Neutrophil extracellular traps mediate cardiomyocyte ferroptosis via the Hippo-Yap pathway to exacerbate doxorubicin-induced cardiotoxicity.

Doxorubicin-induced cardiotoxicity (DIC), which is a cardiovascular complication, has become the foremost determinant of decreased quality of life and mortality among survivors of malignant tumors, in addition to recurrence and metastasis. The limited ability to accurately predict the occurrence and severity of doxorubicin-induced injury has greatly hindered the prevention of DIC, but reducing the dose to mitigate side effects may compromise the effective treatment of primary malignancies. This has posed a longstanding clinical challenge for oncologists and cardiologists. Ferroptosis in cardiomyocytes has been shown to be a pivotal mechanism underlying cardiac dysfunction in DIC. Ferroptosis is influenced by multiple factors. The innate immune response, as exemplified by neutrophil extracellular traps (NETs), may play a significant role in the regulation of ferroptosis. Therefore, the objective of this study was to investigate the involvement of NETs in doxorubicin-induced cardiomyocyte ferroptosis and elucidate their regulatory role. This study confirmed the presence of NETs in DIC in vivo. Furthermore, we demonstrated that depleting neutrophils effectively reduced the occurrence of doxorubicin-induced ferroptosis and myocardial injury in DIC. Additionally, our findings showed the pivotal role of high mobility group box 1 (HMGB1) as a critical molecule implicated in DIC and emphasized its involvement in the modulation of ferroptosis subsequent to NETs inhibition. Mechanistically, we obtained preliminary evidence suggesting that doxorubicin-induced NETs could modulate yes-associated protein (YAP) activity by releasing HMGB1, which subsequently bound to toll like receptor 4 (TLR4) on the cardiomyocyte membrane, thereby influencing cardiomyocyte ferroptosis in vitro. Our findings suggest that doxorubicin-induced NETs modulate cardiomyocyte ferroptosis via the HMGB1/TLR4/YAP axis, thereby contributing to myocardial injury. This study offers a novel approach for preventing and alleviating DIC by targeting alterations in the immune microenvironment.

Protective effect of low-intensity pulsed ultrasound on immune checkpoint inhibitor-related myocarditis via fine-tuning CD4+ T-cell differentiation.

PURPOSE: Immune checkpoint inhibitors (ICIs) have transformed traditional cancer treatments. Specifically, ICI-related myocarditis is an immune-related adverse event (irAE) with high mortality. ICIs activate CD4+ T-lymphocyte reprogramming, causing an imbalance between Th17 and Treg cell differentiation, ultimately leading to myocardial inflammatory damage. Low-intensity pulsed ultrasound (LIPUS) can limit inflammatory responses, with positive therapeutic effects across various cardiovascular inflammatory diseases; however, its role in the pathogenesis of ICI-related myocarditis and CD4+ T-cell dysfunction remains unclear. Accordingly, this study investigated whether LIPUS can alleviate ICI-related myocarditis inflammatory damage and, if so, aimed to elucidate the beneficial effects of LIPUS and its underlying molecular mechanisms. METHODS: An in vivo model of ICI-related myocarditis was obtained by intraperitonially injecting male A/J mice with an InVivoPlus anti-mouse PD-1 inhibitor. LIPUS treatment was performed via an ultrasound-guided application to the heart via the chest wall. The echocardiographic parameters were observed and cardiac function was assessed using an in vivo imaging system. The expression of core components of the HIPPO pathway was analyzed via western blotting. RESULTS: LIPUS treatment reduced cardiac immune responses and inflammatory cardiac injury. Further, LIPUS treatment alleviated the inflammatory response in mice with ICI-related myocarditis. Mechanistically, in the HIPPO pathway, the activation of Mst1-TAZ axis improved autoimmune inflammation by altering the interaction between the transcription factors FOXP3 and RORγt and regulating the differentiation of Treg and Th17 cells. CONCLUSION: LIPUS therapy was shown to reduce ICI-related myocarditis inflammatory damage and improve cardiac function, representing an exciting finding for irAEs treatment.

Enhanced forward scattering of a cell in line optical tweezers with an astigmatic beam.

