A Metabolic Basis for Endothelial-to-Mesenchymal Transition.

Endothelial-to-mesenchymal transition (EndoMT) is a cellular process often initiated by the transforming growth factor ß (TGF-ß) family of ligands. Although required for normal heart valve development, deregulated EndoMT is linked to a wide range of pathological conditions. Here, we demonstrate that endothelial fatty acid oxidation (FAO) is a critical in vitro and in vivo regulator of EndoMT. We further show that this FAO-dependent metabolic regulation of EndoMT occurs through alterations in intracellular acetyl-CoA levels. Disruption of FAO via conditional deletion of endothelial carnitine palmitoyltransferase II (Cpt2E-KO) augments the magnitude of embryonic EndoMT, resulting in thickening of cardiac valves. Consistent with the known pathological effects of EndoMT, adult Cpt2E-KO mice demonstrate increased permeability in multiple vascular beds. Taken together, these results demonstrate that endothelial FAO is required to maintain endothelial cell fate and that therapeutic manipulation of endothelial metabolism could provide the basis for treating a growing number of EndoMT-linked pathological conditions.

The Application of CT Radiomics in the Diagnosis of Vein Wall Invasion in Patients With Renal Cell Carcinoma Combined With Tumor Thrombus.

OBJECTIVE: The objective of this study was to explore the application of radiomics combined with machine learning to establish different models to assist in the diagnosis of venous wall invasion in patients with renal cell carcinoma and venous tumor thrombus and to evaluate the diagnostic efficacy. MATERIALS AND METHODS: We retrospectively reviewed the data of 169 patients in Peking University Third Hospital from March 2015 to January 21, who was diagnosed as renal mass with venous invasion. According to the intraoperative findings, 111 patients were classified to the venous wall invasion group and 58 cases in the non-invasion group. ITK-snap was used for tumor segmentation and PyRadiomics 3.0.1 package was used for feature extraction. A total of 1598 features could be extracted from each CT image. The patients were divided into training set and testing set by time. The elastic-net regression with 4-fold cross-validation was used as a dimension-reduction method. After feature selection, a support vector machines (SVM) model, a logistic regression (LR) model, and an extra trees (ET) model were established. Then the sensitivity, specificity, accuracy, and the area under the curve (AUC) were calculated to evaluate the diagnostic performance of each model on the testing set. RESULTS: Patients before September 2019 were divided into the training set, of which 88 patients were in the invasion group and 42 patients were in the non-invasion group. The others were in the testing set, of which 32 patients were in the invasion group and 16 patients were in the non-invasion group. A total of 34 radiomics features were obtained by the elastic-net regression. The SVM model had an AUC value of 0.641 (95% CI, 0.463-0.769), a sensitivity of 1.000, and a specificity of 0.062. The LR model had an AUC value of 0.769 (95% CI, 0.620-0.877), a sensitivity of 0.913, and a specificity of 0.312. The ET model had an AUC value of 0.853 (95% CI, 0.734-0.948), a sensitivity of 0.783, and a specificity of 0.812. Among the 3 models, the ET model had the best diagnostic effect, with a good balance of sensitivity and specificity. And the higher the tumor thrombus grade, the better the diagnostic efficacy of the ET model. In inferior vena cava tumor thrombus, the sensitivity, specificity, accuracy, and AUC of ET model can be improved to 0.889, 0.800, 0.857, 0.878 (95% CI, 0.745-1.000). CONCLUSION: Machine learning combined with radiomics method can effectively identify whether venous wall was invaded by tumor thrombus and has high diagnostic efficacy with an AUC of 0.853 (95% CI, 0.734-0.948).

The antioxidant enzyme Prdx1 controls neuronal differentiation by thiol-redox-dependent activation of GDE2.

The six-transmembrane protein GDE2 controls the onset and progression of spinal motor neuron differentiation through extracellular glycerophosphodiester phosphodiesterase metabolism. Although this process is likely to be tightly regulated, the relevant mechanisms that modulate its activity are unknown. Here we show that the antioxidant scavenger peroxiredoxin1 (Prdx1) interacts with GDE2, and that loss of Prdx1 causes motor neuron deficits analogous to GDE2 ablation. Prdx1 cooperates with GDE2 to drive motor neuron differentiation, and this synergy requires Prdx1 thiol-dependent catalysis. Prdx1 activates GDE2 through reduction of an intramolecular disulfide bond that bridges its intracellular N- and C-terminal domains. GDE2 variants incapable of disulfide bond formation acquire independence from Prdx1 and are potent inducers of motor neuron differentiation. These findings define Prdx1 as a pivotal regulator of GDE2 activity and suggest roles for coupled thiol-redox-dependent cascades in controlling neuronal differentiation in the spinal cord.

