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Objective:To evaluate the efficacy and safety of lenalidomide plus dexamethasone (LD) in patients with proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID).Methods:The clinicopathological data of PGNMID patients who were treated with LD protocol from January 2010 to October 2019 were retrospectively analyzed.Results:All of 6 patients received LD treatment for≥3 months after renal biopsy in Jinling Hospital. During the follow-up period of 6 to 19 months, 3 patients achieved renal remission, and the renal remission rate was 50%(3/6). Light microscopy showed membranoproliferative glomerulonephritis and immunofluorescence showed single kappa type IgG3 was deposited in the mesangial region and the vascular loop. Before taking LD scheme, the median urinary protein were 7.76(1.27, 14.57) g/24 h, the median serum creatinine was 118.5(70.7, 289.1) μmol/L, and the median albumin was 34.5(22.4, 37.5) g/L. The concentration of serum free kappa and lambda light chain was increased in 5 patients, but the serum free light chain ratio was normal. Hypocomplementemia was detected in two cases. Six patients underwent bone marrow flow cytometry, and 2 patients had elevated monoclonal plasma cells, accounting for 0.7% and 0.5%, respectively. Immunofixation electrophoresis suggested that 1 patient had positive serum M protein for kappa type IgG3. At the last follow-up, median urine protein was 3.33(0.33, 11.23) g/24 h, median serum creatinine was 108.7(80.4, 160.9) μmol/L, and median albumin was 35.9(24.5, 45.6) g/L. The concentration of serum free light chain in 4 patients from 5 patients with elevated serum free light chain was lower than that before taking the drug. Decreased level of serum complement in two cases returned to normal after treatment. The M spike did not turn negative during the follow-up in one patient. Adverse events included anemia, neutropenia, limb numbness and upper respiratory tract infection.Conclusion:This study reports for the first time that LD protocol may be effective in treating PGNMID, but more attention should be paid to the hematological adverse events of lenalidomide.
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Objective:To investigate the correlation between psychological capital, job burnout and coping style of psychiatric nurses.Methods:Using cluster sampling method, 139 psychiatric nurses from a third grade a psychiatric hospital in Nanjing City, Jiangsu Province were selected as the objects of investigation. General information questionnaire, psychological capital questionnaire, job burnout scale and simple coping style questionnaire were used to investigate.Results:The psychological capital of psychiatric nurses was positively correlated with positive coping style ( r=0.801, P<0.01), negatively correlated with job burnout ( r=-0.864, P < 0.01), and negatively correlated with negative coping style ( r=-0.774, P < 0.01). The results of stepwise regression showed that job burnout, monthly income, positive coping style and negative coping style could predict 84.0% of the variance of psychological capital. Conclusion:Psychiatric nurses'psychological capital level is above the middle level. Monthly income and positive coping positively predicted nurses'psychological capital, job burnout and negative coping negatively predicted nurses' psychological capital. Managers can improve the coping style of nurses, rationally distribute the income of nurses, and improve the psychological capital of psychiatric nurses, so as to alleviate the burnout of psychiatric nurses.
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Objective@#To explore the clinical effects of artificial dermis combined with vacuum sealing drainage (VSD) and autologous split-thickness skin graft in repair of scar contracture deformity after extensive burn.@*Methods@#A total of 8 patients with scar hyperplasia and contracture deformity on joint after healing of extensive burn were admitted to our hospital from August 2015 to August 2017. There were 5 females and 3 males aged 8 to 45 years with an average of 23 years. In the first stage operation, scar tissue on contracture site was removed, and the wound was covered by artificial dermis followed by continued VSD treatment. On 10-14 d after the first stage operation, the artificial dermis tissue formed, and the second stage autologous split-thickness skin grafting and continued VSD treatment were performed. Routine anti-scar therapy was carried out after healing of wounds. Time of wound healing after the second stage operation was recorded. Colour and texture of the split-thickness skin graft, scar formation condition of the donor site, and action condition of the operation site during follow-up were observed.@*Results@#The wounds of 8 patients were healed in 10-14 d after the second stage operation. During follow-up of 6-24 months, the split-thickness skin graft was with smooth surface and good elasticity, and the function of joint recovered well. The donor site in head healed well with no scar. Only pigmentation was left in the donor site of thigh, and scar was not obvious. The patients and their family members were satisfied.@*Conclusions@#After application of artificial dermis combined with VSD and autologous split-thickness skin graft in repair of scar contracture deformity after extensive burn, the skin grafting area and donor site were with unobvious scar hyperplasia, and the joint function in the operation area was good.
