Investigation of the Functional Components in Health Beverages Made from Polygonatum cyrtonema Rhizomes Provides Primary Evidence to Support Their Claimed Health Benefits.

This study aims to understand the functional component compositions of traditional herbal health beverages made from Polygonatum cyrtonema rhizomes and to reveal the pharmacodynamic chemical basis for their claimed health benefits. Two traditional methods, rhizome decoction and rhizome infusion, were used to make health herbal beverages, including "Huangjin" tea and "Huangjin" wine, respectively. The secondary metabolites of "Huangjin" beverages were investigated and compared by widely targeted metabolomics. The results clearly showed that the major functional components in "Huangjin" beverages were phenolic acids, flavonoids, and alkaloids. The "Huangjin" wine has a greater variety of flavonoids and alkaloids than "Huangjin" tea, and the functional components in "Huangjin" wine were more abundant than those in "Huangjin" tea. Homoisoflavones and amide alkaloids were the dominating flavonoids and alkaloids in "Huangjin" wine, respectively. Continuous rhizome infusion could not increase the content of functional components in "Huangjin" wine. In conclusion, this study not only provides primary evidence to support the claimed health benefits of "Huangjin" beverages but also suggests that making traditional herbal beverages by rhizome infusion has superior health benefits than making them by rhizome decoction, which is attributed to the higher yields of functional components extracted by Chinese liquor than hot water. Therefore, Chinese liquor shows advantages in its use as a superior binary ethanol-water solvent in making herbal health beverages to enhance the solubility of poorly water-soluble functional components.

Discovery of Aurovertin B as a Potent Metastasis Inhibitor against Triple-Negative Breast Cancer: Elucidating the Complex Role of the ATF3-DUSP1 Axis.

Triple-negative breast cancer (TNBC) is characterized by high mortality rates primarily due to its propensity for metastasis. Addressing this challenge necessitates the development of effective antimetastatic therapies. This study aimed to identify natural compounds with potential antimetastatic properties mainly based on the high-throughput phenotypic screening system. This system, utilizing luciferase reporter gene assays combined with scratch wound assays, evaluates compounds based on their influence on the epithelial-mesenchymal transition (EMT) marker E-cadherin. Through this approach, aurovertin B (AVB) was revealed to have significant antimetastatic capability. Notably, AVB exhibited substantial metastasis suppression in many TNBC cell lines, including MDA-MB-231, HCC1937 and 4T1. Also, its remarkable antimetastatic activity was demonstrated in vivo via the orthotopic breast cancer mouse model. Further exploration revealed a pronounced association between AVB-induced upregulation of DUSP1 (dual-specificity phosphatase 1) and its inhibitory effect on TNBC metastasis. Additionally, microarray analysis conducted to elucidate the underlying mechanism of the AVB-DUSP1 interaction identified ATF3 (activating transcription factor 3) as a critical transcription factor instrumental in DUSP1 transcriptional activation. This discovery, coupled with observations of enhanced ATF3-DUSP1 expression and consequent reduction in TNBC metastatic foci in response to AVB, provides novel insights into the molecular mechanisms driving metastasis in TNBC. Significance Statement We construct a high-throughput phenotypic screening system utilizing EMT marker E-cadherin promoter luciferase reporter gene combined with scratch wound assays. Aurovertin B was revealed to possess significant antimetastatic activity through this approach, which was further demonstrated via in vivo and in vitro experiments. The discovery of the regulatory role of the ATF3-DUSP1 pathway enriches our understanding of TNBC metastasis mechanism and suggests the potential of ATF3 and DUSP1 as biomarkers for diagnosing TNBC metastasis.

Deep learning promoted target volumes delineation of total marrow and total lymphoid irradiation for accelerated radiotherapy: A multi-institutional study.