Neural oscillations reflect the individual differences in the temporal perception of audiovisual speech.

Multisensory integration occurs within a limited time interval between multimodal stimuli. Multisensory temporal perception varies widely among individuals and involves perceptual synchrony and temporal sensitivity processes. Previous studies explored the neural mechanisms of individual differences for beep-flash stimuli, whereas there was no study for speech. In this study, 28 subjects (16 male) performed an audiovisual speech/ba/simultaneity judgment task while recording their electroencephalography. We examined the relationship between prestimulus neural oscillations (i.e. the pre-pronunciation movement-related oscillations) and temporal perception. The perceptual synchrony was quantified using the Point of Subjective Simultaneity and temporal sensitivity using the Temporal Binding Window. Our results revealed dissociated neural mechanisms for individual differences in Temporal Binding Window and Point of Subjective Simultaneity. The frontocentral delta power, reflecting top-down attention control, is positively related to the magnitude of individual auditory leading Temporal Binding Windows (auditory Temporal Binding Windows; LTBWs), whereas the parieto-occipital theta power, indexing bottom-up visual temporal attention specific to speech, is negatively associated with the magnitude of individual visual leading Temporal Binding Windows (visual Temporal Binding Windows; RTBWs). In addition, increased left frontal and bilateral temporoparietal occipital alpha power, reflecting general attentional states, is associated with increased Points of Subjective Simultaneity. Strengthening attention abilities might improve the audiovisual temporal perception of speech and further impact speech integration.

Oncological and reproductive outcomes of endometrial atypical hyperplasia and endometrial cancer patients undergoing conservative therapy with hysteroscopic resection: A systematic review and meta-analysis.

INTRODUCTION: Our objective was to conduct a systematic review and meta-analysis of studies evaluating the oncological and reproductive outcomes of patients with endometrial atypical hyperplasia (AH) and endometrioid endometrial cancer (EEC) undergoing conservative therapy with hysteroscopic resection (HR). MATERIAL AND METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for systematic reviews and meta-analyses. The study strictly followed the methodological framework proposed by the Cochrane Handbook and was retrospectively registered in PROSPERO (CRD42023469986). Searches were conducted in PubMed, Embase, and the Cochrane Library, from inception to October 10, 2023. A checklist based on items of the Newcastle-Ottawa Scale and the Methodological Index for Non-randomized Studies was used for quality assessment. The primary end points for this meta-analysis were complete response (CR), pregnancy, and live birth rates following HR-based therapy in patients with EEC or AH. The secondary end point was the recurrence rate (RR). RESULTS: Twenty-one articles involving 407 patients with clinical stage IA, low or intermediate grade, EEC, and 444 patients with AH managed with HR-based conservative treatment were included for this systematic review. CR to HR-based conservative therapy was achieved in 88.6% of patients with EEC and 97.0% of patients with AH. Of these, 30.6% and 24.2%, respectively, had live births. The overall pooled disease RR was 18.3% and 10.8% in patients with EEC and AH, respectively. Further subset analyses revealed that EEC patients with body mass index (BMI) ≤28 kg/m2 had higher CR rates as well as higher chances of pregnancy and live birth (91.6% CR, 32.9% pregnancy, 31.1% live birth) compared with patients with BMI >28 kg/m2 (86.4% CR, 28.4% pregnancy, 23.0% live birth). The HR followed by oral progestogen subgroup had higher CR rates and higher chances of pregnancy and live birth (91.8% CR, 36.3% pregnancy, 28.2% live birth) than the HR followed by the levonorgestrel intrauterine system subgroup (82.5% CR, 25.3% pregnancy, 16.3% live birth). CONCLUSIONS: Hysteroscopic resection followed by progestins appears to be a promising choice for fertility-sparing treatment in young patients with AH and EEC, with effective and safe responses. The live birth rate remains to be improved by providing medical guidance and encouragement.

Effect of Phase Clustering Bias on Phase-Amplitude Coupling for Emotional EEG.

