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ObjectiveTo investigate the effect of the protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2α (eIF2α) pathway in endoplasmic reticulum stress on the activation of hepatic stellate cells (HSC). MethodsPathological sections of normal liver tissue after surgery were collected from 11 patients with hepatic fibrosis (S1-S4) and 9 patients with hepatic hemangioma and hepatic adenoma confirmed by liver biopsy, and immunohistochemistry was used to measure the protein expression levels of PERK, eIF2α, and C/EBP homologous protein (CHOP). Human HSC-LX2 cells were treated with different concentrations of the endoplasmic reticulum stress inducer thapsigargin (0, 125, 250, 500, and 1 000 nmol/L), and qRT-PCR was used to measure the mRNA expression level of PERK, while Western blot was used to measure the protein expression levels of PERK, inositol requiring protein 1 (IRE1), activating transcription factor 6 (ATF6), CHOP, and α-smooth muscle actin (α-SMA). The method of lentivirus transfection was used to construct a PERK stable overexpression LX-2 group and a control group; qRT-PCR was used to measure the mRNA expression levels of PERK, eIF2α, and α-SMA, Western blot was used to measure the protein expression levels of PERK, phosphorylated eIF2α (p-eIF2α), and α-SMA, and immunofluorescence assay was used to measure the expression of collagen type I alpha 1 (COL1A1). The independent samples t-test was used for comparison of normally distributed continuous data between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. ResultsCompared with normal liver tissue, the liver tissue of patients with hepatic fibrosis had significantly higher expression levels of PERK, eIF2α, and CHOP (Z=-3.56, t=-5.75, Z=-3.52, all P<0.001). Compared with the solvent group, the groups treated with different concentrations of thapsigargin had significant increases in the expression levels of the endoplasmic reticulum-associated proteins PERK, CHOP, IRE1, ATF6, and α-SMA (all P<0.05). Compared with the control group, the PERK stable overexpression group had significant increases in the mRNA expression levels of PERK, eIF2α, and α-SMA and the protein expression levels of PERK, p-eIF2α, and α-SMA (all P<0.05), and immunofluorescence assay showed a significant increase in the expression level of COL1A1 in the PERK stable overexpression group (P<0.05). ConclusionPERK overexpression can induce the expression of α-SMA and COL1A1 in LX-2 cells, suggesting that the PERK signaling pathway might be one of the important mechanisms of HSC activation.
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Autoimmune hepatitis (AIH) is an autoimmune disease characterized by chronic liver inflammation, with a gradually increasing incidence rate, and its social and medical burdens cannot be neglected. Intestinal microecology is becoming a research hotspot in the field of autoimmune disease. In recent years, it has been believed that changes in intestinal microecology can cause changes in autoimmune state, microbial metabolites, and intestinal barrier, which is one of the driving factors for the onset of AIH. Early diagnosis and correct treatment can help to improve the prognosis of AIH patients. This article introduces the characteristics of gut microbiota in AIH patients, elaborates on the impact of intestinal microflora imbalance on the pathogenesis of AIH, and briefly describes related treatment regimens from the perspective of intestinal microecology, so as to comprehensively understand and explain the role of intestinal microecology in AIH and the impact of intestinal microecology balance on the pathogenesis, diagnosis, and treatment of AIH.
