Because the influence of fibrin on the reaction of plasm inogen activation by various plasminogen activators is different, the kinetic co nstant of the reaction of plasminogen activation catalyzed by InB with and witho ut fibrin were detected. The result is: Kfibrinm＝4.2 μmol*L -1，greater than the normal Km=0.379 μmol*L-1; kfib rincat＝0.107 s-1，greater than the normal kcat=0.0165 s-1. The results suggest that existence of fibrin in the reaction system of plasminogen activation depress the affinity between InB and plasminog en, but accelerates the hydrolysis of plasminogen by InB. The count up effect is inhibition.

Objective:To isolate and culture the pulp cells from human young permanent teeth (pDPC),and to observe their biological characteristics and the expression of some specific markers,and to induce these pulp cells to differentiate into osteoblast, adipocyte, neuron and chondrocyte lineages. Methods:Pulp cells were isolated and cultured from orthodontic extracted premolars of children. The attached cells after at least 3 passages were used for the following experiments:1. Morphology and ultrastructure analysis; 2. Cell cycle and phenotype were analyzed by flowcytometry; 3. Growth curve were recorded;4. pDPC were induced to differentiate into osteoblast,adipocyte,neuron in vitro,and were identified by histochemical methods and RT-PCR. Results: 1. Attached pDPCs were fibrablast-like cells,which were distinguished from BMSC. 2. The cell organs in dDPCs were well developed. 3. pDPCs were highly positive for CD90, CD44, CD147,which are mesenchymal stem-cell markers,but were negative for other markers including CD34, CD38, CD45, HLA-DR. 4. pDPCs showed high growth rate. 5. pDPCs could be induced to differentiate into osteoblast, adipocyte, and neuron lineages,but not chondrocyte lineages. Conclusion:pDPCs were characterized by their ability to proliferate with high growth rate in vitro. The expression of some BMSC markers in these cells were observed. They showed the potential to differentiate into multiple mesenchymal lineages such as osteoblst,adipocyte, neuron lineages under specific conditions in vitro.

Objective To investigate the effects of ulinastatin (UTI) combined with magnesium isoglycyrrhizinate (MgIG) on the expression of transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) in lung tis?sue of rats with pulmonary fibrosis induced by bleomycin (BLM). Methods Ninety Wistar rats were randomly divided into five groups: BLM group, methylprednisolone (MTH) group, UTI group, MgIG group and UTI combined with MgIG (UTI+MgIG) group, n=18 for each group. The rat model of pulmonary fibrosis was established by injecting bleomycin through tra?chea in five groups. Twenty-four hours after treatment with BLM,rats were treated with normal saline every day in BLM group, and rats were treated by corresponding drugs in other groups. Six rats of each group were killed at the 7th,14th and 28th day respectively. The pathological changes of alveolitis and pulmonary fibrosis were evaluated by HE staining, and ex?pression levels of TGF-β1 and CTGF in lung tissues were detected by immunohistochemistry method. Results (1) Com?pared with BLM group, the degree of alveolitis and pulmonary fibrosis was reduced in other groups. There was significant dif?ference in alveolitis at the 7th and 14th day between UTI+MgIG group and BLM group. And there was significant difference in pulmonary fibrosis at the 14th and 28th day between UTI+MgIG group and BLM group (P<0.05). (2) Compared with BLM group, the expression levels of TGF-β1 and CTGF were decreased in other groups. In UTI+MgIG group, the expres?sion levels of TGF-β1 were significantly lower at the 7th and 14th day compared with those in UTI group and MgIG group, and which were significantly lower at the 28th day than those in MTH group, UTI group and MgIG group (P<0.05). The ex?pression levels of CTGF were significantly lower at the 7th day in UTI + MgIG group than those in UTI group and MgIG group, and which were significantly lower at the 14th and 28th day than those in MTH group, UTI group and MgIG group (P<0.05). Conclusion The combination of UTI and MgIG can alleviate alveolitis and fibrosis in BLM-induced pulmonary fibrosis rats, which might related with the down-regulation of TGF-β1 and CTGF expressions.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Cytokines ; genetics ; Ethanol ; administration & dosage ; toxicity ; Gene Expression Regulation ; drug effects ; Interleukin-18 ; genetics ; Liver Diseases, Alcoholic ; blood ; genetics ; pathology ; Male ; Platelet-Derived Growth Factor ; genetics ; Rats ; Rats, Wistar ; Transforming Growth Factor beta ; genetics ; Triglycerides ; blood