BACKGROUND: Emotions are thought to be related to distinct patterns of neural oscillations, but the interactions among multi-frequency neural oscillations during different emotional states lack full exploration. Phase-amplitude coupling is a promising tool for understanding the complexity of the neurophysiological system, thereby playing a crucial role in revealing the physiological mechanisms underlying emotional electroencephalogram (EEG). However, the non-sinusoidal characteristics of EEG lead to the non-uniform distribution of phase angles, which could potentially affect the analysis of phase-amplitude coupling. Removing phase clustering bias (PCB) can uniform the distribution of phase angles, but the effect of this approach is unknown on emotional EEG phase-amplitude coupling. This study aims to explore the effect of PCB on cross-frequency phase-amplitude coupling for emotional EEG. METHODS: The technique of removing PCB was implemented on a publicly accessible emotional EEG dataset to calculate debiased phase-amplitude coupling. Statistical analysis and classification were conducted to compare the difference in emotional EEG phase-amplitude coupling prior to and post the removal of PCB. RESULTS: Emotional EEG phase-amplitude coupling values are overestimated due to PCB. Removing PCB enhances the difference in coupling strength between fear and happy emotions in the frontal lobe. Comparable emotion recognition performance was achieved with fewer features after removing PCB. CONCLUSIONS: These findings suggest that removing PCB enhances the difference in emotional EEG phase-amplitude coupling patterns and generates features that contain more emotional information. Removing PCB may be advantageous for analyzing emotional EEG phase-amplitude coupling and recognizing human emotions.

Fusion of Multi-domain EEG Signatures Improves Emotion Recognition.

BACKGROUND: Affective computing has gained increasing attention in the area of the human-computer interface where electroencephalography (EEG)-based emotion recognition occupies an important position. Nevertheless, the diversity of emotions and the complexity of EEG signals result in unexplored relationships between emotion and multichannel EEG signal frequency, as well as spatial and temporal information. METHODS: Audio-video stimulus materials were used that elicited four types of emotions (sad, fearful, happy, neutral) in 32 male and female subjects (age 21-42 years) while collecting EEG signals. We developed a multidimensional analysis framework using a fusion of phase-locking value (PLV), microstates, and power spectral densities (PSDs) of EEG features to improve emotion recognition. RESULTS: An increasing trend of PSDs was observed as emotional valence increased, and connections in the prefrontal, temporal, and occipital lobes in high-frequency bands showed more differentiation between emotions. Transition probability between microstates was likely related to emotional valence. The average cross-subject classification accuracy of features fused by Discriminant Correlation Analysis achieved 64.69%, higher than that of single mode and direct-concatenated features, with an increase of more than 7%. CONCLUSIONS: Different types of EEG features have complementary properties in emotion recognition, and combining EEG data from three types of features in a correlated way, improves the performance of emotion classification.

Follicular fluid progesterone downregulated HPGD and COX2 in granulosa cells via suppressing NF-ĸB in endometriosis†.

Increasing evidences showed that ovulatory dysfunction, possibly caused by luteinized unruptured follicular follicle syndrome (LUFS), is one of the reasons for endometriosis-related infertility. The present study was conducted to explore the potential effect of elevated progesterone in follicular fluid (FF) on ovulation in endometriosis. A prospective study including 50 ovarian endometriosis patients and 50 control patients with matched pairs design was conducted with alterations in FF and peritoneal fluid (PF) components identified by metabolomics analyses and differentially expressed genes in granulosa cells (GCs) identified by transcriptome analysis. Patients with endometriosis exhibited a significantly higher progesterone level in serum, FF, and PF. Granulosa cells from endometriosis patients revealed decreased expression of HPGD, COX-2, and suppressed NF-ĸB signaling. Similarly, progesterone treatment in vitro downregulated HPGD and COX2 expression and suppressed NF-ĸB signaling in granulosa tumor-like cell line KGN (Bena Culture Collection, China) and primarily cultured GCs, as manifested by decreased expressions of IL1R1, IRAK3, reduced pIĸBα/IĸBα ratio, and nucleus translocation of p65. On the contrary, TNF-α treatment increased expression of IL1R1, IRAK3, pIĸBα, p65, and HPGD in GCs. One potential p65 binding site was identified in the promoter region of HPGD by chromatin immunoprecipitation. In conclusion, we found that intrafollicular progesterone might downregulate HPGD and COX-2 in GCs via suppressing the NF-ĸB signaling pathway, shedding light on the mechanism underlying the endometriosis-related ovulatory dysfunction.

CircKDM5B sponges miR-128 to regulate porcine blastocyst development by modulating trophectoderm barrier function.