The line optical tweezers (LOT) has been proven to be an alternative technique to manipulating the biological cells because of the bigger potential compared with traditional optical tweezers with a highly focused spot. We deduce the 4 × 4 optical matrix of the astigmatic LOT to investigate the optical characteristics related to the systematic parameters. The comparison of the initial and scattered electric fields by the cell under the astigmatic and stigmatic LOT is implemented to illustrate that the forward scattered light from the astigmatic LOT is much stronger than that from the stigmatic LOT, so as to the cell deformations. It is demonstrated that the astigmatic LOT could provide a more efficient way to deform the cell not only in the focal plane, but also along the optical axis to screen large biomaterials in biomechanics.

Evaluation of standard breast ultrasonography by adding two-dimensional and three-dimensional shear wave elastography: a prospective, multicenter trial.

OBJECTIVE: To reduce the number of biopsies performed on benign breast lesions categorized as BI-RADS 4-5, we investigated the diagnostic performance of combined two-dimensional and three-dimensional shear wave elastography (2D + 3D SWE) with standard breast ultrasonography (US) for the BI-RADS assessment of breast lesions. METHODS: A total of 897 breast lesions, categorized as BI-RADS 3-5, were subjected to standard breast US and supplemented by 2D SWE only and 2D + 3D SWE analysis. Based on the malignancy rate of less than 2% for BI-RADS 3, lesions assessed by standard breast US were reclassified with SWE assessment. RESULTS: After standard breast US evaluation, 268 (46.1%) participants underwent benign biopsies in BI-RADS 4-5 lesions. By using separated cutoffs for upstaging BI-RADS 3 at 120 kPa and downstaging BI-RADS 4a at 90 kPa in 2D + 3D SWE reclassification, 123 (21.2%) participants underwent benign biopsy, resulting in a 54.1% reduction (123 versus 268). CONCLUSION: Combining 2D + 3D SWE with standard breast US for reclassification of BI-RADS lesions may achieve a reduction in benign biopsies in BI-RADS 4-5 lesions without sacrificing sensitivity unacceptably. CLINICAL RELEVANCE STATEMENT: Combining 2D + 3D SWE with US effectively reduces benign biopsies in breast lesions with categories 4-5, potentially improving diagnostic accuracy of BI-RADS assessment for patients with breast lesions. TRIAL REGISTRATION: ChiCTR1900026556 KEY POINTS: • Reduce benign biopsy is necessary in breast lesions with BI-RADS 4-5 category. • A reduction of 54.1% on benign biopsies in BI-RADS 4-5 lesions was achieved using 2D + 3D SWE reclassification. • Adding 2D + 3D SWE to standard breast US improved the diagnostic performance of BI-RADS assessment on breast lesions: specificity increased from 54 to 79%, and PPV increased from 54 to 71%, with slight loss in sensitivity (97.2% versus 98.7%) and NPV (98.1% versus 98.7%).

[Development and Application of Catheter Electrodes for Rat Airway High-Voltage Pulsed Electric Field Ablation].

High-voltage pulsed electric field (HV-PEF) ablation technology has demonstrated promising applications in the clinical treatment of chronic obstructive pulmonary disease (COPD). However, its use has been limited to exploratory applications in a small number of cases, and the underlying mechanisms remain largely undefined. To facilitate broader clinical implementation, comprehensive molecular mechanism studies via extensive animal experimentation are essential. Rats, due to their ease of modeling COPD and the availability of comprehensive molecular reagents, serve as an optimal model for such studies. Consequently, the development of electrodes specifically designed for HV-PEF respiratory ablation in SD rats is of significant importance. In this study, we meticulously examined the anatomical structure of rat airways and investigated various equipment parameters, including material composition, rigidity, diameter, electrode ring dimensions, spacing between positive and negative poles, insulation coating for the catheters, welding techniques between the guidewire and electrode ring, and the design of vent holes in the catheter. Based on these considerations, we fabricated PVC ablation electrode catheters with integrated ventilation functionality. Subsequently, we employed finite element simulation to estimate the field strengths that could be applied by these electrodes. The simulation results were then validated in normal rats to assess the electrical safety and efficacy of the electrodes. These findings laid the groundwork for further investigation into the mechanisms of HV-PEF treatment for COPD.

Ultrasound and microbubble-mediated delivery of miR-424-5p has a therapeutic effect in preeclampsia.

