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Objective@#To investigate the effect and regulatory mechanism of Smurf2 on the negative regulator Smad7 of TGF-β1/Smad signaling pathway in hypertrophic scar fibroblasts.@*Methods@#From January to October 2014, 8 patients with hypertrophic scar after burn were admitted. The age of patients ranged from 1 year 8 months to 7 years, and the time of scar hyperplasia ranged from 2 to 12 months. The residual normal skin of the same patient was used as the control. The fibroblasts were isolated from hypertrophic scar and normal skin respectively and cultured. The third to fifth passage cells were used for the experiments. ① The protein expression of Smad7 in the two groups was detected by Western Blot. ② Hypertrophic scar fibroblasts and normal skin fibroblasts were treated with exogenous TGF-β1 at concentration of 10 ng/ml for 0 min, 5 min, 15 min, 30 min, 1 h, 2 h and 12 h. The expression of Smad7 protein and mRNA were detected by Western Blot and RT-PCR, respectively. ③ The cell lysates of the two groups were collected and incubated with the ubiquitin mixture for 1 h, 2 h and 6 h at 37℃, respectively. The degradation level of Smad7 protein was detected by Western Blot. ④ The cell lysate of hypertrophic scar fibroblasts was collected and incubated with ubiquitin mixture with or without proteasome inhibitor (MG132: MG115=1: 1) to study its inhibitory effect on the degradation of Smad7 in vitro. ⑤ Immunoprecipitation (IP) technique was used to detect the interaction between Smad 7 and E3 ubiquitin ligase Smurf2 in hypertrophic scar fibroblasts. ⑥ The expression of Smad7 protein in hypertrophic scar fibroblasts stimulated by TGF-β1 after Smurf2 silencing by small interference RNA (siRNA) technique were detected by Western blot.@*Results@#① There was no significant difference in the expression level of Smad7 protein between hypertrophic scar and normal skin fibroblasts(t=0.76, P=0.46). ② Expressions of Smad7 mRNA and protein in normal skin fibroblasts stimulated by exogenous TGF-β1 gradually increased in a time-dependent manner(P<0.05). The expression of Smad7 mRNA in the hypertrophic scar fibroblasts increased at all-time points except at 5min , (P<0.05), while there was no significant difference in the expression level of Smad7 protein at all-time points with or without TGF-β1 stimulation(P>0.05). ③ Degradation of Smad7 protein was enhanced in hypertrophic scar fibroblasts (the expression level of Smad 7 protein at each time point was compared with that of the control group and the last time point, P<0.05), while there was no significant difference in Smad7 protein degradation in normal skin fibroblasts(P=0.162). ④ Enhanced degradation of Smad7 in hypertrophic scar fibroblasts was blocked by the addition of the proteasome inhibitors MG132/MG115. ⑤ In hypertrophic scar fibroblasts, the Smurf2-Smad7 complex was detected, which indicated the interaction between Smurf2 and Smad7 in hypertrophic scar fibroblasts. ⑥ The expression of Smad7 protein was not increased in the hypertrophic scar fibroblasts stimulated by TGF-β1, whereas the stimulation of TGF-β1 increased the expression of Smad7 protein after silencing of Smurf2 gene expression.@*Conclusions@#In the hypertrophic scar fibroblasts, Smurf 2 attenuates the inhibitory effect of Smad 7 on TGF-β1 signaling pathway through the degradation of Smad7 by ubiquitination, which may be involved in the formation of hypertrophic scar.
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Medullary thyroid carcinoma (MTC) is an endocrine tumor originating from the parafollicular cells of the thyroid gland.The mutation of RET gene has been considered as the molecular basis of MTC.Different types of MTC have different RET mutation sites,and the corresponding clinical manifestations and prognosis are also very different.RET gene detection is helpful for individual accurate gene diagnosis,molecular risk assessment,individual analysis and early prevention management.Nowadays,targeted therapy for RET gene mutations in MTC has developed rapidly.Some of those drugs,which have been approved for clinical application,bring new hope for advanced MTC.