Circular RNAs (circRNAs), which exert critical functions in the regulation of transcriptional and post-transcriptional gene expression, are found in mammalian cells but their functions in mammalian preimplantation embryo development remain poorly understood. Here, we showed that circKDM5B mediated miRNA-128 (miR-128) to regulate porcine early embryo development. We screened circRNAs potentially expressed in porcine embryos through an integrated analysis of sequencing data from mouse and human embryos, as well as porcine oocytes. An authentic circRNA originating from histone demethylase KDM5B (referred to as circKDM5B) was abundantly expressed in porcine embryos. Functional studies revealed that circKDM5B knockdown not only significantly reduced blastocyst formation but also decreased the number of total cells and trophectoderm (TE) cells. Moreover, the knockdown of circKDM5B resulted in the disturbance of tight junction assembly and impaired paracellular sealing within the TE epithelium. Mechanistically, miR-128 inhibitor injection could rescue the early development of circKDM5B knockdown embryos. Taken together, the findings revealed that circKDM5B functions as a miR-128 sponge, thereby facilitating early embryonic development in pigs through the modulation of gene expression linked to tight junction assembly.

Preoperative predictive model of early urinary continence recovery after laparoscopic radical prostatectomy.

PURPOSE: To develop and validate a predictive model include magnetic resonance imaging (MRI) parameters preoperatively which can assess the risk of incontinence after laparoscopic radical prostatectomy (LRP) accurately. METHODS: We retrospectively reviewed and included 170 patients with prostate cancer who underwent LRP between July 2015 and June 2018 in our institution. All 170 patients were randomly resampled and divided into training set (n = 124) and verification set (n = 46) according to the ratio of 7:3. The Nomogram prediction model of the risk of incontinence after LRP was established through the training set and verified by the verification set. Baseline patient characteristics were obtained, including age, body mass index, and prostate volume. Perioperative characteristics such as pre-biopsy prostate specific antigen, biopsy Gleason score, clinical staging, and NVB sparing status were also collected. MRI parameters preoperatively including membranous urethral length (MUL), prostate apex depth ratio (PADR), and intravesical prostatic protrusion length (IPPL) were obtained. The C index and visual inspection of calibration curve were used to evaluate the discrimination and calibration of the model. RESULTS: According to the urinary incontinence (UI) at 3 months postoperatively, the patients were divided into 104 cases (61.2%) in the group with no incontinence and 66 patients (38.8%) in the group with incontinence. Multivariate logistic regression analysis of training set showed that cT3a (OR = 0.427, 95% CI 0.142-1.281, P = 0.1288), MUL (OR = 0.237, 95% CI 0.102-0.551, P < 0.01), PADR (OR = 0.276, 95% CI 0.116-0.655, P < 0.01), and IPPL (OR = 0.073, 95% CI 0.030-0.179, P < 0.01) were independent predictors of urinary incontinence at 3 months postoperatively. The model showed good discrimination with an area under the receiver operating characteristic (ROC) curve of 0.880, with the sensitivity and specificity 0.800 and 0.816, respectively, and good calibration (Hosmer-Lemeshow test result of 5.57, P = 0.695). Decision curve analysis demonstrated that the model was clinically useful. CONCLUSION: This study developed and validated a preoperative model in the form of a nomogram to predict the risk of UI after LRP at 3 months. MUL, PADR, and IPPL were significant independent predictive factors of the postoperative early urinary continence.

Comparative analysis of surgical and oncologic outcomes of robotic, laparoscopic and open radical nephrectomy with venous thrombectomy: a propensity-matched cohort study.

OBJECTIVE: To provide insight into the surgical and oncological outcomes of robotic, laparoscopic and open radical nephrectomy with venous thrombectomy (RALRN-VT, LRN-VT, ORN-VT) in patients with renal tumor and venous thrombus. MATERIALS AND METHODS: A propensity-matched retrospective cohort study containing 324 patients with renal tumor and venous thrombus from January 2014 to August 2021 was analyzed. We compared surgical outcomes and we used the Kalan-Meier method to assess the overall survival (OS), tumor-specific survival (TSS), metastasis-free survival (MFS) and local recurrence-free survival (LRFS). The Pearson chi-square test and Fisher exact test, Wilcoxon rank sum test, Cox proportional hazards regression model and log-rank test were used. RESULTS: After matching, baseline characteristics were comparable in the RALRN-VT, LRN-VT and ORN-VT group. The RALRN-VT group had the least operative time (median 134 min vs 289 min vs 330 min, P < 0.001), the least blood loss (median 250 ml vs 500 ml vs 1000 ml, P < 0.001) and the fewest packed red blood cells transfusion (median 400 ml vs 800 ml vs 1200 ml, P < 0.001). The ORN-VT group had the highest complication rate (18.2 vs 22.7 vs 43.2%, P = 0.005), the highest Clavien grade (P = 0.001) and the longest postoperative hospital stay (median 7d vs 8d vs 10d, P < 0.001). No significant difference in OS, TSS and MFS between the minimally invasive procedures (MIP, including RALRN-VT and LRN-VT) group and ORN-VT group was found. The hazard ratio of LRFS for the MIP group was 0.20 (95% CI 0.06-0.70, P = 0.01) compared with ORN-VT group. CONCLUSIONS: RALRN-VT can result in the best surgical outcomes compared with LRN-VT and ORN-VT. The MIP group had a better LRFS compared with ORN-VT group.