OBJECTIVE: To determine the influence of ultrasound/microbubble-mediated miR-424-5p delivery on trophoblast cells and the underlying mechanism. METHODS: Blood pressure and 24-h proteinuria of patients with preeclampsia (PE) were measured as well as the levels of miR-424-5p and amine oxidase copper containing 1 (AOC1) in placental tissues. HTR-8/Svneo and TEV-1 cells were subjected to cell transfection or ultrasonic microbubble transfection for determination of the expression of miR-424-5p, AOC1, ß-catenin and c-Myc as well as cell proliferation, apoptosis, migration and invasiveness. The concentrations of placental growth factor (PLGF), human chorionic gonadotropin (ß-hCG) and tumor necrosis factor-α (TNF-α) were measured in HTR-8/Svneo and TEV-1 cells. RNA immunoprecipitation (RIP) and dual luciferase reporter assay detected the binding of miR-424-5p to AOC1. A PE mouse model was induced by subcutaneous injection of L-NAME, where the influence of ultrasound/microbubble-mediated miR-424-5p delivery was evaluated. RESULTS: miR-424-5p was downregulated while AOC1 was upregulated in the placental tissues from PE patients. Overexpression of miR-424-5p activated Wnt/ß-catenin signaling pathway and promoted the proliferation of HTR-8/Svneo and TEV-1 cells as well as enhanced the migratory and invasive behaviors. AOC1 overexpression partly eliminated the effects of miR-424-5p on HTR-8/Svneo and TEV-1 cells. Ultrasound and microbubble mediated gene delivery enhanced the transfection efficiency of miR-424-5p and further promoted the effects of miR-424-5p in trophoblast cells. Ultrasound/microbubble-mediated miR-424-5p delivery alleviated experimental PE in mice. CONCLUSION: Ultrasound and microbubble-mediated miR-424-5p delivery targets AOC1 and activates Wnt/ß-catenin signaling pathway, thus promoting the aggressive phenotype of trophoblast cells, which indicating that miR-424-5p/AOC1 axis might be involved with PE pathogenesis.

Peripheral atherosclerosis in acute coronary syndrome patients with plaque rupture vs plaque erosion: A prospective coronary optical coherence tomography and peripheral ultrasound study.

BACKGROUND: Plaque rupture (PR) and plaque erosion (PE) are 2 distinct, different, and most common culprit lesion morphologies responsible for acute coronary syndrome (ACS). However, the prevalence, distribution, and characteristics of peripheral atherosclerosis in ACS patients with PR vs PE has never been studied. The aim of this study was to assess peripheral atherosclerosis burden and vulnerability evaluated by vascular ultrasound in ACS patients with coronary PR vs PE identified by optical coherence tomography (OCT). METHODS: Between October 2018 and December 2019, 297 ACS patients who underwent preintervention OCT examination of the culprit coronary artery were enrolled. Peripheral ultrasound examinations of carotid, femoral, and popliteal arteries were performed before discharge. RESULTS: Overall, 265 of 297 (89.2%) patients had at least one atherosclerotic plaque in a peripheral arterial bed. Compared with coronary PE, patients with coronary PR had a higher prevalence of peripheral atherosclerotic plaques (93.4% vs 79.1%, P < .001), regardless of location: carotid, femoral, or popliteal arteries. The number of peripheral plaques per patient was significantly larger in the coronary PR group than coronary PE (4 [2-7] vs 2 [1-5], P < .001). Additionally, there was a greater prevalence of peripheral vulnerable characteristics including plaque surface irregularity, heterogeneous plaque, and calcification in patients with coronary PR vs PE. CONCLUSIONS: Peripheral atherosclerosis exists commonly in patients presenting with ACS. Patients with coronary PR had greater peripheral atherosclerosis burden and more peripheral vulnerability compared to those with coronary PE, suggesting that comprehensive evaluation of peripheral atherosclerosis and multidisciplinary cooperative management maybe necessary, especially in patients with PR. TRIAL REGISTRATION: clinicaltrials.gov (NCT03971864).

