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Peter Grzesik, June K Wu Department of Surgery, Columbia University College of Physicians and Surgeons, New York, NY, USA Abstract: Infantile hemangiomas (IHs) are the most common benign tumor of infancy. As our understanding of their pathobiology has evolved, treatment has become more focused and tailored to specifically treat IH while minimizing adverse effects. Propranolol has gained FDA approval as the first medical therapy for a traditionally surgical disease. This review provides readers with an overview of IH, treatment modalities, and addresses specific considerations in IH disease management. Keywords: infantile hemangioma, medical treatment indications, propranolol, complications of infantile hemangioma

Aihong Meng,1 Xiaopeng Zhang,2 Siyu Wu,1 Mingxia Wu,1 Jing Li,1 Xixin Yan,1 Kamilla Kopec-Harding,3 Jiakai Wu41Respiratory Division, The Second Hospital of Hebei Medical University, 2Department of Thoracic Surgery, Hebei Province General Hospital, Shijiazhuang, Hebei, Peoples’ Republic of China; 3Centre for Musculoskeletal Research, 4Centre for Respiratory and Allergy, Institute of Inflammation and Repair, University of Manchester, Manchester, UKBackground: Systemic inflammation and steroid resistance are the hallmarks of COPD. We examined the impact of p38 inhibitor (SB203580) in in vitro assays of systemic inflammation using pulmonary cells and patients’ sera.Objective and methods: Data from 66 COPD patients and 15 age-/sex-matched healthy controls were compared. Interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and CCL5 were measured in serum samples and culture media from peripheral blood mononuclear cells. The impact of sera on IL-10 and CCL5 expression in alveolar macrophage cell line (MH-S) was examined. The in vitro effects of SB203580 on lipopolysaccharide-induced inflammation were investigated.Results: Peripheral blood mononuclear cells from Global Initiative for Chronic Obstructive Lung Disease (GOLD) D patients produced more CCL5 and TNF-α, and less IL-10 compared to GOLD A–C patients. SB203580 treatment suppressed CCL5 and TNF-α and stimulated IL-10 production; however, the effect of SB203580 on IL-10 was lower in the COPD group. Culture of MH-S cells with COPD serum showed a significant increase in CCL5 and a significant decrease in IL-10 compared to healthy serum. This effect was not suppressed with SB203580 treatment.Conclusion: COPD serum has a potent proinflammatory effect on pulmonary cells. Inhibition of p38 phoshorylation had a limited effect in restoring impaired lymphocyte function and suppressing inflammation induced by COPD serum, implying important p38-independent inflammatory mechanisms in COPD. Keywords: COPD, p38MAPK inhibitor, macrophage, CCL5, TNF-α, IL-10

Here, we employed a fluorescence-based single molecule method called nuclease-induced stepwise photodropping (NISP) to measure in real time the DNA degradation mediated by mitochondrial genome maintenance exonuclease 1 (MGME1), a bidirectional single-stranded DNA (ssDNA)-specific exonuclease. The method detects a stepwise decrease in fluorescence signals from Cy3 fluorophores labeled on an immobilized DNA substrate. Using NISP, we successfully determined the DNA degradation rates of 6.3 ± 0.4 and 2.0 ± 0.1 nucleotides (nt) s-1 for MGME1 in the 5'-to-3' and 3'-to-5' directions, respectively. These results provide direct evidence of the stronger 5' directionality of MGME1, consistent with its established role in mitochondrial DNA maintenance. Importantly, when we employed NISP to investigate mung bean nuclease, an ss-specific endonuclease, we observed a markedly different NISP pattern, suggesting a distributive cleavage activity of the enzyme. Furthermore, we applied NISP to determine the ssDNA degradation behavior of the double-stranded-specific exonuclease, λ exonuclease. These findings underscore the capability of NISP to accurately and reliably measure the degradation of ssDNA by both exo- and endonucleases. Here, we demonstrate NISP as a powerful tool for investigating the ssDNA degradation behavior of nucleases at the single-molecule level., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Microwave gas sensors have garnered attention for their high sensitivity and selectivity in the detection of volatile organic compounds (VOCs). However, traditional gas sensors generally rely on sensitive materials that degrade over time and are easily affected by the environment, compromising their stability and accuracy. This study proposes a microwave VOC gas sensor based on the condensation effect. The sensor adopts a novel design without sensitive materials, utilizing the condensation effect to detect acetone gas. The sensor system consists of a microwave sensor and a temperature control device. As the sensor temperature is lowered below the boiling point of acetone, the condensation of acetone gas on the sensor surface is achieved, enabling accurate detection of acetone gas. Experimental results indicate that the accumulated amount of acetone on the sensor surface is positively correlated with its response, with the maximum response of 3000 ppm acetone gas reaching 0.34 dB. Additionally, this study investigated the detection mechanism of the sensor after adding the sensitive material MXene and compared the performance of the sensor at different temperatures (-10 °C, 0 °C, and 60 °C). The results show that at -10 °C the sensor mainly captures acetone through physical adsorption, while at 25 and 60 °C, it primarily responds through chemical adsorption, with a maximum response of 0.29 dB. The VOC sensor based on the condensation effect without sensitive materials not only achieves the same sensitivity as traditional microwave sensors but also demonstrates stronger stability and anti-interference capabilities.

Background: Most breast cancer-related deaths are caused by distant metastases and drug resistance. It is important to find appropriate biomarkers to monitor the disease and to predict patient responses after treatment early and accurately. Many studies have found that clustered circulating tumor cells, with more correlations with metastatic cancer and poor survival of patients than individual ones, are promising biomarkers., Methods: Eighty samples from eleven patients with breast cancer during follow-up visits were examined. By using a microfluidic chip and imaging system, the number of circulating tumor cells and microemboli (CTC/CTM) were counted to assess the distribution in stratified patients and the potential in predicting the disease condition of patients after treatments during follow-up visits. Specific components and subtypes of CTM were also preliminarily investigated., Results: Compared to CTC, CTM displayed a distinguishable distribution in stratified patients, having a better AUC value, in predicting the disease progression of breast cancer patients during follow-up visits in this study. Four subtypes were categorized from the identified CTM by considering different components. In combination with CEA and CA153, enumerated CTC and CTM from individual patients were applied to monitor the disease condition and patient response to the therapy during follow-up visits., Conclusions: The CTM and its subtypes are promising biomarkers and valuable tools for studying cancer metastasis and longitudinally monitoring cancer patients during follow-up visits.

