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AIM:This study was performed to investigate the impact of neutrophil extracellular traps(NETs)on scar formation following urethral trauma.METHODS:(1)Clinical samples were derived from patients of Department of Urology,The First Affiliated Hospital of Fujian Medical University,from June 2021 to December 2022.Levels of NETs in the blood and urine were compared between patients with urethral trauma(n=20)and those without urethral trauma(controls,n=20).The relationship between NETs and scar formation was analyzed.(2)Urethral fibroblasts were isolated from urethral scar tissues,and neutrophils were induced to produce NETs in vitro.The urethral fibroblasts were treated with normal saline,0.5 mg/L NETs,or 1.5 mg/L NETs to investigate the effects of NETs on activation and collagen syn-thesis of urethral fibroblasts.Additionally,a rabbit model of urethral trauma was established and the animals were dioided into four groups to explore the therapeutic potential of deoxyribonuclease I(DNase I)in preventing urethral scar forma-tion:control,operation + transforming growth factor-β1(TGF-β1),operation + normal saline,and operation+DNase I.RESULTS:The level of NETs in urine increased after urethral trauma(P<0.05),but the level of NETs in blood did not change(P>0.05).In the animal models,the urethral scar became more severe as the level of NETs in the urine increased(P<0.05).At the cellular level,NETs promoted the viability,migration,and collagen synthesis of urethral fibroblasts(P<0.05)..Additionally,urethral injection of DNase I after trauma reduced the level of NETs and inhibited the formation of urethral scar tissue in the animal models(P<0.05).CONCLUSION:Infiltration of NETs promotes activation of urethral fibroblasts and scar formation after urethral trauma.
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Objective To evaluate the safety of the low glucoside composites of Epimedii Folium and clarify the pharmacokinetic characteristics of its five low glucosides.Methods Four groups of KM mice were orally administrated of corn oil,1 968,2 625 and 3 500 mg·kg-1 low glucoside composites of Epimedii Folium,respectively.Then,the living conditions,toxic symptoms,and death of the mice were observed for 7 consecutive days.After the mice were dissected,the viscera/body ratio and the viscera/brain ratio were calculated.Besides,the contents of alanine aminotransferase(ALT)and aspartate transaminase(AST)in plasma were determined by ELISA,and the pathological changes of the liver were observed by HE staining.C57BL/6J mice were intravenously or orally administered of baohuoside I,baohuoside II,sagittatoside A,sagittatoside B and sagittatoside C.Then,blood samples were collected at different time points.The plasma concentrations of the five low glucosides were measured by UHPLC-MS/MS.Results When compared with the control group,no significant differences were found in the body mass,viscera/body ratio,viscera/brain ratio,contents of ALT and AST in plasma after oral administration of different doses of low glucoside composites to mice.Moreover,no pathological changes or damages were found in the liver sections.After intravenous injection,the AUC0-t values of baohuoside Ⅰ,baohuoside Ⅱ,sagittatoside A,sagittatoside B and sagittatoside C in mice were 4.82,82.54,276.64,88.77 and 178.02 min·μg·mL-1,respectively.Meanwhile,the t1/2 values were 60.42,115.27,67.63,131.61 and 129.87 min,respectively.After oral administration,the AUC0-t values of the five low glucosides were 31.64,18.59,3.48,2.41 and 2.42 min·μg·mL-1,respectively.The Cmax values were 147.23,86.76,15.58,24.34 and 26.12 ng·mL-1,respectively.The tmax values were 21.00,78.00,78.00,30.00 and 28.00 min,respectively.The bioavailability of baohuosideⅠ,baohuosideⅡ,sagittatoside A sagittatoside B and sagittatoside C were 1.91%,0.51%,0.05%,0.06%and 0.04%,respectively.Conclusion The low glucoside composites of Epimedii Folium has high safety,and no hepatotoxicity were observed at dose of 3 500 mg·kg-1.The 5 low glucosides are quickly absorbed and rapidly eliminated in mice,and all of them have low bioavailability.
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Objective To investigate the role of clinical pharmacists in individualized treatment and pharmaceutical care for a Crohn’s disease patient with non-response to infliximab. Methods The clinical pharmacist participated in the pharmaceutical care for a Crohn’s disease patient with hypoalbuminemia. Clinical pharmacists interpreted the blood concentration results of infliximab based on literature review, analyzed the pharmacokinetic process of drugs, and suggested that low serum albumin levels may cause the accelerated drug elimination and resulted in reduced drug concentration and secondary non-response. Results Clinical pharmacists assisted clinician adjusting the medication regimen and the patient recovered well after the new treatment plan. Conclusion With good understanding in medication pharmacokinetics and the blood test results, clinical pharmacists can help to solve the drug therapy related problems and establish an individual treatment plan to improve the safety and effectiveness of the biological medications.