Radiogenomic analysis of prediction HER2 status in breast cancer by linking ultrasound radiomic feature module with biological functions.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) overexpressed associated with poor prognosis in breast cancer and HER2 has been defined as a therapeutic target for breast cancer treatment. We aimed to explore the molecular biological information in ultrasound radiomic features (URFs) of HER2-positive breast cancer using radiogenomic analysis. Moreover, a radiomics model was developed to predict the status of HER2 in breast cancer. METHODS: This retrospective study included 489 patients who were diagnosed with breast cancer. URFs were extracted from a radiomics analysis set using PyRadiomics. The correlations between differential URFs and HER2-related genes were calculated using Pearson correlation analysis. Functional enrichment of the identified URFs-correlated HER2 positive-specific genes was performed. Lastly, the radiomics model was developed based on the URF-module mined from auxiliary differential URFs to assess the HER2 status of breast cancer. RESULTS: Eight differential URFs (p < 0.05) were identified among the 86 URFs extracted by Pyradiomics. 25 genes that were found to be the most closely associated with URFs. Then, the relevant biological functions of each differential URF were obtained through functional enrichment analysis. Among them, Zone Entropy is related to immune cell activity, which regulate the generation of calcification in breast cancer. The radiomics model based on the Logistic classifier and URF-module showed good discriminative ability (AUC = 0.80, 95% CI). CONCLUSION: We searched for the URFs of HER2-positive breast cancer, and explored the underlying genes and biological functions of these URFs. Furthermore, the radiomics model based on the Logistic classifier and URF-module relatively accurately predicted the HER2 status in breast cancer.

Ultrasound-based deep learning in the establishment of a breast lesion risk stratification system: a multicenter study.

OBJECTIVES: To establish a breast lesion risk stratification system using ultrasound images to predict breast malignancy and assess Breast Imaging Reporting and Data System (BI-RADS) categories simultaneously. METHODS: This multicenter study prospectively collected a dataset of ultrasound images for 5012 patients at thirty-two hospitals from December 2018 to December 2020. A deep learning (DL) model was developed to conduct binary categorization (benign and malignant) and BI-RADS categories (2, 3, 4a, 4b, 4c, and 5) simultaneously. The training set of 4212 patients and the internal test set of 416 patients were from thirty hospitals. The remaining two hospitals with 384 patients were used as an external test set. Three experienced radiologists performed a reader study on 324 patients randomly selected from the test sets. We compared the performance of the DL model with that of three radiologists and the consensus of the three radiologists. RESULTS: In the external test set, the DL model achieved areas under the receiver operating characteristic curve (AUCs) of 0.980 and 0.945 for the binary categorization and six-way categorizations, respectively. In the reader study set, the DL BI-RADS categories achieved a similar AUC (0.901 vs. 0.933, p = 0.0632), sensitivity (90.98% vs. 95.90%, p = 0.1094), and accuracy (83.33% vs. 79.01%, p = 0.0541), but higher specificity (78.71% vs. 68.81%, p = 0.0012) than those of the consensus of the three radiologists. CONCLUSIONS: The DL model performed well in distinguishing benign from malignant breast lesions and yielded outcomes similar to experienced radiologists. This indicates the potential applicability of the DL model in clinical diagnosis. KEY POINTS: • The DL model can achieve binary categorization for benign and malignant breast lesions and six-way BI-RADS categorizations for categories 2, 3, 4a, 4b, 4c, and 5, simultaneously. • The DL model showed acceptable agreement with radiologists for the classification of breast lesions. • The DL model performed well in distinguishing benign from malignant breast lesions and had promise in helping reduce unnecessary biopsies of BI-RADS 4a lesions.

Adverse childhood experiences and depressive symptoms among lesbian and bisexual women in China.