Abstract: Quercetin is known for its antihypertensive effects. However, its role on hypertensive renal injury has not been fully elucidated. In this study, hematoxylin and eosin staining, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining, and Annexin V staining were used to assess the pathological changes and cell apoptosis in the renal tissues of angiotensin II (Ang II)-infused mice and Ang II-stimulated renal tubular epithelial cell line (NRK-52E). A variety of technologies, including network pharmacology, RNA-sequencing, immunohistochemistry, and Western blotting, were performed to investigate its underlying mechanisms. Network pharmacology analysis identified multiple potential candidate targets (including TP53, Bcl-2, and Bax) and enriched signaling pathways (including apoptosis and p53 signaling pathway). Quercetin treatment significantly alleviated the pathological changes in renal tissues of Ang II-infused mice and reversed 464 differentially expressed transcripts, as well as enriched several signaling pathways, including those related apoptosis and p53 pathway. Furthermore, quercetin treatment significantly inhibited the cell apoptosis in renal tissues of Ang II-infused mice and Ang II-stimulated NRK-52E cells. In addition, quercetin treatment inhibited the upregulation of p53, Bax, cleaved-caspase-9, and cleaved-caspase-3 protein expression and the downregulation of Bcl-2 protein expression in both renal tissue of Ang II-infused mice and Ang II-stimulated NRK-52E cells. Moreover, the molecular docking results indicated a potential binding interaction between quercetin and TP53. Quercetin treatment significantly attenuated hypertensive renal injury and cell apoptosis in renal tissues of Ang II-infused mice and Ang II-stimulated NRK-52E cells and by targeting p53 may be one of the potential underlying mechanisms., Competing Interests: The authors reports no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The protein-induced fluorescence change technique was employed to investigate the interactions between proteins and their DNA substrates modified with the Cy3 fluorophore. It has been reported that the human hepatoma-derived growth factor (HDGF), containing the chromatin-associated N-terminal proline-tryptophan-tryptophan-proline (PWWP) domain (the N-terminal 100 amino acids of HDGF) capable of binding the SMYD1 promoter, participates in various cellular processes and is involved in human cancer. This project investigated the specific binding behavior of HDGF, the PWWP domain, and the C140 domain (the C-terminal 140 amino acids of HDGF) sequentially using protein-induced fluorescence change. We found that the binding of HDGF and its related proteins on Cy3-labeled 15 bp SMYD1 dsDNA will cause a significant decrease in the recorded Cy3 fluorophore intensity, indicating the occurrence of protein-induced fluorescence quenching. The dissociation equilibrium constant was determined by fitting the bound fraction curve to a binding model. An approximate 10-time weaker SMYD1 binding affinity of the PWWP domain was found in comparison to HDGF. Moreover, the PWWP domain is required for DNA binding, and the C140 domain can enhance the DNA binding affinity. Furthermore, we found that the C140 domain can regulate the sequence-specific binding capability of HDGF on SMYD1 .

Background: Hyponatremia is a common complication following endoscopic endonasal resection (EER) of pituitary adenomas. We report a single-center, multisurgeon study detailing baseline clinical data, outcomes, and factors associated with postoperative hyponatremia., Methods: This was a retrospective cohort study of patients undergoing EER for pituitary adenoma at Tufts Medical Center. Most procedures were performed by the senior author (C.B.H.). Cases were included if at least 1 postoperative sodium value was available and pathology confirmed pituitary adenoma. Hyponatremia was defined as a postoperative sodium level <135 mEq/L., Results: A total of 272 patients underwent 310 EER procedures that met the study inclusion criteria. The mean patient age was 53.3 years, and mean tumor size was 18.8 mm. Postoperative hyponatremia occurred in 12.6% of cases, with 3.6% developing hyponatremia prior to discharge. Lower preoperative sodium level was associated with an increased risk of developing any postoperative hyponatremia. Older age, prolactinoma pathology, and use of selective serotonin reuptake inhibitors were associated with moderate to severe hyponatremia (≤129 mEq/L), and lower preoperative sodium was associated with mild hyponatremia (130-134 mEq/L). Hyponatremia-related readmissions within 30 days occurred in 3.9% of patients. Both African-American race and postoperative hyponatremia were associated with an increased risk of 30-day readmission. The mean nadir sodium for hyponatremic patients was 129.9 mEq/L. Growth hormone-secreting pathology was associated with lower postoperative nadir sodium, whereas higher preoperative sodium was associated with higher postoperative nadir sodium., Conclusions: Hyponatremia is a common postoperative complication of EER for pituitary lesions that can cause significant morbidity, increased readmissions, and increased healthcare costs., (Copyright © 2024 Elsevier Inc. All rights reserved.)

A pilot randomized controlled trial was conducted to examine the effectiveness of a storybook package for enhancing the perceived knowledge and confidence of health and social care professionals in working with bereaved child siblings and their parents before and after the loss. Open-ended questions were asked to collect feedback, and thematic analyses were conducted to generate the themes. Quantitative findings provided preliminary but not strong evidence of its effectiveness, but qualitative findings showed that participants perceived their knowledge about supporting bereaved siblings and their parents was enhanced and considered the storybook package a useful tool for facilitating their practice. Participants also reflected on how real and specific the stories in the storybook should be. This study is the first step in developing an evidence-based practice tool for health and social care professionals. Future studies are required to further examine its effectiveness for practice.

