Impact of residual stress on coronary plaque stress/strain calculations using optical coherence tomography image-based multi-layer models.

Introduction: Mechanical stress and strain conditions play an important role in atherosclerosis plaque progression, remodeling and potential rupture and may be used in plaque vulnerability assessment for better clinical diagnosis and treatment decisions. Single layer plaque models without residual stress have been widely used due to unavailability of multi-layer image segmentation method and residual stress data. However, vessel layered structure and residual stress have large impact on stress/strain calculations and should be included in the models. Methods: In this study, intravascular optical coherence tomography (OCT) data of coronary plaques from 10 patients were acquired and segmented to obtain the three-layer vessel structure using an in-house automatic segmentation algorithm. Multi- and single-layer 3D thin-slice biomechanical plaque models with and without residual stress were constructed to assess the impact of residual stress on stress/strain calculations. Results: Our results showed that residual stress led to a more uniform stress distribution across the vessel wall, with considerable plaque stress/strain decrease on inner wall and increase on vessel out-wall. Multi-layer model with residual stress inclusion reduced inner wall maximum and mean plaque stresses by 38.57% and 59.70%, and increased out-wall maximum and mean plaque stresses by 572.84% and 432.03%. Conclusion: These findings demonstrated the importance of multi-layer modeling with residual stress for more accurate plaque stress/strain calculations, which will have great impact in plaque cap stress calculation and plaque rupture risk assessment. Further large-scale studies are needed to validate our findings.

Plaque Ruptures Are Related to High Plaque Stress and Strain Conditions: Direct Verification by Using In Vivo OCT Rupture Data and FSI Models.

BACKGROUND: While it has been hypothesized that high plaque stress and strain may be related to plaque rupture, its direct verification using in vivo coronary plaque rupture data and full 3-dimensional fluid-structure interaction models is lacking in the current literature due to difficulty in obtaining in vivo plaque rupture imaging data from patients with acute coronary syndrome. This case-control study aims to use high-resolution optical coherence tomography-verified in vivo plaque rupture data and 3-dimensional fluid-structure interaction models to seek direct evidence for the high plaque stress/strain hypothesis. METHODS: In vivo coronary plaque optical coherence tomography data (5 ruptured plaques, 5 no-rupture plaques) were acquired from patients using a protocol approved by the local institutional review board with informed consent obtained. The ruptured caps were reconstructed to their prerupture morphology using neighboring plaque cap and vessel geometries. Optical coherence tomography-based 3-dimensional fluid-structure interaction models were constructed to obtain plaque stress, strain, and flow shear stress data for comparative analysis. The rank-sum test in the nonparametric test was used for statistical analysis. RESULTS: Our results showed that the average maximum cap stress and strain values of ruptured plaques were 142% (457.70 versus 189.22 kPa; P=0.0278) and 48% (0.2267 versus 0.1527 kPa; P=0.0476) higher than that for no-rupture plaques, respectively. The mean values of maximum flow shear stresses for ruptured and no-rupture plaques were 145.02 dyn/cm2 and 81.92 dyn/cm2 (P=0.1111), respectively. However, the flow shear stress difference was not statistically significant. CONCLUSIONS: This preliminary case-control study showed that the ruptured plaque group had higher mean maximum stress and strain values. Due to our small study size, larger scale studies are needed to further validate our findings.

Phenotypic comparison and the potential antitumor function of immortalized bone marrow-derived macrophages (iBMDMs).