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Objective:To investigate correlations between blood lipid levels and clinical characteristics of patients with psoriasis vulgaris (PsV) in Fujian province.Methods:Totally, 245 PsV patients were enrolled from Department of Dermatology of the First Affiliated Hospital of Fujian Medical University from March 2019 to March 2022, and 250 gender-, age-, and body mass index-matched health checkup examinees served as controls. Their biochemical indicators, such as blood lipids, liver function, and kidney function, were evaluated. Clinical data, such as disease courses, involvement of specific sites, history of smoking and alcohol consumption, and family history of psoriasis, were collected from the PsV patients, and correlations between these clinical data and dyslipidemia were analyzed. Measurement data were compared using t test or Mann-Whitney U test, and enumeration data were compared using chi-square test. Results:There were 122 (50.8%) patients with dyslipidemia in the PsV group and 94 (37.6%) in the control group, and the prevalence of dyslipidemia significantly differed between the two groups ( χ2 = 7.48, P = 0.006). The prevalence of hypo-high-density lipoprotein cholesterolemia was significantly higher in the PsV group (29.8%) than in the control group (18.8%; χ2 = 8.15, P = 0.004). The PsV group showed significantly decreased serum levels of total cholesterol (4.5[3.9, 5.2] mmol/L), high-density-lipoprotein cholesterol (1.1[1.0, 1.3] mmol/L), and apolipoprotein A1 (1.2[1.1, 1.4] g/L) compared with the control group (4.9[4.3, 5.4] mmol/L, 1.3[1.1, 1.5] mmol/L, 1.3[1.2, 1.5] g/L, respectively; all P < 0.001). The proportions of males, patients with a history of alcohol consumption, and patients with involvement of the palmoplantar sites were significantly higher in the PsV patients with dyslipidemia (92.6%, 13.1%, 13.8%, respectively) than in those without dyslipidemia (70.7%, 6.0%, 5.0%, respectively; all P < 0.001). Multifactorial logistic regression analysis showed that "male" and "BMI ≥ 25 kg/m 2" were independent risk factors for dyslipidemia in the PsV patients ( OR [95% CI]: 3.94 [1.74, 9.74], 3.18 [1.71, 6.09], respectively), and "involvement of the palmoplantar sites" was independently associated with increased risk of hyperlipidemia ( OR [95% CI]: 3.38 [1.18, 11.01]) . Conclusion:The prevalence of dyslipidemia was higher in PsV patients than in healthy populations, and PsV patients being males, having BMI ≥ 25 kg/m 2 and with involvement of palmoplantar sites may be prone to develop lipid metabolism disorders.
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Objective:To observe the characteristics of the phagocytosis and bactericidal function of multidrug-resistant Mycobacterium tuberculosis(MDR- Mtb)-infected macrophage model, and the changes of the immune response and metabolic function in the process of phagocytosis and bactericidal function, aiming to provide reference for studying the role and mechanism of macrophages in the occurrence and development of multidrug-resistant tuberculosis(MDR-TB). Methods:We established MDR- Mtb and H37Rv-infected macrophage models, and used the colony-forming unit (CFU), Magnetic Luminex ? Assay and Cholesterol Assay kit to observe the effects on phagocytosis and bactericidal function, the secretion of Th1(IL-12/23 p40, IL-27 and TNF-α) and Th2 cytokines (IL-6 and IL-10) and cholesterol metabolism. The data were analyzed by SPSS25.0 software. The data were expressed as Mean± SD and analyzed by t test or F test. P<0.05 was considered statistically significant. Results:(1) After MDR- Mtb-infected macrophages, the intracellular CFU gradually increased and reached the highest at 24 h, while the extracellular CFU gradually decreased and reached the lowest at 24 h. The intracellular CFU at 48 h was lower than that at 24 h, while the extracellular CFU was higher than that at 24 h ( P<0.05). Both intracellular and extracellular CFU at 48 h were close to those at 4 h ( P>0.05). The intracellular CFU was lower than the H37Rv group at 8-48 h, while the extracellular CFU was higher than the H37Rv group ( P<0.05). (2) The level of IL-12/23 p40, IL-27, TNF-α, IL-6 and IL-10 of MDR-TB group were higher than those of blank group ( P<0.05), but the level of TNF-α and IL-6 at 24 h and 48 h were higher than that at 4 h ( P<0.05). IL-12/23 p40 and TNF-α at 48 h and IL-6 at 24 h were lower than those of the H37Rv group, while IL-27 at 48 h was higher than that of the H37Rv group ( P<0.05). (3) The levels of cholesterol of MDR-TB group at 24 h and 48 h were lower than those of 4 h and blank group ( P<0.05), but the level of cholesterol was similar to the H37Rv group at any time ( P>0.05). (4) TNF-α reached the highest when the intracellular CFU reached the highest at 24 h, and IL-6 reached the highest when the intracellular CFU decreased at 48 h. With the decreasing of cholesterol expression, the intracellular CFU increased and then decreased. Conclusions:MDR- Mtb could induce the phagocytosis and bactericidal function of macrophages, increase the expression of Th1 and Th2 cytokines and promote the utilization and consumption of cholesterol, but this function was weaker than that of H37Rv strain.