BACKGROUND: Despite the relationship between Adverse childhood experiences (ACEs) and depressive symptoms, which has been well researched in general populations, little is known about homosexual and bisexual populations, especially lesbian and bisexual women in China. This study aims to investigate the prevalence of ACEs and depressive symptoms and to analyze the relationship between them among lesbian and bisexual women in China. METHODS: The eligible participants were aged 16 years or older who report their sexual orientation as homosexual or bisexual. The data was collected through anonymous questionnaires with the help of Lespark in Beijing from July 18 to December 29, 2018, and all participants had informed consent to this study. Univariate analysis and multiple linear regression analyses were performed to explore the relationship between ACEs and depressive symptoms among lesbian and bisexual women. All statistical analyses were conducted by the software of SPSS 22.0. RESULTS: Among 301 lesbian and bisexual women, 81.4% were lesbian, 18.4% were bisexual women, and the majority were 21-30 years. As for ACEs, 51.5% reported at least one ACE, in which emotional neglect (22.6%) and emotional abuse (22.3%) were common ACEs. As for depressive symptoms of lesbian and bisexual women, the detection rate was 56.1%. The multiple linear regression analyses showed that abuse (ß = 2.95, 95%CI:1.07-4.83) and neglect (ß = 3.21, 95%CI:1.09-5.31) were positively associated with depressive symptoms and lesbian and bisexual women with three (ß = 4.11, 95%CI: 0.99-7.22) or more (ß = 6.02, 95%CI: 3.23-8.78) ACEs suffered from more depressive symptoms than others. CONCLUSION: Adverse childhood experiences (ACEs) and depressive symptoms were at high prevalence among lesbian and bisexual women in China. ACEs were associated with depressive symptoms, especially childhood abuse and neglect experiences that have a significant effect on lesbian and bisexual women mental health.

A Hybrid Power-Rate Management Strategy in Distributed Congestion Control for 5G-NR-V2X Sidelink Communications.

The accelerated growth of 5G technology has facilitated substantial progress in the realm of vehicle-to-everything (V2X) communications. Consequently, achieving optimal network performance and addressing congestion-related challenges have become paramount. This research proposes a unique hybrid power and rate control management strategy for distributed congestion control (HPR-DCC) focusing on 5G-NR-V2X sidelink communications. The primary objective of this strategy is to enhance network performance while simultaneously preventing congestion. By implementing the HPR-DCC strategy, a more fine-grained and adaptive control over the transmit power and transmission rate can be achieved. This enables efficient control by dynamically adjusting transmission parameters based on the network conditions. This study outlines the system model and methodology used to develop the HPR-DCC algorithm and investigates its characteristics of stability and convergence. Simulation results indicate that the proposed method effectively controls the maximum CBR value at 64% during high congestion scenarios, which leads to a 6% performance improvement over the conventional DCC approach. Furthermore, this approach enhances the signal reception range by 20 m, while maintaining the 90% packet reception ratio (PRR). The proposed HPR-DCC contributes to optimizing the quality and reliability of 5G-NR-V2X sidelink communication and holds great promise for advancing V2X applications in intelligent transportation systems.

Psychosocial characteristics pattern correlated with HIV-related risky sexual behavior among HIV-negative men who have sex with men: a latent profile analysis.

BACKGROUND: Men who have sex with men (MSM) have become a high risk population of HIV infection due to their risky sexual behaviors. The latent pattern of psychosocial characteristics plays an important effect in HIV-related risky behaviors among HIV-negative MSM. METHOD: Participants were recruited from Wuhan, Nanchang, and Changsha city from September 2017 to January 2018. Social support was assessed by the multidimensional scale of social support, Connor-Davidson Resilience scale-10 items for reliance, the assessment of Stigma towards Homosexuality for sexual minority stigma, the Likert subscale of nondisclosure for identity concealment, the ACE questionnaire-Kaiser-CDC for adverse childhood experience, the Centers for Epidemiological Studies Depression Scale for depression. Latent profile analysis (LPA) and multivariate regression were used to analyze the data. RESULTS: Three psychosocial characteristic patterns were revealed by the LPA. "Social support and resilience group" (SR group), "Identity concealment group" (IC group) and "Adverse childhood experience" (ACE group) were identified, respectively. In comparison with "SR group", "IC group" have a higher likelihood of one-night male partners (AOR = 2.74, 95%CI = [1.54, 4.90]), both fixed and one-night male partners (AOR = 2.01, 95%CI = [1.34, 3.01]) and HIV-unsure male partner (AOR = 2.12, 95%CI = [1.44, 3.13]). Similarly, "ACE group" were more likely having inconsistent condom use (AOR = 2.58, 95%CI = [1.41, 4.73]), and having sex with HIV-positive male partner (AOR = 4.90, 95%CI = [1.95, 12.30]) with comparison of "SR group". In addition, we further revealed that "ACE group" had a higher ratio (90.0%) of inconsistent condom use among MSM whose male partners were HIV-positive. CONCLUSIONS: Six important psychosocial factors were divided into three latent pattern classes. Compared with "SR group", "IC group" and "ACE group" were more likely to engage in HIV-related risky sexual behaviors. Further research may pay more attention to "IC group" and "ACE group" for targeted intervention.

