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Objective:To evaluate the clinical value of temporal pole and external capsule white matter hyperintensities (WMHs) on the diagnosie of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) by meta-analysis.Methods:PubMed, Cochrane, Embase, VIP database, China Biomedical Literature database, CNKI, Wanfang Data Service Platform were retrieved. The relevant literature of temporal pole and external capsule WMHs for the diagnosis of CADASIL was collected. The retrieval time limit was from the establishment of the databases to April 1, 2020. Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used to evaluate the quality of literature. Stata 15.1 software was used for statistical analysis. The fitted Summary Receiver Operating Characteristic (SROC) curve and combined diagnostic effect size were used to evaluate the diagnostic value of temporal pole and external capsule WMHs for CADASIL.Results:A total of 9 articles involving 10 studies were enrolled, including 880 patients. The combined sensitivities of temporal pole and external capsule WMHs for CADASIL were 0.67 (95% confidence interval [ CI] 0.54-0.78) and 0.84 (95% CI 0.72-0.91) respectively, the combined specificities were 0.64 (95% CI 0.47-0.78) and 0.44 (95% CI 0.36-0.53) respectively, the combined positive likelihood ratios were 1.9 (95% CI 1.4-2.6) and 1.5 (95% CI 1.2-1.8) respectively, the combined negative likelihood ratios were 0.51 (95% CI 0.42-0.63) and 0.37 (95% CI 0.20-0.69) respectively, the odds ratios of combined diagnosis were 4 (95% CI 3-5) and 4 (95% CI 2-9) respectively, and the area under the SROC curves were 0.71 (95% CI 0.66-0.74) and 0.62 (95% CI 0.58-0.66) respectively. Conclusions:The temporal pole and external capsule WMHs have limited diagnostic value for CADASIL, and other factors need to be comprehensively considered in the clinical diagnosis process.
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Objective:To investigate the effect of high mobility group box-1 protein (HMGB1)-nuclear factor-κB (NF-κB) signaling pathway on autophagy and chemosensitivity of human hepatocellular carcinoma cells and its possible mechanism.Methods:Human hepatocellular carcinoma BEL-7402 cells were cultured in vitro and divided into control group (BEL-7402 cells without any treatment), doxorubicin group, recombinant human HMGB1+doxorubicin group, anti-HMGB1 neutralizing antibody+doxorubicin group, pyrrolidine dithiocarbamate+doxorubicin group and 3-methyladenine + doxorubicin group. The methyl thiazolyl tetrazolium (MTT) method was used to detect cell proliferation inhibition rate. Western blot method was used to detect the expressions of HMGB1 and NF-κB subunit p-p65 protein, the autophagy-related proteins Beclin-1, LC3Ⅰ, LC3Ⅱ and apoptosis-related protein bcl-2. Enzyme labeling method was used to detect Caspase-9 and Caspase-3 activity.Results:The cell proliferation inhibition rates in the control group, doxorubicin group, recombinant human HMGB1+doxorubicin group, anti-HMGB1 neutralizing antibody+doxorubicin group, pyrrolidine dithiocarbamate+doxorubicin group and 3-methyladenine+doxorubicin group were (1.31±0.16)%, (47.80±6.30)%, (31.60±5.68)%, (67.20±6.83)%, (66.60±6.27)%, and (68.60±11.19)%, respectively, and the difference was statistically significant ( F = 75.91, P < 0.01), suggesting that doxorubicin had a proliferation inhibitory effect on BEL-7402 cells; the expression levels of HMGB1 were 1.17±0.11, 1.37±0.15, 1.43±0.15, 0.70±0.09, 1.27±0.12, 1.29±0.18, and the difference was statistically significant ( F = 18.70, P < 0.01), suggesting that doxorubicin could increase the expression of HMGB1 in BEL-7402 cells, and the anti-HMGB1 neutralizing antibody could block or attenuate this effect; after pretreatment with recombinant human HMGB1, the proliferation inhibitory effect of doxorubicin on BEL-7402 cells was weakened; after pretreatment with anti-HMGB1 neutralizing antibody, pyrrolidine dithiocarbamate and 3-methyladenine, the proliferation inhibitory effect of doxorubicin on BEL-7402 cells was