Background: Infantile hemangiomas (IHs) are benign endothelial cell (EC) tumors that undergo a predictable natural history, with rapid proliferation, stabilization, and involution. However, mechanisms regulating these transitions are not well understood. We have observed loss of vascular endothelial cadherin (VECAD) in involuting/involuted IHs. VECAD plays a critical role in angiogenesis, cell cycle progression, and EC survival. We hypothesize that loss of VECAD is associated with apoptosis occurring during IH involution., Methods: Resected IH samples were clinically categorized as proliferating (n = 4), stable (n = 4), or involuting/involuted (n = 5). Neonatal dermal tissues were used as controls (n = 5). Immunohistochemistry was conducted on sectioned specimens using antibodies against EC markers VECAD and CD31. Apoptosis was assessed with terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay., Results: CD31 signal intensity in proliferating, stable, and involuting/involuted IH ECs was unchanged relative to each other and to control ECs. VECAD signal significantly and progressively diminished as IHs progressed from proliferation to involution. Involuting/involuted IHs had significantly reduced VECAD expression compared with control ECs ( P < 0.0001), proliferating IHs ( P < 0.0001), and stable IHs ( P < 0.001). As expected, the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling-positive ECs was significantly higher in involuting/involuted IHs ( P < 0.05) relative to control ECs and proliferating IHs., Conclusions: Loss of VECAD expression in IH endothelium corresponded to IH involution and increased apoptosis. It is unclear whether loss of VECAD is causative of IH involution; further studies are needed to elucidate the role of VECAD function in EC survival., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Background: Multiple studies have shown that skeletal muscle index (SMI) measured on abdominal computed tomography (CT) is strongly associated with bone mineral density (BMD) and fracture risk as estimated by the fracture risk assessment tool (FRAX). Although some studies have reported that SMI at the level of the 12th thoracic vertebra (T12) measured on chest CT images can be used to diagnose sarcopenia, it is regrettable that no studies have investigated the relationship between SMI at T12 level and BMD or fracture risk. Therefore, we further investigated the relationship between SMI at T12 level and FRAX-estimated BMD and fracture risk in this study., Methods: A total of 349 subjects were included in this study. After 1∶1 propensity score matching (PSM) on height, weight, hypertension, diabetes, hyperlipidemia, hyperuricemia, body mass index (BMI), age, and gender, 162 subjects were finally included. The SMI, BMD, and FRAX score of the 162 participants were obtained. The correlation between SMI and BMD, as well as SMI and FRAX, was assessed using Spearman rank correlation. Additionally, the effectiveness of each index in predicting osteoporosis was evaluated through the receiver operating characteristic (ROC) curve analysis., Results: The BMD of the lumbar spine (L1-4) demonstrated a strong correlation with SMI ( r  = 0.416, p  < 0.001), while the BMD of the femoral neck (FN) also exhibited a correlation with SMI ( r  = 0.307, p  < 0.001). SMI was significantly correlated with FRAX, both without and with BMD at the FN, for major osteoporotic fractures ( r  = -0.416, p  < 0.001, and r  = -0.431, p  < 0.001, respectively) and hip fractures ( r  = -0.357, p  < 0.001, and r  = -0.311, p  < 0.001, respectively). Moreover, the SMI of the non-osteoporosis group was significantly higher than that of the osteoporosis group ( p  < 0.001). SMI effectively predicts osteoporosis, with an area under the curve of 0.834 (95% confidence interval 0.771-0.897, p  < 0.001)., Conclusion: SMI based on CT images of the 12th thoracic vertebrae can effectively diagnose osteoporosis and predict fracture risk. Therefore, SMI can make secondary use of chest CT to screen people who are prone to osteoporosis and fracture, and carry out timely medical intervention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hu, Jin, Wu and Ni.)