CCNE1 is a predictive and immunotherapeutic indicator in various cancers including UCEC: a pan-cancer analysis.

BACKGROUND: CCNE1 plays an important oncogenic role in several tumors, especially high-stage serous ovarian cancer and endometrial cancer. Nevertheless, the fundamental function of CCNE1 has not been explored in multiple cancers. Therefore, bioinformatics analyses of pan-cancer datasets were carried out to explore how CCNE1 regulates tumorigenesis. METHODS: A variety of online tools and cancer databases, including GEPIA2, SangerBox, LinkedOmics and cBioPortal, were applied to investigate the expression of CCNE1 across cancers. The pan-cancer datasets were used to search for links between CCNE1 expression and prognosis, DNA methylation, m6A level, genetic alterations, CCNE1-related genes, and tumor immunity. We verified that CCNE1 has biological functions in UCEC cell lines using CCK-8, EdU, and Transwell assays. RESULTS: In patients with different tumor types, a high mRNA expression level of CCNE1 was related to a poor prognosis. Genes related to CCNE1 were connected to the cell cycle, metabolism, and DNA damage repair, according to GO and KEGG enrichment analyses. Genetic alterations of CCNE1, including duplications and deep mutations, have been observed in various cancers. Immune analysis revealed that CCNE1 had a strong correlation with TMB, MSI, neoantigen, and ICP in a variety of tumor types, and this correlation may have an impact on the sensitivity of various cancers to immunotherapy. CCK-8, EdU and Transwell assays suggested that CCNE1 knockdown can suppress UCEC cell proliferation, migration and invasion. CONCLUSION: Our study demonstrated that CCNE1 is upregulated in multiple cancers in the TCGA database and may be a promising predictive biomarker for the immunotherapy response in some types of cancers. Moreover, CCNE1 knockdown can suppress the proliferation, migration and invasion of UCEC cells.

The prognostic utility of preoperative geriatric nutritional risk index on survival outcomes of locally advanced oral cancer.

PURPOSE: This retrospective cohort study was to assess the prognostic value of preoperative geriatric nutritional risk index (GNRI) on survival outcomes for patients with locally advanced oral squamous cell carcinoma (LAOSCC). METHODS: Patients with LAOSCC receiving upfront radical surgery at a single institute from January 2007 to February 2017 were enrolled. The primary outcomes in the study were 5-year overall survival (OS) and cancer-specific survival (CSS) rates, and a nomogram based on GNRI and other clinical-pathological factors was established for individualized OS prediction. RESULTS: There were 343 patients enrolled in this study. The optimal cut-off value of GNRI was observed to be 97.8. Patients in the high-GNRI group (GNRI ≥97.8) had statistically significantly better outcomes in 5-year OS (74.7% vs. 57.2%, p = 0.001) and CSS (82.2% vs. 68.9%, p = 0.005) when compared with the low-GNRI group (GNRI <97.8). In Cox models, low GNRI remained an independent negative prognosticator of OS (HR: 1.6; 95% CI: 1.124-2.277; p = 0.009) and CSS (HR: 1.907; 95% CI: 1.219-2.984; p = 0.005). The c-index of the proposed nomogram, incorporating assorted clinicopathological factors and GNRI, had a statistically significant increase compared with the predictive nomogram constructed by the TNM staging system alone (0.692 vs. 0.637, p < 0.001)." CONCLUSION: Preoperative GNRI is an independent prognostic factor of OS and CSS in patients with LAOSCC. A multivariate nomogram that includes GNRI may better help us to accurately estimate individual survival outcomes.

Minimally invasive, single-stage, multilevel surgery for obstructive sleep apnoea: A systematic review and meta-analysis.

