained from patients with PeAF via surgical intervention. Adipocyte markers, that is, Uncoupling Protein 1, Transcription Factor 21, and CD137, were examined. On the basis of expression of adipocyte markers, patients with PeAF were categorized into subgroups by using unsupervised clustering analysis. Clinical characteristics, histological analyses, and outcomes were subsequently compared across the clusters. External validation was performed in a validation cohort.RESULTS:The ranking of feature importance revealed that the 3 adipocyte markers were the most relevant factors for atrial fibrosis compared with other clinical indicators. On the k-medoids analysis, patients with PeAF could be categorized into 3 clusters in the discovery cohort. The histological studies revealed that patients in cluster 1 exhibited statistically larger size of adipocytes in EATs and severe atrial fibrosis in left atrial appendages. Findings were replicated in the validation cohort, where severe atrial fibrosis was noted in cluster 1. Moreover, in the validation cohort, there was a high degree of overlap between the supervised classification results and the unsupervised cluster results from the k-medoids method.CONCLUSION:Machine learning-based cluster analysis could identify subtypes of patients with PeAF having distinct atrial fibrosis profiles. Additionally, EAT whitening (increased proportion of white adipocytes) may be involved in the process of atrial fibrosis.
The effects of D2O in the reaction mixture and temperature change on the oxidation of Fe(II) by crystalline human ferroxidase (ferrous-O2-oxidoreductate, EC 1.12.3) were studied. It was found that the enzymic activity of ferroxidase was inhibited 42–43% in 66% deuterium containing buffer, which was observed by Fe (III)-transferrin formation or by a stopped-flow method. It was concluded that a part of the D2O effect on the enzyme activity may be due to the exchange of hydrogen closely related either geometrically or electronically to the active center of the enzyme. The following thermodynamic parameters of Fe (II) oxidation by ferroxidase were obtained: ΔH∗ = 10.3kcal/mole, ΔF∗ = 17 kcal/mole, and ΔS∗ = -22.9cal/mole/degree, for the reaction in 100% H2O medium with nondeuterated enzyme; and ΔH∗ = 9.9 kcal/mole, ΔF∗ = 17.3 kcal/mole, and ΔS∗ = -25.3 cal/mole/degree, for the reaction in 66% D2O + 34% H2O medium with deuterated enzyme, respectively. The relatively large entropy change, and its more negative value in the deuterated reaction mixture, suggest that geometrical or electronical rearrangements, or both, of hydrogen atoms closely related to active site of the enzyme molecule may be involved in the rate-determining step of the ferroxidase activity.
Purpose: Neuroimaging has demonstrated altered static functional connectivity in patients with premature ejaculation (PE), while studies examining dynamic changes in spontaneous brain activity in PE patients are still lacking. We aimed to explore the reconfiguration of dynamic functional connectivity (DFC) states in lifelong PE (LPE) patients and to distinguish LPE patients from normal controls (NCs) using a machine learning method based on DFC state features. Methods: Thirty-six LPE patients and 23 NCs were recruited. Resting-state functional magnetic resonance imaging (fMRI) data, the clinical rating scores on the Chinese Index of PE (CIPE), and intravaginal ejaculatory latency time (IELT) were collected from each participant. DFC was calculated by the sliding window approach. Finally, the Lagrangian support vector machine (LSVM) classifier was applied to distinguish LPE patients from NCs using the DFC parameters. Two DFC state metrics (reoccurrence times and transition frequencies) were introduced and we assessed the correlations between DFC state metrics and clinical variables, and the accuracy, sensitivity, and specificity of the LSVM classifier. Results: By k-means clustering, four distinct DFC states were identified. The LPE patients showed an increase in the reoccurrence times for state 3 (p < 0.05, Bonferroni corrected) but a decrease for state 1 (p < 0.05, Bonferroni corrected) compared to the NCs. Moreover, the LPE patients had significantly less frequent transitions between state 1 and state 4 (p < 0.05, uncorrected) while more frequent transitions between state 3 and state 4 (p < 0.05, uncorrected) than the NCs. The reoccurrence times and transition frequencies showed significant associations with the CIPE scores and IELTs. The accuracy, sensitivity, and specificity of the LSVM classifier were 90.35, 87.59, and 85.59%, respectively. Conclusion: LPE patients were more inclined to be in DFC states reinforced intra-network and inter-network connection. These features correlated with clinical syndromes and can classify the LPE patients from NCs. Our results of reconfiguration of DFC states may provide novel insights for the understanding of central etiology underlying LPE, indicate neuroimaging biomarkers for the evaluation of clinical severity of LPE.
The establishment of endometrial receptivity is a prerequisite for successful pregnancy. Women with adenomyosis possess a lower chance of clinical pregnancy after assisted reproductive technology, which is partially due to impaired endometrial receptivity. The establishment of endometrial receptivity requires the participation of multiple processes, and proper endometrial epithelial cell (EEC) proliferation is indispensable. Monoamine oxidase A (MAOA) is a key molecule that regulates neurotransmitter metabolism in the nervous system. In the present study, we demonstrated a novel role for MAOA in the establishment of endometrial receptivity in women with adenomyosis and in an adenomyotic mouse model. Attenuated MAOA impairs endometrial receptivity by promoting inappropriate proliferation of EECs via the downregulation of FOXO1 during the window of implantation. These results revealed that MAOA plays a vital role in endometrial receptivity in female reproduction.
We aimed to determine the alterations in the subcortical structures of patients with idiopathic generalized epilepsy with tonic–clonic seizures (IGE-GTCS) via MRI volumetry and vertex-based shape analysis and to evaluate the relationships between MRI measures and drug responses. In a follow-up sample of 48 patients with IGE-GTCS and 48 matched normal controls (NCs), high-resolution 3D T1WI was performed at baseline. After 1 year of follow-up, 31 patients were classified as seizure free (SF) and 17 as drug resistant (DR). The volumes of subcortical structures were extracted, and vertex-based shape analysis was performed using FSL-Integrated Registration and Segmentation Toolbox (FSL-FIRST). Comparisons among groups were calculated adjusting for covariates [age, sex, and intracranial volume (ICV)]. Analysis of the relationships among imaging biomarkers along with frequency and duration was assessed using partial correlations. The differential imaging indicators were used as features in a linear support vector machine (LSVM). The DR group displayed significant regional atrophy in the volume of the left amygdala compared with NCs (p = 0.004, false discovery rate corrected) and SF patients (p = 0.029, uncorrected). Meanwhile, vertex-based shape analysis showed focal inward deformation in the basolateral subregion of the left amygdala in DR compared with the results for SF and NC (p < 0.05, FWE corrected). There were significant correlations between the volume changes and seizure frequency (r = −0.324, p = 0.030) and between shape (r = −0.438, p = 0.003) changes and seizure frequency. Moreover, the volume of the left thalamus in the DR group was significantly correlated with seizure frequency (r = −0.689, p = 0.006). The SVM results revealed areas under the receiver operating characteristic curve of 0.82, 0.68, and 0.88 for the classification between SF and DR, between SF and NC, and between DR and NC, respectively. This study indicates the presence of focal atrophy in the basolateral region of the left amygdala in patients with IGE drug resistance; this finding may help predict drug responses and suggests a potential therapeutic target.