Introduction: Macrophages are an important component of innate immunity and involved in the immune regulation of multiple diseases. The functional diversity and plasticity make macrophages to exhibit different polarization phenotypes after different stimuli. During tumor progression, the M2-like polarized tumor-associated macrophages (TAMs) promote tumor progression by assisting immune escape, facilitating tumor cell metastasis, and switching tumor angiogenesis. Our previous studies demonstrated that functional remodeling of TAMs through engineered-modifying or gene-editing provides the potential immunotherapy for tumor. However, lack of proliferation capacity and maintained immune memory of infused macrophages restricts the application of macrophage-based therapeutic strategies in the repressive tumor immune microenvironment (TIME). Although J2 retrovirus infection enabled immortalization of bone marrow-derived macrophages (iBMDMs) and facilitated the mechanisms exploration and application, little is known about the phenotypic and functional differences among multi kinds of macrophages. Methods: HE staining was used to detect the biosafety of iBMDMs, and real-time quantitative PCR, immunofluorescence staining, and ELISA were used to detect the polarization response and expression of chemokines in iBMDMs. Flow cytometry, scratch assay, real-time quantitative PCR, and crystal violet staining were used to analyze its phagocytic function, as well as its impact on tumor cell migration, proliferation, and apoptosis. Not only that, the inhibitory effect of iBMDMs on tumor growth was detected through subcutaneous tumor loading, while the tumor tissue was paraffin sectioned and flow cytometry was used to detect its impact on the tumor microenvironment. Results: In this study, we demonstrated iBMDMs exhibited the features of rapid proliferation and long-term survival. We also compared iBMDMs with RAW264.7 cell line and mouse primary BMDMs with in vitro and in vivo experiments, indicating that the iBMDMs could undergo the same polarization response as normal macrophages with no obvious cellular morphology changes after polarization. What's more, iBMDMs owned stronger phagocytosis and pro-apoptosis functions on tumor cells. In addition, M1-polarized iBMDMs could maintain the anti-tumor phenotypes and domesticated the recruited macrophages of receptor mice, which further improved the TIME and repressed tumor growth. Discussion: iBMDMs can serve as a good object for the function and mechanism study of macrophages and the optional source of macrophage immunotherapy.

Efficacy and safety of radiofrequency ablation versus surgical sympathectomy in palmar hyperhidrosis.

Radiofrequency ablation (RFA) comparative efficacy of treatments using video-assisted thoracoscopic sympathectomy (VATS) in the long term remains uncertain in patients with palmar hyperhidrosis (PHH). This study aimed to compare the efficacy and safety of RFA and VATS in patients with PHH. We recruited patients aged ≥ 14 years with diagnosed PHH from 14 centres in China. The treatment options of RFA or VATS were assigned to two cohort in patients with PHH. The primary outcome was the efficacy at 1-year. A total of 807 patients were enrolled. After propensity score matching, the rate of complete remission was lower in RFA group than VATS group (95% CI 0.21-0.57; p < 0.001). However, the rates of palmar dryness (95% CI 0.38-0.92; p = 0.020), postoperative pain (95% CI 0.13-0.33; p < 0.001), and surgery-related complications (95% CI 0.19-0.85; p = 0.020) were lower in RFA group than in VATS group, but skin temperature rise was more common in RFA group (95% CI 1.84-3.58; p < 0.001). RFA had a lower success rate than VATS for the complete remission of PHH. However, the symptom burden and cost are lower in patients undergoing RFA compared to those undergoing VATS.Trial Registration: ChiCTR2000039576, URL: http://www.chictr.org.cn/index.aspx .

AChE activity self-breathing control mechanisms regulated by H2Sn and GSH: Persulfidation and glutathionylation on sulfhydryl after disulfide bonds cleavage.

Hydrogen sulfide (H2S), or dihydrogen sulfane (H2Sn), acts as a signal molecule through the beneficial mechanism of persulfidation, known as the post-translational transformation of cysteine residues to persulfides. We previously reported that Glutathione (GSH) could regulate enzyme activity through S-desulfurization or glutathionylation of residues to generate protein-SG or protein-SSG, releasing H2S. However, little is known about the mechanisms by which H2Sn and GSH affect the disulfide bonds. In this study, we provide direct evidences that H2Sn and GSH modify the sulfhydryl group on Cys272, which forms disulfide bonds in acetylcholinesterase (AChE), to generate Cys-SSH and Cys-SSG, respectively. Glutathionylation of disulfide is a two-step reaction based on nucleophilic substitution, in which the first CS bond is broken, then the SS bond is broken to release H2S. H2Sn and GSH controlled self-breathing motion in enzyme catalysis by disconnecting specific disulfide bonds and modifying cysteine residues, thereby regulating AChE activity. Here, we elucidated H2Sn and GSH mechanisms on disulfide in the AChE system and proposed a self-breathing control theory induced by H2Sn and GSH. These theoretical findings shed light on the biological functions of H2Sn and GSH on sulfhydryl and disulfide bonds and enrich the theory of enzyme activity regulation.

Impact of 2.5 mg versus 5 mg letrozole co-treatment in an antagonist protocol for IVF: a retrospective study.