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Objective@#To explore the development trajectories of quality of life and acceptance of disability of burn patients in the rehabilitation treatment stage and the influencing factors.@*Methods@#Totally 207 burn patients, including 157 males and 50 females, aged (40±13) years, who were in the rehabilitation treatment stage were selected by convenient sampling method from October 2016 to July 2017 in the Department of Burns of Fujian Medical University Union Hospital for this longitudinal study. At discharge and 1, 3, and 6 months after discharge, the patient′s quality of life and acceptance of disability were scored using the Burn Specific Health Scale-Brief and Chinese Version of Acceptance of Disability Scale-Revised respectively. Taking the intercept, the slope, and the curve slope as latent variables, the latent second growth curve model was constructed for the quality of life and the acceptance of disability. The robust maximum likelihood estimation (MLR) method was used to estimate the mean, the variance, and the covariance, so as to analyze the discharge level, the growth rate, the acceleration, and the correlation among them. Taking the acceptance of disability, the gender, the cause of burn, the severity of burn, the existence of complications, the payment way, and the education level as covariates, the latent second growth curve model was constructed for the quality of life. The MLR method was used to estimate the influence of covariates on the discharge level, the growth rate, and the acceleration of the quality of life.@*Results@#At discharge and 1, 3, and 6 months after discharge, the quality of life scores of patients were (102±36), (111±36), (118±37), and (122±37) points respectively, and the acceptance of disability scores were (73±17), (75±17), (77±17), and (78±18) points respectively. The estimated mean intercept of the quality of life and the acceptance of disability were 101.680 and 72.993 respectively at discharge, both of which showed a curve increasing trend in 1, 3, and 6 months after discharge (estimated mean slope=11.024, 3.086, t=15.376, 7.476, P<0.01), and the increasing rate (acceleration) gradually slowed down (estimated mean curve slope=-1.393, -0.426, t=-13.339, -4.776, P<0.01). There were significant individual differences in the discharge level and the acceleration of quality of life of patients (estimated intercept variance=1 174.527, t=9.332; estimated curve slope variance=2.379, t=6.402; P<0.01). There were significant individual differences in the discharge level, the growth rate, and the acceleration of patients′ acceptance of disability (estimated intercept variance=267.017, t=9.262; estimated slope variance=32.264, t=2.356; estimated curve slope variance=0.882, t=2.939; P<0.05 or P<0.01). There was no significant correlation among the discharge level, the growth rate, and the acceleration of the quality of life and those of the acceptance of disability of patients (estimated intercept and slope=37.273, -1.457, t=0.859, -0.131; estimated intercept and curve slope=-6.712, -0.573, t=-1.089, -0.248; estimated slope and curve slope=-5.494, -5.988, t=-0.930, -2.512; P>0.05). Among the time-constant covariates, only the severity of burn and the presence of complications had a significant impact on the quality of life of patients at discharge (estimated intercept=-10.721, 5.522, t=-6.229, 1.977, P<0.05 or P<0.01). At discharge and 1, 3, and 6 months after discharge, the level of acceptance of disability had a positive impact on the quality of life of patients (standardized regression coefficient=0.616, 0.669, 0.681, 0.678, t=18.874, 21.660, 22.824, 22.123, P<0.01).@*Conclusions@#The initial levels of quality of life and acceptance of disability of burn patients in the rehabilitation treatment stage are relatively low, both with a curve increasing trend over time, and the increasing rate gradually slows down. Patients with complications and serious burns have poor quality of life at discharge, while the acceptance of disability has a positive impact on the quality of life.