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Objective:To understand the current situation of physicians′ competency in China and statistically analyze its influencing factors, hence providing referential evidences for promoting their competency.Methods:The evaluation scale for Chinese physicians′ competency was developed by referring to sophisticated overseas evaluation frameworks. Based on the electronic platform of the medical alliance, stratified sampling was conducted at 39 hospitals in 13 provinces, from which 2 156 physicians were surveyed, and statistical analysis was made on the current situation and influential factor of their competency in 6 dimensions(medical knowledge, diagnosis and treatment, scientific research and teaching, interpersonal communication, spirit of professionalism, population health)Results:The score range in multiple dimensions of physicians′ competency was between 2.85 and 3.89(5 in total), among which spirit of professionalism dimension scores the highest, and teaching and research dimension scores the lowest. Logistic regression analysis shows that their competency level in 6 dimensions is correlated to a range of factors, including gender, degree, title, supervisor qualifications, standardized training program of specialist physicians, and affiliation or not to teaching hospitals( P<0.05). Conclusions:Their overall competency is expected to be elevated. To name a few, they are lack of teaching and research abilities, and need to conduct clinical-oriented scientific research; they are expected to enrich knowledge structure, and need to embrace a wider concept of health; they need to improve their non-technical service abilities, and should further emphasize their humanistic quality; physicians′ practice competency depends upon their extent of medical education, and ensuring the quality of standardized training becomes the key measure.
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Objective To observe the protective effect of polypyrimidine bundle-binding proteinrelated splicing factor (PSF) over-expression on RPE cell injury induced by advanced glycation end products (AGEs).Methods The human RPE cells cultured in vitro were divided into three groups:normal control group (N group),blank control group (N + AGEs group),empty vector control group (Vec + AGEs group),and PSF high expression group (PSF + AGEs).group).RPE cells in N group were routinely cultured;RPE cells in N + AGEs group were only transfected but did not introduce any exogenous genes combined with AGEs induction;Vec +AGEs group and PSF + AGEs group were transfected with pcDNA The empty vector or pcDNA-PSF eukaryotic expression plasmid was introduced into RPE cells and induced by AGEs.Except the N group,the other 3 groups of cells were transfected accordingly,and were stimulated with 150 μg/ml AGEs for 72 h after 24 h.HE staining and Hoechst 33258 staining were used to observe the effect of high PSF expression on the morphological changes of RPE cells;ROS level detection was used to analyze the effect of PSF high expression on the ROS expression of RPE cells induced by AGEs;MTT colorimetric method was used to detect the high PSF expression Effects on the viability of RPE cells;Western blot was used to detect the effects of different time and dose of PSF on the expression of heme oxygenase 1 (HO-1).Results HE staining and Hoechst 33258 staining observation showed that the cells in group N were full in shape,the nucleus was round,the cytoplasm was rich,and the staining was uniform;the cells in N + AGEs group and Vec + AGEs group were reduced in size,the eosinophilic staining was enhanced,and the nucleus was densely densely stained.Pyrolysis and even fragmentation;the morphology of cells in the PSF + AGEs group was still full,the cytoplasm staining was more uniform,and the nucleus staining was uniform.The results of MTT colorimetry showed that high expression of PSF can effectively improve the viability of RPE cells,but this effect can be effectively antagonized by ZnPP,and the difference is statistically significant (F=33.26,P<0.05).DCFH-DA test results showed that compared with the N + AGEs group and Vec + AGEs group,the ROS production in PSF + AGEs group decreased,the difference was statistically significant (F=1 1.94,P<0.05).Western blot analysis showed that PSF protein upregulated HO-1 expression in a time-and dose-dependent manner.The relative expression level of HO-1 at 24,48,and 72 h after PSF protein was significantly higher than that at 0 h,and the difference was statistically significant (F=164.91,P<0.05).The relative expression level of HO-1 under the action of 0.1,0.5,1.0,1.5,and 2.0 μg PSF protein was significantly higher than 0.0 μg,and the difference was statistically significant (F=104.82,P<0.05).Conclusion PSF may inhibit the production of ROS by up-regulating the expression of HO-1,thus protecting the RPE cells induced by AGEs.
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Objective To investigate the inhibitory effect oflentivirus-mediated polypyrimidine bundle binding protein-associated splicing factor (PSF) on retinal neovascularization (RNV) in mice model of oxygeninduced retinopathy (OIR).Methods One hundred and twelve 5-day-old C57BL/6J mice were randomly divided into normal control group,simple OIR model group,OIR model + lentivirus empty vector treatment group (Vec group) and OIR model + PSF lentivirus treatment group (PSF group),with 16,32,32 and 32 mice,respectively.When the mice were 7 days old,the mice in the normal control group were fed in a routine environment,and the mice in the OIR model group,Vec group and PSF group were established OIR model.The mice in the Vec group and PSF group were given an intravitreal injection of 1 μl of lentiviral vector and PSF lentivirus (titer 1 × 10~ TU/ml) at the age of 12 days.No injection was performed in the normal control group and simple OIR group.RNV was evaluated by counting the number of pre-retinal neovascular cells and analysis of non-perfusion area by immunofluorescent staining of the mouse retina.Real-time quantitative PCR was applied to detect the mRNA expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase1 (HO-1).Western blot analysis was applied to detect the protein expression ofNrf2,HO-1 and PSF.Results Of the normal control group,simple OIR model group,Vec group and PSF group,the number of pre-retinal neovascular cell nuclei were 0.00,14.36 ± 5.50,15.67 ± 4.96,8.13 ± 2.09,the non-perfusion area were 0.00%,(35.71 ± 2.81)%,(36.57 ± 4.53)%,(15.33 ± 4.75)%,respectively.The differences of the number of pre-retinal neovascular cell nuclei and non-perfusion area among 4 groups were significant (F=24.87,165.70;P<0.05).Compared with the normal control group,there were more pre-retinal neovascular cell nucleis and larger nonperfusion area in the simple OIR model group and Vec group (P<0.05).Compared with the simple OIR model group and Vec group,there were lower pre-retinal neovascular cell nucleis and smaller non-perfusion area in the PSF group (P<0.05).Real-time quantitative PCR and Western blot showed that the mRNA expression of Nrf2,HO-1 (F=53.66,83.54) and protein expression ofNrf2,HO-1 and PSF (F=58.38,52.69,24.79) among 4 groups were significant (P<0.05).The rnRNA expression ofNrf2,HO-1 and protein expression of Nrf2,HO-1 and PSF in the simple OIR model group and Vec group decreased significantly than those in the normal control group (P<0.05).The mRNA expression ofNrf2,HO-1 and protein expression ofNrf2,HO-1 and PSF in the PSF group were increased significantly than those in the simple OIR model group and Vec group (P<0.05).model group and Vec group (P<0.05).Conclusion Intravitreal injection of lentivirus-mediated PSF inhibits RNV in mice model of OIR possibly through up-regulating the expression of Nrf2 and HO-1.
