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Antibiotics and organic residues from Tetracycline (TC) and other pharmaceuticals administered to aquatic living organism have negative impacts on aquatic environment by killing-off non-target living organisms and developing antibiotic-resistant bacteria. In this study, Micro-Nano Bubble (MNB) system was used to remove TC residues. MNB system demonstrated good level of degradation efficiency, as resulted in experiment where in time of 100 min, the TC degraded at rate of 82.66% from its initial concentration of TC when the initial concentration was 1 mg/L. When the initial concentration was increased to 10 mg/L, MNB system degraded TC at 64.35% of their initial, this means MNB system demonstrated good level of efficiency for TC removal and indicated that it is more efficient in TC degradation under the conditions of low initial TC concentration and high availability of dissolved oxygen (DO). In the system as the temperature increased there was a significant decrease in DO saturation which was related to the TC complex structure that contain multiple function groups such as amino groups, hydroxyl and carboxyl which possess high strong affinity with oxygen that leads to their adsorption onto bubble surface. This study provides significant insights into the application of MNB system for the removal of organic residues within aquatic ecosystem and underscores the need for further exploration of MNB technology for environmental remediation.
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Tetraciclina , Tetraciclina/química , Tetraciclina/análisis , Contaminantes Químicos del Agua/química , Adsorción , Oxígeno/química , Antibacterianos/químicaRESUMEN
Immune checkpoint inhibitor (ICI) rechallenge in non-small cell lung cancer (NSCLC) is a promising therapeutic strategy. The situation for ICI rechallenge can be divided into three categories: adverse events (AEs); resistance to ICIs, and rechallenge becomes compulsive because of tumor relapse while the patients had completed a 2 year course of immunotherapy. However, these categories are still controversial and should be explored further. Through voting at the 6th Straits Summit Forum on Lung Cancer, in this study we summarize the consensus of 147 experts in ICI rechallenges. A total of 97.74% experts agreed to rechallenge; 48.87% experts rechallenge with the original drug, and the others rechallenge with a different drug; 40.3% agreed to rechallenge directly after progression; 88.06% experts agreed to ICI rechallenge with a combination regimen; and factors such as previous performance status score, PD-1 expression, and age should also be considered. Understanding the the clinical studies in ICI rechallenge could bring us one step closer to understanding the consensus. In patients with advanced NSCLC who have suffered recurrent or distant metastasis after immunotherapy, the option of rechallenge with ICIs is a promising treatment option.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Consenso , InmunoterapiaRESUMEN
BACKGROUND:Intervertebral disc degeneration is one of the most common underlying factors causing low back pain.Recent studies have shown that melatonin has a positive effect on alleviating intervertebral disc degeneration.However,the underlying mechanism of melatonin remains to be elucidated. OBJECTIVE:To explore the biological effect and potential mechanism of melatonin in inhibiting hydrogen peroxide(H2O2)-induced injury of human nucleus pulposus cells. METHODS:Human nucleus pulposus cells insolated from degenerative intervertebral disc were cultured in vitro.Cell proliferation and the optimal intervention concentration of melatonin and H2O2 were detected by cell counting kit-8.The Human nucleus pulposus cells treated with H2O2 were used as a model group;the cells treated with H2O2 and intervened with melatonin were used as a melatonin group;the cells cultured in simple medium were used as a control group.The reactive oxygen species levels were detected by 2',7'-dichlorofluorescin diacetate(DCFH-DA),the expression levels of BAX and Caspase3 were detected by immunofluorescence,and the mRNA expression levels of BAX,BCL-2,Casepase3,PI3K and AKT were detected using the real-time fluorescent quantitative reverse transcription PCR. RESULTS AND CONCLUSION:The results of cell counting kit-8 experiment showed that the optimal intervention concentration of H2O2 was 400 μmol/L and the optimal intervention concentration of melatonin was 5 μmol/L.The reactive oxygen species level in the melatonin group was significantly lower than that in the model group.The average fluorescence intensity of BAX and Caspase3 in the melatonin group was significantly lower than that in the model group.The mRNA expressions of BAX and Caspase3 in the melatonin group were lower than those in the model group,while the mRNA expression of Bcl-2 was increased.In addition,the mRNA expressions of PI3K and AKT were also higher in the melatonin group compared with the model group.To conclude,melatonin may protect human nucleus pulposus cells from H2O2-induced oxidative damage through the PI3K/AKT signaling pathway.