Background: Recent trials have demonstrated clinical benefits to a combined orthoplastic approach for complex reconstructive surgery of the hand, upper and lower extremity., Purpose: We sought to assess recent trends in exposure to orthoplastic-type procedures among plastic surgery residents training in the United States., Methods: Independent plastic surgery residents' case logs were extracted from the Accreditation Council for Graduate Medical Education (2011-2022). Select reconstructive procedure were taken as proxies for orthoplastic-type cases and analyzed by descriptive statistical analysis., Results: The average number of orthoplastic-type cases completed per resident per year increased from 168.2 to 189.2 (12.5% increase) between 2011-2022. The greatest increase was in exposure to peripheral nerve injury repair of the hand and upper extremity (22.6 to 39.1, 73% increase). As a proportion of total procedures during the study period, orthoplastic-type procedures remained relatively unchanged (range 9.5-10.4%)., Conclusions: Our findings suggest that plastic surgery residents may be increasingly well-prepared to contribute to orthoplastic care during and following their training. The steady proportion of cases that orthoplastic-type procedures represented over the study period suggests the increase in relevant orthoplastic case volume may be incidental and secondary to an overall rise among all procedures. Given evidence of the benefits of an orthoplastic approach, we recommend consideration of explicit benchmarks for orthoplastic training among plastic surgery residents., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Objective: Radiofrequency ablation is a viable option in the treatment of benign thyroid nodules. Some reports suggest that thermal ablation may also be safe for the management of low-risk thyroid cancer. In this study, we applied transient heat treatment to thyroid cancer cells to mimic clinical scenarios in which insufficient ablation leads to incomplete eradication of thyroid cancer., Methods: Differentiated thyroid cancer cell lines B-CPAP, TPC-1, and FTC-133 were subjected to heat treatment at different temperatures for 10 min. Effects on cell growth, clonogenicity, wound healing assay, and Transwell invasion were determined., Results: Heat treatment at 45°C or higher reduced cell growth, whereas viability of thyroid cancer cells was not changed after heat treatment at 37, 40, or 42°C. Heat treatment at 40°C increased the number of colony formations by 16% to 39%. Additionally, transient heat treatment at 40°C resulted in a 1.75-fold to 2.56-fold higher migratory activity than treatment at 37°C. Invasive capacity was increased after heat treatment, ranging from 115% to 126%. Expression of several epithelial-mesenchymal transition markers, including ZEB1, N-cadherin, and MMP2, was upregulated following heat treatment at 40°C., Conclusion: We for the first time demonstrate that sublethal thermal stress may increase clonogenicity, migration, and invasion of thyroid cancer cells., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kuo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The use of magnetic resonance linear accelerators (MR-LINACs) for clinical treatment has opened up new possibilities and challenges in the field of radiation oncology. However, annual quality assurance (QA) is relatively understudied due to practical considerations. Thus, to overcome the difficulty of measuring the dose with a small water phantom for TRS-398 or TG-51 in all external beam radiation treatment unit environments, such as MR compatibility, we designed a remote phantom with a three-axis changeable capacity for QA., Methods: The designed water phantom was tested under an MR environment. The water phantom system comprised of three parts: a phantom box, a dose measurement tool, and a PMD401 drive system. The UNIDOSE universal dosimeter was used to collect beam data. The manufacturer's developer tools were utilized to position the measurement. To ensure magnetic field homogeneity, a distortion phantom was prepared using sixty fish oil capsules aligned radially to distinguish the oil and free air. The phantom was scanned in both the MR simulator and computed tomography (CT), and the acquired images were analyzed to determine the position shift., Results: The dimensions of the device are 30 cm in the X-axis, 20 cm in the Y-axis, and 17 cm in the Z-axis. Total cost of materials was no more than $10,000 US dollars. Our results indicate that the device can function normally in a regular 1.5 T MR environment without interference from the magnetic field. The water phantom's traveling speed was found to be approximately 5 mm/s with a position difference confined within 6 cm intervals during normal use. The distortion test results showed that the prepared MR environment has uniform magnetic field homogeneity., Conclusions: In this study, we constructed a prototype water phantom device that can function in an MR simulator without interference between the magnetic field and electronic components. Compared to other commercially available MR-LINAC water phantoms, our device offers a more cost-effective solution for routine monthly QA. It can shorten the duration of QA tests and relieve the burden on medical physicists., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-189/coif). The authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Micro/nanomotors (MNMs) emerge as a vital candidate for biosensing due to its nano-size structure, high surface-to-area ratio, directional mobility, biocompatibility, and ease of functionalization, therefore being able to detect objects with high efficiency, precision, and selectivity. The driving mode, nanostructure, materials property, preparation technique, and biosensing applications have been thoroughly discussed in publications. To promote the MNMs-based biosensors from in vitro to in vivo, it is necessary to give a comprehensive discussion from the perspective of sensing performances enhancement. However, until now, there is few reviews dedicated to the systematic discussion on the multiple performance enhancement schemes and the current challenges of MNMs-based biosensors. Bearing it in mind and based on our research experience in this field, we summarized the enhancement methods for biosensing properties such as sensitivity, selectivity, detection time, biocompatibility, simplify system operation, and environmental availability. We hope that this review provides the readers with fundamental understanding on performance enhancement schemes for MNMs-based biosensors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Vascular anomalies (VAs) are heterogeneous lesions. Symptoms vary widely by lesion type and complexity. VA patients often require life-long interdisciplinary care; however, there is a paucity of data on the healthcare utilization of VA patients, and their burden on the healthcare system remains largely unquantified. We hypothesize that healthcare utilization by complex lymphatic malformation (LM) and venous malformation (VM) patients will be significantly higher compared with simple LM and VM patients., Methods: A retrospective, longitudinal study was performed of LM/VM patients seen through multidisciplinary VA clinics between January 1, 2019 and December 31, 2020. Data were collected from each patient's first presentation through December 31, 2021 and included number of office visits, imaging studies, specialists involved, procedures, hospitalization data, and approximate costs, normalized to per year utilization. Patients were divided into "simple" and "complex" LMs/VMs. Involvement of the airway, more than one anatomic area, and/or complex lymphatic anomalies were defined as "complex.", Results: In total, 28 simple and 29 complex LM patients and 51 simple and 18 complex VM patients were identified. Complex LM and VM patients had significantly higher numbers of imaging studies, specialists involved, procedures and hospitalizations, and costs incurred. Complex LM patients also had significantly higher per year office visits., Conclusions: VA care is chronic and costly, especially for complex LM/VM patients. LM/VM complexity was a predictor for increased inpatient and outpatient healthcare utilization and higher costs. Better awareness of the healthcare utilization trends of LM/VM patients will allow for improved counseling for these patients regarding prognosis and expectations., Competing Interests: The authors have no financial interest to declare in relation to the content of this article. Disclosure statements are at the end of this article, following the correspondence information., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Quantum dots (QDs) have been widely used for bioimaging in vivo because of their excellent optical properties. As part of the preparation process of QD-based nanohybrids, purification is an important step for minimizing contaminants and improving the quality of the product. In this work, we describe high-performance size exclusion chromatography (HPSEC) used to purify nanohybrids of CdSe/ZnS QDs and anti-human epidermal growth factor receptor 2 antibodies (QD-HER2-Ab). The unbound antibody and suspended agglomerates were removed from freshly prepared QD-HER2-Ab via HPSEC. Pure and homogeneous QD-HER2-Ab were then used as immunofluorescence target imaging bioprobes in vivo. The QD-HER2-Ab did not cause any obvious acute toxicity in mice one week after a single intravenous injection of 15 nmol/kg. The purified QD-HER2-Ab bioprobes showed high tumor targeting ability in a human breast tumor xenograft nude mouse model (24 h after injected) with the possibility of in vivo immunofluorescence tumor imaging. The immunofluorescence imaging background signal and acute toxicity in vivo were minimized because of the reduction of residual QDs. HPSEC-purified QD-HER2-Ab is an accurate and convenient tool for in vivo tumor target imaging and HER2 detection, thus providing a basis for the purification of other QD-based bioprobes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aims: We aimed to investigate child mortality, perinatal morbidities and congenital anomalies born by women with substance misuse during or before pregnancy (DP or BP)., Methods: Taiwan Birth Registration from 2004 to 2014 linking Integrated Illicit Drug Databases used to include substance misuse participates. Children born by mothers convicted of substance misuse DP or BP were the substance-exposed cohort. Two substance-unexposed comparison cohorts were established: one comparison cohort selected newborns from the rest of the population on a ratio of 1:1 and exact matched by the child's gender, child's birth year, mother's birth year and child's first use of the health insurance card; another comparison cohort matched newborns from exposed and unexposed mothers by their propensity scores calculated from logistic regression., Results: The exposure group included 1776 DP, 1776 BP and 3552 unexposed individuals in exact-matched cohorts. A fourfold increased risk of deaths in children born by mothers exposed to substance during pregnancy was found compared to unexposed group (hazard ratio [HR] = 4.54, 95% confidence interval (CI): 2.07-9.97]. Further multivariate Cox regression models with adjustments and propensity matching substantially attenuated HRs on mortality in the substance-exposed cohort (aHR = 1.62, 95% CI: 1.10-2.39). Raised risks of perinatal morbidities and congenital anomalies were also found., Conclusions: Increased risks of child mortality, perinatal morbidities or congenital anomalies were found in women with substance use during pregnancy. From estimates before and after adjustments, our results showed that having outpatient visits or medical utilizations during pregnancy were associated with substantially attenuated HRs on mortality in the substance-exposed cohort. Therefore, the excess mortality risk might be partially explained by the lack of relevant antenatal clinical care. Our finding may suggest that the importance of early identification, specific abstinence program and access to appropriate antenatal care might be helpful in reducing newborn mortality. Adequate prevention policies may be formulated.