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ABSTRACT Objective: To assess the susceptibility of the hOGG1 genetic polymorphism for bladder cancer and evaluate the impact of smoking exposure. Materials and Methods: Articles included in PubMed, Medline and Springer databases were retrieved using the following key words: “human 8-oxoguanine DNA glycosylase”, “OGG”, “OGG1”, “hOGG1”, “genetic variation”, “polymorphism” , “bladder cancer”, and “bladder carcinoma” to Meta-analysis was performed to detect whether there were differences between the bladder cancer group and the control group about the distribution of genotypes of the hOGG1 gene. Results: The results showed that there are no significant associations between the hOGG1 326Cys polymorphism and bladder cancer: GG vs. CC (OR: 1.09, 95% CI: 0.85–1.40, p=0.480); GC vs. CC (OR: 1.05, 95% CI: 0.85–1.28, p=0.662); GG+GC vs. CC (OR: 1.04, 95% CI: 0.89–1.21, p=0.619); GG vs. GC+CC(OR: 1.02, 95% CI: 0.78–1.33, p=0.888); G vs. C (OR: 1.01, 95% CI: 0.91–1.13, p=0.818). In the smoker population, no significant associations between the hOGG1 326Cys polymorphism and bladder cancer were observed for all the models. However, individuals carrying the hOGG1 Cys326Cys genotype have increased risk for bladder cancer compared to those carrying the hOGG1 Ser326Ser genotype in the non-smoker Asian population. Conclusion: The hOGG1 326Cys polymorphisms aren't a risk factor for bladder cancer, especially in the smoker population. But GG genotype is a risk factor for bladder cancer to the non-smoker Asian population compared with CC genotype.
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Objective To compare the efficacy and safety of tamsulosin with nifedipine for medical expulsive therapy (MET) in patients with lower ureteral stones (LUS).Methods Randomized controlled trials(RCTs) in comparison of tamsulosin and nifedipine in treatment of LUS published in Pubmed, Cochrane Library,Embase,CNKI,CBM, Wanfang and VIP from databases establishment to July 2015 were retrieved.According to Cochrane handbook, the quality of included RCTs were assessed, and the relevant data including the number of participants, stone size, stone expulsion rate, time to stone expulsion, drug-related side effect,the incidence of ESWL or ureteroscopy lithotripsy (URSL) after MET and analgesic dose were extracted by two reviewers independently.The statistical software RevMan 5.2 was used for meta-analysis with regard to the stone expulsion rate, the incidence of ESWL or URSL and adverse effects.This study lasted more than one month from June to July 2015.Results A total of 13 RCTs with 4 831 patients were eligible.The results showed that the stone expulsion rate and the incidence rate of ESWL or URSL after MET were 92％ (2 221/2 423) and 8％ (27/333) in the tamsulosin group,and 73％ (1 748/2 408) and 20％ (67/328) in the nifedipine group.There are statistically significant differences (RR =1.24,95 ％ CI 1.13-1.37, P ＜ 0.05;RR =0.40,95 ％ CI 0.27-0.60, P ＜ 0.05, respectively).The subgroup analysis indicated no statistically significant differences in drug-related adverse effects between tamsulosin and nifedipine with 5％ (99/1 804)and 7％ (117/1 796) minor adverse effects respectively and less than 1％ severe adverse effects in both groups (RR =0.85,95％ CI 0.65-1.10, P =0.21;RR =0.49,95 ％ CI 0.09-2.59, P =0.40).Conclusion Compared to nifedipine, tamsulosin has higher stone expulsion rate and lower incidence rates for ESWL or URSL.Since there was no obvious adverse effects, tamsulosin could be considered as a preferable option for patients with LUS.
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Objective:To investigate whether pORF5 plasmid protein of Chlamydia trachomatis(Ct) induces 1L-1βand 1L-18 production in THP-1 cells,and its potential molecular mechanism.Methods:pORF5 plasmid protein was used to stimulate THP-1 cells at different concentrations(0,3,6,12,24,36 μg/ml),then the inflammatory cytokines IL-18 and IL-1βwere detected by ELISA at the time of 0,8,16,24,36 h;The mRNA expression of NALP3 inflammasome were detected by Realtime-PCR,and Caspase-1 activity was determined by Western blot analysis.THP-1 cells were transfected with siRNA targeting NALP3 and ASC gene for 24 h or pretreated with Caspase-1 inhibitor(Z-YVAD-FMK) for 30 min,and subsequently stimulated with pORF5(24 μg/ml) for 24 h,then secretion of IL-1βand IL-18 were analyzed by ELISA.Results: The pORF5 plasmid protein induced THP-1 cells to secrete IL-1βand IL-18 by dose-and time-dependent manners,production of IL-1βand IL-18 reached their peaks(491 pg/ml and 186 pg/ml) at concentration of 24 μg/ml,and the peak amount of IL-1βand IL-18 occurred at 24 h and 16 h post-stimulation respectively.pORF5 plasmid protein in-creased mRNA expression of NALP3 inflammasome and activated Caspase-1 in THP-1 cells.NALP3 siRNA,ASC siRNA and Z-YVAD-FMK reduced pORF5-induced IL-1βand IL-18 production when compared with control groups(P<0.05).Conclusion:pORF5 plasmid protein could induce THP-1 cells to produce IL-1βand IL-18 through NALP3 inflammasome activation,which may play an important role in the pathogenesis in Ct infection.
