Abivertinib, a third-generation tyrosine kinase inhibitor, is originally designed to target epidermal growth factor receptor (EGFR)-activating mutations. Previous studies have shown that abivertinib has promising antitumor activity and a well-tolerated safety profile in patients with non-small-cell lung cancer. However, abivertinib also exhibited high inhibitory activity against Bruton's tyrosine kinase and Janus kinase 3. Given that these kinases play some roles in the progression of megakaryopoiesis, we speculate that abivertinib can affect megakaryocyte (MK) differentiation and platelet biogenesis. We treated cord blood CD34⁺ hematopoietic stem cells, Meg-01 cells, and C57BL/6 mice with abivertinib and observed megakaryopoiesis to determine the biological effect of abivertinib on MK differentiation and platelet biogenesis. Our in vitro results showed that abivertinib impaired the CFU-MK formation, proliferation of CD34⁺ HSC-derived MK progenitor cells, and differentiation and functions of MKs and inhibited Meg-01-derived MK differentiation. These results suggested that megakaryopoiesis was inhibited by abivertinib. We also demonstrated in vivo that abivertinib decreased the number of MKs in bone marrow and platelet counts in mice, which suggested that thrombopoiesis was also inhibited. Thus, these preclinical data collectively suggested that abivertinib could inhibit MK differentiation and platelet biogenesis and might be an agent for thrombocythemia.
Acrylamides/pharmacology* ; Animals ; Blood Platelets/drug effects* ; Cell Differentiation ; Megakaryocytes/drug effects* ; Mice ; Mice, Inbred C57BL ; Piperazines/pharmacology* ; Pyrimidines/pharmacology*

【Objective】 To understand the current situation of blood components distribution in domestic prefecture-level blood stations through analyzing the components distribution data of 24 prefecture-level blood stations in China. 【Methods】 The data of components distribution of 24 blood stations from 2017 to 2020 as well as the data of blood deployment of 24 blood stations from 2019 to 2020 were collected and analyzed. 【Results】 From 2017 to 2020, positive annual growth in red blood cells, plasma and cryoprecipitate was observed in 22, 19 and 15 out of the 24 blood stations, and the annual growth median rate of above three components was 5.24%, 3.80% and 3.25%, respectively. Among the 24 prefecture-level blood stations, 23 carried out the preparation of cryoprecipitate. 【Conclusion】 The distribution of red blood cells, cryoprecipitate and plasma in prefecture-level blood stations is increasing year by year. However, there is a overstock of plasma, and most blood stations need blood employment.

This study aimed to investigate the prevalence, clinical characteristics, and prognostic impact of 1p32.3 deletion in patients with newly diagnosed multiple myeloma (MM). A retrospective analysis was conducted on 411 patients with newly diagnosed MM; among which, 270 received bortezomib-based therapies, and 141 received thalidomide-based therapies. Fluorescence in situ hybridization (FISH) was performed to detect six cytogenetic abnormalities, namely, del(1p32.3), gain(1q21), del(17p13), del(13q14), t(4;14), and t(11;14). Results showed that 8.3% of patients with MM were detected with del(1p32.3) and had significantly more bone marrow plasma cells (P = 0.025), higher β2-microglobulin levels (P = 0.036), and higher lactate dehydrogenase levels (P = 0.042) than those without del(1p32.3). Univariate analysis showed that patients with del(1p32.3) under thalidomide-based therapies (median PFS 11.6 vs. 31.2 months, P = 0.002; median OS 16.8 vs. 45.9 months, P < 0.001) were strongly associated with short progression-free survival (PFS) (P = 0.002) and overall survival (OS) (P < 0.001). Multivariate analysis revealed that del(1p32.3) remained a powerful independent factor with worse PFS (P = 0.006) and OS (P = 0.016) for patients under thalidomide-based treatments. Patients with del(1p32.3) under bortezomib-based treatments tended to have short PFS and OS. In conclusion, del(1p32.3) is associated with short PFS and OS in patients with MM who received thalidomide- or bortezomib-based treatments.