Background: Slow-flow vascular malformations include venous, lymphatic, and lymphaticovenous malformations. Recent studies have linked genetic variants hyperactivating either the PI3K/AKT/mTOR and/or RAS/RAF/MAPK signaling pathways with slow-flow vascular malformation development, leading to the use of pharmacotherapies such as sirolimus and alpelisib. It is important that clinicians understand basic and translational research advances in slow-flow vascular malformations., Methods: A literature review of basic science publications in slow-flow vascular malformations was performed on Pubmed, using search terms "venous malformation," "lymphatic malformation," "lymphaticovenous malformation," "genetic variant," "genetic mutation," "endothelial cells," and "animal model." Relevant publications were reviewed and summarized., Results: The study of patient tissues and the use of primary pathogenic endothelial cells from vascular malformations shed light on their pathological behaviors, such as endothelial cell hyperproliferation and disruptions in vessel architecture. The use of xenograft and transgenic animal models confirmed the pathogenicity of genetic variants and allowed for preclinical testing of potential therapies. These discoveries underscore the importance of basic and translational research in understanding the pathophysiology of vascular malformations, which will allow for the development of improved biologically targeted treatments., Conclusion: Despite basic and translation advances, a cure for slow-flow vascular malformations remains elusive. Many questions remain unanswered, including how genotype variants result in phenotypes, and genotype-phenotype heterogeneity. Continued research into venous and lymphatic malformation pathobiology is critical in understanding the mechanisms by which genetic variants contribute to vascular malformation phenotypic features., Competing Interests: The authors declare that they have no conflicts of interest with regard to the content of this report., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The International Society for the Study of Vascular Anomalies.)

The purpose of this study was to investigate the effect of notoginsenoside R&#95;1(NGR&#95;1) on alleviating kidney injury by regulating renal oxidative stress and the Nrf2/HO-1 signaling pathway in mice with IgA nephropathy(IgAN) and its mechanism. The mouse model of IgAN was established using a variety of techniques, including continuous bovine serum albumin(BSA) gavage, subcutaneous injections of carbon tetrachloride(CCl&#95;4) castor oil, and tail vein injections of lipopolysaccharide(LPS). After successful modeling, mice with IgAN were randomly separated into a model group, low, medium, and high-dose NGR&#95;1 groups, and a losartan group, and C57BL6 mice were utilized as normal controls. The model and normal groups were given phosphate buffered saline(PBS) by gavage, the NGR&#95;1 groups were given varying dosages of NGR&#95;1 by gavage, and the losartan group was given losartan by gavage for 4 weeks. The 24-hour urine of mice was collected after the last administration, and serum and kidney tissues of mice were taken at the end of the animal experiment. Then urine red blood cell count(URBCC), 24-hour urine protein(24 h protein), serum creatinine(Scr), and blood urea nitrogen(BUN) levels were measured. The enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of galactose-deficient IgA1(Gd-IgA1), kidney injury molecule 1(Kim-1), and neutropil gelatinase-associated lipocalin(NGAL) in the mouse serum. The assay kits were used to detect the levels of malondialdehyde(MDA) and superoxide dismutase(SOD), and immunofluorescence(IF) was used to detect the expression level of glutathione peroxidase 4(GPX4) in the mesangial region. Western blot was used to detect the protein expression of nuclear transcription factor E2 related factor 2(Nrf2)/heme oxygenase 1(HO-1) signaling pathway in the renal tissue. Hematoxylin-eosin(HE) staining was used to observe pathological alterations in the glomerulus of mice. The results revealed that, as compared with the model group, the serum Gd-IgA1 level, URBCC, 24 h protein level, renal damage markers(Kim-1 and NGAL) in the high-dose NGR&#95;1 group decreased obviously and renal function indicators(BUN, Scr) improved significantly. The activity of SOD activity and expression level of GPX4 increased significantly in the high-dose NGR&#95;1 group, whereas the expression level of MDA reduced and protein expression levels of Nrf2 and HO-1 increased. Simultaneously, HE staining of the renal tissue indicated that glomerular damage was greatly decreased in the high-dose NGR&#95;1 group. In conclusion, this study has clarified that NGR&#95;1 may alleviate the kidney injury of mice with IgAN by activating the Nrf2/HO-1 signaling pathway, improving antioxidant capacity, and reducing the level of renal oxidative stress.

Since glioblastomas (GBMs) are radioresistant malignancies and most GBM recurrences occur in radiotherapy, increasing the effectiveness of radiotherapy by gene-silencing has recently attracted attention. However, the difficulty in precisely tuning the composition and RNA loading in nanoparticles leads to batch-to-batch variations of the RNA therapeutics, thus significantly restricting their clinical translation. Here, we bioengineer bacteriophage Qβ particles with a designed broccoli light-up three-way junction (b-3WJ) RNA scaffold (contains two siRNA/miRNA sequences and one light-up aptamer) packaging for the silencing of genes in radioresistant GBM cells. The in vitro results demonstrate that the cleavage of de novo designed b-3WJ RNA by Dicer enzyme can be easily monitored in real-time using fluorescence microscopy, and the TrQβ@b-3WJ Let-7g siEGFR successfully knocks down EGFR and IKKα simultaneously and thereby inactivates NF-κB signaling to inhibit DNA repair. Delivery of TrQβ@b-3WJ Let-7g siEGFR through convection-enhanced delivery (CED) infusion followed by 2Gy X-ray irradiation demonstrated that the median survival was prolonged to over 60 days compared with the 2Gy X-ray irradiated group (median survival: 31 days). Altogether, the results of this study could be critical for the design of RNAi-based genetic therapeutics, and CED infusion serves as a powerful delivery system for promoting radiotherapy against GBMs without evidence of systemic toxicity.