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Anaplastic lymphoma kinase (ALK) is the most common fusion gene involved in non-small cell lung cancer (NSCLC), and remarkable response has been achieved with the use of ALK tyrosine kinase inhibitors (ALK-TKIs). However, the clinical efficacy is highly variable. Pre-existing intratumoral heterogeneity (ITH) has been proven to contribute to the poor treatment response and the resistance to targeted therapies. In this work, we investigated whether the variant allele frequencies (VAFs) of ALK fusions can help assess ITH and predict targeted therapy efficacy. Through the application of next-generation sequencing (NGS), 7.2% (326/4548) of patients were detected to be ALK positive. On the basis of the adjusted VAF (adjVAF, VAF normalization for tumor purity) of four different threshold values (adjVAF < 50%, 40%, 30%, or 20%), the association of ALK subclonality with crizotinib efficacy was assessed. Nonetheless, no statistical association was observed between median progression-free survival (PFS) and ALK subclonality assessed by adjVAF, and a poor correlation of adjVAF with PFS was found among the 85 patients who received first-line crizotinib. Results suggest that the ALK VAF determined by hybrid capture-based NGS is probably unreliable for ITH assessment and targeted therapy efficacy prediction in NSCLC.
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Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Quinasa de Linfoma Anaplásico/uso terapéutico , Crizotinib/uso terapéutico , Neoplasias Pulmonares/patología , Inhibidores de Proteínas Quinasas/farmacología , Frecuencia de los GenesRESUMEN
Objective:To evaluate the value of preoperative aspartate aminotransferaseto platelet ratio index (APRI) and fibrosis index 4 (Fib4) in predicting posthepatectomy liver failure (PHLF) of primary hepatocellular carcinoma.Methods:The data of 587 patients with hepatocellular carcinoma admitted to the First Affiliated Hospital of Xinjiang Medical University from January 2014 to January 2020 were retrospectively collected and analyzed, including 412 males and 175 females, aged (56.8±11.2) years. Univariate and multivariate logistic regression were used to analyze the influencing factors of PHLF. The ability of Child-Pugh score, model for end-stage liver diseas (MELD) score, APRI and Fib4 to predict PHLF was evaluated through the receiver operating characteristic (ROC) curve of subjects.Results:Among 587 patients, 186 (31.7%) had liver failure after hepatectomy. In multivariate logistic regression analysis, APRI ( OR=2.660, 95% CI: 1.314-5.384, P=0.007) and Fib4 ( OR=1.322, 95% CI: 1.157-1.511, P<0.001) were risk factors for PHLF in patients with hepatocellular carcinoma. The higher the number, the greater the risk of PHLF. The predicted area under the ROC curve of PHLF in patients with hepatocellular carcinoma was Fib4(0.719)>APRI(0.686)>MELD score(0.618)>Child-Pugh score(0.565). Conclusion:APRI and Fib4 were risk factors of PHLF in patients with hepatocellular carcinoma. They predict the occurrence of PHLF better than Child-Pugh score and MELD score.
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BACKGROUND@#Dabrafenib+Trametinib/Dabrafenib targeted therapy has been approved for V-RAF murine sarcoma viral oncogene homolog B1 with amino acid substitution for valine at position 600 (BRAF V600E) in lung cancer patients, however, the targeted therapy strategy for lung cancer patients with BRAF non-V600E mutations has not been determined yet. This study intends to explore the efficacy of targeted therapy for BRAF non-V600E mutant lung cancer, and provide a reference for clinical treatment.@*METHODS@#Computer search of PubMed, Cochrane Library, Embase, Web of Science, Clinicaltrials.gov, CBM, CNKI, Wanfang database. Collect the relevant literature relevant on the targeted therapy of BRAF non-V600E mutant lung cancer, and conduct a descriptive analysis of the included literature.@*RESULTS@#There were 10 articles that met the inclusion criteria, including 3 cohort studies and 7 case reports. 18 patients with BRAF non-V600E mutant lung cancer were ineffective to vermurafenib; 1 patient obtained partial response (PR) after applying vermurafenib, 5 patients did not respond to BRAF inhibitors; 9 patients showed a potential clinical benefit rate of 34% after monotherapy with trametinib; 7 patients have different degrees of benefit from dabrafenib and trametinib on progression-free survival (PFS); 1 patient is effective to sorafenib.@*CONCLUSIONS@#At present, there is no standard treatment specification for BRAF non-V600E mutation targeted therapy. The challenge lies in the heterogeneous mutation of BRAF gene. Different mutation types respond differently to targeted therapy. In addtion, real-world research evidence is scarce, so it is necessary to carry out further large-sample high-quality research to provide reference for clinical practice.
