Objective:To explore the potent effects of denatonium benzoate(DB)on Mas-related G protein-coupled receptor-B2(MrgprB2)-mediated rat mast cell degranulation.Methods:RBL-2H3 cells were treated with DB overnight,before challenged with MrgprB2 ligands substance P(SP).The release of β-hex from MrgprB2-activated RBL-2H3 was detected by substrate method.Detec-tion of LTC4,IL-6,TNF-α and cPLA2 activity were performed by ELISA.The Ca2+influx and the expression of RBL-2H3 MrgprB2 re-ceptors were measured by fluorescence assay.Results:The results showed 10 μmol/L,50 μmol/L,80 μmol/L,100 μmol/L DB treat-ments promoted β-hex and LTC4 releases from activated RBL-2H3,accompanied by increased Ca2+mobilization and cPLA2 activa-tion.DB treatments did not affect IL-6 and TNF-α LTC4 releases in MrgprB2-activated RBL-2H3,as well as the levels of MrgprB2 ex-pression in mast cells.Conclusion:Taken together,DB enhanced the MrgprB2-mediated RBL-2H3 degranulation in vitro,probably by up-regulating Ca2+mobilization in activated cells.

Infection is a common medical problem at present. Different pathogens can lead to different infections. Severe infections can ultimately lead to sepsis, resulting in multiple organ dysfunction and the high mortality of patients. Therefore, studying the occurrence and development of severe infections is essential to improve the survival rate of patients. More and more studies have revealed the important role of connection between intestine and liver in infectious diseases. The maintenance of intestinal mechanical barrier and biological barrier function and the regulation of intestinal flora metabolites can reduce infectious liver injury. Bile acids are important metabolites in the liver, which can inhibit the progression of certain infectious intestinal injuries and promote intestinal damage caused by certain pathogens. In this article, the mechanism of action of the intestinal-liver axis in infection was reviewed to find a new target for the treatment of clinical infection.

Objective: To explore the clinical value of magnetic resonance T₂-mapping imaging in the diagnosis of early intervertebral disc degeneration in obese people. Methods: From January 2018 to June 2019, 30 obese volunteers and 30 healthy volunteers with normal weight underwent T₂-mapping scan, while their routine MRI examination showed no abnormalities were slected.The T2 value of nucleus pulposus in both two groups were measured and compared. Results: The T2 values of nucleus pulposus of intervertebral disc of lumbar 1-2, lumbar 2-3, lumbar 3-4, lumbar 4-5 and lumbar 5-sacral 1 in the control group were (108.17±10.87)ms, (113.93±11.54)ms, (126.65±10.22)ms, (118.62±8.86)ms and (111.61±10.65)ms, respectively, which of nucleus pulposus in different segments was statistically significant(F=14.28, P<0.001). The T2 values of nucleus pulposus of intervertebral disc of lumbar 1-2, lumbar 2-3, lumbar 3-4, lumbar 4-5, lumbar 5-sacral 1 in the simple obesity group were (104.90±7.67)ms, (101.10±6.61)ms, (112.65±5.75)ms, (98.27±6.18)ms, (89.82±6.34)ms, respectively, , which of nucleus pulposus in different segments was statistically significant(F=49.52, P<0.001). There were statistically significant differences in the T2 values of nucleus pulposus of intervertebral disc of lumbar 2-3, lumbar 3-4, lumbar 4-5, lumbar 5-sacral 1 between the two groups(t=5.283, 6.535, 10.327, 9.626, all P<0.001). Conclusion Magnetic resonance T₂-mapping can detect early changes in tissue composition of intervertebral disc degeneration.Therefore, magnetic resonance T₂-mapping imaging technology can provide an important reference for the early diagnosis of intervertebral disc degeneration in obese people.

Objective:To explore the effects of electronic nursing hand-over schedule based on "knowledge-to-action" frame and evidence-based nursing in orthopedics nursing.Methods:We selected 150 patients of the Department of Orthopedics at the Hangzhou First People's Hospital from May to October 2018 in control group with the traditional handover, and selected 150 patients from November 2018 to April 2019 in intervention group with the electronic nursing hand-over schedule based on "knowledge-to-action" frame and evidence-based nursing. We compared the quality of nursing hand-over between two groups.Results:The nursing hand-over time of intervention group and control group was (2.45±1.05) min and (5.17±1.26) min respectively with a statistical difference ( t=11.726, P<0.05) . In intervention group, there were no missing items in the nursing hand-over, and the incidence of nursing risk events was 1.33% (2/150) , and the qualified rate of nursing measures was 98.0% (147/150) which were better than those in control group with statistical differences (χ 2=4.252, 4.624, 4.795; P<0.05) . Conclusions:The electronic nursing hand-over schedule based on "knowledge-to-action" frame and evidence-based nursing can improve the quality of nursing hand-over for orthopedics patients.