Objective: The present study aimed to compare the effectiveness of two different doses of letrozole (2.5 mg and 5 mg daily) in an antagonist protocol for infertile women with normal ovarian reserve. Methods: This retrospective cohort study included infertile women who underwent in vitro fertilization treatment with letrozole co-treatment at doses of 2.5 mg and 5 mg from 2007 - 2021 at Shanghai Ninth People's Hospital (Shanghai, China). The control group comprised infertile women who received gonadotropin-releasing hormone antagonist alone. The primary outcome was the cumulative live birth rate, while secondary outcomes included follicular phase endocrine parameters, ovarian stimulation outcomes, pregnancy outcomes, and the incidences of maternal and neonatal complications. Baseline and follow-up data were compared between the groups using ANOVA for normally distributed variables, the Kruskal-Wallis test for non-normally distributed variables, and the Chi-square test for categorical variables. Results: A total of 422 participants were enrolled in the study, with 211 women in the antagonist group, 109 women in the 2.5 mg letrozole co-treatment group, and 102 women in the 5 mg letrozole co-treatment group. Letrozole co-treatment significantly suppressed oestradiol and follicle-stimulating hormone concentrations from stimulation day 5 and onwards, while increasing luteinizing hormone levels on stimulation day 5 and trigger day. The effect was more pronounced with a 5 mg dose of letrozole compared to a 2.5 mg dose (P < 0.05). Administration of 5 mg letrozole reduced the gonadotropin dose (P < 0.05) without negatively affecting the number of oocytes retrieved and subsequent embryo parameters (P > 0.05). The analysis of cumulative live birth rates showed rates of 29.4% in the letrozole 5 mg group, 27.5% in the letrozole 2.5 mg group, and 33.6% in the control group, with no statistically significant difference (P > 0.05). There were no reported pregnancy complications in the two letrozole groups. Additionally, there were no significant differences among the three groups in terms of gestational age and birth weight for both singleton and twin births. Conclusion: This study indicates that the administration of letrozole in an antagonist protocol, at both 2.5 mg and 5 mg dosages, results in comparable clinical outcomes.

GM-CSF improves endometrial receptivity in a thin endometrium rat model by upregulating HOXA10.

Endometrial receptivity is a prerequisite for the success of assisted reproduction. Patients with a consistently thin endometrium frequently fail to conceive, owing to low endometrial receptivity, and there are currently very few therapeutic options available. Our previous study demonstrated that intrauterine granulocyte-macrophage colony-stimulating factor (GM-CSF) administration resulted in a significant improvement in clinical pregnancy and implantation rates and was an effective means of increasing endometrial thickness on the day of embryo transfer in patients with thin endometrium. In order to explore the underlying process, an animal model with a thin endometrium was constructed, the homeobox A10 gene (HOXA10) was downregulated, and an inhibitor of the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway (MAPK/ERK) was employed. Our findings strongly suggest a marked decrease in GM-CSF levels in the thin endometrial rat model, and the suppression of HOXA10 impeded the therapeutic efficacy of GM-CSF in this model. Moreover, we showed that GM-CSF significantly increases endometrial receptivity in the rat model and upregulates HOXA10 via the MAPK/ERK pathway. Our data provide new molecular insights into the mechanisms underlying formation of a thin endometrium and highlight a novel, potential clinical treatment strategy as well as directions for further research.

Comparison of multilayer and single-layer coronary plaque models on stress/strain calculations based on optical coherence tomography images.

Mechanical stress and strain conditions are closely related to atherosclerotic plaque progression and rupture and have been under intensive investigations in recent years. It is well known that arteries have a three-layer structure: intima, media and adventitia. However, in vivo image-based multilayer plaque models are not available in the current literature due to lack of multilayer image segmentation data. A multilayer segmentation and repairing technique was introduced to segment coronary plaque optical coherence tomography (OCT) image to obtain its three-layer vessel structure. A total of 200 OCT slices from 20 patients (13 male; 7 female) were used to construct multilayer and single-layer 3D thin-slice models to calculate plaque stress and strain and compare model differences. Our results indicated that the average maximum plaque stress values of 20 patients from multilayer and single-layer models were 385.13 ± 110.09 kPa and 270.91 ± 95.86 kPa, respectively. The relative difference was 42.2%, with single-layer stress serving as the base value. The average mean plaque stress values from multilayer and single-layer models were 129.59 ± 32.77 kPa and 93.27 ± 18.20 kPa, respectively, with a relative difference of 38.9%. The maximum and mean plaque strain values obtained from the multilayer models were 11.6% and 19.0% higher than those from the single-layer models. Similarly, the maximum and mean cap strains showed increases of 9.6% and 12.9% over those from the single-layer models. These findings suggest that use of multilayer models could improve plaque stress and strain calculation accuracy and may have large impact on plaque progression and vulnerability investigation and potential clinical applications. Further large-scale studies are needed to validate our findings.