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Objective:To study the predictive values of umbilical artery blood gas analysis(UABG) plus amplitude-integrated electroencephalography(aEEG) monitoring within 6 h after birth for early complications and short term neurological outcomes in low Apgar score neonates.Methods:From January 2020 to February 2022, neonates with gestational age (GA) ≥35 weeks and 1 min or 5 min Apgar score ≤7 admitted to NICU of our hospital were retrospectively reviewed. According to UABG pH values, the neonates were assigned into pH<7.2 group and pH ≥7.2 group, and further grouped into abnormal aEEG group and normal aEEG group. The ttest, rank sum test and χ2 test were used to compare laboratory results, incidences of diseases, physical growth and neurological prognosis at 6 month of age. Results:A total of 105 neonates with low Apgar scores were enrolled, including 73 cases in the pH<7.2 group and 32 cases in the pH≥7.2 group. In the pH<7.2 group, 52(71.2%) had abnormal aEEG and 21 had normal aEEG. In the pH≥7.2 group, 6(18.8%) had abnormal aEEG and 26 had normal aEEG. The incidence of abnormal aEEG in the pH<7.2 group was higher than the pH≥7.2 group ( P<0.001). The degree of aEEG abnormality was negatively correlated with UABG pH ( r=-0.463, P<0.001). In the pH<7.2 group, the levels of creatine kinase isozymes (CK-MB), activated partial thromboplastin time and the incidence of hypoxic-ischemic encephalopathy (HIE) in neonates with abnormal aEEG were significantly higher than those with normal aEEG, and the head circumference (HC) at 6 month was significantly smaller in neonates with abnormal aEEG (all P<0.05). In the pH≥7.2 group, the level of CK-MB, incidences of HIE and respiratory failure in neonates with abnormal aEEG were higher than those with normal aEEG, HC at 6 month was smaller and the incidence of adverse neurological prognosis was higher in neonates with abnormal aEEG (all P<0.05). Conclusions:UABG plus aEEG monitoring within 6 h after birth shows predictive values for early complications and short term neurological outcomes in low Apgar scores neonates.
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Objective:To analyze the risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.
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Objective:To study the neurodevelopmental outcomes and risk factors of premature infants with gestational age (GA) <34 weeks.Methods:From June 2016 to June 2018, premature infants with GA<34 weeks admitted to the Neonatology Department of our hospital were retrospectively reviewed. Bayley Scales of Infant DevelopmentⅡwas used to assess the neurodevelopmental outcomes at corrected GA 18~24 months. The incidence of neurodevelopmental impairment (NDI) was determined. Mental developmental index (MDI) and psychomotor developmental index (PDI) were calculated. The infants were assigned into three groups according to their MDI and PDI scores:≥85 group, 70~84 group and <70 group. Risk factors of low MDI and PDI scores were analyzed.Results:A total of 202 premature infants with GA<34 weeks were included, including 131 males (64.9%) and 71 females (35.1%). 91 cases (45.0%) developed NDI, including 77 mild NDI (38.1%) and 14 severe NDI (6.9%). Univariate analysis found that the incidences of severe asphyxia, multiple births, Grad≥3 ROP and endotracheal intubation in the MDI<70 group were higher. At corrected GA 40 weeks, 3, 6, 12 months, MDI<70 group showed less cases of head circumference >-2SD. PDI<70 group had higher incidences of intrauterine distress, maternal gestational hypertension, multiple birth, Grade 3~4 RDS, Grade 3~4 germinal matrix-intraventricular hemorrhage and tracheal intubation ( P<0.05). Logistic regression showed gestational hypertension, history of tracheal intubation and invasive ventilation were the risk factors for low PDI score ( OR=9.176, 4.547 and 3.227, P<0.05). The head circumference >-2SD at corrected age 6m was protective factor for low MDI and PDI scores ( OR=0.063 and 0.041, P<0.001). Conclusions:Preterm infants with GA<34 weeks are likely to develop severe NDI. Avoiding unnecessary tracheal intubation and invasive ventilation and improving gestational hypertension management may be beneficial to the neurodevelopmental outcomes of preterm infants.