Objective To compare the cognitive function of patients with carotid stenosis combined with white matter lesions (WML)after carotid artery stenting (CAS). Methods Total 166 patients with carotid artery stenosis were collected.According to MRI imaging,30 patients with no white matter lesions were included in the control group and 136 patients with white matter lesions were included in the white matter lesions group. They were treated with carotid artery stenting and underwent evaluation on the safety and efficacy of perioperative surgery. CAS failed in two patients because of the inability of guidewire crossing in WML group. Two patients died after CAS (one for cardiac death and one for traumatic accident) in WML group. 162 patients received 1 year follow-up. Cognitive function was assessed before and after CAS. Results Before CAS,WML group's MMSE, digit span forward/backward test, verbal fluency test and MoCA scores (21.8±3.3、6.3±2.1、4.1±1.0、15.1±3.6、20.6±3.1) were lower compared with control (24.3±3.9、7.3±2.6、4.7±1.8、17.7±5.2、22.7±4.2) and ADAS-Cog score was higher compared with control ((15.1±3.3) vs.(12.7±3.3)), P=0.000、0.026、0.039、0.012、0.000、0.011.Three months after CAS,the MMSE,digit span forward test and MoCA scores (23.7±3.6,7.5± 2.4, 23.1±6.9) was higher significantly than those before treatment (21.8±4.3, 6.3±2.09, 20.6±4.13), P<0.05.And the scores of ADAS-Cog was lower((13.2±4.)vs.(15.1±4.3),P<0.05).The scores of digit span backward test in 6 months after treatment was significant higher than those before treatment (4.9 ±2.8,4.1 ±2.2,P<0.05). After 1 year of CAS, the improvement in scores of MMSE, digit span forward test, ADAS-Cog and MoCA in patients with carotid stenosis complicated with WML(3.5±1.3,1.6±0.6,-2.6±0.8,3.6±1.1)was higher significant than control(2.7±1.8, 1.2±0.8, -2.0± 1.3, 2.7 ±1.5),P<0.05. Conclusion CAS can improve cognitive function in Patients with carotid artery stenosis complicated with WML than those who without WML.

Objective To investigate the effect of E1A gene on the radiosensitivity of human nasopharyngeal carcinoma cells and its possible mechanism. Methods The E1A gene was transfected into nasopharyngeal carcinoma CNE-2R cells by adenovirus vector. The expression of E1A gene was detected by RT-PCR. Untransfected CNE-2R cells(PBS group)and CNE-2R cells transfected with empty vector Ad-β-gal(Ad-β-gal group)and E1A(Ad-E1A group)were given 0 Gy,2 Gy,4 Gy,6 Gy,8 Gy 6 MV X-ray irradiation. The changes in radiosensitivity of CNE-2R cells were determined by colony-forming assay. Flow cytometry was used to analyze cell apoptosis in each group. The expression of NF-κB, CK2α, Bcl-2, and cleaved caspase-3 was measured by Western blot. Results RT-PCR confirmed that the E1A gene was transfected into CNE-2R cells and stably expressed. The Ad-E1A group had a significantly lower plating efficiency than the PBS group and the Ad-β-gal group(P<0.05). The Ad-E1A group had significantly lower cell survival rate at 2 Gy irradiation than the PBS group and the Ad-β-gal group(0.217 vs. 0.602, P<0.05;0.217 vs. 0.585, P<0.05). The Ad-E1A group had a significantly higher α/β value than the PBS group and the Ad-β-gal group(24.680 vs. 5.268, P<0.05;24.680 vs. 5.132, P<0.05). Flow cytometry results showed that irradiation alone could promote the apoptosis of CNE-2R cells,when combined with E1A gene,the apoptosis rate was significantly increased(P<0.05). Western blot results showed that E1A gene down-regulated the expression of NF-κB/p65,CK2α,and Bcl-2 and up-regulated the expression of cleaved caspase-3. Conclusions E1A gene can enhance the radiosensitivity of nasopharyngeal carcinoma cells by inhibiting the expression of CK2 to block the NF-κB signaling pathway and promoting cell apoptosis.