Vertigo is one of the most common symptoms in general practice. During the standardized training in theory and practice of vertigo diagnosis and treatment, researchers from group of vertigo subspe-cialty of department of neurology analyzed the epidemiological characteristics of vertigo disease and the present teaching situation of theory and practice teaching. They put forward and adopted the "Three Steps"(laying firm foundation, consolidating and strengthening, and improving skills) which is based on multidis-cipline and conforming to trainees' understanding of the disease. It helped general practitioners tofamiliarize themselves with the etiology, diagnosis, and treatment of vertigo, to perfect their multidisciplinary knowl-edge structure, to establish scientific clinical thinking, and to improve their levels of the diagnosis and treatment of diseases relating to vertigo, which has produced good effects and has been playing an important role in improving the prognosis for vertigo patients.

Objective To study the therapeutic effects and related mechanism of Tongmai Yizhi granules on vascular dementia in rats. Methods Bilateral carotid artery ligation was used to establish rat model of vascular dementia (VD). The rats were randomly divided into 6 groups: sham operated,the model control,piracetam (0. 375 g·kg-1 ·d-1 ) as positive con-trol,low dose (2. 5 g·kg-1 ·d-1 ),middle dose(5. 0 g·kg-1 ·d-1 ),and high dose (10. 0 g·kg-1 ·d-1 ) of Tongmai Yizhi granules. Each group was intragastrically administered with 10 mL·kg-1 of corresponding medications for 31 days after the VD model was established. The sham group was given with 0. 9% NaCl solution. Y-electric maze was used to test the learning and memory function of rats at the second and fourth weeks. On the day 32,hippocampal tissues were collected for pathological analy-sis by microscope. The activities of SOD and content of MDA in serum and tissue homogenate were tested. Results Compared with model control group,each dose of Tongmai Yizhi granules obviously shortened the incubation period of VD rats in electric maze test,and accuracy of learning and memory was improved (P<0. 05 or P<0. 01). The activity of SOD was decreased,and the content of MDA was increased after treatment with Tongmai Yizhi granules (P < 0. 01). Hippocampal neuronal cells were disar-ranged,and the number of cone cells was decreased significantly in the model control group. In contrast,the necrosis and degener-ation of hippocampal neurons were alleviated in all Tongmai Yizhi treatment groups. Conclusion Tongmai Yizhi granule can apparently improve learning and memory function of VD rats. It can also improve the activity of SOD and reduce the content of MDA in serum and hippocampus,effectively remove free radicals,and alleviate the injury of hippocampal pyramidal cells.

Neonatal hyperinsulinism/hyperammonemia syndrome is a genetic disease result from glutamate dehydrogenase gene mutations.The clinical manifestations are hypoglycemia,hyperinsulinemia and mild hyperammonemia.Hypoglycemia may occur quickly due to eating protein.It is a rare neonatal disease that was easily ignored or delayed diagnosis and treatment causing serious sequelae of nervous system.This review summarized pathogenesis,clinical manifestation and diagnosis of the disease.

Objective To investigate the effects of 10 mg and 20 mg atorvastatin and 10 mg rosuvastatin on inflammatory factors in patients with acute coronary syndrome (ACS).Methods 66 patients with ACS were randomly divided into three groups:the 10 mg atorvastatin group,the 20 mg atorvastatin group and the 10 mg rosuvastatin group(n=22 for each group).The levels of blood lipids,serum matrix metalloproteinases-9 (MMP-9)and plasminogen activator inhibitor-1 (PAI-1)were measured before and after two-week treatment.19 patients with normal coronary angiography were assigned to the control group.Results The concentration of serum MMP-9 and PAI-1 was higher significantly in patients with ACS than those in control subjects(P＜0.05 or P＜0.01).After two weeks'treatment,the serum MMP-9 and PAI-1 levels were lowered significantly (P＜0.01),which were much better in groups of 20mg atorvastatin and of 10mg rosuvastatin than those in group of 10mg atorvastatin (P＜0.05 or P＜0.01 ).No relationship was observed between the levels of above inflammatory markers and serum hpids levels(P＞0.05).Conclusion 10 mg Rosuvastatin can greatly reduce the serum level of MMP-9 and PAI-1 as compared to 10 mg atorvastatin in patients with ACS ,equivalent to the effect of 20 mg atorvastatin,suggesting that the anti-inflammatory effect is independent of lipid-lowering action.