OBJECTIVES: Minimally invasive, single-staged multilevel surgery (MISS MLS) could be an optimal treatment for selected patients with obstructive sleep apnea (OSA). We aim to systematically review the efficacy of MISS MLS for patients with OSA, as well as the clinical outcomes and possible complications in OSA patients before and after MISS MLS. DESIGN AND SETTING: Systematic review and meta-analysis. Six databases were searched, and the PRISMA guideline was followed. PARTICIPANTS: Patients with OSA receiving MISS MLS. MAIN OUTCOME MEASURES: The random-effects model was adopted for the statistical synthesis. The percentage and 95% confidence interval (CI) were adopted as the effect measurements of MISS MLS for OSA. Subgroup analyses and sensitivity analyses were also performed to identify the heterogeneity among the studies. RESULTS: There were initially 154 articles for identification. Eventually, six studies with a total of 848 OSA patients completely met the inclusion criteria and were further enrolled for analysis. The pooled analysis showed statistically significant lower AHI (apnea/hypopnea index, /hr.; mean difference: -8.931, 95% CI: -11.591 to -6.271, I2 = 87.4%), ESS (mean difference: -2.947, 95% CI: -4.465 to -1.429, I2 = 94.9%), and snoring severity with 0-10 visual analog scale after surgery (mean difference: -4.966, 95% CI: -5.804 to -4.128, I2 = 96.4%). The success rate was 46% in mild/moderate OSA; however, 18% in severe OSA. There were no major complications occurred. CONCLUSIONS: The acceptable surgical outcomes, esp. in mild/moderate OSA, and rare complications are the major advantages of MISS MLS. The evidence of this study could aid the decision making in selecting suitable treatment programs for OSA patients.

[Predictive model of early urinary continence recovery based on prostate gland MRI parameters after laparoscopic radical prostatectomy].

OBJECTIVE: Constructing a predictive model for urinary incontinence after laparoscopic radical prostatectomy (LRP) based on prostatic gland related MRI parameters. METHODS: In this study, 202 cases were included. All the patients were diagnosed with prostate cancer by prostate biopsy and underwent LRP surgery in Peking University Third Hospital. The preoperative MRI examination of all the patients was completed within 1 week before the prostate biopsy. Prostatic gland related parameters included prostate length, width, height, prostatic volume, intravesical prostatic protrusion length (IPPL), prostate apex shape, etc. From the first month after the operation, the recovery of urinary continence was followed up every month, and the recovery of urinary continence was based on the need not to use the urine pad all day long. Logistic multivariate regression analysis was used to analyze the influence of early postoperative recovery of urinary continence. Risk factors were used to draw the receiver operator characteristic (ROC) curves of each model to predict the recovery of postoperative urinary continence, and the difference of the area under the curve (AUC) was compared by DeLong test, and the clinical net benefit of the model was evaluated by decision curve analysis (DCA). RESULTS: The average age of 202 patients was 69.0 (64.0, 75.5) years, the average prostate specific antigen (PSA) before puncture was 12.12 (7.36, 20.06) µg/L, and the Gleason score < 7 points and ≥ 7 points were 73 cases (36.2%) and 129 cases (63.9%) respectively, with 100 cases (49.5%) at T1/T2 clinical stage, and 102 cases (50.5%) at T3 stage. The prostatic volume measured by preoperative MRI was 35.4 (26.2, 51.1) mL, the ratio of the height to the width was 0.91 (0.77, 1.07), the membranous urethral length (MUL) was 15 (11, 16) mm, and the IPPL was 2 (0, 6) mm. The prostatic apex A-D subtypes were 67 cases (33.2%), 80 cases (39.6%), 24 cases (11.9%) and 31 cases (15.3%), respectively. The training set and validation set were 141 cases and 61 cases, respectively. The operations of all the patients were successfully completed, and the urinary continence rate was 59.4% (120/202) in the 3 months follow-up. The results of multivariate analysis of the training set showed that the MUL (P < 0.001), IPPL (P=0.017) and clinical stage (P=0.022) were independent risk factors for urinary incontinence in the early postoperative period (3 months). The nomogram and clinical decision curve were made according to the results of multivariate analysis. The AUC value of the training set was 0.885 (0.826, 0.944), and the AUC value of the validation set was 0.854 (0.757, 0.950). In the verification set, the Hosmer-Lemeshow goodness-of-fit test was performed on the model, and the Chi-square value was 5.426 (P=0.711). CONCLUSION: Preoperative MUL, IPPL, and clinical stage are indepen-dent risk factors for incontinence after LRP. The nomogram developed based on the relevant parameters of MRI glands can effectively predict the recovery of early urinary continence after LRP. The results of this study require further large-scale clinical research to confirm.

[Near-infrared targeted probe designed for intraoperative imaging of prostatic neurovascular bundles].

