Being a key player in intercellular communications, nanoscale extracellular vesicles (EVs) offer unique opportunities for both diagnostics and therapeutics. However, their cellular origin and functional identity remain elusive due to the high heterogeneity in their molecular and physical features. Here, for the first time, multiple EV parameters involving membrane protein composition, size and mechanical properties on single small EVs (sEVs) are simultaneously studied by combined fluorescence and atomic force microscopy. Furthermore, their correlation and heterogeneity in different cellular sources are investigated. The study, performed on sEVs derived from human embryonic kidney 293, cord blood mesenchymal stromal and human acute monocytic leukemia cell lines, identifies both common and cell line-specific sEV subpopulations bearing distinct distributions of the common tetraspanins (CD9, CD63, and CD81) and biophysical properties. Although the tetraspanin abundances of individual sEVs are independent of their sizes, the expression levels of CD9 and CD63 are strongly correlated. A sEV population co-expressing all the three tetraspanins in relatively high abundance, however, having average diameters of less then 100 nm and relatively low Young moduli, is also found in all cell lines. Such a multiparametric approach is expected to provide new insights regarding EV biology and functions, potentially deciphering unsolved questions in this field.Aldrich et al. clearly described the clinical features of immune checkpoint inhibitor-related myositis (ICI-myositis) divided by the presence or absence of myasthenia gravis (MG) (1). Veliparib concentration From the viewpoint of a neurologist, I emphasize that making a diagnosis of MG that has occurred as immune-related adverse event is difficult when anti-acetylcholine receptor (AChR) antibodies are undetectable.Here, we report a rare case involving a 66-year-old man with epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma and antisynthetase syndrome (ASS) treated with osimertinib. The patient presented with respiratory failure and bilateral pulmonary opacities; he was diagnosed with ASS accompanied by interstitial lung disease (ILD), consistent with paraneoplastic syndrome. After steroid pulse therapy, osimertinib was administered for lung adenocarcinoma without ILD exacerbation. Osimertinib could therefore be a treatment option for EGFR-mutant lung cancer with paraneoplastic ILD.Chronic myeloid leukemia (CML) is a neoplasm characterized by BCR-ABL1, an oncoprotein with vital role in leukemogenesis. Its inhibition by tyrosine kinase inhibitors represents the main choice of treatment. However, therapeutic failure is worrying given the lack of pharmacological options. Pentacyclic triterpenes are phytochemicals with outstanding antitumoral properties and have also been explored as a basis for the design of potential leads. In this review, we have gathered and discuss data regarding both natural and semisynthetic pentacyclic triterpenes applied to CML cell treatment. We found consistent evidence that the class of pentacyclic triterpenes in general exerts promising pro-apoptotic and antiproliferative activities in sensitive and resistant CML cells, and thus represents a rich source for drug development. We also analyze the predicted drug-like properties of the molecules, discuss the structural changes with biological implications and show the great opportunities this class represents, as well as the perspectives they provide on drug discovery for CML treatment.

To report a case series of calcaneal fracture-dislocations, which have not been described previously in China, and to provide a systematic review to explore the clinic manifestations, methods for diagnoses, and treatments.

Between January 2018 and December 2019, 4 patients (4 men; average age, 33.0 ± 16.67 years; range, 15-50 years) were diagnosed with fracture-dislocation of the calcaneus and treated by surgery. We also reviewed published cases and studies of calcaneal fracture-dislocations through the databases of PubMed and Web of Science between January 1977 and December 2019.

Between January 2018 and December 2019, 4 cases were identified as calcaneal fracture-dislocations in our hospital. The main clinical manifestations include hindfoot pain, swelling, and deformity. The diagnoses were confirmed via radiographic examination. Two patients underwent open reduction and internal fixation (ORIF) and two were treated with a minimally invasive approach. Diagnosis had been missed in one patient and, cons this rare injury pattern. Timely surgical intervention is essential for satisfactory clinic outcomes. Orthopaedic surgeons should be aware of this uncommon injury to avoid misdiagnosis or inappropriate treatment.The primary objective of this randomized, double-blind, parallel-controlled study (from December 2016 to October 2018) was to evaluate pharmacokinetic (PK) equivalence of adalimumab biosimilar HLX03 and reference adalimumab in healthy volunteers, and to assess safety, and immunogenicity of HLX03. The primary PK endpoints were maximum observed plasma concentration (Cmax ) and area under the concentration curve from time zero to the last quantifiable concentration (AUC0-t ). Equivalence was determined if the 90% confidence interval (CI) of geometric least square mean ratio between the two treatment groups were within the predefined range of 80%-125%. Safety and immunogenicity were monitored during the study. Healthy Chinese males (N = 220) were randomized 11 to receive a single subcutaneous 40 mg dose of HLX03 or China (CN)-sourced adalimumab. The ratios of the geometric mean of Cmax and AUC0-t were 102.2% and 105.7%, respectively, with corresponding 90% CIs falling in the predefined margins, which demonstrated PK equivalence between HLX03 and CN-adalimumab. The incidence of treatment-emergent adverse events (TEAEs) was similar in the two groups (73.8% and 66.0% in the HLX03 and CN-adalimumab groups, respectively). Grade 3-4 TEAEs were reported in 7.5% and 5.7% of participants, respectively. The incidences of participants with antidrug antibodies (HLX03 96.2%; CN-adalimumab 93.4%) or neutralizing antibodies (HLX03 40.6%, CN-adalimumab 41.4%) were comparable between groups. This study demonstrated PK bioequivalence between HLX03 and CN-adalimumab, with similar safety and immunogenicity profiles. These data support further clinical development of HLX03 as an adalimumab biosimilar.