BACKGROUND AND PURPOSE: One of the current roadblocks to the widespread use of Total Marrow Irradiation (TMI) and Total Marrow and Lymphoid Irradiation (TMLI) is the challenging difficulties in tumor target contouring workflow. This study aims to develop a hybrid neural network model that promotes accurate, automatic, and rapid segmentation of multi-class clinical target volumes. MATERIALS AND METHODS: Patients who underwent TMI and TMLI from January 2018 to May 2022 were included. Two independent oncologists manually contoured eight target volumes for patients on CT images. A novel Dual-Encoder Alignment Network (DEA-Net) was developed and trained using 46 patients from one internal institution and independently evaluated on a total of 39 internal and external patients. Performance was evaluated on accuracy metrics and delineation time. RESULTS: The DEA-Net achieved a mean dice similarity coefficient of 90.1 % ± 1.8 % for internal testing dataset (23 patients) and 91.1 % ± 2.5 % for external testing dataset (16 patients). The 95 % Hausdorff distance and average symmetric surface distance were 2.04 ± 0.62 mm and 0.57 ± 0.11 mm for internal testing dataset, and 2.17 ± 0.68 mm, and 0.57 ± 0.20 mm for external testing dataset, respectively, outperforming most of existing state-of-the-art methods. In addition, the automatic segmentation workflow reduced delineation time by 98 % compared to the conventional manual contouring process (mean 173 ± 29 s vs. 12168 ± 1690 s; P < 0.001). Ablation study validate the effectiveness of hybrid structures. CONCLUSION: The proposed deep learning framework achieved comparable or superior target volume delineation accuracy, significantly accelerating the radiotherapy planning process.

Infrared and Visual Image Fusion Based on a Local-Extrema-Driven Image Filter.

The objective of infrared and visual image fusion is to amalgamate the salient and complementary features of the infrared and visual images into a singular informative image. To accomplish this, we introduce a novel local-extrema-driven image filter designed to effectively smooth images by reconstructing pixel intensities based on their local extrema. This filter is iteratively applied to the input infrared and visual images, extracting multiple scales of bright and dark feature maps from the differences between continuously filtered images. Subsequently, the bright and dark feature maps of the infrared and visual images at each scale are fused using elementwise-maximum and elementwise-minimum strategies, respectively. The two base images, representing the final-scale smoothed images of the infrared and visual images, are fused using a novel structural similarity- and intensity-based strategy. Finally, our fusion image can be straightforwardly produced by combining the fused bright feature map, dark feature map, and base image together. Rigorous experimentation conducted on the widely used TNO dataset underscores the superiority of our method in fusing infrared and visual images. Our approach consistently performs on par or surpasses eleven state-of-the-art image-fusion methods, showcasing compelling results in both qualitative and quantitative assessments.

Numerical Study on the Effect of Coarse Aggregate Shape during Concrete Mixing Process.

The shape of coarse aggregate is an important factor determining the performance of concrete, and it also affects the whole mixing process. This article selected four typical coarse aggregates and simulated the motion behavior of the coarse aggregate and mortar in a dual horizontal axis mixer using discrete element software, EDEM. The mixing motion of coarse aggregates with different shapes and mortar was studied using average velocity, contact rate, and dispersion coefficient as indicators. The results show that the largest average speed in the mixing process was achieved with the spherical coarse aggregate. Flat coarse aggregates have the highest velocity in the vertical direction, while ellipsoidal coarse aggregates have the lowest velocity. The spherical coarse aggregate mixes best with mortar while the ellipsoidal coarse aggregate mixes worst with mortar. The results of the study could provide strategies for the concrete mixing process considering the shape of the aggregate.

[Comparison of the efficacy of TiRobot orthopaedic robot assisted F screw technique and inverted triangle parallel nail internal fixation in the treatment of unstable femoral neck fractures].