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Objective@#To explore the effects of different doses of dopamine on organ function of rats at early stage of severe scald.@*Methods@#Thirty-two male Wistar rats aged 8 to 12 weeks were divided into sham injury (SI) group, simple resuscitation (SR) group, small dose (SD) group, and moderate dose (MD) group according to the random number table, with 8 rats in each group. After rats in the 4 groups were performed cardiac catheterization, rats in group SI were sham injured on the back by immersing in 37 ℃ warm water for 18 s, and rats in the other 3 groups were inflicted with 30% total body surface area (TBSA) full-thickness scald on the back by immersing in 97 ℃ hot water for 18 s. Rats in group SI were not treated after the injury, while rats in the other 3 groups were performed fluid resuscitation for 24 h through jugular vein catheter with micro syringe pump according to the Parkland formula. They were given 4.0 mL·kg-1·% TBSA-1 normal saline during the first 24 h, of which they were given half of the total amount for the first 8 h, and they were given half of the total amount for the second and third 8 h. Rats in group SR were infused normal saline only, while rats in group SD and group MD were infused normal saline+ 1.25 μg·kg-1·min-1dopamine and normal saline+ 6.00 μg·kg-1·min-1 dopamine respectively. Volume of 0.5 mL venous blood of all rats were taken through the cardiac catheter with serum separated at post injury hour (PIH) 1, 3, 6, 12, and 24. Serum content of cardiac troponin I (cTnI) was determined by enzyme-linked immunosorbent assay; serum content of diamine oxidase (DAO) was detected by ultraviolet spectrophotometer; serum content of β2-microglobulin (β2-MG) was determined by latex-enhanced immunoturbidimetric assay; serum content of total bile acid (TBA) was determined by enzyme colorimetry; serum content of lactic acid, malondialdehyde, and myeloperoxidase (MPO) was determined by ultraviolet spectrophotometer. Data were processed with analysis of variance for repeated measurement, one-way analysis of variance, least significant difference test, and Bonferroni correction.@*Results@#(1) At PIH 1, 3, 6, 12, and 24, serum content of cTnI of rats in group SR, group SD, and group MD [(2.69±0.19), (3.04±0.19), (4.96±0.25), (6.88±0.28), (4.75±0.31) μg/L, (2.70±0.14), (3.08±0.13), (5.06±0.19), (7.11±0.21), (4.89±0.16) μg/L, (2.18±0.14), (2.54±0.09), (3.97±0.14), (5.46±0.34), (3.32±0.33) μg/L] were higher than that in group SI [(1.70±0.08), (1.70±0.08), (1.69±0.11), (1.69±0.08), (1.70±0.08) μg/L, P<0.05], serum content of cTnI of rats in group SR and group SD was similar (P>0.05), and serum content of cTnI of rats in group MD was lower than that in group SR and group SD (P<0.05). (2) At PIH 1 to 24, serum content of DAO of rats in group SR, group SD, and group MD was higher than that in group SI (P<0.05), serum content of DAO of rats in group SR and group MD was similar (P>0.05), and serum content of DAO of rats in group SD was lower than that in group SR and group MD (P<0.05). (3) At PIH 1 to 24, serum content of β2-MG of rats in group SR, group SD, and group MD was higher than that in group SI (P<0.05), serum content of β2-MG of rats in group SR and group MD was similar (P>0.05), and serum content of β2-MG of rats in group SD was lower than that in group SR and group MD (P<0.05). (4) At PIH 1 to 24, serum content of TBA of rats in group SR, group SD, and group MD was similar (P>0.05) and higher than that in group SI (P<0.05). (5) At PIH 1 to 24, serum content of lactic acid of rats in group SR, group SD, and group MD was higher than that in group SI (P<0.05), serum content of lactic acid of rats in group SR and group MD was similar (P>0.05), and serum content of lactic acid of rats in group SD was lower than that in group SR and group MD (P<0.05). (6) At PIH 1 to 24, serum content of malondialdehyde and MPO of rats in group SR, group SD, and group MD was higher than that in group SI (P<0.05), serum content of malondialdehyde and MPO of rats in group SR and group MD was similar (P>0.05), and serum content of malondialdehyde and MPO of rats in group SD was significantly lower than that in group SR and group MD (P<0.05).@*Conclusions@#With effective liquid recovery, dopamine of MD can improve early cardiac function of rats with severe scald, while dopamine of SD can alleviate tissue ischemia and hypoxia, reduce oxygen free radical damage in internal organs, and improve functions of intestine and kidney.