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Objective:To study the nutritional status of very preterm infants (VPIs) with bronchopulmonary dysplasia (BPD) during hospitalization and the risk factors of extrauterine growth retardation (EUGR).Methods:From January 2017 to June 2020, clinical data of VPIs with BPD hospitalized in the department of neonatology of our hospital were retrospectively studied. The infants were assigned into EUGR group and non-EUGR group and their nutritional status and the risk factors of EUGR were compared.Results:A total of 225 VPIs were enrolled, including 143 cases of EUGR (63.6%) and 82 non-EUGR (36.4%). The EUGR group had significantly lower birth weight (BW) than non-EUGR group ( P<0.001). No significant difference existed in the gestational age (GA) between the two groups ( P=0.733). The incidences of EUGR in VPIs with mild, moderate and severe BPD were 41.9%, 70.8% and 90.7%, respectively and the differences were statistically significant ( P<0.001). Compared with non-EUGR group, EUGR group received less full-course antenatal corticosteroids (47.6% vs. 63.4%, P=0.022). EUGR group had longer duration of parenteral nutrition, fasting time and achieving full enteral nutrition ( P<0.05). EUGR group also showed slower increment of enteral feed volumes, slower growth velocity and higher incidence of feeding intolerance ( P<0.05). Multivariate logistic regression analysis showed that moderate/severe BPD, BW <1 000 g and feeding intolerance were independent risk factors for EUGR in VPIs. The use of pulmonary surfactant at birth was a predictive factor for EUGR in VPIs with BPD. Growth velocity >13 g/(kg·d) and full-course of antenatal corticosteroids were protective factors of EUGR for BPD infants. Conclusions:It is necessary to improve the use of full-course antenatal corticosteroids to reduce the application of pulmonary surfactant at birth in VPIs. Better enteral nutrition and improved growth velocity will help reducing the incidence of EUGR in VPIs with BPD.
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Objective:To investigate the serotype features of group B Streptococcus (GBS) vaginal colonization in late pregnancies and their relationship with early-onset neonatal GBS disease (GBS-EOD). Methods:Thirty-two strains were isolated from neonates delivered by GBS-positive mothers and hospitalized for GBS-EOD in Xiamen Maternal and Child Care Hospital from June 2016 to June 2018. Another 266 strains were isolated from vaginal samples from randomly selected late pregnant women who received antenatal screening and delivered in the same hospital during the same period with an allocation ratio of 12∶1. A total of 298 strains from mothers and 32 strains from neonates were involved. Every isolate was serotyped with latex agglutination assay. GBS infection caused by eleven serotypes and the correlation between GBS serotypes in late pregnant women and neonatal GBS-EOD were analyzed. Qualitative variables were compared using Chi-square or Fisher's exact test. A correlation analysis was presented by the column contact number C. Multiple analysis of multiple sample rates was performed with Post hoc testing. Differences between groups were analyzed according to the adjusted standardized residual. Results:A total of nine serotypes were identified among the 298 strains isolated from the mothers. The most prevalent serotype wasⅢ [55.0% (164/298)], followed byⅠb [16.4% (49/298)], Ⅰa [11.1% (33/298)], Ⅴ [9.4% (28/298)], Ⅱ [5.0% (15/298)], non-typable [NT, 1.0% (3/298)], and Ⅵ, Ⅷ and Ⅸ [0.7% (2/298) in each]. Neither Ⅳ nor Ⅶ serotype was identified. The 32 strains isolated from neonates with GBS-EOD belonged to five serotypes, which were Ⅲ [18/32 (56.3%)], Ⅰa [8/32 (25.0%)], Ⅰb [3/32 (9.4%)], Ⅱ [2/32 (6.2%)] and Ⅴ [1/32 (3.1%)]. The positive rates of GBS Ⅲ serotype in neonates with pneumonia, sepsis, and meningitis were 6/13, 7/14, and 5/5. However, no statistically significant difference was observed in the distribution of the five serotypes in GBS-EOD neonates ( P=0.654). Thirty neonates (93.7%) were cured, while two (6.3%) died. There were statistically significant differences among neonatal GBS-EOD caused by vertical transmission with Ⅰa, Ⅰb, Ⅱ, Ⅲ and Ⅴ, Ⅵ, Ⅷ, Ⅸ and NT serotypes ( P=0.046, contingency coefficient: 0.183). Further analysis showed that the adjusted absolute value of the standardized residual of serotype Ⅰa was 2.7 (>2), and the difference was statistically significant. However, the adjusted absolute value of the standardized residual of serotype Ⅲ was only 0.1, which was not statistically significant. Conclusions:Serotype Ⅲ is the most prevalent GBS serotype in late pregnant women and GBS-EOD neonates, and also the predominant serotype in infants with early-onset meningitis. Serotype Ⅰa could be highly vertically transmitted, while the virulence of serotypes Ⅲ and Ⅰa strains of GBS are the strongest.
