Objective Through investigating the effect of mesenchymal stem cells (MSCs) on the expression of yon Willebrand factor (vWF) and soluble thrumbomodulin (sTM) of vascular endothelial cells stimulated by serum of systemic lupus erythematosus (SLE) patients to discuss the repairing effect of MSCs on injured endothelium of SLE patients.Methods When human umbilical vein endothelial cell strain ECV-304 was co-cultivated with serum of SLE patients in vitro for twelve hours in order to induce endothelial cells injury,then MSCs were seeded for three days.Enzyme linked immunosorbent assay (ELISA) was used to detect the expression of vWF and sTM in the supernatant.Results When ECV-304 was stimulated by serum of SLE patients,the expression of vWF and sTM in the supernatant was significantly higher than that in the groups not stimulated by serum of SLE patients;When MSCs were seeded ,the expression of vWF in the Lupus serum stimulated group in which MSCs were seeded was significantly lower than that in the lupus serum stimulated group in which MSCs were not seeded,but the expression of sTM between the lupus serum stimulated group which MSCs were seeded and the lupus serum stimulated group in which MSCs were not seeded was not significantly deviatied.Conclusion Serum of lupus patients at active stage can cause injure vascular endothelial cells.MSCs can downregulate the expression of vWF of vascular endothelial cells.These suggest it may participate in the repairing of injured vascular endothelium of SLE patients.

Objective To investigate the effect and mechanism of placental protein 14 on the proliferation and differentiation of B cells.Methods The lymphocyte of human peripheral blood was separated by gradient centrifugation.Flow cytometry was used to detect the proportion of CD4+CXCR5+follicular helper T cells (Tfh cells),CD4+CXCRS+Foxp3+ follicular regulatory T cells (Tfr cells),CD3-CD19+B cells and CD3-CD38+ plasma cells.ELISA method was used to detect the concentration of IL-21,IL-10 and TGF-beta in the supernatant,and the co-culture of cells was performed by Transwell chamber;t test was used for comparison between groups.Results The proportion of Tfh cells and Tfr cells in the control group was (2.52±0.16)％ and (1.26±0.24)％,respectively,and that of the placental protein 14 groups were (0.84±0.09)％ and (4.64±0.68)％,respectively.There was a significant difference between the two groups (t=9.150,P=0.000 8 and t=4.669,P=0.009 5).Pplacental protein 14 could further inhibit the secretion of IL-21 (t=5.086,P=0.007 1),and promote the increase of IL-10 and TGF-β concentration (t=3.599,P=0.022 8 and t=6.651,P=0.002 7).The percentage of B cells and plasma cells in the placental protein 14 group were (4.87±0.20)％ and (5.41±0.54)％,which were significantly different from those in the Tfh cell group (t=4.997,P=0.007 5;t=5.110,P=0.006 9).Conclusion Placental protein 14 can inhibit the proliferation of B cells and differentiate into plasma cells by inhibiting the differentiation of Tfh cells and increasing the proportion of Tfr cells.

Objective To explore the efficacy and safety of multiple cervical suture in treating stripping surface intractable hemorrhage after cesarean section in the patients with placenta previa centralis.Methods Twenty-three patients with stripping surface intractable hemorrhage during cesarean section caused by placenta previa centralis from January 2012 to December 2015 in this hospital were selected and conducted multiple cervical suture,and 21 patients with the same disease undergoing intraoperative conventional hemostasis method from January 2008 to December 2011 served as the control group.The operation time,intraoperative and postoperative blood loss volume,red blood cell transfusion,hysterectomy and postoperative recovery were compared between the two groups.Results The operation time,intraoperative and postoperative blood loss volume,blood transfusion volume and hysterectomy rate in the observation group were significantly less than those in the control group(P＜0.05),while There were no statistical difference in the aspects of postoperative incision infection,bloody lochiorrhea persisting time,menstrual recovery time and menstrual volume between the two groups(P＞0.05).Conclusion The application of multiple cervical suture in the treatment of stripping surface intractable hemorrhage after cesarean section in the patients with placenta previa centralis has better hemostatic effect,had no complications in short term follow up and is worthy clinical promotion and ap plication.

Objective: To study the expression of miRNA-181a in acute myeloid leukemia (AML) patients with normal karyotype to probe its prognosis significance. Methods: The expression level of miRNA-181a in bone marrow mononuclear cells of 120 de novo AML patients with normal karyotype was detected by real time fluorescence quantitative PCR. The direct sequencing method was used to detect IDH1, IDH2, NPM1, FLT3-ITD, DNMT3A and CEBPα mutations in CN-AML patients after PCR. The relationship between miRNA-181a expression and gene mutation, the clinical parameters and prognosis were analyzed. Results: The rates of overall surviva1 (OS) in high expression and low expression groups were 25.0 months and 15.0 months, respectively (P<0.05) . Relapse free survival (RFS) in high expression and low expression groups were 21.4 months and 11.2 months, respectively (P<0.05) . Significantly higher level hemoglobin, complete remission rate and proportion of wild type NPM1 expression in the high expression of miRNA-181a group were observed when compared with the lower expression of miRNA-181a group (P<0.05) . Multivariate Cox regression analysis showed miRNA-181a overexpression was an independent prognostic factor for CN-AML (HR=2.219, 95%CI 1.601~2.432, P=0.018) . Conclusion Higher expression of miRNA-181a was a good prognostic factor independent of clinical parameters and high frequency gene mutations, which implicated that the miRNA-181a expression level could be used as an important prognostic indicator of AML patients with normal karyotype.