enhanced. Compared with the control group, the expression of p-p65 protein in the doxorubicin group, recombinant human HMGB1+doxorubicin group and 3-methyladenine+doxorubicin group increased (all P < 0.05). The expression of p-p65 protein in the recombinant human HMGB1+doxorubicin group, anti-HMGB1 neutralizing antibody+doxorubicin group and pyrrolidine dithiocarbamate+doxorubicin group was lower than that in the doxorubicin group (all P < 0.05). Compared with the control group, the expression of bcl-2 protein in doxorubicin group, anti-HMGB1 neutralizing antibody+doxorubicin group, pyrrolidine dithiocarbamate+doxorubicin group and 3-methyladenine+ doxorubicin group decreased (all P < 0.05), and the activity of Caspase-9 and Caspase-3 was enhanced (all P < 0.05); after adding recombinant human HMGB1 pretreatment, the expression of bcl-2 protein in the cells increased compared with doxorubicin alone, and the activity of Caspase-9 and Caspase-3 was weakened (all P < 0.05). The expression levels of autophagy-related protein Beclin-1 in the control group, doxorubicin group, recombinant human HMGB1+doxorubicin group, anti-HMGB1 neutralizing antibody+doxorubicin group, pyrrolidine dithiocarbamate+doxorubicin group, and 3-methyl adenine+doxorubicin group were 0.77±0.12, 0.92±0.07, 1.29±0.10, 0.51±0.03, 0.49±0.06, and 0.42±0.05, and the difference was statistically significant ( F = 97.01, P < 0.01). The expression levels of LC3Ⅱ were 0.24±0.04, 0.39±0.04, 0.49±0.07, 0.23±0.05, 0.20±0.06, and 0.20±0.05, and the difference was statistically significant ( F = 26.98, P < 0.01). Conclusion:The activation of HMGB1-NF-κB signaling pathway can reduce the chemosensitivity of hepatocellular carcinoma cells to doxorubicin, and its mechanism may be related to the regulation of autophagy and down-regulation of doxorubicin inducing apoptosis of hepatocellular carcinoma cells.
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Objective:To summarize the clinical and imaging features of five patients of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) with cysteine-sparing NOTCH3 gene missense mutations and explore potential pathogenicity of gene mutations.Methods:The clinical data from five patients who were admitted to the People′s Hospital of Zhengzhou University from March 2017 to November 2018 were collected. The patients were found to carry cysteine-sparing NOTCH3 gene mutations through genetic testing and diagnosed pathologically. They were probands confirmed from five unrelated family and all five patients were performed full exon detection and skin biopsy.Results:Genetic testing identified five patients with cysteine-sparing NOTCH3 gene missense mutations, a total of five different mutations, including p.R75Q, p.D80G, p.V237M, p.S1418L and p.R1761H. The first three mutations were found in the epidermal growth factor-like repeats (EGFr), the latter two mutations near the transmembrane domain. Granular osmiophilic material was identified in all cases examined with skin biopsy. The age at initial symptom onset of these five cases was ranged from 22 to 58 years and three cases presented cardiovascular risk factors. The primary clinical manifestations included migraine in one case, ischemic stroke in three cases, psychiatric disturbances in four cases, cognitive dysfunction in five cases, while gait disturbance, pseudobulbar palsy, and seizures accounted for only one case each. Magnetic resonance imaging of five patients all showed white matter hyperintensities (WMLs) and lacunar infarcts, and WMLs involved the anterior temporal pole and external capsules in three cases separately. According to the criteria proposed by Mui?o et al for evaluating the pathogenicity of cysteine-sparing NOTCH3 mutations, all five mutations are potentially pathogenic.Conclusions:Most characteristics of CADASIL patients with cysteine-sparing NOTCH3 gene mutations are similar to those of CADASIL patients with cysteine NOTCH3 gene mutations. Mutations not involving the EGFr may also have potential pathogenicity, and the specific mechanism still needs further study.