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OBJECTIVE: To explore the relationship among perceived organizational support,job burnout and depressive tendency in nursing staffs. METHODS: A total of 807 nurses from 7 municipal hospitals in Zhengzhou City,Henan Province were selected as the study subjects by multi-stage cluster random sampling method. The questionnaires of Perceived Organizational Support,Maslach Burnout Inventory-General Survey and Center for Epidemiological Survey-Depression Scale were used to conduct the survey. RESULTS: The total scores of perceived organizational support and job burnout were( 69. 3 ± 18. 5) and( 36. 3 ± 13. 7) respectively. The median of the total score of depression tendency was 17. 00. The total score of nurses' perceived organizational support was negatively correlated with the total scores of job burnout and depression tendency( P < 0. 01). The total score of job burnout was positively correlated with the total score of depression tendency( P < 0. 01). The degree of explanations for the change of perceived organizational support and job burnout on depression tendency were 9. 1% and 13. 1%,respectively. CONCLUSION: Perceived organizational support and job burnout play important roles in predicting depression tendency. Job burnout plays a mediating role in the relationship between perceived organizational support and depression tendency.
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Objective To investigate the association between high-frequency oscillatory ventilation (HFOV) and the incidence of brain injury in premature infants(BIPI) with respiratory distress syndrome (RDS).Methods A total of 136 premature infants who were diagnosed as RDS and treated with mechanical ventilation between January 1,2014 and June 30,2016 were enrolled.Atter stratified by gestational age of 36-34 weeks,33-32 weeks,31-28 weeks and ≤ 27 weeks,the neonates were randomly divided into two groups (68 cases each):conventional mechanical ventilation (CMV) and HFOV groups.Duration of ventilation and changes in blood gas parameters following 24,48 and 72 hours of ventilation were monitored and compared between the two groups.Incidences of BIPI and complications in the two groups were calculated and their associations with gestational age and birth weight were analyzed.Moreover,incidences of cure rates in the two groups were comparatively analyzed.Independent samples t-test,two-way analysis of variance,Chi-square test or Fisher's exact test was used for statistical analysis.Results (1)Significant difference was observed neither in the perinatal factors (prenatal glucocorticoid usage,and incidences of premature rupture of membrane and gestational diabetes mellitus),nor in the severity of RDS between the two groups (all P>0.05).(2) The average duration of ventilation in the CMV group was higher than that of the HFOV group [(68.44±10.3) vs (64.7±8.5) h,t=2.285,P<0.05].No significant difference in the values of pH,partial pressure of carbon dioxide (PaCO2) or partial pressure of oxygen (PaO2) before and after 24,48 or 72 hours of ventilation treatment was found between the two groups (all P>0.05).(3) Neither the incidence of hemorrhagic brain injury nor that of non-hemorrhagic brain injury showed any significant difference between the CMV and HFOV groups [36.8% (25/68) vs 39.7% (27/68);16.2% (11/68)vs 14.7% (10/68),both P>0.05].The total incidence of BIPI showed no significant difference [44.1%(30/68) vs 45.8%(33/68),22=0.266,P=0.606].The smaller gestational age at birth and the lower birth weight,the higher incidence of BIPI,although no significant difference was shown in the incidence of BIPI when compared among different gestational age groups and different birth weight groups (all P>0.05).(4) The incidence of complications in the CMV group was higher than that in HFOV group [25.0%(17/68) vs 11.8%(8/68),22=3.970,P=0.044],while the cure rate of RDS was similar [94.1%(64/68) vs 95.6%(65/68),x2=0.151,P=0.703].Conclusions HFOV is a safe and reliable therapy for preterm infants with RDS.Compared with CMV,HFOV can shorten the duration of ventilation and reduce the incidence of complications without increasing the risk of BIPI.However,the cure rate of RDS is not increased by HFOV.