Background: A increasing number of studies have revealed associations between country-level determinants and coronavirus disease 2019 (COVID-19) outcomes. This ecological study was conducted to analyze country-level parameters related to COVID-19 infections and deaths during the first year of the pandemic., Methods: The examined predictors comprised demographics, economic factors, disease prevalence and healthcare system status, and the relevant data were obtained from public databases. The index dates were set to 15 July 2020 (Time 1) and 15 December 2020 (Time 2). The adjusted spatial autoregression models used a first-order queen contiguity spatial weight for the main analysis and a second-order queen contiguity spatial weight for a sensitivity analysis to examine the predictors associated with COVID-19 case and mortality rates., Results: Obesity was significantly and positively associated with COVID-19 case and mortality rates in both the main and sensitivity analyses. The sensitivity analysis revealed that a country's gross domestic product, population density, life expectancy and proportion of the population older than 65 y are positively associated with COVID-19 case and mortality rates., Conclusions: With the increasing global prevalence of obesity, the relationship between obesity and COVID-19 disease at the country level must be clarified and continually monitored., (© The Author(s) 2022. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

The aim of this study was to investigate the correlation between Silva pattern system and clinicopathological features of endocervical adenocarcinoma. Moreover, it was to find molecular markers helpful for Silva classification, and thus we also explored the expression levels of invasion, adhesion and proliferation biomarkers in cases of Silva non-invasive and invasive types. The survival based on Silva pattern system was analysed by Kaplan-Meier survival analysis, Log-rank test and  a COX risk proportionality model. Sixty samples were chosen to detect the MMP-2, MMP-9, u-PA, E-cadherin, β-catenin, EGF, TGF-α, HDGF, c-Met and RGN expression by immunohistochemistry. Multivariate analysis showed that pattern A/pattern B/pattern C Silva pattern system provided independent risk factors for prognosis. Our results found the levels of MMP-2, MMP-9 and u-PA were significantly higher in endocervical adenocarcinoma with destructive growth than in the  nondestructive group. The levels of E-cadherin and β-catenin were significantly lower in endocervical adenocarcinoma with destructive growth than in the nondestructive group. The levels of EGF, TGF-α and HDGF were significantly higher in endocervical adenocarcinoma with destructive growth than in the nondestructive group. Compared with 'non-invasive/invasive Silva pattern', this study suggests 'pattern A/pattern B/pattern C Silva pattern' could be a better criteria for predicting the prognosis. Furthermore, the dual-marker combination of 'MMP-2 and u-PA' and 'E-cadherin and β-catenin' is very important in the diagnosis of Silva pattern classification., (© 2023 Company of the International Journal of Experimental Pathology (CIJEP).)

Background: Brain gliomas are malignant tumors with high postoperative recurrence rates. Early prediction of prognosis using specific indicators is of great significance., Aim: To assess changes in ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) levels in patients with glioma pre-and postoperatively., Methods: Between June 2018 and June 2021, 91 patients with gliomas who underwent surgery at our hospital were enrolled in the glioma group. Sixty healthy volunteers were included in the control group. Serum UCH-L1 and GFAP levels were measured in peripheral blood collected from patients with glioma before and 3 d after surgery. UCH-L1 and GFAP levels in patients with glioma with different clinicopathological characteristics were compared before and after surgery. The patients were followed-up until February 2022. Postoperative glioma recurrence was recorded to determine the serum UCH-L1 and GFAP levels, which could assist in predicting postoperative glioma recurrence., Results: UCH-L1 and GFAP levels in patients with glioma decreased significantly 3 d after surgery compared to those before therapy ( P < 0.05). However, UCH-L1 and GFAP levels in the glioma group were significantly higher than those in the control group before and after surgery ( P < 0.05). There were no statistically significant differences in preoperative serum UCH-L1 and GFAP levels among patients with glioma according to sex, age, pathological type, tumor location, or number of lesions ( P > 0.05). Serum UCH-L1 and GFAP levels were significantly lower in the patients with WHO grade I-II tumors than in those with grade III-IV tumors ( P < 0.05). Serum UCH-L1 and GFAP levels were lower in the patients with tumor diameter ≤ 5 cm than in those with diameter > 5 cm, in which the differences were statistically significant ( P < 0.05). Glioma recurred in 22 patients. The preoperative and 3-d postoperative serum UCH-L1 and GFAP levels were significantly higher in the recurrence group than these in the non-recurrence group ( P < 0.05). Receiver operating characteristic curves were plotted. The areas under the curves of preoperative serum UCH-L1 and GFAP levels for predicting postoperative glioma recurrence were 0.785 and 0.775, respectively. However, the efficacy of serum UCH-L1 and GFAP levels 3 d after surgery in predicting postoperative glioma recurrence was slightly lower compared with their preoperative levels., Conclusion: UCH-L1 and GFAP efficiently reflected the development and recurrence of gliomas and could be used as potential indicators for the recurrence and prognosis of glioma., Competing Interests: Conflict-of-interest statement: The authors have no conflict of interest to declare., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Purpose: To explore the utility of four-phase computed tomography (CT) in distinguishing renal oncocytoma with central hypodense areas from clear cell renal cell carcinoma (ccRCC)., Methods: Eighteen patients with oncocytoma and 63 patients with ccRCC presenting with central hypodense areas were included in this study. All patients underwent four-phase CT imaging including the excretory phases later than 20 min after contrast injection. Two blinded experienced radiologists visually reviewed the enhancement features of the central hypodense areas in the excretory phase images and selected the area demonstrating the greatest degree of enhancement of the tumor in the corticomedullary phase images. Regions of interest (ROIs) were placed in the same location in each of the three contrast-enhanced imaging phases. Additionally, ROIs were placed in the adjacent normal renal cortex for normalization. The ratio of the lesion to cortex attenuation (L/C) for the three contrast-enhanced imaging phases and absolute de-enhancement were calculated. The receiver operating characteristic curve was used to obtain the cut-off values., Results: Complete enhancement inversion of the central areas was observed in 12 oncocytomas (66.67%) and 16 ccRCCs (25.40%) ( P = 0.003). Complete enhancement inversion combined with L/C in the corticomedullary phase lower than 1.0 ( P < 0.001) or absolute de-enhancement lower than 42.5 HU ( P < 0.001) provided 86.42% and 85.19% accuracy, 61.11% and 55.56% sensitivity, 93.65% and 93.65% specificity, 73.33% and 71.43% positive predictive value (PPV), and 89.39% and 88.06% negative predictive value (NPV), respectively, for the diagnosis of oncocytomas. Combined with complete enhancement inversion, L/C in the corticomedullary phase lower than 1.0 and absolute de-enhancement lower than 42.5 HU provided 87.65%, 55.56%, 96.83%, 83.33%, and 88.41% of accuracy, sensitivity, specificity, PPV, and NPV, respectively, for the diagnosis of oncocytomas., Conclusion: The combination of enhancement features of the central hypodense areas and the peripheral tumor parenchyma can help distinguish oncocytoma with central hypodense areas from ccRCC.