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Objective@#To explore the pain experiences of adult burn patients so as to lay foundation for practical analgesic measures.@*Methods@#Using phenomenological method in qualitative research, semi-structured interviews were conducted on 12 adult burn patients hospitalized in our burn units from May to November 2015, aiming at pain experiences from immediately after burns to 3 to 7 months after being discharged from hospital. Then the Colaizzi′s analysis method was applied to analyze, induce, and refine themes of interview data.@*Results@#After analysis, pain experiences of adult burn patients were generalized into 6 themes: deep pain experiences, heavy psychological burden, limited daily life, poor assessment and treatment of pain, different attributions of pain, and different ways of coping of pain.@*Conclusions@#Burn pain brings harm to the patients′ physiology, mentality, and daily life. Nevertheless, pain processing modes of medical staff and patients themselves are the key factors affecting patients′ pain experiences. Therefore, according to the deficiency of current situation of pain management, the targeted analgesic intervention measures should be carried out from the perspectives of medical staff and patients.
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Zebrafish have been emerging as a valuable model for kidney research , including podocyte biology , nephrogenesis and kidney disease .The zebrafish kidney has similar structure , common function and the same cell types with human kidney .Rapid development and feasible genetic editing approaches in zebrafish provide an ideal model for high -throughput gene screening involved in kidney disease and developmental process .Loss or injury of podocytes is the key mechanism , which can lead to proteinuria , glomerulo-sclerosis and renal failure .Here, we introduce structure and function of zebrafish kidney , filtration estimating assays , podocytes injury model and the highlights of recent zebrafish podocytes studies .
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<p><b>OBJECTIVE</b>To analyze the epidemiological characteristics of hospitalized children with burn injuries in Fujian Medical University Union Hospital, so as to provide evidence to complete an adequate, timely, and effective prevention and treatment system of children with burn injuries.</p><p><b>METHODS</b>Medical records of children with burn injuries, aged 14 and under, hospitalized in the Department of Burns from July 2012 to June 2015 were collected. Data of gender and age, location and cause of injury, time of injury, state of injury, admission time after injury, first aid, length of hospital stay, and treatment and so on were recorded. They were divided into 4 age brackets: less than or equal to 1 year old, more than 1 year old and less than or equal to 3 years old, more than 3 years old and less than or equal to 7 years old, more than 7 years old and less than or equal to 14 years old, then gender and cause of injury of children in the 4 age brackets were analyzed. Admission months of the children were divided into spring (March to May), summer (June to August), autumn (September to November) and winter (December to February of the following year), and then the cause of injury of children in each season was analyzed. Severities of male and female children, length of hospital stay of children with different causes of injury were analyzed. Data were processed with chi-square test, Wilcoxon rank-sum test.</p><p><b>RESULTS</b>Out of 2 608 inpatients with burn injuries, 1 407 children with burn injuries, aged 14 and under, accounting for 53.9%, were admitted in the recent 3 years. The ratio of male to female was 1.6 ∶1.0. Children more than 1 year old and less than or equal to 3 years old ranked the largest number (68.3%, 961/1 407) in the 4 age brackets. There was statistically significant difference in constituent ratios of gender of children among the 4 age brackets (χ(2)=11.00, P=0.012). One thousand three hundred and seventy-two children were burned indoors (97.5%), while 35 children were burned outdoors (2.5%). Scalding with hot fluids was the most common cause of burn (95.0%, 1 337/1 407). There was statistically significant difference in constituent ratios of injury cause of children among the 4 age brackets (χ(2)=107.23, P<0.01). There was statistically significant difference in constituent ratios of injury cause of children more than 7 years old and less than or equal to 14 years old compared with those of the other 3 age brackets (with χ(2) values from 12.88 to 119.85, P values below 0.01). Most burn accidents occurred between 17: 00-20: 59 (33.5%, 472/1 407). Burns were more likely to happen in April to October. July (10.4%, 146/1 407) and August (10.5%, 148/1 407) were the crest-time. Most of the children were burned in summer (35.3%, 496/1 407). There was statistically significant difference in the injury cause of children among each season (χ(2)=14.61, P=0.024). The burn degrees of male and female children were mainly mild or moderate, and there was no statistically significant difference in the severity (Z=-0.39, P>0.05). The trunk was the most involved anatomic site (61.1%, 859/1 407). Most of children were admitted to hospital within 2 hours post burn (79.7%, 1 121/1 407). Majority of children were taken off clothes as first aid on spot or did not receive any treatment. Most of the children were discharged within 2 weeks after admission (80.0%, 1 126/1 407). There was statistically significant difference in length of hospital stay of children with causes of hot liquid scald, flame burn, electric burn, high temperature solid burn, chemical burn (χ(2) =17.33, P=0.002). Most of the children were treated with non-surgical methods, and the majority of the children got better condition or totally recovered and then discharged.</p><p><b>CONCLUSIONS</b>The majority of hospitalized children with burn injuries in our unit are young boys in preschool period, who were burnt by hot fluid at the time of dinner and bathing at home during summer. So we should make more effort on popularization of prevention about burn.</p>
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Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Burns , Classification , Epidemiology , Burns, Chemical , Burns, Electric , Child, Hospitalized , Hospitalization , Inpatients , Length of StayABSTRACT
<p><b>OBJECTIVE</b>We propose a cross-correlation method for automatic extraction of the pennation angle (PA) of the gastrocnemius (GM) muscle from ultrasound radiofrequency (RF) signals.</p><p><b>METHODS</b>The ultrasound RF signals of the GM muscles in tension condition from normal subjects and the simulated ultrasound signals were collected. After the starting point of tracking, a fascicle was selected in the reconstructed GM ultrasound image from the RF signals, and the fascicle and deep aponeurosis could be automatically tracked using the cross-correlation algorithm. The lines of the fascicle and deep aponeurosis were then drawn and the PA was calculated. The reproducibility of the proposed method and its consistency with the manual measurement method were tested.</p><p><b>RESULTS</b>The angles of the simulated fascicles were precisely extracted automatically. The difference between the experimental measurement and the theoretical values was less than 1°. The PA measured automatically and manually was 20.48°∓0.47° and 21.49°∓1.79°, respectively. The coefficient of variation (CV) of the two methods was less than 3% and the root-mean square error (RMSE) was less than 1°. Bland-Altman plot showed a good agreement between the proposed automatic method and the manual method.</p><p><b>CONCLUSION</b>The proposed cross-correlation automatic measurement method can detect the orientation of the fascicle and deep aponeurosis and measure the PA based on ultrasound RF signals with serious speckle noise.</p>
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Humans , Algorithms , Image Processing, Computer-Assisted , Muscle, Skeletal , Diagnostic Imaging , Radio Waves , Reproducibility of Results , UltrasonographyABSTRACT
Objectives To investigate the pathogenic mechanism of herpes simplex encephalitis (HSE) and the mecha-nism of action of dexamethasone and acyclovir. Methods 102 male mice were randomly assigned to normal control group, HSV-1 infection group, acyclovir-treated group and combination-treated group. The model of HSE was established by in-tracranial injection of HSV-1 in mice except normal controls. One day after intracranial injection, mice in acyclovir-treated group and combination-treated group were intragastrically administrated with acyclovir, and mice in normal control group and HSV-1 infection group were intragastrically administrated with normal saline. Three days after intracranial injection, mice in combination-treated group were intraperitoneally injected with dexamethasone and mice in other groups were in-traperitoneally injected with normal saline. The neurological injury score and the expressions of IL-2 and IL-10 of the mice brain tissues in each group were compared at 3, 6 and 9 days after model establishment. Results The survival rate of mice was lowest in HSV-1 infection group and highest in combination-treated group (P0.05). Conclusions In comparison with acyclovir monotherapy, combined treatment with dexamethasone and acyclovir for HSE can reduce the expression of IL-2 and IL-10, relieve the clinical symptoms, and increase the survival rate.