This study was aimed to investigate the aggregation of rehydrated-lyophilized platelets. The aggregation rate of fresh and rehydrated-lyophilized platelets were measured by using thrombin, ristocetin, ADP and collagen as inductors and APACT2 aggregameter; the effects of intra- and extra-cellular trehalose on maximum aggregation rate of rehydrated-lyophilized platelets were detected by using ADP as an inductor. The results showed that the aggregation rate of fresh platelets was all about 100%, while aggregation rate of rehydrated lyophilized platelets was (70.17 +/- 7.36)%, (15.3 +/- 2.81)%, (68.67 +/- 6.86)%, (64.67 +/- 11.6)% respectively, when the concentration of thrombin, ristocetin, ADP and collagen was 1 U/ml, 1.6 mg/ml, 20 micromol/L and 2 microg/ml. The maximum aggregation rates of rehydrated-lyophilized platelets in intra- and extra-cellular trehalose, extracellular trehalose and blank control groups were (66.0 +/- 4.69)%, (25.3 +/- 2.42)% and (11.5 +/- 1.87)% (P < 0.01), meanwhile there was significant difference of rehydrated-lyophilized platelet aggregation rate between intra- and extra-cellular trehalose and extracellular trehalose groups (P < 0.01). It is concluded that the concentrations of thrombin (1 U/ml), ristocetin (1.6 mg/ml), ADP (20 micromol/L) and collagen (2 microg/ml) are optimal for platelets aggregation tests, the internal and extracellular trehalose significantly enhance the aggregation of rehydrated-lyophilized platelets.
Blood Platelets ; cytology ; drug effects ; metabolism ; Blood Preservation ; methods ; Freeze Drying ; methods ; Humans ; Platelet Aggregation ; physiology

BACKGROUNDLung cancer invading left atrium or base of pulmonary vein belongs to locally advanced lung cancer (T4). The prognosis of treatment without surgery is poor. The aim of this study is to explore the feasibility and the value of surgical method in the treatment of this disease.

METHODSFrom April, 1993 to April, 2005, lobectomy or pneumonectomy combined with extended resection of left atrium were carried out in 46 patients with locally advanced lung cancer. The operations included left low lobectomy in 20 cases, left pneumonectomy in 6 cases, right middle and low lobectomy in 12 cases, right low lobectomy in 3 cases and right pueumonectomy in 5 cases respectively. The base of the pulmonary vein was invaded by the tumor in 34 patients, while left atriums were invaded obviously in 12 patients. Two patients were operated using extracoporeal circulation because of main pulmonary artery and left atrium being invaded. The Kaplan-Meier method (Log rank test) and a COX model were used to analyse the survival and the prognosis.

RESULTSThere was no operative mortality in this series, 15 patients had operative complication, including arrhythmia in 13 cases, pneumonia in 8 cases and heart failure in 1 case. The median survival was 35 months. The 1-, 3-, 5-year survival rates were 84.2%, 43.7%, 30.5% respectively. The survival of patients with N0/1 was better than that of patients with N2 disease, the median survival of them were 38 months and 19 months respectively (P=0.002). Using a Cox model analysis, lymph node stage (N0/1 or N2) was independent prognostic factor, while preoperative chemotherapy, sex, age and the pathologic type were not independent prognostic factors.

CONCLUSIONSSurgical treatment for lung cancer invading the left atrium or the base of pulmonary vein is feasible, especially for N0 patients.

0.05). While in D_2 and D_1+D_2 groups, the AI (0.54?0.05,0.64?0.04,0.63?0.04,0.65?0.11, 0.67?0.07) were increased, and the latter was more obviously. There were significant differences compared with sham-irradiated group(P