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Objectives To analyze the links of the in-hospital delay by investigating the status of in-hospital delay in patients with acute ischemic stroke in a tertiary hospital in Beijing and to shorten the in-hospital delay by intervention. Methods From August 2016 to July 2017,98 patients with ischemic stroke treated by endovascular therapy and met the inclusion criteria in the Xuanwu Hospital, Capital Medical University were collected prospectively. According to before and after intervention,the patients were divided into before intervention (from August 2016 to January 2017,n=44) and after intervention (from February to July 2017,n=54). The questionnaire was designed by the authors. The survey included the basic information of patients,clinical features,and key time point of hospital treatment process. The delay links were analyzed through the value flow diagram,and the targeted interventions were given to shorten the time of in-hospital delay. Results (1) The main links of the presence of in-hospital delay are physician evaluation,disease notification, signing of the informed consent, and preoperative preparation. ( 2 ) The intervention effect was significant. The median total nosocomial process time before and after intervention were 138. 0 (118. 5,188. 8) min and 93. 5 (80. 0,114. 0) min respectively. There was significant difference(Z=5. 929,P<0. 01). Compared with before intervention,the time of examination,imaging examination, preoperative preparation and femoral artery puncture were shorter ( 16. 5 [ 10. 0, 27. 2 ] min vs. 35. 0 [18. 2,51. 8] min;10. 0 [9. 0,11. 0] min vs. 12. 5 [10. 0,23. 8] min;48. 0 [30. 0,67. 5] min vs. 60. 5 [45. 5,90. 8] min;15. 0 [12. 0,18. 2] min vs. 21. 0 [13. 0,33. 0] min,Z=4. 150,3. 685,2. 801,and 2. 852,respectively;all P<0. 05). Conclusions The nosocomial process of endovascular treatment in patients with ischemic stroke is seriously delayed. Through continuous improvement of the nosocomial process,setting up a parallel treatment modality,strengthening the stroke team training,and improving the docking measures of the information system platform can significantly shorten the in-hospital time.
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Objective To investigate the effect of prehospital transport mode on delay care in patients withacutestroke.Methods From March 2016 to August 2016,a total of 255 consecutive patients with acute stroke who met the inclusion criteria in Xuanwu Hospital,Capital Medical University were analyzed prospectively. Seven patients were excluded because of incomplete data. A total of 248 valid cases were enrolled. They were divided into either an ambulance transport group (n=88)or a non-ambulance transport group (n=160)according to whether they were transported by ambulance or not. The differences of the baseline data,prehospital status,onset-to-door time,door-to-examination time,door-to-CT scan time,door-to-intravenous thrombolysis time of the 2 groups were compared,and the related factors of ambulance use were analyzed in patients with acute stroke. Results (1)The ambulance utilization rate of 248 patients was 35. 5%. The age,the coronary heart disease rate,National Institutes of Health Stroke Scale (NIHSS)score of the patients in the ambulance transport group were higher than those of the non-ambulance transport group. There were significant differences between the two groups (65 ± 11 vs. 61 ± 11 years,15. 9%[14/88]vs. 5. 6%[9/160],9 [3,17]vs. 2 [1,5];all P <0. 05). The stroke rate of the patients in the ambulance transport group was lower than that of the non-ambulance transport group(23. 9%[21/88]vs. 37. 5%[60/160],P<0. 05). (2)There were significant differences in self-identified acute disease and self-health care consciousness between the ambulance transport group and the non-ambulance transport group (all P<0. 01). (3)Compared with the non-ambulance transport group,the onset-to-door time,door-to-examination time,door-to-CT scan time,door-to-intravenous thrombolysis time were shorter in patients of the ambulance transport group (102[64,150]min vs. 136[86,230]min,3[1,8]min vs. 7[4,11]min, 15[18,23]min vs. 16[22,27]min,and 41 ± 9 min vs. 50 ± 10 min;all P <0. 05). (4)The result of Logistic regression analysis showed that the acute stroke patients with advanced age (OR,1. 04,95%CI 1. 01-1. 08,P =0. 01),higher NIHSS score (OR,1. 13,95%CI 1. 08-1. 19,P <0. 01),they or the insiders thought that the disease was emergent (OR,17. 08,95%CI 5. 78-50. 41,P<0. 01),they would seek medical advice in time when they felt sick (OR,38. 13,95%CI 10. 13-143. 61,P<0. 01),and they would take medicine by themselves when they felt sick (OR,6. 82,95%CI 2. 33-19. 99,P<0. 01)were more likely to be transported to hospital by ambulance.Conclusion Using ambulance can reduce the treatment de-lay for patients with acute stroke. The patients with self-health care consciousness are more likely to choose am-bulance transport. The importance of using ambulance should be strengthened for patients with stroke.