Spatiotemporal changes of aerosol optical depth and its response to urbanization: a case study of Jinan City, China, 2009-2018.

With the insidiously growing impact of urban development on the environment, the issue of air quality has attracted extensive attention nationally and globally. It is of great significance to study the influence of urbanization on air quality for the rational development of cities. MODIS-MAIAC (Moderate Resolution Imaging Spectroradiometer-Multi-Angle Implementation of Atmospheric Correction) Aerosol optical depth (AOD) product, DMSP/OLS (Defense Meteorological Satellite Program/Operational Linescan System) and NPP/VIIRS (Suomi National Polar-orbiting Partnership/Visible Infrared Imaging Radiometer Suite) night-light were used to explore the spatiotemporal variation and correlation between AOD and urbanization development before and after the promulgation of environmental governance policies in Jinan City from 2009 to 2018. Results show that (1) the spatial distribution of AOD in Jinan had the characteristics of high in the north and low in the south, high in the west and low in the east, and low in some parts of the central region; there was a significant seasonal variation in time, with the highest AOD in summer and the lowest in winter. During 2009-2013, the annual average variation of AOD increased by 20.6%, while during 2014-2018, it decreased by 35.3%; (2) The distribution of night-light in Jinan City has progressively expanded, mirroring the city's ongoing development. The spatial distribution of aerosols in urban areas was relatively low compared to the surrounding areas of the city. (3) From 2009 to 2013, there existed a significant positive correlation between the spatial and temporal distribution of AOD and night-light. However, from 2014 to 2018, with the implementation of environmental governance policies, this relationship shifted to a significant negative correlation between the spatial and temporal distribution of AOD and night-light. Through an analysis of the correlation between urban development and aerosol depth in Jinan City over the past decade, it can be concluded that urban development does not inevitably result in elevated AOD levels. Notably, the Jinan government has achieved remarkable results in controlling the atmospheric environment, as evidenced by recent years' improvements.

Relationships between birth weight discordance and maternal and perinatal risks among twin pregnancies conceived following frozen embryo transfer.

STUDY QUESTION: Is intertwin birth weight discordance associated with adverse maternal and perinatal outcomes following frozen embryo transfer (FET)? SUMMARY ANSWER: For twins conceived following FET, intertwin birth weight discordance is related to elevated risks of neonatal mortality irrespective of chorionicity, and the risk of hypertensive disorders of pregnancy (HDP) is elevated for the mothers of dichorionic twins affected by such birth weight discordance. WHAT IS KNOWN ALREADY: While the relationships between intertwin birth weight discordance and adverse maternal or fetal outcomes have been studied for naturally conceived twins, similarly comprehensive analyses for twins conceived using ART remain to be performed. STUDY DESIGN, SIZE, DURATION: This was a retrospective cohort study of all twin births from 2007 to 2021 at Shanghai Ninth People's Hospital in Shanghai, China that were conceived following FET (N = 6265). PARTICIPANTS/MATERIALS, SETTING, METHODS: Intertwin birth weight discordance was defined as a 20% difference in neonatal birth weights. The primary study outcome was the incidence of HDP and neonatal death while secondary outcomes included gestational diabetes, placenta previa, placental abruption, intrahepatic cholestasis of pregnancy, preterm premature rupture of the membranes, Cesarean delivery, gestational age, birth weight, stillbirth, birth defect, neonatal jaundice, necrotizing enterocolitis, and pneumonia incidence. Logistic regression models were used to estimate adjusted odds ratios (aORs) and 95% CIs for maternal and neonatal outcomes. Subgroup analyses were conducted, and Kaplan-Meier survival analysis was used to estimate the survival probability. The sensitivity analysis was performed with a propensity score-based patient-matching model, an inverse probability weighting model, a restricted cubic spline analysis, and logistic regression models using other percentage cutoffs for discordance. MAIN RESULTS AND THE ROLE OF CHANCE: Of 6101 females that gave birth to dichorionic twins during the study interval, birth weight discordance was observed in 797 twin pairs (13.1%). In this cohort, intertwin birth weight discordance was related to an elevated risk of HDP (aOR 1.56; 95% CI 1.21-2.00), and this relationship was confirmed through sensitivity analyses. Hypertensive disease risk rose as the severity of this birth weight discordance increased. Discordant birth weight was also linked to increased odds of neonatal mortality (aOR 2.13; 95% CI 1.03-4.09) and this risk also increased with the severity of discordance. Of the 164 women with monochorionic twins, the discordant group exhibited an elevated risk of neonatal death compared to the concordant group (crude OR 9.00; 95% CI 1.02-79.3). LIMITATIONS, REASONS FOR CAUTION: The limitations of this study are its retrospective nature and the fact that the available data could not specify which twins were affected by adverse outcomes. There is a lack of an established reference birth weight for Chinese twins born at a gestational age of 24-41 weeks. WIDER IMPLICATIONS OF THE FINDINGS: These findings suggest that twins exhibiting a birth weight discordance are related to an elevated risk of adverse maternal and perinatal outcomes, emphasizing a potential need for higher levels of antenatal surveillance in these at-risk pregnancies. STUDY FUNDING/COMPETING INTEREST(S): Authors declare no conflict of interest. This study was funded by the Clinical Research Program of Shanghai Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine (JYLJ202118) and the National Natural Science Foundation of China (Grant Nos 82271693 and 82273634). TRIAL REGISTRATION NUMBER: N/A.