Objective To investigate the effect of Tiopronin (TIP) on interleukin (IL)-2 immunotherapy of human leukemia KG-1 cells and its possible mechanism.Methods KG-1 ceils in logarithmic growth phase were randomly divided into KG-1 + IL-2 group and KG-1 + IL-2 + TIP group.Methyl thiazolyl tetrazolium (MTI) assay and colony formation assay were used to detect the sensitivity and proliferation of KG-1 cells.The changes of reactive nitric metabolites (RNM) were detected with nitrate reductase method.The production of tumor necrosis factor (TNF)-3 and interferon (IFN)-γ,was detected with enzyme linked immunosorbent assay (ELISA).The expression of CD3ξ was detected with Western blot and real time polymerase chain reaction (RT-PCR).Results IL-2 and IL-2 + TIP could inhibit the growth of KG-1 cells.The inhibitory rate of KG-1 + IL-2 + TIP group was significantly higher than that of KG-1 + IL-2 group,and the sensitivity of KG-1 cells to IL-2 was 6.2 times higher.Both IL-2 and IL-2 + TIP group inhibited the colony formation of KG-1 cells.Compared to KG-1 + IL-2 group,KG-1 + IL-2 + TIP group inhibited the colony formation of KG-1 cells by 3.5 times.The RNM production of KG-1 + IL-2 group was (158.26 ± 3.82) μmol/ml,which was significantly higher than (45.18 ± 4.29) μ mol/ml of KG-1 + IL-2 + TIP group (P ＜ 0.05).The levels of TNF-β and IFN-γin KG-1 + IL-2 + TIP group were (253.28 ± 7.84) pg/ml and (181.25 ±6.41) pg/ml,which was significantly higher than (98.45 ±6.43) pg/ml and (68.74 ±8.26) pg/ml of KG-1 +IL-2 group (P＜0.05).The expression of CD3ξ in KG-1 +IL-2 +TIP group was significantly higher than that in KG-1 + IL-2 group.Conclusions Tiopronin can promote NK/T cell activity and increase the sensitivity of leukemia KG-1 cells to IL-2 by eliminating reactive nitrogen metabolites.

Objective To investigate the effects and its possible mechanisms of tiopronin (TIP) on interleukin-2 (IL-2) immunotherapy of human leukemia KG-1 cells transplanted in nude mice.Methods KG-1 cells (1 x 107/ml) in logarithmic growth phase were injected subcutaneously into the groin of the left hind leg of the 45 5-week-old nude mice.When the subcutaneous tumor diameter was about 8 mm,nude mice were randomly divided into three groups (n =15):Control group (intraperitoneal injection of phosphate buffer),IL-2 group (hypodermic injection of IL-2),IL-2 + TIP group (hypodermic injection of IL-2 and intraperitoneal injection of TIP).The therapeutic effect of TIP combined with IL-2 on human leukemia KG-1 cells transplanted in nude mice was observed.The number of nature killer (NK) cells in peripheral blood of nude mice was detected by flow cytometry.Nitrate reductase assay was used to detect reactive nitric metabolite (RNM) levels in peripheral blood of nude mice.Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of tumor necrosis factor-β (TNF-β) and interferon-γ (IFN-γ) in peripheral blood of nude mice.Terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay was used to analyze apoptosis.Results Both IL-2 and IL-2 + TIP could inhibit the growth of transplanted tumor.Compared with IL-2 group [(54.32 ± 4.32) ％],the tumor inhibition rate of IL-2 + TIP group was (90.15 ± 3.75)％,and its inhibition of tumor growth was more obvious (t =11.893,P ＜ 0.001).The tumor weights of Control group,IL-2 group and IL-2 + TIP group were (0.95 ± 0.05)g,(0.58 ± 0.03)g and (0.27 ± 0.07)g,and there was statistically significant difference among the three groups (F =52.716,P ＜ 0.001).Compared with IL-2 group,the tumor weight of IL-2 + TIP group was significantly reduced (P =0.008).The number of NK cells in IL-2 + TIP group was (0.658 ±0.157)/L,which was significantly higher than (0.452 ±0.124)/L of IL-2 group (P =0.021).The concentration of RNM in IL-2 + TIP group was (42.92 ± 4.68)μmol/ml,which was significantly lower than (163.38 ± 5.49)μmol/ml in IL-2 group (P =0.007).The concentrations of TNF-β and IFN-γin IL-2 + TIP group were (247.68 ± 8.24) pg/ml and (185.61 ±7.58) pg/ml,which were significantly higher than (97.48 ± 7.28)pg/ml (P =0.021) and (70.62 ± 8.47)pg/ml (P =0.015) in IL-2 group.The apoptotic rate of tumor cells in IL-2 + TIP group was (47.38±4.25)％,which was significantly higher than (21.41 ±2.79)％ in IL-2 group (P ＜0.001).Conclusion TIP can increase the sensitivity of leukemia cells to IL-2 immunothe-rapy by removing RNM,promoting NK cells activity and increasing NK cells-induced tumor cell apoptosis.