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Animales , Humanos , Ratones , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/genética , Mutación , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas B-raf/genéticaRESUMEN
Objective ToinvestigatethefeasibilityofpredictingtheKi-67expressionusing MRandclinicalfeaturesofbreast cancer.Methods 52patientswith56invasivebreastcarcinomawereretrospectivelyinvestigated.Eachsubjectunderwentpresurgical breastMRI,whichincludeddynamiccontrastenhancementandDWI(b=0s/mm2,1000s/mm2).Clinicalcharacteristicsand MR findingswerecollected,includingage,ER ,PR ,HER2,tumorsize,location,number,spiculesign,lobulationsign,margin,TICandADCvalues. Ki-67expressionwasrecordedbyimmunohistochemicalstaining,whichwasdividedintohighexpression(≥20%)andlowexpression (<20%).Leastabsoluteshrinkageandselectionoperator(Lasso)wereperformedtoselectthefeaturesmostassociatedwithKi-67 expression.ThenomogramwasconstructedtopredictKi-67expression,aswellasAUCand95%confidenceinterval(CI)werecalculated.Results TICtypesandADCvaluesassociatedwithKi-67expressionwereidentifiedbyLassoregression.Thenomogram predictedthehigh andlow Ki-67expressionwithanAUCof0.827 (95% CI:0.713-0.940).TheKi-67expressionwasnegativelycorrelatedwiththe ADCvalues(r=-0.430,P=0.003).Ki-67expressionwassignificantlycorrelatedwithTICtype,andTICⅢwasmorelikelytohavehigher expressionofKi-67.Conclusion ThereisindividualandrespectivecorrelationbetweentheexpressionlevelofKi-67andTICtype, ADCvalue.TheexpressionlevelofKi-67canbepredictedtosomeextentbyADCvaluesandTICtypes.
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Objective@#To investigate the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) on patients with lung adenosquamous carcinoma, and to analyze relative factors.@*Methods@#From August 2007 to July 2017, 40 patients who were pathologically diagnosed as lung adenosquamous carcinoma in our hospital and received EGFR TKIs treatment were retrospectively analyzed. All patients underwent EGFR mutation detection, resulted in 11 wild type, 13 19Del, 13 21L858R mutations, and 3 uncommon EGFR mutations in 20 exon and 19/21 complex mutation. A higher frequency of EGFR mutation was found in non-smokers and patients with adenocarcinoma components over 50.0%.@*Results@#Twenty-six (65.0%) patients had disease progression after EGFR TKIs treatment, with a median progression-free survival (PFS) of 5.5 months (95% CI 0.52-10.49 months). A total of 20 (50.0%) patients died with an median overall survival (OS) of 15 months (95% CI 11.03-18.97 months). Multivariate analysis showed that gender, age, smoking, histopathological subtypes, EGFR mutations, and brain metastasis had no influence on PFS (all P>0.05). Gender, age, smoking, histopathological subtypes, and the presence of brain metastasis during TKI treatment had no influence on OS (P>0.05), while EGFR mutation is the only influencing factor of OS (P<0.05) in the current study.@*Conclusions@#EGFR TKIs had modest efficacy in lung adenosquamous carcinoma, especially in patients with EGFR mutation. Based on the pathological features, EGFR mutation and EGFR TKIs treatment should be introduced into the routine clinical practice to improve the survival of patients with lung adenosquamous carcinoma.
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Objective To evaluate the feasibility of T2 *mapping T2 *value combined with DWI ADC value in quantitative assessment of the activity of sacroiliitis.Methods 30 patients diagnosed with ankylosing spondylitis (AS)were divided into 2 groups as acute group (n=17)and chronic group (n=13)according to the BASDAI scores of the clinical severity of disease.And 20 healthy adults were recruited as control group.All groups were examined by MR with traditional sequence,T2 *mapping and DWI in the sacroiliac joint.The T2 *value and ADC value of the bone marrow edema region and normal region were measured.Furthermore,the imaging data and the clinical scores were statistical analysis and compared among three groups.Results T2 *values and ADC values in acute group of AS patients were higher than chronic group (P0.05).Positive correlation between ADC value and BASDAI was observed in patients group.Conclusion T2 *mapping combined with DWI imaging in AS is beneficial for early diagnosis and quantitative analysis of the activity of sacroiliitis.
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Objective To investigate the effect of the choice of the different models of venous indwelling needle on coronary flash dual-source computed tomography (CT) angiography.Methods 120 patients were randomly divided into three groups (40 cases in each group) who were selected to use 18G,20G,22G indwelling needle.They underwent CT coronary imaging.We measured the CT value of left and right coronary artery opening,right vein opening plane and the right ventricular cavity.We also compared the pain of patients during puncture.Results 120 cases were completed inspection.There was significant difference in the strengthen value of left and right coronary artery and CT value of the right ventricle cavity between 18G and 20G.The difference in the strengthen value of left and right coronary artery and CT value of the right ventricle cavity between 18G and 22G was also significantly different.There was no significant difference in all monitoring points between 20G and 22G.Three types of right coronary vein were not statistically significant.Conclusions Model 20G indwelling needle get the best flash dual-source CT image and better patients' acceptance.