Application of fluorescence endoscopy with methylene blue dye and indocyanine green dual-tracer method in sentinel lymph node biopsy for women with breast cancer.

Background: Indocyanine green (ICG) allows for the real-time visualization of lymphatic drainage and provides favorable performance for sentinel lymph node (SLN) mapping. However, the limited ability of tissue penetration of the near-infrared fluorescence of ICG may lead to the failure of lymph node detection in the traditional open approach of sentinel lymph node biopsy (SLNB) for breast cancer, especially in overweight or obese patients. To accurately and quickly detect SLNs, we applied fluorescence endoscopy with a dual-tracer method using ICG and methylene blue dye (MBD) in SLNB for breast cancer. We conducted this study to assess the feasibility and application value of this method in minimally invasive surgery. Methods: A total of 117 patients who received dual-tracer injection of ICG and MBD prior to endoscopic SLNB from November 2020 to September 2021 were examined in this study. The number of SLNs identified, the SLN identification rate, the time to identify the first SLN, the procedure duration, and the postoperative morbidity were analyzed. Results: Biopsied SLNs could be identified in 116 patients (99.15%) with an average number of 5.12±1.87 per patient. Blue-stained SLNs were found in 99 patients (84.62%) and fluorescent SLNs in 112 patients (95.73%). A total of 34 patients (29.06%) had positive SLNs. In 6 cases (5.13%), the positive SLNs were only stained with ICG fluorescence. In 1 case (0.85%), the positive SLNs were only blue-stained with no fluorescence staining. The mean durations for the identification of the first SLN and endoscopic SLNB were 7.14±6.31 and 37.75±16.94 min, respectively. Upper-limb lymphoedema was observed 5 cases (4.27%) during a median follow-up period of 10 months. Conclusions: The fluorescence endoscopy method assisted by dual tracer facilitates SLN detection with a comparatively short procedure duration and low complication rate. This approach could serve as a new method for SLNB for patients with breast cancer.

Mechanism of active acetylcholinesterase inhibition by organic sulfanes in garlic: Non-covalent binding and covalent modifications.

Numerous secondary metabolites in medicinal food homology plants such as Allium inhibit the activity of acetylcholinesterase (AChE), but the current understanding of the inhibition mechanism is limited. In this study, we employed ultrafiltration, spectroscopic, molecular docking, and matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry (MALDI-TOF-MS/MS) techniques to investigate the inhibition mechanism of AChE by garlic organic sulfanes, including diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS). The results of UV-spectrophotometry and ultrafiltration experiments showed the inhibition of AChE activity by DAS and DADS was reversible (competitive inhibition), but inhibition by DATS was irreversible. Molecular fluorescence and molecular docking indicated DAS and DADS changed the positions of key amino acids inside the catalytic cavity through hydrophobic interactions with AChE. By using MALDI-TOF-MS/MS, we found DATS irreversibly inhibited AChE activity by opening disulfide-bond switching of disulfide bond 1 (Cys-69 and Cys-96) and disulfide bond 2 (Cys-257 and Cys-272) in AChE, as well as by covalently modifying Cys-272 in disulfide bond 2 to generate AChE-SSA derivatives (strengthened switch). This study provides a basis for further exploration of natural AChE inhibitors using organic active substances in garlic and presents a hypothesis of U-shaped spring force arm effect based on the disulfide bond-switching reaction of DATS that can be used to evaluate the stability of disulfide bonds in proteins.

The role of AFAP1-AS1 in mitotic catastrophe and metastasis of triple-negative breast cancer cells by activating the PLK1 signaling pathway.