Congenital chylothorax is a rare and often severe anomaly without well-established medical therapies. Previously, propranolol use in patients with lymphatic malformations and secondary chylothorax was associated with improvement in clinical signs. We hypothesized that propranolol treatment would be beneficial for severe congenital chylothorax. We reviewed medical records of neonates born from 2015 to 2019 at our tertiary center with a prenatal diagnosis of congenital chylothorax for whom either prenatal or postnatal propranolol therapy was initiated. Inclusion was limited to fetuses diagnosed with severe congenital chylothorax without significant genetic, infectious, or cardiac anomalies, and who underwent prenatal interventions to mitigate consequences of the condition. Propranolol was administered orally to pregnant women at 20 mg 4 times daily and increased to a maximum dose of 40 mg 4 times daily, or to infants at 0.3 mg/kg/d and increased to 1 to 2 mg/kg/d. Primary outcomes were the time course of resolution of ultrasonographical, clinical, and/or radiologic signs of chylothorax after treatment with propranolol. Four neonates met the inclusion criteria. In 2 cases, prenatal initiation of propranolol led to resolution of the chylothoraxes before delivery (38 and 32 days after treatment) on a dose of 40 mg/day 4 times daily. Neonates had a normal postnatal course. Postnatal propranolol was initiated in 2 neonates with respiratory failure when chylothoraces were refractory to standard management. Stabilization and improvement of their pleural effusion was observed by imaging at 29 and 13 days after initiation of propranolol. There were no significant maternal or neonatal complications from prenatal or postnatal propranolol use. Propranolol may be efficacious in treating severe fetal congenital chylothorax., (Copyright © 2023 by the American Academy of Pediatrics.)

Importance: Glioblastoma is the most lethal primary brain cancer. Clinical outcomes for glioblastoma remain poor, and new treatments are needed., Objective: To investigate whether adding autologous tumor lysate-loaded dendritic cell vaccine (DCVax-L) to standard of care (SOC) extends survival among patients with glioblastoma., Design, Setting, and Participants: This phase 3, prospective, externally controlled nonrandomized trial compared overall survival (OS) in patients with newly diagnosed glioblastoma (nGBM) and recurrent glioblastoma (rGBM) treated with DCVax-L plus SOC vs contemporaneous matched external control patients treated with SOC. This international, multicenter trial was conducted at 94 sites in 4 countries from August 2007 to November 2015. Data analysis was conducted from October 2020 to September 2021., Interventions: The active treatment was DCVax-L plus SOC temozolomide. The nGBM external control patients received SOC temozolomide and placebo; the rGBM external controls received approved rGBM therapies., Main Outcomes and Measures: The primary and secondary end points compared overall survival (OS) in nGBM and rGBM, respectively, with contemporaneous matched external control populations from the control groups of other formal randomized clinical trials., Results: A total of 331 patients were enrolled in the trial, with 232 randomized to the DCVax-L group and 99 to the placebo group. Median OS (mOS) for the 232 patients with nGBM receiving DCVax-L was 19.3 (95% CI, 17.5-21.3) months from randomization (22.4 months from surgery) vs 16.5 (95% CI, 16.0-17.5) months from randomization in control patients (HR = 0.80; 98% CI, 0.00-0.94; P = .002). Survival at 48 months from randomization was 15.7% vs 9.9%, and at 60 months, it was 13.0% vs 5.7%. For 64 patients with rGBM receiving DCVax-L, mOS was 13.2 (95% CI, 9.7-16.8) months from relapse vs 7.8 (95% CI, 7.2-8.2) months among control patients (HR, 0.58; 98% CI, 0.00-0.76; P < .001). Survival at 24 and 30 months after recurrence was 20.7% vs 9.6% and 11.1% vs 5.1%, respectively. Survival was improved in patients with nGBM with methylated MGMT receiving DCVax-L compared with external control patients (HR, 0.74; 98% CI, 0.55-1.00; P = .03)., Conclusions and Relevance: In this study, adding DCVax-L to SOC resulted in clinically meaningful and statistically significant extension of survival for patients with both nGBM and rGBM compared with contemporaneous, matched external controls who received SOC alone., Trial Registration: ClinicalTrials.gov Identifier: NCT00045968.

