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Aims. Giant cell tumor of the bone (GCTB) is associated with considerable morbidity. As GCTB epidemiological data for China are limited, this study is aimed at describing the disease characteristics of GCTB in China and establishing the historical context for its treatment before recent advances in treatment options. Methods. The disease characteristics, treatment patterns, and local GCTB recurrence rate after primary surgery for GCTB were evaluated in this single-center, retrospective, noninterventional, observational study of patients treated for GCTB at Ji Shui Tan Hospital, Beijing, from 2009 to 2016 based on medical chart review. Patients with unmet need were defined as those whose surgical treatment was difficult or who had to undergo high-morbidity surgery. Results. Among the 668 patients with a primary GCTB diagnosis, 578 (86.5%) of target lesions were in the extremities, and 89 (13.3%) were in the pelvic or axial bone. Of these, 173 (25.9%) were characterized as having an unmet need. Almost all GCTB patients received surgical treatment at both primary diagnosis (666/668 (99.7%)) and last disease recurrence (196/200 (98.0%)). Additionally, about one-third of patients received nonsurgical treatment at primary diagnosis (205/668 (30.7%)) and disease recurrence (67/200 (33.5%)), with neoadjuvant therapy being the most common treatment. The rate of high-morbidity surgery increased for recurrent disease (65/200 (32.5%)) compared with primary diagnosis (111/668 (16.6%)). The 2-year cumulative incidence of postoperative disease recurrence was 29.2%, in line with rates observed in prior studies. Conclusion. As many patients with primary and recurrent disease received high-morbidity surgery, more effective treatments are needed.

SUMMARY To reach Earth’s surface, magma must ascend from the hot, ductile asthenosphere through cold and brittle rock in the lithosphere. It does so via fluid-filled fractures called dykes. While the continuum mechanics of ductile asthenosphere is well established, there has been little theoretical work on the cold and brittle regime where dyking and faulting occurs. Geodynamic models use plasticity to model fault-like behaviour; plasticity also shows promise for modelling dykes. Here we build on an existing model to develop a poro-viscoelastic–viscoplastic theory for two-phase flow across the lithosphere. Our theory addresses the deficiencies of previous work by incorporating (i) a hyperbolic yield surface, (ii) a plastic potential with control of dilatancy and (iii) a viscous regularization of plastic failure. We use analytical and numerical solutions to investigate the behaviour of this theory. Through idealized models and a comparison to linear elastic fracture mechanics, we demonstrate that this behaviour includes a continuum representation of dyking. Finally, we consider a model scenario reminiscent of continental rifting and demonstrate the consequences of dyke injection into the cold, upper lithosphere: a sharp reduction in the force required to rift.

Circulating platelets are sometimes exposed to high shear rate environments due to vascular stenosis, and the effect of transiently elevated pathological high shear rates on platelet activation and aggregation function has not been clarified. The aim of this study was to investigate the effect of pathological high shear rate (8302s - 1) exposure time (3.16-25.3 ms) on platelet activation and aggregation function. In addition, by adding active ingredients of antiplatelet drugs such as ASA (an active ingredient of aspirin), Ticagrelor, Tirofiban and GP1BA (platelet membrane protein GPIb inhibitor) in vitro, we studied TXA2, P2Y12-ADP, GPIIb/IIIa-fibrinogen and GPIb /IX/V-vWF receptor pathways to determine platelet activation function mediated by pathological high shear rate. In this study, we designed a set of microfluidic chips with stenosis lengths of 0.5 mm, 1 mm, 2 mm, 3 mm, and 4 mm, all with 80% stenosis, to generate pathological high shear forces that can act at different times. The whole blood flowing through the microchannels was collected by perfusion of sodium citrate anticoagulated whole blood at a physiological arterial shear rate (1500 s - 1), and the expression levels of platelet surface activation markers (P-selectin and GP IIb/IIIa) and the degree of platelet aggregation were analyzed by flow cytometry; platelet aggregation patterns were observed by microscopic examination of blood smears. The results showed that shearing significantly increased platelet activation and aggregation levels compared to un-sheared whole blood, and the activation and aggregation levels increased with increasing duration of pathological high shear rate. In vitro inhibition studies showed that ASA barely inhibited the expression of P-selectin and PAC-1 on the platelet surface; Ticagrelor effectively inhibited the expression of both P-selectin and PAC-1; Tirofiban significantly inhibited the expression of PAC-1 on the platelet surface and slightly inhibited the expression of P-selectin; GP1BA significantly inhibited the expression of both.ur results suggest that transient pathological high shear rate (8302s - 1) exposure can induce platelet activation in a time-dependent manner; however, the mechanism is more complex and may be due to the following reasons: transient elevated pathological high shear rate activates platelets through the GPIb/IX/V-vWF receptor pathway, and after platelet activation, its surface membrane protein GPIIb/IIIa receptors activate platelets through fibrinogen to form platelet-platelet aggregates, and further activation of active substances such as ADP and TXA2 released by platelet alpha particles, which contribute to the formation of irreversible platelet aggregation.