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Objective To explore the MR features of granulomatous mastitis and to improve the diagnosis of the disease.Methods MR findings of 1 1 patients with granulomatous mastitis confirmed by pathology were retrospectively reviewed.Results Nine (81.82%)lesions showed regional or diffused hyperintensity on T2 WI with heterogeneous gridding features.2 (18.18%)lesions showed mass-like enhancement and 9 lesions showed non-mass-like enhancement.Of 9 (81.82%)lesions with non-mass-like en-hancement,the enhancement patterns included diffused in 2 (18.18%)cases,regional in 4 (36.36%)cases,multiple-regional in 2 (18.18%)cases,and focal in 1 (9.09%)case,respectively.All the lesions showed early heterogeneous enhancement,and clumped-ring enhancement was seen in 6 lesions.The signal intensity of the lesions was increased and more uniform in the later stage.The time-signal intensity curve was type I in 7(63.64%)cases,type II in 3 (27.27%)cases and type III in 1 (9.09%)case.The mean ADC value was (1.82±0.1 7)×10 -3 mm2/s,and there was no significant difference between lesions and normal regions (t=1.766, P >0.05).Concomitant signs included barymastia,thickening of skin,edema surrounding the lesions,and axillary lymph node en-largement.The BI-RADS category was 3 degree in 1 (9.09%)case,4a degree in 5 (45.45%)cases,4b degree in 2 (18.18%)ca-ses,4c degree in 2 (18.18%)cases and 5 degree in 1 (9.09%)case.The misdiagnosis ratio was 54.55%.Conclusion Granuloma-tous mastitis has certain characteristic MR features.The misdiagnosis ratio of granulomatous mastitis is high.Therefore,clinical data should be referred when making diagnosis.
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Objective To undertake an updated genetic spectrum analysis in patients with hereditary spinocerebellar ataxia (SCA) in mainland China. Methods SCA 1, 2, 3, 6, 7, 8, 10, 12, 17 and dentatorubral-pallidoluysian atrophy (DRPLA) nucleotide repeat mutations were detected in 430 families with autosomal dominant SCA (ADCA) and 237 patients with sporadic ataxias by PCR and DNA sequencing. Subsequently, point and Indel (Insertion/deletion) mutation analyses of SCA5, SCA11, SCA13, SCA14, SCA15/16/29, SCA27, SCA31 and SCA35 were detected in 91 families with ADCA and 196 patients with sporadic ataxias excluded from SCA1, 2, 3, 6, 7, 8, 10, 12, 17 and DRPLA genotypes via PCR and Denaturing High Performance Liquid Chromatography (PCR-DHPLC), Multiplex ligation-dependent probe amplification and DNA direct sequencing analysis. Results Among the 430 ADCA families, there were 25 SCA1 (5.81%), 27 SCA2 (6.28%), 267 SCA3/MJD (62.09%), 8 SCA6 (1.86%), 8 SCA7 (1.86%), 1 SCA12 (0.23%), 1 SCA17 (0.23%) and 2 SCA35 (0.47%), and the remaining 91 families (21.16%) were genetically unidentified. Among the 237 sporadic SCA patients, there were 6 SCA1 (2.53%), 9 SCA2 (3.80%), 23 SCA3/MJD (9.70%) and 3 SCA6 (1.27%), and the remaining 196 (82.7%) were genetically unidentified. No pathogenic point mutation causing SCA5, SCA11, SCA13, SCA14, SCA27 or SCA31 subtypes was found. Conclusion SCA3/MJD is substantially the most common subtype in patients with ADCA and sporadic forms in mainland China, followed by SCA2, SCA1, SCA6 and SCA7. While SCA12, SCA17 and SCA35 are seldom found, SCA5, SCA8, SCA10, SCA11, SCA13, SCA27, SCA31 and DRPLA are very rare. The high proportion of genetically unidentified cases further verify that SCAs are of highly genetic heterogeneity, suggesting that other disease-causing genes might be involved in the negative ADCA pedigrees, and other etiological factors may involve in those sporadic cases other than genetics.
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Objective To detect the regulation of CXCL16 synthesis and shedding in first-trimester human trophoblasts. Methods Firstly, we analyzed the expression and secretion of chemokine CXCL16 in primary cultured trophoblasts by immunochemical staining and ELISA. Then we determined the soluble and cell-associated CXCLI6 respectively with and without treatments of cytokine IFN-γ, TNF-α, IL-4 and ADAM10 by ELISA. Results Trophoblast expressed and secreted CXCL16 in a stable level. Cytokine IFN-γ induced both synthesis and secretion of CXCL16 significantly ( P <0. 01 ) in trophoblasts. ADAM10 increased the shedding of chemokine domain of CXCL16 from trophoblasts but didn't influence the synthesis of CXCL16 protein in trophoblast. Conclusion IFN-γ and ADAM10 play important roles in production and shedding of transmembrane CXCL16 in first-trimester trophublasts.