Melatonin alleviates doxorubicin-induced mitochondrial oxidative damage and ferroptosis in cardiomyocytes by regulating YAP expression.

Doxorubicin (Dox) is a high-efficiency agent for cancer therapy. However, it causes cardiotoxicity which limits its clinical application. Despite more efforts has been made to seek protective decisions, unfortunately, the poor prognosis suggests the need for new treatments. As a powerful mitochondrial antioxidant, melatonin (Mel) has been found to confer cardioprotection against various cardiovascular diseases. Currently, the mechanism through which Mel confers protection is not well understood. In this study, we established a Dox-induced cardiotoxicity model in H9c2 cardiomyocytes, zebrafish, and SD rats to explore the mechanism by which Mel alleviates Dox-induced cardiotoxicity. In vivo and in vitro experiments showed that Dox significantly decreased the viability of H9c2 cells, induced apoptosis, myocardial injury, and effectively up-regulated the expression of p-YAP but down-regulated the expression of YAP. Furthermore, we found that Dox significantly up-regulated the expression of ferroptosis-associated protein ACSL4 and down-regulated expression of GPX4. Interestingly, these effects of Dox were reversed following treatment with Mel, indicating that ferroptosis mediated the protective effects of Mel against Dox-induced cardiomyocyte injury. Furthermore, we used YAP-siRNA in vitro and verteporfin (Ver) in vivo to down-regulate the expression level of YAP. The results showed that YAP down-regulation abolished the protective effects of Mel including apoptosis, mitochondrial lipid peroxidation, and ferroptosis. Collectively, these results show that Mel regulates ferroptosis by modulating YAP expression to counteract Dox-induced cardiotoxicity.

Nomograms based on preoperative multimodal ultrasound of papillary thyroid carcinoma for predicting central lymph node metastasis.

OBJECTIVES: To establish a nomogram for predicting central lymph node metastasis (CLNM) based on the preoperative clinical and multimodal ultrasound (US) features of papillary thyroid carcinoma (PTC) and cervical LNs. METHODS: Overall, 822 patients with PTC were included in this retrospective study. A thyroid tumor ultrasound model (TTUM) and thyroid tumor and cervical LN ultrasound model (TTCLNUM) were constructed as nomograms to predict the CLNM risk. Areas under the curve (AUCs) evaluated model performance. Calibration and decision curves were applied to assess the accuracy and clinical utility. RESULTS: For the TTUM training and test sets, the AUCs were 0.786 and 0.789 and bias-corrected AUCs were 0.786 and 0.831, respectively. For the TTCLNUM training and test sets, the AUCs were 0.806 and 0.804 and bias-corrected AUCs were 0.807 and 0.827, respectively. Calibration and decision curves for the TTCLNUM nomogram exhibited higher accuracy and clinical practicability. The AUCs were 0.746 and 0.719 and specificities were 0.942 and 0.905 for the training and test sets, respectively, when the US tumor size was ≤ 8.45 mm, while the AUCs were 0.737 and 0.824 and sensitivity were 0.905 and 0.880, respectively, when the US tumor size was > 8.45 mm. CONCLUSION: The TTCLNUM nomogram exhibited better predictive performance, especially for the CLNM risk of different PTC tumor sizes. Thus, it serves as a useful clinical tool to supply valuable information for active surveillance and treatment decisions. KEY POINTS: • Our preoperative noninvasive and intuitive prediction method can improve the accuracy of central lymph node metastasis (CLNM) risk assessment and guide clinical treatment in line with current trends toward personalized treatments. • Preoperative clinical and multimodal ultrasound features of primary papillary thyroid carcinoma (PTC) tumors and cervical LNs were directly used to build an accurate and easy-to-use nomogram for predicting CLNM. • The thyroid tumor and cervical lymph node ultrasound model exhibited better performance for predicting the CLNM of different PTC tumor sizes. It may serve as a useful clinical tool to provide valuable information for active surveillance and treatment decisions.