Objective To investigate the low-dose hyper-radiosensitivity (HRS)/induced radioresistance (IRR) in A549 cells synchronized at G2 phase and the role of ATM kinase in the process.Methods Human lung adenocarcinoma cell line A549 was synchronized at G2 phase by aphidicolin.The ATM-specific activator and inhibitor,chloroquine and KU55933,were used to regulate the activity of ATM.The colony formation assay was used to evaluate cell survival.Flow cytometry was used to determine the cell cycle of radiation-exposed A549 cells synchronized at G2 phase.Immunofluorescence was used to observe the dynamics of γ-H2AX fluorescence and evaluate the efficiency of DNA repair in A549 cells synchronized at G2 phase.Western blot was used to detect the expression of phosphorylated ATM (Ser1981) and ATM.Results A549 cells synchronized at G2 phase had substantially enhanced HRS than non-synchronized cells.The dose-induced transition from HRS to 1RR was in accordance with the dose-response pattern of early G2/M checkpoint.However,with the same threshold dose,the activation of early checkpoint occurred earlier and lasted longer than normal.The activation of ATM kinase inhibited HRS and enhanced DNA repair,while the inhibition of ATM kinase enhanced HRS and hindered DNA repair.Conclusions ATM kinase-mediated early G2+M checkpoint is a molecular switch for HRS in synchronized A549 cells.Low-dose irradiation with G2-phase synchronization and ATM inhibitor can enhance the low-dose radiosensitivity.

OBJECTIVETo evaluate the predictive value of a combination of anatomy scoring system and physiological scoring system for the diagnosis of multiple organ dysfunction syndrome (MODS) in patients with severe trauma.

METHODSThe clinical data of 539 patients with severe trauma hospitalized in ICUs of the First Affiliated Hospital of Chengdu Medical College, Daping Hospital of the Third Military Medical University, and the Affiliated Hospital of Zunyi Medical College from January 2010 to December 2014, conforming to the study criteria, were retrospectively analyzed. The patients were divided into MODS group (n=361) and non-MODS group (n=178) according to the diagnostic criteria of MODS. The data of Injury Severity Score (ISS), New Injury Severity Score (NISS), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, ISS+ APACHE II score, and NISS+ APACHE II score of patients on the first day of ICU admission were calculated and compared between the two groups. Data were processed with t test, chi-square test, and receiver operating characteristic (ROC) curves of the various scoring systems in 539 patients with severe trauma were plotted, and DeLong-DeLong non parametric test was used to evaluate the predictive ability for MODS of the various scoring systems.

RESULTSThe scores of ISS, NISS, APACHE II, ISS+ APACHE II, and NISS+ APACHE II of patients in MODS group were respectively (26±8), (36±12), (21±7), (47±10), and (56±14) points, and they were significantly higher than those of patients in non-MODS group [respectively (24±6), (28±7), (16±5), (39±8), and (44±9) points, with t values from 4.970 to 12.120, P values below 0.01]. The total areas under ROC curves (95% confidence interval) of ISS, NISS, APACHE II score, ISS+ APACHE II score, and NISS+ APACHE II score in MODS prediction of patients with severe trauma were respectively 0.611 (0.569-0.653), 0.693 (0.652-0.731), 0.719 (0.679-0.756), 0.727 (0.687-0.764), and 0.764 (0.726-0.799). The total areas under ROC curves of NISS, APACHE II score, ISS+ APACHE II score, and NISS+ APACHE II score were significantly larger than the total area under ROC curve of ISS (with Z values from 3.505 to 7.179, P values below 0.001). The total areas under ROC curves of APACHE II score and ISS+ APACHE II score were larger than the total area under ROC curve of NISS, but there were no significant differences (with Z values respectively 0.931 and 1.657, P values above 0.05), while the total area under ROC curve of NISS+ APACHE II score was significantly larger than that of NISS (Z=5.478, P<0.001). The total area under ROC curve of ISS+ APACHE II score was larger than that of APACHEⅡ score, but there was no significant difference (Z=0.450, P=0.653), and the total area under ROC curve of NISS+ APACHE II score was significantly larger than that of APACHE II score (Z=2.554, P<0.05). The total area under ROC curve of NISS+ APACHE II score was significantly larger than that of ISS+ APACHE II score (Z=2.989, P<0.01).

CONCLUSIONSThe combination of NISS and APACHE II score is more significant than ISS, NISS, APACHE II score, and ISS+ APACHE II score in prediction of MODS in patients with severe trauma.

APACHE ; Humans ; Injury Severity Score ; Intensive Care Units ; Multiple Organ Failure ; diagnosis ; physiopathology ; Organ Dysfunction Scores ; Outcome Assessment (Health Care) ; Predictive Value of Tests ; ROC Curve ; Retrospective Studies ; Sensitivity and Specificity