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ObjectiveTo study the chromosome genetic changes in hepatocellular carcinoma (HCC) with double exposure to hepatitis B virus/aflatoxin B1 (HBV/AFB1) in Guangxi.Method Differences in genomic alterations in 32 patients with HCC were analyzed using comparative genomic hybridization(CGH).Results(1) The majority of chromosome copy number in the 32 HCC samples had varying degrees of change.The amplification of chromosome regions were 1q,7q,8q,with the high frequency regions being 1q,8q.The deletion of chromosome regions were 1p,4q,8p,9p,13q,14q,16p,16q,17p,18q,19p,Y,with the high frequency regions being 1p,4q,8p,16q,17p,19p;(2) There were also some high copy number amplification or deletion of small regions,such as 2p25.1-p25.2,3q22.3-q23,7p14.1-p14.3,and 9p13.2-9p21; (3) Hierarchical clustering analysis showed that the rate of deletion of chromosome 13q decreased progressively in the following 4 groups:-HBsAg(+)/AFB1 (+),HBsAg(+)/AFB1 (-),HBsAg( - )/AFB1 ( + ),and HBsAg( - )/AFB1 (-) (x2=6.452,P<0.05).4p was found mainly to be amplified in the HBsAg(+)/AFB1(-)group,but it was mainly deleted in the HBsAg(-)/AFB1(+),and HBsAg( - )/AFB1(-) groups.19q was found mainly to be amplified in the HBsAg(+)/AFB1(+) group,but it was mainly deleted in the HBsAg(-)/AFB1(+),and HBsAg(-)/AFB1(-) groups.ConclusionThe chromosome genetic changes of HCC in Guangxi showed multiplicity.The deletion of chromosome 19p,2p25.1-25.2,3q22.3-q23,7p14.1-p14.3 and amplification of chromosome 9p13.2-9p21 are probably unique genetic characteristics of HCC in this region.The combined effects of Hepatitis B virus and aflatoxin B1 may contribute to deletion of chromosome 13q of HCC in Guangxi.
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BACKGROUND: Alport syndrome (AS) is a clinically and genetically heterogeneous nephropathy. The goal of the present study is to delineate clinical characteristics and the distribution of type IV collagen chains in Chinese AS patients and to identify any alpha(IV)-chain expression and clinical phenotype correlation. METHODS: A total of 126 biopsy-proven patients meeting immunofluorescence criteria for the diagnosis of AS were investigated retrospectively. RESULTS: Microscope haematuria associated with proteinuria was observed as the initial symptom in 77.8% of the patients; 59.8% showed hearing impairment and 22.9% had ocular abnormalities. Renal biopsies from 118 patients revealed mesangial proliferative glomerulonephritis (61.9%) and focal and segmental sclerosis glomerulonephritis (37.3%). Ten different distribution patterns for the type IV collagen alpha-chains were found in the kidney; six of these are presented here for the first time. Based on renal immunofluorescence findings, 113 patients (89.7%) were classified as X-linked dominant inherited AS (XLAS) and 13 (10.3%) as autosomal recessive AS (ARAS). The XLAS group was divided into typical and non-typical subgroups according to the expression patterns for the alpha3(IV)-chain. Clinical phenotypes were more severe in XLAS patients than in ARAS patients and the prognosis was poorer in typical XLAS patients than non-typical XLAS patients. CONCLUSION: In China, the incidence of XLAS is 89.7% and 10.3% for ARAS. Chinese patients with AS have various distribution patterns of type IV collagen alpha-chains. The distribution pattern of type IV collagen alpha-chains in the kidney may correspond to the severity of the clinical phenotype.