Objective: Primary spinal cord astrocytomas are rare, fatal, and poorly studied., Methods: This study included a 2-center, retrospective analysis of primary spinal cord astrocytoma patients from 1997 to 2020. Patients with drop metastases or without at least one follow-up were excluded., Results: Seven World Health Organization grade I, 6 grade II, 7 grade III, and 4 grade IV astrocytoma patients were included. Older patients had higher grades (median 20 years in grade I vs. 36.5 in grade IV). The median follow-up was 15 months. Thirteen patients were discharged to rehabilitation. Eight patients demonstrated radiographic progression. Adjuvant therapy was utilized more in higher grades (5 of 13 grades III vs. all 11 grades IIIIV). Six patients died (1 death in grades III vs. 5 in grades IIIIV). Ten patients had worsened symptoms at the last follow-up. The median progression-free survival in grade I, II, III, and IV tumors was 116, 36, 8, and 8.5 months, respectively. The median overall survival in grade I, II, III, and IV tumors was 142, 69, 19, and 12 months, respectively. Thrombotic complications occurred in 2 patients, one with isocitrate dehydrogenasewild type glioblastoma., Conclusions: Outcomes worsen with higher grades and lead to difficult postoperative periods. Clinicians should be vigilant for thromboembolic complications. Further research is needed to understand these rare tumors., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Systemic chemotherapy including monotherapy with temozolomide (TMZ) or bevacizumab (BEV); two-drug combinations, such as irinotecan (IRI) and BEV, TMZ and BEV and a three-drug combination with TMZ, IRI and BEV (TIB) have been used in treating patients with progressive high-grade gliomas including glioblastoma (GBM). Most patients tolerated these regimens well with known side effects of hypertension, proteinuria, and reversible clinical myelosuppression (CM). However, organ- or system- specific toxicities from chemotherapy agents have never been examined by postmortem study. This is the largest cohort used to address this issue in glioma patients., Methods: Postmortem tissues (from all major systems and organs) were prospectively collected and examined by standard institution autopsy and neuropathological procedures from 76 subjects, including gliomas (N = 68, 44/M, and 24/F) and brain metastases (N = 8, 5/M, and 3/F) between 2009 and 2019. Standard hematoxylin and eosin (H&E) were performed on all major organs including brain specimens. Electronic microscopic (EM) study was carried out on 14 selected subject's kidney samples per standard EM protocol. Medical records were reviewed with adverse events (AEs) analyzed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. A swimmer plot was utilized to visualize the timelines of patient history by treatment group. The binary logistic regression models were performed to explore any associations between treatment strategies and incident myelosuppression., Results: Twenty-four glioma subjects were treated with TIB [median: 5.5 (range: 1-25) cycles] at tumor recurrence. Exposure to IRI significantly increased the frequency of CM (p = 0.05). No unexpected adverse events clinically, or permanent end-organ damage during postmortem examination was identified in glioma subjects who had received standard or prolonged duration of BEV, TMZ or TIB regimen-based chemotherapies except rare events of bone marrow suppression. The most common causes of death (COD) were tumor progression (63.2%, N = 43) followed by aspiration pneumonia (48.5%, N = 33) in glioma subjects. No COD was attributed to acute toxicity from TIB. The study also demonstrated that postmortem kidney specimen is unsuitable for studying renal ultrastructural pathological changes due to autolysis., Conclusion: There is no organ or system toxicity by postmortem examinations among glioma subjects who received BEV, TMZ or TIB regimen-based chemotherapies regardless of durations except for occasional bone marrow suppression and reversible myelosuppression clinically. IRI, but not the extended use of TMZ, significantly increased CM in recurrent glioma patients. COD most commonly resulted from glioma tumor progression with infiltration to brain stem and aspiration pneumonia., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To investigate the expression of Ki-67 and CD34 in the differential diagnosis of ductal carcinoma in situ (DCIS) and DCIS-like invasive breast cancer (DLIBC). Methods: A total of 100 cases of DCIS and 150 cases of DLIBC diagnosed pathologically in Yantai Yuhuangding Hospital from January 2019 to March 2022 were collected. The expression of p63, CK5/6, Ki-67 and CD34 in both groups were detected by immunohistochemical (IHC) staining and evaluated. Results: The 100 cases of DCIS included 11 cases of low-grade DCIS, 28 cases of intermediate-grade DCIS and 61 cases of high-grade DCIS. IHC staining of p63 and CK5/6 showed the myoepithelial cells around cancerous duct were complete or partial absence. Ki-67 expression showed two patterns: high expression in the basal layers and scattered expression within the tumor. Most cases showed mainly high basal expression (77/100, 77%), and the proportion of this pattern was significantly different between low grade and high grade DCIS ( P <0.05). All cases showed complete CD34 expression surrounding the cancerous duct with different proportion (vascular necklace) suggested small vessels proliferation. The 150 cases of DLIBC included 142 cases of invasive ductal carcinoma (IDC) (three cases of basal-like breast cancer was included), two cases of secretory carcinoma, three cases of solid papillary carcinoma, two cases of adenoid cystic carcinoma and one case of acinar cell carcinoma. Among 142 cases of IDC, 13 cases were grade Ⅰ, 77 were grade Ⅱ and 52 were grade Ⅲ. IHC staining of p63 showed complete absence of myoepithelium. CK5/6 was negative in most cases and only positively expressed within the tumor in 3 cases of basal-like breast cancer. Ki-67 indicated a scattered expression pattern within the tumor. In most cases, CD34 immunostaining showed scattered positive blood vessels within the tumor while only two cases showed incomplete expression of CD34 around the tumor (2/150, 1.3%). The different expression patterns of Ki-67 and CD34 in DCIS and DLIBC was statistically significant ( P <0.05). Conclusions: The different expression patterns of Ki-67 and CD34 are helpful to distinguish DLIBC from DCIS. The appearance of "vascular necklace" with CD34 and the high expression of Ki-67 around the cancerous duct highly support the diagnosis of DCIS, and the scattered expression pattern of CD34 supports DLIBC.

The strong adhesion of thermally conductive silicone encapsulants on highly integrated electronic devices can avoid external damages and lead to an improved long-term reliability, which is critical for their commercial application. However, due to their low surface energy and chemical reactivity, the self-adhesive ability of silicone encapsulants to substrates need to be explored further. Here, we developed epoxy and alkoxy groups-bifunctionalized tetramethylcyclotetrasiloxane (D 4 H-MSEP) and boron-modified polydimethylsiloxane (PDMS-B), which were synthesized and utilized as synergistic adhesion promoters to provide two-component addition-cured liquid silicone rubber (LSR) with a good self-adhesion ability for applications in electronic packaging at moderate temperatures. The chemical structures of D 4 H-MSEP and PDMS-B were characterized by Fourier transform infrared spectroscopy. The mass percentage of PDMS-B to D 4 H-MSEP, the adhesion promoters content and the curing temperature on the adhesion strength of LSR towards substrates were systematically investigated. In detail, the LSR with 2.0 wt% D 4 H-MSEP and 0.6 wt% PDMS-B exhibited a lap-shear strength of 1.12 MPa towards Al plates when curing at 80 °C, and the cohesive failure was also observed. The LSR presented a thermal conductivity of 1.59 W m -1 K -1 and good fluidity, which provided a sufficient heat dissipation ability and fluidity for potting applications with 85.7 wt% loading of spherical α-Al 2 O 3 . Importantly, 85 °C and 85% relative humidity durability testing demonstrated LSR with a good encapsulation capacity in long-term processes. This strategy endows LSR with a good self-adhesive ability at moderate temperatures, making it a promising material requiring long-term reliability in the encapsulation of temperature-sensitive electronic devices.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder for which no effective treatment is available. Studies have demonstrated that improving insulin resistance in type 2 diabetes mellitus (T2DM) can benefit patients with PD. In addition, a neuroprotective effect of glucagon-like peptide-1 (GLP-1) receptor agonists was demonstrated in experimental models of PD. In addition, there are some clinical trials to study the neuroprotective effect of GLP-1 analog on PD patients. Semaglutide is a long-acting, once-a-week injection treatment and the only available oral form of GLP-1 analog. In the present study, we treated the human neuroblastoma SH-SY5Y cell line with 6-hydroxydopamine (6-OHDA) as a PD in vitro model to explore the neuroprotective effects and potential mechanisms of semaglutide to protect against PD. Moreover, we compared the effect of semaglutide with liraglutide given at the same dose. We demonstrated that both semaglutide and liraglutide protect against 6-OHDA cytotoxicity by increasing autophagy flux and decreasing oxidative stress as well as mitochondrial dysfunction in SH-SY5Y cells. Moreover, by comparing the neuroprotective effects of semaglutide and liraglutide on PD cell models at the same dose, we found that semaglutide was superior to liraglutide for most parameters measured. Our results indicate that semaglutide, the new long-acting and only oral GLP-1 analog, may be represent a promising treatment for PD., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Dong-xing Liu et al.)