Potential unreliability of ALK variant allele frequency in the efficacy prediction of targeted therapy in NSCLC / 医学前沿

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.

The value of Fib4 and APRI in predicting liver failure after hepatectomy in patients with hepatocellular carcinoma / 中华肝胆外科杂志

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.

Strategic Exploration of Targeted Therapy for BRAF Non-V600E Mutant Lung Cancer / 中国肺癌杂志

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.

TopredicttheKi-67expressioninbreastcancerbasedon MRappearences / 实用放射学杂志

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.

The efficacy and influence factors analysis of EGFR TKIs on patients with lung adenosquamous carcinoma / 中华肿瘤杂志

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.

Quantitative analysis of early ankylosing spondylitis sacroiliac joint by multiple functional MR imaging / 实用放射学杂志

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.

The effect of the choice of venous indwelling needle on coronary flash dual-source computed tomography angiography / 中国实用护理杂志

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.

The MR features of granulomatous mastitis / 实用放射学杂志

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.

Spinocerebellar ataxias in mainland China: an updated genetic analysis among a large cohort of familial and sporadic cases / 中南大学学报(医学版)

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.

The synthesis and shedding of transmembrane CXCL16 in first-trimester human trophoblast / 中华微生物学和免疫学杂志

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.