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Autoantigens/metabolism , Collagen Type IV/metabolism , Nephritis, Hereditary/metabolism , Adolescent , Adult , Autoantigens/genetics , Child , Child, Preschool , China , Cohort Studies , Collagen Type IV/genetics , Female , Humans , Infant , Male , Middle Aged , Nephritis, Hereditary/genetics , Nephritis, Hereditary/pathology , Phenotype , Retrospective Studies , Severity of Illness IndexABSTRACT
As a rising medical science,evidence-based medicine should be extensively used.Applying the principle of evidence-based medicine to the clinical teaching of burns has positive significance for improving teaching quality,which is helpful to the cultivation of students'clinical thinking abilities.
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<p><b>OBJECTIVES</b>To investigate the effect of rhein on endothelial plasminogen activator inhibitor-1 (PAI-1) mRNA expression and protein production induced by transforming growth factor beta1 (TGFbeta1), and to explore the mechanism of the protective action of rhein on endothelial cells.</p><p><b>METHODS</b>A human umbilical endothelium derived cell line (ECV-304) from ATCC was used in this study. The PAI-1 mRNA expression and protein synthesis in the endothelial cells were detected by Northern blot and flow cytometry analysis, respectively. The activity of phospho-p44/p42 MAP kinase induced by TGFbeta1 was determined by immunoprecipitation analysis and western blot.</p><p><b>RESULTS</b>TGFbeta1 rapidly increased PAI-1 mRNA expression in the endothelial cells, and this effect lasted at least 24 hours. The upregulation of PAI-1 mRNA expression induced by TGFbeta1 in endothelial cells was inhibited by rhein in a dose-dependent manner. In addition, rhein inhibited endothelial PAI-1 protein production. Further study revealed that rhein had a significant inhibitory effect on the activity of phospho-p44/p42 MAP kinase induced by TGFbeta1 in human endothelial cells.</p><p><b>CONCLUSIONS</b>Our results showed that rhein may have a protective effect on the endothelial dysfunction by inhibiting overexpression of PAI-1, indicating a way for the treatment of vascular diseases.</p>
Subject(s)
Humans , Anthraquinones , Pharmacology , Cells, Cultured , Dose-Response Relationship, Drug , Endothelium, Vascular , Metabolism , Mitogen-Activated Protein Kinase 1 , Metabolism , Mitogen-Activated Protein Kinase 3 , Mitogen-Activated Protein Kinases , Metabolism , Plasminogen Activator Inhibitor 1 , Genetics , RNA, Messenger , Transforming Growth Factor beta , Transforming Growth Factor beta1ABSTRACT
<p><b>OBJECTIVE</b>To explore the relationship of plasminogen activator inhibitor-1 (PAI-1) gene -675 4G/5G and beta fibrinogen gene -455 G/A variations to glomerular microthrombosis(T) in lupus nephritis(LN).</p><p><b>METHODS</b>One hundred and one patients with biopsy proven LN were divided into two groups according to the presence or absence of glomerular microthrombus, i.e. group LN+T(n=46) and group LN-T(n=55). The genotypes of PAI-1 gene and beta fibrinogen gene were profiled by polymerase chain reaction-sequence length polymorphism (PCR-SLP) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) respectively. Clinical baseline data at the time of renal biopsy were collected. Normal controls consisted of 128 unrelated healthy adults. The etiologic fractions (EF) were calculated for estimating the contribution of risk genotypes of the two candidate genes to an increase in susceptibility to glomerular microthrombosis in LN patients.