Triple-negative breast cancer (TNBC) is characterized by fast growth, high metastasis, high invasion, and a lack of therapeutic targets. Mitosis and metastasis of TNBC cells are two important biological behaviors in TNBC malignant progression. It is well known that the long noncoding RNA AFAP1-AS1 plays a crucial role in various tumors, but whether AFAP1-AS1 is involved in the mitosis of TNBC cells remains unknown. In this study, we investigated the functional mechanism of AFAP1-AS1 in targeting Polo-like Kinase 1 (PLK1) activation and participating in mitosis of TNBC cells. We detected the expression of AFAP1-AS1 in the TNBC patient cohort and primary cells by in situ hybridization (ISH), northern blot, fluorescent in situ hybridization (FISH) and cell nucleus/cytoplasm RNA fraction isolation. High AFAP1-AS1 expression was negatively correlated with overall survival (OS), disease-free survival (DFS), metastasis-free survival (MFS) and recurrence-free survival (RFS) in TNBC patients. We explored the function of AFAP1-AS1 by transwell, apoptosis, immunofluorescence (IF) and patient-derived xenograft (PDX) models in vitro and in vivo. We found that AFAP1-AS1 promoted TNBC primary cell survival by inhibiting mitotic catastrophe and increased TNBC primary cell growth, migration and invasion. Mechanistically, AFAP1-AS1 activated phosphorylation of the mitosis-associated kinase PLK1 protein. Elevated levels of AFAP1-AS1 in TNBC primary cells increased PLK1 pathway downstream gene expression, such as CDC25C, CDK1, BUB1 and TTK. More importantly, AFAP1-AS1 increased lung metastases in a mouse metastasis model. Taken together, AFAP1-AS1 functions as an oncogene that activates the PLK1 signaling pathway. AFAP1-AS1 could be used as a potential prognostic marker and therapeutic target for TNBC.

Diagnostic Value of Artificial Intelligence-Assistant Diagnostic System Combined With Contrast-Enhanced Ultrasound in Thyroid TI-RADS 4 Nodules.

OBJECTIVES: This study evaluated the diagnostic value of artificial intelligence-assistant diagnostic system combined with contrast-enhanced ultrasound in The American College of Radiology Thyroid Imaging, Reporting and Data System (ACR TI-RADS) 4 category thyroid nodules. METHODS: Thyroid nodules that were evaluated as ACR TI-RADS 4 by conventional ultrasound were selected, all of which had pathological or fine needle aspiration (FNA) results. All nodules were examined by contrast-enhanced ultrasound (CEUS) and artificial intelligence (AI) analysis. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of AI, CEUS and their combined diagnosis were compared; Analyzed and compared the diagnostic efficiency of AI, CEUS and their combined diagnosis. RESULTS: A total of 148 thyroid nodules were included in 140 patients, including 58 malignant nodules and 89 benign nodules. The sensitivity of combined diagnosis was significantly higher than that of AI or CEUS alone (P < .05). The NPV of AI, CEUS and combined diagnosis were statistically significant (P < .05). There was no significant difference in the diagnostic efficacy between AI and CEUS (P > .05), but there was a significant difference in NPV between AI and combined diagnosis (P < .05). The AUC of the combined diagnosis was 0.859, which was higher than that of AI, CEUS alone. CONCLUSIONS: AI has a high diagnostic efficiency, which was helpful for radiologists to make rapid assessment. AI combined CEUS can significantly improve the diagnostic sensitivity and NPV, which was beneficial for the early detection of malignant nodules.

MLR-SNet: Transferable LR Schedules for Heterogeneous Tasks.

The learning rate (LR) is one of the most important hyperparameters in stochastic gradient descent (SGD) algorithm for training deep neural networks (DNN). However, current hand-designed LR schedules need to manually pre-specify a fixed form, which limits their ability to adapt to practical non-convex optimization problems due to the significant diversification of training dynamics. Meanwhile, it always needs to search proper LR schedules from scratch for new tasks, which, however, are often largely different with task variations, like data modalities, network architectures, or training data capacities. To address this learning-rate-schedule setting issue, we propose to parameterize LR schedules with an explicit mapping formulation, called MLR-SNet. The learnable parameterized structure brings more flexibility for MLR-SNet to learn a proper LR schedule to comply with the training dynamics of DNN. Image and text classification benchmark experiments substantiate the capability of our method for achieving proper LR schedules. Moreover, the explicit parameterized structure makes the meta-learned LR schedules capable of being transferable and plug-and-play, which can be easily generalized to new heterogeneous tasks. We transfer our meta-learned MLR-SNet to query tasks like different training epochs, network architectures, data modalities, dataset sizes from the training ones, and achieve comparable or even better performance compared with hand-designed LR schedules specifically designed for the query tasks. The robustness of MLR-SNet is also substantiated when the training data are biased with corrupted noise. We further prove the convergence of the SGD algorithm equipped with LR schedule produced by our MLR-SNet, with the convergence rate comparable to the best-known ones of the algorithm for solving the problem. The source code of our method is released at https://github.com/xjtushujun/MLR-SNet.

