Abstract. Sarcoma is a rare and heterogeneous type of cancer with an early mean onset age and a poor prognosis. However, its genetic basis remains unclear. A series of recent genomic studies in sarcomas have identified the occurrence of mutations in the α-thalassemia/mental retardation syndrome X-linked (ATRX) gene. The ATRX protein belongs to the SWI/SNF family of chromatin remodeling proteins, which are frequently associated with α-thalassemia syndrome. Cancer cells depend on telomerase or the alternative lengthening of telomeres (ALT) pathway to overcome replicative programmed mortality. Loss of ATRX is associated with ALT in sarcoma. In the present review, recent whole genome and/or whole exome genomic studies are summarized. In addition ATRX immunohistochemistry and ALT fluorescence in situ hybridization in sarcomas of various subtypes and at diverse sites, including osteosarcoma, leiomyosarcoma, liposarcoma, angiosarcoma and chondrosarcoma are evaluated. The present review involves certain studies associated with the molecular mechanisms underlying the loss of ATRX controlling the activation of ALT in sarcomas. Identification of the loss of ATRX and ALT in sarcomas may provide novel methods for the treatment of aggressive sarcomas.

Background : During the current COVID-19 pandemic, offline clinical education was mandated to suspend at the neurology department of many teaching hospitals globally, yet there is insufficient evidence regarding the preferred practice and methods for online neurology intern training course. Objective : The investigation aimed to examine whether the online neurology training course based on Small Private Online Course (SPOC) and blending learning mode can achieve a good effect and cater for interns from different medical programs and whether the learning group size affects the teaching effect. Design : The subjects were 92 students enrolled in the neurology internship at the Second Xiangya Hospital of China from 9 March to 9 August 2020. After completing the online course, the final scores and evaluation results were compared among different groups of interns, and their preference to distinct contents of the course was analyzed. Statistical analysis was performed using the SPSS program (version 22.0). Results : Our online course received consistent positive recognition from the interns. Ninety-nine percent of the interns recommended incorporating the online course into the conventional offline training program after the pandemic. There was no significant difference between interns from different programs concerning the final scores and course evaluation. A smaller learning group size (<15 students) could achieve a better teaching effect than a larger group size (p < 0.05). The interns preferred interactive discussions, and course contents that they can get practice and feedback from, rather than video watching and didactic lectures. Conclusions : The online neurology intern training course based on SPOC and blending learning mode is worthy of popularization in a large student base. The teaching effect of an online intern training program may be improved by limiting the group size to less than 15 students and encouraging more interactive discussion, more practice and feedback.

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Neurodegenerative disorders (NDs) are characterized by a gradual loss of neurons and functions that eventually leads to progressive neurological impairment. In view of the heavy burden on the healthcare system, efficient and reliable biomarkers for early diagnosis and therapeutic treatments to reverse the progression of NDs are in urgent need. There has been an increasing interest in using exosomal miRNAs as biomarkers or targeted therapies for neurological diseases recently. In this review, we overviewed the updated studies on exosomal miRNAs as biomarkers and potential therapeutic approaches in NDs, as well as their association with the pathophysiology of this group of disorders, especially Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD). The exosomal miRNAs that are commonly dysregulated across different NDs or are commonly used as therapeutic candidates were also identified and summarized. In summary, the feasibility of exosomal miRNAs as biomarkers and potential targeted therapy for NDs has been verified. However, due to the limitations of existing studies and the discrepancies across different studies, high quality laboratory and clinical investigations are still required.

Diabetes mellitus and pancreatic ductal adenocarcinoma are two common diseases worldwidely which are both derived from different components of pancreas. The pancreatic and duodenal homeobox-1 (PDX1) is an essential transcription factor for the early development of pancreas that is required for the differentiation of all pancreatic cell lineages. Current evidence suggests an important role of PDX1 in both the origin and progression of pancreatic diseases. In this review, we discussed recent studies of PDX1 in diabetes mellitus and pancreatic cancer, and the therapeutic strategies derived from this transcription factor.

Alzheimer's disease (AD) is the most prevalent dementia worldwide, but its pathophysiology and molecular events remain unknown. Herein, we first analyzed the differential expression pattern of patients' AD hippocampus through gene expression array data from the GEO database. Notch2nl, TGFB1I1, and LTF were up-regulated in AD patients, while ARPC1A, CHGB, and MPV17 down-regulated. Second, dysregulation of ferroptosis related genes was demonstrated from our data: PCBP2 and FTL significantly up-significant in AD hippocampus, while VDAC2, LPCAT3, GSS, ACSL4, and ACSL6 significantly down-regulated. The protein-protein interactions (PPI) network revealed that FTL was involved in iron metabolism and utilization, while ACSL4 and ACSL6 were involved in a polyunsaturated fatty acids metabolism network. Gene correlation analysis on differential expressed genes (DEGs) indicated that ferroptosis regulates a series of biological processes and pathways related to AD pathogenesis. Third, ferroptosis-related DEGs regulated the immune cell infiltration pattern in the AD hippocampus, characterized by decreased memory B cells, increased memory resting CD4 + T cells, memory activated CD4 + T cells, and resting NK cells. The altered expression of ferroptosis-related DEGs affected the infiltration of specific immune cell types. The model constructed by the seven ferroptosis-related differential genes may accurately predict the outcome of AD occurrence. Finally, qPCR validation on these ferroptosis-related DEGs in APPswe/PSEN1dE9 mice confirmed the dysregulated expression of Pcbp2, FTL, GSS, and ACSL4 in the AD hippocampus and forebrain. In conclusion, our results supported the conception that the AD brain revealed dysregulated ferroptosis and immune cell infiltration.

BackgroundDespite significant progress in treating methanol poisoning, the lack of training, hazard communication, and occupational safety protection education contributes to the risk of occupational exposure and methanol toxicity. In addition, early diagnosis and timely medical care are essential to reduce the risk of morbidity and mortality, yet it remains a challenging procedure.Case ReportA 35-year-old man working in a fireworks factory came to our emergency department with acute mental change and progressive disturbance of consciousness. The patient's vital signs were stable, and he presented with enlargement of both pupils with a weak reaction to light. Head computed tomography showed low signal intensities in the bilateral basal ganglia. He was admitted to the neurologic intensive care unit, where additional laboratory workup showed high anion-gap metabolic acidosis. Methanol poisoning was thus considered. Before being treated with sodium bicarbonate infusion, hemodialysis, folate, and high-dose vitamin B, the blood and urine samples were collected for toxicity tests, which turned out to be methanol poisoning. After 8 hours of hemodialysis, the patient's consciousness recovered, but he complained of a complete loss of vision in both eyes. Brain and optic nerve magnetic resonance images showed bilateral symmetric putamen lesions and optic neuropathy. Ophthalmic tests indicated visual pathway impairment and optic disc swelling but no fluorescein leakage. The right eye's vision was partially restored on the third day, but he could only count fingers at 20 cm. Unfortunately, his eyesight ceased to improve during the 6 months of follow-up.ConclusionsEarly diagnosis and prompt treatment will improve the prognosis of methanol poisoning in terms of vision and patient survival. Awareness and supervision of commercial alcohol use are indispensable for similar industrial processes.

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