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Objective To observe the effects of quercetin liposome (LQ) on formation of advanced glycation end prod-ucts(AGEs)and receptor for advanced glycation end products (RAGE) in kidney of diabetic rats. Methods LQ was made by rotary evaporation, and the model of type 2 diabetic rats were established by being fed on high-sugar and high-fat diet combined with intraperitoneally injection of streptozotocin (STZ). Then type 2 diabetic rats were randomly divided into six groups:diabetic model group (group DM), low level of LQ group (group LQ-L ), medium level of LQ group (group LQ-M), high level of LQ group (group LQ-H), positive control group (group aminoguanidine, AG) and control group (group N). After 8 weeks of interventions, blood glucose, body weight, kidney hypertrophy index (KI), blood urea nitrogen (BUN) and serum creatinine (Scr) were measured in each group. ELISA was used to detect serum AGEs, and 24 h urine albumin. The pathologi-cal change of glomerular basement membranes was observed by PAS staining and the expressions of AGEs in kidney was as-sessed by immunohistochemical method. The transcription level of RAGE mRNA in kidney was determined by RT-PCR. Re-sults Compared with the group N, the level of blood glucose, KI, BUN, Scr, serum AGEs and 24 h urine albumin were in-creased significantly in group DM, while the level of body weight decreased. Also the volume of kidney glomerulus increased and glomerular basement membranes thickened, the transcription levels of AGEs and RAGE mRNA in kidney tissue in-creased in DM group (P<0.05). Compared with group DM, the level of blood glucose, KI, BUN, Scr, serum AGEs and 24 h urinary albumin decreased, while the level of body weight increased in all three LQ groups. Meantime, the change of patho-logical morphology of glomerular basement membranes reduced and the expressions of AGEs and RAGE mRNA in kidney tissue decreased in all three LQ groups. All changes in the medium LQ dose group were more obvious than those of other two LQ groups (P<0.05). Conclusion Similar to AG, LQ has effect on inhibiting the action of proteinum unenzymatic glycosyl-ation and on decreasing the production of AGEs in serum as well as the expression of RAGE mRNA in kidney. Therefore, LQ play important protective role in kidneys of diabetic rats.
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Objective To investigate the incidence of brain injury and analyze the risk factors in very low birth weight infants (VLBWI),in order to explore methods to improve neurodevelopmental outcome.Methods This was a retrospective study in which we reviewed the incidence of brain injury in 326 VLBWI who admitted to our NICU from October 2007 to September 2014.The differences of general characteristics,high-risk perinatal factors,complications of prematurity and respiratory support in brain injury group (n =132) and no brain injury group(n =194) were analyzed,and Logistic regression was used to analyze the related risk factors.Results In 326 VLBWI,premature brain injury was observed in 132 cases(incidence of 40.49%).Hemorrhagic brain injury was observed in 80 cases(incidence of 24.54%,80/326),in whom total 66 cases (20.25%,66/326) with periventricular-intraventricular hemorrhage (PVH-IVH),41 cases with PVH-IVH grade Ⅰ-Ⅱ,25 cases with PVH-IVH grade Ⅲ-ⅣV.Non-hemorrhagic brain injury was observed in 52 cases (incidence of 15.95 %,52/326),in whom 46 cases with periventdcular leukomalacia (14.11%,46/326).There were no statistically significant differences in general characteristics except gender differences between the two groups.Further analysis of the 28 factors including high-risk perinatal factors,premature complications and respiratory support between the two groups,showed that there were significant differences in 16 factors including asphyxia,chorioamnionitis,antenatal steroid use,neonatal respiratory distress syndrome,hypoxemia,apnea,pulmonary hemorrhage,patent ductus artedosus,hypotension,acidosis,hypocapnia,anemia,hyperglycemia,thrombocytopenia,high frequency ventilation and extrautedne growth retardation.Further binary Logistic regression analysis showed that antenatal steroids use was negatively correlated with brain injury,chorioamnionitis,acidosis,and patent ductus arteriosus were positively correlated with brain damage,the relative risks of premature brain injury was 0.108,7.222,3.045 and 4.565 respectively.Conclusion The mortality rate and the incidence of brain injury in VLBWI are still high.Chorioamnionitis,acidosis and patent ductus arteriosus are closely associated with premature brain damage.Antenatal steroids can prevent premature brain injury.We should pay much attention to these risk factors in the perinatal management of VLBWI,in order to decrease the incidence of premature brain injury.