Ultrasound assessment of bladder descent and its correlation with prolapse severity in Chinese women: a prospective multicenter study.

INTRODUCTION AND HYPOTHESIS: Translabial ultrasound is currently regarded as one of the most promising modalities in the evaluation of female pelvic organ prolapse. However, abnormal bladder descent on pelvic floor ultrasound has not been established among Chinese women. This study aimed to establish optimal cutoffs for defining bladder prolapse among Chinese women using translabial ultrasound. METHODS: In this prospective multicenter study, 674 women with symptoms of lower urinary tract dysfunction and/or pelvic floor dysfunction were finally included and underwent interview, Pelvic Organ Prolapse Quantification (POP-Q) examinations and 4D translabial ultrasound. The receiver-operating characteristic (ROC) statistic was used to assess accuracy and define the optimal cutoffs. RESULTS: The mean patient age was 42.6 (range, 19-82) years. Multivariable analysis showed that both POP-Q assessment and translabial ultrasound findings for anterior compartment were significantly associated with prolapse symptoms. The ROC statistics suggested an optimal cutoff value of 10 mm below the symphysis pubis of bladder position on Valsalva for predicting prolapse symptoms, with an area under the curve (AUC) of 0.73. Compared to translabial ultrasound, POP-Q stage showed similar accuracy for predicting prolapse symptoms (AUC: 0.74; P = 0.79), with an optimal cutoff of POP-Q stage ≥ 2. CONCLUSIONS: This study proposed that the descent of the bladder to ≥ 10 mm below the symphysis pubis on Valsalva should be proposed as an optimal cutoff value for defining abnormal bladder prolapse on translabial ultrasound among the Chinese population. These cutoff values are nearly identical to those previously established in mainly Caucasian women.

Two-dimensional speckle tracking echocardiography in assessing the subclinical myocardial dysfunction in patients with gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) may increase the risk of cardiovascular disease and accompany asymptomatic deterioration of the myocardial function. This study aims to identify the subclinical impact of GDM on maternal left ventricular function by two-dimensional speckle tracking echocardiography (2D-STE). METHODS: We prospectively recruited 47 women with GDM and 62 healthy pregnant women who underwent transthoracic echocardiography (TTE) at 24 to 28 weeks of pregnancy. GDM diagnosis agreed with the IADPSG criteria. TTE was performed according to the criteria of the American Society of Echocardiography. Conventional echocardiographic data and 2D-STE parameters were compared between the two groups. RESULTS: Age, gestational weeks, heart rate, and conventional echocardiographic parameters had no difference between the two groups. The average LV global longitudinal strain (LV-GLS) of GDM patients was lower than controls (18.14 ± 2.53 vs. 22.36 ± 6.33, p < 0.001), and 31 patients (66%) in our study had an absolute LV-GLS less than 20%. The LA reservoir and conduit strain in patients with GDM were also significantly reduced (32.71 ± 6.64 vs. 38.00 ± 7.06, 20.41 ± 5.69 vs. 25.56 ± 5.73, p < 0.001). However, there was no significant difference in LA contractile function between the two groups. In multiple regression analysis, LV-GLS and LA conduit strain independently associated with GDM. CONCLUSIONS: 2D-STE could detect the subclinical myocardial dysfunction more sensitively than conventional echocardiography, with LV-GLS and LA conduit strain as independent indicators of the GDM impact on maternal cardiac function during pregnancy.

Establishment and Validation of a Predictive Model for Long-Term Severe Functional Tricuspid Regurgitation after Mitral Valve Replacement.

BACKGROUND: The objective was to develop and validate an individualized nomogram to predict severe functional tricuspid regurgitation (S-FTR) after mitral valve replacement (MVR) via retrospective analysis of rheumatic heart disease (RHD) patients' pre-clinical characteristics. METHODS: Between 2001-2015, 442 MVR patients of RHD were examined. Transthoracic echocardiography detected S-FTR, and logistic regression model analyzed its independent predictors. R software established a nomogram prediction model, and Bootstrap determined its theoretical probability, which subsequently was compared with the actual patient probability to calculate the area under the curve (AUC) and calibration plots. Decision curve analysis (DCA) identified its clinical utility. RESULTS: Ninety-six patients developed S-FTR during the follow-up period. Both uni- and multivariate analyses found significant correlations between S-FTR occurrence with gender, age, atrial fibrillation (AF), pulmonary arterial hypertension (PH), left atrial diameter (LAD), and tricuspid regurgitation area (TRA). The individualized nomogram model had the AUC of 0.99 in internal verification. Calibration test indicated high agreement of predicted and actual S-FTR onset. DCA also showed that utilization of those six aforementioned factors was clinically useful. CONCLUSION: The nomogram for the patient characteristics of age, gender, AF, PH, LAD, and TRA found that they were highly predictive for future S-FTR onset within 5 years. This predictive ability therefore allows clinicians to optimize postoperative patient care and avoid unnecessary tricuspid valve surgeries.