This study examined the effect of intensive insulin therapy on immune function and inflammatory factors at the early phase after severe trauma. At day 1, 3, 5, 7 after admission, subsets of CD4(+) helper T lymphocytes (Th1/Th2) and human leukocyte antigen (HLA)-DR expression on CD14(+) monocytes were flow cytometrically measured. Levels of cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10) and other immunity markers, such as IgA, IgG, IgM, C3, C4 and C reaction protein (CRP) were examined in two groups. The results showed that TNF-α, IL-6 and CRP levels in the intensive insulin therapy group were significantly lower than those in the conventional therapy group, whereas IL-10 levels were substantially increased after intensive insulin therapy. C3 level at day 3, 5, 7 and C4 levels at day 5, 7 were lower in the intensive therapy group than in the conventional therapy group. Th1/Th2 ratios decreased gradually over time in both groups, and were much lower at day 3, 5, 7 in intensive therapy group. There were significant differences among day 3 to day 7 after admission in HLA-DR expression in CD14(+) monocytes. It was concluded that the intensive insulin therapy could decrease pro-inflammatory cytokines and increase anti-inflammatory cytokines in the elderly suffering from severe trauma, at the same time, with complement recovery being delayed. Moreover, intensive insulin therapy promoted immune suppression and, therefore, measures need be taken to address the issue.

This study examined the effect of intensive insulin therapy on immune function and inflammatory factors at the early phase after severe trauma. At day 1, 3, 5, 7 after admission, subsets of CD4(+) helper T lymphocytes (Th1/Th2) and human leukocyte antigen (HLA)-DR expression on CD14(+) monocytes were flow cytometrically measured. Levels of cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10) and other immunity markers, such as IgA, IgG, IgM, C3, C4 and C reaction protein (CRP) were examined in two groups. The results showed that TNF-α, IL-6 and CRP levels in the intensive insulin therapy group were significantly lower than those in the conventional therapy group, whereas IL-10 levels were substantially increased after intensive insulin therapy. C3 level at day 3, 5, 7 and C4 levels at day 5, 7 were lower in the intensive therapy group than in the conventional therapy group. Th1/Th2 ratios decreased gradually over time in both groups, and were much lower at day 3, 5, 7 in intensive therapy group. There were significant differences among day 3 to day 7 after admission in HLA-DR expression in CD14(+) monocytes. It was concluded that the intensive insulin therapy could decrease pro-inflammatory cytokines and increase anti-inflammatory cytokines in the elderly suffering from severe trauma, at the same time, with complement recovery being delayed. Moreover, intensive insulin therapy promoted immune suppression and, therefore, measures need be taken to address the issue.
Aged ; Aged, 80 and over ; Cytokines ; immunology ; Female ; Humans ; Hyperglycemia ; drug therapy ; immunology ; Hypoglycemic Agents ; therapeutic use ; Immunity, Innate ; drug effects ; immunology ; Immunologic Factors ; immunology ; Insulin ; therapeutic use ; Male ; Treatment Outcome ; Wounds and Injuries ; drug therapy ; immunology

Objective:To explore the efficacy and safety of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and human granulocyte colony-stimulating factor (G-CSF) for the prevention of post-chemotherapy infections in pediatric hematologic neoplasms.Methods:A total of 134 children hospitalized for chemotherapy in 6 tertiary hospitals from July 2016 to June 2018 were collected, including 60 cases in Children's Hospital of Fudan University, 38 cases in Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 29 cases in Children's Hospital Affiliated to Soochow University, 4 cases in the Affiliated Hospital of Qingdao University, 2 cases in Northwestern Women and Children's Hospital, and 1 case in Shandong Provincial Qianfoshan Hospital. The children were divided into GM-CSF group (38 cases), G-CSF group (45 cases) and GM-CSF+G-CSF group (51 cases) by using random number table method. The incidence of infections, the recovery time of absolute neutrophil counting (ANC), the decrease of blood platelet count (Plt) and the incidence of adverse reactions were compared among the three groups.Results:In all children, a total of 64 cases (47.8%) had infections during the myelosuppression phase after chemotherapy, of which 18 cases (47.4%) in GM-CSF group, 20 cases (44.4%) in G-CSF group, and 26 cases (51.0%) in GM-CSF+G-CSF group. The incidence of respiratory infection in G-CSF group was higher than that in GM-CSF group and GM-CSF+ G-CSF group [22.2% (10/45) vs. 2.6% (1/38), 4.0% (2/51), χ2 = 12.00, P = 0.002]. The median time to recovery of ANC > 1.5×10 9/L was 10.5 d (8 d, 15 d) in all children, 12 d (10 d, 16 d) in GM-CSF group, 9 d (8 d, 12 d) in G-CSF group, and 10 d (8 d, 16 d) in GM-CSF+G-CSF group. In all children, a total of 101 cases (75.4%) had Plt<50×10 9/L during the myelosuppression phase, and 79 cases (59.0%) had Plt <20×10 9/L. The differences in the incidence of Plt <50×10 9/L and <20×10 9/L among the three groups were not statistically significant (both P > 0.05). In all children, the adverse reactions occurred in 24 cases (17.9%), including 20 cases (14.9%) of fever, 2 cases (1.5%) of sore throat, 1 case (0.7%) of nausea, and 1 case (0.7%) of diarrhea; no adverse reactions of grade 2 or above occurred. The difference in the incidence of adverse reactions among the three groups was not statistically significant ( P>0.05). Conclusions:The efficacy of GM-CSF and G-CSF for the prevention of infections in pediatric hematologic neoplasms during the myelosuppression phase after chemotherapy is roughly equivalent, and combination of both has a good tolerance. The incidence of respiratory infection using GM-CSF alone or GM-CSF+G-CSF is low, which might benefit from the effect of GM-CSF on lung infections.