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<p><b>OBJECTIVE</b>To analyze the detection, drug resistance, and status of infection of Acinetobacter baumannii (AB) in burn ICU during 3 years.</p><p><b>METHODS</b>A total of 2 010 specimens of wound secretion, blood, venous catheter attachment, sputum, stool and urine were collected from 505 burn patients hospitalized in our burn ICU from January 2011 to December 2013, and bacterial culture was performed. Pathogens were identified by automatic microorganism identifying and drug sensitivity analyzer. Drug resistance of all the obtained AB to 16 antibiotics commonly used in clinic, including cefoperazone/sulbactam, polymyxin, etc., was tested with K-B paper disk diffusion method. Patients with AB infection were ascertained. The WHONET 5.6 software was used to analyze the distribution of pathogens during 3 years, the isolation of AB with different sources and the status of drug resistance of AB to 16 antibiotics each year, and the status of patients with AB infection, and their outcome.</p><p><b>RESULTS</b>A total of 961 strains of pathogens were isolated, among which 185 (19.25%) strains were Gram positive cocci, 728 (75.75%) strains were Gram negative bacilli, and 48 (4.99%) strains were fungi. A total of 172 strains of AB were isolated, ranking the second place among all the detected pathogens, with 67 (38.95%) strains from wound secretion, 11 (6.40%) strains from blood, 23 (13.37%) strains from venous catheter attachment, and 71 (41.28%) strains from sputum, no AB strain was isolated from feces or urine. The AB strains were found sensitive to polymyxin and with relatively low drug resistance rate to minocycline, while the drug resistance rates were over 80.0% to the other 14 antibiotics commonly used in clinic in 2013. AB culture of wound secretion was positive in 27 patients. Among them, 7 patients suffered from wound infection, and the wound infection was caused by AB in 1 out of the 7 patients. AB culture of blood was positive in 7 patients. Among them, 3 patients suffered from bloodstream infection, and the infection was due to AB invasion in 1 out of the 3 patients. AB culture of venous catheter attachment was positive in 20 patients. Among them, 8 patients suffered from bloodstream infection, and the infection was due to AB invasion in 1 out of the 8 patients. AB culture of sputum was positive in 35 patients. Among them, 13 patients suffered from ventilatory associated pneumonia, and 2 out of the 13 patients were diagnosed as AB infection. A total of 69 patients were AB culture positive, among them 64 patients were cured, 2 patients were transferred to other hospitals, and 3 patients died, with the mortality rate of 4.35%.</p><p><b>CONCLUSIONS</b>AB in our burn ICU has a high detection rate and extensive drug resistance in above-mentioned 3 years. However, AB was mainly colonized in patients with extensive burns with a low mortality rate.</p>
Subject(s)
Humans , Acinetobacter Infections , Drug Therapy , Epidemiology , Microbiology , Acinetobacter baumannii , Anti-Bacterial Agents , Pharmacology , Burns , Microbiology , Cross Infection , Drug Resistance , Gram-Negative Bacteria , Intensive Care Units , Microbial Sensitivity TestsABSTRACT
Objective To assess the association between interleukin-10-1082 (IL-10-1082) gene polymorphisms and susceptibility of gastric cancer in the Chinese population.Methods Cochrane systematic evaluation was adopted for the analysis.Articles published in Medline,Embase,Cochrane library,CBM,CJFD and CSJD from 1966 to 2012 were retrieved.Case control studies on the correlation between the 1L-10-1082 polymorphism and gastric cancer in Chinese population were collected.Gastric cancer patients were in the gastric cancer group,and healthy individuals were in the control group.Two researchers extracted data and evaluated the quality of literatures independently.Meta analysis was performed to detect whether there were differences between the gastric cancer group and the control group about the distribution of genotypes of IL-10-1082 gene (GG,AA,AG,AA,alleles G and A).The heterogeneity was analyzed using the Q test or I2 test.Fixed effect model or random effect model was adopted,and the results of the meta analysis were presented with odds ratio (OR) and 95％ confidence interval (95％ CI).Results Thirteen literatures including 5252 patients were included in the analysis.There were 2077 patients in the gastric cancer group and 3175 patients in the control group.The results of meta analysis showed that population with the genotypes GG and AG have higher risk of having gastric cancer when compared with population with the genotype AA (OR =1.76,95％ CI 1.33-2.33 ; OR =2.08,95％ CI 1.62-2.66,P ＜0.05).Population with the allele G have higher risk of having gastric cancer when compared with population with allele A (OR =1.67,95％ CI 1.31-2.13,P ＜ 0.05).Conclusion The genotypes GG,AG and the allele G of IL-10-1082 gcne of the Chincse population are significantly associated with the increased risk of gastric cancer.