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OBJECTIVE To study the bacterial infections in ICU,pathogens distribution and their drug-resistance characteristics,so as to offer a reference to the prevention and control of hospital infection.METHODS Specimens from ICU from Jan 2003 to Dec 2004 were underwent a process of germ culture,identification and drug-sensitivity test.Germ culture-positive cases were confirmed by Diagnostic Standards of Hospital Infections.RESULTS Ninety three pathogens were identified from ICU in two years.Of all cases,63.44% were Gram-negative,30.1% were Gram-positive,and 9.68% were epiphyte.Among them,19.35% were Pseudomonas aeruginosa and it was the main one of Gram-negatives;9.68% were Staphylococcus aureus and it composed the most of Gram-positives;6.45% were epiphyte.Of all 93 pathogens,60 gained from respiratory tract,and 23 gained from urinary tract.CONCLUSIONS To emphasize on the strictly control of ICU,hospital infections and high risk disease,and to adopt certain preventive measures are the ways to control and decrease hospital infections.
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Aim To express hepatitis C virus glycoprotein E (gE) deleting carboxy-terminal 31 amino acids, and detect anti-E antibody in HCV patients using expressed gE. Methods E gene derived from HCV H strain was inserted into baculovirus transfer vector containing a polyhedrin promotor. The recombinant plasmid was cotransfected into insect cell sf9 with a viral expression vector. The expression of gE was analyzed with Western blot, and the cells were used for dectecting antibodies against E1 and E2 in 35 hepatitis C patients by indirect immunofluorescence. Results A series of proteins with different relative molecular masses(Mr) could be detected by Western blot. Results from indirect immunofluorescence staining showed and only 4 patients were anti-E antibody positive gE was located in cytoplasm. Conclusion HCV gE is expressed successfully in insect cells, the study lay the foundation for further developing HCV vaccine.
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Objective: To determine the potency of QN-2013, a derivative of quinoxaline 1,4-N-oxide, as a hypoxia-selective cytotoxin or a radiosensitizer. Methods: In vitro cytotoxicity and radiosensitization, as well as in vivo antitumor activity were determined by colony formation and tumor growth delay respectively. The changes in the cell cycle, DNA damage and repair of damaged DNA were assayed by FCM and “comet” assay, separately. Results: ICN250 and ICair50 of QN-2013 for HeLa-S3 cells were 0.08 and 1.7 mmol*L-1 respectively, namely, HCR=21. This suggested that QN-2013 was a fairly hypoxic cytotoxin, but inferior to SR-4233. QN-2013 had an evident radiosensitization either in vitro or in vivo. It was noted, however, that the value of in vitro SERs increased exponentially with increasing concentration of the drug, but the in situ antitumor activity seemed to be independent of doses of the drug. The systemic toxicity of QN-2013 was superior to an LD50 of 265 mg*kg-1 compared with 80 mg*kg-1 for SR-4233. In hypoxic condition QN-2013 induced S retension effect and G2M block in HeLa-S3 cells, caused DNA double strand break, and inhibited the repair of radiation-induced DNA damages. All of these reactivenesses might be involved in the action mechanism of QN-2013. Conclusion: QN-2013 is a fair hypoxia-selective cytotoxin, and has shown improved antitumor activity in vivo in combination with radiation. In general, These results suggest that the series of quinoxaline di-N-oxide derivatives hold out bright prospect for the development of novel bioreductive antitumor drugs.
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The total glucosides of Paeony root ( TGPs ) extracted from Anhui Boxian Paeonia lactiflora Pall can dialet the vessels of rabbit's ears in vitro and increased both the number of drops and the volume (ml) per minute. TGPs had no definite effects on the isolated aorta strips of rabbits directly, but it significantly increased the contraction of aorta strips induced by NA. In vivo, TGPs raised the diasto-lic pressure (which could not be blocked by phentolamine) , and increased the dp/dtmax and decreased the heart rate. TGPs also strengthened the effect of raising the blood pressure and increasing the heart sound intensity induced by NA. The results about the blood pressure and heart function studied on cats were almost the same as on rabbits