Objective    To explore the efficacy of a novel detection technique of circulating tumor cells (CTCs) to identify benign and malignant lung nodules. Methods     Nanomagnetic CTC detection based on polypeptide with epithelial cell adhesion molecule (EpCAM)-specific recognition was performed on enrolled patients with pulmonary nodules. There were 73 patients including 48 patients with malignant lesions as a malignant group and 25 patients with benign lesion as a benign group. There were 13 males and 35 females at age of 57.0±11.9 years in the malignant group and 11 males and 14 females at age of 53.1±13.2 years in the benign group. e calculated the differential diagnostic efficacy of CTC count, and conducted subgroup analysis according to the consolidation-tumor ratio, while compared with PET/CT on the efficacy. Results     CTC count of the malignant group was significantly higher than that of the benign group  (0.50/ml vs. 0.00/ml, P<0.05). Subgroup analysis according to consolidation tumor ratio (CTR) revealed that the difference was statistically significant in pure ground glass (pGGO) nodules 1.00/ml vs. 0.00/ml, P<0.05), but not in part-solid or pure solid nodules. For pGGO nodules, the area under the receiver operating characteristic (ROC) curve of CTC count was 0.833, which was significantly higher than that of maximum of standardized uptake value (SUVmax) (P<0.001). Its sensitivity and specificity was 80.0% and 83.3%, respectively. Conclusion     The peptide-based nanomagnetic CTC detection system can differentiate malignant tumor and benign lesions in pulmonary nodules presented as pGGO. It is of great clinical potential as a noninvasive, nonradiating method to identify malignancies in pulmonary nodules.

Objective    To explore the diagnostic value of circulating tumor cells (CTC) measured by magnetic nanoparticle method in lung cancer. Methods    (1) We measured binding capability of A549 or NCI-H1965 cell lines with recognition peptide and capture efficiency by adding tumor cells into the whole blood of healthy human. (2) We measured CTC of 34 patients suspected with lung cancer, and the counting results of CTC were compared with the following pathological results. Results    (1) The binding capability was 80.0%±6.0% for A549 and 70.1%±4.8% for H1957, while the capture efficiency was 57.3%±7.0% for A549 and 37.3%±6.1% for H1975. (2) CTCs were identified in 71.9% of patients with lung cancer. The specificity was 83.3%, and area under receiver operating characteristic (ROC) curve was 0.792 (P=0.003). Conclusion    CTC measured by magnetic nanoparticle method has promising application in the diagnosis of lung cancer.

Induction of cancer cell ferroptosis has been proposed as a potential treatment in several cancer types. Tumor-associated macrophages (TAMs) play a key role in promoting tumor malignant progression and therapy resistance. However, the roles and mechanisms of TAMs in regulating tumor ferroptosis is still unexplored and remains enigmatic. This study shows ferroptosis inducers has shown therapeutic outcomes in cervical cancer in vitro and in vivo. TAMs have been found to suppress cervical cancer cells ferroptosis. Mechanistically, macrophage-derived miRNA-660-5p packaged into exosomes are transported into cancer cells. In cancer cells, miRNA-660-5p attenuates ALOX15 expression to inhibit ferroptosis. Moreover, the upregulation of miRNA-660-5p in macrophages depends on autocrine IL4/IL13-activated STAT6 pathway. Importantly, in clinical cervical cancer cases, ALOX15 is negatively associated with macrophages infiltration, which also raises the possibility that macrophages reduce ALOX15 levels in cervical cancer. Moreover, both univariate and multivariate Cox analyses show ALOX15 expression is independent prognostic factor and positively associated with good prognosis in cervical cancer. Altogether, this study reveals the potential utility of targeting TAMs in ferroptosis-based treatment and ALOX15 as prognosis indicators for cervical cancer.