Human Coronary Plaque Optical Coherence Tomography Image Repairing, Multilayer Segmentation and Impact on Plaque Stress/Strain Calculations.

Coronary vessel layer structure may have a considerable impact on plaque stress/strain calculations. Most current plaque models use single-layer vessel structures due to the lack of available multilayer segmentation techniques. In this paper, an automatic multilayer segmentation and repair method was developed to segment coronary optical coherence tomography (OCT) images to obtain multilayer vessel geometries for biomechanical model construction. Intravascular OCT data were acquired from six patients (one male; mean age: 70.0) using a protocol approved by the local institutional review board with informed consent obtained. A total of 436 OCT slices were selected in this study. Manually segmented data were used as the gold standard for method development and validation. The edge detection method and cubic spline surface fitting were applied to detect and repair the internal elastic membrane (IEM), external elastic membrane (EEM) and adventitia-periadventitia interface (ADV). The mean errors of automatic contours compared to manually segmented contours were 1.40%, 4.34% and 6.97%, respectively. The single-layer mean plaque stress value from lumen was 117.91 kPa, 10.79% lower than that from three-layer models (132.33 kPa). On the adventitia, the single-layer mean plaque stress value was 50.46 kPa, 156.28% higher than that from three-layer models (19.74 kPa). The proposed segmentation technique may have wide applications in vulnerable plaque research.

The Impact of Improved Oral Care Methods on the Oral Health of Patients Undergoing Transoral Mechanical Ventilation.

Objective: To explore the effects of improved oral care on the number of oropharyngeal bacteria and the incidence of ventilator-associated pneumonia in patients undergoing mechanical ventilation through oral endotracheal intubation by improving conventional oral care methods and operating procedures and to evaluate the quality of improved oral care and effect. Methods: A total of 100 cases of mechanically ventilated patients with oral endotracheal intubation who met the inclusion criteria were randomly divided into the observation group and control group with 50 cases each. The control group took routine oral care, that is, scrubbing 3 times per day, and the oral care solution was selected as physiological brine. The observation group improved the conventional oral care method, namely, oral scrubbing before intubation, brushing and washing after intubation, 3 times per day, and 0.1% povidone-iodine in oral care solution. Analysis and comparison of the oral bacterial flora, oral cleanliness, and incidence of ventilator-associated pneumonia, mechanical ventilation time, ICU hospitalization time, and mortality rate of the two groups of patients were analyzed and compared. The relevant data were collected and processed for statistical processing. Results: The oral bacterial flora of the two groups of patients before oral care after mechanical ventilation after oral tracheal intubation was compared, and there was no significant statistical difference (P > 0.05). After nursing, the oral bacterial flora of the observation group at 8 h, 16 h, and 24 h after intubation was significantly lower than that of the control group. Statistics showed that the difference was statistically significant (P < 0.05). After nursing, the number of patients with oral cleanliness in the observation group was significantly higher than that of the control group, while the incidence of ventilator-associated pneumonia in the observation group was 8% significantly lower than that of the control group 14%. Statistics show that this difference is statistically significant (P < 0.05). After nursing, the observation group's oral cleanliness score, mechanical ventilation time, ICU hospitalization time, and GCS score were better than those of the control group. Statistics showed that the difference was statistically significant (P < 0.05). The mortality of the observation group was significantly lower than that of the control group, which was not statistically significant (P > 0.05). Conclusion: Oral care can effectively reduce the number of oropharyngeal bacteria in patients who are mechanically ventilated through orotracheal intubation and significantly reduce the incidence of ventilator-associated pneumonia.

Exosomes Derived From CTF1-Modified Bone Marrow Stem Cells Promote Endometrial Regeneration and Restore Fertility.