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Objective:To observe the effect of pyrimidine bundle-binding protein-associated splicing factors (PSF) on the function of hypoxia-induced human retinal microvascular endothelial cells (hRMECs).Methods:A three-plasmid system was used to construct lentivirus (LV)-PSF. After LV-PSF infected hRMECs in vitro, the infection efficiency was measured by flow cytometry. Real-time quantitative PCR (RT-PCR) was used to detect the expression of PSF mRNA in hRMECs infected with LV-PSF. The experiment was divided into two parts, in vivo and in vitro. In vivo experiments: 20 healthy C57B/L6 mice at the age of postnatal 7 were randomly divided into normal group, oxygen-induced retinopathy (OIR) group, OIR+LV-Vec group, and OIR+LV-PSF group, each group has five mice. Mice in 3 groups were constructed with OIR models except the normal group and the mice in OIR group were not treated. The mice in the OIR + LV-Vec group and the OIR+LV-PSF group were injected with an empty vector (LV-Vec) or LV-PSF in the vitreous cavity, respectively. The effect of LV-PSF on the formation of retinal neovascularization (RNV) was observed then. In vitro experiments: hRMECs were divided into normal group, hypoxia group, vector group, and PSF high expression group. HRMECs in the normal group were cultured in vitro; hRMECs in the hypoxic group were restored to normal culture conditions for 3 h after 3 h of hypoxia stimulation; hRMECs in the vector group and PSF high expression group were infected with LV-Vec and LV-PSF for 48 h, and hRMECs were returned to normal culture conditions for 24 h with hypoxia stimulation for 3 h. The effect of PSF on cell proliferation was observed by MTT colorimetry. Cell scratch test and Transwell migration experiment were used to observe the effect of PSF on cell migration ability under hypoxia stimulation. RT-PCR was used to observe the mRNA expression of HIF-1α, VEGF and PSF in each group of cells.Results:The LV-PSF of stably expressing PSF was successfully constructed. The infection efficiency was 97% determined by flow cytometry. The level of PSF mRNA in hRMECs infected with LV-PSF was significantly increased and detected by RT-PCR. In vivo experiments: The RNV area of the mice in the OIR group and the OIR + LV-Vec group was significantly increased compared to the normal group ( t=18.31, 43.71), and the RNV area of the mice in the OIR + LV-PSF group was smaller than that in the OIR group ( t=11.30) and OIR + The LV-Vec group ( t=15.47), and the differences were statistically significant ( P<0.05). In vitro experiments: MTT colorimetry results showed that the proliferative capacity of hRMECs in the hypoxic group was significantly enhanced compared with the normal group ( t=2.57), and the proliferative capacity of hRMECs in the PSF high expression group was significantly lower than that of the normal, hypoxic, and vector groups ( t=5.26, 5.46, 3.73), the differences were statistically significant ( P<0.05). The results of cell scratch test showed that the hRMECs could be stimulated by the hypoxia stimulation for 3 hours to restore the normal condition for 24 hours or 48 hours ( t=8.35, 13.84; P<0.05). Compared with the vector group, cell migration rate in the PSF-high expression group was not significant ( t=10.99, 18.27, 9.75, 8.93, 26.94, 7.01; P<0.05). Transwell experiments showed that the number of cells stained on the microporous membrane was higher in the normal group and the vector groups, while the number of cells stained in the PSF high expression group was significantly reduced ( t=9.33, 6.15; P<0.05). The results of RT-PCR showed that the mRNA expression of HIF-1α and VEGF in hRMECs in the hypoxic and vector groups increased significantly compared with the normal group ( t=15.23, 21.09; P<0.05), but no change in the mRNA expression of PSF ( t=0.12, 2.15; P>0.05); compared with the hypoxia group and the vector group, the HIF-1α and VEGF mRNA expression in hRMECs in the PSF high expression group were significantly decreased ( t=10.18, 13.10; P<0.05), but the PSF mRNA expression increased ( t=65.00, 85.79; P<0.05). Conclusion:PSF can reduce the RNV area in OIR model mice. PSF may inhibit hypoxia-induced proliferation and migration of hRMECs through the HIF-1α/VEGF signaling pathway.