OBJECTIVE: To investigate the imaging effect of a near-infrared fluorescent targeted probe ICG-NP41 on the neurovascular bundles (NVB) around the prostate in rats. METHODS: A near-infrared fluorescent targeted probe ICG-NP41 was synthesized. An animal model for NVB imaging was established using Sprague-Dawley rats (250-400 g). Experiments were conducted using a custom-built near-infrared windowⅡ(NIR-Ⅱ) small animal in vivo imaging system, and images collected were processed using ImageJ and Origin. The fluorescence signal data were statistically analyzed using GraphPad Prism. The signal-to-background ratio (SBR) for NVB was quantitatively calculated to explore the effective dosage and imaging time points. Finally, paraffin pathology sections and HE staining were performed on the imaging structures. RESULTS: Except for rats in the control group (n=2), right-sided NVB of the rats injected with ICG-NP41 (n=2 per group) were all observed in NIR-Ⅱ fluorescence mode 2 h and 4 h after administration. At 2 h and 4 h, average SBR of cavernous nerve in 2 mg/kg group in fluorescence mode was 1.651±0.142 and 1.619±0.110, respectively, both higher than that in white light mode (1.111±0.036), with no significant difference (P>0.05); average SBR of 4 mg/kg group in fluorescence mode were 1.168±0.066 and 1.219±0.118, respectively, both higher than that in white light mode (1.081±0.040), with no significant difference (P>0.05). At 2 h and 4 h, the average SBR of 2 mg/kg and 4 mg/kg groups in fluorescence mode were higher than that of the control group (SBR=1), the average SBR of the 2 mg/kg group was higher than that of the 4 mg/kg group, and all the above with no significant difference (P>0.05). The average diameter of the nerve measured by full width at half maxima method was about (178±15) µm. HE staining of paraffin sections showed the right major pelvic ganglion. CONCLUSION: The near-infrared fluorescent targeted probe ICG-NP41 can be used for real-time imaging of the NVB around the prostate in rats, providing a potential feasible solution for localizing NVB in real time during nerve-sparing radical prostatectomy.

Embryo morphologic quality in relation to the metabolic and cognitive development of singletons conceived by in vitro fertilization and intracytoplasmic sperm injection: a matched cohort study.

BACKGROUND: Embryos with higher morphologic quality grading may have a greater potential to achieve clinical pregnancy that leads to a live birth regardless of the type of cleavage-stage embryos or blastocysts. Few studies have investigated the impacts of embryo grading on the long-term health of the offspring. OBJECTIVE: This pilot study aimed to examine the associations between embryo morphologic quality and the physical, metabolic, and cognitive development of singletons conceived by in vitro fertilization and intracytoplasmic sperm injection at preschool age. STUDY DESIGN: This matched cohort study included singletons born to infertile couples who underwent fresh cleavage-stage embryo transfer cycles with good- or poor-quality embryos from 2014 to 2016 at the reproductive center of the Women's Hospital, School of Medicine, Zhejiang University. A total of 144 children, aged 4 to 6 years, participated in the follow-up assessment from 2020 to 2021, and the response rate of poor-quality embryo offspring was 39%. Singletons in the good-quality embryo group were matched with singletons in the poor-quality embryo group at a 2:1 ratio according to the fertilization method and the children's age (±1 year). We measured the offspring's height, weight, body mass index, blood pressure, thyroid hormone levels, and metabolic indicators. Neurodevelopmental assessments were performed using the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition, and the Adaptive Behavior Assessment System, Second Edition. We also collected data from the medical records. A linear regression model was used to analyze the association between embryo morphologic quality and offspring health outcomes. RESULTS: A total of 48 singletons conceived with poor-quality embryo transfer and 96 matched singletons conceived with good-quality embryo transfer were included in the final analysis. Age, sex, height, weight, body mass index, blood pressure, thyroid function, and metabolic indicators were comparable between the 2 groups. After adjustment for potential risk factors by linear regression model 1 and model 2, poor-quality embryo offspring exhibited a tendency toward higher free thyroxine levels than offspring of good-quality embryo transfers (beta, 0.22; 95% confidence interval, 0.09-0.90; beta, 0.22; 95% confidence interval, 0.09-0.91, respectively), but this difference was not clinically significant. Regarding neurodevelopmental assessments, there was no difference in the full-scale intelligence quotient based on the Wechsler Preschool and Primary Scale of Intelligence (109.96±12.42 vs 109.60±14.46; P=.88) or the general adaptive index based on the Adaptive Behavior Assessment System (108.26±11.70 vs 108.08±13.44; P=.94) between the 2 groups. The subindices of the 2 tests were also comparable. These findings remained after linear regression analysis. CONCLUSION: At 4 to 6 years of age, singletons born from poor-quality embryo transfers have comparable metabolic and cognitive development as those born from good-quality embryo transfers using fresh cleavage-stage embryos. The results of this pilot study indicate that poor-quality embryos that can survive implantation and end in live birth are likely to have a developmental potential comparable to that of good-quality embryos.