Low-Dose CT Image Post-Processing Based on Learn-Type Sparse Transform.

As a detection method, X-ray Computed Tomography (CT) technology has the advantages of clear imaging, short detection time, and low detection cost. This makes it more widely used in clinical disease screening, detection, and disease tracking. This study exploits the ability of sparse representation to learn sparse transformations of information and combines it with image decomposition theory. The structural information of low-dose CT images is separated from noise and artifact information, and the sparse expression of sparse transformation is used to improve the imaging effect. In this paper, two different learned sparse transformations are used. The first covers more organizational information about the scanned object. The other can cover more noise artifacts. Both methods can improve the ability to learn sparse transformations to express various image information. Experimental results show that the algorithm is effective.

Association between VEGF single nucleotide polymorphism and breast cancer in the Northern China Han population.

PURPOSE: To investigate the associations of four commonly studied single nucleotide polymorphisms (SNP) of the vascular endothelial growth factor (VEGF), including -460T/C (rs833061), - 634G/C (rs2010963), - 2578C/A (rs699947), and +936T/C (rs3025039), with the incidence, aggressiveness, and tumor markers expression of breast cancer in the Northern China Han population. METHODS: Followed the genomic DNA extraction, a total of 259 patients with breast cancer (case group) and 273 healthy women (control group) underwent genotyping by PCR-LDR SNP assays. The associations between VEGF gene polymorphisms and the incidence, aggressiveness, and tumor markers expression of breast cancer were analyzed. RESULTS: Significant differences were observed in allele frequency and genotype distribution of - 634G/C between breast cancer cases and healthy controls (p = 0.006, 0.013). Individuals who carry the G allele more likely had a lower risk of breast cancer (OR, 0.866, 95% CI 0.782-0.959). Compared with CC genotype carriers, women who had the CG and GG genotypes demonstrated a relatively lower risk (OR, 0.860, 95% CI 0.757-0.978, p = 0.022; OR, 0.778, 95% CI, 0.656-0.924, p = 0.004, respectively). When we stratified the group of patients according to the status of tumor markers, a significant association of - 634G/C SNP and Ki-67 expression was observed. The CC genotype carriers were more likely to be characterized by high expression of Ki-67 (p = 0.031). Further analysis showed that the - 460T/-634C/-2578C/+936C haplotype was more associated with a higher risk of breast cancer (OR, 1.445, 95% CI 1.123-1.859, p = 0.004), whereas the - 460T/- 634G/- 2578C/+936C one was associated with a lower risk (OR, 0.736, 95% CI 0.563-0.963, p = 0.025). CONCLUSIONS: In the present study, we concluded that VEGF gene - 634G/C polymorphism is related to the incidence of breast cancer in the Han population in Northern China and also might be associated with tumor proliferation index Ki-67.

Concise Synthesis of Chromene/Chromane-Type Aryne Precursors and Their Applications.

The gram-scale synthesis of 5,6-, 6,7-, and 7,8-chromene/chromane-type aryne precursors and their applications in regioselective transformation to other functional derivatives is reported. Chromene/chromane-type arynes are generated under mild conditions, which can further undergo [2 + 2], [3 + 2], and [4 + 2] cycloaddition reactions, nucleophilic addition reactions, and σ-insertion reactions to produce structurally novel substituted chromenes and chromanes. The excellent regioselectivity of the reaction is facilitated by the oxygen-containing guiding groups at the ortho-position of the triple bond, which can be removed or switched to other functional groups including alkenyl, aryl, heteroaryl, and arylamino groups.