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Objective:To investigate the protection and the corresponding molecular mechanisms of polypyramidine tract binding protein-associated splicing factor (PSF) overexpression on human retinal microvascular endothelial cells (hRMECs) induced by advanced glycation end-products (AGEs).Methods:The hRMECs were divided into the normal group, the vector group, PSF group, zinc protoporphyrin (ZnPP) group and PSF+ZnPP group for experiment. Cells in the normal group were cultured in a DMEM medium containing 10% fetal calf serum, penicillin/streptomycin, and placed in a closed constant temperature incubator at 37 °C, 95% air, and 5% CO 2. Cells in the vector group were infected with empty lentivirus. The cells in the PSF group were infected with overexpressing PSF lentivirus. Cells in the ZnPP group were treated with ZnPP (10 mol/L) for 2 h. The PSF+ZnPP group cells were infected with overexpressing PSF lentivirus, and then pretreated with ZnPP (10 mol/L) for 2 h. With the last four groups of cells stimulated with AGEs, HE, Hoechst33258 staining and flow cytometry were used to observe the protective effect of high expression of PSF on cell damage and the antagonistic effect of ZnPP on PSF. Western blot was used to detect the protein expression of heme oxygenase-1 (HO-1), phosphorylated (p) extracellular regulatory protein kinase (ERK), and Nrf2 in the cells. U0126, a specific antagonist of ERK pathway, was introduced, and Western blot verified the reversal effect of U0126 on the expression of HO-1 induced by PSF protein. Results:HE staining and Hoechst33258 staining showed that the number of nuclei of damaged cells of PSF group were significantly increased compared with control group, while decreased compared with PSF+ZnPP group ( F=27.5, 38.7; P<0.05). The results of flow cytometry showed that the ROS produced by cells in the PSF group was significantly increased compared to the normal group, and significantly decreased compared to the PSF+ZnPP group, the difference was statistically significant ( F=126.4, P<0.05). Western blot results showed that HO-1 expression of PSF group was significantly increased compared with control and the vector group ( F=70.1, P<0.05). AGEs inducement of 30, 60, 120 and 240 min could significantly improve pERK expression compared with 15 min ( F=474.0, P<0.05). The expression of HO-1 and Nrf2 proteins in the PSF+/U0126- group was significantly more than those in the PSF-/U0126-group, the expression of HO-1 and Nrf2 proteins in the PSF+/U0126+ group was significantly lower than that in the PSF+/U0126- group, and the differences were statistically significant ( F=30.2, 489.4; P<0.05). Conclusion:Over expression of PSF can promote the HO-1 expression by activating ERK pathway and promoting the Nrf2 to the nucleus, thus protect hRMECs against AGEs-induced oxidative damage.
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Objective@#To evaluate the role of mitochondrion-dependent apoptosis in reduction of bupivacaine-induced cardiotoxicity by lipid emulsion in rats.@*Methods@#Forty-five healthy adult male Sprague-Dawley rats, weighing 300-350 g, were divided into 3 groups by a random number table method: sham operation group (Sham group, n=5), bupivacaine group (B group, n=20), and lipid emulsion group (L group, n=20). Cardiac arrest was induced by intravenously injecting 0.4% bupivacaine 30 mg/kg over 20 s to establish the cardiotoxicity model.Twenty percent lipid emulsion was intravenously injected in a dose of 5 ml/kg during resuscitation in group L, and normal saline was intravenously injected in a loading dose of 5 ml/kg during resuscitation in group B, followed by a 3-min infusion of 1 ml·kg-1·min-1in two groups.The successful resuscitation and survival rate at 120 min of return of spontaneous circulation (ROSC) were recorded.Systolic blood pressure, heart rate, mean arterial pressure, rate-pressure product (RPP) and ratio of RPP at each time point after recovery of spontaneous heart beat to baseline value (RPPh) were recorded every 10 min after ROSC.The time from administration to cardiac arrest (T0), time from beginning of cardiopulmonary resuscitation to appearance of the first spontaneous heart beat (Ts) and time from beginning of cardiopulmonary resuscitation to appearance of ROSC (Tr) were recorded.Rats were sacrificed at 120 min of ROSC, and left ventricular tissues were obtained for determination of the expression of Bax, Bcl-2, cleaved caspase-9, cleaved caspase-3, cytochrome C (Cyt c) in cytoplasm and mitochondria (by Western blot) and expression of Bax and Bcl-2 mRNA (by real-time polymerase chain reaction) and for examination of myocardial ultrastructure.@*Results@#Compared with Sham group, the expression of Bcl-2 protein and mRNA and mitochondrial Cyt c was significantly down-regulated, and the expression of Bax protein and mRNA, cleaved caspase-9, cleaved caspase-3 and cytoplasmic Cyt c was up-regulated in B group (P<0.05). Compared with B group, the rate of successful resuscitation and survival rate were significantly increased, Tr was shortened, systolic blood pressure, heart rate, RPP and RPPh were increased after ROSC, the expression of Bcl-2 protein and mRNA and mitochondrial Cyt c was up-regulated, the expression of Bax protein and mRNA, cleaved caspase-9, cleaved caspase-3 and cytoplasmic Cyt c was down-regulated (P<0.05), no significant change was found in To or Ts (P>0.05), and the pathological changes of myocardium were significantly attenuated in L group.@*Conclusion@#The mechanism by which lipid emulsion reduces bupivacaine-induced cardiotoxicity may be related to inhibiting mitochondrion-dependent apoptosis in rats.