</p><p><b>RESULTS</b>Both the 4G/4G genotype and the 4G allele of PAI-1 gene occurred more frequently in group LN+T (47.83% and 0.685) than in group LN-T (23.64% and 0.507)(P<0.05) and normal controls (28.13% and 0.570) (P<0.05). The PAI-1 4G/4G genotype was significantly associated with microthrombosis (OR=2.96, 95%CI:1.26-6.92). Besides, the prevalence of the genotypes carrying the A allele of beta fibrinogen gene, i.e. G/A and A/A, as well as the prevalence of the A allele per se, was increased in group LN+T (47.83% and 0.261) versus group LN-T (27.27% and 0.145)(P<0.05). LN patients carrying the A allele had a high risk of glomerular thrombosis(OR=2.44, 95%CI:0.98-5.59). In addition, the presence of the PAI-1 4G/4G genotype together with the A allele of the beta fibrinogen gene was found to be a greater risk factor (OR=4.5, 95%CI: 1.34-15.12) for glomerular thrombosis in LN than the 4G/4G genotype or the A allele alone. The pooled EF (45.98%) for the risk genotypes of both PAI-1 gene and beta fibrinogen gene was also higher than that for the risk genotypes of either gene (31.67% and 28.23%).</p><p><b>CONCLUSION</b>The above findings indicated that genetic variations in PAI-1 and beta fibrinogen loci might represent risk factors for glomerular microthrombosis in LN. They may have synergetic impact and present gene dosage effect on the susceptibility to this pathological subphenotype.</p>
Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Alleles , Capillaries , Pathology , Confidence Intervals , Fibrinogen , Genetics , Gene Dosage , Kidney Glomerulus , Pathology , Lupus Nephritis , Genetics , Odds Ratio , Plasminogen Activator Inhibitor 1 , Genetics , Polymorphism, Genetic , Thrombosis , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To investigate the relationship between codon 54 gene polymorphism of the host defense molecule, mannose-binding protein (MBP), and the patterns of glomerular immune deposition in IgA nephropathy (IgAN).</p><p><b>METHODS</b>IgAN patients with different patterns of glomerular immune deposition were selected and divided into two groups. Group A consisted of 77 patients with glomerular IgA and C3 deposits, and Group AGM consisted of 70 patients with glomerular IgA, IgG, IgM, C3 and Clq deposits. Clinical features and laboratory relevant data of all patients were collected. One-hundred and forty healthy adults were recruited as normal controls. The MBP gene codon 54 GGC/GAC polymorphism was investigated by using polymerase chain reaction and restriction fragment length polymorphism.</p><p><b>RESULTS</b>The genotype frequency of GGC/GAC heterozygotes was significantly higher in Group AGM as compared with that of Group A (41.4% vs 19.5%, P < 0.01) or normal subjects (41.4% vs. 26.4%, P < 0.05), while no difference was found in the distribution of MBP genotypes between Group A and normal subjects. GAC allele frequency was also higher in Group AGM than that in Group A (0.24 vs. 0.14, P < 0.05) or normal subjects (0.24 vs. 0.15, P < 0.05). The variant allele (GAC) was markedly associated with Group AGM (OR = 1.95, 95% CI: 1.06 - 3.58). In both Group A and Group AGM, more patients carrying the variant allele had episodes of upper respiratory or gastrointestinal infections prior to the onset of IgAN than those with wild homozygotes (GGC/GGC).</p><p><b>CONCLUSIONS</b>Genetic variation of the host defense molecule, MBP, may be involved in the formation of the diverse patterns of glomerular immune deposition in IgAN. The variant allele of the MBP gene may partially account for abundant immune deposits in some IgAN patients.</p>
Subject(s)
Adult , Female , Humans , Male , Alleles , Carrier Proteins , Genetics , Collectins , DNA , Genetics , Gene Frequency , Genetic Variation , Genotype , Glomerulonephritis, IGA , Genetics , Allergy and Immunology , Kidney Glomerulus , Allergy and Immunology , Pathology , Polymorphism, Restriction Fragment LengthABSTRACT
Objective To evaluate the role of angiotensin-converting enzyme (ACE) gene polymorphism in the progression of renal diseases. Methods ACE gene polymorphism was analyzed in 77 patients with end stage renal failure (ESRF) and 150 normal control. Results The frequences of DD and DI genotype were significantly higher in ESRF patients than normal control (DD, 15.6% VS 6.0%, P