Background: Thin endometrial tissue is a leading cause of embryo transfer failure, potentially contributing to sustained infertility and associated adverse outcomes. The application of exosomes derived from autologous or allogeneic bone marrow-derived stem cells (BMSCs) has been used to promote uterine repair following injury, and there is also prior evidence that stem cell transplantation can bolster fertility. Genetic modifications represent a primary approach to enhancing exosomal therapy strategies. The present study thus explored the effects of Cardiotrophin-1 (CTF1)-modified BMSCs-exo on fertility-related outcomes. Methods: An adenoviral vector was used to generate CTF1-overexpressing BMSCs (C-BMSCs), after which exosomes were isolated from control BMSCs (BMSC-exos) and C-BMSCs (C-BMSC-exos). The angiogenic effects of C-BMSC-exo treatment were assessed through analyses of endothelial cell proliferation and tube formation. Model rats exhibiting endometrial thinning were administered C-BMSCs-exo, after which the effects of such treatment were assessed through H&E staining, Masson's trichrome staining, and immunofluorescence analyses. The mechanistic basis for the proangiogenic effects of CTF1 as a driver of endometrial regeneration was additionally explored. Results: C-BMSC-exo treatment of HUVECs was associated with enhanced neovascularization, as evidenced by improved in vitro proliferation, migration, and tube formation. Importantly, such treatment was also linked to tissue regeneration, neovascularization, and the suppression of localized tissue fibrosis in vivo. Regenerated endometrial tissue exhibited higher embryo receptivity and was associated with higher birth rates in treated rats. The upregulation of the JAK/PI3K/mTOR/STAT3 signaling pathways in C-BMSC-exo-treated rats may underscore the mechanistic basis whereby CTF1 can positively impact endometrial angiogenesis and regeneration. Conclusion: Our data suggest that exosomes produced by CTF1-modified BMSCs can more effectively promote the regeneration of endometrial and myometrial tissues, driving neovascularization in a manner that improves endometrial receptivity in a rat model system, highlighting the therapeutic promise of this approach for patients diagnosed with endometrial thinning.

Changes in sexual frequency among 51 150 infertile Chinese couples over the past 10 years.

STUDY QUESTION: How did the sexual frequency change and what are the related influencing factors among infertile Chinese couples over the past 10 years? SUMMARY ANSWER: Sexual frequency has declined among infertile Chinese couples over the past decade, with such declines being most pronounced for women between the ages of 18 and 39. WHAT IS KNOWN ALREADY: Many researchers have explored trends in coital frequency and variables associated among healthy individuals in other nations. There have been major changes in all aspects of Chinese life and society over the past decade, including two major fertility policy adjustments. The sexual habits of infertile couples in China remain poorly understood and warrant further investigation. STUDY DESIGN, SIZE, DURATION: A retrospective cohort study of 51 150 infertile couples that visited our facility between January 2011 and December 2020 at a tertiary care academic medical centre. PARTICIPANTS/MATERIALS, SETTING, METHODS: The primary outcome for this study was whether couples had engaged in sexual intercourse ≤4 times/month or >4 times/month. Multivariable logistic regression analyses were performed to detect the association between the variables and sexual frequency. Analyses were further performed to determine whether observed trends remained evident in women from different age subgroups. To assess whether these trends differed before and after the introduction of the universal two-child policy in China (January 2016), we additionally assessed trends in these age subgroups of women relative to the time at which this policy was introduced. MAIN RESULTS AND THE ROLE OF CHANCE: The proportion of couples reporting having engaged in sexual intercourse >4 times/month fell over the past decade from 62.7% (2011-2013) to 55.9% (2014-2015) to 52.7% (2016-2020). Declines in sexual frequency were evident for women between the ages of 18 and 39 (P < 0.05), whereas no such changes were evident for women between the ages of 40 and 50. Younger men and women, as well as individuals with a less than junior college education level, reported higher frequencies of sexual intercourse. For women, being remarried and having a more recent diagnosis of infertility were associated with increased coital frequency. This frequency decreased progressively for women as BMI values increased. There was no detected relationship between coital frequency and nationality or history of prior births. LIMITATIONS, REASONS FOR CAUTION: These analyses were dependent on self-reported data, and may thus have been impacted by the over- or under-reporting of sexual frequency as a consequence of social desirability bias. In addition, not all potentially relevant variables were assessed in all analyses, and certain potentially relevant variables such as family income or pornography use were not measured in any analyses. WIDER IMPLICATIONS OF THE FINDINGS: Sexual frequency is closely related to infertility risks. This general downward trend in sexual frequency may warrant concern. At present, these reductions remain an interesting yet unexplained topic worthy of further study. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the National Key Research and Development Program of China (Grant no. 2018YFC1003000) and the National Natural Science Foundation of China (Grant no. 81771533). The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.