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Objective To evaluate the role of mitochondrion-dependent apoptosis in reduction of bupivacaine-induced cardiotoxicity by lipid emulsion in rats.Methods Forty-five healthy adult male Sprague-Dawley rats,weighing 300-350 g,were divided into 3 groups by a random number table method:sham operation group (Sham group,n =5),bupivacaine group (B group,n =20),and lipid emulsion group (L group,n =20).Cardiac arrest was induced by intravenously injecting 0.4% bupivacaine 30mg/kg over 20 s to establish the cardiotoxicity model.Twenty percent lipid emulsion was intravenously injected in a dose of 5 ml/kg during resuscitation in group L,and normal saline was intravenously injected in a loading dose of 5 ml/kg during resuscitation in group B,followed by a 3-min infusion of 1 ml · kg-1 · min-1 in two groups.The successful resuscitation and survival rate at 120 min of return of spontaneous circulation (ROSC) were recorded.Systolic blood pressure,heart rate,mean arterial pressure,rate-pressure product (RPP) and ratio of RPP at each time point after recovery of spontaneous heart beat to baseline value (RPPh) were recorded every 10 min after ROSC.The time from administration to cardiac arrest (T0),time from beginning of cardiopulmonary resuscitation to appearance of the first spontaneous heart beat (Ts) and time from beginning of cardiopulmonary resuscitation to appearance of ROSC (Tr) were recorded.Rats were sacrificed at 120 min of ROSC,and left ventricular tissues were obtained for determination of the expression of Bax,Bcl-2,cleaved caspase-9,cleaved caspase-3,cytochrome C (Cyt c) in cytoplasm and mitochondria (by Western blot) and expression of Bax and Bcl-2 mRNA (by real-time polymerase chain reaction) and for examination of myocardial ultrastructure.Results Compared with Sham group,the expression of Bcl-2 protein and mRNA and mitochondrial Cyt c was significantly down-regulated,and the expression of Bax protein and mRNA,cleaved caspase-9,cleaved caspase-3 and cytoplasmic Cyt c was up-regulated in B group (P<0.05).Compared with B group,the rate of successful resuscitation and survival rate were signif-icantly increased,Tr was shortened,systolic blood pressure,heart rate,RPP and RPPh were increased after ROSC,the expression of Bcl-2 protein and mRNA and mitochondrial Cyt c was up-regulated,the expression of Bax protein and mRNA,cleaved caspase-9,cleaved caspase-3 and cytoplasmic Cyt c was downregulated (P<0.05),no significant change was found in To or Ts (P>0.05),and the pathological changes of myocardium were significantly attenuated in L group.Conclusion The mechanism by which lipid emulsion reduces bupivacaine-induced cardiotoxicity may be related to inhibiting mitochondrion-dependent apoptosis in rats.
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Objective To evaluate the predictors of gleason score pathological downgrading after radical prostatectomy in patients with biopsy-proven level 2 of grading groups (Gleason Score 3 + 4 =7).Methods Data of 252 patients,diagnosed with level 2 of grading groups(Gleason score 3 + 4 =7) prostate cancer by biopsy,with subsequent laparoscopic radical prostatectomy,were retrospectively analyzed.The mean age was 64.3,ranged from 46 to 82 years.The average body mass index (BMI) was 23.2 kg/m2,ranged from 15.2 to 30.4 kg/m2.The median prostate volume,transition zone volume(TZV) and transition zone index(TZI) were 48.9 ml (30.3-73.1 ml),21.4 ml(13.5-31.2 ml) and 0.46% (0.37%-0.58%),respectively.The median value of tPSA,fPSA and PSAD were 1.53 ng/ml(0.67-3.92 ng/ml),9.65 ng/ml (4.13-18.68 ng/ml) and 0.18 ng/(ml · cm3) [0.09-0.50 ng/ (ml · cm3)],respectively.Clinical T stage was also evaluated,including 153 (60.7%) diagnosed as T1e stage,78 (3 1.0%) diagnosed as T2 stage,and 21 (8.3%) diagnosed as T3 stage.There were 58(23.0%) with extracapsular extension,47 (18.7%) patients with seminal vesicle invasion,and 2(0.8%) with lymph node metastasis.Pathological T stage includes 112 (44.4%) diagnosed as T2 stage,55 (21.8%) diagnosed as T3a stage,35 (13.9%) diagnosed as T3b stage,and 50(19.8%) diagnosed as T4 stage.The patients were assigned Prostate ImagingReporting and Data System version 2 scores of 1,2,3,4,and 5 were 45 (17.9%),36 (14.3%),51 (20.2%),68(27.0%)and 52(20.6%),respectively.The patients were categorized into 2 groups with and without pathological downgrading,including downgrade and no downgrade group.Univariate and multivariate logistic regression analysis were done to determine the predictors of pathological downgrading.Results The patients were categorized into downgrade(n =31) and no downgrade group(n =221) of 252 patients.The pathological downgrading was identified in 31 (12.3%).The tPSA,PSAD and PI-RADS scores in patients with downgrade group which were lower than those in without downgrade group (P < 0.05).The logistic regression analysis revealed PI-RADS score was the independent predictor of downgrading(OR =0.364,95% CI 0.253-0.522,P < 0.01).The area under the ROC curve of PI-RADS score was 0.810 and the diagnostic value was the best.Conclusions These findings suggested that PI-RADS scores was predictor for pathological downgrading after radical prostatectomy in patients with biopsy-proven level 2 of grading groups,reduced PI-RADS score (PI-RADS score ≤ 3) is correlated with increased pathological downgrading after radical prostatectomy.