Objective To analyze the predictive value of cyclin-dependent activator 3(CDKN3)in the prog-nosis of oral squamous cell carcinoma(OSCC)and its relationship with immune cell infiltration,and to ex-plore the biological function of CDKN3 in the occurrence and development of OSCC.Methods RNAseq data related to OSCC were obtained from the Cancer Genome Atlas and Gene Expression Omnibus database.The expression level of CDKN3,prognostic value,clinicopathological features and immune cell infiltration were an-alyzed by R language and statistical methods.Gene enrichment analysis was used to analyze the biological role of CDKN3 in OSCC.Results Compared with normal tissues,CDKN3 was highly expressed in OSCC tumor tissues(P＜0.01),and the area under curve for the receiver operating characteristic curve was 0.955.The pa-tients with high expression of CDKN3 had a poor prognosis(P=0.024).The expression of CDKN3 was cor-related with pathological stage(P＜0.05)and histological grade(P＜0.001).There was a significant differ-ence in the level of immune cell infiltration between the CDKN3 high and low expression groups(P＜0.05).Functional enrichment analysis showed that CDKN3 was closely related to cell cycle.Conclusion CDKN3 may be a potential carcinogenic risk factor of OSCC,which is related to the clinicopathological characteristics,prog-nosis and immune cell infiltration of patients.CDKN3 may be a diagnostic biomarker and a potential therapeu-tic target for OSCC.

Combined with the relevant policies promulgated by the state, the paper elaborates three basic modes of prescription refill management for chronic diseases: community model, pharmacy model, and distribution model. Then from multiple perspectives including the internal strengths and weaknesses of chronic disease management reform, as well as external opportunities and threats, the paper uses the SWOT analysis method to analyze the feasibility of establishing and popularizing the management of refilled prescriptions for chronic diseases during the COVID-19 epidemic and the advantages and disadvantages of carrying out this management mode. At the same time, medical institutions, doctors and patients are required to change the concept of chronic disease management mode in the context of COVID-19 prevention and control. On the premise of ensuring the safety of patients’ medication and the safety of national medical insurance funds during this period, we should promote the implementation of prescription refills for chronic diseases.

OBJECTIVETo investigate the clinicopathologic features, immunohistochemic phenotypes and genetic alterations of extrapulmonary inflammatory myofibroblastic tumor (IMT) and the correlation with prognosis.

METHODSThirty cases of IMT with follow-up were analyzed morphologically and immunohistochemically. ALK FISH was also performed to determine the ALK gene status.

RESULTSPatients ranged in age from 12 to 73 years (mean 43.4 years). The male-to-female ratio was 1.0: 1.1. The tumors were located in various anatomical sites including gastrointestinal tract, liver, spleen, kidney, pelvic, retroperitoneum, mediastinum etc. Histologically, the majority of cases were composed of spindled fibroblastic and myofibroblastic cells accompanied by an inflammatory infiltrate of plasma cells, lymphocytes, and eosinophils. Most cases with aggressive behavior had features including prominent nucleoli and edematous myxoid background. Lymphohistiocytic reactions were usually absent. Some cases showed multinucleation, nuclear pleomorphism and mitoses. One case demonstrated epithelioid morphology with round-to-epithelioid cells. The immunohistochemical study showed vimentin, SMA, CK, desmin, and ALK were expressed in 100% (30/30), 70% (21/30), 13% (4/30), 27% (8/30), and 27% (8/30) of IMT, respectively. Diffuse cytoplasmic ALK staining was detected in seven cases. One case (containing round-to-epithelioid cells) demonstrated ALK nuclear membrane staining, coupled with positive reaction for CD30 and negative reaction for LCA. EMA, CD34, CD117 and S-100 protein, and MyoD1 were negative for all cases. Six ALK protein positive cases harbored ALK gene rearrangement, but not the remaining 22 cases. Follow-up data were available in 21 patients. After initial resection, 14 patients were alive with no evidence of disease, while 4 patients were alive with tumor recurrence and 3 patients died of the disease.

CONCLUSIONSMost IMT with aggressive behavior have features including prominent nucleoli, edematous myxoid background, and positive expression of ALK. Lymphohistiocytic reaction is usually absent. ALK may be a potential novel therapeutic target for IMT.

Adolescent ; Adult ; Aged ; Child ; Female ; Fibroblasts ; pathology ; Granuloma, Plasma Cell ; genetics ; pathology ; Humans ; Inflammation ; pathology ; Male ; Middle Aged ; Myofibroblasts ; pathology ; Prognosis ; Receptor Protein-Tyrosine Kinases ; genetics ; Young Adult

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.

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*