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Sepsis is considered as an uncontrolled inflammatory response, while wound healing is a process involving the joint participation of many elements, including inflammatory cells, repair cells, inflammatory mediators, growth factors, and extracellular matrix. This review summarizes the effects of changes in immune function, coagulation function, and metabolism after sepsis as a complication of burn on wound healing, and looks into the prospect of prevention and treatment of burn complicated by sepsis, hoping to accelerate wound healing by reducing the incidence of sepsis.
Subject(s)
Humans , Burns , Allergy and Immunology , Metabolism , Sepsis , Tumor Necrosis Factor-alpha , Wound HealingABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of lung protective ventilation strategy combined with lung recruitment maneuver on ARDS complicating patients with severe burn.</p><p><b>METHODS</b>Clinical data of 15 severely burned patients with ARDS admitted to our burn ICU from September 2011 to September 2013 and conforming to the study criteria were analyzed. Right after the diagnosis of acute lung injury/ARDS, patients received mechanical ventilation with lung protective ventilation strategy. When the oxygenation index (OI) was below or equal to 200 mmHg (1 mmHg = 0. 133 kPa), lung recruitment maneuver was performed combining incremental positive end-expiratory pressure. When OI was above 200 mmHg, lung recruitment maneuver was stopped and ventilation with lung protective ventilation strategy was continued. When OI was above 300 mmHg, mechanical ventilation was stopped. Before combining lung recruitment maneuver, 24 h after combining lung recruitment maneuver, and at the end of combining lung recruitment maneuver, variables of blood gas analysis (pH, PaO2, and PaCO2) were obtained by blood gas analyzer, and the OI values were calculated; hemodynamic parameters including heart rate, mean arterial pressure (MAP), central venous pressure (CVP) of all patients and the cardiac output (CO), extravascular lung water index (EVLWI) of 4 patients who received pulse contour cardiac output (PiCCO) monitoring were monitored. Treatment measures and outcome of patients were recorded. Data were processed with analysis of variance of repeated measurement of a single group and LSD test.</p><p><b>RESULTS</b>(1) Before combining lung recruitment maneuver, 24 h after combining lung recruitment maneuver, and at the end of combining lung recruitment maneuver, the levels of PaO2 and OI of patients were respectively (77 ± 8), (113 ± 5), (142 ± 6) mmHg, and (128 ± 12), (188 ± 8), (237 ± 10) mmHg. As a whole, levels of PaO2 and OI changed significantly at different time points (with F values respectively 860. 96 and 842. 09, P values below 0. 01); levels of pH and PaCO2 showed no obvious changes (with F values respectively 0.35 and 3.13, P values above 0.05). (2) Levels of heart rate, MAP, CVP of all patients and CO of 4 patients who received PiCCO monitoring showed no significant changes at different time points (with F values from 0. 13 to 4. 26, P values above 0.05). Before combining lung recruitment maneuver, 24 h after combining lung recruitment maneuver, and at the end of combining lung recruitment maneuver, the EVLWI values of 4 patients who received PiCCO monitoring were respectively (13.5 ± 1.3), (10.2 ± 1.0), (7.0 ± 0.8) mL/kg ( F =117.00, P <0.01). (3) The patients received mechanical ventilation at 2 to 72 h after burn, lasting for 14-32 (21 ± 13) d. At post injury day 3-14 (7 ± 5) d, lung recruitment maneuver was applied for 2-5 (3.0 ± 2.0) d. All 15 patients recovered without other complications.</p><p><b>CONCLUSIONS</b>Lung protective ventilation strategy combining lung recruitment maneuver can significantly improve the oxygenation in patients with severe burn complicated with ARDS and may therefore improve the prognosis.</p>
Subject(s)
Humans , Acute Lung Injury , Therapeutics , Blood Gas Analysis , Burns , Extravascular Lung Water , Hemodynamics , Positive-Pressure Respiration , Respiration, Artificial , Methods , Respiratory Distress Syndrome , Therapeutics , Treatment OutcomeABSTRACT
Objective To evaluate the application effect of mind map in admission guidance of patients receiving gamma knife treatment.Methods 153 cases of hospitalized patients admitted in our hospital were selected for this study,which had been divided according to the random number table method,the observation group(77 cases) was guided with the hospital mind map method,and the control group (76 cases) was given traditional oral hospital instruction,respectively.The database was established for the double entry,calibration and data cleaning,which were obtained from the result of gamma knife treatment of intracranial tumor disease related knowledge questionnaire,hospital satisfaction questionnaire and also patient adherence questionnaire assessment.Results The comparison of knowledge assessment questionnaire outcome,the admission guide satisfaction questionnaire assessment,the patients compliance questionnaire assessment outcome showed that the observation group was significantly different from the control group.Conclusions Application of mind map in admission guidance for hospitalized patients was a more efficient method than the traditional oral admission instruction,the method is simple,practical and effective,which is worthy of clinical practice.