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Objective:To explore the relationship among emotional intelligence,emotional labor and job satisfaction.Methods:Totally 257 bus drivers [158 males and 99 females,aged 17 to 50 years,mean age (32 ± 7)years] in Jinan were surveyed with the Emotional Intelligence Scale (EIS),the Emotional Labor Scale (ELS) and the Minnesota Satisfaction Questionnaire (MSQ).Bootstrap was used to test the mediating effect.Results:The scores of EIS and ELS were both positively correlated with the MSQ scores (r =0.28,0.23,Ps <0.01) in the bus drivers.The surface acting (SA) scores were negatively correlated with the MSQ scores (r =-0.18,P < 0.01),and the deep acting (DA) score were positively correlated with the MSQ scores (r =0.40,P < 0.01).Mediating effect test showed that the indirect effect of surface acting was 0.07 (95% CI:0.01-0.16),and the indirect effect of deep acting was 0.10 (95% CI:0.03-0.21).Correspondingly,the direct effect of emotional intelligence on job satisfaction respectively was 0.35 (95% CI:0.20-0.58) and 0.33 (95% CI:0.12-0.53).Conclusion:These findings support that the bus drivers with higher emotional intelligence may be more satisfied with their job.Emotional intelligence is found to indirectly influence job satisfaction through surface acting and deep acting,and it may affect the bus drivers more effectively choose and use emotion regulation strategies.
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Objective To investigate the abuse tendency of disabled elderly caregivers and analyze its causes.Methods With the convenience sampling method,The main caregivers of 300 disabled elderly people were investigated by the general questionnaire, Activities Daily Living Scale (ADLs) and Caregiver Abuse Screen (CASE) in Guangzhou. Results The degree of disability of the elderly was moderate to severe degree.The average score of the elderly caregiver′s propensity for abuse tendency was(3.3 ± 2.3).178 (59.4 %, 178/300) of the elderly caregivers have abuse tendency (the average score was more than 3). Conclusion Caregivers′ abuse tendency against the elderly is high. The situation of the elderly is not optimistic.
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Objective To summarize the clinical characteristics and prognosis of lacrimal gland adenoid cystic carcinoma with high-grade transformation (LACC-HGT).Methods A retrospective study was adopted.Seventeen patients with lacrimal gland adenoid cystic carcinoma (LACC) were collected from August 2008 to March 2017 in Tianjin Medical University Eye Hospital.Hematoxylin-eosin staining and immunohistochemical staining were performed on tumor sections of 17 LACC patients.According to the pathology results,the patients were divided into LACC-HGT group (6 patients) and non-LACC-HGT (NLACC-HGT)group (11 patients),and the clinical characteristics and prognosis of the two groups were analyzed by using Fisher's exact test and Log-Rank test.Results The medical histories,clinical features,imaging features,TNM staging and treatment protocols were not significantly different between the two groups (all at P> 0.05).The 2-year local recurrence rate,5-year distant metastasis rate and 5-year death rate of patients with LACC-HGT were significantly higher than patients with NLACC-HGT (all at P<0.05).Survival analysis results showed that the survival time of LACC-HGT group was obviously shorter than that of NLACC-HGT group.Conclusions LACC-HGT accelerate the invasion process of local recurrence and distant metastasis,and enhance the death rate.The detection of HGT components should be considered in the process of LACC diagnosis.