OBJECTIVE: To compare the effectiveness of TiRobot assisted F screw technique and inverted triangle parallel nail internal fixation in the treatment of unstable femoral neck fractures. METHODS: A retrospective analysis was conducted on 72 patients with unstable femoral neck fractures who were treated with percutaneous cannulated screw fixation assisted with TiRobot Orthopaedic robot from December 2019 to April 2021. Among them, 37 patients were treated with F screw internal fixation, including 16 males and 21 females, aged 47 to 64 years old with an average of （53.87±5.28） years old；According to Pauwels classification, there were 1 case of type Ⅰ, 19 cases of type Ⅱ, 17 cases of type Ⅲ；8 cases of combined medical diseases；17 cases of falling, 8 cases of traffic accident and 12 cases of falling from height；The time from injury to operation was 29 to 49 hours with average of （35.00±7.34） hours. Another 35 cases used internal fixation with an inverted triangle parallel nail, including 13 males and 22 females with an average age of 46 to 63 years old （52.36±5.05） years old；According to the Pauwels injury classification：there were 2 cases of type Ⅰ, 21 cases of type Ⅱ, 12 cases of type Ⅲ；6 cases of medical diseases, 15 cases of falling injury, 9 cases of traffic accident, 11 cases of falling injury；The time from injury to operation was 30 to 45 hours with an average of （33.00±6.83） h. The intraoperative blood loss, operation time, intraoperative fluoroscopy times, follow-up time, fracture healing time, postoperative complications were observed and compared between the two groups. The hip joint function was evaluated by Harris score at 6 months and 12 months after operation. RESULTS: There was no significant difference in operation time, intraoperative blood loss, intraoperative fluoroscopy times and other intraoperative data between two groups（P>0.05）. Both groups were followed up regularly, and the follow-up time was 12 to 16 months. The fracture healing time and Harris score of the F screw internal fixation group were better than those of the inverted triangle parallel nail internal fixation group （P<0.05）. There was 1 case of femoral neck shortening in the F screw internal fixation group, 1 case of nonunion, 1 case of nail withdrawal, and 1 case of lower extremity deep vein thrombosis in the inverted triangle internal fixation group. The incidence of complications in the F screw internal fixation group was lower than that in the inverted triangle parallel nail internal fixation group（P<0.05）. CONCLUSION: Percutaneous cannulated F screw technique using Tirobot navigation positioning system is a safe and effective treatment for patients with unstable femoral neck fractures. It can significantly shorten the fracture healing time, reduce the incidence of postoperative complications, significantly improve hip joint function, and improve the quality of life.

Effect of Remimazolam Supplementation on Propofol Requirements During Hysteroscopy: A Double-Blind, Dose-Response Study.

BACKGROUND: Propofol is commonly used for procedural sedation but may increase side effects in a dose-dependent manner. Remimazolam, an ultrashort-acting benzodiazepine, has been approved for procedural sedation but may delay awakening. This study tested the hypothesis that remimazolam as a supplement reduces effect-site propofol concentration (Ceprop) required to suppress response to cervical dilation in patients undergoing hysteroscopy. METHODS: One hundred and fifty patients who were scheduled for hysteroscopy were randomized to receive 0, 0.05, 0.1, 0.15, or 0.2 mg·kg-1 intravenous remimazolam, followed by a bolus of sufentanil 0.15 µg⋅kg-1, and a target-controlled propofol infusion. The initial target Ceprop was 3.5 µg·mL-1 and was increased or decreased in subsequent patients by steps of 0.5 µg·mL-1 according to whether there was loss of response to cervical dilation in the previous patient. We used up-down sequential analysis to determine values of Ceprop that suppressed response to cervical dilation in 50% of patients (EC50). RESULTS: The EC50 of propofol for suppressing response to cervical dilation was lower in patients given 0.1 mg·kg-1 (2.08 [95% confidence interval, CI, 1.88-2.28] µg·mL-1), 0.15 mg⋅kg-1 (1.83 [1.56-2.10] µg·mL-1), and 0.2 mg⋅kg-1 (1.43 [1.27-1.58] µg·mL-1) remimazolam than those given 0 mg⋅kg-1 (3.67 [3.49-3.86] µg·mL-1) or 0.05 mg⋅kg-1 (3.47 [3.28-3.67] µg·mL-1) remimazolam (all were P < .005). Remimazolam at doses of 0.1, 0.15, and 0.2 mg·kg-1 decreased EC50 of propofol by 43.3% (95% CI, 41.3%-45.5%), 50.3% (48.0%-52.8%), and 61.2% (58.7%-63.8%), respectively, from baseline (remimazolam 0 mg⋅kg-1). Propofol consumption was lower in patients given 0.1 mg⋅kg-1 (4.15 [3.51-5.44] mg·kg-1), 0.15 mg⋅kg-1 (3.54 [3.16-4.46] mg·kg-1), and 0.2 mg⋅kg-1 (2.74 [1.73-4.01] mg·kg-1) remimazolam than those given 0 mg⋅kg-1 (6.09 [4.99-7.35] mg·kg-1) remimazolam (all were P < .005). Time to anesthesia emergence did not differ significantly among the 5 groups. CONCLUSIONS: For women undergoing hysteroscopic procedures, remimazolam at doses from 0.1 to 0.2 mg·kg-1 reduced the EC50 of propofol inhibiting response to cervical dilation and the total propofol requirement. Whether the combination could improve perioperative outcomes deserves further investigation.