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Terahertz waves have unique properties and advantages, which makes it gain increasing attention and applications in the biomedical field. Burns is a common clinical trauma. Since the water-sensitive and non-destructive characteristics of terahertz, terahertz imaging techniques can be used to detect burns. So far, terahertz imaging technology in the assessment of burn injuries has been developed from ex vivo to in vivo, and high-resolution images can be obtained through the gauzes and plasters. In this paper, we mainly introduces the application of terahertz imaging technology and development in the assessment of burn injuries.
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Humanos , Vendajes , Quemaduras , Diagnóstico , Imágen por TerahertzRESUMEN
AIM:To determine the therapeutic efficacy of recombinant adenovirus containing hyper-interleu-kin-6 (HIL-6) and hepatocyte growth factor (HGF) (Ad-HGF-HIL-6) on acute-on-chronic liver failure (ACLF) in rats u-sing that of recombinant adenovirus HIL-6 or HGF ( Ad-HIL-6 or Ad-HGF) for comparison.METHODS:The rat model of ACLF was established and the model rats were randomly divided into model group, Ad0 group, Ad-HGF group, Ad-HIL-6 group and Ad-HGF-HIL-6 group.The sera and liver tissues were collected for biochemical, pathological and molecular bio-logical examinations.RESULTS:Compared with Ad0 group, prothrombin time ( PT) and the serum levels of alanine amin-otransferase (ALT), tumor necrosis factor-α(TNF-α), interferon-γ(IFN-γ) and high-mobility group box-1 (HMGB1) were markedly reduced in the ACLF rats treated with Ad-HGF, Ad-HIL-6 and Ad-HGF-HIL-6, and similarly, reduced he-patic damages and apoptotic activity, reduced Bax at protein level, and increased expression of Ki67 and Bcl-2 at protein levels were observed.Among them, treatment with Ad-HGF-HIL-6 showed the most significant therapeutic efficacy without obvious side effects.CONCLUSION:The therapeutic efficacy of Ad-HGF-HIL-6 is more potent than that of Ad-HGF or Ad-HIL-6 alone on ACLF rats with no significant side effects.
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Objective To investigate the relationship between tumor metastasis-related Rac1 mRNA expression levels and gastric carcinomas metastasis, and to investigate the significance of Rac1 as a tumor marker for the evaluation of gastric carcinomas metastasis and distinguish between benign and malignant lesions. Methods This experiment used fluorescence quantitative RT-PCR TaqMan probe technology, chose Rac1 target gene fragment, which was cloned into the pET-20b (+) vector, constructed recombinant plasmid, and established the Rac1 mRNA fluorescence quantitative RT-PCR standard curve. And then the Rac1 mRNA levels were detected in 52 cases of gastric carcinoma tissues,52 cases of para-carcinoma tissues and 12 cases of benign gastric disease tissues. Its association with the metastasis of gastric carcinomas was analyzed. Results The positive rates and levels (median, P25-P75) of Rac1 mRNA were 100. 0% ,7.41 ×105 (3. 50 × 105-4. 36 × 106) copies/μl in gastric carcinomas, 46. 2% ,0(0-1.73 × 104) copies/μl in parscarcinoma tissues, 33. 3%, 0(0-3.55 × 103) copies/μl in benign tissues. The positive rates and leves(x2 =43.16,x2Xk-w = 64. 19, P ＜0. 01)among the three groups were significantly different. When the critical value of Rac1 mRNA level was 1.73 × 104 copies/μl determined by ROC, the sensitivity and specificity were 88. 5% and 100% respectively. When the critical value of Rac1 level was 7.49 × 105 copies/μl, the sensitivity and specificity were 57.9% and 78. 6% respectively. ConclusionThe Rac1 mRNA level detected with fluorescence quantitative RT-PCR has reference value to distinguish between benign and malignant lesions and evaluate gastric carcinoma metastasis.