Ultrasound (US) is reported to improve the delivery efficiency of drugs loading onto large nanoparticles due to the sonoporation effect. Microbubbles (MBs) can be used as contrast agents of US expanding and contracting under low-amplitude US pressure waves. Ultrasound-stimulated microbubbles (USMBs) therapy is a promising option for the treatment of various cancers as a radiosensitizer. However, its role in esophageal squamous cell carcinoma (ESCC) remains unknown. In our study, human ESCC cell lines (KYSE-410, KYSE-1140) were treated with radiation solely, US alone, or radiation in combination with US or USMBs. The migration and invasion abilities of ESCC cells were examined by wound healing and Transwell assays. ESCC cell apoptosis was assessed using flow cytometry analysis and TUNEL assays. The levels of proteins associated with cell apoptosis and angiogenesis were measured by western blot analysis. A tube formation assay was performed to detect the ESCC cell angiogenesis. We found that USMBs at high levels most effectively most efficiently enhanced the effect of radiation, and significant changes in the viability (48%-51%), proliferation (1%), migration (63%-71%), invasion (52%) and cell apoptosis (31%-50%) of ESCC cells were observed compared with the control group in vitro. The ESCC angiogenesis was inhibited by US or radiation treatment and further inhibited by a combination of radiation and US or USMBs. USMBs at high levels most effectively enhanced the inhibitory effect of radiotherapy on ESCC cell apoptosis. Overall, USMBs enhanced the radiosensitivity of esophageal squamous cell carcinoma cells.Graphical abstract USMBs treatment enhanced the anti-tumor effect of radiation on ESCC cell proliferation, migration, invasion, angiogenesis and apoptosis in vitro.1USMBs enhance the radiation-induced inhibition on ESCC cell growth 2USMBs promote the radiation effect on ESCC cell apoptosis 3USMBs enhance radiation-caused suppression on ESCC cell migration and invasion 4USMBs enhance the suppression of radiation on ESCC angiogenesis ARTICLE HISTORY

Abstract. Langerhans cell histiocytosis (LCH) is a rare disease of unknown cause, which encompasses a set of disorders of multiple organs with various clinical presentations that share the common characteristic of sizeable Langerhans cell infiltration. The clinical spectrum of LCH ranges from solitary bone lesions to involvement of other organs. Lung involvement in LCH may be part of a multisystem disease, which almost exclusively occurs in adult smokers, while it is overlooked or misdiagnosed in the majority of non-smokers. High-resolution computed tomography (HRCT) of the chest is crucial for diagnosis; however, the treatment and prognosis of this disease have not been clearly determined. We herein present the case of a non-smoking adult patient who presented with lower limb pain and was diagnosed via biopsy with LCH with multisystem involvement, including the bone and lungs. Lytic lesions in the corpus of the sacroiliac joint, sacrum, acetabulum and femoral head by a soft tissue mass were observed on diagnostic CT. In addition, chest HRCT revealed multiple cysts in the bilateral lungs, predominantly in the upper lobes. The final diagnosis of LCH was confirmed by histopathological examination and immunohistochemical staining for CD1a and S-100. Corticosteroid treatment alleviated lower limb pain and improved the patient's quality of life; thus, corticosteroids may be considered as a potential treatment option for patients with LCH. IntroductionLangerhans cell histiocytosis (LCH) is a rare disease of unknown etiology characterized by mixed cellular infiltration. Although the etiology of LCH has not been fully elucidated, the gold standard for the diagnosis of LCH is the presence of Birbeck granules, and positivity for CD1a, S-100 and/or CD45 on pathological examination (1,2). LCH may occur at any age, although it is more common in children, and has various clinical manifestations, depending on the type and number of systems or organs involved throughout the body (3).Specific acute symptoms may include local pain, weight loss, fatigue, fever, skin rash and neurological changes, while the bone and lung are the most commonly involved organs (4). It has been reported that the proportion of LCH with lung involvement in adults is higher compared with that in children (4). Furthermore, the disease is self-limited in the majority of pediatric patients, which is not the case in adults. A variety of factors have been implicated in the prognosis of LCH, such as patient age and extent of the disease. Several therapeutic approaches may be considered, including surgery, radiotherapy and chemotherapy; however, there is currently no standard treatment for LCH patients with multisystem involvement (MS-LCH). Case reportA 38-year-old male patient with a 2-year history of left leg pain, involving numbness extending from the left thigh to the knee, was referred to Nanjing Chest Hospital, Medical School of Southeast University. The pain and numbness in the left thigh were aggravated by exertion, such as walking or running, and they ...

This study aimed to explore the effect of ultrasound-stimulated microbubbles (USMBs) on tumor radiosensitivity in esophageal carcinoma (EC). The human EC cell line KYSE-510 and human umbilical vein endothelial cells (HUVECs) were exposed to radiation alone or in combination with USMBs. CCK-8, colony formation, and EdU assays were used to determine cell viability and proliferation. Cell apoptosis was assessed using flow cytometry. Cell migration and invasion were examined by wound healing and transwell assays. Western blotting showed that the protein levels were associated with apoptosis, epithelial–mesenchymal transition (EMT), and angiogenesis. An endothelial tube-forming assay was used to detect the angiogenic activity of HUVECs. Xenograft experiments were used to examine the effect of USMBs on EC radiosensitivity in vivo. The expression of Ki-67 in tumors was detected using immunohistochemistry. USMBs enhanced the suppressive effect of radiation on proliferation, migration, invasion, and EMT, and promoted radiation-induced apoptosis in EC cells in vitro. Angiogenesis in EC was suppressed by radiation and further inhibited by the combination of radiation and USMBs. In vivo experiments revealed that USMBs increased the radiosensitivity of ECs to tumor growth. Collectively, USMBs enhanced the effects of radiotherapy in esophageal carcinoma.

We developed a low-cost polymer-film spiral inertial microfluidic device for the effective size-dependent separation of malignant tumor cells. The device was fabricated in polymer films by rapid laser cutting and chemical bonding. After fabricating the prototype device, the separation performance of our device was evaluated using particles and cells. The effects of operational flow rate, cell diameter, and cell concentration on the separation performance were explored. Our device successfully separated tumor cells from polydisperse white blood cells according to their different migration modes and lateral positions. Then, the separation of rare cells was carried out using the high-concentration lysed blood spiked with 200 tumor cells. Experimental results showed that 83.90% of the tumor cells could be recovered, while 99.87% of white blood cells could be removed. We successfully employed our device for processing clinical pleural effusion samples from patients with advanced metastatic breast cancer. Malignant tumor cells with an average purity of 2.37% could be effectively enriched, improving downstream diagnostic accuracy. Our device offers the advantages of label-free operation, low cost, and fast fabrication, thus being a potential tool for effective cell separation.

All the results demonstrated that magnesium may elicit protective effect against radiationinduced brain injury by reducing calcium overload, improving redox and inhibiting cell apoptosis. Moreover, magnesium significantly down-regulated the protein or mRNA levels of NF-κB and ICAM- 1. The findings may provide references for the application of magnesium in clinic for brain injury induced by radiation.