Predicting fluid responsiveness in spontaneously breathing parturients undergoing caesarean section via carotid artery blood flow and velocity time integral measured by carotid ultrasound: a prospective cohort study.

BACKGROUND: Present evidence suggests that the Doppler ultrasonographic indices, such as carotid artery blood flow (CABF) and velocity time integral (VTI), had the ability to predict fluid responsiveness in non-obstetric patients. The purpose of this study was to assess their capacity to predict fluid responsiveness in spontaneous breathing parturients undergoing caesarean section and to determine the effect of detecting and management of hypovolemia (fluid responsiveness) on the incidence of hypotension after anaesthesia. METHODS: A total of 72 full term singleton parturients undergoing elective caesarean section were enrolled in this study. CABF, VTI, and hemodynamic parameters were recorded before and after fluid challenge and assessed by carotid artery ultrasonography. Fluid responsiveness was defined as an increase in stroke volume index (SVI) of 15% or more after the fluid challenge. RESULTS: Thirty-one (43%) patients were fluid responders. The area under the ROC curve to predict fluid responsiveness for CABF and VTI were 0.803 (95% CI, 0.701-0.905) and 0.821 (95% CI, 0.720-0.922). The optimal cut-off values of CABF and VTI for fluid responsiveness was 175.9 ml/min (sensitivity of 74.0%; specificity of 78.0%) and 8.7 cm/s (sensitivity of 67.0%; specificity of 90.0%). The grey zone for CABF and VTI were 114.2-175.9 ml/min and 6.8-8.7 cm/s. The incidence of hypotension after the combined spinal-epidural anaesthesia (CSEA) was significantly higher in the Responders group 25.8% (8/31) than in the Non-Responders group 17.1(7/41) (P < 0.001). The total incidence of hypotension after CSEA of the two groups was 20.8% (15/72). CONCLUSIONS: Ultrasound evaluation of CABF and VTI seem to be the feasible parameters to predict fluid responsiveness in parturients undergoing elective caesarean section and detecting and management of hypovolemia (fluid responsiveness) could significantly decrease incidence of hypotension after anaesthesia. TRIAL REGISTRATION: The trial was registered at the Chinese Clinical Trial Registry (ChiCTR) ( www.chictr.org ), registration number was ChiCTR1900022327 (The website link: https://www.chictr.org.cn/showproj.html?proj=37271 ) and the date of trial registration was in April 5, 2019. This study was performed in accordance with the Declaration of Helsinki and approved by the Research Ethics Committee of Women's Hospital, Zhejiang University School of Medicine (20,180,120).

Neuron-derived exosomes mediate sevoflurane-induced neurotoxicity in neonatal mice via transferring lncRNA Gas5 and promoting M1 polarization of microglia.