Towards Efficient Detection for Small Objects via Attention-Guided Detection Network and Data Augmentation.

Small object detection has always been a difficult direction in the field of object detection, especially the detection of small objects in UAV aerial images. The images captured by UAVs have the characteristics of small objects and dense objects. In order to solve these two problems, this paper improves the performance of object detection from the aspects of data and network structure. In terms of data, the data augmentation strategy and image pyramid mechanism are mainly used. The data augmentation strategy adopts the method of image division, which can greatly increase the number of small objects, making it easier for the algorithm to be fully trained during the training process. Since the object is denser, the image pyramid mechanism is used. During the training process, the divided images are up-sampled into three different sizes, and then sent to three different detectors respectively. Finally, the detection results of the three detectors are fused to obtain the final detection results. The small object itself has few pixels and few features. In order to improve the detection performance, it is necessary to use context. This paper adds attention mechanism to the yolov5 network structure, while adding a detection head to the underlying feature map to make the network structure pay more attention to small objects. By using data augmentation and improved network structure, the detection performance of small objects can be significantly improved. The experiment in this paper is carried out on the Visdrone2019 dataset and DOTA dataset. Through experimental verification, our proposed method can significantly improve the performance of small object detection.

Disease-Modifying Activity of Huperzine A on Alzheimer's Disease: Evidence from Preclinical Studies on Rodent Models.

(1) Background: Huperzine A, a natural cholinesterase (AChE) inhibitor isolated from the Chinese herb Huperzia Serrata, has been used as a dietary supplement in the United States and a drug in China for therapeutic intervention on Alzheimer's disease (AD). This review aims to determine whether Huperzine A exerts disease-modifying activity through systematic analysis of preclinical studies on rodent AD models. (2) Methods: Sixteen preclinical studies were included based on specific criteria, and the methodological qualities were analyzed by SYRCLE's risk of bias tool. Some outcomes were meta-analyzed: latencies and time spent in quadrant of Morris water maze, soluble amyloid-ß (Aß) level measured by ELISA in the cortex and hippocampus, Aß plaque numbers measured by immunohistochemistry in hippocampus, choline acetyltransferase (ChAT) activity, and AChE activity. Finally, the mechanisms of Huperzine A on AD models were summarized. (3) Conclusions: The outcomes showed that Huperzine A displayed AChE inhibition, ChAT activity enhancement, memory improvement, and Aß decreasing activity, indicating the disease-modifying effect of Huperzine A. However, due to the uneven methodological quality, the results need to be rationally viewed, and extensively repeated.

Angiotensin II receptor blockers valsartan and losartan improve survival rate clinically and suppress tumor growth via apoptosis related to PI3K/AKT signaling in nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a common type of head and neck cancer in Asia. Adverse effects occur in over 90% of NPC patients treated with radiotherapy or chemoradiation. Angiotensin II receptor blockers (ARBs) are commonly used to treat hypertension without serious adverse effects. However, the anticancer activity of ARBs in NPC remains unclear. METHODS: We investigated the survival impacts of ARBs among NPC patients in a retrospective study. The anticancer effects and related signaling pathways of the ARBs valsartan and losartan were also evaluated in vitro and in vivo. RESULT: A total of 927 patients with NPC who had hypertension were enrolled in the study, 272 (29.3%) of whom received ARBs. Kaplan-Meier analysis revealed that patients who used ARBs had higher rates of 5-year overall survival (OS; 87.8% vs 75.1%; P = .002) and disease-specific survival (DSS; 95.4% vs 77.7%; P < .001) than those who did not receive this treatment. Additionally, ARBs inhibited cell proliferation and induced apoptosis by increasing levels of cleaved caspase-3, cleaved caspase-9, and cytochrome C; the cell population in the sub-G1 phase; and caspase-3 activity in NPC-TW01 cells. ARBs inhibited tumor growth and angiogenesis via apoptosis in an NPC xenografts model. Interestingly, ARBs inhibited phosphorylation of PI3K/AKT signaling in vitro and in vivo, which is markedly attributed to their antitumor effects in NPC. CONCLUSION: These data indicate that ARBs not only improve 5-year OS and DSS among patients with NPC but also exert antiproliferative and antiangiogenesis effects by inducing apoptosis in NPC, supporting that ARBs may be promising agents for treatment of NPC.