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Background Pterygium is one of the common ocular surface disorders,and the main drugs for pterygium include dexamethasone (DXM),interferon α-2b (IFN-α2b),mitomycin C (MMC),5-fluorouracil (5-FU),cyclosporin A (CsA) and tacrolimus (FKS06).However,the efficacy of these drugs on the fibroblasts from recurrence pterygium is unelucidated.Objective This study was to compare the efficacy of DXM,IFN-o2b,MMC,5-FU,CsA and FK506 on proliferation and apoptosis of recurrent pterygium-derived fibroblasts in vitro.Methods The specimens of recurrence pterygium were collected during surgery in Tianjin Medical University Ophthalmological Hospital from May 2015 to July 2016 under the written informed consent.Fibroblasts were isolated and cultured by explant culture method and identified by immunochemistry.DXM,IFN-α2b,MMC,5-FU,CsA and FK506 were added into the medium for 48 hours,respectively,and the cells cultured without drug were used as the control group.The inhibitory efficiency of different concentrations of DXM,IFN-α2b,MMC,5-FU,CsA and FK506 on the cell proliferation was assayed by cell counting kit-8 (CCK-8),and 50% inhibiting concentration (IC50) of the drugs was calculated.The cells were treated by the IC50 dose of drugs for 48 hours,and cell apoptotic proportion and cell cycle were assessed by flow cytometry analysis.The expression of proliferating cell nuclear antigen (PCNA) in the cells after treated by drugs was detected by immunochemistry.Results Cultured cells grew well with the fusiform shape and radial arrangement.Vimentine showed the positive expression and keratin was absently expressed in the cells.The IC50 to the cells was (3.5×103±2.83×10-2)mg/L,(6.1×102±3.6×10-3)mg/L,(3.2×10-1±1×10-4)mg/L,(2.2× 101 ± 1.2× 10-3) mg/L,(6.3 × 101 ±2.5 × 10-3) mg/L and (6.0× 101 ± 0.0× 100) mg/L in the DXM,IFN-α2b,MMC,5-FU,CsA and FK506,respectively.In the 48 hours after treated by the IC50 drugs,the apoptotic ratio was (35.00± 3.21)%,(30.37±1.67)%,(26.11±0.75)%,(22.01±0.07)%,(20.95±1.68)% and (19.85±0.52)% in the IFN-α2b group,CsA group,MMC group,FK506 group,DXM group and 5-FU group,which was significantly higher than (11.38±2.18) % in the control group (all at P<0.05).The cell proportion of G0/G1 phase,S phase and G2/M phase was (85.64±2.62)%,(5.29±1.56)% and (2.73-±2.66)% in the control group,and the cell proportion of G0/G1 phase was reduced,while that of S phase or G2/M phase was considerably increased in various drug groups (all at P<0.05),with the blocking efficiency of cell cycle was in turn MMC,CsA,5-FU,DXM,IFN-α2b and FK506.The expressional rate of PCNA in the cells was (95.00 ± 2.00) %,(82.67 ± 5.04) %,(80.00 ± 2.78) %,(64.00± 6.55)%,(38.00±3.00)%,(32.00±4.36)% and (29.67±3.02)% in the control group,FK506 group,DXM group,5-FU group,IFN-α2b group,CsA group and MMC group,showing a significant difference among the groups (F=25.995,P<0.01),and the expressional rate of PCNA was significant lower in various drug groups than that in the control group (all at P<0.05).Conclusions DXM,IFN-α2b,MMC,5-FU,CsA and FK506 are all able to inhibit the proliferation and promote the apoptosis of recurrent pterygium-derived fibroblasts in vitro,and MMC and CsA appear to have a stronger effect.
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Purpose To explore the feasibility of optimizing monochromatic images in reducing iodinated contrast dose in CT pulmonary angiography (CTPA). Materials and Methods Sixty-eight patients undergoing CTPA were randomly divided into two groups, with half in research group and half in conventional group to evaluate image quality. Research group underwent spectral CT imaging with the injection of 30 ml Omnipaque (300 mgI/ml) and optimal monochromatic images were postprocessed using the software of GSI viewer. Conventional group underwent conventional CTPA with the injection of 80 ml Ultravist (370 mgI/ml). The CT values were measured respectively in the main pulmonary artery, left pulmonary trunk, right pulmonary trunk, left lobe artery and right lobe artery. The contrast noise ratio (CNR) in two groups were calculated, and image quality were subjectively assessed. Results The total iodine intake in research group (9000 mg) was significantly lower than that of conventional group (29 600 mg). CNR in the main pulmonary artery, left pulmonary trunk, right pulmonary trunk, left lobe artery and right lobe artery in research group was significantly higher than that of conventional group (t=2.07-2.71, P0.05), while there was a good agreement between the two readers (Kappa=0.8, P<0.05). Conclusion It is possible to reduce iodinated contrast dose using spectral CT imaging and improve the image quality of CTPA.
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Brain delivery of macromolecular therapeutics (e.g., proteins) remains an unsolved problem because of the formidable blood-brain barrier (BBB). Although a direct pathway of nose-to-brain transfer provides an answer to circumventing the BBB and has already been intensively investigated for brain delivery of small drugs, new challenges arise for intranasal delivery of proteins because of their larger size and hydrophilicity. In order to overcome the barriers and take advantage of available pathways (e.g., epithelial tight junctions, uptake by olfactory neurons, transport into brain tissues, and intra-brain diffusion), a low molecular weight protamine (LMWP) cell-penetrating peptide was utilized to facilitate nose-to-brain transport. Cell-penetrating peptides (CPP) have been widely used to mediate macromolecular delivery through many kinds of biobarriers. Our results show that conjugates of LMWP-proteins are able to effectively penetrate into the brain after intranasal administration. The CPP-based intranasal method highlights a promising solution for protein therapy of brain diseases.
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Objective To study the effects of the numbers of the canalith repositioning procedure on the treatment of benign paroxysmal positional vertigo(BPPV).Methods A clinical study was conducted on 68 BPPV patients using randomized controlled methods.The canalith repositioning procedure was performed on 34 patients in the treatment group only a day for 3 consecutive days,whereas it was performed on 34 patients in the control group once only,patients in both groups took betahistine mesylate tablets and flunarizine hydrochloride on the basis of ma-nipulative reduction.After one week and three months,the efficacy was evaluated,and the recovery situation was observed.ResuIts After 1 week of treatment,the cure rate was 82.4% in the treatment group,and 58.8% in the control group.The difference was statistically significant (P0.05 ).ConcIusion Based on the classifications of BPPV ,several times of manipulative reduction combined with drug treatment can im-prove short-term cure rates of BPPV and shorten healing time.