Sevoflurane exposure during rapid brain development induces neuronal apoptosis and causes memory and cognitive deficits in neonatal mice. Exosomes that transfer genetic materials including long non-coding RNAs (lncRNAs) between cells play a critical role in intercellular communication. However, the lncRNAs found in exosomes derived from neurons treated with sevoflurane and their potential role in promoting neurotoxicity remain unknown. In this study, we investigated the role of cross-talk of newborn mouse neurons with microglial cells in sevoflurane-induced neurotoxicity. Mouse hippocampal neuronal HT22 cells were exposed to sevoflurane, and then co-cultured with BV2 microglial cells. We showed that sevoflurane treatment markedly increased the expression of the lncRNA growth arrest-specific 5 (Gas5) in neuron-derived extracellular vesicles, which inhibited neuronal proliferation and induced neuronal apoptosis by promoting M1 polarization of microglia and the release of inflammatory cytokines. We further revealed that the exosomal lncRNA Gas5 significantly upregulated Foxo3 as a competitive endogenous RNA of miR-212-3p in BV2 cells, and activated the NF-κB pathway to promote M1 microglial polarization and the secretion of inflammatory cytokines, thereby exacerbating neuronal damage. In neonatal mice, intracranial injection of the exosomes derived from sevoflurane-treated neurons into the bilateral hippocampi significantly increased the proportion of M1 microglia, inhibited neuronal proliferation and promoted apoptosis, ultimately leading to neurotoxicity. Similar results were observed in vitro in BV2 cells treated with the CM from HT22 cells after sevoflurane exposure. We conclude that sevoflurane induces the transfer of lncRNA Gas5-containing exosomes from neurons, which in turn regulates the M1 polarization of microglia and contributes to neurotoxicity. Thus, modulating the expression of lncRNA Gas5 or the secretion of exosomes could be a strategy for addressing sevoflurane-induced neurotoxicity.

A new method to estimate the histological stage of primary biliary cholangitis.

OBJECTIVE: To analyze the diagnostic efficacy of the periportal hypoechoic band (PHB) in the histological stage of patients with primary biliary cholangitis (PBC). METHODS: We prospectively included 77 cases of PBC pathologically or clinically confirmed, and high-frequency ultrasound (HFUS) measurements of the PHB were performed in all included patients. Ludwig staging system of histopathology was used as the gold standard. RESULTS: The width of the PHB was positively correlated with histological staging (r = 0.844, p < 0.001). By area under the receiving operating characteristic curve (AUROC), the best cutoff value for PHB for advanced stage (≥ stage 3) was 2.4 mm (AUROC: 0.934; 95%CI: 0.841-0.981) and 0.93 for sensitivity, and 0.91 for specificity, the concordance rates of PHB vs. liver biopsy was 90.3%. The correct rate for early-stage PBC was 87.9% and for the progressive stage was 93.1%. After multi-factor regression analysis, the PHB (OR = 1.331, CI = 1.105-1.603, p = 0.003) and total bilirubin (OR = 1.156, CI = 1.041-1.285, p = 0.007) were independent influencing factors for progressive PBC. CONCLUSIONS: Measurement of the PHB to assess advanced PBC is a simple and effective method. This method may complement current methods for the histological staging assessment of patients with PBC. REGISTRATION: Clinical trial registration: ChiCTR 2000032053, 2020/04/19. CLINICAL RELEVANCE STATEMENT: The measurement of periportal hypoechoic band (PHB) provides a simple and easy assessment of the degree of disease progression in patients with PBC and provides an important clinical reference in predicting the histological staging of PBC from an ultrasound perspective. KEY POINTS: • The PHB is correlated with histological staging in the patient with PBC. • The area under the ROC curves of PHB for detecting advanced stage (≥ stage 3) were 0.934 and 0.93 for sensitivity, and 0.91 for specificity, the concordance rates of PHB vs. liver biopsy was 90.3%. The application of PHB can better assess the advanced PBC. • Measurement of the PHB to assess advanced PBC is a simple and effective method that can significantly reduce the need for liver biopsy.

Ultrasound imaging findings in primary biliary cholangitis.

