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Background: Breast cancer is a significant health issue affecting women worldwide, including Malaysia, where the incidence of breast cancer is increasing. Early detection of breast cancer plays a crucial role in improving treatment outcomes and reducing mortality rates. Aims and Objectives: This study examines the impact of adjunctive breast ultrasound (BUS) on screening for Malaysian women, offering evidence to enhance future protocols and decisions in the early detection. Materials and Methods: This study involved 5807 women aged 40 and above undergoing breast screening at Beacon Hospital from January to December 2022. Data collected included mammography and BUS results, categorized by breast imaging reporting and data system (BI-RADS) and diagnostic criteria. Suspicious cases on both modalities had histopathology examination (HPE) for confirmation. A subset of 1690 cases underwent both mammography and BUS screening and was compared to those who only had mammography using BI-RADS scores. Results: This study revealed that the majority of mammograms, 94.69% (5499 cases), were categorized as BI-RADS category 0, 1, 2, and 3, while 5.3% (307 cases) were classified as BI-RADS 4 and 5. Among the cases that underwent ultrasound (1688 cases), 23.43% of them were categorized as BI-RADS 4–5. Using ultrasound in addition to mammography increased the number of cases (BI-RADS 4–5) by 33.48%, resulting in a total of 460 cases identified compared to 307 cases, detected by mammography alone. Significantly, 39% (74 cases) of the 190 cases with confirmed malignancies (BI-RADS 6) by HPE were initially classified as negative mammography (BI-RADS 0–3) but were later identified as BI-RADS 5 on ultrasound. Conclusion: Ultrasound as a supplementary screening method holds the potential for boosting breast cancer detection sensitivity and reducing false negatives, thereby aiding in early detection and better treatment outcomes.

Abstract Background Macrophage-like transformation of vascular smooth muscle cells (VSMCs) is a risk factor of atherosclerosis (AS) progression. Transcription factor homeobox A1 (HOXA1) plays functional roles in differentiation and development. This study aims to explore the role of HOXA1 in VSMC transformation, thereby providing evidence for the potential mechanism of AS pathogenesis. Methods High fat diet (HFD)-fed apolipoprotein E knockout (ApoE−/−) mice were applied as an in vivo model to imitate AS, while 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POV-PC)-treated VSMCs were applied as an in vitro model. Recombinant adeno-associated-virus-1 (AAV-1) vectors that express short-hairpin RNAs targeting HOXA1, herein referred as AAV1-shHOXA1, were generated for the loss-of-function experiments throughout the study. Results In the aortic root of AS mice, lipid deposition was severer and HOXA1 expression was higher than the wide-type mice fed with normal diet or HFD. Silencing of HOXA1 inhibited the AS-induced weight gain, inflammatory response, serum and liver lipid metabolism disorder and atherosclerotic plaque formation. Besides, lesions from AS mice with HOXA1 knockdown showed less trans-differentiation of VSMCs to macrophage-like cells, along with a suppression of krüppel-like factor 4 (KLF4) and nuclear factor (NF)-κB RelA (p65) expression. In vitro experiments consistently confirmed that HOXA1 knockdown suppressed lipid accumulation, VSMC-to-macrophage phenotypic switch and inflammation in POV-PC-treated VSMCs. Mechanism investigations further illustrated that HOXA1 transcriptionally activated RelA and KLF4 to participate in the pathological manifestations of VSMCs. Conclusions HOXA1 participates in AS progression by regulating VSMCs plasticity via regulation of NF-κB p65 and KLF4. HOXA1 has the potential to be a biomarker or therapeutic target for AS.

Mounting evidences indicate that circular RNAs (circRNAs) play vital roles in the development and progression of various cancers. However, the detailed functions and underlying mechanisms of circRNAs in hepatocellular carcinoma (HCC) remain largely unknown. The expression profile of circRNAs was screened by circRNA microarrays. Quantitative real-time PCR was used to determine the level-10 circRNAs selected from the top five upregulated (hsa_circ_0001955, hsa_circ_0001535, hsa_circ_0061395, hsa_circ_0000502, and hsa_circ_0066659) and top five downregulated circRNAs (hsa_circ_0046366, hsa_circ_0003418, hsa_circ_0026134, hsa_circ_0005692, and hsa_circ_0014130). The effects of circTMEM45A in HCC cells were studied both in vitro (in a Cell Counting Kit-8 assay, apoptosis analysis, and cell cycle assays) and in vivo (by means of tumor xenografts in nude mice). Luciferase reporter, RNA immunoprecipitation (RIP), and rescued assays were used to confirm the interactions between circTMEM45A, miR-665, and insulin growth factor 2 (IGF2). We found that the level of circTMEM45A was significantly upregulated in HCC and was positively correlated with clinicopathological features and poor prognosis of patients with HCC. Functionally, circTMEM45A promoted cell mobility in vitro, as well as in vivo tumorigenesis. Mechanistically, circTMEM45A acted as a miR-65 sponge to relieve the repressive effect of miR-665 on its target IGF2. Moreover, circTMEM45A was upregulated in serum exosomes from HCC patients. circTMEM45A promotes HCC progression through the miR-665/IGF2 axis and may serve as a novel diagnostic marker and target for treatment of HCC patients.