What is Known and Objective. Almonertinib was newly approved for treating non-small-cell lung cancer (NSCLC) patients with EGFR T790M mutation, and the therapeutic effect of almonertinib needed to be investigated. This study aims to investigate the efficacy and safety of almonertinib compared with osimertinib in EGFR-T790M+ patients who used earlier-generation EGFR-TKI and experienced disease progression. Methods. Among all 160 patients, 80 received osimertinib, while the other 80 patients took almonertinib once daily. The objective response rate (ORR) and disease control rate (DCR) were analyzed, while overall survival (OS) and progression-free survival (PFS) were estimated. In terms of safety, adverse events (AEs) were compared. Results and Discussions. The ORR and DCR were significantly higher in patients who received almonertinib than those in the osimertinib group (70.0% vs. 47.5%, P = 0.004 ; 90.0% vs. 77.5%, P = 0.032 ). The OS was significantly higher in the almonertinib group than in patients who received osimertinib ( P = 0.031 ), while the PFS was similar between the two groups ( P = 0.226 ). Of 28 patients with brain metastasis, the OS was not raised after using almonertinib compared with the osimertinib group ( P = 0.626 ). The number of AEs was similar between the almonertinib and osimertinib groups (all P > 0.05 ). Treatment-related AEs of grade ≥3 occurred in 20.0% and 15.0% of patients in the osimertinib and almonertinib arms, respectively. What is New and Conclusion. Almonertinib may become an alternative option for EGFR-T790M + NSCLC patients after earlier-generation EGFR-TKI for its promising efficacy and manageable tolerability. However, the treatment option for patients with brain metastasis remains to be explored further.

Objectives Nephrotic syndrome (NS) remains a therapeutic challenge for nephrologists. Piceatannol-3ʹ-O-β-d-glucopyranoside (PG) is a major active ingredient in Quzha. The purpose of the study was to assess the renoprotection of PG. Methods In vitro, the podocyte protection of PG was assessed in MPC-5. SD rats were injected with adriamycin to induce nephropathy in vivo. The determination of biochemical changes and inflammatory cytokines was performed, and pathological changes were examined by histopathological examination. Immunostaining and western blot analyses were used to analyse expression levels of proteins. Key findings The results showed that PG improved adriamycin-induced podocyte injury, attenuated nephropathy, improved hypoalbuminemia and hyperlipidaemia, and lowered cytokine levels. The podocyte protection of PG was further verified by reduction of desmin and increasing synaptopodin expression. Furthermore, treatment with PG down-regulated the expression of HMGB1, TLR4 and NF-κB along with its upstream regulator, IKKβ and yet up-regulated IκBα expression by western blot analysis. Conclusions Overall, our data showed that PG has a favourable renoprotection in experimental nephrosis, apparently by amelioration of podocyte injury. PG might mediate these effects via modulation of the HMGB1/TLR4/NF-κB signalling pathway. The study first provides a promising leading compound for the treatment of NS.

When galaxies move through the intracluster medium (ICM) inside galaxy clusters, the ram pressure of the ICM can strip the gas from galaxies. The stripped gas forms tails on the trailing side. These galaxies are hence dubbed ``jellyfish galaxies''. ESO 137-001 is a quintessential jellyfish galaxy located in the nearest rich cluster, the Norma cluster. Its spectacular multiphase tail has complex morphology and kinematics both from the imprinted galaxy's interstellar medium (ISM) and as a result of the interactions between the stripped gas and the surrounding hot plasma, mediated by radiative cooling and magnetic fields. We study the kinematics of the multiphase tail using high-resolution observations of the ionized and the molecular gas in the entire structure. We calculate the velocity structure functions (VSFs) in moving frames along the tail and find that turbulence driven by Kelvin-Helmholtz (KH) instability quickly overwhelms the original ISM turbulence and saturates at $\sim 30$ kpc. There is also a hint that the far end of the tail has possibly started to inherit pre-existing large-scale ICM turbulence likely caused by structure formation. Turbulence measured by the molecular gas is generally consistent with that measured by the ionized gas in the tail but has a slightly lower amplitude. Most of the measured turbulence is below the mean free path of the hot ICM ($\sim 11$ kpc). Using warm/cool gas as a tracer of the hot ICM, we find that the isotropic viscosity of the hot plasma must be suppressed below 0.01 percent Spitzer level., Comment: 7 pages, 6 figures, accepted for publication in MNRAS

Background. To explore the use of teicoplanin among Chinese patients with Gram-positive infections in a tertiary hospital. Methods. The medical records of patients, who were monitored for teicoplanin plasma concentration (TPC) from December 2017 to February 2019, were collected. By combining the therapeutic drug monitoring (TDM) and nonlinear mixed-effects model, a population pharmacokinetic (PPK) model of teicoplanin was established. Results. The proportions of TPCs lower and higher than 10 mg/L were nearly the same (102 vs. 108 cases). A two-compartment model of teicoplanin PPK in Chinese patients was established. Compared with 400 mg, the 600 mg regimen was more able to reach the target concentration (10 mg/L), especially for high-weight patients. Conclusions. The standard regimen of teicoplanin, 400 mg, failed to reach the target value in the present population. Moreover, the 600 mg regimen was feasible for high-weight patients based on TDM and individualized pharmacokinetic dosing adjustment.

Combination cancer chemotherapy is one of the most useful treatment methods to achieve a synergistic effect and reduce the toxicity of dosing with a single drug. Here, we use a combination of two well-established anticancer DNA intercalators, actinomycin D (ActD) and echinomycin (Echi), to screen their binding capabilities with DNA duplexes containing different mismatches embedded within Watson-Crick base-pairs. We have found that combining ActD and Echi preferentially stabilised thymine-related T:T mismatches. The enhanced stability of the DNA duplex–drug complexes is mainly due to the cooperative binding of the two drugs to the mismatch duplex, with many stacking interactions between the two different drug molecules. Since the repair of thymine-related mismatches is less efficient in mismatch repair (MMR)-deficient cancer cells, we have also demonstrated that the combination of ActD and Echi exhibits enhanced synergistic effects against MMR-deficient HCT116 cells and synergy is maintained in a MMR-related MLH1 gene knockdown in SW620 cells. We further accessed the clinical potential of the two-drug combination approach with a xenograft mouse model of a colorectal MMR-deficient cancer, which has resulted in a significant synergistic anti-tumour effect. The current study provides a novel approach for the development of combination chemotherapy for the treatment of cancers related to DNA-mismatches.