BACKGROUND: Our study aimed to analyze the characteristics of ultrasound images corresponding to each histological stage of primary biliary cholangitis (PBC). METHODS: We prospectively analyzed 75 confirmed cases of PBC and used liver biopsy as the gold standard to determine the disease stage. RESULTS: The typical ultrasound images of patients with PBC were characterized by a thickening of the portal vein wall (PVW) and periportal hypoechoic band (PHB) width with increasing histological stages, and significant increases in the left hepatic lobe diameter (LHLD) in stage II (by 64.0%) and stage III (by 69.2%). PHB width (r = 0.857, p < 0.001), PVW thickness (r = 0.488, p < 0.001), and spleen area (r = 0.8774, p < 0.001) were positively correlated with the histological stage. Significant changes were noted in the liver surface, echo texture, and edge between different stages. The areas under the receiver operating characteristic curve of composite indicators were 0.965 for predicting progressive PBC(≥ stage 2), and 0.926 for predicting advanced PBC(≥ stage 3). CONCLUSIONS: The ultrasound imaging characteristics of patients with PBC varied according to the histological staging. LHLD, PVW thickness, and PHB width were significantly correlated with the histological stage. A combination of high- and low-frequency ultrasound imaging can provide relevant cues regarding the degree of PBC progression and important clinical reference values. The application of all the ultrasound image findings as the composite indicators can better predict progressive and advanced PBC, providing important clinical reference values.

Enhanced CD19 activity in B cells contributes to immunodeficiency in mice deficient in the ICF syndrome gene Zbtb24.

Immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is a rare autosomal recessive disorder characterized by DNA hypomethylation and antibody deficiency. It is caused by mutations in DNMT3B, ZBTB24, CDCA7, or HELLS. While progress has been made in elucidating the roles of these genes in regulating DNA methylation, little is known about the pathogenesis of the life-threatening hypogammaglobulinemia phenotype. Here, we show that mice deficient in Zbtb24 in the hematopoietic lineage recapitulate the major clinical features of patients with ICF syndrome. Specifically, Vav-Cre-mediated ablation of Zbtb24 does not affect lymphocyte development but results in reduced plasma cells and low levels of IgM, IgG1, and IgA. Zbtb24-deficient mice are hyper and hypo-responsive to T-dependent and T-independent type 2 antigens, respectively, and marginal zone B-cell activation is impaired. Mechanistically, Zbtb24-deficient B cells show severe loss of DNA methylation in the promoter region of Il5ra (interleukin-5 receptor subunit alpha), and Il5ra derepression leads to elevated CD19 phosphorylation. Heterozygous disruption of Cd19 can revert the hypogammaglobulinemia phenotype of Zbtb24-deficient mice. Our results suggest the potential role of enhanced CD19 activity in immunodeficiency in ICF syndrome.

Influence of plastic aggregate geometry on strength properties of cement-stabilized macadam.

In order to improve the toughness and flexibility of cement-stabilized macadam and inhibit crack formation and propagation, the influence of plastic aggregate geometry on the strength properties of cement-stabilized macadam is studied. The surface roughness of plastic aggregate was designed into Ra 12.5 and Ra 25. When the content of plastic coarse aggregate was gradually increased from 4 to 8%, 12%, 16%, 20%, and 24%, the compressive strength, splitting strength, and the tensile-compression ratio of the cement-stabilized macadam made of aggregate with rough surface texture were found higher than those of aggregate with smooth surface texture. The rough cylindrical, spherical, spindle, and dumbbell-shaped plastic coarse aggregates were designed and prepared for testing. The test results showed the maximum compressive strength, splitting strength, and tensile-compression ratio of cement-stabilized macadam with the dumbbell-shaped plastic coarse aggregate. The tensile-compression ratio increased by 15.2% compared to natural aggregate cement-stabilized macadam. The results show that under the same conditions, the plastic aggregate with different geometry can improve the compressive and splitting strengths of cement-stabilized macadam and significantly improve the toughness and flexibility, with dumbbell-shaped plastic coarse aggregate having the greatest improvement, especially compared with natural aggregate cement-stabilized crushed stone. This research provides insights for improving pavement engineering quality and new ideas for utilizing waste plastics.