Introduction: Coronary artery disease originates from the blockage of the inner walls of the coronary arteries due to a plaque buildup. Accumulating studies have highlighted the role of microRNAs (miRs) delivered by exosomes in the progression of coronary artery disease. Thus, the current study was to elucidate the role and mechanism by which miR-25-3p influences oxidized low density lipoprotein (ox-LDL)-induced coronary vascular endothelial cell (CVEC) inflammation.Methods: Primarily isolated CVECs were treated with ox-LDL to induce inflammation. Atherosclerosis models were induced in ApoE−/− mice and the peripheral blood platelet exosomes (PLT-Exo) were extracted and induced by thrombin, followed by co-culture with CVECs. The relationship between miR-25-3p and A disintegrin and metalloprotease 10 (Adam10) as well as the involvement of the NF-κB signaling pathway was evaluated. In order to evaluate the effect of PLT-Exo containing miR-25-3p on ox-LDL-induced CVEC inflammation, lipid accumulation and fibrosis, miR-25-3p mimic/inhibitor (in vitro), miR-25-3p agomir (in vivo), and si-Adam10 were delivered.Results: MiR-25-3p was expressed poorly in ox-LDL-induced CVECs and vascular tissues but exhibited high levels of expression in thrombin-induced PLT-Exo of atherosclerosis models of ApoE−/− mice. CVECs endocytosed PLT-Exo upregulated the miR-25-3p expression. Adam10 was identified as a target gene of miR-25-3p. The thrombin-induced activated PLT-Exo carrying miR-25-3p reduced Adam10 expression to inhibit ox-LDL-induced CVEC inflammation and lipid deposition through downregulating levels of α-smooth muscle actin, Collagen I a1, Collagen III a1, triglycerides, total cholesterol, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. Furthermore, the NF-κB signaling pathway participated in the inhibitory effect of PLT-Exo carrying miR-25-3p.Conclusion: Collectively, PLT-Exo overexpressing miR-25-3p attenuates ox-LDL-induced CVEC inflammation in ApoE−/− mouse models of atherosclerosis.

Objective To analyze the high risk factors of obstetric brachial plexus palsy （OBPP）, and to explore how to evaluate the relationship between fault medical behavior and OBPP in the process of medical damage forensic identification. Methods A retrospective analysis was carried out on 25 cases of medical damage liability disputes related to OBPP from 2017 to 2021 in Beijing Fayuan Judicial Science Evidence Appraisal Center. The shortcomings of hospitals in birth weight assessment, delivery mode selection, labor process observation and shoulder dystocia management, and the causal relationship between them and the damage consequences of the children were summarized. Results Fault medical behavior was assessed as the primary cause in 2 cases, equal cause in 10 cases， secondary cause in 8 cases, minor cause in 1 case, no causal relationship in 1 case, and unclear causal force in 3 cases. Conclusion In the process of forensic identification of OBPP, whether medical behaviors fulfill diagnosis and treatment obligations should be objectively analyzed from the aspects of prenatal evaluation, delivery mode notification, standardized use of oxytocin, standard operation of shoulder dystocia, etc. Meanwhile, it is necessary to fully consider the objective risk of different risk factors and the difficulty of injury prevention, and comprehensively evaluate the causal force of fault medical behavior in the damage consequences.

We investigate the "roughness" of the energy landscape of a system that diffuses in a heterogeneous medium with a random position-dependent friction coefficient α(x). This random friction acting on the system stems from spatial inhomogeneity in the surrounding medium and is modeled using the generalized Caldira–Leggett model. For a weakly disordered medium exhibiting a Gaussian random diffusivity D(x) = kBT/α(x) characterized by its average value ⟨D(x)⟩ and a pair-correlation function ⟨D(x1)D(x2)⟩, we find that the renormalized intrinsic diffusion coefficient is lower than the average one due to the fluctuations in diffusivity. The induced weak internal friction leads to increased roughness in the energy landscape. When applying this idea to diffusive motion in liquid water, the dissociation energy for a hydrogen bond gradually approaches experimental findings as fluctuation parameters increase. Conversely, for a strongly disordered medium (i.e., ultrafast-folding proteins), the energy landscape ranges from a few to a few kcal/mol, depending on the strength of the disorder. By fitting protein folding dynamics to the escape process from a metastable potential, the decreased escape rate conceptualizes the role of strong internal friction. Studying the energy landscape in complex systems is helpful because it has implications for the dynamics of biological, soft, and active matter systems. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is a significant health issue affecting women worldwide, including Malaysia, where the incidence of breast cancer is increasing. Early detection of breast cancer plays a crucial role in improving treatment outcomes and reducing mortality rates. Aims and Objectives: This study examines the impact of adjunctive breast ultrasound (BUS) on screening for Malaysian women, offering evidence to enhance future protocols and decisions in the early detection. Materials and Methods: This study involved 5807 women aged 40 and above undergoing breast screening at Beacon Hospital from January to December 2022. Data collected included mammography and BUS results, categorized by breast imaging reporting and data system (BI-RADS) and diagnostic criteria. Suspicious cases on both modalities had histopathology examination (HPE) for confirmation. A subset of 1690 cases underwent both mammography and BUS screening and was compared to those who only had mammography using BI-RADS scores. Results: This study revealed that the majority of mammograms, 94.69% (5499 cases), were categorized as BI-RADS category 0, 1, 2, and 3, while 5.3% (307 cases) were classified as BI-RADS 4 and 5. Among the cases that underwent ultrasound (1688 cases), 23.43% of them were categorized as BI-RADS 4-5. Using ultrasound in addition to mammography increased the number of cases (BI-RADS 4-5) by 33.48%, resulting in a total of 460 cases identified compared to 307 cases, detected by mammography alone. Significantly, 39% (74 cases) of the 190 cases with confirmed malignancies (BI-RADS 6) by HPE were initially classified as negative mammography (BI-RADS 0-3) but were later identified as BI-RADS 5 on ultrasound. Conclusion: Ultrasound as a supplementary screening method holds the potential for boosting breast cancer detection sensitivity and reducing false negatives, thereby aiding in early detection and better treatment outcomes. [ABSTRACT FROM AUTHOR]