Quantitative SERS detection of multiple breast cancer miRNAs based on duplex specific nuclease-mediated signal amplification.

Simultaneous and ultrasensitive detection of multiple microRNA (miRNA) biomarkers is an essential precondition for early cancer diagnosis and treatment. Here we developed a sandwich surface-enhanced Raman scattering (SERS) sensor based on Au@Ag core-shell nanorods combined with duplex specific nuclease-mediated signal amplification (DSNSA) for quantitative detection of multiple breast cancer miRNA biomarkers. The DSNSA strategy enables quantitative detection of target miRNA through rehybridizing the capture probe DNA-SERSnanotag conjugates to trigger signal amplification. The Au@Ag core-shell nanorods coated with an Ag shell exhibit excellent SERS performance, implying that molecules can be concentrated by the Ag shell at the hot spots. By monitoring the Raman signal attenuation of hot spots in the presence of target miRNAs, three breast cancer associated miRNAs (miR-21, miR-155, and let 7b) were simultaneously determined using the sandwich SERS sensor, and their detection limits (LODs) were 0.05 fM, 0.063 fM and 0.037 fM, respectively. These results indicated that our sandwich SERS sensor combined with the DSNSA strategy holds remarkable promise for multiplex detection of cancer biomarkers and contributes to early diagnosis of cancer.

Development and validation of an artificial neural network prediction model for postpartum hemorrhage with placenta previa.

BACKGROUND: Postpartum hemorrhage (PPH) is a leading cause of maternal morbidity worldwide and placenta previa is one of the major risk factors for PPH in overall population. However, the clinical prediction of PPH remains challenging. This study aimed to investigate an ideal machine learning-based prediction model for PPH in placenta previa parturients with cesarean section. METHODS: The clinical data of 223 placenta previa parturients who underwent cesarean delivery in our hospital from 2016 to 2019 were retrospectively collected for analysis. An artificial neural network model was designed to predict PPH, defined as blood loss exceeding 1000 mL with 24h after delivery. Twenty clinical variables were selected as predictors. We also applied six conventional machine learning methods as reference models, including support vector machine, decision tree, random forest, gradient boosting decision tree, adaboost and logistic regression. All the models were validated using 5-fold cross-validation. The area under the receiver operating characteristic curve (AUC), precision, recall and the prediction accuracy of each model were reported. RESULTS: A total of 223 pregnant women were enrolled in this study, including 101 cases (45.29%) experienced PPH. The proposed model achieved superior prediction performance with an AUC of 0.917, an accuracy of 0.851, a precision score of 0.829 and a recall score of 0.851, which outperformed other six conventional machine learning methods. CONCLUSIONS: Compared to the conventional machine learning approaches, artificial neural network model shows discriminative ability in identifying women's risk of PPH with placenta previa during cesarean section.

A boundary-guided transformer for measuring distance from rectal tumor to anal verge on magnetic resonance images.

Accurate measurement of the distance from the tumor's lowest boundary to the anal verge (DTAV) provides an important reference value for treatment of rectal cancer, but the standard measurement method (colonoscopy) causes substantial pain. Therefore, we propose a method for automatically measuring the DTAV on sagittal magnetic resonance (MR) images. We designed a boundary-guided transformer that can accurately segment the rectum and tumor. From the segmentation results, we estimated the DTAV by automatically extracting the anterior rectal wall from the tumor's lowest point to the anal verge and then calculating its physical length. Experiments were conducted on a rectal tumor MR imaging (MRI) dataset to evaluate the efficacy of our method. The results showed that our method outperformed surgeons with 6 years of experience (p < 0.001). Furthermore, by referring to our segmentation results, attending and resident surgeons could improve their measurement precision and efficiency.

Characterization of a mouse model of ICF syndrome reveals enhanced CD19 activation in inducing hypogammaglobulinemia.

Immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome is a rare autosomal recessive disorder characterized by DNA hypomethylation and antibody deficiency. It is caused by mutations in DNMT3B, ZBTB24, CDCA7 or HELLS . While progress has been made in elucidating the roles of these genes in regulating DNA methylation, little is known about the pathogenesis of the life-threatening hypogammaglobulinemia phenotype. Here we show that mice deficient for Zbtb24 in the hematopoietic lineage recapitulate major clinical features of patients with ICF syndrome. Specifically, Vav-Cre-mediated ablation of Zbtb24 does not affect lymphocyte development but results in reduced plasma cells and low levels of IgM, IgG1 and IgA. Zbtb24 -deficient mice are hyper- and hypo-responsive to T-dependent and Tindependent type 2 antigens, respectively, and marginal zone B cell activation is impaired. B cells from Zbtb24 -deficient mice display elevated CD19 phosphorylation. Heterozygous disruption of Cd19 can revert the hypogammaglobulinemia phenotype in these mice. Mechanistically, Il5ra (interleukin-5 receptor subunit alpha) is derepressed in Zbtb24 -deficient B cells, and elevated IL-5 signaling enhances CD19 phosphorylation. Our results reveal a novel link between IL-5 signaling and CD19 activation and suggest that abnormal CD19 activity contributes to immunodeficiency in ICF syndrome. SIGNIFICANCE STATEMENT: ICF syndrome is a rare immunodeficiency disorder first reported in the 1970s. The lack of appropriate animal models has hindered the investigation of the pathogenesis of antibody deficiency, the major cause of death in ICF syndrome. Here we show that, in mice, disruption of Zbtb24 , one of the ICF-related genes, in the hematopoietic lineage results in low levels of immunoglobulins. Characterization of these mice reveals abnormal B cell activation due to elevated CD19 phosphorylation. Mechanistically, Il5ra (interleukin-5 receptor subunit alpha) is derepressed in Zbtb24 -deficient B cells, and increased IL-5 signaling enhances CD19 phosphorylation.

Durable Rapid Self-Disinfection, Reusable Protective Clothing Based on the Ag-Pd@MoS2 Nanozyme with Enhanced Triple-Mode Synergistic Antibacterial Effect.

Personal protective clothing plays an important role in isolating microorganisms and harmful ultrafine dust, but it cannot quickly inactivate bacteria intercepted on the surface, making it a potential source of infection. However, spontaneous and durable rapid sterilization is a major challenge for commercial protective clothing. Herein, we exquisitely engineered a visible light-enhanced Ag-Pd@MoS2 nanozyme-based fabric, named PVDF/Ag-Pd@MoS2/PAN fabric (PAPMP fabric), with prominent triple-mode synergistic antibacterial effect through the replacement reaction, electrospinning technique, and vacuum filtration method. The modification of Ag-Pd greatly strengthened the absorption of MoS2 nanosheets to the visible light spectrum (390-780 nm) and its corresponding catalytic performance. Meanwhile, the combination of MoS2 nanosheets significantly enhanced the oxidase-like characteristics of Ag-Pd under sunlight irradiation, increasing the yield of surface-bound 1O2 ∼4.54 times in 5 min. In addition, the obtained Ag-Pd@MoS2 nanozyme showed an excellent photo-to-thermal conversion property (36.12%), which enabled the sharp increase in the surface temperature of the PAPMP fabric to 62.8 °C in 1 min under a solar simulator (1 W/cm2). Correspondingly, the obtained PAPMP fabric exhibited excellent intrinsic antibacterial effect and greatly shortened the sterilization time from 4 h to only 5 min under sunlight stimulation. The rapid antibacterial effect of the fabric was attributable to the enhanced production rate of surface-bound reactive oxygen species and the increased temperature by solar irradiation. Notably, the fabric still maintained the efficient germicidal effect even after 30 washing cycles. In addition to high reusability, the fabric also had outstanding biological compatibility and water resistance. Our work provides a novel strategy to improve the inherent timely sterilization and heat preservation efficiency of protective clothing.